HPN 2021 December

HOSPITAL PROFESSIONAL NEWS IRELAND

HPN December 2021 Professional 100 Issue HOSPITALPROFESSIONALNEWS.IE

Ireland’s Dedicated Hospital Professional Publication

D

NEWS: Updated Statements of Hospital Pharmacy Page 6

AT ED C I F

O R

IN

IN THIS ISSUE:

PsA | RA | UC

ANTIMICROBIALS: Surgical Antibiotic Prophylaxis Duration Page 12 REVIEW: End of Year Review for Irish Pharmaceutical Healthcare Authority Page 14 CPD: Management and Treatment of Prostate Cancer Page 41

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

XELJANZ® is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent.

XELJANZ® in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs.

XELJANZ® in combination with MTX is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy.

PP-XEL-IRL-0681 Date of preparation: November 2021

This Publication is for Healthcare Professionals Only

PROFESSIONAL 100: Annual Hospital Professional 100 Listing Page 47 FEATURE: Keeping Track of Covid Vaccines Page 94 CONFERENCE: Coverage from the European Association for the Study of Diabetes Page 100

Now reimbursed in Republic of Ireland.

Onpattro® (patisiran) Abbreviated Prescribing Information - Republic of Ireland Please refer to the Summary of Product Characteristics for further information.

Name of the Medicinal Product: Onpattro (patisiran) 2 mg/mL concentrate for solution for infusion. Qualitative and quantitative composition: Each mL contains patisiran sodium equivalent to 2 mg patisiran. Each vial contains patisiran sodium equivalent to 10 mg patisiran formulated as lipid nanoparticles. Therapeutic Indication: Onpattro is indicated for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy. Posology and method of administration: The recommended dose of Onpattro is 300 micrograms per kg body weight administered via intravenous (IV) infusion once every 3 weeks. Dosing is based on actual body weight. For patients weighing ≥ 100 kg, the maximum recommended dose is 30 mg. Vitamin A supplementation at approximately 2500 IU vitamin A per day is advised for patients treated with Onpattro. All patients should receive premedication prior to Onpattro administration to reduce the risk of infusion- related reactions (IRRs). Each of the following medicinal products should be given on the day of Onpattro infusion at least 60 minutes prior to the start of infusion: • Intravenous corticosteroid (dexamethasone 10 mg, or equivalent) • Oral paracetamol (500 mg) • Intravenous H1 blocker (diphenhydramine 50 mg, or equivalent) • Intravenous H2 blocker (ranitidine 50 mg, or equivalent). If clinically indicated, the corticosteroid may be tapered in decrements no greater than 2.5 mg to a minimum dose of 5 mg of dexamethasone (intravenous, IV), or equivalent. The patient should receive at least 3 consecutive IV infusions of Onpattro without experiencing IRRs before each reduction in corticosteroid premedication. Therapy should be initiated under the supervision of a physician knowledgeable in the management of amyloidosis. Consult the summary of product characteristics for further details about the method of administration. Contraindications: Severe hypersensitivity (e.g., anaphylaxis) to the active substance or any of the excipients. Special warnings and precautions for use: IRRs have been observed in patients treated with Onpattro. In patients experiencing an IRR,

the majority experienced the first IRR within the first 2 infusions. Across clinical studies, the most common symptoms (reported in ≥ 2% of patients) of IRRs were flushing, back pain, nausea, abdominal pain, dyspnoea, and headache. IRRs may also include but are not limited to hypotension, syncope and pruritus. To reduce the risk of IRRs, patients should receive premedications on the day of Onpattro infusion, at least 60 minutes prior to the start of infusion. If an IRR occurs, slowing or interrupting the infusion and institution of medical management (e.g., corticosteroids or other symptomatic treatment) should be considered, as clinically indicated. If the infusion is interrupted, resumption of the infusion at a slower infusion rate may be considered after symptoms have resolved. The Onpattro infusion should be discontinued in the case of a serious or life-threatening IRR. Some patients who experience IRRs may benefit from a slower infusion rate or additional or higher doses of one or more of the premedications with subsequent infusions to reduce the risk of IRRs. By reducing serum TTR protein, Onpattro treatment leads to a decrease in serum vitamin A (retinol) levels. Serum vitamin A levels below the lower limit of normal should be corrected and any ocular symptoms or signs due to vitamin A deficiency should be evaluated prior to initiation of treatment with Onpattro. Patients receiving Onpattro should take oral supplementation of approximately 2500 IU vitamin A per day to reduce the potential risk of ocular toxicity due to vitamin A deficiency. Referral for ophthalmological assessment is recommended if patients develop ocular symptoms suggestive of vitamin A deficiency, including reduced night vision or night blindness, persistent dry eyes, eye inflammation, corneal inflammation or ulceration, corneal thickening or corneal perforation. Serum vitamin A levels should not be used to guide vitamin A supplementation during treatment with Onpattro. Fertility, pregnancy and lactation: There are no data on the effects of Onpattro on human fertility. No impact on male or female fertility was detected in animal studies.There are no data on the use of Onpattro in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. Due to the potential teratogenic risk

ONPATTRO®

(patisiran) is indicated for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy1

ONPATTRO®: Your opportunity to reset treatment expectations in hereditary ATTR amyloidosis with polyneuropathy

Regardless of the mutation or predominant symptomatology, all patients with hereditary ATTR amyloidosis develop mixed symptoms2 ONPATTRO® has demonstrated benefits vs placebo across the multi-system manifestations typically seen in patients with hereditary ATTR amyloidosis with stage 1 or 2 polyneuropathy1,3,4

arising from unbalanced vitamin A levels, Onpattro should not be used during pregnancy, unless the clinical condition of the woman requires treatment. As a precautionary measure, vitamin A and thyroid stimulating hormone (TSH) levels should be obtained early in pregnancy. Close monitoring of the foetus should be carried out in the event of an unplanned pregnancy, especially during the first trimester. Women of childbearing potential have to use effective contraception during treatment with Onpattro. It is unknown whether Onpattro is excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Onpattro, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Undesirable effects: The most frequently occurring adverse reactions reported in Onpattro-treated patients were peripheral oedema (29.7%) and infusion-related reactions (18.9%). The only adverse reaction resulting in the discontinuation of Onpattro was an infusion-related reaction (0.7%). The adverse reactions are presented below as MedDRA preferred terms under the MedDRA System Organ Class (SOC) by frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency of the adverse reactions is expressed according to the following categories: Very common (≥ 1/10): Infusion-related reaction, Peripheral oedema. Common (≥ 1/100 to < 1/10): Bronchitis, Sinusitis, Rhinitis, Vertigo, Dyspnoea, Dyspepsia, Erythema, Arthralgia, Muscle spasms. Uncommon (≥ 1/1,000 to < 1/100): Extravasation. Prescribers should consult the Summary of Product Characteristics for further details of the above and for details of other adverse reactions. Marketing Authorisation Number: EU/1/18/1320/001. Additional information is available from the Marketing Authorisation Holder: Alnylam Netherlands B.V. Antonio Vivaldistraat 150 1083 HP Amsterdam, Netherlands. Legal Classification: Medicinal product subject to restricted medical prescription. Pack size and Price: €8520.84 per vial (10mg/5ml) of Onpattro (patisiran) concentrate for solution for infusion. Date of last revision: 09/2021. Version Final: TTR02-IRL-00016.

References 1. ONPATTRO®. Summary of Product Characteristics, November 2020. 2. Coelho T, et al. Curr Med Res Opin. 2013;29(1):63–76. 3. Adams D, et al. N Engl J Med. 2018;379(1):11–21. 4. Solomon SD, et al. Circulation.

2019;139(4):431–443.

ATTR, TTR amyloidosis; hATTR, hereditary ATTR amyloidosis; TTR, transthyretin.

Developed and produced by Alnylam Pharmaceuticals Adverse events should be reported. Reporting forms and information can be found at HPRA Pharmacovigilance, Website: https://www.hpra.ie/homepage/about-us/ report-an-issue/human-adverse-reaction-form Adverse events should also be reported to Alnylam Netherlands B.V. at 1800 924260 (+353 7 667 05596) or medinfo@alnylam.com

For Healthcare Professionals only.

ONPATTRO® is a trademark of Alnylam Pharmaceuticals, Inc. © 2021 Alnylam Pharmaceuticals, Inc. All rights reserved.

October 2021 | TTR02-IRL-00028

OYAVAS®: THE NEW BEVACIZUMAB BIOSIMILAR FROM CLONMEL HEALTHCARE1 SIMPLY CONVINCING – with similar efficacy, safety and quality to the reference product*2 SIMPLY RELIABLE – with European production supported by over 20 years of biosimilars experience† SIMPLY DEDICATED – with a continuously expanding oncology portfolio ABBREVIATED PRESCRIBING INFORMATION Oyavas 25 mg/ml concentrate for solution for infusion. Each ml contains 25 mg of bevacizumab. Each 4 ml vial contains 100 mg of bevacizumab.

Each 16 ml vial contains 400 mg of bevacizumab. Presentation: Glass vial. Indications: 1) Oyavas in combination with fluoropyrimidine based chemotherapy is indicated for treatment of adult patients with metastatic carcinoma of the colon or rectum. 2) Oyavas in combination with paclitaxel is indicated for first line treatment of adult patients with metastatic breast cancer. 3) Oyavas in combination with capecitabine is indicated for first line treatment of adult patients with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. Patients who have received taxane and anthracycline containing regimens in the adjuvant setting within the last 12 months should be excluded from treatment with Oyavas in combination with capecitabine. 4) Oyavas in addition to platinum-based chemotherapy is indicated for first line treatment of adult patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology. 5) Oyavas in combination with erlotinib, is indicated for first line treatment of adult patients with unresectable advanced, metastatic or recurrent non squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations. 6) Oyavas in combination with interferon alfa 2a is indicated for first line treatment of adult patients with advanced and/or metastatic renal cell cancer. 7) Oyavas in combination with carboplatin and paclitaxel is indicated for the front line treatment of adult patients with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. 8) Oyavas in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel is indicated for treatment of adult patients with first recurrence of platinum sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. 9) Oyavas in combination with topotecan or pegylated liposomal doxorubicin is indicated for the treatment of adult patients with platinum resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. 10) Oyavas in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix.

Dosage: Refer to Summary of Product Characteristics. Method of administration: Oyavas is for intravenous use. The initial dose should be delivered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion may be administered over 60 minutes. If the 60 minute infusion is well tolerated, all subsequent infusions may be administered over 30 minutes.

Contraindications: Hypersensitivity to the active substance or excipients, hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies, pregnancy. Warnings and precautions: GI perforations and fistulae, GI vaginal fistulae, non-GI fistulae, wound healing complications, hypertension, posterior reversible encephalopathy syndrome, proteinuria, arterial thromboembolism, venous thromboembolism, haemorrhage, pulmonary haemorrhage/haemoptysis, aneurysms and artery dissections, congestive heart failure, neutropenia and infections, hypersensitivity reactions/infusion reactions, osteonecrosis of the jaw. Oyavas is not formulated for intravitreal use. Eye disorders, systemic effects following intravitreal use, female fertility impairment. Interactions: Refer to Summary of Product Characteristics. Fertility, pregnancy and lactation: Women of childbearing potential have to use effective contraception during (and up to 6 months after) treatment. Oyavas is contraindicated in pregnancy. Women must discontinue breast-feeding during therapy and not breast-feed for at least six months following the last dose of bevacizumab.

Repeat dose toxicity studies in animals have shown that bevacizumab may have an adverse effect on female fertility. Long term effects of the treatment with bevacizumab on fertility are unknown. Driving and operation of machinery: Bevacizumab has no or negligible influence on the ability to drive and use machines. However, somnolence and syncope have been reported with bevacizumab use. If patients are experiencing symptoms that affect their vision or concentration, or their ability to react, they should be advised not to drive and use machines until symptoms abate. Undesirable effects: Very common: Febrile neutropenia, leukopenia, neutropenia, thrombocytopenia, anorexia, hypomagnesaemia, hyponatraemia, peripheral sensory neuropathy, dysarthria, headache, dysgeusia, eye disorder, lacrimation increased, hypertension, thromboembolism (venous), dyspnoea, rhinitis, epistaxis, cough, rectal haemorrhage, stomatitis, constipation, diarrhoea, nausea, vomiting, abdominal pain, wound healing complications, exfoliative dermatitis, dry skin, skin discolouration, arthralgia, myalgia, proteinuria, ovarian failure, asthenia, fatigue, pyrexia, pain, mucosal inflammation, weight decreased.

A copy of the SmPC is available upon request or go to www.clonmel-health.ie Pack size: 1 vial of 4 ml or 16 ml. Marketing authorisation holder: STADA Arzneimittel AG, Stadastrasse 2-18, 61118 Bad Vilbel, Germany. Marketing authorisation number: EU/1/20/1510/001-002. Medicinal product subject to medical prescription. Date last revised: May 2021. *Avastin® (bevacizumab) † STADA founded Bioceuticals Arzneimittel AG in 2000 1. Oyavas® SmPC (Apr. 2021). 2. Oyavas® EPAR Public Assessment Report. Available at: https://www.ema.europa.eu/en/documents/ assessment-report/oyavas-epar-public-assessment-report_en.pdf. Last accessed Apr. 2021. 2021/ADV/OYA/027H.

oyavas.ie

December Issue Professional 100 Issue

5

Contents

Foreword

St Vincent’s Private Hospital Pharmacy team scoop Award P7

Editor In one of our leading news stories this issue, The Irish Medical Organisation has acknowledged the additional Health funding announced in Budget 2022 but also warned that it will not be enough to tackle the enormous challenges in the service.

Urgent calls for reform of Health Information System P8 New Appointment at Accord Healthcare Ireland P10

President Dr Ina Kelly says that a capacity crisis was now endemic across health services. “We keep loading more demand on fewer healthcare professionals. We are losing GPs, losing consultants and losing young, newly-trained doctors yet Government is not tackling the underlying problem of too few doctors and too little capacity,” she comments. You can read more about this on page 6.

7

New Drug Research on Secondary Breast Cancer P13 HPN Professional Top 100 P46 Working together to improve HIV Care P82 10

Keeping track of the COVID-19 Vaccine in the Centralised Vaccination Clinics P94 REGULARS

Feature: Surgical Antibiotic Prophylaxis Duration P12 Feature: Immunotherapy Update in Lung Cancer P26

13

CPD: Management of Prostate Cancer P41 Feature: Diabetes Care in Pregnancy P106 Clinical R&D: P111 Hospital Professional News is a publication for Hospital Professionals and Professional educational bodies only. Subscription rate for Hospital Professional News ¤60 plus vat per year.

All rights reserved by Hospital Professional News. All material published in Hospital Professional News is copyright and no part of this magazine may be reproduced, stored in a retrieval system of transmitted in any form without written permission. IPN Communications Ltd have taken every care in compiling the magazine to ensure that it is correct at the time of going to press, however the publishers assume no responsibility for any effects from omissions or errors.

PUBLISHER IPN Communications Ireland Ltd Clifton House, Lower Fitzwilliam Street, Dublin 2 (01) 669 0562 GROUP DIRECTOR Natalie Maginnis n-maginnis@btconnect.com EDITORIAL editorial@hospitalprofessionalnews.ie

82

ACCOUNTS Rachel Wilson cs.ipn@btconnect.com DIGITAL MARKETING & EDITORIAL EXECUTIVE Carla Fulton carla@hospitalprofessionalnews.ie CPD Lead Sibongile Swan Mude swan@ipn.ie CONTRIBUTORS Marie Philbin Dr Iseult Browne Dr Mark Doherty D Philbin MJ Barrett Stephen O’Hare Siobhan Duggan Ciara Coveney DESIGN DIRECTOR Ian Stoddart Design HOSPITALPROFESSIONALNEWS.IE

@HospitalProNews HospitalProfessionalNews

This being our final issue of 2021, we carry our annual End of Year Reports from some of the leading representative and regulatory bodies, including the Health Products Regulatory Authority. Chief Executive Dr Lorraine Nolan reflects, “The Covid-19 pandemic continued to affect every facet of life in Ireland, and around the world, during the last year.

Unfortunately, we are all too well aware of the awful effects and devastation caused by Covid-19. As the scale of the impact of the pandemic became clear, we witnessed a direct and almost instant response from the global scientific community.”

On page 16 Ann Marie O’Neill, CEO of Thrombosis Ireland comments on what has been an incredibly busy year for her team. “It has been the busiest year in the history of Thrombosis Ireland,” she says. “The worry of Covid-19 and the different vaccines has caused confusion and so much added anxiety and fear among thrombosis patients, their families & carers. We have worked hard to ensure that everyone had access to the latest guidelines and recommendations from the National Coagulation Centre, St. James Hospital, so that they could make correct and informed decisions for themselves.”

The December issue also carries our hugely anticipated, HPN Professional Top 100. The HPN Top Professional Top 100 is a carefully constructed network of the most influential hospital professionals across a range of disciplines, both in the healthcare and pharma industries, who act as ambassadors and role models for their peers, colleagues and the rising stars of tomorrow. Over the past many months, our team of writers has reached out to pharmacists, consultants, clinical specialists, representative bodies and organisations throughout the sector and encouraged them to put forward those colleagues they feel are redrawing the landscape for the future. Those who have made our final list have displayed motivating behaviour and inspirational leadership affecting the development of hospital services across Ireland.

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

6

News

New Version of European Statements of Hospital Pharmacy Delegates from the European Association of Hospital Pharmacy (EAHP’s) 35 members countries came together (virtually) on the 11th and 12th of June for the 51st EAHP General Assembly. During the General Assembly, the commented version of the European Statements of Hospital Pharmacy was voted on and approved by all members.

Adopted in 2014 following a Delphi process involving more than 100 stakeholders, the European Statements represent the future of the profession. In 2016, EAHP set up an implementation programme that started to work to bring about the full achievement of the European Statements within all our member countries. Much progress has been made since then, including the development

of an online tool allowing hospital pharmacists to assess the level of implementation of the European Statements within their pharmacies.

It was in 2019 when EAHP decided to conduct a review of the Statements to check their continued relevance and whether they effectively covered emerging issues. The EAHP Board with the support of all EAHP Members determined that the European Statements are still remarkably resilient. However, the working group in charge of reviewing the Statements decided that some of them could benefit from the addition of comments to further clarify their meaning.

The EAHP Board and all EAHP national associations agreed with this approach.

Thus, after a process that involved a working group of highly qualified hospital pharmacists and all 35 national associations, EAHP adopted this commented version of the European Statements.

“If Covid-19 has taught us one thing, it is the need for better preparedness for pandemics and the importance of the hospital pharmacy profession in the healthcare setting. We believe that the European Statements set the vision for what should be expected of Hospital Pharmacy and Hospital Pharmacists across Europe to ensure we are prepared for that next challenge to the health of our citizens,” said an EAHP statement.

EAHP President András Süle added, “By working together

on the implementation of the European Statements we will not only be better prepared for future crises like the Covid-19 pandemic, but we will also improve the safety and efficacy of hospital pharmacy services.

The provision of a patientcentered care is at the core of the Statements and reflects what we believe is the future of the profession” EAHP Project Director Tony West remarked “The continued relevance of the Statements, especially as the world is still struggling with the pandemic, reflects the work put in to initially develop them by patients, our healthcare professional colleagues and hospital pharmacists.”

Budget 2022 Reaction – ‘Not Enough’ Dr Ina Kelly, President, Irish Medical Organisation

• Doctors in training are leaving for other health services due to poor conditions and career pathways • GP services are under extreme pressure with increased demand

The Irish Medical Organisation has acknowledged the additional Health funding announced in Budget 2022 but also warned that it will not be enough to tackle the enormous challenges in the service where: • Almost 1 million patients will be on a waiting list by year end with almost 300,000 waiting over a year • 1 in 5 consultant posts are vacant • There are only 3 hospital beds per 1000 population when the OECD average is 5

and sustainable solutions. In our view, now is the time to be bold, face up to the challenges and not continue to paper over the cracks.

The additional and unexpected resources available to Government could have been used to invest in the health of our nation.”

Dr Clive Kilgallen, Vice President and Chair of the IMO Consultant Committee, said: “With 1 in 5 consultant posts vacant and the need to recruit even more consultants, it is more than disappointing that Government have not seriously addressed the manpower crisis in our services which in turn is leading to long waiting lists.

“This crisis in manpower is one of the Government’s making

The President of the IMO, Dr Ina Kelly, said that a capacity crisis was now endemic across health services: “We keep loading more demand on fewer healthcare professionals. We are losing GPs, losing consultants and losing young, newly-trained doctors yet Government is not tackling the underlying problem of too few doctors and too little capacity. We are still dealing with the effects of the pandemic and the recent cyberattack but even before these shocking events our health service was not resourced to meet patient needs and incapable of providing timely access to care.

“Patients and the medical profession need to see tangible

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

as they introduced a unique and discriminatory pay cut on consultants since 2012 (30% more than cuts imposed on other public servants during the years of austerity). Waiting lists are inevitable when we have too few doctors coupled with a lack of capacity in beds, theatre time, diagnostics and outpatient clinics.

“The funding for tackling waiting lists while welcome will not deal with the significant problem that has been created by successive governments through lack of investment in the public system and a policy of relying on the private system. It is no surprise that we cannot recruit and that our NCHDs continue to pursue their careers abroad where they are supported and valued.”

News

7

Local Award for SVPH Pharmacy Team The Hospital Clinical Pharmacy Team from St Vincent’s Private Hospital in Dublin recently won the Acute Hospital Quality Improvement award at the inaugural Thrombosis Ireland Exemplar Awards.

The Awards were held earlier this year by Thrombosis Ireland.

Using Meg audit tools, an app was developed with the help of VTE Ireland, Professor Fionnuala Ni Ainle, Dr Barry Kevane and Dr. Tomas Breslin to audit VTE Prophylaxis efficiently.

Their new, award-winning app has enabled SVPH to develop a quality of service and improve patient safety by identifying areas that are underperforming and areas that continue to improve.

Auditing of VTE Prophylaxis is also reported in real time and can be acted on immediately.

The long term vision is that it will be used in all Irish hospitals and that all data would be collected into a National System.

The Hospital Clinical Pharmacy Team from St Vincent’s Private Hospital in Dublin

Mater Private Network Ranked Top 5 Mater Private Network is delighted to have been ranked 5th out of 100 of Ireland’s largest organisations for Sustainability reputation. The Ireland RepTrak® Sustainability Index 2021 study ranks the largest, most familiar and most important organisations in Ireland by the public’s perceptions of their performance across the three Sustainability dimensions of Citizenship, Governance, and Workplace. The independent study was carried out

by The Reputations Agency and The Reptrak® Company.

The Ireland RepTrak® Sustainability Index 2021 study asked 6,500 members of the public to rate how well they felt 100 organisations performed across three dimensions and nine attributes; measuring the degree to which they are seen to act responsibly towards their communities and the environment in which they operate, ensuring that their businesses are responsibly run and treating their staff well. The online survey also asked members of the public to name examples of what companies do to make them a good corporate citizen. The study found that the more genuine and authentic an organisation is in its activities and its communication, the higher their Sustainability reputation.

Speaking about their 5th place ranking, Mike Rutter, Deputy CEO, Mater Private Network, said, “We believe this reflects our commitment to the highest standards across our network of hospitals and clinics, and it’s great to have this recognised by the general public. We continually strive to implement and improve the highest quality of medical care for our patients, and this extends to all of our behaviours throughout every aspect of how we operate throughout our network, including our commitment to Sustainability values.”

Health Index Published for 2021 The 2021 Pfizer Health Index has shown that 40% of people surveyed were concerned about developing heart disease in the future.

The research, which was published just last month, revealed that people are anxious about their long-term health and the prospect of developing a variety of serious illnesses such as heart disease and cancer.

Of those who stated they were concerned about developing cancer in the future (50%), some 21% of respondents (41% of women) said they were concerned about getting breast cancer, 18% had concerns about contracting cervical cancer (35% of women) and 39% were concerned about all other forms of cancer.

The Pfizer Index shows that respondents had similar concerns about getting other diseases, with 40% concerned about heart disease; 37% worried about developing Alzheimer’s and over one-quarter of those surveyed (28%) responding that they have concerns about developing depression later in life.

The Index also revealed that one in five people (21%) are worried that they could have missed out on a diagnosis and treatment due to the Covid-19 pandemic with approximately 50% either cancelling or missing scheduled appointments.

The 2021 Pfizer Health Index found that appointments cancelled by hospitals were higher among older age-groups

with 28% of over 65s having a hospital appointment cancelled compared with 16% of 25-34 year-olds. Meanwhile, one in ten (11%) adults did not seek treatment despite feeling unwell during this period.

The annual Pfizer Health & Science Index also revealed that people were less worried about visiting the hospital in 2021 compared with last year with almost one-fifth (18%) stating that they were very or quite worried and would not visit a hospital – a nine-point drop compared to 27% in 2020. Similarly, just 16% of people are very or quite worried and would not visit their GP.

implication of the pandemic with mental health, diet and weight and a lack of exercise being the most common.

Paul Reid, Managing Director, Pfizer Healthcare Ireland said; “It’s clear from the research that people have put off going to their doctor and it is really important that anyone with an ongoing health issue visits their GP to seek help. It is understandable that people are worried about having a stroke or getting cancer, however scientific advancement and health outcomes are getting better, and with early diagnosis and access to treatments patients have a better chance of a positive outcome.”

The research also found that 43% of people believe that they experienced a negative health

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

8

News

Calls for Urgent Reform of Health Information System HIQA’s Director of Health Information and Standards Rachel Flynn

even gets a blood test — health information is being created.

The Health Information and Quality Authority (HIQA) has launched a report calling for reform of the health information system for health and social care in Ireland. The report makes six recommendations across strategy, leadership, legislation, workforce, standards and health information infrastructure needed to establish an effective and efficient national health information system.

Recent events, such as Covid-19 and the cyberattack on the Health Service Executive (HSE), have highlighted the key role that health information plays in the planning, management and delivery of health and social care services.

The report outlines how health information systems — such as electronic health records,

electronic prescribing, eReferrals and national data collections — can be used across the health service, from service users to clinicians to public health officials and policy-makers to help to improve patient outcomes, inform research and influence policymaking decisions.

Launching the report, HIQA’s Director of Health Information and Standards, Rachel Flynn, said, “Reforming how health information is managed and governed is central to the success of Sláintecare. The most significant gaps in our health and social care system are the major deficiencies that exist around the collection, use and sharing of information.

Every time a patient visits their GP, attends a hospital, a specialist or

This valuable data is usually managed on different electronic systems or is paper-based, which is inefficient and can impact on people’s safety. Our front-line staff require high-quality, timely and accurate patient information to ensure the best possible care is being provided. Urgent reform is needed, otherwise Irish health and social care services will remain inefficient and ineffective.

“Unlike some other jurisdictions, there is no single entity in Ireland with responsibility for health information across both public and private services, whose sole purpose is to ensure co-ordination of the health information system at a national level. We believe that an entity should be established to provide strategic leadership and governance for health information outside of the HSE. This needs to be adequately funded and resourced. Legislation is needed as, currently, no overarching legal framework exists for the collection, use and sharing of health information.

“While our Covid-19 vaccination programme has been exceptionally successful by international standards, its rollout also required

deployment of a new system to support its implementation.

The absence of a digital system to manage not just Covid-19 vaccinations, but all vaccination programmes was notable.

During the cyberattack on the HSE, our health service returned to paper records and suffered from increased waiting lists and rescheduled appointments, which had an impact on people’s safety.

This clearly demonstrates that our health service cannot operate without health information and that IT security must be enhanced.”

HIQA has researched international best practice for national health information strategies for Ireland to emulate, with examples such as Canada, Denmark and New Zealand highlighted in today’s report. HIQA believes that a health information strategy must cover the entire system for people using all health and social care services. The strategy must be assigned appropriate funding to support its full implementation and progress should be reported on an annual basis. Setting standards, ensuring compliance and investing in infrastructure and security to ensure personal information is protected, are identified as specific recommendations.

HIQA’s Rachel Flynn concluded: “The success of Sláintecare requires urgent reform of health information and this will require reform being made a political priority. Today’s report is calling for urgent reform and should serve as a wake-up call for all stakeholders in health and social care to make health information a high priority.”

77,000 people on ENT Waiting Lists A Consultant Ear, Nose and Throat (ENT) Surgeon in the North-West has warned of the long-term impact on patients across the country who face delays of up to 5 years on hospital waiting lists for some of the most common ENT conditions and procedures.

Speaking on behalf of the Irish Hospital Consultants Association (IHCA), Ms Mary Bresnihan, a Consultant ENT Surgeon at Sligo University Hospital, said that ENT procedures are often subject to delays and have some of the longest waiting lists as a result.

“We’re talking about common conditions like tonsillectomies, for example, where surgery could

be managed through day-case procedures without a need for complex surgery or lengthy stays in hospital.

“But we face challenges even getting to see and assess the patient in the first place. When we do, and we schedule treatment, these patients can unfortunately—regularly—be at the mercy of emergency or other priorities taking theatre slots at the last minute.”

Such delays have led to a situation where there are now almost 77,000 people nationally on some form of ENT waiting list. The outpatient waiting lists alone have increased by more than 20,000 over the past six years (+20,948, or 41%).

The number of people waiting longer than a year for an outpatient ENT appointment with a hospital consultant has increased by over 29,000 since 2015, a three-fold increase to 42,565. In all, 57% of those awaiting either an assessment by a Hospital Consultant or inpatient/ day case treatment have been waiting longer than a year.

Ms Bresnihan believes that until the Government gives greater priority to tackling waiting lists for scheduled essential surgery and procedures, many patients will continue to face long waits and reduced health outcomes.

“People are getting worse while they’re sitting on these lists,

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

to the point where we can no longer reverse the problems like we could have if they had been operated on in a timely manner.

“One of the biggest concerns is the potential for missed cancer diagnoses. People with voice or throat issues, for example, who may not seem urgent initially, could in fact be presenting with symptoms of a tumour that, without the chance for investigation or assessment, risk going undiagnosed while they sit on a waiting list deemed ‘non-essential’”, said Ms Bresnihan.

The solution to all your sourcing pains

For more information please contact: Free Phone 1800 440 440 I PharmaSource@uniphar.ie I www.uniphar.ie

10

News

¤30m for new medicines will help to give patients access to innovation pipeline clinical, and other tests, can be funded. That creates the headroom for higher standards of care, allowing doctors to broaden the range of treatments for patients.

The medicines the originator biopharmaceutical industry brings forward are the product of years of research and development. The Government has signalled that it values this innovation and believes in the often transformational impact it can have on patients’ lives.

The Government’s allocation of ¤30 million for new medicines in Budget 2022 will help to give more patients access to new treatments in the innovation pipeline, according to the Irish Pharmaceutical Healthcare Association (IPHA), the representative organisation for the originator biopharmaceutical industry.

Next year, IPHA member companies expect to launch almost 40 new medicines for a range of medical conditions,

including arthritis, multiple sclerosis, Parkinson’s disease, gastrointestinal diseases and many forms of cancer. These medicines would treat some 17,500 patients.

In his Budget speech, the Minister for Public Expenditure and Reform, Michael McGrath TD, allocated ¤30 million for “new drugs to ensure our citizens have access to the best high-tech drugs available globally.”

The move in Budget 2022 builds on a ¤50 million allocation for new

medicines in last year’s Budget, showing the Government’s commitment to integrating innovation into the care pathway.

IPHA welcomed today’s announcement by the Government.

“Our goal is to move towards a situation where we have a continuous, steady flow of new medicines to the health system,” said Oliver O’Connor, Chief Executive of IPHA. “Today’s announcement means more medicines that satisfy the HSE’s

“As we work with the State towards a new medicines supply Agreement, this announcement is a significant step on that journey. We believe investment in medicines is an investment in our futures. We want the adoption of new medicines to complement our high-performing biopharmaceutical manufacturing industry. This Government deserves great credit for backing innovation. While we have much ground to make up to make Ireland as fast as other western European countries in making new medicines available to patients, this funding enables significant progress. Through a new medicines supply Agreement, we can take that effort forward,” said Mr O’Connor.

See ipha.ie and our social channels for the latest on recent campaigns like #InvestInOurFutures and #InnovateForLife.

New Appointment at Accord Healthcare Ireland Accord Healthcare Ireland is delighted to announce the appointment of Padraic O’Brien as Managing Director from November 1st. Padraic will replace the current Managing Director Tony Hynds who recently announced his intention to retire from the business in December.

Mr O’Brien, a native of Monaghan and a graduate of DIT and Trinity College Dublin has held a number of senior management positions within the company, most recently as Commercial Director where he has overseen the implementation of the Accord Sales Strategy.

Tony Hynds & Padraic O'Brien MD Accord Healthcare

“It is an exciting time in Accord Healthcare Ireland”, says Mr O’Brien, “Tony leaves us in a great position, he has grown the

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

company during his tenure and leaves at a time when Accord is one of the leading generic suppliers in Ireland, with a diverse portfolio of products across retail, hospitals and speciality brands and a dedicated and committed team in Cork. We have many new and exciting launches coming in 2022 which demonstrate our commitment to the health of the Irish people and we will continue our ethos of working with healthcare professionals across the country for the betterment of Irish patients.”

Padraic will also take over the role as Chair of Medicines for Ireland at the AGM at the end of November, he has served as Vice-Chair for the past two years.

Pelgraz® PFI Patient Support App The Pelgraz® PFI App is designed to support patients self-administering Pelgraz® PFI at home

How severe is you Wellness Close

ptom

Select your sym

Fatigue

Wellness Your next Pelgraz

®

Thu 11 July S h

Muscle or joint pain

Loss of appetite

Changes in libido & sexual function

ion

1-day

Nausea

pain

Allergic reaction

4

Download the Pelgraz® PFI App in the App store, or Google Play store, today 0

Mon 8

Tue 9

Wed 10

Thu 11

Fri 12

Sat 13

Sun 14

Hide

Entries

7

Mon 8 Jul

Always administe r Pelgraz® exactly as your doctor has told you to. The following instructio ns should act as a helpful remin der, der but if you are unsure 1 about anything you should check with your docto doct r or pharmacist.

session Last chemotherapy

Constipation

of hands or Numbing/tingling

2

tions

Itching or rash

Shortness of breath

6

Injection instruc

am

Vomiting

wing

8

10:15

and feet Swelling of hands

Difficulty swallo

10

5

Loss of appetite

Diarrhoea

3-day

7-day

14-day

Severity scale

Wed 10 July

Muscle or joint

Sun 7 Jul Mon 8 Jul

Self-inject supprration or t tool

5am th Wed 10 Jul at 10:1

feet

Don’t forget to keep

3

Mild

Pre-injection prepa

Edit your reminder

Fever or chills

Sore mouth

2

Preparation

® the fridge your Pelgraz in

Injecting the solut

Further symptoms

ion step-by-step

5

Tue 9 Jul

6

Wed 10 Jul

DASHBOARD

GUIDE

SER

MORE

Dashboard

Guide

SER

More

3

Fri 12 Jul DASHBOARD

GUIDE

SER

MORE

Use your smart phone to scan the QR code and be directed straight to the Pelgraz® PFI App

Pre-Filled Injector One Dose for ANC Recovery

Confidence, Convenience, Compliance ABBREVIATED PRESCRIBING INFORMATION Please refer to the Summary of Product Characteristics (SmPC) before prescribing Pelgraz▼(pegfilgrastim) 6 mg solution for injection in pre-filled syringe or prefilled injector. Presentation: Each pre-filled syringe or pre-filled injector contains 6 mg of pegfilgrastim* in 0.6 mL solution for injection. The concentration is 10 mg/mL based on protein only**. *Produced in Escherichia coli cells by recombinant DNA technology followed by conjugation with polyethylene glycol (PEG). ** The concentration is 20 mg/mL if the PEG moiety is included. Indications: Reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes). Dosage and Administration: Pelgraz therapy should be initiated and supervised by physicians experienced in oncology and/or haematology.

Posology: One 6 mg dose (a single pre-filled syringe or pre-filled injector) of Pelgraz is recommended for each chemotherapy cycle, given at least 24 hours after cytotoxic chemotherapy. Safety and efficacy of Pelgraz in children and adolescents has not yet been established and no recommendation on a posology can be made. No dose change is recommended in patients with renal impairment, including those with end-stage renal disease. Method of administration: Pelgraz is for subcutaneous use. The injections should be given subcutaneously into the thigh, abdomen or upper arm. See SmPC for instructions on handling of the medicinal product before administration.

Contraindications: Hypersensitivity to pegfilgrastim or any of the excipients in Pelgraz.

Warnings and precautions: To improve the traceability of biological medicinal products, the trade name of the administered product should be clearly recorded. The long-term effects of pegfilgrastim have not been established in acute myeloid leukaemia (AML); therefore, it should be used with caution in this patient population. Granulocytecolony stimulating factor (G-CSF) can promote growth of myeloid cells in vitro and similar effects may be seen on some non-myeloid cells in vitro. The safety and efficacy of pegfilgrastim have not been investigated in patients with myelodysplastic syndrome, chronic myelogenous leukaemia, and in patients with secondary AML; therefore, it should not be used in such patients. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from AML. The safety and efficacy of pegfilgrastim administration in de novo AML patients aged < 55 years with cytogenetics t(15;17) have not been established. The safety and efficacy of pegfilgrastim have not been investigated in patients receiving high dose chemotherapy. This medicinal product should not be used to increase the dose of cytotoxic chemotherapy beyond established dose regimens. Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported after G-CSF administration. Patients with a recent history of pulmonary infiltrates or pneumonia may be at higher risk. The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological signs of pulmonary infiltrates, and deterioration in pulmonary function along with increased neutrophil count may be preliminary signs of adult respiratory distress syndrome (ARDS). In such circumstances pegfilgrastim should be discontinued at the discretion of the physician and the appropriate treatment given. Glomerulonephritis has been reported in patients receiving filgrastim and pegfilgrastim. Generally, glomerulonephritis resolved after dose reduction

or withdrawal of filgrastim and pegfilgrastim. Urinalysis monitoring is recommended.

Capillary leak syndrome has been reported after G-CSF administration and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. Generally asymptomatic cases of splenomegaly and cases of splenic rupture, including some fatal cases, have been reported following administration of pegfilgrastim. Spleen size should be carefully monitored (e.g. clinical examination, ultrasound). A diagnosis of splenic rupture should be considered in patients reporting left upper abdominal pain or shoulder tip pain. Treatment with pegfilgrastim alone does not preclude thrombocytopenia and anaemia because full dose myelosuppressive chemotherapy is maintained on the prescribed schedule. Regular monitoring of platelet count and haematocrit is recommended. Special care should be taken when administering single or combination chemotherapeutic medicinal products which are known to cause severe thrombocytopenia. Pegfilgrastim in conjunction with chemotherapy and/or radiotherapy has been associated with development of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) in breast and lung cancer patients. Patients treated in these settings should be monitored for signs and symptoms of MDS/AML. Sickle cell crises have been associated with the use of pegfilgrastim in patients with sickle cell trait or sickle cell disease. Therefore, use caution when prescribing pegfilgrastim in patients with sickle cell trait or sickle cell disease, monitor appropriate clinical parameters and laboratory status and be attentive to the possible association of this medicinal product with splenic enlargement and vasoocclusive crisis. White blood cell (WBC) counts of 100 × 109/L or greater have been observed in less than 1% of patients receiving pegfilgrastim. No adverse reactions directly attributable to this degree of leukocytosis have been reported.

Such elevation in WBCs is transient, typically seen 24 to 48 hours after administration and is consistent with the pharmacodynamic effects of this medicinal product. Consistent with the clinical effects and the potential for leukocytosis, a WBC count should be performed at regular intervals during therapy. If leukocyte counts exceed 50 × 109/L after the expected nadir, this medicinal product should be discontinued immediately. Hypersensitivity, including anaphylactic reactions, have been reported with pegfilgrastim. Permanently discontinue pegfilgrastim in patients with clinically significant hypersensitivity. Do not administer pegfilgrastim to patients with a history of hypersensitivity to pegfilgrastim or filgrastim. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. Stevens-Johnson syndrome (SJS), which can be life-threatening or fatal, has been reported rarely in association with pegfilgrastim treatment. If the patient has developed SJS with the use of pegfilgrastim, treatment must not be restarted at any time. As with all therapeutic proteins, there is a potential for immunogenicity. Rates of generation of antibodies against pegfilgrastim is generally low.

Binding antibodies do occur as expected with all biologics; however, they have not been associated with neutralising activity at present. Aortitis has been reported after filgrastim or pegfilgrastim administration in healthy subjects and in cancer patients. The symptoms experienced included fever, abdominal pain, malaise, back pain and increased inflammatory markers (e.g. C-reactive protein and WBC count). In most cases aortitis was Associated member of:

Oncology & Haematology

www.accord-healthcare.ie

exhaus

th y Thursday 11 Jul

Fatigue

Chemotherapy sess Pelgraz dose

Feeling weary or

injection is due

diagnosed by CT scan and generally resolved after withdrawal of filgrastim or pegfilgrastim. The safety and efficacy of Pelgraz for the mobilisation of blood progenitor cells in patients or healthy donors has not been adequately evaluated. Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging findings. This should be considered when interpreting bone-imaging results. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. Pelgraz contains less than 1 mmol sodium (23 mg) per 6 mg dose, that is to say essentially ‘sodium-free’. The needle cover contains dry natural rubber (a derivative of latex), which may cause allergic reactions. Pregnancy and Lactation: Pegfilgrastim is not recommended during pregnancy and in women of childbearing potential not using contraception. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from pegfilgrastim therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman. Adverse Events include: Adverse events which could be considered serious include: Common: Thrombocytopenia. Uncommon: Myelodysplastic syndrome, acute myeloid leukaemia, sickle cell anaemia with crisis, capillary leak syndrome, glomerulonephritis, hypersensitivity reactions (including angioedema, dyspnoea, anaphylaxis), splenic rupture (including some fatal cases), Sweet’s syndrome (acute febrile neutrophilic dermatosis), pulmonary adverse reactions including interstitial pneumonia, pulmonary oedema and pulmonary fibrosis have been reported.

Uncommonly cases have resulted in respiratory failure or ARDS which may be fatal. Rare: Aortitis, pulmonary haemorrhage, Stevens-Johnson syndrome. Other Very Common adverse events: Headache, nausea, bone pain. Other Common adverse events: Leukocytosis, musculoskeletal pain (myalgia, arthralgia, pain in extremity, back pain, musculoskeletal pain, neck pain), injection site pain, non-cardiac chest pain. See SmPC for details of other adverse events. Shelf Life: 3 years. Store in a refrigerator (2∞C – 8∞C).

Pelgraz may be exposed to room temperature (not above 25°C ± 2°C) for a maximum single period of up to 72 hours. Pelgraz left at room temperature for more than 72 hours should be discarded. Do not freeze. Accidental exposure to freezing temperatures for a single period of less than 24 hours does not adversely affect the stability of Pelgraz. Keep the container in the outer carton in order to protect from light. Pack Size: One prefilled syringe or prefilled syringe injector with one alcohol swab, in a blistered packaging.

Marketing Authorisation Numbers: Pre-filled syringe: EU/1/18/1313/001, Prefilled injector: EU/1/18/1313/002. Marketing Authorisation Holder (MAH): Accord Healthcare S.L.U, World Trade Center, Moll de Barcelona, s/n, Edifici Est, 6a planta, Barcelona, 08039 Spain. Legal Category: POM. Full prescribing information including the SmPC is available on request from Accord Healthcare Ireland Ltd, Euro House, Little Island, Co. Cork, Tel: 021-4619040 or www.accord-healthcare.ie/products. Adverse reactions can be reported to Medical Information at Accord Healthcare Ltd. via E-mail: medinfo@accord-healthcare.com or Tel: +44(0)1271385257.

Date of Generation of API: May 2021. IE-01426

Adverse events should be reported. Reporting forms and information can be found on the HPRA website (www.hpra.ie), or by e-mailing medsafety@hpra.ie. Adverse events should also be reported to Medical Information via email; medinfo@accord-healthcare.com or tel:0044 (0) 1271 385257

July 2021. IE-01663

4

5

Mo

12

Antimicrobial

Surgical Antibiotic Prophylaxis Duration Written by Marie Philbin, Chief Antimicrobial Pharmacist, National Antimicrobial Resistance and Infection Control Team

showed that prophylaxis exceeded a single dose in 62% of patients.

For comparison, a 2017 European study performed in Scotland demonstrated that only 35% of patients received more than a single dose of antibiotic for prophylaxis. This suggests there is scope for quality improvement.

Continuing an antibiotic beyond the recommended duration postsurgery does not further reduce SSI. In fact, extended duration of surgical antibiotic prophylaxis is associated with increases in acute kidney injury and Clostridioides difficile infection.

infection at the surgical site.

Surgical antibiotic prophylaxis plays an important role in reducing the rate of surgical site infections (SSI). Optimisation of prophylaxis requires an understanding of its role, agent, dose, timing of administration and duration.

It should be noted that many other non-antibiotic factors and practices, such as infection prevention and control strategies, surgical technique and preoperative preparation and management, can also influence the rate of SSI. Maximising benefit of surgical antibiotic prophylaxis A position statement on duration of surgical antibiotic prophylaxis has recently been published by the HSE. This was developed by the HSE Antimicrobial Resistance and Infection Control Team (AMRIC), the HSE Antimicrobial Stewardship Advisory Group & the National Clinical Programme for Surgery (NCPS). Other HSE national clinical programmes and the postgraduate training bodies for surgery, anaesthesia and obstetrics also provided valuable feedback in the joint development of this document. The extensive process of consultation means this document represents a consensus opinion of experts in this field in Ireland and is supported by all the key stakeholders.

What is surgical antibiotic prophylaxis?

Surgical antibiotic prophylaxis refers to the planned administration of antibiotics to a patient without a confirmed or suspected infection in order to reduce the risk of post-operative

Surgical antibiotic prophylaxis is a critical step in preventing SSI. The maximum benefit with the least harm is gained by administering an appropriate agent at the right time and for the right duration.

Giving an antibiotic for longer than is needed does not reduce the risk of infection and does increase the risk of harm.

Unnecessary antibiotic use is a major driver in the emergence of antimicrobial resistance.

Antibiotic use helps infectious microorganisms that are resistant to antibiotics to colonise and multiply. A shift to more resistant microorganisms occurs quickly after someone starts on antibiotics. This means that if the person develops infection after surgery the infection may be harder to treat.

The primary drive for this initiative is to reduce the risk of patient harm from unnecessary doses of preventative antibiotics around the time of surgery.

Surgical antibiotic prophylaxis duration

Evidence shows that the majority of patients need just one preoperative dose of antibiotic to prevent SSI. An Irish audit in September and October 2020

clinically indicated duration of antibiotic prophylaxis for a particular surgical procedure. The position statement outlines that for most procedures, the standard of a single dose within 60 minutes prior to incision is applicable.

An additional intra-operative dose may be required in certain circumstances such as significant blood loss or if the procedure duration extends beyond three or four hours of the initial dose (timing will depend on the half-life of the antibiotic).

For a smaller number of procedures, a duration of 24 or 48 hours can be justified given uncertainty of current evidence and differences in expert opinion.

However, locally agreed maximum durations may be less.

There is no evidence to support prophylaxis longer than 48 hours for any surgical procedure. This applies equally to antibiotic administered by parenteral or oral route. It should be noted that antibiotic prophylaxis should not be continued beyond the limits specified even if drains remain in place.

It is important to recognise that treatment is not the same as prophylaxis. When an infection is suspected or confirmed prior, during or after a surgical procedure, then the model of antibiotic prophylaxis no longer applies. Infection requires treatment, not prophylaxis.

The right agent and duration of treatment should be based on relevant therapeutic guidelines and/or advice from an infection specialist, for example, a clinical microbiologist or infectious disease physician.

Resources to support quality improvement

The position statement is intended to represent clear recommendations, supported by evidence and the broadest possible consensus of expert opinion in Ireland, regarding generally accepted maximum durations of surgical antibiotic prophylaxis for different types of surgery.

Most procedures do not require post-operative antibiotics. The right duration is the maximum,

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

A collaborative group, from the NCPS and AMRIC, has developed resources to support the implementation of this position statement, including: • An Excel audit tool to be used as part of a quality improvement project, and a YouTube video explaining its use.

• A PowerPoint presentation that can be used for local delivery.

• An eLearning module on all aspects of surgical antibiotic

Antimicrobial 13 prophylaxis including “the right duration” is available on HSeLanD aimed at anyone who prescribes, dispenses or administers surgical antibiotic prophylaxis.

• A3 posters and pens with key messaging which have been distributed to hospital Antimicrobial Pharmacists across the country

• A patient information leaflet entitled “Antibiotics before an operation to reduce risk of infection”.

Resources, unless otherwise specified, are available on at this link: bit.ly/3eGoCKw at www.antibioticprescribing.ie The position statement, alongside the suite of support resources, is

seen as a valuable tool to support best practice across the acute hospital setting and provides a nationally agreed platform for quality improvement The HSE Antimicrobial Resistance and Infection Control (AMRIC) team was established to ensure that the control of healthcare associated infection and antimicrobial resistance are pillars

that our health services are built on. The AMRIC team provide guidance and operational support to HSE in relation to antimicrobial stewardship and infection control by supporting the work of the HSE AMRIC Implementation Team and AMRIC HSE Oversight group.

News New Drug Research on Secondary Breast Cancer A new study led by RCSI University of Medicine and Health Sciences will explore if the drug talazoparib (Talzenna) could be used to treat people with incurable secondary (metastatic) breast cancer which has spread to the brain.

Dr Damir Vareslija and Professor Leonie Young, Department of Surgery, RCSI University of Medicine and Health Sciences (Photo taken in 2019)

The study, funded by Breast Cancer Now, is led by Professor Leonie Young and Dr Damir Vareslija whose team will investigate if the drug could be used to treat secondary breast cancer in the brain.

Secondary breast cancer occurs when breast cancer cells spread from a primary tumour in the breast, through the lymphatic or blood system to other parts of the body where it becomes incurable.

There are limited treatment options for people with breast cancer that has spread to the brain and a lot of drugs are unable to reach these tumours because of the brain's natural protection, meaning new treatment discoveries are urgently needed.

Talazoparib is an existing PARP inhibitor drug which works by preventing cancer cells with altered BRCA genes from repairing their DNA, forcing them to die.

Through previous research, which analysed tumour samples donated by people whose breast cancer has spread to the brain, the team established that almost half of the tumours had changes in the way they repair their DNA and this could make these tumours vulnerable to PARP inhibitors like talazoparib.

Using tumours and breast cancer cells donated by patients, researchers will now test in the lab if talazoparib is effective in treating secondary breast cancer in the brain. The researchers aim to identify key features of a tumour that responds to this type of treatment to establish who could benefit most.

Professor Leonie Young, Professor in the Department of Surgery at RCSI University of Medicine and Health Sciences, says, "Our previous research has shown that, in many cases, secondary breast cancer tumours in the brain have changes in the way they repair their DNA and we believe this could make them vulnerable to PARP inhibitor drugs like talazoparib.

"People are always at the heart of the research we do and we are always trying to answer questions

that are important to our patients.

The support of Breast Cancer Now will enable us to learn more about the effectiveness of these powerful drugs to hopefully treat people with secondary breast cancer which has spread to the brain in the future."

Professor Fergal O'Brien, Director of Research and Innovation at RCSI, congratulated Professor Young and Dr Vareslija on their project: "This study exemplifies the high quality translational cancer research at RCSI which is attracting prestigious international funding to help address the pressing clinical need for new treatment strategies for advanced cancer."

The study is funded by the Breast Cancer Now Catalyst Programme, which aims to accelerate progress in world-class breast cancer research through innovation

and collaboration. As part of the Programme, Pfizer have provided Breast Cancer Now with an independent medical research grant and given the charity's researchers access to several Pfizer medicines.

Commenting on the secondary breast cancer study, Dr Simon Vincent, Director of Research, Support and Influencing at Breast Cancer Now, said: "We desperately need to discover new ways to treat this incurable disease, including for those whose breast cancer has spread to the brain and who have very limited treatment options. That's why we're delighted to announce that we're funding Professor Young's project through The Breast Cancer Now Catalyst Programme. We hope this study will be successful and lead to effective new treatments for those who badly need them."

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

End of Year: IPHA Lessons Learned from Covid The pandemic should renew our trust in science for better health, writes Bernard Mallee Covid-19 has taught us many lessons, most of them harrowing.

More than five million people globally have died. The true mortality rate is likely to be much higher. Every day, the path of the pandemic looks increasingly likely to hinge on vaccinations - how many of us, wherever we live, can get protected against serious illness and death and how fast that happen. On their own, vaccines for Covid-19 won’t be enough to stop the disease. They need to be allied with responsible behaviours like social distancing, mask-wearing, hand-washing and cough etiquette.

In Ireland, the vaccination rate for Covid-19 is among the highest in the world. Vaccine-hesitancy is among the lowest. It wasn’t always that way. In January, one in four people said they either wouldn’t get vaccinated for Covid-19 or they weren’t sure. That figure has since dropped to well below 10%.

Vaccination has been among the best public health interventions ever. It has eliminated smallpox, rubella and measles, among other diseases.

Covid-19 has taught us other lessons, especially about science. The world needs more collaboration, not less, in the discovery and development of vaccines and medicines to prevent and treat diseases. We need a policy ecosystem that generates greater investment in biopharmaceutical research and development, and encourages scientific collaboration among private companies, public agencies and academic institutions.

In Ireland, our research shows that the biopharmaceutical industry is considered favourably by the public. The role of biopharmaceutical innovation in finding answers for health challenges, and in creating jobs across the regions, is well acknowledged. In recent months, we put on screen this story of

economic and social value creation through a film-led campaign called Innovate For Life.

Along with partners Amgen, Lilly, Novo Nordisk and LEO Pharma, we created a series of minidocumentary films that captured the human experience of disease and hope through science. We explored four therapy areas dementia, heart, obesity and skin.

How many of us know someone who has been affected by dementia? Alzheimer's disease, a progressive, degenerative condition that affects the brain, is the most common form of dementia. Dementia affects some 64,000 people in Ireland. So far, there is no cure.

What about cardiovascular diseases which account for 36% of all deaths in Ireland? About 10,000 people in Ireland die annually from cardiovascular diseases. Globally, almost 18 million people die from cardiovascular diseases every year.

Obesity, too, is a big problem, in Ireland and globally. About 60% of Ireland's population lives with overweight or obesity. Within a decade, the proportion of men in Ireland living with overweight and obesity will rise to 89%.

For women, the figure is 85%.

There are strong correlations between obesity and higher rates of mortality.

know someone for whom daily living is a struggle. Skin conditions affect people physically and emotionally. Between 15% and 20% of GP consultations specifically relate to the skin.

These stories are hard but, in them, there is hope. Often, we can prevent or manage medical conditions through lifestyle changes like better exercise, healthier diet and more sleep.

But medical interventions can be transformational, too. Between 1994 and 2013, five-year net survival rates for cancer increased from 40% to 61% for men and from 38% to 60% for women.

Between 2008 and 2018, the mortality rate for heart attacks dropped 51%. The mortality rate for stroke fell 34%. Medicines made a major contribution to these gains.

Rare conditions, many of them making our children sick, are more treatable now than ever. In the past 20 years, the European Medicines Agency has approved more than 190 new orphan medicines.

Although all of this sounds like progress, we have a long way to go. We need to get faster at making the latest medicines available to patients in Ireland. We need to conduct far more clinical trials in our laboratories and build

With one in three people in Ireland suffering from skin disease or disorder, many of us probably

Featuring in IPHA’s Innovate for Life campaign is Zoe Ryan

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

a health data infrastructure that measures health outcomes. We need to find ways to attract new investments in cell and gene therapies across supply chain and manufacturing, and understand how best to adopt these new treatments at scale and pace in our health services.

We need to prepare for tomorrow’s treatments and cures with newly skilled human capital and digitalised manufacturing processes. We need to make the research ecosystem work for unmet medical needs, turning Ireland into a place where breakthroughs in science can both start and scale. We need to protect intellectual property rights as the scaffolding for medicines innovation.

Above all, we need to place our trust in science in the battle against cancer, heart disease and many other chronic conditions.

We need to arm ourselves against future global health crises.

All of this is possible through partnership. Out of Covid-19, let us resolve to work more as a community to solve the problems that affect us all.

Bernard Mallee is Director of Communications and Advocacy at the Irish Pharmaceutical Healthcare Association.

TOGETHER. LONGER. Superior 5-year Overall Survival vs. DA 3+71 In patients with AML-MRC and t-AML1 Who were fit for IC¹ Regardless of their HSCT eligibility1,2 Similar safety profile with prolonged myelosuppression vs. DA 3+73

For more data and a wealth of educational resources, visit www.vyxeos.co.uk or scan the QR code

6

5

4

In AML-MRC and t-AML, consider Vyxeos Liposomal first

Prescribing Information Vyxeos® Liposomal 44mg/100mg powder for concentrate for solution for infusion (daunorubicin and cytarabine) Please refer to the Summary of Product Characteristics before prescribing.

Presentation: Purple lyophilised cake of powder for concentrate for solution for infusion. Each vial contains 44 mg of daunorubicin and 100 mg of cytarabine. After reconstitution the solution contains 2.2 mg/mL daunorubicin and 5 mg/mL cytarabine encapsulated in liposomes in a fixed combination in a 1:5 molar ratio. Indication: For the treatment of adults with newly diagnosed, therapy-related acute myeloid leukaemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Dosage and administration: FOR INTRAVENOUS USE ONLY. An in-line membrane filter may be used provided the minimum pore diameter of the filter is greater than or equal to 15 μm. It must not be administered via an intramuscular, intrathecal, or subcutaneous route. Refer to the full SmPC for detailed information on preparation of solution for infusion. Treatment should be initiated and monitored under the supervision of a physician experienced in the use of chemotherapeutic medicines. Recommended dosing schedule for induction of remission: 44 mg/100 mg/m2, administered intravenously over 90 minutes on days 1, 3, and 5 as the first course of induction therapy; then on days 1 and 3 as subsequent course of induction therapy, if needed. Recommended dosing schedule for consolidation: The first consolidation cycle should be administered 5 to 8 weeks after the start of the last induction. The recommended dosing schedule is 29 mg/65 mg/m2, administered intravenously over 90 minutes on days 1 and 3 as subsequent courses of consolidation therapy, if needed. Dose adjustments during treatment may be required in hypersensitivity symptoms and cardiotoxicity. Assessment of cardiac function prior to start of treatment is recommended. Renal impairment: Dose adjustment is not required for patients with mild (creatinine clearance [CrCL] 60 - 89 mL/min by Cockcroft Gault equation [C-G]) or moderate (CrCL 30 - 59 mL/min) renal impairment. There is no experience in patients with severe renal impairment (CrCL 15 - 29 mL/min) or endstage renal disease. It should only be used in patients with severe renal impairment if the benefits outweigh the risks. Hepatic impairment: Dose adjustment is not required for patients with a bilirubin ≤50 μmol/L. There is no experience in patients with hepatic impairment resulting in a bilirubin level >50 μmol/L. It should only be used in patients with severe hepatic impairment if the benefits outweigh the risks. Elderly population (≥65 years): No dose adjustment is required. Paediatric population: The safety and efficacy in children aged 0–18 years has not yet been established. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings, precautions and interactions: Do not substitute or interchange with other daunorubicin and/or cytarabine-containing products. Severe myelosuppression and serious or fatal haemorrhagic events have been reported. Due to the long plasma half-life of Vyxeos liposomal, time to recovery of ANC and platelets may be prolonged and require additional monitoring. Prophylactic anti-infectives may be administered during the period of profound neutropenia until ANC returns to ≥500/μL. If myelosuppressive complications occur, appropriate supportive measures should be used. Blood counts should be regularly monitored until recovery. As cardiotoxicity is a known risk, prior therapy with anthracyclines, pre-existing cardiac disease, previous radiotherapy of the mediastinum, or concomitant use of cardiotoxic products may increase the risk. Hepatotoxic medicinal products may impair liver function and increase toxicity. Evaluation of hepatic and renal function is recommended prior to administration and periodically during treatment.

Blood uric acid levels should be monitored and appropriate therapy initiated if hyperuricemia develops. Each vial contains 100 mg of copper gluconate. It should only be used in patients with a history of Wilson’s disease or other copper-related disorder if the benefits outweigh the risks. To avoid local tissue necrosis care should be taken to ensure that there is no extravasation of Vyxeos liposomal during administration. Administration of live or live-attenuated vaccines should be avoided. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.

The absorption of oral accompanying medicinal products may be considerably influenced by gastrointestinal mucositis and/ or diarrhoea frequently occurring in association with intensive chemotherapy. Effect on ability to drive and use machines; Minor influence, fatigue and dizziness reported, caution is advised. Pregnancy, lactation and fertility: There are no data on use in pregnant women. It should not be used during pregnancy unless the benefit of treatment outweighs the risk. It is not known if Vyxeos liposomal is excreted in human milk therefore mothers should be advised to discontinue breastfeeding during therapy. Patients should be advised to avoid becoming pregnant while receiving Vyxeos liposomal.

Male patients and women of childbearing potential must use an effective method of contraception during treatment and for 6 months following the last dose. Male fertility may be compromised by treatment. Undesirable effects: Please refer to the full SmPC for the complete list of undesirable effects. The most frequently occurring adverse reactions were hypersensitivity, febrile neutropenia, oedema, diarrhoea/colitis, mucositis, fatigue, musculoskeletal pain, abdominal pain, decreased appetite, cough, headache, chills, arrhythmia, pyrexia, sleep disorders, and hypotension. The most serious and frequently occurring ADRs were infection, cardiotoxicity and haemorrhage. Overdose: There is no specific antidote for overdose and treatment should be symptomatic. Storage and Handling: Store in a refrigerator (2°C - 8°C). Shelf life of unopened vials: 2 years. Keep vial in the original carton to protect from light and store in an upright position. Vyxeos liposomal is a cytotoxic medicinal product intended for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic agents. Legal category: POM. Marketing authorisation number: EU/1/18/1308/001. Package quantity and Cost: 1 × 50 mL vial. UK: £4581 per vial. IE: Price on Application. Marketing Further information is available from the Marketing Authorisation Holder: Jazz Pharmaceuticals Ireland, 5th Floor, Waterloo Exchange, Waterloo Road, Dublin D04 E5W7, Ireland. Date of preparation: February 2021.

Job Code: UK-VYX-2100042. Vyxeos® is a registered trade mark.

Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse reactions. For the UK, reporting forms and information can be found at: www.mhra.gov.uk/yellowcard For Ireland, reporting forms and information can be found at: www.hpra.ie Adverse events should also be reported by email: AEreporting@jazzpharma.com References: 1. Lancet JE, et al. E-poster EP556. EHA25 Virtual Congress 2020. 2. Lin TL, et al. E-poster EP562. EHA25 Virtual Congress 2020. 3. Lancet JE, et al. J Clin Oncol 2018;36(26):2684–2692. 4. National Institute for Health and Care Excellence. Technology Appraisal Guidance [TA552]. December 2018. 5. Scottish Medicines Consortium. SMC2130.

March 2019. 6. Health Service Executive. Regimen code 00613a. February 2021 Abbreviations: AML-MRC, acute myeloid leukaemia with myelodysplasia-related changes; DA, daunorubicin/cytarabine; HSCT, haematopoietic stem-cell transplantation; HSE, Health Service Executive; IC, intensive chemotherapy; NICE, National Institute for Health and Care Excellence; SMC, Scottish Medicines Consortium; t-AML, therapy-related AML

August 2021 | IE-VYX-2100019

End of Year: Thrombosis Ireland

A Year in Review Written by Ann Marie O’Neill, CEO, Thrombosis Ireland

It has been the busiest year in the history of Thrombosis Ireland. The worry of Covid-19 and the different vaccines has caused confusion and so much added anxiety and fear among thrombosis patients, their families & carers. We have worked hard to ensure that everyone had access to the latest guidelines and recommendations from the National Coagulation Centre, St. James Hospital, so that they could make correct and informed decisions for themselves.

Our phone lines remained open, VTE education sessions with healthcare professionals and patients/families continued throughout the year but were moved online. Our continued effort to reach every household in the country in 2020-2021 with our VTE National awareness advertising campaigns on television, national radio, local radio, digital media and all social media platforms, was a great success, reaching millions of Irish citizens with our life saving message but we are acutely aware that there is so much more to to.

(VTE). 60% of all blood clots happen as a direct result of a hospital stay or in the 90 days post discharge.

Thrombosis refers to abnormal, life-threatening blood clots that form in the artery or vein. A clot in the vein (usually in the leg or pelvis) is known as a deep vein thrombosis (DVT) and a clot that breaks off and travels to the lungs is known as a pulmonary embolism (PE). Together, DVT and PE make up venous thromboembolism

Thrombosis patients frequently report that they were unaware of the signs and symptoms of VTE prior to their diagnosis and were not aware of their own level of risk. This has been reported, particularly in the setting of patients with cancer. The risk of thrombosis is significantly elevated in this population and VTE is

The devastating impact of VTE cannot be over-stated. We frequently encounter patients who have survived a life-altering thrombotic event, but are left with significant physical, psychological and emotional burdens. More-over, despite advances in care, many people who experience VTE do not survive. It is alarming to note that VTE remains a leading cause of death for hospitalized patients, it is the leading cause of death in cancer patients, after the cancer itself and the No.1 cause of direct maternal death in our maternity hospitals. It is also disappointing to learn that many VTE related deaths are potentially preventable but that opportunities to identify high-risk individuals and to implement preventative measures, such as VTE risk assessment of all patients and pharmacological thromboprophylaxis, are frequently missed.

recognised as being the second leading cause of death among patients with cancer, second only to cancer progression itself.

Efforts to improve awareness of thrombosis risk in this patient group but also among others including pregnant women and hospitalised patients must be prioritised in order to avoid any unnecessary delays in obtaining a diagnosis and initiating potentially life-saving treatment. Efforts to ensure that healthcare providers are continually reminded of the risk of thrombosis must also be made in our hospitals and in community practice/primary care.

high levels of achievement in a number of key areas and are intended to showcase outstanding individuals and hospital teams/ hospital groups who have excelled in areas such as leadership & education, quality improvement, research & innovation and patient safety.

However, in recent years, significant advances have been made in the field of VTE and Thrombosis Ireland are proud to support the efforts being made by hospitals and many of our healthcare providers to improve the quality of VTE prevention and treatment in this country.

In recognition of these efforts, Thrombosis Ireland launched our inaugural VTE Exemplar Awards 2021. These awards celebrated

• VTE Best Hospital Award

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

The entry categories: • VTE Scientific Advancement Award Maternity Hospital/Acute Hospital • VTE Quality Improvement Award Maternity Hospital/Acute Hospital

• VTE Best Hospital Group Award • VTE National Champion Award We are delighted to announce the winners in each category 2021 VTE Scientific Advancement Award in our Maternity Hospitals was awarded to Prof. Brian Cleary, Chief Pharmacist & Dr. Jennifer Donnelly,

Consultant Obstetrician and their multidisciplinary team in The Rotunda Hospital, Dublin. Brian & Jennifer and their multidisciplinary team, developed an electronic risk assessment tool called Thrombocalc, which calculates a simple risk score and makes recommendations on thromboprophylaxis based on each woman’s VTE risk factors.

Through collaborative research and quality improvement, Thrombocalc was embedded in routine care in the Rotunda Hospital, leading to increased compliance with VTE risk assessment, appropriate prevention and a trend to reducing the number of blood clots.

2021 VTE Quality Improvement in our Maternity Hospitals was awarded to Sile Gill, ADON and Dr. Samah Hassan and the maternity team in Mayo University Maternity Hospital.

Sile & Samah led a QI program to monitor the hospitals practice regarding VTE prophylaxis in mothers and to implement measures to increase compliance.

The introduction of a specially designed preforma, visual aids for staff and mothers ‘Do you know your VTE Score?’ and education sessions for doctors and nurses.

The service was audited in January and then July 2021 and showed a huge increase in compliance with VTE Risk Assessment.

2021 VTE Scientific Advancement Award in our Acute Hospitals was awarded to Ireland East Hospital Group, VTE Service Review Working Group, with particular acknowledgement to the work of Mick Fitzpatrick for their VTE Incidence Data Dashboard. Developed in 2018, the VTE dashboard shows VTE incidents and burden of Hospital Acquired Thrombosis. This gives real-time VTE incidence patterns, which is crucial to VTE improvement, service provisions and advancement of clinical research. It is the first of its kind in Ireland and inpatient episodes are extracted, processed and uploaded for analysis.

Management and teams at group and hospital level, now have line of sight of VTE activity, raising VTE awareness and local initiatives.

2021 VTE Quality Improvement Award in our Acute Hospitals was awarded to St. Vincents Private Hospital Clinical Pharmacy Team for their VTE Prophylaxis Dashboard. Using the Meg audit tools, an app was developed with the help of VTE Ireland, Prof. Fionnuala Ni Ainle, Dr. Barry Kevane & Dr. Tomas Breslin to audit VTE Prophylaxis efficiently. This App has enabled SVPH to develop a quality of service and improve patient safety. It identifies areas that are underperforming and areas that continue to improve. Auditing of VTE prophylaxis is reported in real time and can be acted on immediately. The long-term vision is that it would be used in all Irish hospitals and that all data would be collected into a National System.

2021 VTE Best Hospital was awarded to Limerick University Hospital. This hospital DVT nurse led service was set up in 2019 with referrals from ED or directly from GP’s. It has a 98% patient satisfaction rating. Out of 2100 patients seen to date only 2% have been admitted and 78% are discharged from clinic within 2-4 hours. In 2020 a virtual nurse-led clinic was set up to review and discharge patients with superficial thrombophlebitis, reducing attendance to the anticoagulation clinic. They have ongoing education of staff, patients and public in prevention and treatment of VTE. There are plans to set up a stand-alone Thrombosis Unit with a Warfarin Clinic & DVT and low risk PE management clinic.

This will include an initiative surrounding the psychological impact of VTE on patient’s health and well-being.

2021 Best Hospital Group was awarded to Ireland East Hospital Group. IEHG comprises 11 hospitals and cover greater than 1,000,000 people. This group

demonstrates above others its commitment to the provision of VTE excellence. Their focus is to promote evidence based care pathways for prevention of, diagnosis of and treatment of VTE and to harmonise pathways across hospitals with a Patient/ HCP collaborative approach.

They are the first group nationally to determine VTE incidents and the burden of hospital acquired thrombosis events within their hospital.

VTE Working Group in Our Lady’s Hospital, Navan, this team have managed to:-

Thrombosis Ireland also wanted to honour the following VTE Warriors for their commitment on a daily basis, to ensure their patients receive optimal safe care and education in a truly compassionate and holistic way. This kind of care aids both physical and psychological recovery.

• Electronic prompt for Wells Score when ordering ultrasound, Doppler/CTPA

• 2021 VTE Warrior in our Maternity Hospitals was awarded to Jacinta Byrne, CNMS, National Maternity Hospital.

• 2021 VTE Warrior, Catriona O’Leary, CNS Anticoagulation Services and cANP at Cork University Hospital.

• 2021 VTE Warrior, Sarah Garvey, ANP, Emergency Department, Beaumont Hospital, Dublin.

• 2021 VTE Warrior, Ciara Kirke, Clinical Lead, National Medication Safety Program, HSE. • 2021 VTE Warrior, Niamh O’Hanlon, Chief II Pharmacist, St. Vincents University Hospital, Dublin.

• 2021 VTE Team Warriors, Prof. Fionnuala Ni Ainle & Dr. Barry Kevane, Consultant Haematologists, The Mater Misericordiae University Hospital, Dublin.

2021 VTE National Champions was awarded to Dr. Su Maung & her exceptional VTE Working Group in Our Lady’s Hospital, Navan, Co. Meath. In the three years since the formation of the

• Implement VTE Risk Assessment and appropriate prophylaxis for all patients.

• Prospective data collection and incidence reporting for HAT • Guidelines for management of superficial thrombophlebitis • DVT diagnostic pathway & nurse led DOAC Clinic.

• Ongoing staff & Patient education • Plans to set up VTE Patient support group Congratulations to all our award winners. We look forward to many more 2022 nominations when the competitions open next April.

Thrombosis Ireland continue to advocate for a National VTE Clinical Program. VTE patients deserve a fully funded, clear, streamlined pathway through diagnosis, treatment and recovery no matter what hospital they attend, to ensure the best possible outcome. Mandatory VTE risk assessment for all patient will save lives. Every patient should be informed of their risk, the signs and symptoms of blood clots and the importance of getting medical attention fast. This is particularly important when they are being discharged from hospital, as they are still at increased risk of thrombosis for a further 90 days. Blood clots are preventable in many cases and treatable if diagnosed in a timely manner but potentially fatal if ignored.

Preventable death from VTE is not and never will be acceptable.

Continuous education of healthcare professionals is crucial to VTE Patient Safety. It is a matter of life and death.

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

End of Year: Irish Cancer Society Strong Focus in Catching Undetected Cancer Written by Ciarán D'Arcy, Communications Officer, Irish Cancer Society

The dual threats of Covid and the HSE cyberattack meant that 2021 was a particularly challenging year for cancer care, and one in which the Irish Cancer Society dedicated a resultant strong focus on catching cancers that may have gone undetected during the pandemic.

Research carried out on behalf of the Society in May of this year found that 1 in 6 people were choosing not to attend a GP with health concerns amid the ongoing uncertainty caused by the pandemic, prompting concern in relation to symptomatic potential cancer cases.

In response to this the Society rolled out a series of early detection campaigns to encourage anyone with cancer symptoms to see their doctor, utilising the heightened focus associated with high-profile awareness events for a range of malignancies including lung, breast, bowel and skin cancers to connect with members of the public about their health concerns and signpost them for help.

These efforts culminated in the Society’s first-ever Your Health Matters early detection roadshow visiting shopping centres around

the country from September, offering free health checks and providing information on cancer symptoms, how they can be recognised and what to do if someone has a health worry.

Beyond the importance of physical wellbeing, we are also acutely aware of the great emotional hardship visited on cancer patients over the course of a turbulent and unpredictable year.

Thanks to the generosity of public support for the second annual Daffodil Day in a row where our fundraisers could not be on the streets we were able to redouble our efforts to attempt to meet this new level of need, dedicating a record ¤800k in funding to provide access to free counselling sessions both on an in-person and a remote basis for anyone affected by cancer in 2021.

The success of Daffodil Day also allowed the Society to substantially increase its funding to Cancer Trials Ireland to a total of ¤1m in 2021, with further attention being drawn to the challenges faced by cancer researchers with clinical trials activity falling by almost half during the height of Covid disruption.

Our nurses continued to provide helpful information, advice and support to those impacted by cancer both through our Freephone 1800 200 700 Support Line, our Daffodil Centres and our end-of-life Night Nursing service, and we were able to welcome back many of our dedicated Volunteer Drivers who were forced to cocoon during the pandemic as they once again took up the mantle to transport cancer patients to treatment sessions.

The Society’s Decoding Cancer podcast returned for a second series this year to help answer the public’s big cancer questions, with clinicians, patients and survivors joining host and Irish Cancer Society Director of Research Dr Robert O’Connor to discuss a diverse set of topics such as exercise, nutrition and cancer, Ireland’s proud contribution to global cancer research breakthroughs, and what cancer advice is trustworthy.

In addition to the practical support provided by our services we were delighted to partner in the launch of a new one-stopshop online resource for reliable, relevant and evidence-based information on gynaecological cancers on ThisIsGo.ie.

The Clinician Research Leadership Award scheme aimed at protecting dedicated research time for clinicians is going from strength to strength with consultant plastic and reconstructive surgeon and researcher Dr Shirley Potter and consultant medical oncologist Dr Dearbhaile Collins selected to advance projects focusing on melanoma and lung cancer in 2021.

The platform, which was developed in association with the Irish Cancer Society Women’s Health Initiative by consultant gynaecological oncologist Prof Donal Brennan and psychotherapist Yvonne O’Meara, features over 130 different articles, videos and audio content covering every stage of cancer diagnosis, treatment, and life with and after cancer through a personalised experience tailored to the stage and needs of individual users, including a specific section for partners of women who have or have had cervical cancer.

We were delighted to be able to offer a range of extended supports for the families of children, adolescents and young adults who have been dealt a cancer diagnosis in 2021 including increasing our Children’s Fund grant to ¤3k and making it easier to access so that more families can be supported through treatment, and the introduction of a funded nurse liaison post in Children’s Health Ireland Crumlin.

We are also looking forward to extending our Volunteer Driver Service specifically for children to start in the Greater Dublin Area on an initial pilot basis from early next year.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Our advocacy work continued apace with a series of reports focusing on waiting lists for cancer genetic services, the issues that cancer patients and survivors face in returning to work, and costs associated with a diagnosis of childhood cancer for families.

We also heard an update from the Childhood Cancer Fertility Project in which we are partnered with the Merrion Fertility Clinic that a total of 17 young people were assisted with fertility preservation over the course of the project’s first year.

All the while our commitment to helping cancer patients navigate their way through a troubling and at times traumatic period caused by the pandemic and the fallout from the cyberattack remains steadfast, and as we hope and prepare for better times ahead for our cancer community we continue to encourage anyone in need of help, advice or even just a listening ear to get in touch with our Support Line on 1800 200 700 and SupportLine@IrishCancer.ie.

End of Year: HPRA Excelling in Health Product Regulation Written by Dr Lorraine Nolan, Chief Executive, Health Products Regulatory Authority

The Covid-19 pandemic continued to affect every facet of life in Ireland, and around the world, during the last year.

Unfortunately, we are all too well aware of the awful effects and devastation caused by Covid-19.

As the scale of the impact of the pandemic became clear, we witnessed a direct and almost instant response from the global scientific community.

We have gone from the emergence of an unknown infectious disease at the end of 2019, to the development of safe and effective vaccines and therapeutics within a year, with billions of doses administered across the globe.

That is phenomenal progress, and could only have been achieved by the incredible dedication of so many key stakeholders, including biomedical researchers, medicines regulators, the pharmaceutical industry and indeed clinical trial volunteers, whose role is sometimes

forgotten. The HPRA was an active participant in this global response, both through our work at the EMA and our contribution to international efforts to coordinate and streamline regulatory processes and decision-making.

Of course, the development of safe and effective vaccines is only part of the process; we still needed an efficient and agile national Covid-19 vaccination strategy to facilitate the rollout of vaccines that would substantially reduce the impact of the pandemic when combined with non-pharmaceutical interventions.

As vaccine supply volumes increased throughout the year, additional capacity was required to facilitate our national vaccination campaign. Thanks to the incredible efforts of GP clinics and community pharmacies around the country, in addition to our network of vaccination centres, our ability to administer life-saving doses was only ever limited by supply. Community

pharmacies began administering Covid-19 vaccines in June 2021, initially providing Janssen vaccines for people aged 50 and over and then facilitating an “opt-in” model for those in the 18-34 year-old age-group. With over 1,000 pharmacies nationwide providing broad geographic coverage, it enabled Ireland to achieve some of the highest rates of vaccine coverage across the world.

This incredible public health response could only be achieved by the efforts of everyone across the entire healthcare system working together to protect our communities.

From a regulatory perspective, the role of the HPRA did not stop with the authorisation of Covid-19 vaccines. As expected with a nationwide vaccination campaign of this magnitude, there has been an associated increase in the volume of suspected adverse reactions reports.

As far back as December 2020, the HPRA encouraged everyone, including healthcare professionals and members of the public, to report suspected side effects following vaccination.

Again, healthcare professionals, including pharmacists across Ireland, have answered that call through their continued safety reporting. This valuable contribution has helped ensure the close monitoring of the benefit-risk profile for each vaccine, which, in turn, enables regulators take any necessary action to ensure their continued safety. As we go through the winter flu season and the rollout of booster doses of Covid-19 vaccines, we again ask everyone involved to continue their efforts in reporting any suspected sideeffects following vaccination to the HPRA. During 2021, Brexit and the pandemic continued to present challenges to the medicine supply chain. While, in the

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

Lm/gm 52 dexertemeP End of Year: HPRA continued main, lower shortages were observed in the aftermath of the Brexit transition period, there were still some challenging developments, including for time-sensitive products. However, meaningful interaction between all stakeholders, such as the Department of Health, regulators, the HSE, the pharmaceutical industry and healthcare professionals, in preparation for Brexit, helped to mitigate the impact of these supply challenges.

The pandemic continued to influence the use and supply of medicines, often in unpredictable ways. As a result, the HPRA is committed to continued, sustained and closer cooperation with all stakeholders involved in the shortages framework.

To this end, the HPRA began stakeholder engagements to actualise shortage prevention and mitigation strategies to ensure the continued availability of medicines to patients.

We are now at the end of the first year of our new strategic plan to 2025. Reviewing our five strategic goals, namely, health system partnership, progressive regulation, communication and engagement, and enabling

innovation, they may well appear somewhat familiar. That is because through the extensive development and consultation process for the strategy, we did not identify a need for a radical overhaul. We have instead refined our approach to better reflect our stage of development as a leading medicines regulatory agency within the European network.

There are, however, three key changes that I would especially like to highlight that differentiate our new strategic plan.

1. Continued strengthening of partnerships across all areas of the health system will be a key focus for the HPRA during this five year period. We have seen the value of close collaborative relationships established between the HPRA and key partners, including, the Department of Health, NPHET, NIAC and HSE, in dealing with the current pandemic. It is important that we continue to work toward strengthening our collaborations across all areas of the health system to better address current and future health challenges, optimise safe and effective use of health products, and enhance national

elbats erutarepmet moor A etarboth tnhuman ecno3.cFinally, etuthelid -owill t-ycontinue daer systems to protect HPRA and animal health.

2. As the national regulator for health products, it is imperative we continue to add value.

Consequently, the HPRA will be taking a more progressive approach to regulation using a proportionate and adaptive style to maximise the opportunities presented by the introduction of new legislation.

We will also prioritise a more risk-based approach to regulation, including the utilisation of intelligencebased sources of information to proactively manage risk, combined with data-driven regulatory decision-making. The ever-increasing globalisation of the pharmaceutical industry also means there will be a requirement for greater mutual reliance among regulators, combined with international convergence and harmonisation of regulatory standards. The HPRA is determined to promote and leverage the benefits of intelligence sharing among global regulators to ensure a more progressive, effective and efficient approach to health product regulation.

to promote communication and interaction with all of our stakeholders, by improving our models of engagement to strengthen public trust and confidence. It is vitally important we proactively engage with stakeholders as greater clarity and transparency will help strengthen trust in the regulatory system.

We are certainly in a different position at the end of 2021 compared to last year. The authorisation of safe and effective vaccines, combined with the incredible rate of uptake in Ireland which has been supported by all partners across the national health system, has helped to protect our communities. It has also demonstrated the value of an effective and agile regulatory approach. As the HPRA continues to contribute to the national, European and indeed global pandemic response, we will also work towards achieving our ambitious strategic goals and objectives to excel in health product regulation through science, collaboration and innovation.

News

My OT & Me Launch Pilot Programme 24:41 1202/40/72

Jane O’Flynn, Programme Manager, Health Innovation Hub Ireland working with MY OT&Me resources

Founder Innovators Jess Kennedy and Sean O’Tuama saw a clinical need for an on-line Paediatric Occupational Therapy (OT) resource to help children. Working with North Lee Primary Care Occupational Therapy Department,

HSE and supported by Health Innovation Hub Ireland, My OT & Me has successfully launched a pilot programme for this valuable resource. The Covid-19 pandemic worldwide has underlined the need for on-line OT resource to help children and parents in their own home. My OT & Me’s innovative platform addresses that need.

Paediatric Occupational Therapy helps children and young people with different needs and abilities to become as independent as possible by developing the skills they need to perform the purposeful activities that make up everyday life. The HSE Primary Care Occupational Therapy Services are experiencing increased numbers of referrals.

This can be challenging particularly in times of limited resources, long waiting lists and redeployment of existing staff to COVID-19 testing duties. There is also a significant demand for private paediatric OT services in Ireland amongst parents, caregivers, educators, professionals and students.

My OT & Me’s platform is a unique solution to this clinical need and the team responded by developing a telehealth based product as an online paediatric occupational

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

therapy resource to support children and families who are in need of OT support. It supports and empowers as many families as possible in an innovative, 1 ddni.A_noitpO_4v_eruhcorB_pp4_4A_dexertem accessible and interactive way.

My OT & Me provides information through structured high quality educational videos for parents covering a range of OT topics.

Children are provided with My OT & Me’s product, Octobox, which is a telehealth-based solution to support them with skill acquisition in a fun and interactive way.

Health Innovation Hub Ireland is supporting the My OT & Me Innovation Journey and is currently running a pilot with North Lee Primary Care Occupational Therapy Department, HSE with thirty children and their families in Cork City who are awaiting intervention services.

Pemetrexed Pemetrexed25 25mg/mL mg/mL

Launching Launching AA room roomtemperature temperaturestable stable ready-to-dilute ready-to-diluteconcentrate concentrate

Pemetrexed Pemetrexed25 25mg/mL mg/mL A multi-targetedanti-cancer anti-cancerantifolate antifolate agent agent A multi-targeted In three presentations In three presentations 100mg/4ml 100mg/4ml

500mg/20ml 500mg/20ml

1,000mg/40ml 1,000mg/40ml

PRESCRIBING INFORMATION: Consult the Summary of Product Characteristics for further information. Additional Paediatric population – No relevant use in malignant pleural mesothelioma and non-small cell lung cancer. Renal information is available upon request. Pemetrexed Fresenius Kabi 25mg/ml concentrate for solution for infusion. impairment – (Standard Cockcroft and Gault formula or GFR measured Tc99m-DPTA serum clearance method). In clinical Active INFORMATION: ingredients: Pemetrexed diacid.

One vialofofProduct 4ml concentrate containsfor100mg pemetrexed.

OneAdditional vial of 20ml Paediatric studies patients with –creatinine clearance 45ml/min pleural requiredmesothelioma no dose adjustments other thancell those recommended population No relevant use inof ≥ malignant and non-small lung cancer. Renal PRESCRIBING Consult the Summary Characteristics further information. concentrate contains pemetrexed.

One vial of 40mlKabi concentrate contains 1,000mgfor pemetrexed.

Excipients for all patients.

Not recommended in patients with creatinine clearanceTc99m-DPTA below 45ml/min.

Hepatic impairment – Patients – (Standard Cockcroft and Gault formula or GFR measured serum clearance method).

In clinical information is available upon500mg request.

Pemetrexed Fresenius 25mg/ml concentrate solution for infusion.with impairment known effectPemetrexed – 4ml vial - 964mg 20ml vial –contains 4820mg hydroxypropylbetadex, 40mlvial vialof– 9640mg with hepatic have not been specifically studied.

Contraindications: Hypersensitivity to thethose activerecommended substance patientsimpairment with creatinine clearance of ≥ 45ml/min required no dose adjustments other than Active ingredients: diacid.hydroxypropylbetadex, One vial of 4ml concentrate 100mg pemetrexed. One 20ml studies hydroxypropylbetadex.

Indications: In combination with cisplatin treatment of chemotherapy naïve patients with or to any of the excipients, breast-feeding, concomitant yellow fever vaccine.

Special warnings and precautions for use: concentrate contains 500mg pemetrexed. One vial of 40ml concentrate contains 1,000mg pemetrexed. Excipients with for all patients. Not recommended in patients with creatinine clearance below 45ml/min. Hepatic impairment – 3Patients and unresectable malignant mesothelioma, first20ml line treatment of locally advanced or metastatic cell lung with Monitor patients for myelosuppression.

Pemetrexed shouldContraindications: not be given until Hypersensitivity ANC returns to ≥to1500 cells/mm hepatic impairment have not been3 specifically studied. the active substance known effect – 4ml vial - 964mgpleural hydroxypropylbetadex, vial – 4820mg hydroxypropylbetadex, 40mlnon-small vial – 9640mg .

Dose reductions for subsequent cycles based on nadir ANC, platelet count anduse: platelet count to ≥ 100,000 cells/mm cancer other than predominantly squamous cell histology.

Monotherapy – Maintenance treatment of locally advanced or hydroxypropylbetadex. Indications: In combination with cisplatin - treatment of chemotherapy naïve patients with or to any of the excipients, breast-feeding, concomitant yellow fever vaccine. Special warnings and precautions for maximum non-haematologic toxicity seen from previous cycle. All patients must be instructed to take folic acid and metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has unresectable malignant pleural mesothelioma, first line treatment of locally advanced or metastatic non-small cell lung Monitor patients for myelosuppression. Pemetrexed should not be given until ANC returns to ≥ 1500 cells/mm3 and to reduce treatment-related toxicity. Pre-treatment with dexamethasone (or not progressed immediately following platinum-based chemotherapy, second line treatment of locally advanced or vitamin B12 as a prophylactic measure to ≥ 100,000 cells/mm3. Dose reductions for subsequent cycles based on nadir ANC, platelet count and cancer other than predominantly squamous cell histology. Monotherapy – Maintenance treatment of locally advanced or platelet count metastatic non-small cell lung cancer other than predominantly squamous cell histology. Posology and method of equivalent) can reduce the incidence and severity of skin reactions. Not recommended in patients with creatinine toxicity seen previousrenal cycle.insufficiency All patients(creatinine must be instructed to take folicshould acid and metastatic non-small cellOnly lung cancer other cell histology patients whose disease has maximum clearancenon-haematologic of < 45ml/min. Patients with mildfrom to moderate clearance 45-79ml/min) administration: administer underthan the predominantly supervision of asquamous physician qualified in theinuse of anti-cancer chemotherapy. a prophylactic measureacid to (>reduce treatment-related Pre-treatment dexamethasone B12 as NSAIDs, not progressed immediately followinginfusion platinum-based chemotherapy, second treatment of locally advanced or vitamin avoid taking or acetylsalicylic 1.3g daily) for 2 days before,toxicity. on the day of, and 2 dayswith following pemetrexed (or Administer as an intravenous over 10 minutes on the first day ofline each 21-day cycle.

See SmPC for further can reduce the with incidence severity of skin reactions.

Not with recommended in patients with creatinine metastatic non-smalloncell lung cancer other and thandilution. predominantly squamous cell histology.

Posologydose and ismethod of2 of equivalent) administration.

In patients mild toand moderate renal insufficiency NSAIDs long elimination half-lives should be information handling, administering In combination with cisplatin – Recommended 500mg/m of <for 45ml/min. with to day moderate insufficiency (creatinine clearance 45-79ml/min) should administration: Only administer under the supervision of a physician in the use body surface area (BSA) administered as an intravenous infusionqualified over 10 minutes on of theanti-cancer first day of chemotherapy. each 21-day cycle. clearance interrupted at least 5Patients days prior to,mild on the of, and renal at least 2 days following pemetrexed administration.

Patients taking or monitored acetylsalicylic 1.3g daily) for 2 days before, on thefunction day of, and pemetrexed Administer as an intravenous infusionisover 10 2minutes on over the first day of each 21-day30cycle.

Seeafter SmPC for further BSA infused two hours approximately minutes completion of the avoid Recommended dose of cisplatin 75mg/m should be NSAIDs, regularly for acid acute(> tubular necrosis, decreased renal and2 days signs following and symptoms of 2 In patients with mild to moderate insufficiency NSAIDs withto long elimination half-lives should information on handling, administering In combination with cisplatin – Recommended dose is 500mg/m pemetrexed infusion on the firstand day dilution. of each 21-day cycle. Patients must receive adequate anti-emetic treatmentofand administration. nephrogenic diabetes insipidus.

Drainage of thirdrenal space fluid collection prior pemetrexed treatment should be be body surface area (BSA) administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle. interrupted for at least 5 days prior to, on the day of, and at least 2 days following pemetrexed administration.

Patients appropriate hydration prior to and/or after receiving cisplatin (see also cisplatin SmPC). As single agent – In the treatment considered but may not be necessary. Patients should receive adequate antiemetic treatment and appropriate hydration 2 infused over two hours approximately 30500mg/m minutes after of the Recommended dose ofcell cisplatin is 75mg/m regularly for acute Serious tubularcardiovascular necrosis, decreased renal function andhave signsbeen anduncommonly symptoms of BSAcompletion administered as an should of non-small lung cancer after2 BSA prior chemotherapy, recommended dose is prior be to and/or aftermonitored receiving treatment. and cerebrovascular events pemetrexed infusioninfusion on the first of eachon 21-day cycle.day Patients receive anti-emetic treatment andthe nephrogenic diabetes insipidus. of third usually space fluid prior to pemetrexed treatment intravenous over day 10 minutes the first of eachmust 21-day cycle.adequate Pre-medication regimen: To reduce reported during clinical studies Drainage with pemetrexed, when collection given in combination with another cytotoxicshould agent. be appropriate hydration prior to of and/or after receiving cisplatin (see alsobecisplatin As single agent In the incidence and severity skin reactions, a corticosteroid should given theSmPC). day prior to, on the day– of, andtreatment the day after considered but use mayofnot necessary.

Patients should receive adequate treatment and appropriate Concomitant livebe attenuated vaccines is not recommended.

Sexuallyantiemetic mature males are advised not to fatherhydration a child pemetrexed administration. should berecommended equivalent to 4mg orally twice daily.as Patients during treatment up to 6 months thereafter. measures or abstinence areevents recommended.

Possibility of administered an prior of non-small cell lung cancer afterCorticosteroid prior chemotherapy, doseof isdexamethasone 500mg/m2 BSA to and/or afterand receiving treatment.

SeriousContraceptive cardiovascular and cerebrovascular have been uncommonly mustinfusion also receive vitamin supplementation; oraloffolic or acycle. multivitamin containing folic acid (350 tothe 1000 reported irreversible infertility; advised to seek counselling sperm before starting treatment.

Womenagent. of intravenous over 10 minutes on the first day eachacid 21-day Pre-medication regimen: To reduce during clinical men studies with pemetrexed, usually on when givenstorage in combination with another cytotoxic micrograms) on a daily basis.

At least five doses of folic acid must be taken during the seven days preceding the first dose childbearing potential must use effective contraception during treatment with pemetrexed.

Cases of radiation incidence and severity of skin reactions, a corticosteroid should be given the day prior to, on the day of, and the day after Concomitant use of live attenuated vaccines is not recommended. Sexually mature males are advised not to father a child of pemetrexed and dosing must continue during the full to course of therapy and for 21orally daystwice after daily. the last dose of during pneumonitis reported in patients treated with Contraceptive radiation eithermeasures prior, during or subsequent to pemetrexedPossibility therapy; of pemetrexed administration.

Corticosteroid should be equivalent 4mg of dexamethasone Patients treatment and up to 6 months thereafter. or abstinence are recommended.

P_KF_36791 19763_FK_Pemetrexed_A4_4pp_Brochure_v4_Option_A.indd 1 27/04/2021 14:42 24:41 1202/40/7 (1000 micrograms) in the(350 weektopreceding pemetrexed.

Patients supplementation; must also receive anoral intramuscular of vitamin B12containing particular attention paid totothese and caution with other radiosensitising agents.

Cases of radiation must also receive vitamin folic acidinjection or a multivitamin folic acid 1000 irreversible infertility;should men be advised seekpatients counselling on sperm storage before starting treatment.

Women of injections the mayfirst be given the first pemetrexed every three cycles Subsequent vitamin B12preceding recall reported in patients radiotherapy weeksduring or years previously.with Accumulation of cyclodextrins may micrograms) on adose dailyofbasis.

At leastand fiveonce doses of folic acid mustthereafter. be taken during the seven days dose on childbearing potential mustwho usereceived effective contraception treatment pemetrexed.

Cases of radiation the sameand daydosing as pemetrexed.

Monitoring: Before dose complete bloodand count whitedose cell count occur in patients withinmoderate severe with renalradiation dysfunction.

Mayprior, causeduring fatigue,orpatients shouldtobepemetrexed cautioned against of pemetrexed must continue during theeach full course of therapy forincluding 21 days differential after the last of pneumonitis reported patientstotreated either subsequent therapy; 791 19763_FK_Pemetrexed_A4_4pp_Brochure_v4_Option_A.indd 1 administration blood chemistry tests should be collected to driving or operating machinery if this occurs. Undesirable effects: (Associated with pemetrexed 27/04/2021 14:42 or in 24:41 1202/4 (WCC)Patients and platelet count.

Prior an to intramuscular each chemotherapy monotherapy pemetrexed. must also receive injection of vitamin B12 (1000 micrograms) in the week preceding particular attention should be paid to these patients and caution with other radiosensitising agents.

Cases of radiation evaluate renal and hepatic function.

Before the start of any cycle of chemotherapy, patients are required to have absolute combination with cisplatin) Infection, pharyngitis, sepsis, dermo-hypodermitis, neutropenia, leukopenia, decreased the first dose of pemetrexed and once every three cycles thereafter. Subsequent vitamin B12 injections may be given on recall reported in patients who received radiotherapy weeks or years previously. Accumulation of cyclodextrins may should be ≥ 45 ml/min. haemoglobin, febrile neutropenia, decreased platelet count, pancytopenia, autoimmune haemolytic anaemia, neutrophil count (ANC) ≥ 1500 cells/mm3 and platelets ≥ 100,000 cells/mm3. Creatinine clearance the same day as pemetrexed. Monitoring: Before each dose complete blood count including differential white cell count occur in patients with moderate to severe renal dysfunction. May cause fatigue, patients should be cautioned against Total bilirubin should be ≤ 1.5 times upper limit of normal. Alkaline phosphatase (AP), aspartate aminotransferase (AST or hypersensitivity, anaphylactic shock, dehydration, taste disorder, peripheral motor neuropathy, peripheral sensory (WCC) and platelet count.

Prior to each chemotherapy administration blood chemistry tests should be collected to or operating machinery if this occurs. Undesirable effects: (Associated with pemetrexed monotherapy or in SGOT) and alanine aminotransferase (ALT or SGPT) should be ≤ 3 times upper limit of normal. AP, AST and ALT ≤ 5 times driving neuropathy, dizziness, cerebrovascular accident, ischemic stroke, intracranial haemorrhage, conjunctivitis, dry eye, evaluateupper renal limit and hepatic function.

Beforeifthe any cycle of chemotherapy, patients At arethe required absolute with cisplatin) Infection, pharyngitis, sepsis, dermo-hypodermitis, neutropenia, decreased of normal is acceptable liverstart has of tumour involvement.

Dose adjustments: start oftoa have subsequent cycle combination increased lacrimation, keratoconjunctivitis sicca, eyelid oedema, ocular surface disease, cardiacleukopenia, failure, arrhythmia, 3 3 and platelets cells/mm . Creatinine clearance should ≥ 45 ml/min. neutrophil countbe(ANC) 1500 cells/mm febrileinfarction, neutropenia, decreased plateletsupraventricular count, pancytopenia, haemolytic anaemia, should based≥ on nadir haematologic counts≥or100,000 maximum non-haematologic toxicity from the be preceding cycle of haemoglobin, angina, myocardial coronary artery disease, arrhythmia,autoimmune peripheral ischaemia, pulmonary Total bilirubin should be ≤ 1.5 times upper limit of normal.

Alkaline phosphatase (AP), aspartate aminotransferase (AST or hypersensitivity, anaphylactic shock, dehydration, taste disorder, peripheral motor neuropathy, peripheral sensory therapy. Treatment may be delayed to allow sufficient time for recovery. Upon recovery patients should be retreated embolism, interstitial pneumonitis, stomatitis, anorexia, vomiting, diarrhoea, nausea, dyspepsia, constipation, abdominal SGOT) and alanine aminotransferase (ALT or SGPT) should be ≤ 3 times upper limit of normal.

AP, AST and ALT ≤ 5 times neuropathy, dizziness, cerebrovascular accident, ischemic stroke, intracranial haemorrhage, conjunctivitis, dry eye, using the guidelines as follows, which are applicable for pemetrexed Fresenius Kabi used as single agent or in pain, rectal haemorrhage, gastrointestinal haemorrhage, intestinal perforation, oesophagitis, colitis, increased alanine upper limit of normalwith is acceptable if liver has tumour involvement.

Dose adjustments: thecisplatin) start of –aNadir subsequent cycle 3 increased lacrimation, keratoconjunctivitis sicca, eyelid oedema, surface disease,hyperpigmentation, cardiac failure, arrhythmia, combination cisplatin. Haematologic toxicities (dose modify both pemetrexedAt and ANC < 500/mm aminotransferase, increased aspartate aminotransferase, hepatitis,ocular rash, skin exfoliation, pruritis, 3 should be nadir ≥haematologic counts or maximum non-haematologic toxicity from75% the of preceding of angina, myocardial infarction, coronary disease, supraventricular arrhythmia, peripheral ischaemia, pulmonary nadir platelets < 50,000/mm regardless of nadir ANC: previous cycle dose. Nadir andbased nadir on platelets 50,000/mm3, or erythema multiforme, alopecia, urticaria,artery erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigoid, 3 therapy. platelets Treatment may be delayed to allow sufficientoftime Upon recovery patients shouldtoxicities be retreated interstitial pneumonitis, stomatitis, anorexia, vomiting, oedema, diarrhoea, nausea, dyspepsia, constipation, abdominal with bleeding regardless nadirfor ANC:recovery.

50% of previous dose. Non-haematologic ≥ Grade embolism, < 50,000/mm dermatitis bullous, acquired epidermolysis bullosa, erythematous pseudocellulitis, dermatitis, eczema, prurigo, using the guidelinesneurotoxicity) as follows, - which are applicable for should pemetrexed Fresenius used toasless single ortointhe pain, rectal haemorrhage, gastrointestinal haemorrhage, perforation, colitis, increased alanine 3 (excluding pemetrexed Fresenius Kabi be withheld until Kabi resolution than agent or equal decreased creatinine clearance, increased blood creatinine,intestinal renal failure, decreasedoesophagitis, GFR, nephrogenic diabetes insipidus, 3 combination withpre-therapy cisplatin. Haematologic toxicities modifyaccordingly both pemetrexed and cisplatin) – Nadirexcept ANC < mucositis, 500/mm or aminotransferase, increased aspartate aminotransferase, hepatitis, skininflammation, exfoliation, hyperpigmentation, pruritis, patient’s value. Treatment should(dose be resumed – Any grade 3 or 4 toxicities renal tubular necrosis, fatigue, pyrexia, pain, oedema, chest pain, rash, mucosal increased GGT, radiation 2 3 3 ) of pemetrexed diarrhoea requiring hospitalisation or grade 3 or 4 diarrhoea: 75%ofofnadir previous oesophagitis, radiation pneumonitis, recall phenomenon.

Legal Category: POMtoxic Marketing Authorisation , or nadir platelets < 50,000/mm regardless ANC:dose 75%(mg/m of previous dose. Nadirand erythema and nadirany platelets ≥ 50,000/mm multiforme, alopecia, urticaria, erythema, Stevens-Johnson syndrome, epidermal necrolysis, Numbers: pemphigoid, ) and Non-haematologic 100% of previous cisplatin dose (mg/m2). dermatitis Grade3 with 3 or 4bleeding mucositis: 50% of previous dose (mg/m2dose.

EU/1/16/1115/003, EU/1/16/1115/005.

Authorisation Holder: Freseniusdermatitis, Kabi Deutschland regardless of nadirpemetrexed ANC: 50% of previous toxicities ≥ Grade plateletscisplatin. < 50,000/mm bullous,EU/1/16/1115/004, acquired epidermolysis bullosa,Marketing erythematous oedema, pseudocellulitis, eczema,GmbH, prurigo, Neurotoxicity – Patients should discontinue if Grade 3 or 4 neurotoxicity is observed.

CTC Grade 0-1:to100% Else-Kroner-Straße 61352 Badincreased Homburgblood v.d.Höhe, Germany.

Further See the SmPC fordiabetes further details.

3 (excluding neurotoxicity) - pemetrexed Fresenius therapy Kabi should be withheld until resolution to less than or equal the of decreased creatinine 1,clearance, creatinine, renal failure,Information: decreased GFR, nephrogenic insipidus, 2 2 ). CTCaccordingly Grade 2: 100% of previous pemetrexed (mg/m ) and 50% pemetrexed and cisplatin dosebe (mg/m Adverse events should fatigue, be reported.

Healthcare professionals askedmucosal to reportinflammation, any suspectedincreased adverse reactions via patient’sprevious pre-therapy value. Treatment should resumed – Any grade 3 or 4 toxicitiesdose except mucositis, or of renal tubular necrosis, pyrexia, pain, oedema, chestarepain, GGT, radiation treatment with pemetrexed Fresenius if a2)patient experiences previous cisplatinhospitalisation dose (mg/m2). Discontinue HPRA Pharmacovigilance, Earlsfort Terrace, - Dublin 2, Tel:Legal +353 Category: 1 6764971, Fax: 1 6762517.Authorisation Website: www.hpra.ie, of pemetrexed andany oesophagitis, any diarrhoea requiring or grade 3 or 4 diarrhoea: 75% of previous doseKabi (mg/m radiation pneumonitis, recall IRL phenomenon.

POM+353 Marketing Numbers: 2dose reductions or immediately if Grade 3 2or 4 haematologic or non-haematologic Grade 3 or 4 toxicity after 2 E-mail: medsafety@hpra.ie.

Adverse events should also be reported to Fresenius Kabi Limited via email Pharmacovigilance. cisplatin. Grade 3 or 4 mucositis: 50% of previous pemetrexed dose (mg/m ) and 100% of previous cisplatin dose (mg/m ). EU/1/16/1115/003, EU/1/16/1115/004, EU/1/16/1115/005. Marketing Authorisation Holder: Fresenius Kabi Deutschland GmbH, neurotoxicity is observed.

Elderly – Notherapy dose reductions those recommended forCTC all patients are100% necessary.

GB@Fresenius-Kabi.com.

Preparation: May 2021 Job code: API/Pemetrexed/02 Neurotoxicity – Patients should discontinue if Grade 3other or 4than neurotoxicity is observed.

Grade 0-1: of Else-Kroner-Straße 1, 61352Date BadofHomburg v.d.Höhe, Germany.

Further Information: See the SmPC for further details. previous pemetrexed and cisplatin dose (mg/m2). CTC Grade 2: 100% of previous pemetrexed dose (mg/m2) and 50% of Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse reactions via 2 previous cisplatin dose (mg/m ). Discontinue treatment with pemetrexed Fresenius Kabi if a patient experiences any HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517. Website: www.hpra.ie, haematologic or non-haematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 E-mail: medsafety@hpra.ie. Adverse events should also be reported to Fresenius Kabi Limited via email Pharmacovigilance. neurotoxicity is observed. Elderly – No dose reductionsFresenius other than those recommended Date of Preparation: May 2021 Job code: API/Pemetrexed/02 Kabi Limitedfor all patients are necessary.

Website:GB@Fresenius-Kabi.com. www.fresenius-kabi.com/ie/ Date of Prep: May 2021

Fresenius Kabi Ireland Unit 3B Fingal Bay, Balbriggan, Co. Dublin, Ireland Fresenius Kabi Limited Fresenius Kabi Ireland

Email: FK-enquiries.ireland@fresenius-kabi.com Phone: +353 (0)1 841 3030

Ref: IV/ONCO/PEME/01/2021

Website: www.fresenius-kabi.com/ie/ Email: FK-enquiries.ireland@fresenius-kabi.com

Date of Prep: May 2021 Ref: IV/ONCO/PEME/01/2021

End of Year: IHCA Ongoing Shortages of Concern temporary or agency basis (as at May 2021) that is one third of the 727 posts nationally not filled as needed. One in five permanent hospital consultant posts are currently either vacant or filled on a temporary basis across the country.

However, in CHOs 6, 7 and 9, which provide the capital's mental health and community services, the Consultant vacancy rates are almost 1 in 4.

Commenting on the waiting lists and Consultant vacancies across Dublin's hospitals, IHCA President Professor Alan Irvine, says, "Our public hospital and mental health services in the capital need fully funded plans in place to fill the 240 vacant consultant posts across Dublin's services to increase hospital capacity, ahead of what may be the most challenging winter ever for the health service.

The scale of vacancies in the capital has directly contributed to some of the longest hospital “It is still unclear how bad the flu season will be waiting lists in the country. Analysis from the this winter on top of growing Covid challenges.

The Irish Hospital Consultants Association (IHCA) has warned that ongoing IHCA shows that between September 2015 and The concern is that with lessIrelands flu immunity in the shortage hospital consultants across a large number of specialties in Dublin's acute Septemberof 2021, the hospitals experiencing the population we could see an increase in people greatest growth in their outpatient waiting lists hospital and mental health services is restricting patients from accessing timely, highcoming to hospital with severe symptoms, shown inmedical the table and below.surgical care and is contributing resulting inmassively further increased pressure on an lists quality to growing waiting already overstretched public hospital service. in the region.

In the specialty of Dermatology, for example, This would make catching up on the backlog the Outpatient waiting lists in Dublin have of missed care during the pandemic increased almost 8,500 (+61%) A total ofby241,925 people aresince currently awaiting an outpatient appointment with a extremely challenging.

September 2015 to 22,400. A quarter of these

Consultant at hospitals across the capital, an increase of almost 87,000 (+56%) since (5,633) are children waiting for an assessment “Growing waiting lists at Dublin hospitals 2015.* at the three Dublin paediatric hospitals.

Professor Alan Irvine, President, Irish Hospital Consultants Association The Irish Hospital Consultants Association (IHCA) has warned that Irelands ongoing shortage of hospital consultants across a large number of specialties in Dublin's acute hospital and mental health services is restricting patients from accessing timely, high-quality medical and surgical care and is contributing massively to growing waiting lists in the region.

A total of 241,925 people are currently awaiting an outpatient appointment with a Consultant at hospitals across the capital, an increase of almost 87,000 (+56%) since 2015.

More than 33,500 patients are currently waiting for inpatient or day case treatment at Dublin hospitals, which is 45% of the national figure of 74,869 at the end of September. Of these, more than 7,300 are waiting more than 12 months, an increase of almost 2,200 (42%) in such 'longer waiters' over the past six years.

A further 9,637 people are currently awaiting a gastrointestinal (GI) endoscopy, which brings the total number of people in Dublin awaiting hospital treatment or assessment by a consultant to 285,104.

Across the capital's public hospitals and three Community Health Organisations serving the region, 246 out of a total of 1,714 approved Consultant posts were vacant or filled on a

demonstrate the impact of years of consultant

shortages and underinvestment in capacity The number of patients waitingare longer than a waiting More than 33,500 patients currently for inpatient or day case treatment at across these public hospitals. year for inpatient/day case treatment in the Dublin hospitals, which is 45% of the national figure of 74,869 at the end of September. region increased by 2,181 (42%) over the past “We have12 a chronic recruitment and retention Of these, more than 7,300 are waiting more than months, an increase of almost six years, with the largest increases again seen crisis six with 1 in 5 permanent hospital consultant 2,200 (42%) in such 'longer waiters' over the past years. in children waiting for care at Children's Health

posts across the country Ireland at Crumlin, Tallaght and Temple Street, either vacant or filled on a temporary basis.

A further 9,637 people are currently which combined saw a four-fold increase.awaiting a gastrointestinal (GI) endoscopy, which “We knowhospital what the treatment problems are, we brings the total number of people in Dublin awaiting orand assessment These waiting lists are likely to worsen in the know what it takes to fix them: fill these vacant by a consultant to 285,104. coming weeks, amidst growing concerns over permanent consultant posts, open the required the severity of the flu season this year and its number of beds and other facilities on a Across the oncapital's public and three Community Health potential impact health service capacity.hospitals properly resourced and staffed basis. Yet there Organisations serving the region**, 246 out of a totalcommitment of 1,714 approved is no clear to doing thisConsultant from Consultants say that putting in place a clear posts were vacant or filled on solutions a temporary or basis (as at May 2021) - that is theagency Government. plan containing practical, workable one third timely of thecare 727toposts nationally to provide patients in Ireland'snot filled as needed.*** One in five permanent “The success of the ongoing consultant public acute hospitals isposts criticalare andcurrently must be either vacant or filled on a temporary basis hospital consultant contract discussions will be critical to the delivered immediately. across the country. However, in CHOs 6, 7 and 9, which provide theservice capital's mental survival of our public health not only health and community services, the Consultant vacancy rates are almost 1 ahead in 4. during the challenging winter months The Association has called on the Department but for years to come. It is essential these talks of Health to bring forward the long-awaited deliver contributed on the 'unambiguous commitment' multi-annual list reduction and has directly The scale ofwaiting vacancies in theplan capital to some of the longest made by the Health that to resolve the to providewaiting realistic yet hospital listsambitious in the targets country. Analysis from theMinister IHCA*forshows between pay inequity issue for all Consultants contracted and timescales for the reduction of Ireland's September 2015 and September 2021, the hospitals experiencing the greatest growth shocking waiting lists. since 2012.”

in their outpatient waiting lists were: Hospital St Columcille's Hospital Royal Victoria Eye & Ear St James's Hospital Mater Hospital St Vincent's Hospital Tallaght Hospital

Outpatients September 2015 2,512 7,599 13,607 23,820 14,901 21,209

Outpatients September 2021 5,962 15,440 26,302 45,645 25,760 36,075

Change +137% +103% +93% +92% +73% +70%

In the specialty of Dermatology, for example, the Outpatient waiting lists in Dublin

have increased by almost 8,500 (+61%) since September 2015 to 22,400. A quarter of | HOSPITALPROFESSIONALNEWS.IE DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN

these (5,633) are children waiting for an assessment at the three Dublin paediatric

End of Year: Asthma Society of Ireland Talking Strategy in Asthma Care Written by Sarah O’Connor, CEO, Asthma Society of Ireland

week one, then the small cushion of funding went away. And funding became the pressing need once again.

We found some new funders, including new corporate partners and trusts and foundations who saw that we were doing good work for patients and wanted to support that - these new organisations got behind us when it was most needed.

“Fear of me or my asthmatic child getting the virus and the terror of being separated from him if he had to go to hospital.”

In December 2019, the Asthma Society had an operational plan agreed for the year 2020.

It was an excellent plan.

It didn’t happen.

Things started as per our strategic direction, our General Election and Programme for Government work in January and February opened doors for important structural asthma management discussions. Our February SafetyCare campaign about SABA over-reliance (subsequently awardwinning) made front page news, making our services very busy.

So far, so good. And March 2020 was, as we know, when it all changed.

There was an urgency to the rest of the year for members of the Asthma Society team. We have always been a small team who together delivered important results with a big impact. But in 2020 we continued to show up when having asthma as an “underlying condition” added huge anxiety for any patient, while they also had decreased access to healthcare, as a result of COVID-19.

In our survey in April 2020 (2400+ respondents), we asked patients (or carers) about their greatest concern and we got answers like:

“Not being considered for an indemand ventilator due to asthma.”

“That I would be considered not worth saving.”

Evidence indicated that patients were not more likely to contract COVID-19 but were potentially more likely to experience severe symptoms if their asthma/COPD was uncontrolled, so we met both COVID-19 and asthma/COPD needs squarely.

We worked hard to create centralised, healthcare professional approved, evidenceled patient information, with the help of our own patient services team, our Medical Advisory Group and the HSE’s Clinical Programme for Asthma. We disseminated this approved respiratory-specific advice through every channel available to us, leaflets, website, videos, campaigns, live broadcasts, graphics – and obviously, through our existing one-to-one patient support services.

Wave after wave of supports, changes, adaptations, funding applications, campaigns, engagements – we kept going, we kept helping. The team did phenomenal work, clever work, impactful work - every single one of them as individuals and collectively as a whole.

At the time, we thought it was a three week choice, then a six

I especially also want to thank many of our pre-existing funders from across the corporate world and within the HSE. Many times we brought them ideas of how pre-existing funded projects could be adapted to meet patients’ urgent and pressing needs during COVID-19 and when we were agile and smart like this, nobody refused.

Moreover, the public didn’t refuse either. They gamely tried Facebook birthday fundraisers, walked 10 Million Steps for Asthma, and responded to our Crisis COVID-19 appeal.

We were forced by COVID to stop many aspects of our fundraising but collectively, these state, corporate and individual donors helped us - but only sufficiently to keep our deficit to circa ¤80,000.

We relied on our reserves.

We launched our new strategy, Stopping Asthma Deaths in Ireland, 2020-2025, mid-way through 2020 – at the time we also believed we were more than mid-way through the pandemic.

The pandemic threw a spotlight on many things for the public, including this one known to us and patients for so long: the need for our new strategy, for a transformation of the broader respiratory healthcare system in Ireland has never been more urgent. If COVID-19 provided that spotlight for the public, we cannot let it fade.

Amárach Research kindly undertook some pro-bono research for the Asthma Society (admittedly in July 2021 rather than in 2020), with a representative survey of 1000 people, which

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

reflects some key things which simply must be changed:  Only 23% of people with asthma have a written up-to-date Asthma Action Plan,  Only 12% of the general public have heard of the 5 Step Rule,  Only 30% of people with asthma have heard of the 5 Step Rule.

People are still dying in this country as a result of their asthma. We need improved support for patients, better educated patients and carers, more changes at healthcare decision-maker level, more healthcare professionals having the best asthma management interventions possible. It is only through these changes can we eliminate asthma deaths in Ireland.

Those same findings from Amárach Research showed:  78% of the general public have heard of the Asthma Society  25% of people with asthma have used our services  9% of the general public have used our services  33% of the general public have a close family member with asthma, both indicating that a large number of people care about this condition and can be motivated to improving it.

We do not purport to be the only people invested in asthma control in Ireland. But we do play a key role as change-makers. And so, we have to survive and thrive in our work. We have to.

Writing now from the vantage point of 2021, I can now see that the financial impact of COVID-19 was initially slow to manifest and is now tough and long. We are relying more deeply on our reserves in 2021.

We cannot do this alone. We need your help. As you are reading this article, I encourage you to consider if you can support us by becoming a donor. In advance of that: we thank you, patients thank you, carers thank you.

NOW AVAILABLE

IND/GLY/MF 114/46/136μg

1x

ONCE DAILY ENERZAIR® BREEZHALER® + SENSOR*

daily

The 1st LABA/LAMA/ICS combination for asthma1 Now available to prescribe as a co-pack with a Sensor* and App2, which provides: INHALATION CONFIRMATION3

MEDICATION REMINDERS3

REAL DATA** TO SUPPORT THERAPEUTIC DECISIONS3

* The Propeller® Sensor for the BREEZHALER® device (referred to here as “Sensor”) and the Propeller® mobile app are property of Propeller Health®. ** When patients opt in to data collection & sharing, real data includes information on the patient’s rescue medication use and maintenance medication adherence collected via the sensor and app, as well as information on the patient’s asthma control status (as measured by Asthma Control Test, ACT).

ENERZAIR® BREEZHALER® is indicated as a maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta2-agonist and a high dose of an inhaled corticosteroid who experienced one or more asthma exacerbations in the previous year.2 Abbreviated Prescribing Information Please refer to Summary of Product Characteristics (SmPC) before prescribing.

Enerzair® Breezhaler® (indacaterol (as acetate), glycopyrronium bromide, mometasone furoate) inhalation powder, hard capsules.

Presentation: Hard capsules for inhalation each containing 150 mcg of indacaterol (as acetate), 63 mcg of glycopyrronium bromide equivalent to 50 mcg of glycopyrronium and 160 mcg of mometasone furoate.

Each delivered dose contains 114 mcg of indacaterol acetate, 46 mcg of glycopyrronium and 136 mcg of mometasone furoate. Indications: Maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta2-agonist and a high dose of an inhaled corticosteroid who experienced one or more asthma exacerbations in the previous year. Dosage and Administration: One capsule once daily, administered at the same time of the day each day, using the Enerzair Breezhaler inhaler. No dose adjustment is required in elderly patients, in patients with mild to moderate renal impairment, or in patients with mild or moderate hepatic impairment. Caution should be observed in patients with severe renal impairment or end-stage renal disease requiring dialysis. No data available for patients with severe hepatic impairment, only use in these patients if the expected benefit outweighs the potential risk. The safety and efficacy in paediatric patients below 18 years of age have not been established. Contraindications: Hypersensitivity to the active substances, lactose monohydrate or magnesium stearate. Warnings/Precautions: Deterioration of disease: Should not be used to treat acute asthma symptoms, including acute episodes of bronchospasm. Treatment should not be stopped abruptly. Hypersensitivity: Immediate hypersensitivity reactions have been observed after administration. If signs suggesting allergic reactions occur, in particular angioedema, urticaria or skin rash, treatment should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm: If paradoxical bronchospasm occurs, treatment should be discontinued immediately and alternative therapy instituted. Cardiovascular effects: Like other medicinal products containing beta2-adrenergic agonists, may produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms. Use with caution in patients with cardiovascular disorders (coronary artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension), convulsive disorders, thyrotoxicosis, and in patients who are unusually responsive to beta2-adrenergic agonists. Long acting beta2-adrenergic agonists (LABA) or LABA containing combination products such as Enerzair Breezhaler should be used with caution in patients with known or suspected prolongation of the QT interval or who are being treated with medicinal products affecting the QT interval.

Hypokalaemia: Beta2-adrenergic agonists may produce significant hypokalaemia in some patients, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. In patients with severe asthma hypokalaemia may be potentiated by hypoxia and concomitant treatment, which may increase the susceptibility to cardiac arrhythmias. Hyperglycaemia: Inhalation of high dose of beta2-adrenergic agonists and corticosteroids may produce increases in plasma glucose. Upon initiation of treatment, plasma glucose should be monitored more closely in diabetic patients. Anticholinergic effect related to glycopyrronium: use with caution in patients with narrow-angle glaucoma or urinary retention. Prevention of oropharyngeal infections: In order to reduce the risk of oropharyngeal candida infection, patients should be advised to rinse their mouth or gargle with water without swallowing it or brush their teeth after inhaling the prescribed dose. Systemic effects of corticosteroids: Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. Should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections. Excipients: Contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicinal product. Interactions: No specific interaction studies

December 2020 | 103207

ONCE DAILY

Indacaterol acetate / glycopyrronium bromide / mometasone furoate inhalation powder

were conducted with indacaterol/glycopyrronium/mometasone furoate. Information on the potential for interactions is based on the potential for each of the monotherapy components. Medicinal products that prolong QTc interval: Should be administered with caution in patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or medicinal products known to prolong the QT-interval.

Hypokalaemic treatment: Concomitant treatment with methylxanthine derivatives, steroids, or nonpotassium sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists.

Beta-adrenergic blockers: Should not be given together with beta-adrenergic blockers unless there are compelling reasons for their use. Where required, cardioselective beta-adrenergic blockers should be preferred, although they should be administered with caution. CYP3A4 and P-glycoprotein inhibitors: Inhibition of CYP3A4 and P-gp has no impact on the safety of therapeutic doses of Enerzair Breezhaler.

Cimetidine and inhibitors of organic cation transport: No clinically relevant drug interaction is expected when glycopyrronium is co-administered with cimetidine or other inhibitors of the organic cation transport.

Other long-acting antimuscarinics and LABAs: Co-administration with other medicinal products containing long-acting antimuscarinics or LABAs is not recommended. Fertility, Pregnancy and Lactation: Should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus. No information available on the presence of indacaterol, glycopyrronium or mometasone furoate in human milk, on the effects on a breast-fed infant, or on the effects on milk production. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Studies do not indicate a concern regarding fertility in either males or females. Undesirable Effects: Very common (≥1/10): nasopharyngitis, asthma (exacerbation). Common (≥1/100 to <1/10): upper respiratory tract infection, candidiasis, urinary tract infection, hypersensitivity, headache, tachycardia, oropharyngeal pain, cough, dysphonia, gastroenteritis, musculoskeletal pain, muscle spasms, pyrexia. Uncommon (≥1/1,000 to <1/100): hyperglycaemia, cataract, dry mouth, rash, pruritus, dysuria. Please consult the Summary of Product Characteristics for a detailed listing of all adverse events before prescribing. Pack Size(s): Single pack containing 30 x 1 hard capsules, together with one inhaler. Pack containing 30 x 1 hard capsules, together with 1 inhaler and 1 sensor. The sensor and App are not required for administration to the patient. The sensor and App do not control or interfere with delivery of the medicinal product using the inhaler. Legal Category: POM. Product (Marketing) Authorisation Number(s): EU/1/20/1438/002 & 003. Product (Marketing) Authorisation Holder: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland. Full prescribing information is available upon request from: Novartis Ireland Limited, Vista Building, Elm Park Business Park, Elm Park, Dublin 4. Tel: 01-2601255 or at www.medicines.ie. Detailed information on this product is also available on the website of the European Medicines Agency http://www.ema.europa.eu Prescribing Information last revised: July 2020.

Reporting suspected adverse reactions of the medicinal product is important to Novartis and the HPRA. It allows continued monitoring of the benefit/risk profile of the medicinal product. All suspected adverse reactions should be reported via HPRA Pharmacovigilance, website www.hpra.ie.

Adverse events could also be reported to Novartis preferably via www.report.novartis.com or by email: drugsafety.dublin@novartis.com or by calling 01 2080 612.

References: 1. European Medicines Agency CHMP Press Release. Available at: https://www.ema. europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-28-30-april-2020 Date accessed: January 2021. 2. ENERZAIR® BREEZHALER®. Summary of Product Characteristics.

Available at www.medicines.ie Date accessed: January 2021. 3. Propeller® Sensor for Enerzair® Breezhaler® Instructions for Use. Available in each pack of Enerzair® Breezhaler® plus Sensor.

26 Lung Cancer

Immunotherapy Update in Lung Cancer Written by Dr Iseult Browne, Oncology Specialist Registrar and Dr Mark Doherty, Consultant Medical Oncologist, St Vincent’s University Hospital Fig.2

Dr Iseult Browne, Oncology Specialist Registrar

Dr Mark Doherty, Consultant Medical Oncologist, St Vincent’s University Hospital

Lung cancer is the fourth most common cancer in Ireland and about 2749 are people diagnosed annually. The majority of patients who are diagnosed with lung cancer are over the age of 50, with less than 1% occurring before the age of 40. There are two main types of lung cancer; Non-small cell lung cancer (NSCLC) accounts for 80%–90% of lung cancers, while small cell lung cancer (SCLC) has been decreasing in frequency in many countries over the past two decades.

The staging of lung cancer determines the treatment goal and overall survival rate (OS) ranging from a 6% 5 year OS in stage 4 disease to 35% in stage 1 disease, with these rates continuing to improve with new advances in systemic treatment such as immunotherapy and targeted drugs. Until 2015 the mainstay of systemic treatment in Ireland for the management of lung cancer was chemotherapy, either on its own or in combination with radiotherapy depending on

Fig.1

Figure 2

the treatment plan decided upon at the Lung Multidisciplinary Meeting. The treatment of patients with lung cancer has undergone a transformational change in the past decade and long-term results with immunotherapy agents and targeted therapies are providing the hope of long term survival for a substantial number of patients even with advanced disease.

The concept of immune surveillance of cancer was conceived over 100 years ago and understanding of the mechanisms of cancer immunoediting have resulted in increased interest with immune evasion now considered one of the hallmarks of cancer, (Figure 1).

Immune checkpoints are a normal component of the immune system and their role is to prevent an immune response destroying healthy cells, (Figure 2). These checkpoints engage when proteins on the surface of T Cells bind to partner proteins on other cells, such as tumour cells (TCs) , and on binding send an ‘off’ signal to the T Cells. In physiologic circumstances, this represents an important balance in the management of an activated T cell response, but it has been discovered that cancer cells can use this mechanism to avoid

Figure 1

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

immune surveillance. Immune checkpoint inhibitors (ICIs) are monoclonal antibodies, directed against T-cell or stromal/tumour cells and work by blocking checkpoint proteins from binding with their partner proteins preventing the ‘off’ signal, (Figure 3). Examples of ICIs include CTLA-4 inhibitors, PD-1 inhibitors and PDL-1 inhibitors listed in Figure 4, and in this article we will focus on PD-1 and PDL-1 inhibitors, as they have had the most impact in lung cancer to date.

PD-1 is expressed on activated T-cells and limits cytotoxic activity in peripheral tissues. Lung cancers were previously considered poorly immunogenic, with minimal benefit seen in historical studies of cytokine modulation or vaccines.

However, the recent development of ICIs has upended this belief and provided proof of principle that immunotherapy can play an important role in the treatment of patients with lung cancers.

In 2015, the US Food and Drug Administration (FDA) approved the first immunotherapy (Nivolumab) for the treatment of metastatic NSCLC that has progressed during or after treatment with platinumbased chemotherapy and this has led to a paradigm shift in the management of lung cancer.

This approval was based on the results from the CheckMate 057 Clinical Trial; with a median OS of 12.2 months (95% CI, 9.7 to 15.0) among the nivolumab group

27 Fig.3 proportion score (TPS, presence of PD-L1 signal on tumour cell membranes) ≥ 50% in first line and ≥ 1% in second line. PD-L1 IHC is an approved biomarker test for immunotherapeutics in NSCLC but it is not a perfect biomarker; less than half of biomarkerselected patients benefit from treatment and some responses may be encountered in ‘biomarkernegative’ cohorts. Much work is underway to identify alternative, or more likely, additional biomarkers to enrich patient populations for response.

Figure 3

Fig.4

CTLA-4

• Ipilimumab • Tremelimumab

PD-1

• Nivolumab • Pembrolizumab

PDL-1

• Durvalumab • Atezolizumab • Avelumab

and 9.4 months (95% CI, 8.1 to 10.7) in docetaxel group (HR for death. 0.73; 96% CI, 0.59 to 0.89; P=0.002).

Since this major trial there have been multiple FDA approvals of different ICIs for various indications in lung cancer. In an Irish context, the National Cancer Care Programme (NCCP) Technology Review Committee makes recommendations on reimbursement to the HSE Drug Committee. The ICIs licenced for reimbursement in Ireland for the treatment of lung cancer alongside their indications are listed in Table 1. Another route for patients with lung cancer to access ICIs which may be licensed by both the FDA and EMA but not reimbursed in Ireland is through a compassionate access programme. This is a treatment option whereby some pharmaceutical companies offer certain drugs based on trials in progress or approval in other countries, where no licensed or reimbursed option is available.

The use of ICIs has moved to the first line setting in the treatment of metastatic NSCLC and the

Table 1

Figure 4

approval of the anti-PD-1 agent pembrolizumab as a standard-ofcare first-line treatment in selected patients has made programmed death-ligand (PD-L1) testing by immmunohistochemistry a mandatory test in all patients with advanced NSCLC. There is a relationship between the

extent of PD-L1 expression on TCs, or in some trials in tumour infiltrating immune cells (ICs), and the probability of clinical benefit from numerous anti-PD-1 or PD-L1 agents, in first- and second-line monotherapy. For pembrolizumab, the mandatory treatment threshold is a tumour

Based on the phase III KEYNOTE-024 study Pembrolizumab is considered a standard first-line option for patients with advanced NSCLC and PD-L1 expression ≥ 50% who do not otherwise have contraindications to use of immunotherapy (such as severe autoimmune disease or organ transplantation). This study included patients with a PDL1 score of ≥ 50% compared pembrolizumab to platinumdoublet chemotherapy. All efficacy measures favoured pembrolizumab and continued follow-up has further emphasised the effectiveness of pembrolizumab, with the 5 year analysis showing pembrolizumab roughly doubles the 5-year overall survival (OS) rates, from 16% to 32%, versus chemotherapy in patients with metastatic non–small cell lung cancer (NSCLC) with PDL1 tumour proportion scores (TPS) above 50%. Quality of life scores were also compared and favoured pembrolizumab with decreased toxicities. This was approved for reimbursement in Ireland in 2018 and has become the standard of care for these patients since then.

Table 1 Drug

Indication(s)

Atezolizumab

1)Treatment of patients with locally advanced or metastatic NSCLC after prior chemotherapy.

2) First-line treatment of patients with metastatic NSCLC with PDL1≥ 50% tumour cells (TC) or ≥ 10% tumour-infiltrating immune cells (IC) and who do not have EGFR mutant or ALKpositive NSCLC

Durvalumab

As monotherapy for locally advanced, unresectable NSCLC with PD-L1 ≥1% on TCs and whose disease has not progressed following platinum-based chemo-radiation therapy

Pembrolizumab monotherapy

First-line treatment of NSCLC with PD-L1 ≥50% tumour proportion score (TPS) with no EGFR mutations or ALK translocations.

Pembrolizumab (in combination w/ chemotherapy)

First-line treatment of Patients with metastatic NSCLC

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

28 Lung Cancer Fig 6

Hypophysitis

Dry mouth, mucositis Thyroiditis Hypo/hyperthyroidism Hepatitis

Uveitis

Pancreatitis Autoimmune diabetes Rash and vitiligo

Arthralgia

Given the benefits seen in the setting of metastatic lung cancer, there has been much interest in incorporating immunotherapy drugs into treatment protocols for earlier stage disease. The intention is to improve cure rates in these patients rather than prolong life expectancy with incurable disease.

The phase III PACIFIC trial changed practice in the management of locally advanced, unresectable NSCLC with the addition of durvalumab maintenance to standard chemoradiotherapy leading to a 45% reduction in the relative risk of death or recurrence and a 10% absolute improvement in overall survival at 5 years. Prior to this study, there had been

Pneumonitis Myocarditis Adrenal insufficiency

Enterocolitis

Thrombocytopenia Anemia

Survival curves from immunotherapy based clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Statistical modelling of long-term survival from the KEYNOTE trials estimates that onequarter of appropriately selected patients with advanced NSCLC may attain long-term survival, which is an extremely exciting concept in an area with previously dismal survival outcomes.

Figure 6

very little change in outcome of patients with unresectable lung cancer in two decades. Large scale trials of pre- and post-operative immunotherapy, generally in combination with chemotherapy, are ongoing and offer the promise of better cure rates for patients with early stage lung cancer.

Although some patients have the benefit of being able to forgo chemotherapy and the associated side-effects, ICIs bring their own risk of toxicities which need to be carefully monitored and promptly treated if identified. Most of the ICI specific toxicities are known as immune-related adverse events Fig.7 (irAEs), (Figure 6). The majority of irAEs are mild to moderate, however it is important to note severity can be asymptomatic to life-threatening thus prompt recognition is crucial.

Vasculitis

is receiving and define whether they may have been exposed to an ICI in the past, (Figure 7).

Most irAEs are reversible with steroids however some require discontinuation. It is important to educate care team, patient, and caregivers on signs and symptoms of irAEs. Grade 1-2 irAEs may be managed in an outpatient/ community setting with PO steroids and stopping treatment, however grade 3 or above generally requires hospital admission for IV steroids.

Steroids are generally started at 1mg/kg and slowly tapered over 4-6 weeks. Rapid taper is not advised as this may results in

With ICIs the onset of toxicity is variable, from days after first dose up to a year after completing treatment thus it is extremely important to know what a patient

Figure 7: Time of occurrence of immune-related adverse events following ipilimumab treatment

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

recurrence / flare. An important thing to note and to reassure patients is that discontinuing ICIs due to treatment-related adverse events does not negatively affect survival or response.

It is evident that ICIs have been the biggest advance in systemic anti-cancer therapy this century and the treatment of selected cancers, including lung cancer, has been transformed. Selection of appropriate patients for treatment is vital, with the requirement to find additional biomarkers to enrich patient populations for response. Although the toxicity profile is different than conventional chemotherapy, patients must be educated on early detection and prompt action when toxicity occurs. While there have been major advances in the treatment of lung cancer in the past decade, there remains a need to improve outcomes for the patients with lung cancer who do not experience durable survival, and this research is ongoing.

30 News

Representing Medicines Makers in Brussels David Delaney, Chair, Medicines for Ireland/Board Member, Medicines for Europe along with Ireland Ambasaador to The EU, Mr Tom Hanney and Director General of Medicines for Europe, Adrian Van Den Hoven

David Delaney, Chair of Medicines for Ireland, recently attended a meeting in Brussels with Ireland’s Ambassador to the EU Tom Hanney and his team at Permanent Representation of Ireland to the EU. He said, “Representing the makers of the majority of medicines used in Europe daily, via our Trade Associations Medicines for Ireland and Medicines for Europe, we focussed on post-Brexit solutions for stable patient access to medicines in Northern Ireland.

“Time is running out to fix the uncertainty in certain quarters

around patient access post Brexit.

In Dublin, London and Brussels, let’s redouble all our efforts to give patients in Northern Ireland maximum confidence in their supply of medicines when the current temporary fixes derogations expire in a few weeks.”

David exclusively told Hospital Professional News, “It is currently an extremely busy time representing the companies who supply the majority of medicines daily in Ireland and across Europe, via our Trade Associations, Medicines for Europe, and Medicines for Ireland.

“Access to medicines in Northern Ireland looks problematic from January 2022 onwards. When the current, temporary postBrexit policies expire at the end of December, the rules look very unclear. Despite words from some stakeholders, there is nothing in law yet agreed with the key parties.

“This isn’t how the pharmaceutical industry normally operates, planning R&D and production months in advance, with only the basis of oral assurances with no legal footing. Understandably, some patients are beginning to get concerned and the industry is unclear on what rules will apply.

“Key questions abound, such as; ‘What labelling of medicines boxes will apply?’

‘Where to file certain regulatory filings, in the UK or the EU?’

“The industry needs clarity as it must produce legally valid medicines packaged correctly with fully compliant paperwork behind each medicine. Our recent meeting in Brussels with Ireland’s Ambassador to the EU, Mr Hanney and his team was a useful and frank exchange of views and potential solutions. This followed our Medicines for Ireland and Medicines for Europe meetings with other key Irish MEPs and their teams, including Sean Kelly MEP, and the team from Mick Wallace MEP and Clare Daly MEP. “The solution for the short term is to extend the current temporary fixes for medicines taking their standard route into the UK before being sent to Northern Ireland. This breathing space would give time for the EU to publish its planned legislation and get it through a busy Parliamentary timetable in Brussels, and for the UK to continue to be flexible and formulate its policy framework.

“We call on all parties in Belfast, London, Brussels, and Dublin to re-double their trojan efforts to ensure peace of mind for patients in Northern Ireland and to give industry time to plan and produce medicine for Northern Ireland.

“Thanks Mr Ambassador, Emma and Declan in the Embassy team and Katarína Gatialová and Giuliana Pennisi from our team for your time and the positive discussion today in Brussels.”

Co-ordinated Strategy ‘Vital’ for Children Ireland is "very far from where it should be" in the treatment of children with Type 1 diabetes, an expert in the disease has claimed.

A co-ordinated national strategy is vital to confronting the chronic condition, said consultant Colin Hawkes ahead of World Diabetes Day which was held on November 14th.

He and the team at Cork University Hospital treats almost 500 children with Type 1 diabetes, but insufficient resources mean it is not possible to see children every three months, as recommended - with some waiting six-eight months between appointments.

"We are also totally unequipped to address the psychological burden of this disease," said Dr Hawkes, a paediatric endocrinologist at CUH. Dr Colin Hawkes

"We are very far from where we should be, there is a lot more that

we need to be doing to meet the needs of these children and their families.

live. There is not equity in Ireland in access to a full diabetes multidisciplinary team.

"In CUH alone, we have an exceptional team but we should have six diabetes nurses for the number of children we care for and we only have three.

We have submitted a business case requesting three more. It is extremely difficult to provide the care these children deserve at such low staffing levels.

"CUH is a regional centre of excellence for children with type 1 diabetes in the South/Southwest Hospital Group. In addition to our local children, we provide diabetes expertise for children in Kerry and as far as Clonmel (Tipperary).

"We also should be at the forefront of research in this condition and are working to generate energy and funding to build a research team and programme. This will help change the future of this condition.

"The aspiration should be that every child should have access to the same and the best standard of care, regardless of where they

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

"Rather than bringing children long distances to us, appropriate staffing of the diabetes programme at Cork would allow our diabetes team to perform regional outreach clinics. In my view, that should be the model."

Dr Hawkes warns that diabetes becomes a "disease of the family", which can have detrimental effects - fuelling a higher rate of divorce, anxiety and depression amongst parents of children with this condition.

Enabling people with depression to feel, think and do better1

Brintellix is indicated for the treatment of major depressive episodes in adults1 Brintellix® (vortioxetine) film-coated tablets Prescribing information: Please refer to the full Summary of Product Characteristics (SPC) before prescribing, particularly in relation to side effects, precautions and contraindications.

Presentation: Tablets containing 5, 10, 15 or 20mg vortioxetine. Indication: Treatment of major depressive episodes in adults. Dosage: 10mg once daily. May be increased to a maximum 20mg daily or reduced to 5mg if necessary. After symptoms resolve, treatment recommended for at least 6 months. Can be taken with or without food. Elderly (≥65 years): Initial dosage is 5mg once daily. Caution advised if using doses above 10mg daily. Children (7-11 years): Not recommended. Adolescents (12-17 years): Not recommended in major depressive disorder; efficacy not established. Cytochrome P450 inhibitors and inducers: Consider a dose reduction of vortioxetine if a strong CYP2D6 inhibitor is added. Consider a dose adjustment if a broad CYP450 inducer is added to treatment. Renal or hepatic impairment: No dose adjustment; subpopulations are vulnerable and data on the use of Brintellix are limited.

Contraindications: Hypersensitivity to the active substance or excipients. Concomitant use with non-selective, monoamine oxidase inhibitors (MAOIs) or selective MAO-A inhibitors (e.g. moclobemide). Fertility, pregnancy and lactation: Limited data; should only be administered to pregnant women if the expected benefits outweigh the potential risk to the foetus. Animal studies showed reproductive toxicity. Use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Potential risk of postpartum haemorrhage following exposure to an SSRI or SNRI within the month prior to birth. Excreted into human milk, risk to the breastfeeding child cannot be excluded. Animal data showed no effect on fertility, sperm quality or mating performance. Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed. Please refer to SPC for more detail. Warnings & Precautions: Closely supervise patients, especially those at high risk for suicide-related behaviours during first few weeks of treatment and during dose changes. Use with caution in patients: at risk of hyponatraemia; with a history of mania/hypomania; aggression/agitation; undergoing ECT; with unstable epilepsy (discontinue if seizures begin for the first time or increase in frequency); with bleeding tendencies/disorders, taking anticoagulants or medicines affecting platelet function; in patients on lithium or tryptophan; with increased intraocular pressure, or those at risk of acute narrow angle glaucoma. Monitor patients for appearance of serotonin syndrome or neuroleptic malignant syndrome and discontinue if occurs. Patients may experience feelings of aggression, anger, agitation and irritability. Patients/caregivers should seek medical advice if such behaviour emerges or aggravates. SSRIs/SNRIs may increase the risk of postpartum haemorrhage. Brintellix tablets contain sodium (<1mmol/tablet). Drug interactions: Alcoholic drinks not advisable.

Vortioxetine is extensively metabolised in the liver. Potential for interactions with: MAOIs, MAO-A and MAO-B inhibitors; serotonergic medicines; St John’s wort; products which may lower the seizure threshold, e.g. antidepressants, neuroleptics, mefloquine or bupropion. Lower dose may be considered if strong CYP2D6 inhibitor is added to treatment depending on patient response, these effects may be greater in patients who are poor metabolisers of CYP2D6. Dose adjustment may be considered if a broad cytochrome P450 inducer is added to treatment. Reports of false positive results in urine enzyme immunoassays for methadone in patients taking vortioxetine.

Exercise caution in interpreting positive drug screen results. Effects on ability to drive and operate machines: No or negligible influence, dizziness has been reported; use caution at the start of treatment or when the dose is changed. Adverse events: Most common adverse reaction is nausea, usually mild or moderate, transient and occurs within first two weeks of treatment.

The following have been reported in clinical trials and during post-marketing use: Very common (≥1/10 patients): nausea. Common (≥1/100 to <1/10): abnormal dreams, dizziness, diarrhoea, constipation, vomiting, pruritus, including generalised pruritus. Uncommon (≥1/1,000 to <1/100): flushing, night sweats. Rare (≥1/10,000 to <1/1,000): mydriasis (which may lead to acute narrow- angle glaucoma). Not known: anaphylactic reaction, hyponatraemia, insomnia, agitation, aggression, serotonin syndrome, haemorrhage (including contusion, ecchymosis, epistaxis, gastrointestinal or vaginal bleeding), angioedema, urticaria, rash. Sexual dysfunction: 20mg dose was associated with increase in sexual dysfunction. Class effect: Studies in patients ≥50 years of age, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. Not known if relevant to vortioxetine. Paediatrics: Higher incidences reported in adolescents for abdominal pain-related events and suicidal ideation. Prescribers should consult the full SPC in relation to other side effects. Overdose: Management consisting of treating clinical symptoms and relevant monitoring. Legal category: POM, for non-renewable supply. Brintellix Tablets, blisters of: 5mg (EU/1/13/891/002) 28 tablets. 10mg (EU/1/13/891/010) 28 tablets. 15mg (EU/1/13/891/019) 28 tablets. 20mg (EU/1/13/891/028) 28 tablets. Further information available from: Lundbeck Ireland Ltd, 4045 Kingswood Road, Citywest Business Park, Co. Dublin. Tel: 01 468 9800. Date of last revision of PI: November 2020. Reference: IE-BRIN-0254. Brintellix® is a Registered Trade Mark.

Job number: IE-BRIN-0261 Date of preparation: March 2021

Reference: 1. Brintellix Summary of Product Characteristics. Available at https://www.medicines.ie/medicines/brintellix-10-mg-film-coated-tablets-34817/smpc Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to Lundbeck on: 01 468 9800 Email: SafetyLuIreland@lundbeck.com

32 News

Childhood Cancer Diagnosis costs families ¤15K: New Report Reveals Saoírse Ruane with Irish Cancer Society CEO Averil Power

Children’s Fund grant to ¤3,000 and making it easier to access so that more families can be supported through treatment. We are extending our Volunteer Driver Service to children to help with transport costs, and we’re making it easier for families to access our support by establishing an Irish Cancer Society nursing presence in Children’s Health Ireland, Crumlin as well as committing a substantial investment in children’s cancer research.”

Ms Power added, “This substantially increased commitment, which is only possible because of generous donations from the public, must be met with action from Government.

We are calling for lifetime medical cards to be made available to survivors of childhood cancer, as well as the creation of a dedicated grant to cover non-medical expenses for families.”

A childhood cancer diagnosis can cause an average hit of ¤15,300 to annual family incomes on top of other crippling added expenses, new research from the Irish Cancer Society reveals.

Around 200 children are diagnosed with cancer in Ireland each year which has devastating consequences for families.

The Real Cost of Childhood and Adolescent Cancer report by the Irish Cancer Society contains survey findings from Core Research of 100 parents and guardians of a child who is currently going through or has recently experienced a childhood cancer diagnosis.

The research shows that families of children with cancer must also deal with significant added expenses to do with travel to treatment and costs associated with care.

Commenting on the report, Irish Cancer Society CEO Averil Power said, “The words ‘your child has cancer’ are the most devastating that a parent can hear. Cancer is

distressing at any age, but when a child or adolescent is diagnosed with the disease, it throws the world off its axis.

“Life is turned upside down and every facet of a normal childhood is impacted: going to school, taking part in activities, playtime with friends and being away from the family home for prolonged periods at a time.

“Survival is naturally the most important concern for families, but it is the scale of the financial misery layered on top of such a life-changing diagnosis that is the shocking finding from this research.

“When a child is diagnosed it is often the case that one parent will have to give up work. On top of obvious expenses like fuel, food, accommodation for parents and expensive hospital car parking charges, there are a range of ‘hidden costs’ such as childcare, play therapy sessions and higher phone and broadband bills from spending more time away from home.

“We spoke to families who tell us they are simply having to ‘do without’ in a lot of cases as normal life goes out the window and household bills are left to pile up, leaving some in the heartbreaking position of having to raid their life savings, take out additional loans or ask others for financial help.

“The Irish Cancer Society already provides a number of services and support for families including fertility preservation, specialised information on childhood cancers, financial supports, counselling and night nursing to terminally ill children in their own homes, none of which is possible without the generous support we receive from the public.

The family of nine-year-old Saoírse Ruane, from Galway who underwent a life-changing amputation to her leg at the age of seven after being diagnosed with a rare form of cancer in 2019, say they had to contend with financial worries at a “frightening” time.

“When a child becomes critically ill, life comes to a standstill. It was frightening and daunting and I felt sick with worry and I honestly could not stop crying,” said Roseanna Ruane, whose daughter Saoírse became known to households around the country after appearing on last year’s Late Late Toy Show with her new prosthetic limb.

“But these families need more support so they can focus on their child and not have to worry about finances, or navigating their way through complex State supports and welfare entitlements.

“For me I wasn't going to leave her side, but that brought that added worry of how we would survive on one salary. The bills still have to be paid and that's the reality of it all.

We were glad to be able to receive help from the Irish Cancer Society at the time, but more absolutely needs to be done to support families through such a difficult period.”

“That is why we are announcing today new and extended supports for families affected by childhood cancer. We are increasing our

People can donate to support vital childhood cancer services and research from the Irish Cancer Society at www.Cancer.ie/Donate.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

R

IN

O

D

AT ED C I F

PsA | RA | UC

RAPID AND SUSTAINED

EFFICACY A MARK OF XELJANZ

1-6

AN ORAL JAK INHIBITOR FOR THE TREATMENT OF RA, PsA AND UC 7

XELJANZ®• (tofacitinib) Prescribing Information: Please refer to the Summary of Product Characteristics (SmPC) before prescribing XELJANZ 5 mg or 10 mg film-coated tablets, XELJANZ 11 mg prolonged release tablets or X ELJ A NZ 1 mg/mL oral solution..

Presentation: Film-coated tablet containing tofacitinib citrate, equivalent to 5 mg or 10 mg tofacitinib. Prolonged-release tablets containing tofacitinib citrate, equivalent to 11 mg tofacitinib. Oral solution containing tofacitinib citrate, equivalent to 1 mg/mL tofacitinib.

Indications: Please note not all presentations are licensed for all indications, please see dosage section for details: In combination with methotrexate (MTX) for the treatment of moderate to severe active rheumatoid ar thritis (R A) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs. Can be given as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate. In combination with MTX for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease modifying antirheumatic drug (DMARD) therapy. For the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent. For the treatment of active polyarticular juvenile idiopathic ar thr itis (r heumatoid f ac tor positi v e [R F +] or negati v e [R F -] polyarthritis, and extended oligoarthritis), and juvenile psoriatic arthritis (PsA) in patients 2 years of age and older, who have responded inadequately to previous therapy with DMARDs. Can be given in combination with methotrexate (MTX) or as monotherapy in case of intolerance to MT X or where continued treatment with MT X is inappropriate. Dosage: Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of the condition for which tofacitinib is indicated. Tofacitinib is given with or without food. RA and PsA: The recommended dose is 5 mg orally twice daily or 11 mg once daily which should not be exceeded. Treatment with tofacitinib 5 mg film coated tablets twice daily and tofacitinib 11 mg prolonged release tablet once daily may be switched between each other on the day following the last dose of either tablet. UC: The recommended dose is 10 mg given orally twice daily for induction for 8 weeks. For patients who do not achieve adequate therapeutic benefit by week 8, the induction dose of 10 mg twice daily can be extended for an additional 8 weeks (16 weeks total), followed by 5 mg twice daily for maintenance.

Tofacitinib induction therapy should be discontinued in any patient who shows no evidence of therapeutic benefit by week 16. The recommended dose for maintenance treatment is tofacitinib 5 mg given orally twice daily. Tofacitinib 10 mg twice daily for maintenance treatment is not r e comm end e d in p a t i en t s w i t h U C w h o ha v e k n o w n v en o us thromboembolism ( V TE) risk factors, unless there is no suitable alternative treatment available. For patients with UC who are not at increased risk for V TE, tofacitinib 10 mg orally twice daily may be considered if the patient experiences a decrease in response on tofacitinib 5 mg twice daily and failed to respond to alternative treatment options for ulcerative colitis such as tumour necrosis factor inhibitor (TNF inhibitor) treatment. Tofacitinib 10 mg twice daily for maintenance treatment should be used for the shor test duration possible. The lowest effective dose needed to maintain response should be used. Polyarticular JIA and juvenile PsA: The recommended dose in patients 2 years of age and older: 10 kg - < 20 kg: 3.2 mg (3.2 mL of oral solution) twice daily, 20 kg - < 40 kg: 4 mg (4 mL of oral solution) twice daily, and ≥ 40 kg 5 mg (5 mL of oral solution or 5 mg film-coated tablet) twice daily. Patients ≥ 40 kg treated with tofacitinib 5 mL oral solution twice daily may be switched to tofacitinib 5 mg film-coated tablets twice daily. Patients < 40 kg cannot be switched from tofacitinib oral solution.

Dose interruption in adults and paediatric patients: Tofacitinib treatment should be interrupted if a patient develops a serious infection until the infection is controlled. Interruption of dosing may be needed for management of dose-related laborator y abnormalities including lymphopenia, neutropenia, and anaemia. It is recommended not to initiate dosing in patients with an absolute lymphocyte count (ALC) less than 0.75 x 10 9/L, an absolute neutrophil count (ANC) less than 1x10 9 /L or with haemoglobin less than 9 g/dL. It is recommended not to initiate dosing in paediatric patients with an absolute neutrophil count (ANC) less than 1.2 x 10 9/L or with haemoglobin less than 10 g/dL. Renal impairment: No dose adjustment is required in patients with mild or moderate renal impairment. Patients with severe renal impairment the dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal renal function is 5 mg twice daily or 11 mg prolongedrelease tablet once daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal renal function is 10 mg twice daily. Patients with severe renal impairment should remain on a reduced dose even after haemodialysis. Hepatic impairment: No dose

adjustment is required in patients with mild hepatic impairment.

Patients with moderate hepatic impairment dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal hepatic function is 5 mg twice daily or 11 mg prolonged-release tablet once daily.

Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal hepatic function is 10 mg twice daily. Tofacitinib should not be used in patients with severe hepatic impairment. Elderly: No dose adjustment is required in patients aged 65 years and older. Use with caution as increased risk and severity of adverse events. See also Warnings & Precautions for use in patients over 65 years of age.

Interactions: Tofacitinib total daily dose should be reduced by half in adult and paediatric patients receiving potent inhibitors of cytochrome P450 (C YP) 3A4 (e.g. ketoconazole) and in patients receiving 1 or more concomitant medicinal products that result in both moderate inhibition of CYP3A4 as well as potent inhibition of CYP2C19 (e.g. fluconazole).

Coadministration of tofacitinib with potent CYP inducers (e.g. rifampicin) may result in a loss of or reduced clinical response. Coadministration of potent inducers of CYP3A4 with tofacitinib is not recommended. Only in paediatric patients: available data suggest that clinical improvement is observed within 18 weeks of initiation of treatment with tofacitinib.

Continued therapy should be carefully reconsidered in a patient exhibiting no clinical improvement within this timeframe. The safety and ef ficac y of tofacitinib in children less than 2 years of age with polyarticular JIA and juvenile PsA has not been established. The safety and efficacy of tofacitinib in children less than 18 years of age with other indications (e.g. ulcerative colitis) has not been established. The safety and efficacy of tofacitinib prolonged-release formulation in children aged less than 18 years have not been established. Contraindications: Hypersensitivity to any of the ingredients, active tuberculosis (TB), serious infections such as sepsis, or opportunistic infections, severe hepa t ic impair men t , pr egnan c y and la c t a t ion. Warnings and Precautions: Patients treated with tofacitinib should be given a patient alert card. Use in patients over 65 years of age: Considering the increased risk of serious infections, myocardial infarction, and malignancies with tofacitinib in patients over 65 years of age, tofacitinib should only be used in patients over 65 years of age if no suitable treatment alternatives are available. Combination with other therapies: There was a higher incidence of adverse events for the combination of tofacitinib with MTX versus tofacitinib as monotherapy in RA clinical studies. Tofacitinib should b e a v oided in combina t ion w i t h biologic s and p o ten t immunosuppr essant s such as azathiopr ine, 6 -mer captopur ine, ciclosporine and tacrolimus. Venous thromboembolism (VTE): Serious V TE events including pulmonary embolism (PE), some of which were fatal, and deep vein thrombosis (DVT), have been observed in patients taking tofacitinib. Tofacitinib should be used with caution in patients with known risk factors for VTE, regardless of indication and dosage.

Tofacitinib 10 mg t wice daily for maintenance treatment is not recommended in patients with UC who have known V TE risk factors, unless there is no suitable alternative treatment available. Promptly evaluate patients with signs and symptoms of V TE and discontinue tofacitinib in patients with suspected V TE, regardless of dose or indication. Infections: Serious and sometimes fatal infections have been reported in patients administered tofacitinib. Rheumatoid arthritis patients taking corticosteroids may be predisposed to infection. Patients should be closely monitored for infections, with prompt diagnosis and treatment. Treatment should be interrupted if a serious infection develops. As there is a higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used when treating the elderly and patients with diabetes. Tuberculosis: Patients should be evaluated for both active and latent TB prior to being treated with tofacitinib. Patients who test positive for latent TB should be treated with s tandard antimy cobac terial therapy before adminis tering tofacitinib. Viral Reactivation: In clinical studies viral reactivation and cases of herpes zoster have been observed. Screening for viral hepatitis should be performed in accordance with clinical guidelines prior to starting therapy with tofacitinib. The impact on chronic viral hepatitis is not known. Major adverse cardiovascular events (MACE): MACE have been obser ved in patients taking tofacitinib. In a r andomised pos t authorisation safety study in patients with RA who were 50 years of age or older with at least one additional cardiovascular risk factor, an increased incidence of myocardial infarctions was obser ved with tofacitinib compared to TNF inhibitors. In patients over 65 years of age, patients who are current or past smokers, and patients with other cardiovascular risk factors, tofacitinib should only be used if no suitable treatment alternatives are available. Vaccinations: Prior to initiating tofacitinib, it is recommended that all patients, particularly pJIA and jPsA patients, be brought up to date with all immunisations in agreement with current immunisation guidelines. Live vaccines should not be given concurrently with tofacitinib. Malignancy and lymphoproliferative

disorder: Tofacitinib may affect host defences against malignancies. In a randomised post authorisation safety study in patients with RA who were 50 years of age or older with at least one additional cardiovascular risk factor, an increased incidence of malignancies excluding nonmelanoma skin cancer (NMSC), particularly lung cancer and lymphoma, was observed with tofacitinib compared to TNF inhibitors. Lung cancers and lymphoma in patients treated with tofacitinib have also been observed in other clinical studies and in the post marketing setting.

Other malignancies in patients treated with tofacitinib were observed in clinical studies and the post marketing setting, including, but not limited to, breast cancer, melanoma, prostate cancer, and pancreatic cancer. In patients over 65 years of age, patients who are current or past smokers, and patients with other malignancy risk factors (e.g. current malignancy or history of malignancy other than a successfully treated non-melanoma skin cancer) tofacitinib should only be used if no suitable treatment alternatives are available. NMSCs have been reported in patients treated with tofacitinib; the risk of NMSC may be higher in patients treated with tofacitinib 10 mg twice daily than in patients treated with 5 mg twice daily. Periodic skin examination is recommended in patients at increased risk for skin cancer. Interstitial lung disease: Caution is recommended in patients with a history of chronic lung disease as they may be more prone to infection. Asian patients are known to be at higher risk of ILD, caution should be exercised with these patients. Gastrointestinal perforations: Tofacitinib should be used with caution in patients who may be at increased risk, e.g. histor y of diver ticulitis or concomitant use of c o r t i c o s t e r o i d s o r N S A I D s . H y p e r se nsitiv it y: C a s e s o f d r u g hypersensitivity associated with tofacitinib administration have been reported. Allergic reactions included angioedema and urticaria; serious reactions have occurred. If any serious allergic or anaphylactic reaction occurs, tofacitinib should be discontinued immediately. Laboratory Parameters: Increased incidence of lymphopenia and neutropenia have been reported, and decreases in haemoglobin, which should be monitored in accordance with the SmPC. Monitor ANC and haemoglobin at baseline, 4-8 weeks and 3 monthly, ALC at baseline and 3 monthly. Tofacitinib has been associated with increases in lipid parameters, maximal effects were observed within 6 weeks. Monitoring should be performed 8 weeks after initiation and managed according to hyperlipidaemia guidelines.

Increases in liver enzymes greater than 3x ULN were uncommonly repor ted; use caution when initiating with potential hepatotoxic medicinal products. Gastrointestinal obstruction with a non-deformable prolonged-release formulation: C au t ion should b e us ed w hen administering tofacitinib 11 mg prolonged release tablets to patients with pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic).

Pregnancy & Lactation: Use of tofacitinib during pregnancy and breastfeeding is contraindicated. Side Effects: RA: The most common serious adverse reactions were serious infections; pneumonia, cellulitis, herpes zoster, UTIs, diverticulitis, appendicitis and opportunistic infections. The most commonly reported adverse reactions during the first 3 months in controlled clinical trials were headache, upper respirator y trac t infections, nasopharyngitis, diarrhoea, nausea and hypertension. UC: The most commonly repor ted adverse reactions in patients receiving tofacitinib 10 mg twice daily in the induction studies were headache, nasopharyngitis, nausea, and arthralgia. Commonly reported adverse reactions (>1/100 to <1/10) across all indications were pneumonia, influenza, herpes zoster, urinary tract infection, sinusitis, bronchitis, viral upper respirator y tract infection, phar yngitis, anaemia, headache, hypertension, cough, abdominal pain, vomiting, diarrhoea, nausea, gastritis, dyspepsia, rash, arthralgia, pyrexia, oedema peripheral, fatigue, blood creatine phosphokinase increased. Refer to section 4.8 of the SmPC for further information on side effects, including description of s ele c t e d ad v er s e r ea c t ions . L e gal Ca te gor y : S 1 A . Mar ke ting Authorisation Number: EU/1/17/1178/003 – 5 mg (56 film-coated table t s); EU/ 1/ 1 7/ 1 1 7 8/00 7 – 10 mg (5 6 f ilm- coated table t s); E U/ 1 / 1 7/ 1 1 7 8 / 0 1 2 – 1 1 m g ( 2 8 p r o l o n g e d - r e l e a s e t a b l e t s ) ; EU/1/17/1178/015 1mg/mL oral solution. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@pfizer. com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, 9 Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24, + 353 1 467 6500. ˱ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

See section 4.8 of the SmPC for how to report adverse reactions.

Last revised: 08/2021.

Ref: XJ 12_0.

RA = Rheumatoid Arthritis. PsA = Psoriatic Arthritis. UC = Ulcerative Colitis. JAK = Janus Kinase.

1. Mease P, et al. N Engl J Med 2017; 377: 1537–1550. 2. Gladman D, et al. N Engl J Med 2017; 377: 1525–1536. 3. Hanauer S et al. Clinical Gastroenterology and Hepatology 2019;17:139–147. 4. Sandborn WJ et al. N Engl J Med 2017; 376(18): 1723–1736. 5. Fleischmann R et al. N Engl J Med 2012; 267: 495–507. 6. Wollenhaupt et al. Arthritis Research & Therapy (2019) 21:89 7. XELJANZ Summary of Product Characteristics.

PP-XEL-IRL-0656 Date of preparation: September 2021

34 Pain

Management of Pain and Distress in a Paediatric Population Written by: Dr Deirdre Philbin

Written by: Associate Professor Michael Barrett

1. Fellow in Paediatric Emergency Medicine

1. Department of Emergency Medicine, Children's Health Ireland 2. University College Dublin, Children's Health Ireland at Crumlin

Table 1 : Barriers to the treatment of pain in children4 1) The myth that children, especially infants, do not feel pain the way adults do, or if they do, there is no untoward consequence.

2) Lack of formal assessment and reassessment for the presence of pain.

3) Misunderstanding of how to conceptualise and quantify a patient’s subjective pain experience.

4) Lack of knowledge of pain treatments.

5) The notion that addressing pain in children takes too much time and effort.

6) Fears of adverse effects of analgesic medications including respiratory depression and addiction.

7) The notion that addressing pain in children masks clinical signs.

There is NO evidence that provision of early analgesia negatively affects diagnostic accuracy.

Dr Deirdre Philbin

Associate Professor Michael Barrett

Introduction

Recognising pain

Assessment of pain

Most healthcare visits are related to pain and distress. The extensive short and long-term consequences of inadequately treated acute pain have led to universal acceptance that pain management should begin at the earliest opportunity.1 The effective management of pain in children is a priority for patients, parents, and health-care providers.

Current standards recommend simple, timely, sequential processes of recognition, assessment, intervention, reassessment, and maintenance of pain relief.2 ‘Children’ encompasses an extremely broad group from premature neonates to adolescents. There are age-related differences in children which affect all aspects of pain management including assessment, physiological and pharmacological responses, as well as clinical outcomes.3 It is important that these parameters are taken into consideration when managing paediatric pain. There are numerous perceived barriers to the treatment of pain in children outlined in Table 1. These barriers can mean that paediatric pain is frequently under-recognised and unfortunately, under-treated.

It is important for healthcare providers to learn how to recognise that a child is in pain. In the acute setting, behaviour is the main way that infants and preverbal children communicate their pain.4 Always consider co-existing states that may mimic or exacerbate pain (Table 2). A child may present with acute uncontrolled pain (e.g., fracture, appendicitis) or may present with pain due a underlying chronic condition (e.g. sickle cell disease). The expression of pain in both of these circumstances can be quite different e.g. acute distress vs becoming quieter and more withdrawn. As healthcare providers, we must recognise the pain presentation and then manage it appropriately.

The assessment of pain should include history, examination and consideration of the presumed diagnosis.5 There are several validated pain scales available which cover a wide range of ages.6 These pain scales are used in clinical practice to assess a child’s pain and then to classify pain as mild, moderate, or severe. International literature consistently demonstrates that a child self-reporting their pain leads to better assessment and management of pain.7 In general, children greater than 3 years of age can indicate their own pain score (in which case this is more accurate than the score made by the parent or carer). Severe pain is a score of 7 or greater on an age-

8) The notion that NSAIDs usage negatively effect bone healing.

There is no clinical evidence that using NSAIDs affects bone healing in children.

Table 2: Pain exacerbators or mimickers 1) Hunger or ‘Het up’ 2) Anxiety (e.g. stranger anxiety from 9 months onwards) or Anger 3) Lonely 4) Tired 5) Separation from a guardian/parent 6) Stressed

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

appropriate 11-point scale (0-10).

Moderate pain is a score of 3 to 6 and mild pain is a score of 2 of less. Behavioural scales (FLACC) are used for younger infants or children. The pain assessment tools commonly used in clinical practice are outlined in Table 3.

These tools are also used for the reassessment of pain to ensure that analgesia is effective.

Management of pain Interventions in pain management should include both non-pharmacological and pharmacological methods. It must be emphasized that it may not be possible to achieve a completely “pain-free” condition. A realistic target is that the child should be comfortable (or have self-control) with the pain they are experiencing.

Non-pharmacological methods These can be used independently or in combination with pharmacological methods. Parents should remain with their child when in pain or having a painful procedure, as presence of the care giver is shown to reduce pain/distress.8 A Cochrane review examining non pharmacological

XTANDI™ is indicated for the treatment of adult men with metastatic castrationresistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgendeprivation therapy, in whom chemotherapy is not yet clinically indicated.1 XTANDI is also indicated for the treatment of adult men with metastatic castration – resistant prostate cancer whose disease has progressed on or after Docetaxel.1

Abbreviated Prescribing Information - Xtandi (enzalutamide) 40 mg film-coated tablets. Please refer to the Summary of Product Characteristics (SmPC), available on www.medicines.ie, before prescribing. Presentation: Xtandi 40 mg film-coated tablets each containing 40 mg of enzalutamide. Indications: The treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy. The treatment of adult men with high-risk nonmetastatic castration resistant prostate cancer (CRPC). The treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.

The treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy. Posology and administration: Treatment with enzalutamide should be initiated and supervised by specialist physicians experienced in the medical treatment of prostate cancer. The recommended dose is 160 mg enzalutamide (four 40 mg film-coated tablets) as a single oral daily dose. The tablets should be swallowed whole with water, and can be taken with or without food.

Medical castration with a luteinising hormone-releasing hormone (LHRH) analogue should be continued during treatment of patients not surgically castrated. If a patient experiences a ≥ Grade 3 toxicity or an intolerable adverse reaction, dosing should be withheld for one week or until symptoms improve to ≤ Grade 2, then resumed at the same or a reduced dose (120 mg or 80 mg) if warranted. For further details, please refer to the SmPC. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Women who are or may become pregnant. Special warnings and precautions for use: Risk of seizure: Use of enzalutamide has been associated with seizure. The decision to continue treatment in patients who develop seizures should be taken case by case. Posterior reversible encephalopathy syndrome: There have been rare reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving Xtandi. PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of Xtandi in patients who develop PRES is recommended. Second Primary Malignancies: Cases of second primary malignancies have been reported in patients treated with enzalutamide in clinical studies. In phase 3 clinical studies, the most frequently reported events in enzalutamide treated patients, and greater than placebo, were bladder cancer (0.3%), adenocarcinoma of the colon (0.2%), transitional cell carcinoma (0.2%) and bladder transitional cell carcinoma (0.1%). Patients should be advised to promptly seek the attention of their physician if they notice signs of gastrointestinal bleeding, macroscopic haematuria, or other symptoms such as dysuria or urinary urgency develop during treatment with enzalutamide. Concomitant use with other medicinal products: Enzalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products. A review of concomitant medicinal products should therefore be conducted when initiating enzalutamide treatment.

Concomitant use of enzalutamide with medicinal products that are sensitive substrates of many metabolising enzymes or transporters should generally be avoided if their therapeutic effect is of large importance to the patient, and if dose adjustments cannot easily be performed based on monitoring of efficacy or plasma concentrations. Co-administration with warfarin and coumarin-like anticoagulants should be avoided. If Xtandi is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted. Renal impairment: Caution is required in patients with severe renal impairment as enzalutamide has not been studied in this patient population. Severe hepatic impairment: An increased half-life of enzalutamide has been observed in patients with severe hepatic impairment, possibly related to increased tissue distribution. The clinical relevance of this observation remains unknown. A prolonged time to reach steady state concentrations is however anticipated, and the time to maximum pharmacological effect as well as time for onset and decline of enzyme induction may be increased. Recent cardiovascular disease: The phase 3 studies excluded patients with recent myocardial infarction (in the past 6 months) or unstable angina (in the past 3 months), New York Heart Association Class (NYHA) III or IV heart failure except if Left Ventricular Ejection Fraction (LVEF) ≥ 45%, bradycardia or uncontrolled hypertension. This should be taken into account if Xtandi is prescribed in these patients. Androgen deprivation therapy may prolong the QT interval: In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Xtandi. Use with chemotherapy: The safety and efficacy of concomitant use of Xtandi with cytotoxic chemotherapy has not been established. Co-administration of enzalutamide has no clinically References: 1. XTANDI Summary of Product Characteristics.

relevant effect on the pharmacokinetics of intravenous docetaxel; however, an increase in the occurrence of docetaxel-induced neutropenia cannot be excluded.

Hypersensitivity reactions: Hypersensitivity reactions manifested by symptoms including, but not limited to, rash, or face, tongue, lip, or pharyngeal oedema have been observed with enzalutamide. Severe cutaneous adverse reactions (SCARs) have been reported with enzalutamide. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions.

Interactions: Potential for other medicinal products to affect enzalutamide exposures: CYP2C8 plays an important role in the elimination of enzalutamide and in the formation of its active metabolite. Strong inhibitors (e.g. gemfibrozil) of CYP2C8 are to be avoided or used with caution during enzalutamide treatment. If patients must be co-administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily. No dose adjustment is necessary when Xtandi is coadministered with inducers of CYP2C8. CYP3A4 plays a minor role in the metabolism of enzalutamide. No dose adjustment is necessary when Xtandi is co-administered with inhibitors or inducers of CYP3A4. Potential for enzalutamide to affect exposures to other medicinal products: Enzalutamide is a potent enzyme inducer and increases the synthesis of many enzymes and transporters; therefore, interaction with many common medicinal products that are substrates of enzymes or transporters is expected. Enzymes that may be induced include CYP3A in the liver and gut, CYP2B6, CYP2C9, CYP2C19, and uridine 5’-diphospho-glucuronosyltransferase (UGTs glucuronide conjugating enzymes). The transport protein P-gp may also be induced, and probably other transporters as well, e.g. multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein (BCRP) and the organic anion transporting polypeptide 1B1 (OATP1B1). In vivo studies have shown that enzalutamide is a strong inducer of CYP3A4 and a moderate inducer of CYP2C9 and CYP2C19. The full induction potential of enzalutamide may not occur until approximately 1 month after the start of treatment, when steady-state plasma concentrations of enzalutamide are reached, although some induction effects may be apparent earlier. Patients taking medicinal products that are substrates of CYP2B6, CYP3A4, CYP2C9, CYP2C19 or UGT1A1 should be evaluated for possible loss of pharmacological effects (or increase in effects in cases where active metabolites are formed) during the first month of enzalutamide treatment, and dose adjustment should be considered as appropriate.

In consideration of the long half-life of enzalutamide (5.8 days), effects on enzymes may persist for one month or longer after stopping enzalutamide. A gradual dose reduction of the concomitant medicinal product may be necessary when stopping enzalutamide treatment. In vitro data indicate that enzalutamide may be an inhibitor of the efflux transporter P-gp. The effect of enzalutamide on P-gp substrates has not been evaluated in vivo; however, under conditions of clinical use, enzalutamide may be an inducer of P-gp via activation of the nuclear pregnane receptor (PXR). Medicinal products with a narrow therapeutic range that are substrates for P-gp (e.g. colchicine, dabigatran etexilate, digoxin) should be used with caution when administered concomitantly with Xtandi and may require dose adjustment to maintain optimal plasma concentrations. Based on in vitro data, inhibition of BCRP and MRP2 (in the intestine), as well as organic anion transporter 3 (OAT3) and organic cation transporter 1 (OCT1) (systemically) cannot be excluded. Theoretically, induction of these transporters is also possible, and the net effect is presently unknown. Since androgen deprivation treatment may prolong the QT interval, the concomitant use of Xtandi with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated. Fertility, pregnancy and lactation: There are no human data on the use of Xtandi in pregnancy and this medicinal product is not for use in women of childbearing potential. This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant. It is not known whether enzalutamide or its metabolites are present in semen. A condom is required during and for 3 months after treatment with enzalutamide if the patient is engaged in sexual activity with a pregnant woman. If the patient engages in sexual intercourse with a woman of childbearing potential a condom and another form of birth control must be used during and for 3 months after treatment. Enzalutamide is not for use in women. Enzalutamide is contraindicated in women who are, or who may become, pregnant. It is not known if enzalutamide is present in human milk. Enzalutamide and/or its metabolites are secreted in rat milk. Animal studies showed that enzalutamide affected the reproductive system in male rats and dogs. Driving and use of machines: Xtandi may have a moderate influence on the ability to drive and use machines as psychiatric and neurologic events including seizure have been reported. Patients should be advised of the potential risk of experiencing a psychiatric or neurological event while driving or operating machines. Undesirable effects: Summary of the safety profile: The most common adverse reactions are asthenia/fatigue, hot flush, hypertension, fractures, and fall. Other important adverse reactions include cognitive disorder and

XTD_2021_0077_IE Date of preparation: May 2021

neutropenia. Seizure occurred in 0.5% of enzalutamide-treated patients, 0.1% of placebo-treated patients, and 0.3% in bicalutamide-treated patients. Rare cases of posterior reversible encephalopathy syndrome have been reported in enzalutamidetreated patients. List of adverse reactions: Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Adverse reactions identified in controlled clinical trials and post-marketing (Listed by MedDRA System organ class, frequency and adverse reaction): Blood and lymphatic system disorders Uncommon: leucopenia, neutropenia; Not known*: thrombocytopenia Immune system disorders Not known*: face oedema, tongue oedema, lip oedema, pharyngeal oedema Psychiatric disorders Common: anxiety; Uncommon: visual hallucination Nervous system disorders Common: headache, memory impairment, amnesia, disturbance in attention, dysgeusia, restless legs syndrome; Uncommon: cognitive disorder, seizureҰ; Not known*: posterior reversible encephalopathy syndrome Cardiac disorders Common: ischemic heart diseaseǂ; Not known*: QT-prolongation Vascular disorders Very common: hot flush, hypertension Gastrointestinal disorders Not known*: nausea, vomiting, diarrhoea Skin and subcutaneous tissue disorders Common: dry skin, pruritus; Not known*: rash Musculoskeletal and connective tissue disorders Very common: fractures**; Not known*: myalgia, muscle spasms, muscular weakness, back pain Reproductive system and breast disorder Common: gynaecomastia General disorders and administration site conditions Very common: asthenia, fatigue Injury, poisoning and procedural complications Very common: fall. *Spontaneous reports from post-marketing experience. ҰAs evaluated by narrow SMQs of ‘Convulsions’ including convulsion, grand mal convulsion, complex partial seizures, partial seizures and status epilepticus. This includes rare cases of seizure with complications leading to death. ǂAs evaluated by narrow SMQs of ‘Myocardial Infarction’ and ‘Other Ischemic Heart Disease’ including the following preferred terms observed in at least two patients in randomized placebo-controlled phase 3 studies: angina pectoris, coronary artery disease, myocardial infarctions, acute myocardial infarction, acute coronary syndrome, angina unstable, myocardial ischaemia and arteriosclerosis coronary artery. **Includes all preferred terms with the word ‘fracture’ in bones. Description of selected adverse reactions: Seizure In controlled clinical studies, 22 patients (0.5%) experienced a seizure out of 4168 patients treated with a daily dose of 160 mg enzalutamide, whereas three patients (0.1%) receiving placebo and one patient (0.3%) receiving bicalutamide experienced a seizure. Dose appears to be an important predictor of the risk of seizure, as reflected by preclinical data, and data from a dose-escalation study. In the controlled clinical studies, patients with prior seizure or risk factors for seizure were excluded. In the 9785 CL 0403 (UPWARD) single-arm trial to assess incidence of seizure in patients with predisposing factors for seizure (whereof 1.6% had a history of seizures), 8 of 366 (2.2%) patients treated with enzalutamide experienced a seizure. The median duration of treatment was 9.3 months. The mechanism by which enzalutamide may lower the seizure threshold is not known but could be related to data from in vitro studies showing that enzalutamide and its active metabolite bind to and can inhibit the activity of the GABA gated chloride channel. Ischemic Heart Disease In randomized placebocontrolled clinical studies, ischemic heart disease occurred in 3.7% of patients treated with enzalutamide plus ADT compared to 1.5% patients treated with placebo plus ADT. Fifteen (0.4%) patients treated with enzalutamide and 2 (0.1%) patients treated with placebo had an ischemic heart disease event that led to death. Legal category: POM/S1A. Marketing Authorisation number: Xtandi 40 mg film-coated tablets: EU/1/13/846/002 Marketing Authorisation Holder: Astellas Pharma Europe B.V., Sylviusweg 62, 2333 BE Leiden, The Netherlands. Further information is available from: Astellas Pharma Co. Ltd., 5 Waterside, Citywest Business Campus, Dublin 24. Tel.: +353 1 467 1555. SmPC with full prescribing information available upon request.

Job number: XTD_2021_0085_IE Date of preparation of API: May 2021

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance Website: www.hpra.ie

Astellas Pharma Co. Ltd. Tel: + 353 1 467 1555 E- mail: irishdrugsafety@astellas.com

scales (FLACC) are used for younger infants or children. The pain assessment tools commonly used in clinical practice are outlined in Table 3. These tools are also used for the reassessment of pain to

36 Pain

ensure that analgesia is effective.

Table 3: Examples of pain assessment tools Table 3: Examples of pain assessment tools

methods of pain relief found sufficient evidence to support the efficacy of distraction, hypnosis, and cognitive behavioural techniques in reducing needlerelated pain and distress in children and adolescents.9 For infants, strong evidence exists for the use of comfort measures such as swaddling, non-nutritive sucking and breast-feeding for reduction of pain scores in the infant population.10 For older children, distraction techniques are particularly effective. These may include distracting visual aids (e.g. books, smart devices, virtual reality headsets) and play, either with a play therapist or guardian (blowing bubbles, music, conversation/ interaction with caregiver).11 Additional non-pharmacological methods are listed in Table 4.

Suggested language for parents and health care providers should be positive, distracting, truthful with a coaching focus which rewards with praise. Language that is vague, negative, critical or apologetic should be avoided.

Pharmacological methods The pharmacological agent of choice will be dictated by the child’s age-appropriate pain score.

Pain should be reassessed at regular intervals once analgesia has been administered.

For mild pain, paracetamol and ibuprofen should be used. These may be given orally or rectally.

Despite a slow onset of action, oral medications are generally preferred as they can be given painlessly, have a synergistic effect when used with other analgesics, and are usually more acceptable to parents and children.

Administration of analgesia rectally can be particularly useful if the child is vomiting although this route may prove unacceptable for parents and may add to the older child’s distress. Intramuscular administration of pain relief has a limited role in the management of acute pain in children because the injection is often painful, absorption unpredictable, and the onset of effect slow.

For severe pain, immediate administration of opiates in combination with oral medications and non-pharmacological methods is recommended. Morphine and fentanyl are the opioids of choice used for severe pain in children.

The intranasal route is commonly used as it avoids the distress associated with obtaining intra-

Assessment tool

Age range

Assessment

Faces, Legs, Activity, Cry

Non-verbal children other than

Facial expression, leg position, activity

and Consolability

neonates; can be adapted for

pattern, presence of crying and nature of cry,

children, distraction techniques particularly effective. These (FLACC) scale use inare cognitive impairment. ability may to beinclude consoleddistracting visual aids under headsets) 3 years old.and play, either with a play therapist or guardian (e.g., books, smart devices,Typically, virtual reality Wong Baker Faces music, conversation/interaction 3 years onwards Six-line drawn faces generated (blowing bubbles, with caregiver) [11]. Additional non-from children’s for drawings pharmacological methods are listed in Table 4. Suggested language parents and health care Manchester Pain be Ladder 3 years till adulthood Six pictured varying levels pain on providers should positive, distracting, truthful with coaching focus faces whichinrewards with of praise. an ascending ladder with associated pain

Language to avoid is vague, negative, critical, and apologetic.

statements/ability to do activities and a numeric scale.

Table 4: Commonly used non-pharmacological methods of pain relief Management of painMeasures Physical Comfort

Oral Stimulation Breastfeeding, in infants andand neonates Interventions in pain management shouldPacifier includeand bothsucking non-pharmacological pharmacological PhysicalItContact Skin-to-skin cuddling, swaddling and kangaroo care methods. must be emphasized that contact, it may notrocking, be possible to achieve a completely “pain-free” condition. is that the child should Touch A realistic target Stroking, rubbing, pattingbe comfortable (or have self-control) with the pain they are experiencing.

Dressings The covering of an injury may provide psychological benefit. Burns dressings

that may cool, or cellophane wrap, can alleviate the pain in a paediatric burn.

Non-pharmacological methods

Splintage

Simple splintage of fractures may provide analgesia and minimise ongoing

These can be used independently or inbleeding. combination with pharmacological methods. Parents should trauma and remain with their child when in pain or having a painful procedure, as presence of the care giver is

Temperature

Use of cold packs is a standard approach for ligamentous injuries and pain from

regulation

insect and marine stings can be treated by applying cold or heat to the affected

shown to reduce pain/distress [8]. A Cochrane review examining non pharmacological methods of pain relief found sufficient evidence to support the efficacy of distraction, hypnosis, and cognitive

part. Cold spray and ice packs provide immediate short-term relief.

behavioural techniques in reducing needle-related pain and distress in children and adolescents [9].

Distracting Activities and Language

For infants, strong evidence exists for the use of comfort measures such as swaddling, non-nutritive

Visualand aidsbreast-feeding Bubbles, Books of (cartoons or an activity colouring), sucking for reduction pain scores in the infante.g. population.

[10]puppets, For older smart devices (interactive games or more passive videos) and virtual reality headsets.

Communications/

Conversation (e.g. Storytelling, reassurance, positive language and avoidance

auditory aids

of negative language), music, sound, games. Guided imagery and hypnosis

Table 4: Commonly used and prilocaine) and Ametop non-pharmacological methods of (tetracaine) can be used on studies found that intranasal pain relief intact skin in patients older than fentanyl is absorbed rapidly across one month before minor skin the nasal mucosa and provides The pharmacological agent of choice will be dictated by the child’s age -appropriate pain score. Pain procedures. Ametop takes 45 initial pain relief comparable 13,14 minutesonce to anaesthetise the been administered. should be reassessed regular intervals analgesia has to intravenous opiates.12,at Several randomised controlled skin, whereas EMLA takes 60 The doses and indications for trials have shown that it has a minutes.

Ethyl chloride (coolant) commonly used analgesics in similar is less For mild pain, paracetamol and ibuprofen should be used.

These may beefficacy given but orally or painful rectally. spray is an alternative for minor children are outlined in Table 5. to apply.16,17 cutaneous procedures such as Procedural painonset of action, oral medications Despite a slow generally preferredLocal as they can be given painlessly, venepuncture,are especially when anaesthetics for infiltration urgent, but its efficacy is unclear. include lidocaine (with or without Pharmacological agents used have a synergistic effect when usedLAT with analgesics, and and are usually more acceptable to parents gelother (lidocaine, adrenaline, adrenaline) and bupivacaine. for procedural pain (i.e., pain tetracaine) is useful in providing Local nerve blocks (without associated with Administration procedures such of analgesia rectally can be particularly useful if the child is vomiting and children. anaesthesia for the cleaning adrenaline) completely or partially as fracture manipulation, wound and repair of open wounds such anaesthetise the area supplied by exploration) can include topical, as skin lacerations. All simple that nerve. Common examples local, or regional anaesthesia. lacerations less than 5cm in length include digital nerve blocks for Topical anaesthetic preparations can be considered for exploration injuries to the fingers, and the such as EMLA (euteric mixture and repair using LAT gel rather femoral nerve block for femoral than local anaesthetic infiltration. shaft fractures. Specific nerve of local anaesthetics—lidocaine venous access. Well designed Pharmacological methods

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Break the cycle of chronic pain PALEXIA® SR Tablets are indicated for the management of severe chronic pain in adults, which can be adequately managed only with opioid analgesics1

PALEXIA® SR was associated with significant improvements in quality of life and function as measured by the Short Form-12 (SF-12) health survey and the EuroQol-5 Dimension (EQ-5D) health status questionnaire in patients with severe chronic low back pain with a neuropathic component2

PALEXIA SR® Prolonged Release Tablets Prescribing Information. Refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentation: 50 mg (white), 100 mg (pale yellow), 150 mg (pale pink), 200 mg (pale orange) and 250 mg (brownish red) prolonged-release tablets contain 50 mg, 100 mg, 150 mg, 200 mg and 250 mg of tapentadol (as hydrochloride) respectively. Indication: Palexia SR is indicated for the management of severe chronic pain in adults, which can be adequately managed only with opioid analgesics. Dosage and method of administration: Individualise according to severity of pain, the previous treatment experience and the ability to monitor the patient. Swallowed whole with sufficient liquid, not divided or chewed, with or without food. The tablet shell may not be completely digested and eliminated / seen in the patient’s stool which has no clinical significance as the active substance will have already been absorbed. Initial dose 50 mg twice a day. Switching from other opioids may require higher initial doses. Titrate in increments of 50 mg twice a day every 3 days for adequate pain control.

Total daily doses greater than 500 mg not recommended. Discontinuation of treatment: Taper dose gradually to prevent withdrawal symptoms. Renal/hepatic impairment: Not recommended in patients with severe cases. Caution and dose adjustments with moderate hepatic impairment. Elderly: May need dose adjustments. Children below 18 years: Not recommended. Contraindications: Hypersensitivity to ingredients, suspected or having paralytic ileus, acute intoxication with alcohol, hypnotics, centrally acting analgesics or psychotropics. Not for use when mu-opioid receptor agonists are contraindicated (e.g. significant respiratory depression, acute or severe bronchial asthma or hypercapnia). Special warnings and precautions: Abuse and addiction potential of Palexia should be considered where there is increased risk of misuse, abuse, addiction or diversion. All patients should be carefully monitored for signs of abuse and addiction. Concomitant use with sedating medicinal products such as benzodiazepines or related substances may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedating medicinal products should be reserved for patients for whom alternative treatment options are not possible. If used concomitantly, reduction of dose of one or both agents should be considered and the duration of the concomitant treatment should be as short as possible. The patients should be followed closely for signs and symptoms of respiratory depression and sedation. It is strongly recommended to inform patients and caregivers to be aware of these symptoms. At high doses or in mu-opioid receptor agonist sensitive patients, dose-related respiratory depression may occur. Caution and monitoring required with impaired respiratory function.

Should not use in patients susceptible to intracranial effects of carbon dioxide retention (e.g. increased intracranial pressure, impaired consciousness or coma). Use with caution with head injury, brain tumors, moderate hepatic impairment, biliary tract disease including acute pancreatitis. Not recommended if history of or at risk of seizures. May increase the seizure risk in patients taking medicinal products that lower the seizure threshold. Not recommended in severe renal or hepatic impairment. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage. Care should be taken when combining with mixed mu-opioid agonists/antagonists (e.g. pentazocine, nalbuphine) or partial mu-opioid agonists (e.g. buprenorphine). Should not use with hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Interactions: The concomitant use with sedating medicinal products such as benzodiazepines or other respiratory or CNS depressants (other opioids, antitussives or substitution treatments, barbiturates, antipsychotics, H1-antihistamines, alcohol) increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. When combined therapy with a respiratory or CNS depressant is contemplated, the reduction of dose of one or both agents should be considered and the duration of the concomitant use should be limited. Can induce convulsions and increase the potential for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other medicinal products that lower the seizure threshold to cause convulsions. There have been reports of serotonin syndrome in a temporal connection with the therapeutic use of tapentadol in combination with serotoninergic medicinal products (e.g. SSIRs, SNRIs and tricyclic antidepressants). Use with strong inhibitors of uridine diphosphate transferase isoenzymes (involved in glucuronidation) may increase systemic exposure of Palexia SR. Caution if concomitant administration of strong enzyme inducing drugs (e.g. rifampicin, phenobarbital, St John’s Wort) starts or stops as this may lead to decreased efficacy or risk for adverse events, respectively. Avoid use in patients who have taken monoamine oxidase inhibitors (MAOIs) within the last 14 days, due to cardiovascular events. Pregnancy and lactation: Use in pregnancy only if the potential benefit justifies the potential risk to the foetus. Not recommended during and immediately before labour and delivery. Do not use during breast feeding. Driving and using machines: May have major effect on ability to drive and use machines, especially at the beginning or change in dosage, in connection with alcohol or tranquilisers. Undesirable effects: Very common (≥1/10): dizziness, somnolence, headache, nausea, constipation. Common (≥1/100, <1/10): decreased appetite, anxiety, depressed mood, sleep disorder, nervousness, restlessness, disturbance in attention, tremor, involuntary muscle contractions, flushing, dyspnoea, vomiting, diarrhoea, dyspepsia, pruritus, hyperhidrosis, rash, asthenia, fatigue, feeling of body temperature change, mucosal dryness, oedema. Other important undesirable effects observed in clinical trials and/or postmarketing: drug hypersensitivity, depressed level of consciousness, mental impairment, syncope (uncommon ≥1/1000, <1/100), impaired gastric emptying, respiratory depression, convulsion, angioedema, anaphylaxis and anaphylactic shock, drug dependence (rare ≥1/10,000, <1/1000), delirium (unknown). No evidence of increased risk of suicidal ideation or suicide with Palexia SR. Additional information is available on request. Overdose: Seek specialist treatment (see SmPC). Legal classification: POM, CD (Schedule II). Marketing Authorisation numbers and pack sizes: 50 mg: PA 2242/12/4, 28 and 56 packs; 100 mg: PA 2242/12/5, 56 pack; 150 mg: PA 2242/12/6, 56 pack; 200 mg: PA 2242/12/7, 56 pack and 250 mg: PA 2242/12/8, 56 pack. Marketing Authorisation Holder: Grünenthal Pharma Ltd, 4045 Kingswood Road, Citywest Business Park, Citywest, Co. Dublin, Ireland.

M-PLX-IE-03-20-0004. Date of Preparation: March 2020.

References: 1. Palexia SR Summary of Product Characteristics. 2. Baron R, et al. Tolerability, Safety, and Quality of Life with Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR in Patients with Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-label, Phase 3b/4 Trial. Pain Practice. 2016;16(5):600-619.

M-PLX-IE-11-20-0008 – November 2020

38 Pain blocks can be performed for minor surgical procedures around the hand, face, and ears.

Table 5: Doses and indications for commonly used analgesics in children [15] Drug Primary use Dose Paracetamol

Analgesic

Nitrous oxide is an anaesthetic gas which is delivered in variable concentrations with oxygen. It is frequently used for procedural sedation in children e.g., suturing a laceration. It has modest analgesic and sedative properties, with minimal respiratory and cardiovascular depression.18 It can be delivered painlessly through inhalation and its rapid onset and recovery make it ideal for use in the emergency department.

Ketamine is a dissociative anaesthetic agent which is used to facilitate short painful procedures in children. Ketamine acts by binding to N-methyl-Daspartate (NMDA) receptors and creates a dissociation (disconnection) between the cortex and the limbic system and prevents the higher centres from perceiving visual, auditory, or painful stimuli.

Protective airway reflexes, spontaneous respiration as well as cardiovascular stability are maintained which makes ketamine a particularly useful agent for the sedation of children. Numerous large studies have consistently demonstrated its safety for use in children.19,20 Conclusion The safe and effective management of pain in children is a clinical priority. Pain should be assessed using a validated and age-appropriate pain scale and with consideration of pain exacerbators or mimickers.

Non-pharmacological and pharmacological methods should be used to treat pain and distress accordingly. Topical, local, and regional anaesthetic agents may be used for procedural pain. Pain should be reassessed frequently to ensure efficacy of interventions.

Over one month: 15mg/kg (max 1g) 4-6 hourly as required. Max dose in 24 hours: 75mg/kg or 4g, whichever is lower.

Rectal >1 month-<3 months: 15mg/kg PR 4-6 hourly as required. Max dose in 24 hours: 75mg/kg in divided doses. >3 months:15mg/kg (max 1g) PR 4-6 hourly as required. Max dose in 24 hours:75mg/kg, not to exceed 4g.

Intravenous <10 kg: 7.5 mg/kg IVI 4-6 hourly. Max dose in 24 hours: 30mg/kg in divided doses. >10kg: 15mg/kg (max 1g) IVI 4- 6hourly.

Max dose in 24 hours: 60mg/kg or 3g , whichever is lower, in divided doses.

Ibuprofen

Analgesic

Irish Association of Emergency Medicine Clinical Guideline: Pain Management for Paediatric Emergency Care IAEM-PainManagement-in-PaediatricEmergency-Care.pdf Translating Emergency Knowledge For Kids Pain Treatment 2021-03-16_ Pain_Treatment_v2.0.pdf (trekk.ca)

References available on request

Table 5: Doses and indications for commonly used analgesics in children15

Oral > 1 month: 7.5-10mg/kg 8 hourly.

Max single dose 400mg. Do not exceed 30mg/kg/24 hours or 1.6g /24 hours, whichever is lower.

Rectal: >6kg -<8kg: 60mg PR 6-8 hourly.

Do not exceed 180mg/24 hours. >8kg -<12kg: 60mg PR 6 hourly. Do not exceed 240mg/24 hours.

Diclofenac sodium

Analgesic

Oral > 6 months; 0.3-1mg/kg (do not exceed 50mg) PO 8 hourly. Max dose 3mg/kg/day or 150mg daily whichever is lower.

Rectal > 6months: 8-12 kg: 12.5mg PR 12 hourly >12 kg: 1mg/kg (do not exceed 50mg) PR 8 hourly. Round dose to nearest available suppository strength. Max dose 3mg/kg/day or 150mg daily whichever is lower.

Used alone in mild pain e.g. a sprained ankle or as an adjunct in moderate or severe pain

There is no therapeutic advantage with IV paracetamol versus other routes of administration. IV paracetamol has utility where other routes of administration are unavailable for clinical reasons.

Used alone in mild pain (for example, minor head injury) or as an adjunct in moderate or severe pain

Used alone in mild pain (for example, small superficial burn or scald) or as an adjunct in moderate or severe pain

Fentanyl

Analgesic

Intranasal >1 year old and >10kg: First dose 1.5 micrograms/kg dose (mas 100micrograms) Second dose: 0.75-1.5 micrograms/kg (max 100 micrograms). N.B. to be given 10 minutes after the first dose and only if adequate analgesia has not been attained.

Acute moderate to severe pain in the emergency setting.

Can be used in conjunction with other analgesics

Morphine

Analgesic

Oral (Oramorph® liquid)

Lower end of dose range should be used in opioid – naïve patients.

Useful online references Children’s Health Ireland formulary app https://apps.apple.com/ie/ developer/our-ladys-childrenshospital-crumlin/id423768291

Oral >32 weeks: 10-15mg/kg 6-8 hourly as required. Max dose in 24 hours: 60mg/kg

Comment

1 month-1yr: 80-200 micrograms/kg up to 6 times in 24 hrs PO 1-2 yrs: 200-400microgram/kg up to 6 times in 24 hrs PO 2-12 yrs: 200-500 microgram/kg (max 15mg) up to 6 times in 24hrs 12-18 yrs: 5-15mg up to 6 times in 24 hours PO Intravenous: >1month -<12 yrs: 0.05-0.2mg/kg (max initial dose 5mg) IV bolus over at least 5 minutes. These doses may be repeated up to 4 times / day if < 6 months and up to 6 times / day if > 6 months. >12 yrs: 5mg IV bolus over at least 5 minutes, up to 6 times daily.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Chronic pain or palliative patients may require higher doses.

Most reliable method to relieve severe pain is by titrated intravenous opiates.

Can be used in conjunction with other analgesics

▼

‖

ENCLYXTO® REGIMENS: DEEP RESPONSE** AND LONGER PFS WITH FIXED TREATMENT DURATION1,2 ‖ Remission as measured by CR/CRi: 1L: VEN+O FTD 1 year1: CR/CRi(at 15 months): 50% (VEN+O) vs 23% (O+Clb) (P<0.0001)1; 2L+: VEN+R FTD 2 years1: CR/CRi‡(at 9 months): 27% (VEN+R) vs 8% (BR)1; ** Deep response as measured by CR/CRi and MRD negativity (PB): 1L: VEN+O FTD 1 year1: MRD negativity (PB)(at 15 months) 76% (VEN+O) (95% CI: 69–81) vs 35% (O+Clb) (95% CI: 29–42) (P<0.0001)1; 2L+ VEN+R FTD 2 years1: MRD negativity (PB)‡(at 9 months): 62% (VEN+R) (95% CI: 55.2–69.2) vs 13% (BR) (95% CI: 8.9– 18.9)1. PFS 4-year estimates‡: 1L: VEN+O FTD 1 year1: 74% (VEN+O) vs 35% (O+Clb) (HR=0.33; 95% CI: 0.25–0.45)2; 2L+: VEN+R FTD 2 years1: 54 months median PFS‡ (95% CI: 48.4– 57.0) (VEN+R) vs 17 months mPFS (95% CI: 15.5–21.7) (BR)1. ‡ Results are descriptive. PFS=progression free survival; CR(i)=complete remission (incomplete marrow recovery); 1L=1st Line; 2L+=2nd Line+; VEN=VENCLYXTO; O=Obinutuzumab; Clb=Chlorambucil; B=Bendamustine; MRD= Minimal Residual Disease; R=Rituximab; PB=peripheral blood; CI=Confidence Interval. FTD=Fixed Treatment Duration. References: 1. VENCLYXTO® SmPC available at www.medicines.ie. 2. Al Sawaf et al, HemaSphere, 2021;5(S2):27

VENCLYXTO®▼ (venetoclax) 10 mg/50 mg/100 mg film-coated tablets. PRESCRIBING INFORMATION. PRESENTATION: Each film-coated tablet contains 10mg, 50mg or 100mg of venetoclax. Please refer to the Summary of Product Characteristics (SmPC) before prescribing. INDICATION: Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (see section 5.1)†. Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy*. Venclyxto monotherapy is indicated for the treatment of CLL in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B cell receptor pathway inhibitor or in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B cell receptor pathway inhibitor*. Venclyxto in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.† DOSAGE AND ADMINISTRATION: Oral. Treatment to be initiated and monitored by a physician experienced in the use of anticancer medicinal products. Patients treated with venetoclax may develop tumour lysis syndrome (TLS).

Refer to SmPC for specific details on TLS management by disease indication. See SmPC for full posology.

Posology (CLL): Dose-titration schedule: the starting dose is 20 mg of venetoclax, once daily for 7 days. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400 mg. Post-titration dose for venetoclax in combination with rituximab: The recommended dose of venetoclax in combination with rituximab is 400 mg once daily. Administer Rituximab after the patient has completed the dose-titration schedule and has received the recommended daily dose of 400 mg venetoclax for 7 days. Venetoclax is taken for 24 months from Cycle 1 Day 1 of rituximab. Venetoclax in combination with obinutuzumab: Venetoclax is given for a total of 12 cycles, each cycle consisting of 28 days: 6 cycles in combination with obinutuzumab, followed by 6 cycles of venetoclax as a single agent. Administer obinutuzumab 100 mg on Cycle 1 Day 1, followed by 900 mg which may be administered on Day 1 or Day 2. Administer 1000 mg on Days 8 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle, for a total of 6 cycles. Start the 5-week venetoclax dose-titration schedule (see Table 1) on Cycle 1 Day 22 and continue through Cycle 2 Day 28. After completing the dose-titration schedule, the recommended dose of venetoclax is 400 mg once daily from Cycle 3 Day 1 of obinutuzumab to the last day of Cycle 12. Post-titration dose for venetoclax monotherapy: the recommended dose of venetoclax is 400 mg once daily. Treatment should be continued until disease progression or no longer tolerated by the patient. Posology (AML): Day 1: 100mg; Day 2: 200mg; Day 3 (and beyond): 400mg. Azacitidine should be administered at 75 mg/m2 either intravenously or subcutaneously on Days 1-7 of each 28-day cycle beginning on Cycle 1 Day 1. Decitabine should be administered at 20 mg/m2 intravenously on Days 1-5 of each 28-day cycle beginning on Cycle 1 Day 1. Venetoclax dosing may be interrupted as needed for management of hematologic toxicities and blood count recovery. Venetoclax, in combination with a hypomethylating agent, should be continued until disease progression or unacceptable toxicity is observed. Patients should swallow the tablets whole with water at approximately the same time each day. The tablets should be taken with a meal. Prevention of tumour lysis syndrome (TLS): Prior to initiating venetoclax, tumour burden assessment, including radiographic evaluation must be performed for all patients.

The following prophylaxis measures should be followed to minimise the risk of TLS and more intensive measures should be employed as overall risk increases; adequate hydration, administration of antihyperuricaemic agents if necessary, blood chemistry monitoring and correction of abnormalities. Monitoring should be increased for patients at high risk of TLS. All patient comorbidities should be considered for riskappropriate prophylaxis and monitoring, either outpatient or in hospital. Dosing interruption and/or dose reduction for toxicities may be required. Dose modifications for TLS or other toxicities may need to be considered during treatment. See SmPC for full details of prophylaxis measures. Special Populations: Elderly: No dose adjustment required. Renal impairment: No dose adjustment is needed for patients with mild, moderate or severe renal impairment (CrCl ≥15 ml/min and <90 ml/min). Venclyxto should be administered to patients with severe renal impairment (CrCl ≥15 ml/min and <30 ml/min) only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS. Patients with reduced renal function may require more intensive prophylaxis to reduce the risk of TLS and closer monitoring.

Safety in patients with severe renal impairment or on dialysis has not been established, and a recommended dose for these patients has not been determined. Hepatic impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. Patients with moderate hepatic impairment should be monitored more closely for signs of toxicity. A dose reduction of at least 50% throughout treatment is recommended for patients with severe hepatic impairment. These patients should be monitored more closely for signs of toxicity. Paediatric Population: The safety and efficacy of Venclyxto in children aged less than 18 years has not been established. CONTRAINDICATIONS: Hypersensitivity to any of the active substances or excipients. In patients with CLL, concomitant use of strong CYP3A inhibitors at initiation and during the dosetitration phase. In all patients, concomitant use of preparations containing St. John’s wort. SPECIAL WARNINGS AND PRECAUTIONS: Tumour lysis syndrome (TLS): The risk of TLS is a continuum based on multiple factors, including comorbidities (particularly reduced renal function), tumour burden and splenomegaly.

Reduced renal function (CrCL < 80mL/min) further increases the risk. Assess patient-specific factors for level of risk of TLS and provide prophylactic hydration and anti-hyperuricaemics to patients prior to first dose of venetoclax to reduce risk of TLS. . Blood chemistries should be monitored and abnormalities managed promptly. Dosing should be interrupted if needed; when restarting venetoclax, dose modification guidance should be followed. More intensive measures should be employed as overall risk increases. Neutropenia and

infections: In patients with CLL, grade 3 or 4 neutropenia has been reported. In patients with AML, grade 3 or 4 neutropenia are common before starting treatment. The neutrophil counts can worsen with venetoclax in combination with a hypomethylating agent. Neutropenia can recur with subsequent cycles of therapy.

Complete blood counts should be monitored throughout the treatment period. Dose interruptions or reductions are recommended for patients with severe neutropenia. Serious infections, including sepsis with fatal outcome, have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections are to receive prompt treatment, including antimicrobials and dose interruption or reduction as appropriate and the use of growth factors (e.g., G-CSF) as appropriate. Immunisation: Live vaccines should not be administered during treatment and thereafter until B-cell recovery as the safety and efficacy has not yet been established. CYP3A inducers: Co-administration of CYP3A4 inducers may lead to decreased Venclyxto exposure and consequently a risk for lack of efficacy. Concomitant use of Venclyxto with strong or moderate CYP3A4 inducers should be avoided. Women of childbearing potential: Women of childbearing potential must use a highly effective method of contraception while taking Venclyxto. INTERACTIONS: See SmPC for full details. Venetoclax is predominantly metabolised by CYP3A. CYP3A inhibitors: In patients with CLL, concomitant use of venetoclax with strong CYP3A inhibitors is contraindicated at initiation and during the dose-titration phasedue to increased risk for TLS. Alternative treatments should be considered. In all patients, if a CYP3A inhibitor must be used, follow the recommendations for managing drug-drug interactions. If a moderate CYP3A inhibitor must be used, the doses must be reduced and patients should be monitored more closely. Refer to SmPC for full details. Grapefruit, Seville oranges and starfruit should be avoided during treatment. P-gp and BCRP inhibitors: Concomitant use of Venclyxto with P-gp and BCRP inhibitors at initiation and during the dose titration phase should be avoided; if a P-gp and BCRP inhibitor must be used, patients should be monitored closely for signs of toxicities. CYP3A inducers: For patients requiring concomitant use of Venclyxto with strong or moderate CYP3A inducers should be avoided. Preparations containing St. John’s wort are contraindicated during treatment with venetoclax. Bile acid sequestrants: Co-administration of bile acid sequestrants with Venclyxto is not recommended as this may reduce the absorption of venetoclax. If a bile acid sequestrant is to be co-administered with Venclyxto, the SmPC for the bile acid sequestrant should be followed to reduce the risk for an interaction, and Venclyxto should be administered at least 4-6 hours after the sequestrant. Warfarin: It is recommended that the international normalised ratio be monitored closely in patients receiving warfarin. Substrates of P-gp, BCRP, and OATP1B1; Co-administration of narrow therapeutic index P-gp, or BCRP substrates with Venclyxto should be avoided. If a narrow therapeutic index P-gp or BCRP substrate must be used, it should be used with caution. For an orally administered P-gp or BCRP substrate sensitive to inhibition in the gastrointestinal tract its administration should be separated from Venclyxto administration as much as possible to minimise a potential interaction. If a statin is used concomitantly with Venclyxto, close monitoring of statin related toxicity is recommended. FERTILITY PREGNANCY AND LACTATION: Women of childbearing potential/Contraception in females: Women should avoid becoming pregnant while taking Venclyxto and for at least 30 days after ending treatment. Pregnancy: Venclyxto is not recommended during pregnancy and in women of childbearing potential not using highly effective contraception. Breast-feeding: Breast-feeding should be discontinued during treatment with Venclyxto.

Fertility: Before starting treatment, counselling on sperm storage may be considered in some male patients.

SIDE EFFECTS: See SmPC for full details on side effects. In patients with CLL: Very common side effects (≥1/10): Pneumonia, upper respiratory tract infection, neutropenia, anaemia, lymphopenia, hyperphosphataemia, hyperkalaemia, hypocalcaemia, diarrhoea, vomiting, nausea, constipation and fatigue.

Common side effects (≥1/100 to <1/10): Sepsis, urinary tract infection, febrile neutropenia, tumour lysis syndrome, hyperuricaemia, and blood creatinine increased. In patients with AML: Very common side effects (≥1/10): Pneumonia, sepsis, urinary tract infection, neutropenia, febrile neutropenia, anaemia, thrombocytopenia, hypokalaemia, decreased appetite, dizziness, headache, hypotension, haemorrhage, dyspnoea, nausea, diarrhoea, vomiting, stomatitis, abdominal pain, arthralgia, fatigue, asthenia, weight decreased and blood bilirubin increased. Common side effects (≥1/100 to <1/10): Tumour lysis syndrome and cholecystitis. Tumour lysis syndrome (TLS): TLS is an important identified risk when initiating Venclyxto. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

LEGAL CATEGORY: POM (S1A). MARKETING AUTHORISATION NUMBERS/PRESENTATIONS: 10mg filmcoated tablet, 14 tablets, EU/1/16/1138/002; 50mg film-coated tablet, 7 tablets, EU/1/16/1138/004; 100mg film-coated tablet, 7 tablets, EU/1/16/1138/005;100mg film-coated tablet, 14 tablets, EU/1/16/1138/006; 100mg film-coated tablet, 112 tablets, EU/1/16/1138/007. MARKETING AUTHORISATION HOLDER: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany. Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. † Indications are not reimbursed * Indications are reimbursed DATE OF REVISION: June 2021 | PI/1138/009 IE-VNCCLL-210037 | DATE OF PREPARATION: October 2021

KEYTRUDA: helping to redefine overall survival expectations for more patients with mNSCLC1-4 PD-L1 <1% or unknown

PD-L1 1-49%

PD-L1 >50%

NONSQUAMOUS

√

√

√

1st line Combination** Therapy3

SQUAMOUS

√

√

√

1st line*** Monotherapy4

NON-SQUAMOUS AND SQUAMOUS

X

X

√

Line

Histology

1st line Combination* Therapy2

* KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. ** KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults. *** KEYTRUDA, as monotherapy, is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a≥ 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations.

Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie.

Adverse events should also be reported to MSD (Tel: 01-2998700) Reference 1. Keytruda Summary of Product Characteristics, September 2021, available at www.medicines.ie.

2. Gandhi L, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378:2078-2092.

3. Paz-Ares L, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379:2040–2051.

4. Reck, M et al. Pembrolizumab versus chemotherapy for PDL1 positive-non-small cell lung cancer, N Eng J Med 2016, 375(19)1823-1833.

ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; mNSCLC=metastatic non–small cell lung carcinoma; PDL1=programmed death ligand 1.

Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7, Ireland.

Date of Preparation: September 2021

Other clinically significant immune-related adverse reactions: The following additional clinically significant, immune-related adverse reactions, have been reported in clinical studies or in post-marketing experience: uveitis, arthritis, myositis, myocarditis, pancreatitis, Guillain-Barré syndrome, myasthenic syndrome, haemolytic anaemia, sarcoidosis, encephalitis, myelitis, vasculitis, cholangitis sclerosing and gastritis. Refer to SmPC for information on management of significant immune-related adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Allogeneic HSCT after treatment with pembrolizumab: Cases of graft-versushost-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with classical Hodgkin lymphoma undergoing allogeneic HSCT after previous exposure to pembrolizumab. Allogeneic HSCT prior to treatment with pembrolizumab: In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with pembrolizumab.

Infusion-related reactions: For Grades 3 or 4infusion reactions including hypersensitivity and anaphylaxis, stop infusion and permanently discontinue pembrolizumab. With Grades 1 or 2 infusion reactions, infusion may continue with close monitoring. Premedication with antipyretic and antihistamine may be considered. Overdose: There is no information on overdose with pembrolizumab. In case of overdose, monitor closely for signs or symptoms of adverse reactions and treat appropriately. INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. No metabolic drug drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. Corticosteroids can be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. FERTILITY, PREGNANCY AND LACTATION Women of childbearing potential Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Pregnancy No data on use in pregnant women. Do not use during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Breast-feeding It is unknown whether pembrolizumab is secreted in human milk. A risk to newborns/ infants cannot be excluded. Fertility No clinical data available. SIDE EFFECTS Refer to SmPC for complete information on side effects. Pembrolizumab is most commonly associated with immune-related adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-and infusion-related adverse reactions.

Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, rash, pruritus, fatigue. Common: pneumonia, thrombocytopenia, neutropenia, lymphopenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, thyroiditis, insomnia, dizziness, dysgeusia, pneumonitis, colitis, dry mouth, severe skin reactions, vitiligo, dry skin, alopecia, eczema, dermatitis acneiform, erythema, dermatitis, myositis, pain in extremity, arthritis, influenza like illness, chills, AST and ALT increases, hypercalcaemia, increase in blood alkaline phosphatase, blood bilirubin increased, blood creatinine increased, infusion related reaction. Combination with chemotherapy: Very Common: pneumonia, anaemia, neutropenia, thrombocytopenia, hypothyroidism, hyponatraemia, hypokalaemia, decreased appetite, insomnia, dizziness, neuropathy peripheral, headache, dyspnoea, cough, alopecia, nausea, diarrhoea, vomiting, abdominal pain, constipation, rash, pruritus, musculoskeletal pain, arthralgia, pyrexia, fatigue, asthenia, oedema, blood creatinine increased. Common: febrile neutropenia, leukopenia, lymphopenia, infusion related reaction, hyperthyroidism, hypocalcaemia, dysgeusia, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), vasculitis, hypertension, pneumonitis, colitis, dry mouth, gastritis, hepatitis, severe skin reactions, dry skin, erythema, dermatitis, myositis, pain in extremity, arthritis, acute kidney injury, influenza-like illness, chills, hypercalcaemia, ALT increase, AST increased, blood alkaline phosphatase increased, blood bilirubin increased. Combination with axitinib: Very Common: hyperthyroidism, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, dysphonia, diarrhoea, abdominal pain, nausea, vomiting, constipation, palmar-plantar erythrodysaesthesia syndrome, rash, pruritus, musculoskeletal pain, arthralgia, pain in extremity, fatigue, asthenia, pyrexia, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, anaemia, neutropenia, leukopenia, thrombocytopenia, infusion related reaction, hypophysitis, thyroiditis, adrenal insufficiency, hypokalaemia, hyponatraemia, hypocalcaemia, insomnia, dizziness, lethargy, neuropathy peripheral, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, dry mouth, gastritis, hepatitis, severe skin reactions, dermatitis acneiform, dermatitis, dry skin, alopecia, eczema, erythema, myositis, arthritis, tenosynovitis, acute kidney injury, nephritis, oedema, influenza like illness, chills, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased PACKAGE QUANTITIES KEYTRUDA 25 mg/mL: 4 mL of concentrate in a 10 mL Type I clear glass vial. Legal Category: POM. Marketing Authorisation numbers EU/1/15/1024/002 Marketing Authorisation holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: June 2021. © Merck Sharp & Dohme B.V. 2021. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 or from www.medicines.ie. PSUSA-202009-II-097

IE-KEY-00476

KEYTRUDA® (pembrolizumab) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing.

PRESENTATION KEYTRUDA 25 mg/mL: One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. INDICATIONS KEYTRUDA as monotherapy is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with Stage III melanoma and lymph node involvement who have undergone complete resection. KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations.

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 with a ≥1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD L1 with a combined positive score (CPS) ≥ 10. KEYTRUDA as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 1. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic HNSCC in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy. KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma (RCC) in adults. KEYTRUDA as monotherapy is indicated for the first line treatment of metastatic microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in adults. KEYTRUDA, in combination with platinum and fluoropyrimidine based chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10. DOSAGE AND ADMINISTRATION See SmPC for full details. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes. The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL is 2 mg/kg bodyweight (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes. KEYTRUDA must not be administered as an intravenous push or bolus injection. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Treat patients until disease progression or unacceptable toxicity. Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. Recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. For the adjuvant treatment of melanoma, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year. KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued (a) For Grade 4 toxicity except for: endocrinopathies that are controlled with replacement hormones; or haematological toxicity, only in patients with cHL in which KEYTRUDA should be withheld until adverse reactions recover to Grade 0-1; (b) If corticosteroid dosing cannot be reduced to ≤10 mg prednisone or equivalent per day within 12 weeks; (c) If a treatment-related toxicity does not resolve to Grade 0 1 within 12 weeks after last dose of KEYTRUDA; (d) If any event occurs a second time at Grade ≥ 3 severity. Patients must be given the Patient Alert Card and be informed about the risks of KEYTRUDA. Special populations Elderly: No dose adjustment necessary. Data from patients ≥ 65 years are too limited to draw conclusions on cHL population. Data are limited in patients ≥ 75 years for pembrolizumab monotherapy in patients with resected Stage III melanoma and MSI-H or dMMR CRC; for pembrolizumab in combination with axitinib in patients with advanced RCC; for chemotherapy combination in patients with metastatic NSCLC and oesophageal carcinoma; for pembrolizumab (with or without chemotherapy) in patients receiving first line treatment for metastatic or unresectable recurrent HNSCC. Renal impairment: No dose adjustment needed for mild or moderate renal impairment. No studies in severe renal impairment. Hepatic impairment: No dose adjustment needed for mild hepatic impairment. No studies in moderate or severe hepatic impairment. Paediatric population: Safety and efficacy in children below 18 years of age not established except in paediatric patients with cHL. CONTRAINDICATIONS Hypersensitivity to the active substance or to any excipients. PRECAUTIONS AND WARNINGS Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations. Immune-related adverse reactions Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. Most immune related adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Immune related adverse reactions have also occurred after the last dose of pembrolizumab. Immune-related adverse reactions affecting more than one body system can occur simultaneously. See SmPC for full details. Immune-related pneumonitis: Patients should be monitored for signs and symptoms of pneumonitis.. Suspected pneumonitis should be confirmed with radiographic imaging and other causes excluded. Refer to SmPC for information on management of immune-related pneumonitis. Immune-related colitis: Patients should be monitored for signs and symptoms of colitis, and other causes excluded. Consider the potential risk of gastrointestinal perforation. Refer to SmPC for information on management of immune-related colitis. Immune-related hepatitis: Patients should be monitored for changes in liver function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and symptoms of hepatitis, and other causes excluded. Refer to SmPC for information on management of Immune-related hepatitis. Immune-related nephritis: Patients should be monitored for changes in renal function, and other causes of renal dysfunction excluded. Refer to SmPC for information on management of immune-related nephritis. Immune-related endocrinopathies: Severe endocrinopathies, including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism have been observed with pembrolizumab treatment and patients should be monitored for these endocrinopathies. Refer to SmPC for information on management of immune-related endocrinopathies. Immune-related skin adverse reactions: Patients should be monitored for suspected severe skin reactions and other causes should be excluded. Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving pembrolizumab. If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued.

CPD 82: PROSTATE CANCER Continuing Professional Development

CPD 60 Second Summary Multiparametric MRI localizes cancer in the prostate, allowing for MRI guided biopsy (MRIGB) 43 alongside transrectal ultrasound-guided systematic biopsy (TRUS-GB). Three MRIGB approaches exist; visual estimation (COG-TB); fusion software-assisted (FUS-TB) and MRI ‘in-bore’ biopsy (IB-TB). It is unknown whether any of these are superior.

We conducted a systematic review and meta-analysis to address three questions. First, whether MRI-GB is superior to TRUS-GB at detecting clinically significant PCa (csPCa). Second, whether MRI-GB is superior to TRUS-GB at avoiding detection of insignificant PCa. Third, whether any MRI-GB strategy is superior at detecting csPCa. A systematic literature review from 2015 to 2019 was performed in accordance with the START recommendations. Studies reporting PCa detection rates, employing MRI-GB and TRUSGB were included and evaluated using the QUADAS-2 checklist.

1553 studies were found, of which 43 were included in the meta-analysis.

For csPCa, MRI-GB was superior in detection to TRUS-GB (0.83 vs. 0.63 [p = 0.02]). MRI-GB was superior in detection to TRUS-GB at avoiding detection of insignificant PCa. No MRIGB technique was superior at detecting csPCa (IB-TB 0.87; COG TB 0.81; FUS-TB 0.81, [p = 0.55]). There was significant heterogeneity observed between the included studies.

In patients with suspected PCa on MRI, MRI-GB offers superior rates of csPCa detection and reduces detection of insignificant PCa compared to TRUS-GB. No individual MRI-GB technique was found to be better in csPCa detection. Prospective adequately powered randomized controlled trials are required.

41

AUTHOR: E. J. Bass, A. Pantovic, M. J. Connor, S. Loeb, A. R. Rastinehad, M. Winkler, Rhian Gabe & H. U. Ahmed

1. REFLECT - Before reading this module, consider the following: Will this clinical area be relevant to my practice?

knowledge gap - will this article satisfy those needs - or will more reading be required?

2. IDENTIFY - If the answer is no, I may still be interested in the area but the article may not contribute towards my continuing professional development (CPD). If the answer is yes, I should identify any knowledge gaps in the clinical area.

4. EVALUATE - Did this article meet my learning needs - and how has my practise changed as a result?Have I identified further learning needs?

3. PLAN - If I have identified a

5. WHAT NEXT - At this time you may like to record your learning for future use or assessment. Follow the

4 previous steps, log and record your findings.

Published by HPN. Copies can be downloaded from www.irishpharmacytraining.ie Disclaimer: All material published is copyright, no part of this can be used in any other publication without permission of the publishers and author.

Diagnostic accuracy of magnetic resonance imaging targeted biopsy techniques compared to transrectal ultrasound guided biopsy of the prostate: a systematic review and meta-analysis Prostate cancer (PCa) is suspected after either an abnormal digital rectal examination (DRE) or raised prostate-specific antigen (PSA) test, or both. Once suspected, PCa requires tissue confirmation.

Traditionally the method to achieve this is the systematic transrectal, ultrasound-guided prostate biopsy (TRUS-GB). The introduction of multiparametric magnetic resonance imaging (mpMRI) allows the identification of discrete areas of abnormal tissue that have a higher likelihood for harbouring clinically significant prostate cancer (csPCa). Thus, this confers a higher sensitivity than TRUS-biopsy alone, approximately 87% to 93%, depending on the definition of csPCa.1 Current guidance now recommends mpMRI to be carried out prior to the first biopsy.2 Its use prior to biopsy has grown rapidly, to near 100% in the UK.3 The ability of mpMRI to localize disease in the prostate allows for targeted or guided biopsy (MRI-GB).

increase in the use of MRI-GB in the United States in recent years [4]. Currently, there is variation in how MRI-GB is performed. Three major technical approaches to MRI-GB are generally employed.

First, visual estimation or cognitive targeting (COG-TB) in which a region of interest (ROI) is identified prior to biopsy and the biopsy operator estimates where it might be on an ultrasound image.

Second, software-assisted fusion (FUS-TB) involves identifying and contouring ROIs on MR-images before biopsy and overlaying these with the prostate contours on ultrasound images during the biopsy procedure. This can be elastic (deformable registration to reflect deformation of the prostate) or rigid (an overlay of MRI to ultrasound images with some adjustment of rotation). Last, inbore biopsy (IB-TB) (or in-gantry) involves performing the biopsy in the MRI scanner, guided by MR imaging taken immediately after each needle placement.

Alongside the proliferation in MRI use pre-biopsy, there is significant interest in MRI-GB.4 For instance, there was a 20-fold

There is currently no consensus on whether any of these approaches is superior in terms of cancer detection. Thus, we conducted

a systematic review and metaanalysis to address first, whether MRI-GB is superior to TRUS-GB at detecting clinically significant PCa (csPCa). Second, if MRI-GB is better at not detecting insignificant PCa, and third if any of the three MRI-GB strategies is superior at detecting csPCa. Search strategy The current systematic review and meta-analysis aimed to update the results published by Wegelin et al., 20175 and followed the guidelines suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.6 We employed the identical search strategy, using the keywords “Prostate OR Prostatic Neoplasm” AND “Biopsy” AND “Magnetic Resonance Imaging OR Image-Guided Biopsy”. The search was performed in PubMed, Embase, and CENTRAL databases with the language restricted to English. As the review by Wegelin et al.6 included studies published before 15/12/2015, the time frame was restricted to 15/12/2015 to 29/07/2019.

The review was registered on

42

CPD 82: PROSTATE CANCER corresponding measures of variation prior to performing the meta-analysis.

PROSPERO (CRD42020179508).

All references were imported in ‘Zotero’ reference manager.

Study selection For the purposes of this metaanalysis, we included studies reporting PCa detection rates among patients at risk of PCa according to their clinical parameters, of IB-TB, or FUSTB, or COG-TB alongside TRUSGB. The exclusion criteria were: inclusion of patients with previously diagnosed PCa, on active surveillance, or mixed populations where this group were not reported on separately. We also excluded studies if data for patients biopsy status was not reported, or, if a previous negative biopsy population was included, we excluded studies where data for with the population no or at least one negative prior biopsy were not separately reported upon. Finally, we excluded studies if the MRI acquisition was not in accordance with the 2012 ESUR guidelines7, or if studies used alternative targeted biopsy strategies such as multiparametric ultrasound.

Quality assessment The methodological quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.8 The assessment was performed by a single

reviewer (AP) and checked by a second (HUA). QUADAS-2 is a tool recommended for use in systematic reviews to evaluate the risk of bias and the applicability of primary diagnostic accuracy studies.8 Data extraction The initial data extraction was performed by a single reviewer (AP) in accordance with the START recommendations9 and doublechecked by a second (HUA). Data collected were: the recruitment method (clinical parameters); investigated population characteristics and sample size; the method of MRI acquisition and evaluation; MRI findings and/or PIRADS score; the threshold for MRI positivity; biopsy method; whether the comparison between these two methods was made; the definition of csPCa and finally the detection rates of csPCa, and clinically insignificant PCa per patient and per score, where available.

Data analysis The analysis was conducted to answer our three stated aims.

For this, we first focused only on studies that reported detection rates with both MRI-GB and TRUS-GB. Therefore, the final sample size of the study population refers to the number of patients that underwent both techniques. We calculated the effect sizes with their

We combined the data of all studies that reported employing any type of MRI-GB and compared it with TRUS-GB. It was obligatory that the studies reported results of both TRUS-GB and MRI-GB separately. The main accuracy measure – cancer detection rate (CDR) - was calculated by dividing the number of patients with detected cancer by TRUS-GB (or MRI-GB), with the total number of patients who were detected with cancer by the combination of TRUS-GB and MRI-GB. Relative CDR was expressed as the relative ratio between the CDR of MRI-GB and TRUS-GB. The standard error of each of the accuracy statistics was obtained by employing the formula for the standard error of a relative risk without taking the paired nature into account because not all studies reported their data in a paired format.10 Superiority of clinically insignificant PCa detection was determined by comparison of the diagnostic yield (the likelihood that the biopsy procedure provides such a diagnosis) of each approach.

In this respect, a lower number is advantageous and therefore the technique was regarded as ‘superior’. The yield of detecting clinically insignificant PCa (defined by each included study) was calculated by dividing the number of patients with insignificant PCa (the number of patients with any PCa minus the number of patients with csPCa) with the total number of patients that underwent biopsy. The relative yields were calculated by dividing the yield of MRI-GB with the yield of TRUSGB. We pooled the estimates by conducting random-effects meta-analysis on precalculated effect sizes with metagen function of the meta package (R studio Version1.2.1335), using the generic inverse variance method and Sidik-Jonkman as a betweenstudy-variance estimator. We assessed the between-study heterogeneity with Cochrane’s Q and I2 tests.11, 12 I2 > 50% with p < 0.05 indicates significant heterogeneity. All analyses were done for csPCa and insignificant PCa detection rates. Publication bias was explored by inspecting the funnel plot and by employing Eggar’s test.

To answer the third review question, we used the accuracy measurements we defined above and focused on studies that reported one of the MRI-GB techniques (IB-TB or FUS-TB or COG-TB). The within-study variances were calculated based on the exact binomial distribution.

The differences in sensitivity of the three techniques was compared by conducting the mixed subgroup analysis with the use of subgroup. analysis.mixed.effects function (dmetar package).

We conducted two additional subgroup analyses - one based on the methodological quality and the other based on prior biopsy history. The former pooled the effect sizes only from the studies with low risk of bias and low concerns regarding applicability.

The latter included three groups (biopsy naive, negative biopsy and a mixed group of both types of patients). We additionally performed a focused analysis that excluded the mixed population group. These analyses were performed for csPCa and clinically insignificant PCa detection rates.

The extracted data were computed and pre-calculated in Microsoft Excel, version 2010, while the meta-analyses were performed in R studio Version 1.2.1335 (Boston, MA, USA).

Results The systematic search of the three databases yielded a total of 1553 articles after removing 456 duplicates. We identified 40 new studies that assessed the diagnostic accuracy of some of the three MRI-GB techniques.

Out of the identified 40 studies, 14 either did not compare the PCa detection rates between MRI-GB and TRUS-GB, or did not perform these comparisons in the same population of patients, thus they were not included in the meta-analysis. Of the remaining 26 studies, six did not report any information about the biopsy status of the study population, leaving 20 studies that were merged with the studies from the systematic review by Wegelin et al.5 The previous systematic review included 23/43 studies included in their meta-analysis.5 Merging new studies with those 23 from the previously published metaanalysis5 provided a total of 43, including 8456 men, were finally

43 included in our meta-analysis (Supplementary Table 1). The complete selection process of the studies is presented in the PRISMA flow chart (Fig. 1). All 20 newly identified studies, containing an additional 4675 men, were included in the metaanalysis comparing the three MRI-GB techniques.

Quality assessment Quality was evaluated only in studies included in the metaanalysis (n = 43)1. All studies were estimated to have low risk regarding applicability to the current review (Supplementary figure 1b). Twenty-five studies were deemed to have a high risk of selection bias13,14,15,16,17,18,19,20,2 1,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38 ,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55

(Supplementary figure 1a).

Population We observed high variability of study population size, characteristics and mean PSA level in the studies included in the meta-analysis. The sample size varied between 20 and 1003 patients, who were aged between 59.7 and 70 years, who either had no or at least one prior negative biopsy. The mean PSA level ranged from 5.7 to 11.0 ng/ml.

Most studies involved a patient group with PSA < 10 ng/ml (n = 38).

A 3-Tesla scanner was used in 77% of studies (n = 33). The most commonly used MRI-GB technique was FUS-TB (n = 31), followed

by COG-TB (n = 8) and then IBTB (n = 5). The definition of the threshold for performing targeted biopsy differed between studies.

The PI-RADS classification system was the most frequent (n = 34), and a score of >/= 3 was the most used cutoff. The studies varied

Fig. 1: PRISMA Flow Diagram.

From: Diagnostic accuracy of magnetic resonance imaging targeted biopsy techniques compared to transrectal ultrasound guided biopsy of the prostate: a systematic review and meta-analysis

considerably in the definition of csPCa as well; therefore we performed the analysis depending on the definition given in the original articles.

MRI-GB versus TRUS-GB Does MRI-GB result in a higher CDR for clinically significant PCa compared with TRUS-GB? We observed a statistically significant difference between the sensitivity of MRI-GB and TRUS-

GB techniques for csPCa, with a pooled relative CDR of 1.24 [95% CI 1.03; 1.50, p = 0.02] although with significant heterogeneity among the studies (I2 = 95.9%).

The pooled CDR for MRI-GB was 0.83 [95% CI 0.76–0.90] and for TRUS-GB 0.63 [95% CI 0.53–0.74]. Heterogeneity was highly significant––83.7% for MRIGB and 97.7% for TRUS-GB. We observed no significant evidence of publication bias (p = 0.392.

Does MRI-GB result in a lower CDR for insignificant PCa compared with TRUS-GB? MRI-GB was less likely to result in a diagnosis of clinically insignificant PCa. The diagnostic yield for MRI-GB was 0.08 [95% CI 0.06; 0.11] (I2 = 93.1%) and the yield for TRUS-GB was 0.15 [95% CI 0.12; 0.17] (I2 = 92.7%). The pooled analysis showed that MRIGB performed significantly better (p < 0.0001) with a pooled relative

44

CPD 82: PROSTATE CANCER

yield of 0.58 [0.46; 0.74], and moderate heterogeneity between the studies of 63.3%3 There was significant publication bias among the studies (p = 0.003)3.

Which MRI-GB technique performed best at detecting csPCa and avoiding detection of insignificant PCa? We observed no statistically significant differences between the three MRI-GB techniques in detecting csPCa (p = 0.55) with IBTB showing a pooled CDR of 0.87 [95% CI 0.81–0.93], COG-TB 0.81 [95% CI 0.69–1.03] and FUS-TB 0.81 [95% CI 0.73-0.91]. There was no statistically significant difference between the three techniques in detecting clinicallyinsignificant PCa (p = 0.46); IB-TB had a pooled yield of 0.10 [95% CI 0.03–0.31]; COG-TB 0.05 [95% CI 0.02–0.11], and FUS-TB 0.08 [95% CI 0.06–0.11].

Subgroup analysis Due to the high heterogeneity among the included studies, we performed a subgroup analysis including only studies with low risk of bias and low concerns of applicability (n = 18). This revealed a relative pooled CDR of 1.23 (1.02; 1.47) in the detection of csPCa in favour of MRI-GB (n = 11). The heterogeneity was high (I2 = 90.4%).

The analysis also found the pooled relative CDR in detecting csPCa trended towards higher in patients that had at least one prior negative biopsy (1.59 [95% CI 1.16-2.16]) compared to biopsy-naive men (1.06 [95% CI 0.94–1.20]) although this did not reach statistical significance (p = 0.06).

Discussion In summary, we first found a significant difference in CDR between TRUS-GB and MRI-GB for the detection of csPCa. We also observed considerably higher values of relative CDR after updating the analysis with newly identified studies than those in the previously published systematic review5). Third, MRI-GB detected fewer clinically insignificant cancers. Fourth, there was no statistically significant difference between the three techniques in CDR for csPCa.

Whilst the replacement of TRUS-GB with MRI-GB is technically achievable, the removal of systematic biopsy from our diagnostic pathway is controversial. This is due to concerns over missing significant disease ‘hidden’ in areas of the prostate that appear normal on MRI. Indeed, this analysis suggests that whilst superior, an MRI-GB approach alone would miss 17% of cases of csPCa. However, by comparison, TRUS-GB would miss 37% of such cases. This is an expected finding. For example, missing 40% of csPCA is broadly in keeping with the literature.1 The multicentre PRECISION trial demonstrated the superiority of MRI-GB over TRUS-GB in terms of both detection of csPCa and of overdiagnosis of clinically insignificant PCa.56 However, some csPCa that is missed by TRUS-GB is detected by MRI-GB and vice versa.57 A combined approach of both systematic and targeted biopsy may be optimal, although these ‘missed’ cancers are likely to be low volume, low grade or with small amounts of pattern 4, leading to ongoing controversy as to their clinical importance.58 The debate over which targeting approach is more accurate is ongoing. None of the aforementioned approaches has proven its superiority in a direct comparative trial. In our analysis, we did not find any approach superior in the critical aspect of detecting csPCa. A recently published RCT directly comparing all three approaches found no difference in csPCa detection rates, although the study was powered for the detection of any cancer.59 The literature may be limited on this topic with highly expert practitioners conducting the COG-TB from which results are reported. Drawing strong conclusions with regard to the presence or absence of superiority of any technique is also challenging due to the significant heterogeneity between included studies. We also found evidence of publication bias in the studies reporting detection rates of csPCa and clinically insignificant disease.

Our meta-analysis has some limitations. First, there was significant patient selection bias in the included studies as in general only men with suspicious MRIs were included. This does not reflect a biopsy-naive population,

arguably the most clinically relevant patient group to which this effect applies. If men with nonsuspicious MRIs were included, it is likely the effect would be larger.57 It should therefore be kept in mind that these studies all evaluate the efficacy of an mpMRI scan and a biopsy strategy.

reference standard for determining the ideal MRI-GB technique is not optimal. Template mapping biopsies would represent a better reference standard for answering our third question. However, one should bear in mind that a recent RCT also found no advantage to any technique.59

Second, there was significant heterogeneity in the included studies. Some variation was observed in MRI acquisition with variance in scanner resolution, the threshold for biopsy and most importantly, there was inconsistency in the MRI reporting standards. However, all the studies included in the meta-analysis followed the European Society of Genito-Urinary (ESUR) prostate mpMRI guideline standards7 and 34 of 43 studies used PIRADS as their chosen reporting system.

Further, there was variance in the indications for biopsy. As we have already stated, a biopsy-naive population is most relevant and the least biased. We included studies with the multitude of indications that physicians face in clinical practice in order to improve our findings’ generalizability for the reader. Naturally, a more homogeneous group of studies is ideal. However, if only studies with biopsy-naive populations were included only 13 studies with 1878 patients could be included; if only studies using PIRADS with a cutoff score of > /=3 were included in addition to a biopsy-naïve population then only two studies could be included in the meta-analysis.

Finally, there were variations in biopsy technique between studies.

For example, by the number of cores taken, or whether TRUS-GB or MRI-GB was performed first. If the former is true then prostatic swelling may affect diagnostic accuracy due to the swelling altering prostatic morphology.

There are also numerous FUS-TB systems available on the market.

Some use rigid fusion systems where the MR-images simply overlay the USS images, and some use elastic fusion systems where double contouring accounts for prostatic deformation by the ultrasound probe. A definitive, multi-user, multi-centre, multifusion platform randomized controlled trial sufficiently powered for csPCa to overcome these incorporation biases is needed.

Third, the thresholds used for csPCa varied although most used the presence of any Gleason >/= 3 + 4 when it was reported.

Further, and more problematic, is that commonly used definitions of csPCa are modelled from systematic biopsy data and as such their utility in targeted biopsy has inherent challenges. For example, targeted biopsies by design take multiple cores from a single area of interest. Thus, when total cancer core lengths or numbers/percentages of positive cores are used in this setting there is a significant risk of overestimation of risk; something we have described as the potential Will–Rogers phenomenon.60 Fourth, given the aforementioned drawbacks of TRUS-GB [1] we acknowledge that its use as a

Conclusions In men where PCa is suspected on MRI, MRI-GB offers superior rates of csPCa detection and significantly reduces diagnoses of insignificant PCa compared to TRUS-GB. In terms of the superiority of MRI-GB techniques we found no significant differences in CDR for csPCa. More than half of the included studies were subject to significant selection bias and thus conclusions must be tempered. Further, in studies reporting on COG-TB, highly expert practitioners performed the biopsies, possibly overstating the sensitivity of the technique. A robust RCT design appropriately powered for csPCa as the primary outcome measure is required to provide a definitive answer.

Bass, E.J., Pantovic, A., Connor, M.J. et al. Diagnostic accuracy of magnetic resonance imaging targeted biopsy techniques compared to transrectal ultrasound guided biopsy of the prostate: a systematic review and metaanalysis. Prostate Cancer Prostatic Dis (2021). https://doi.org/10.1038/ s41391-021-00449-7 References available on request

FOR YOURSELF, WOULD YOU CONSIDER

BOTH EFFICACY AND SAFETY?

Choose both efficacy and safety with ELIQUIS®

ELIQUIS is a factor Xa inhibitor that offers superior risk reduction in stroke and systemic embolism, with significantly less major bleeding vs. warfarin in non-valvular AF patients.1,* • Superiority demonstrated on stroke / systemic embolism vs. warfarin 1 • Superiority demonstrated on major bleeding vs. warfarin 1 ELIQUIS® (apixaban) PRESCRIBING INFORMATION Ireland Consult Summary of Product Characteristics (SmPC) before prescribing PRESENTATION: Film-coated tablets; 5 mg and 2.5 mg apixaban. INDICATION (SPC section 4.1): Prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation (NVAF) with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA), age ≥ 75 years, hypertension, diabetes mellitus or symptomatic heart failure (NYHA Class ≥ II). Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults (see Special warnings and precautions for information on haemodynamically unstable PE patients). Prevention of venous thromboembolic events (VTE) in adults who have undergone elective hip or knee replacement surgery (2.5 mg only). DOSAGE AND ADMINISTRATION (SPC section 4.2): Oral. Taken with water, with or without food. Prevention of stroke and systemic embolism in patients with NVAF: The recommended dose is 5 mg twice a day. In patients who meet at least two of the following criteria: serum creatinine ≥ 1.5 mg/dL (133 micromole/L), age ≥ 80 years, or body weight ≤ 60 kg the recommended dose is Eliquis, 2.5 mg twice daily. Patients with severe renal impairment (creatinine clearance 15-29 ml/min) should receive Eliquis 2.5 mg twice daily. Therapy should be continued long term. Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt): The recommended dose for the treatment of acute DVT and treatment of PE is 10 mg twice daily for the first 7 days followed by 5 mg twice daily. As per available medical guidelines, short duration of treatment (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation). The recommended dose for the prevention of recurrent DVT and PE is 2.5 mg twice daily. When prevention of recurrent DVT and PE is indicated, the 2.5 mg twice daily dose should be initiated following completion of 6 months of treatment with Eliquis 5 mg twice daily or with another anticoagulant. The duration of overall therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding. Prevention of VTE (VTEp): elective hip or knee replacement surgery: The recommended dose is 2.5 mg twice a day. The initial dose should be taken 12 to 24 hours after surgery. Hip replacement surgery, the recommended duration of treatment is 32 to 38 days. Knee replacement surgery, the recommended duration of treatment is 10 to 14 days. Missed Dose for All Indications: If a dose is missed, Eliquis should be taken immediately and then continue with twice daily dose as before. Switching: Switching treatment from parenteral anticoagulants to Eliquis (and vice versa) can be done at the next scheduled dose. These medicinal products should not be administered simultaneously. Switching treatment from VKA therapy to Eliquis: Warfarin or other VKA therapy should be discontinued and Eliquis started when the international normalized ratio (INR) is < 2. Switching treatment from Eliquis to VKA therapy: Administration of Eliquis should be continued for at least 2 days after beginning VKA therapy. After 2 days of co- administration of Eliquis with VKA therapy, an INR should be obtained prior to next scheduled dose of Eliquis. Co-administration of Eliquis and VKA therapy should be continued until the INR is ≥2. Renal Impairment - mild or moderate renal impairment: For the prevention of VTE in elective hip or knee replacement surgery (VTEp), for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt), no dose adjustment is necessary. For the prevention of stroke and systemic embolism in patients with NVAF and serum creatinine ≥ 1.5 mg/dL (133 micromole/L) associated with age ≥ 80 years or body weight ≤ 60 kg, a dose reduction is necessary. In the absence of other criteria for dose reduction (age, body weight), no dose adjustment is necessary. Severe renal impairment (creatinine clearance 15-29 mL/min): For the prevention of VTE in elective hip or knee replacement surgery (VTEp), for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt), Eliquis is to be used with caution. For the prevention of stroke and systemic embolism in patients with NVAF, patients should receive the lower dose of Eliquis 2.5mg twice daily. In patients with creatinine clearance < 15 mL/min, or in patients undergoing dialysis, there is no clinical experience therefore Eliquis is not recommended. See SmPC for further details. Hepatic impairment: Contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Not recommended in patients with severe hepatic impairment. Use with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B). No dose adjustment is required in patients with mild or moderate hepatic impairment. Use with caution in patients with elevated liver enzymes (ALT/AST >2 x ULN) or total bilirubin ≥ 1.5 x ULN. Prior to initiating Eliquis, liver function testing should be performed. Catheter ablation (NVAF): Patients can continue Eliquis use while undergoing catheter ablation. Cardioversion (NVAF): Eliquis can be initiated or continued in NVAF patients who may require cardioversion. See SmPC for further details. Patients with NVAF and acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI): There is limited experience of treatment with apixaban at the recommended dose for NVAF patients when used in combination with antiplatelet agents in patients with ACS and/or undergoing PCI after haemostasis is achieved. See SmPC for further details. Paediatric population: Eliquis is not recommended in children and adolescents below the age of 18. CONTRAINDICATIONS (SPC section 4.3): Hypersensitivity to active substance or to excipients, active clinically significant bleeding, hepatic disease associated with coagulopathy and clinically relevant bleeding risk, lesion or condition if considered a significant risk factor for major bleeding, see SmPC for further details. Concomitant treatment with any other anticoagulant agent except under specific circumstances of switching anticoagulant therapy or when unfractionated heparin (UFH) is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation, see SmPC for further details. WARNINGS AND PRECAUTIONS (SPC section 4.4): Haemorrhage risk: Carefully observe for signs of bleeding. Use with caution in conditions with increased risk of haemorrhage. Discontinue administration if severe haemorrhage occurs. An agent to reverse the anti-factor Xa activity of apixaban is available. For information on reversal and managing bleeding, see SmPC for further details.

Interaction with other medicinal products affecting haemostasis: Concomitant treatment with any other anticoagulant is contraindicated (see contraindications). Concomitant use of Eliquis with antiplatelet agents increases the risk of bleeding. Care with concomitant SSRIs, SNRIs or NSAIDs, including acetylsalicylic acid. Following surgery, other platelet aggregation inhibitors are not recommended concomitantly with Eliquis. In patients with atrial fibrillation and conditions that warrant mono or dual antiplatelet therapy, a careful assessment of the potential benefits against the potential risks should be made before combining this therapy with Eliquis. A clinical trial enrolled patients with atrial fibrillation with ACS and/or undergoing PCI and a planned treatment period with a P2Y12 inhibitor, with or without ASA, and oral anticoagulant (either apixaban or VKA) for 6 months. Concomitant use of ASA increased the risk of ISTH (International Society on Thrombosis and Hemostasis) major or CRNM (Clinically Relevant Non-Major) bleeding in apixaban-treated subjects. See SmPC for further details. Use of thrombolytic agents for the treatment of acute ischemic stroke: Limited experience. Patients with prosthetic heart valves: safety and efficacy of Eliquis have not been studied in patients with prosthetic heart valves, with or without atrial fibrillation. Therefore, the use of Eliquis is not recommended in this setting. Patients with antiphospholipid syndrome: Direct acting Oral Anticoagulants (DOACs), including Eliquis, are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome (see SmPC for further details). Surgery and invasive procedures: Discontinue at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of bleeding.

Discontinue at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding. If surgery or invasive procedures cannot be delayed, appropriate caution should be exercised, taking into consideration an increased risk of bleeding. Eliquis should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established. For patients undergoing catheter ablation for atrial fibrillation, Eliquis treatment does not need to be interrupted. Temporary discontinuation: Discontinuing anticoagulants, including Eliquis, for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of thrombosis. Lapses in therapy should be avoided and if anticoagulation with Eliquis must be temporarily discontinued for any reason, therapy should be restarted as soon as possible. Spinal/ epidural anaesthesia or puncture: Patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal haematoma which can result in long- term or permanent paralysis. The risk of these events may be increased by the post- operative use of indwelling epidural catheters or the concomitant use of medicinal products affecting haemostasis. Indwelling epidural or intrathecal catheters must be removed at least 5 hours prior to the first dose of Eliquis. The risk may also be increased by traumatic or repeated epidural or spinal puncture.

Patients are to be frequently monitored for signs and symptoms of neurological impairment (e.g., numbness or weakness of the legs, bowel or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is necessary. Prior to neuraxial intervention the physician should consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis. There is no clinical experience with the use of Eliquis with indwelling intrathecal or epidural catheters. See SmPC for further details. Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Eliquis is not recommended as an alternative to unfractionated heparin in patients with pulmonary embolism who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy since the safety and efficacy of Eliquis have not been established. Patients with active cancer: Patients with active cancer can be at high risk of both venous thromboembolism and bleeding events. When apixaban is considered for DVT or PE treatment in cancer patients, a careful assessment of the benefits against the risks should be made. Renal impairment: see dosage and administration section. Elderly patients: Increasing age may increase haemorrhagic risk. Also, the co-administration of Eliquis with ASA in elderly patients should be used cautiously because of a potentially higher bleeding risk. Body weight: Low body weight (< 60 kg) may increase haemorrhagic risk. Hepatic impairment: see dosage and administration section. Interaction with Inhibitors of CYP3A4 and P-gp: Not recommended with strong inhibitors of both CYP3A4 and P-gp. These medicinal products may increase Eliquis exposure by 2-fold or greater in the presence of additional factors that increase Eliquis exposure (e.g. severe renal impairment) see SmPC for further details. Interaction with Inducers of CYP3A4 and P-gp: Eliquis should not be used for the treatment of DVT and PE in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp since efficacy may be compromised. Concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp, Eliquis should be used with caution for the prevention of VTE in elective hip or knee replacement surgery, for the prevention of stroke and systemic embolism in patients with NVAF and for the prevention of recurrent DVT and PE, though no dose adjustment for Eliquis is required during concomitant therapy with such medicinal products. Hip fracture surgery: Eliquis has not been studied in clinical trials in patients undergoing hip fracture surgery.

Therefore, it is not recommended in these patients. Laboratory parameters: Clotting tests (PT, INR, and aPTT) are affected by the mechanism of action of apixaban. Changes observed at the expected therapeutic dose are small and subject to a high degree of variability, see SmPC for further details. Information about excipients: Eliquis contains lactose. Patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take Eliquis. DRUG INTERACTIONS (SPC Section 4.5): Eliquis should be used with caution when co-administered with SSRIs/SNRIs, NSAIDs, ASA and/or P2Y12 inhibitors because these medicinal products typically increase the bleeding risk. There is limited experience of co-administration with other platelet aggregation inhibitors (such as GPIIb/IIIa receptor antagonists, dipyridamole, dextran or sulfinpyrazone) or thrombolytic agents. As such agents increase the bleeding risk, co-administration of these products with Eliquis is not recommended. See SmPC for further details.Due to an increased bleeding risk, concomitant treatment with any other anticoagulants is contraindicated, except under specific circumstances of switching anticoagulant therapy, when UFH is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation. Administration of activated charcoal reduces Eliquis exposure. Also see contraindications and special warnings and precautions section; Consult SmPC (contraindications, special warnings and precautions and drug interactions) for full details on interactions. PREGNANCY AND LACTATION (SPC section 4.6): Pregnancy: As a precautionary measure, it is preferable to avoid the use of apixaban during pregnancy. Breastfeeding: A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from apixaban therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. UNDESIRABLE EFFECTS (SPC section 4.8): Increased risk of occult or overt bleeding from any tissue or organ, which may result in post haemorrhagic anaemia. The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding. Frequencies: common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery (VTEp): Common: anaemia; haemorrhage*; haematoma*; nausea; contusion. Uncommon: thrombocytopenia*; epistaxis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); haematuria*; specific haemorrhage such as gastrointestinal*, abnormal vaginal*, urogenital*, post procedural*, wound secretion*, incision site*, operative*. Rare: hypersensitivity*; anaphylaxis*; haemoptysis*; gingival bleeding*; specific haemorrhage such as eye (including conjunctival)*, rectal*, muscle*. Not known: angioedema*; specific haemorrhage such as brain (encompassing intracranial, intraspinal)*, intra-abdominal*, respiratory tract*, haemorrhoidal*, mouth*, retroperitoneal*, traumatic*, erythema multiforme*. Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors (NVAF): Common: anaemia; haemorrhage*; haematoma*; hypotension (including procedural hypotension); epistaxis*; nausea; gingival bleeding*; gamma-glutamyltransferase increased; haematuria*; contusion; specific haemorrhage such as eye (including conjunctival)*, gastrointestinal*, rectal*. Uncommon: thrombocytopenia*; hypersensitivity*; anaphylaxis*; haemoptysis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); specific haemorrhage such as brain (encompassing intracranial, intraspinal)*, intra-abdominal*, haemorrhoidal*, mouth*, abnormal vaginal*, urogenital*, post procedural*, wound secretion*, incision site*, operative*, traumatic*. Rare: specific haemorrhage such as respiratory tract*, retroperitoneal*, muscle*. Very Rare: erythema multiforme*. Not known: angioedema*.

Treatment of DVT and PE, and prevention of recurrent DVT and PE (VTEt): Common: anaemia; thrombocytopenia*; haemorrhage*; haematoma*; epistaxis*; nausea; gingival bleeding*; gamma-glutamyltransferase increased; alanine aminotransferase increased; skin rash; haematuria*; contusion; specific haemorrhage such as gastrointestinal*, mouth*, rectal*, abnormal vaginal*, urogenital*. Uncommon: hypersensitivity*; anaphylaxis*; haemoptysis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); specific haemorrhage such as eye (including conjunctival)*, haemorrhoidal*, muscle*, post procedural*, wound secretion*, incision site*, operative*, traumatic*. Rare: specific haemorrhage such as brain (encompassing intracranial, intraspinal)*, respiratory tract*. Not Known: angioedema*; specific haemorrhage such as intra-abdominal* and retroperitoneal*, erythema multiforme*. *Denotes serious adverse reaction Refer to SmPC for all other adverse events LEGAL CATEGORY: POM. MARKETING AUTHORISATION NUMBER (SPC section 8): EU/1/11/691/002-3, EU/1/11/691/008, EU/1/11/691/014 PACKAGE QUANTITIES: Carton of 20 film-coated tablets 2.5 mg, 60 film-coated tablets 2.5 mg, 56 film-coated tablets 5 mg, 28 film- coated tablets 5 mg. MARKETING AUTHORISATION HOLDER (SPC section 7): Bristol-Myers Squibb/Pfizer EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland FOR FURTHER INFORMATION CONTACT: medical.information@bms.com or 1 800 749 749 (Ireland) DATE OF PREPARATION: April 2021 ADDITIONAL INFORMATION AVAILABLE ON REQUEST Approval Code: 432-IE-2100041

Adverse events should be reported. Reporting forms and information can be found at: Ireland - via HPRA Pharmacovigilance at www.hpra.ie Adverse events should also be reported to Bristol-Myers Squibb via medical.information@bms.com or 1 800 749 749 (Ireland)

*with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA); age≥ 75 years; hypertension; diabetes mellitus; symptomatic heart failure (NYHA Class ≥ II) AF = Atrial Fibrillation. Reference: 1. Granger CB et al. N Engl J Med 2011; 365: 981–992.

Date of approval: May 2021 Job code: PP-ELI-IRL-0497 www.eliquis.ie

Professional Top 100 2016, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News,

Hospital Professional

The Hospital Professional News – Professional Top 100 serves to recognise Ireland’s leading health and medical professionals who have come together during times of great strain and challenge, to showcase dedication and excellence.

All of the 100 professionals on these pages have demonstrated the impact they make to the delivery of high-quality patient care.

Since March 2020, no one has been immune to the impacts of the Covid-19 pandemic, and the devastation is has caused to the provision of healthcare services across not just Ireland, but on a global scale.

But despite this, we have witnessed an inspiring hospital workforce in this country, that has truly stepped up to the frontline, problem-solved and thought outside the box, continuing to research and shaping and impacting patient care for the better.

Many found innovative solutions to the challenges of the pandemic and stretched their presence far beyond traditional settings to deliver care and meet the moment, with potentially long-lasting impacts on the future of healthcare.

The HPN Professional Top 100 brings you a prestigious annual list which celebrates Ireland’s top hospital and healthcare achievers - a carefully constructed network of the most influential hospital professionals across a range of disciplines, who act as ambassadors and role models for their peers, colleagues and the rising stars of tomorrow. Over the past many months, our team of writers has reached out to pharmacists, consultants, clinical specialists, representative bodies and organisations throughout the sector and encouraged them to put forward those colleagues they feel are redrawing the landscape for the future. Those who have made our final list have displayed motivating behaviour and inspirational leadership affecting the development of hospital services across Ireland.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Professional Top 100 2016, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News, Professional Top 100, Hospital Professional Awards, Professional Top 100, Hospital Professional News,

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

Professional 100 Professor Frank Barry, Professor of Cellular Therapy, Regenerative Medicine Institute, NUI Galway In May of this year, Professor Barry was elected as a Member of the Royal Irish Academy for his exceptional contribution to the sciences, humanities and social sciences as well as to public service.

In further news later this year, Professor Barry was selected as the new director of the C. Wayne McIlwraith Translational Medicine Institute at Colorado State University. Barry’s research and interests include stem cell biology and the development of cell-based repair strategies for osteoarthritis.

His contributions to the fields of tissue engineering and regenerative medicine include developing innovative and successful cellular therapies for tissue repair, joint injury and arthritic disease.

His official appointment begins in January 2022.

Professor Adrian Bracken, School of Genetics and Microbiology, Trinity College Dublin Earlier this year, Professor Bracken led a research team who discovered how a specific genetic mutation called H3K27M causes a devastating, incurable childhood cancer, known as diffuse midline glioma (DMG), and – in lab studies working with model cell types – successfully reverse its effects to slow cancer cell growth with a targeted drug. Their landmark work has been published in leading international journal, Nature Genetics and supported by Worldwide Cancer Research and The Brain Tumour Charity – translates crucial new understanding of the genetics of DMG progression into a highly promising, targeted therapeutic approach and offers significant hope of improved treatments in the future.

The scientists now call for clinical trials to begin imminently, in which an already approved class of drugs called “EZH2 inhibitors” can be assessed. These drugs target the same key biological pathway involved in DMG as they do successfully in lymphomas and sarcomas -- two cancers common in adults.

Dr Catriona Bradley, Executive Director, Irish Institute of Pharmacy Over the past twelve months, Dr. Bradley has continued her ongoing work in the enhancement of professional development for pharmacists, and for the profession more generally, through her work as Executive Director of the IIOP. In Autumn 2020, she led a rapid-research needs-analysis project to understand the supports needed by pharmacists during the COVID pandemic. A range of novel initiatives were developed to respond to those outputs of that analysis, including the IIOP Mentoring Programme, which was launched in March 2021. This is the first mentoring programme available across all areas of pharmacy practice. Its success demonstrates the value of establishing intra-professional support structures. In a project designed to increase awareness of the importance of personal resilience, Catriona hosted the IIOP’s Resilient Pharmacist Podcast series, which featured pharmacist guests talking openly about how they have overcome challenges that they face. During the course of the year, Dr. Bradley has hosted a range of panels, exploring different aspects of professional practice, such as those held during the RCSI Charter Week Programme, and an international series organized in collaboration with Glaxo and GRiT, an international group focused on developing resilience in pharmacy. In June 2021, Dr. Bradley hosted the Life Long Learning in Pharmacy International Conference in RCSI, which attracted over 250 attendees from around the globe, including policy makers, education experts, and global thought leaders. Her commitment to enhancing the professional pharmacy agenda has been demonstrated through these, and numerous other projects and publications, as well as through her support of colleagues across all areas of practice.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Professor Donal Brennan, UCD Professor of Gynaecological Oncology, Consultant Gynaecological Oncologist, The Mater Hospital Professor Brennan and his team have developed a new first-of-its-kind platform for Ireland providing relevant, reliable and evidence-based information for people affected by cervical cancer. The ThisIsGo.ie platform offers a one-stop-shop for helpful resources and advice on cervical cancer as part of the first phase of its development, including over 130 different articles, videos and audio content covering every stage of cancer diagnosis, treatment, and life with and after cancer.

The platform has been co-developed by the Irish Cancer Society through its Women’s Health Initiative. ThisIsGo.ie offers a personalised experience tailored to the stage and needs of individual users, including a specific section for partners of women who have or have had cervical cancer. It contains evidence-based information on everything from the stages of cervical cancer and a step-by-step guide for what to expect from treatment, to important parts of the journey that may often be overlooked including simple tips on preparing for hospital, and talking to children about cancer.

Dr Julie Broderick, Assistant Professor, Discipline of Physiotherapy, School of Medicine, Trinity College Dublin Dr Broderick is one of six winners of the 2021 Dean’s Research Initiatives Fund to study the feasibility of an exercise programme with nutritional supplementation to target frailty and poor physical function in people who are homeless.

Dr Broderick’s work focuses on the most functionally and life-limiting chronic conditions in the areas of oncology, cardiorespiratory and severe mental health. Her recent work at the frontiers for her Discipline has investigated physical functioning measures in previously under-researched populations such as people experiencing homelessness.

Her interest lies in the interaction between social exclusion and chronic disease and how it manifests in physical health outcomes.

Jennifer Brown, Head of Pharmacy Services, Mater Misericordiae University Hospital Jennifer was appointed into her current position, the Clinical Directorate Lead within the Pharmacy & Medicines Optimisation (PAMO) Directorate, and the Head of Pharmacy Services in the MMUH, in June 2020. Leading the directorate during the COVID-19 pandemic presented substantial clinical, financial, safety and human resource challenges. Jennifer has overall responsibility for maintaining continuity of drug supply to the hospital, including the largest critical care complex in Ireland. She oversaw Pharmacy involvement in COVID-related clinical trials. Jennifer was instrumental in the MMUH COVID-19 vaccine programme which involved safe supply of approximately 3,000 COVID-19 vaccine vials for front-line healthcare workers, patients and Residential Care Facilities residents. Jennifer also introduced a weekend pharmacy drug supply service.

While adapting to the ever-changing demands of COVID-19, Jennifer ensured Pharmacy staff were aware and equipped with Infection Prevention and Control measures to minimise transmission of COVID-19 while also ensuring continuity of service provision for the directorate.

Jennifer maintained other professional responsibilities while managing the Pharmacy response to COVID-19, including her involvement and responsibilities associated with the MMUH Drugs and Therapeutics, Drug Safety, Quality and Patient Safety and Drug Expenditure and Reimbursement Monitoring Committees.

Dr Eilish Burke, Ussher Assistant Professor in Ageing And Intellectual Disability Trinity Centre for Ageing and ID. IDS-TILDA Trinity College Dublin Dr Burke was the recent recipient of the 2021 IARSLCE Diversity, Equity and Inclusion Award for her efforts to advance research on service learning and community engagement.

The International Association for Research on Service-Learning and Community Engagement (IARSLCE) is an international non-profit organization devoted to promoting research and discussion about service-learning and community engagement.

In response to the recent COVID-19 pandemic Dr Burke lead the design of an online educational programme for carer's in ID services on recognition and assessment of COVID-19 among those with intellectual disability in collaboration with the HSE and the Office of the Nursing and Midwifery Services Director.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Roisin Cahalan, Senior Lecturer in Physiotherapy, University of Limerick Dr Cahalan is the founder of SingStrong – singing for better lung health in respiratory disease and was awarded a 2018 Irish Research Council New Foundations grant for this work. The project has continued to attract funding from across the private and public sectors and in addition to the expansion of the number of COPDSI SingStrong groups, it has expanded to include cohorts with Long Covid and Pulmonary Fibrosis in partnership with the Irish Lung Fibrosis Association (ILFA). This year, the project facilitated seven online classes per week to patients all over the island of Ireland.

Dr Cahalan is a Senior Lecturer in Respiratory and Cardiovascular Physiotherapy at the University of Limerick (UL).

Donal Carroll, Chief Pharmacist, St. Luke’s General Hospital, Carlow Kilkenny Donal has over 25 years experience as a Chief Pharmacist in St. Luke’s General Hospital Carlow, Kilkenny. When the Covid Pandemic arrived he and his team quickly realised what was required to ensure that a safe and effective working environment was established in the hospital pharmacy. The team embraced a flexible working arrangement which met the requirements of social distancing in the dept. This led to the pharmacy service extending its opening hours to 12 hours a day seven days a week at the height of the pandemic, ensuring that the pharmacy requirements of the hospital patients and staff were met at this time.

With the arrival of the vaccine Donal and his team were front and centre providing due governance in the management of the vaccines. From the outset they provided a centralised vaccine preparation service for the staff and patients in St. Luke’s. This value and benefit of this centralised vaccine preparation service was quickly recognized and a team consisting of Nicola Cantwell, Deirdre Lambert, Sarah Quigley and Nora Norton was set up to provide training to pharmacists and technicians across the region. This centralised vaccination preparation service has been shown to improve safety, reduce the risk of discarded vaccines and improve client flow through the LVCs.

Professor Dympna Casey, Professor of Nursing, School of Nursing & Midwifery, NUI Galway Professor Casey is currently leading an EU Funded Horizon 2020 project entitled MARIO (Managing Active and Healthy Aging with the use of caring service robots) within the thematic section ‘Societal Challenge on Health, Demographic Change and Wellbeing'. She has a clinical background in care of older people and for the past 20 years she has worked in nursing education in the National University of Ireland Galway. Her research interests include care of older people, dementia, self-management of chronic diseases and health promotion. She has a keen interest in promoting healthier lifestyles for older people and in examining ways of supporting and maintaining the health and functional capacity of older people.

Professor Jerome Coffey, Head of Cancer Centre at Mater Private Network, Dublin Professor Jerome Coffey has recently been appointed Head of Cancer Centre at Mater Private Network in Dublin.

Professor Coffey qualified from Trinity College Dublin in 1993. On completion of basic medical training in Ireland he joined the training programme in radiation oncology in St. Luke’s Hospital, Dublin gaining both Irish and UK specialist qualifications. After clinical fellowships in the Princess Margaret Hospital in Toronto he moved to the Academic Urology Unit at the Royal Marsden Hospital in the UK where he completed clinical and lab-based research in urological cancers with peer-reviewed publications in Clinical Oncology, the International Journal of Radiation Oncology, Biology & Physics, Genes, Chromosomes & Cancer, the British Journal of Cancer, Radiotherapy & Oncology and the International Journal of Andrology.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Róisín Colleran, Consultant Interventional Cardiologist, Mater Private Network, Dublin This year Dr Colleran won the 2021 Women as One Escalator Research Award. Women as One is an organisation that promotes talented female cardiologists in a male-dominated specialty. The Escalator Awards were established to "escalate" the careers of women physicians by providing them with unique professional development opportunities and dedicated funding. Dr Colleran received the award for her previous research and current contribution to the SETANTA research project at the Mater Private's Cardiovascular Research Institute. The study aims to learn more about the longer-term cardiac, immunological, and hematological effects of Covid-19 infection.

Dr Dearbhaile Collins, Consultant Medical Oncologist, Cork University Hospital Dr Collins is currently leading a study which measures genetic markers in the blood of patients linked to an aggressive form of small cell lung cancer with very poor survival rates. Her team is collecting blood samples from patients when they are first diagnosed with small cell lung cancer and test for MYC gene levels before the patient starts anti-cancer treatment. The research will increase understanding of the role of the MYC gene in small cell lung cancer. It is hoped that this research will help to identify patients with different risks of cancer progression.

Dr Melissa Conroy, Senior Research Fellow and Principal Investigator, Trinity College Dublin In 2021, Dr Conroy’s team reported that the most viscerally obese oesophageal and gastric cancer patients have the lowest number of crucial cancer-killing natural killer cells in their tumours, confirming that visceral obesity in these patients has devastating consequences for the anti-cancer immune response. The natural killer cells are pulled into the visceral fat of these patients by a protein called fractalkine where they are altered and even depleted. Consequently, the cancer-killing immune cells cannot reach and fight the tumour in sufficient numbers.

Importantly, the team demonstrated that the movement of natural killer cells to the visceral fat of such cancer patients can be significantly reduced by a drug targeting fractalkine. Although it takes considerable time to go from a discovery like this to bringing a new drug to patients, it is nonetheless very exciting that the team have identified a novel therapeutic approach to redirect and reinvigorate the anti-cancer immune response in these poor prognosis cancers. More recently, Dr Conroy was awarded a grant from the Dean’s Research Initiatives Fund at Trinity College Dublin to establish a new research study testing novel drugs for the treatment of the poor prognosis brain cancer, Glioblastoma multiforme (GBM). Such research will address an unmet clinical need of GBM patients who currently face survival rates of less than 5%.

Elmarie Cottrell, Lead Pharmacist Cork Vaccination Centres, Senior Clinical Informatics Pharmacist, MN-CMS/CUMH Elmarie Cottrell is the Lead Pharmacist for the Cork Centralised Vaccination Centres. Elmarie led the Medication Management team that were involved in the vaccination of over 300,000 people in Cork. Elmarie demonstrated exceptional leadership and dedication to the national vaccination programme in her role. She was instrumental in overseeing the safe handling, preparation and storage of COVID vaccines and actively promoted the positive role of hospital pharmacists in the Centralised Vaccination Centres.

Elmarie has a keen interest in digital healthcare and works as a Senior Clinical Informatics Pharmacist with the national Maternal Newborn Clinical Management System (MN-CMS) prior to being seconded to the vaccination centres. She worked with the MN-CMS Medication Workstream to respond rapidly to the HSE cyber-attack and minimize the impact on patient care. She is continuously promoting quality improvement initiatives to enhance patient safety in her informatics role. She also completed a Certificate in Healthcare Innovation with Trinity College Dublin this year and is passionate about driving innovation within the Irish Healthcare system.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Professor Sally-Ann Cryan, Professor of Drug Delivery, Royal College of Surgeons Ireland Professor Cryan led a team who this year developed polypeptide-based materials that act as effective vectors for delivering gene therapies. The first-of-its-kind platform enables the vectors to be adapted to suit the specific gene therapy cargo.

The work was led by researchers from RCSI University of Medicine and Health Sciences who developed a platform that produces bespoke star-shaped polypeptide nanoparticles, which effectively deliver a range of therapies, including gene therapies. Crucially, these polypeptides are more flexible and easier to handle than lipids. To demonstrate the potential of this material, the researchers used it to deliver a gene therapy that regenerated bone.

Professor Cryan is a pharmacist and was a member of the foundation staff that set up the School of Pharmacy in RCSI in 2002.

David Delaney, Chairperson, Medicines for Ireland David has led the trade organization representing the manufacturers of the majority of medicines used daily in Ireland by the HSE through the challenges of Covid-19 and Brexit, to ensure stable patient access to medicines in Ireland and a well-functioning pharma market.

Working in partnership with a very wide range of stakeholders, such as the Irish Pharmacy Union and United Drug / McKesson, David has worked to ensure the trade association syncs on solutions to keep the Irish policy toolkit of the HSE as modern as possible, reflecting best practice across Europe.

David and the team at Medicines for Ireland have worked to become an equal partner at the National Pricing and Supply of Medicines discussions in Ireland, bringing the experience and solutions of the Generics and Biosimilars industry to the table, to help maintain optimum patient access to medicines in Ireland.

Ms Ruth Delaney, Consultant Orthopaedic Surgeon, Beacon Hospital Ms. Delaney performed mixed reality-augmented shoulder replacement for the first time in Ireland at Beacon Hospital in April 2021. Bringing the latest, cutting-edge advances in shoulder surgery to Irish patients is something Ms. Delaney is passionate about. Using the Hololens and mixed reality has now become a routine part of all shoulder replacements Ms. Delaney performs, both at Beacon Hospital and at SSC. It is based on detailed preoperative planning from a CT scan of the shoulder which allows accurate evaluation of the shoulder joint and is entered into planning software which then allows Ms. Delaney to create not only a surgical plan but also mixed reality visualisation for use during the surgery.

Ms Delaney is a consultant orthopaedic surgeon and shoulder specialist. Ruth specializes in the full range of shoulder surgery, including open and arthroscopic (keyhole) procedures. Her subspecialist areas of interest include shoulder instability and shoulder arthroplasty (shoulder replacement surgery).

Laura Dillon, Senior Clinical Pharmacist – Mater Frailty Intervention Team / Education and Training Co-ordinator, Mater Misericordiae University Hospital Since September 2020 Laura has taken up the role of Senior Clinical Pharmacist with the Frailty Intervention Team (FIT) in the MMUH. Laura ensures a patient-centred and collaborative approach to medicines management and has introduced a number of innovative ideas to enhance the pharmaceutical care of patients reviewed by FIT. Laura is the only pharmacist in the Republic of Ireland working full time with a frailty team in the ED. Over the past few months she has introduced a number of innovative ideas to enhance the pharmaceutical care of patients reviewed by FIT, including a novel medication review process to improve FIT patient outcomes. Laura used her innovation and forward thinking to get the hospitals MR form uploaded on to the hospital electronic healthcare record (EHR). She has also designed and implemented a patient Medication Review Form which is also uploaded on to the EHR.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Margaret Donnelly, Lead Pharmacist Helix/ National Show Centre Vaccination centres, HSE Margaret has ten years’ experience as a pharmacist across the community and hospital sectors. She has most recently taken up a post as community antimicrobial stewardship pharmacist in CHO 9. After a few weeks in the post she was redeployed as lead pharmacist of the Covid-19 vaccination programme in CHO 9. There was no medication management team in place so she had to quickly build a team of pharmacists, technicians and students and develop an efficient and reliable process to supply up to 4500 vaccines per day.

Margaret became a central member of the Covid-19 Vaccination Service leadership team ensuring that best practice with regards to medicines management was maintained. She also developed networks with other pharmacists in the Centralised Vaccination Clinics, the acute hospitals, and with wider HSE and community settings.

As the programme progressed, she planned and executed the relocation of the pharmacy of the Vaccination Centre from the Helix to the National Show Centre in Swords at the time of peak vaccine administration. She successfully oversaw the preparation of over 460,000 doses of Covid-19 vaccines across the Helix, National Show Centre and Croke Park CVCs with minimal waste and maximum utilisation of the Centralised Preparation of Syringe Model in CVCs. Margaret has promoted the role of pharmacists in the vaccination programme and maintained high professional standards at all times.

Dr Catriona Dowling, Lecturer in Biomedical Science, University of Limerick In early 2021, Dr Dowling’s discovery of a potential new therapy for chemotherapy-resistant breast cancer was published in the prestigious Science Advances journal. Dr Dowling discovered a molecule which selectively killed breast cancer cells and confirmed the molecule inhibited an enzyme called HDAC6. Using state-of-the art mass spectrometry, Dr Dowling identified, for the first time, that HDAC6 plays a key role in altering energy in these cancer cells. In 2012, Dr Dowling secured a scholarship from the Irish Cancer Society to pursue a PhD in cancer biology at the University of Limerick. Following her PhD, Dr.Dowling undertook post-doctoral work at the Royal College of Surgeons in Ireland, during which time she secured independent fellowships from the Irish Research Council and Marie Skłodowska-Curie Action Global Fellowship.

Dr Frank Doyle, Senior Lecturer, Department of Health Psychology, Royal College of Surgeons in Ireland This year, Dr Doyle led a team who published a network meta-analysis comparing treatments for depression in those with coronary artery disease (CAD). The paper combined trials which investigated antidepressants, psychotherapies, exercise and collaborative care, accounting for different types of comparator groups (e.g. placebo, usual care, treatment control) and found that exercise was likely the best treatment from all of these. This article has had significant online impact (Altmetric=123, in the top 2% of similarly aged articles).

However, just because an intervention is effective does not necessarily mean that it is the most cost-effective, so the team have also followed up this work to investigate the cost-effectiveness of implementing these treatments in the Irish setting. While the results of this follow up are still undergoing peer review and are yet to be published, they also suggest that exercise is the most cost-effective treatment. Overall, this work provides excellent evidence that exercise should be prioritised in the Irish healthcare setting for depression treatment in those with CAD.

Cassandra Doyle, Senior Pharmacy Technician, Mater Misericordiae University Hospital In January 2021, the MMUH began the roll out of their COVID-19 vaccines. Cassie prepared the first MMUH and Ireland East Hospital Group COVID-19 vaccine dose and was involved throughout the vaccination programme. She demonstrated the vaccine preparation process to doctors and nurses, highlighting her leadership skills while ensuring a high standard was met.

Cassie has been an integral part of the MMUH Pharmacy and Medicines Optimisation Directorate team for 2 years. As the Senior ward Pharmacy Technician, Cassie is actively involved in stock optimisation, drug waste reduction and the co-ordination of ward closures and openings. Through teamwork and communication, stock management processes have been optimised. Cassie persistently displays initiative and accomplishes her responsibilities with determination and resourcefulness. Additionally, Cassie has been instrumental in the training and integration of other technicians in various roles within the pharmacy. She delivers high quality training with targeted focus on attention to detail; a testament to Cassie’s dedication and commitment.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Professor Fidelma Dunne, Associate Director, HRB-CRFG/Consultant Endocrinologist, Saolta University Health Care Group Professor Dunne’s research group are conducting a number of studies as part of the ATLANTIC DIP programme including an IMP randomized controlled trial (RCT) of Metformin in GDM pregnancies (EMERGE), investigation of a biomarker (CD59) for GDM diagnosis and a 10 year follow up (metabolic and cardiovascular) of women with prior GDM. In addition, she has been involved in international studies including a multicentre European funded (FP7) trial on prevention of GDM using Vitamin D and lifestyle intervention (DALI), CONCEPTT a Juvenile Diabetes Research Funded (JDRF) trial examining the benefits of continuous glucose monitoring (CGMS) in women with Type 1 Diabetes during pregnancy. More recently she has been the Irish lead for a pan European cohort study examining pregnancy outcomes of women with Type 1 and Type 2 diabetes (EVOLVE) and is currently the Irish lead for the EXPECT study examining Degludec (Tresiba) insulin in women with Type 1 Diabetes in pregnancy.

David Fitzgerald, Chief Pharmacist, National Maternity Hospital As the Chief Pharmacist, David and his team were instrumental in rolling out the Covid-19 vaccine across the National Maternity Hospital setting, with over 450 vaccinated in one day. In October of this year, alongside Linda Kelly RCSN RN and RM(H Dip), RMP, Advanced Midwife Prescriber in Urodynamics and Women’s Health he published an article which examined the therapeutic management of stress incontinence within Ireland.

Professor Gerard Flaherty, Senior Academic, College of Medicine, Nursing and Health Sciences, NUI Galway Professor Flaherty was elected to the prestigious role of President-elect of the International Society of Travel Medicine in May 2021, the first Irish person to receive this distinction, and only the second from the British Isles. He will serve on the Executive Board as President-elect (2021-23), President (2023-25), and Immediate Past President (2025-27).

He has completed 3 Masters degrees, including a Masters in International and Travel Health (Sheffield) and Masters in Medical Education (Dundee). His two doctoral theses (MD, PhD) were based on his original research in travel medicine.

Dr Melanie Föcking, Lecturer in Psychiatric Neuroscience, Royal College of Surgeons in Ireland Dr Melanie Föcking is a Lecturer in Psychiatric Neuroscience in the Department of Psychiatry at the RCSI. Her key scientific discoveries include the identification of protein changes in schizophrenia and bipolar disorder and has published over 40 articles in leading journals including Molecular Psychiatry and JAMA Psychiatry.

Her recent work, published in Molecular Psychiatry, proposes that alterations in immune defense mechanisms – including blood clotting – lead to an increased risk of inflammation, which is thought to contribute to the development of psychosis.

While the idea of psychosis resulting from some form of inflammation and immune activation is not entirely new, the results suggest a new understanding and change of focus towards a combined function of the innate immune complement system and coagulation pathways to the progression to psychotic disorder.

This perception adds to the prevailing ‘two-hit’ hypothesis, where early genetic and/or environmental factors disrupt the developing central nervous system (the “first-hit”) and increases the vulnerability of the individual to subsequent, late environmental disruptions (the “second-hit”).

The approach may provide a further step towards biomarkers of psychosis and allow the identification of therapeutic targets for early and more effective treatment.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Mr Jonathan Gallagher, Senior Psychologist, Department of Cardiology (Cardiac Rehabilitation), Beaumont Hospital Mr Gallagher works primarily with Beaumont Hospital’s multi award-winning Cardiac Rehabilitation (CR) Programme, which is internationally recognised as a centre of excellence for CR. Beaumont Hospital is the first and only centre in Ireland to receive international accreditation - both European and US - in cardiac rehabilitation and secondary prevention, and in December 2020 won the award for ‘Excellence in Healthcare Management’ for the second time at the Irish Healthcare Awards. In 2021 Jonathan also worked closely with the Irish Heart Foundation to conduct a national audit of CR services and was selected to represent Ireland on the International Cardiac Rehabilitation Registry (ICRR).

Jonathan is a passionate advocate of patient-centred care. His clinical and research interests include behavioural cardiology, insomnia, medication adherence and quality improvement in cardiac care.

Professor William Gallagher, Professor of Cancer Biology, School of Biomolecular and Biomedical Science, University College Dublin Professor Gallagher was this year awarded the Science Foundation Ireland Researcher of the Year 2021. Professor Gallagher has co-ordinated many cancer research projects over the years, and is currently leading an SFI Investigator Programme focused on identifying and validating prognostic biomarkers for early-stage breast cancer and prostate cancer.

He previously won SFI’s Entrepreneurship Award for his work with OncoMark, a breast cancer diagnostic start-up he co-founded that was acquired earlier this year.

Professor Patricia Ging, Transplant /Pulmonary Hypertension Pharmacist, Mater Misericordiae University Hospital Professor Patricia Ging, Transplant and Pulmonary Hypertension Pharmacist, has been appointed as the chair of the Standards and Guidelines Committee of the International Society of Heart and Lung Transplant (ISHLT). ISHLT engages in the regular development and update of Professional Practice Guidelines and Consensus Statements to improve the care of patients with advanced heart and/or lung disease.

The role of the chair of this committee is to provide initiative, leadership and guidance to ensure the consistency and quality of the Standards and Guidelines projects prepared by the organisation. Patricia will serve for a two year term as chair, reporting to the board of ISHLT and the publications oversight committee. Patricia is the first pharmacist to be chosen for this role, a great honour.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Lisa Glynn, Respiratory Advanced Nurse Practitioner, Tallaght University Hospital Lisa was instrumental in leading practice and policy change for respiratory patients attending TUH during the coronavirus pandemic.

Awarded a PhD scholarship from Trinity College, Dublin in September 2020. Lisa is a keen, enthusiastic advocate for research and quality improvement in Irish Healthcare resulting in numerous publications and presentations. She is leading a large randomised control trial evaluating digital health intervention among patients with COPD. The findings of this trial will be significant in informing of any associated clinical health outcomes using a digital health intervention among the COPD population. For this research she was awarded the Elizabeth O’ Dwyer medal for Nursing Innovation from the Meath Foundation, the New Initiative Scheme award from the Adelaide Health Foundation and financial support to the sum of ¤45,000 from the Health Service Executive (HSE).

Lisa is a strong advocate for her profession and was selected to represent Advanced Nurse Practitioners in Ireland to speak at the live HSE weekly briefing on RTÉ alongside Paul Reid (CEO HSE), Anne O’ Connor (COO HSE) and Colm Henry (CCO HSE).

Dr Marina Green, Postgraduate Researcher, The Nutrition Research Centre Ireland, Waterford Institute of Technology Dr Green led a research team who this year, published research on sunlight and nutrition as being key contributors to eye health. It is the first study of its kind to describe macular pigment and its determinants for the Mexican population. Additionally, this research investigated the impact of environmental and nutritional factors on macular pigment. Dr Green’s study has discovered that those with high sunlight exposure during the day have significantly higher Macular Pigment.

This finding sheds light on the importance of nutrition and dietary patterns on macular pigment, and consequently, on eye health.

Dr Emily Greenan, Clinical Lecturer, RCSI university of Medicine and Health Sciences Dr Greenan is a member of the Ocular Immunology Research Group (OIRG) in the School of Pharmacy & Biomolecular Sciences (PBS) at RCSI whose focus is defining the molecular pathways that are altered in inflammatory ocular surface diseases and targeting the underlying pathogenesis through the development of novel nanoparticle therapeutics. In particular, Dr Greenan’s research and PhD focus is on the role of ocular surface inflammation in dry eye disease pertaining to the auto- and allo- immune conditions of ocular Graft versus Host Disease (GVHD) and Primary Sjögren’s Syndrome (pSS). More recently, Dr Greenan’s research has focused on the health and vision related quality of life of patients with pSS, and specifically the impact of the pandemic on the on quality of life of this patient cohort.

Dr Emily Greenan is a Trinity graduate, having completed her undergraduate training in 2016. Since then she has worked as an ophthalmologist in Cork University Hospital and in the Royal Victoria Eye and Ear Hospital, Dublin. She is currently clinical lecturer in the Department of Ophthalmology in RCSI, University of Medicine and Health Sciences, Ireland.

Dr Greenan has published extensively in areas relating to ocular disease, including GVHD, methicillinresistant staphylococcus aureus in the delivery of eye care, diabetic retinopathy screening and treatment and corneal graft techniques.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dzana Hadzic, Senior Clinical Pharmacist, Mater Misericordiae University Hospital In October 2020, Dzana was appointed into the critical care pharmacist position in the largest, most demanding critical care unit in the country, providing pharmaceutical expertise to a highly complex patient population, all while pursuing an MSc in her own time.

When a COVID-19 surge hit so early in her new role, Dzana demonstrated efficiency, commitment, and dedication by quickly reacting to and problem-solving emerging medication management issues. She monitored medication usage and planned for adequate supply of critical drugs, liaised with pharmacy and critical care colleagues both on-site and internationally, while also playing an essential role within the multidisciplinary team by providing evidence-based advice and medication optimisation for critically unwell patients.

As the only extracorporeal membrane oxygenation (ECMO) center in Ireland, Dzana showed drive and initiative in researching and advising on complex ECMO-related drug issues, presenting to pharmacy colleagues, and providing critical care training. She is the only clinical pharmacist in the country working directly with adult patients requiring ECMO, use of which amplified during the pandemic. This is a unique position and a huge achievement so early on in Dzana’s career.

Professor Arnold Hill, Head of School of Medicine and Professor of Surgery, Royal College of Surgeons Ireland As Head of the School of Medicine, Professor Hill was at the forefront of an RCSI study conducted in Beaumont Hospital in Dublin this year, which found that surgery, rather than antibiotics only, should remain as the mainstay of treatment for acute uncomplicated appendicitis.

Led by researchers from RCSI University of Medicine and Health Sciences, the study is called the COMMA trial (Conservative versus Open Management of Acute uncomplicated Appendicitis). It examined the efficacy and quality of life associated with antibiotic-only treatment of acute uncomplicated appendicitis versus surgical intervention.

The results revealed that antibiotic-only treatment resulted in high recurrence rates and an inferior quality of life for patients.

Professor Hill is also the Lead Clinician in the Beaumont Hospital Breast Service, which diagnoses and treats up to 300 newly diagnosed breast cancers each year. His laboratory research interests are in the transcriptional control of breast cancer and, in particular, the role of the coregulatory proteins.

Professor Mary Horgan, Consultant in Infectious Diseases, Cork University Hospital/President, Royal College of Physicians of Ireland A world-renowned expert in infectious disease, Professor Mary Horgan is the President of the Royal College of Physicians of Ireland — the first female in this role since its establishment in 1654. She is a consultant in infectious diseases at Cork University Hospital.

Originally from Kerry, Professor Horgan graduated from UCD in 1986. She was awarded her MD in 1995, MRCPI in 1988 and FRCPI in 1997. During her career, Mary has become a national and international leader in medical education and training, in infectious disease and public health and has spearheaded education and scientific education in Ireland. Mary’s work to date in this field has been instrumental in reversing the downward trend in uptake of HPV vaccination from 50% to 71% in one year.

Professor Alan Irvine, Professor in Dermatology, Trinity College Dublin & Children’s Health Ireland, Crumlin/President, Irish Hospital Consultants Association As President of the IHCA, Professor Irvine has been at the forefront of lobbying for better health solutions, and in identifying an urgent need to address recruitment and retention problems and growing waiting lists. His research interests are in epithelial genetics, disease mechanisms in, and therapy of, atopic dermatitis. His work on the genetics of atopic dermatitis with long term collaborative partner Irwin McLean has helped refocus attention on the role of the skin barrier in the pathogenesis of this disease and of allergic disease in general. He is funded by the National Children’s Research Centre and the Wellcome Trust, and has attracted approximately ¤11M funding to date.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100

Dr Rosemary James, School of Medicine, NUI Galway Dr James, a graduate of Medicine in 2021, was honoured by the School of Medicine for her outstanding community outreach and volunteering, as well as research in global health. Dr James, a junior doctor and global health academic with the World Health Organisation, said she was honoured to have been given the award. "I believe that it is important as medical graduates that we are aware of the vulnerabilities certain populations are subject to and act to advocate for, study, and improve their health and wellbeing wherever possible."

Gráinne Johnston, Aseptic Compounding Service Manager, Mater Misericordiae University Hospital Grainne Johnston was appointed as the MMUH Aseptic Compounding Service Manager in March 2021. Taking up this position in the midst of a pandemic, brought immense and unique challenges. Despite this, the Aseptic Compounding Unit (ACU) is running smoother and more efficiently than ever due to workflow streamlining introduced by Grainne. Grainne has modified the microbial monitoring processes in the ACU, resulting in a reduction in drug disposal. Grainne has also significantly modified the chemotherapy protocol development process, aligning MMUH protocols with National Cancer Control Programme protocols where applicable. This has reduced the protocol development time for ACU staff, allowing them to focus their efforts on chemotherapy production. The ACU staff have maintained production output, despite increased demands and on occasions, having a reduction of 25% of staff due to COVID-19 isolation precautions.

With Grainne’s new ACS manager role, she has also taken over the responsibility for staff management within the ACU. Grainne has successfully welcomed and trained a number of new staff to the ACU since her appointment.

Thanks to Grainne’s openness, approachability and management style, the ACU staff have navigated recent challenges together as a team.

Professor Emer Joyce, Consultant Cardiologist / Subspeciality Heart Function and Transplant, Mater Hospital Professor Joyce is a Consultant Cardiologist specializing in Heart Failure, Mechanical Circulatory Support and Cardiac Transplantation at the Mater University Hospital Dublin. In the past 12 months she has continued her work as the National Lead for Advanced Heart Failure, involving a primary focus on driving forward increased awareness and associated referral systems and protocols for this subspeciality of Cardiovascular Medicine through the National Heart Program, in addition to commencing a role as Chair of the Heart Failure Council of the Irish Heart Foundation, with the primary aim of promoting patient advocacy, education and engagement. Research and academic highlights this year include her leadership of a prospective study of COVID-19 antibody detection in vaccinated heart transplant recipients, and being selected as a committee member and co-author of the Heart Failure Society of America’s recently published Scientific Statement on the intersection between COVID-19 and Heart Failure. She was also formally promoted to Professor (adjunct pathway) at University College Dublin.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Professor David Keane, Director, Cardiac Arrhythmia Service, St Vincent’s University Hospital At the start of 2021, Professor Keane presented at the AF Symposium about the research he and his team are carrying out on the cardiac electrophysiology research program, which is focused primarily on catheter ablation of atrial fibrillation.

Professor Keane is Director of the Cardiac Arrhythmia Service at St. Vincent’s University Hospital, Dublin.

Professor Keane received his training at Guy’s Hospital, London, Erasmus University Hospital, Rotterdam, The Netherlands and Massachusetts General Hospital, Boston Massachusetts, where he worked for 8 years and became Director Interventional Cardiac Electrophysiology.

Professor Keane is internationally recognized for his expertise in catheter ablation for cardiac arrhythmia, with a special interest in atrial fibrillation. He is a fellow of the Heart Rhythm Society, European Cardiac Arrhythmia Society, and Royal College of Physicians of Ireland, and is Chair of the EP Subgroup of the Irish Cardiac Society.

Dr Ina Kelly, Consultant in Public Health Medicine, University College Cork/President, Irish Medical Organisation Dr Kelly was appointed as President of the Irish Medical Organisation on International Women’s Day earlier this year. Dr Kelly took on the role during what has been an extremely challenging year for doctors and patients across the health system.

Dr Kelly has been campaigning for barriers that stop women reaching their full potential in their careers, particularly during their training years, to be acknowledged and fixed. “We have many extraordinary women in leadership positions in medicine but we want to see more of our colleagues being supported and having their voices heard,” she says.

Dr Kelly is the public health specialist on the National Asthma Programme Working Group.

She is also a member of the Consultants in Public Health Medicine Environment and Health group, contributing to the development of the National Radon Control Strategy.

Professor Rose Anne Kenny, Head of Medical Gerontology, Trinity College Dublin/ Consultant Geriatrician/Principal Investigator, TILDA During 2021 Professor Kenny has published numerous research, including studies on the benefits of vitamin D and a large-scale, nationally-representative study on ageing. Professor Kenny has also authored a groundbreaking book on ageing, Age Proof — The New Science of Living a Longer and Healthier Life. Using her "cutting-edge" research, the book will reveal why and how some people live longer, fitter, healthier and happier lives than others. Age Proof will also advise readers on the simple steps they can take – at any point in their lives – to ensure that they age in the best way possible.

Professor Kenny is a physician and researcher who has been head of the academic department of Medical Gerontology at Trinity College Dublin since 2006. She is the founding principal investigator of The Irish Longitudinal study on Ageing and has published over 600 scientific publications. She was also admitted as a member of the Royal Irish Academy in 2014.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Professor Steven Kerrigan, Professor of Cellular Pharmacology, RCSI University of Medicine and Health Sciences In the last 12 months Professor Kerrigan’s research has focused on understanding the molecular interactions between SARS-CoV-2 and lung epithelial and vascular endothelial cells. Through his pioneering work Professor Kerrigan’s research group identified a critical motif on the spike protein of SARS-CoV-2 that binds to lung epithelial cells, inducing lung damage and vascular endothelial cell damage that leads to uncontrolled micro-clot formation during COVID-19.

Most importantly Professor Kerrigan’s group identified a drug to prevent the cellular injury and death caused by the virus and in collaboration with Inthelia Therapeutics, Professor Kerrigan is planning a human clinical trial to test the drug as a higher order therapy for the treatment of COVID-19. In addition, he and colleagues in RCSI and Beaumont hospital developed a new less invasive alternative to the nasal/throat COVID-19 swab and could enable greater capacity for, and uptake of, frequent testing of people who require regular screening. Following publication of this study several countries have since amended their testing strategy to implement this approach.

Maríosa Kieran, Pharmacy Head of Operations, Mater Misericordaie University Hospital During COVID-19, Maríosa supported the hospital’s response to the pandemic as a senior PAMO manager. Her responsibilities included co-ordinating the MMUH COVID-19 vaccine supply service that involved managing storage and supply for the COVID-19 vaccine for MMUH staff vaccinations, Residential Care Facilities and patients in vaccination cohort 4.

Maríosa developed COVID-19 vaccine policies for vaccine use and to incorporate the documentation requirements for HSE submission, vaccine security, reconciliation and traceability. Maríosa also co-ordinated the newly implemented pharmacy weekend supply service, pharmacy aspects for new ward openings / ward reconfigurations, the overall PAMO response to COVID-19 and PAMO recruitment during the pandemic.

Maríosa successfully completed a MSc in Healthcare Management in 2021. Her MSc project, Introducing Pharmacy Key Performance Indicators to a Level 4 Dublin Academic Teaching Hospital Dashboard resulted in inclusion of an internationally recognised metric for medicines reconciliation in the study hospital’s data reporting system. This has improved resource, accuracy and data protection concerns for this healthcare priority and aligns with the study hospital and HSE strategies.

Fionnuala King, Chief Pharmacist, HSE Acute Hospital Drug Management Programme Fionnuala King is the Chief Pharmacist for the Acute Hospitals Drugs Management Programme (AHDMP), the Pharmacy function of the Acute Operations division of the HSE. The ADHMP focus is on pharmacy innovation and delivery of medicines management initiatives, safely and cost-effectively.

As the Pharmacy member of the Healthcare Worker Vaccination Working Group, Fionnuala chaired the Medicines Management Working Group that developed the National Medicines Management Guidance for Centralised Vaccination clinics. She provided expert input into the development of the TrackVax software for vaccine management in the Centralised Vaccination Centres.

Fionnuala worked previously on the implementation of the National Cancer Information System (NCIS) and has over 20 years of clinical experience in oncology and haematology leading the haem/onc pharmacy team in St. James Hospital for 16 years. Fionnuala has a strong patient and process focus that is apparent in her particular areas of interest namely Pharmacy Practice, Process Improvement and Medication Safety.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Professor Rob Landers, Consultant Histopathologist, University Hospital Waterford During 2021, Professor Landers has campaigned vigorously for an urgent improvement to mortuary services within Waterford Hospital. He has also been a key figure in compiling waiting list statistics and leading the research team looking into possible healthcare and hospital solutions.

Professor Landers has been a Consultant Histopathologist at Waterford Regional Hospital since 1999.

He has special interests and expertise in the areas of Breast Diseases and Dermatopathology. Since his appointment to WRH in 1999, Professor Landers has played a significant role in major policy development in the South East’s acute hospital services and has acted as Chairman of the hospital’s Medical Board for the last four years.

Dr Michelle Lavin, Lead Author, Researcher at the Irish Centre for Vascular Biology and the RCSI School of Pharmacy and Biomolecular Science Dr Lavin was the lead author of a research paper published in 2021 which has shown that early testing for blood clots in patients who had received the AstraZeneca/ Oxford vaccine led to them being treated successfully, highlighting the need for heightened awareness of the risk among doctors.

The work, led by researchers from RCSI University of Medicine and Health Sciences and the National Coagulation Centre at St James’s Hospital, is published in the British Journal of Haematology.

Professor Aoife Lowery, Personal Professor in Surgery & Consultant Breast & Endocrine Surgeon, NUI Galway/Breastcheck/GUH Professor Aoife Lowery (MB BCh BAO, MMedSci, FRCS, PhD) is a Consultant Breast/Endocrine Surgeon in Galway University Hospital and a Principle Investigator in the Lambe Institute for Translational Research in NUI Galway. Dual trained as a clinician scientist, Professor Lowery is widely published in the field of cancer research. Her research focuses on reducing the burden of cancer treatment and improving care and quality-of-life for people affected by cancer. She works with an interdisciplinary research team combining the expertise of clinicians, bioengineers, translational scientists and patients, addressing cancer survivorship challenges. Professor Lowery is the clinical lead on two cancerrelated disruptive technology innovation funds (DTIF) awarded by Enterprise Ireland in 2021. These projects focus on developing minimally invasive tumour ablation strategies and a novel solution for chemotherapy induced alopecia respectively. Professor Lowery hopes that clinical translation of these technologies will have a tangible impact on those living with and after cancer. Professor Lowery is also a member of the Precision Cardio-Oncology Research Enterprise and a Co-Director of the Cancer Biobank at NUIGalway.

She is actively engaged in surgical education, research training and mentorship as Year 5 Head in the School of Medicine NUIG and a Director on the Irish Clinical Academic Training (ICAT) programme.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Theresa Lowry Lehnen, Clinical Nurse Specialist (General Practice Nursing), Medical Centre IT Carlow Theresa currently runs a nurse-led medical centre for a patient population of almost 10,000. Working as a lone nurse 34/40 hours per week Theresa has a high level of autonomy, clinical knowledge, understanding, multi-tasking, problem solving and decision-making skills. She has written five nursing, health and psychology books, been involved in the development of two health apps and has had over 60 academic articles published in medical and nursing journals over the past two years.

Theresa designs, implements and delivers health promotion interventions and workshops in her area of work and in the wider community. She made a significant contribution to steering change, was instrumental to the introduction of a Smokeless Campus and implemented a smoking cessation counselling service for patients at her current area of practice. Theresa is the national PRO of the Irish General Practice Nurses Educational Association (IGPNEA) and this year alone she developed the IGPNEA ‘Educational Hub’, produced an online educational series of eLearning modules and educational videos and resources for General Practice Nurses, and was instrumental in implementing the provision of monthly educational webinars for IGPNEA General Practice Nurses CPD during Covid-19.

Laura Lyons, Senior Pharmacy Purchasing Technician, Mater Misericordiae University Hospital Laura Lyons, President of the National Association of Hospital Pharmacy Technicians in Ireland, was earlier this year appointed at Secretary of the European Association of Pharmacy Technicians.

Laura is Senior Pharmacy Purchasing Technician with the Mater Misericordiae University Hospital and a contributor to Hospital Professional News.

Laura has been a member of the National Association of Hospital Pharmacy Technicians committee for many years. As a member of the NAHPT she helps publicise the work of the Hospital Pharmacy Technician to a wider forum and encourages fellow Pharmacy Technicians to evolve and develop their roles.

EAPT is a non-profit making association and supports the Pharmacy Technicians in the provision of a safe, effective and efficient pharmaceutical service for the benefit of the patient in all association member countries.

Diana Malata, Advanced Nurse Practitioner, Royal Victoria Eye and Ear Hospital in Dublin Diana is currently an Advanced Nurse Practitioner in Cornea and Anterior Segment in the Royal Victoria Eye and Ear Hospital in Dublin. She played a lead role in the setting up of nurse-led anterior segment clinics in the Eye and Ear Hospital and was a recipient of the JC Coleman research award in 2018 for her work in setting up Ireland's first Nurse-led Corneal Crosslinking Service.

Diana was intergral to the establishment of a clinical site in the RVEEH as part of the VISICORT study. VISICORT is an EU-funded research project to help improve corneal transplant success.

Diana established an online virtual clinic during the COVID-19 pandemic. This clinic permitted the continued provision of treatment aftercare and management for patients attending.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Aoife Murray, Research Associate in Health Innovation, NUI Galway Dr Murray was part of a team who, at the start of 2021, helped connect patients with their loved ones, against a backdrop of Covid-19 restrictions on visits to hospitals. The work saw her team win a National Impact Award.

The university worked with industry partners Cisco and IBM to deliver a state-of-the-art video call system, ICU FamilyLink, specifically for the intensive care unit setting at University Hospital Galway (UHG). The project won the Knowledge Transfer Ireland Impact Award, in the ‘COVID-19 Response’ Category.

This initiative was delivered by Irial Conroy (IBM) and Dr Aoife Murray (NUI Galway), both BioInnovate alumni, Brian O’Donoghue (Cisco), Breda McColgan (IBM), PJ McKenna (IBM), Frank Kirrane (UHG), Leonie Cullen (UHG) and Dr Bairbre McNicholas (UHG).

Cliodhna McDonald, Senior Pharmacist – Oncology / Haematology Clinical Trials, Mater Misericordiae University Hospital (MMUH) Pharmacy Department During the past year, Cliodhna supervised the establishment and activation of 17 clinical trials while also completing the Liverpool John Moore’s University Masters Certificate of Professional Development in Oncology Pharmacy Practice in Secondary Care. To maintain patient adherence and health outcomes during the COVID-19 pandemic, Cliodhna, and her colleague, Conor Moran - Senior Pharmacist, Infectious Disease, developed a service for home delivery of Infectious Disease and Oncology / Haematology oral drugs, from the MMUH Pharmacy Department during the COVID-19 pandemic.

Pharmaceutical Society of Ireland and Health Service Executive guidance for delivery of medicines favoured the use of a volunteer delivery service, and so the Order of Malta was contacted who agreed to act as the volunteer delivery service for the MMUH Pharmacy Department. This service provided reassurances to patients at a difficult time and helped in a small way to control the stress of accessing healthcare during the pandemic.

Professor Gerry McElvaney, Professor of Medicine at RCSI University of Medicine and Health Sciences Professor McElvaney was this year honoured with the Health Research Board (HRB) Impact Award 2021. The award recognises the lasting impact Professor McElvaney has had on people’s health and patient care by applying his respiratory medicine research in practice. His work has informed local, national and international guidelines including European and World Health Organisation developments.

Throughout his career Professor McElvaney has consistently demonstrated the benefits that can be achieved by proactively integrating research into policy and practice. His work focused on a specific genetic disorder called alpha 1 anti-trypsin deficiency (AATD) that leads to an increased risk of developing lung complications such as chronic obstructive pulmonary disease (COPD).

Dr Marie McIlroy, Lecturer, RCSI University of Medicine & Health Sciences A study from RCSI, led by Dr Marie McIlroy, demonstrates for the first time a dynamic steroid response to standard of care therapy linked to long-term patient outcomes in breast cancer.

It has been accepted that sex steroids are mediators of breast cancer development for well over 100 years, however, steroid profiles are not routinely evaluated in patients. This study analysed patients’ hormone profiles to provide researchers with a deeper understanding as to how breast cancer cells are affected by different hormones and why patients respond differently to hormone therapy. The study found that success of the treatment can be influenced by patients’ hormone profiles both before and after hormone therapy treatment. This timely research published in Clinical Cancer Research highlights the therapeutic potential of steroid profiling in postmenopausal breast cancer patients to optimise individual patient care and improve overall survival.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Niamh McMahon, Chief II Pharmacist, St James’s Hospital, Dublin Within her current role is MSc in Hospital Pharmacy Programme Manager within the School of Pharmacy & Pharmaceutical Sciences, Trinity College Dublin, with students based across seven participating hospitals. Niamh's chosen specialty areas are Care of the Older Person and Cardiology. Niamh set up the Cardiology in Clinical Pharmacy Practice CPD module for hospital and community pharmacists with colleagues in 2013, and over 300 pharmacists have completed it.

The MSc in Hospital Pharmacy won the Gradireland Postgraduate Course of the Year in 2018 in the Health Sciences Division. Niamh won the Dean of Health Sciences award, for Outstanding Teaching in Professional Practice in 2019.

Her current research interests relate to addressing polypharmacy & potentially inappropriate prescribing in older people, and clinical teaching and competency development. She is Lead Liaison Pharmacist to the National Integrated Care Programme for Older People & Chairperson of the Hospital Pharmacists’ Association of Ireland, Special Interest Group for the Care of Older People.

Dr Bairbre McNicholas, Honorary Senior Lecturer, NUI Galway/Intensive Care Consultant at University Hospital Galway Dr McNicholas published a study in 2021 which demonstrates that clinicians should treat patients on their stomachs.

Critically ill Covid-19 patients are less likely to die or to require invasive ventilation if lying prone on their stomachs while receiving oxygen, the global research study found.

The study was the first clinical trial of its kind into the practice of awake prone positioning and ran from April 2020 to January 2021. It showed that treating patients in this position, while they received high flow nasal cannula oxygen, reduced death and the need for invasive mechanical ventilation.

Dr Dania Movia, Senior Research Fellow, Trinity Translational Medicine Institute Senior Research Fellow, CRANN The research work of Dr Dania Movia is among those cited in a knowledge base developed by the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM). Early this year, EURL ECVAM undertook a study to review available and emerging non-animal models in the field of respiratory tract diseases, including lung cancer.

From this it produced a unique knowledge base that contains detailed descriptions of non-animal models that can be used for research on respiratory diseases, and for the development of new drugs and therapies. It is expected that the knowledge base will be of particular use to competent authorities in EU Member States to ensure that scientists have properly considered the use of non-animal models and methods in their research.

Geraldine Mullan, Specialist Oncologist Nurse, Letterkenny Hospital Specialist Oncology Nurse Geraldine has, during this year, demonstrated compassion and determination in the wake of personal tragedy, ensuring her patients received optimum care. Geraldine has now established the Mullan HOPE centre, at her family's former garden centre business in Moville. With Hope standing for Hub Of Positive Energy – it is a community based non-profit organisation/ company limited by guarantee, the new hub will serve as a centre for community groups and other events and be a place for people to gather and engage with each other.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Professor Fionnuala Ní Áinle, Consultant Haematologist, Mater Misericordiae University Hospital and Rotunda Hospital/Associate Clinical Professor, University College Dublin Professor Ní Áinle is part of the AI_PREMie team along with Professor Patricia Maguire, UCD School of Biomolecular and Biomedical Science, Dr Paulina Szklanna, and Professor Mary Higgins. Their project this year addressing the significant challenge of diagnosing preeclamptic toxaemia (PET), one of the world’s deadliest pregnancy complications, was awarded a SFI Future Innovator Prize.

AI_PREMie uses cutting-edge biomedical, clinical and machine learning techniques to analyse a combination of biomarker signals and clinically relevant maternal data, to provide a straightforward assessment of pregnancies at risk of PET complications, thereby helping to prevent unnecessary adverse outcomes for mothers and babies.

She serves as Chair of her hospital and regional venous thromboembolism (VTE) committees and is a founding member of VTE Ireland, a National Clinical VTE Working Group. She is co-organizer of the VTE Dublin thrombosis conference and a member of the "Preventing venous thromboembolism in hospitals" National Collaborative Advisory Group of the Irish Health Services Executive Quality Improvement Directorate.

Dr Tríona Ní Chonghaile, Senior Lecturer, Royal College of Surgeons in Ireland Dr Ni Chonghaile’s recent paper in Science Advances was trying to identify new therapeutics for the treatment of refractory triple negative breast cancer. She and her team tested different molecules to see if they could selectively kill breast cancer cells, while sparing normal cells. Through this screening approach they found that a specific molecule, BAS-2, was able to do this.

To better understand how the molecule killed the cells, she confirmed that it inhibited an enzyme called histone deacetylase 6 (HDAC6). She is the first author of the study. The aim now is to develop the small molecule into a more drug-like compound and to assess if the team can harness the new function for potentially improved treatment of patients.

With the help of RCSI’s Office of Research and Innovation, they have submitted a patent around this work and are seeking industry partners to further develop this treatment.

Dr Joan Ní Gabhann-Dromgoole, Lecturer in Immunology and Ophthalmology, RCSI university of Medicine and Health Sciences Dr Ní Gabhann-Dromgoole is currently the scientific lead for the Ocular Immunology Research Group (OIRG) in RCSI. The group successfully operates within a clinician-scientist framework and thus are uniquely positioned within RCSI and the Royal Victoria Eye and Ear Hospital to investigate the immunological component to a range of ocular surface diseases. Dr Ní Gabhann-Dromgoole is currently the scientific lead for the Ocular Immunology Research Group (OIRG) in RCSI. She has been involved in a range of outreach and patient public involvement (PPI) events most recently Dr Ní Gabhann-Dromgoole co-organised the first patient information webinar for Sjögren’s Syndrome patients in Ireland. Dr Ní Gabhann-Dromgoole also designed the first patient information leaflet for Sjögren's patients in Ireland with contribution from a range of medical experts involved in the care and management of Sjögren’s Syndrome.

Demonstrating her commitment to equality, diversity and inclusion Dr Ní Gabhann-Dromgoole co-organised the inaugural Women in Vision and Eye Research Conference for 2021.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Mary Ni Lochlainn, Irish Specialist Registrar in Geriatric and General Internal Medicine; NIHR Doctoral Fellow, St Thomas’ Hospital She was the recipient of a large NIHR grant to pursue a doctorate in geriatric medicine. Her research as part of this NIHR Doctoral Fellowship focuses on ageing muscle, particularly the blunted response of older muscles to a protein bolus, and the role the gut microbiome may play in mediating this response. She is currently running a clinical trial examining this question.

Mary is involved in a number of boards and committees and most recently has led the introduction of a new award in Geriatric Medicine, as part of her role within the European Geriatric Medicine Scoiety (EuGMS). The Stefania Maggi award is named after the first (and only) female president of the EuGMS and is awarded to the top three abstracts submitted by early career geriatricians, who are then invited to present their work in a dedicated symposium at the annual congress. The inaugural award was presented in October 2021 in Athens, but the congress will also be avaialble online.

Professor John Nolan, Principal Investigator, Howard Chair in Human Nutrition, ERC Fellow, Waterford Institute of Technology Professor Nolan led a trial in Waterford this year which showed that "targeted nutrition" can help improve the quality of life of people suffering from Alzheimer’s disease. The trial, titled re-MIND (Memory Intervention with Nutrition for Dementia), was carried out by Professor Nolan and Dr Rebecca Power of the Nutrition Research Centre Ireland (NRCI) at Waterford Institute of Technology (WIT) in collaboration with Professor Ríona Mulcahy, a consultant physician in general and geriatric medicine at University Hospital Waterford.

According to the researchers, the trial is the first “placebo-controlled nutritional interventional trial in patients with Alzheimer’s disease to demonstrate significant improvements in antioxidant and anti-inflammatory nutrients [omega-3 fatty acids and carotenoids] for the active intervention group compared to placebo”.

Professor Tim O’Brien, Chair of Medicine & Director of REMEDI, National University of Ireland Galway/Consultant Endocrinologist, Galway University Hospital/Dean, College of Medicine, Nursing & Health Sciences Professor O’Brien established one of the first gene therapy laboratories at Mayo and published internationally recognised studies on the role of nitric oxide synthase in modulating the vascular endothelium. He is an internationally recognised clinician and scientist with expertise in regenerative medicine applied to the treatment of diabetes complications.

John O’Byrne, Acting Head of the Pharmacy Department, Tallaght University Hospital John was the recent recipient of the CEO Award at the Tallaght University Hospital Hero Awards. This Award was nominated by the Chief Executive, Lucy Nugent, on behalf of herself and the management team recognising individuals that go above and beyond, often behind the scenes that may not be evident to all staff. John is a long standing valued member of the Pharmacy team but also in the wider hospital team.

Lucy Nugent said, “The COVID-19 Pandemic has presented us all both professionally and personally with enormous challenges. No one could ever have envisaged the changes we would have undergone in providing care to our patients or how our own lives would alter.”

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Juliette O’Connell, Assistant Professor in Pharmacy Practice, Trinity College Dublin Dr Juliette O’Connell is one of six winners of the Dean’s Research Initiatives Fund for 2021. The Fund will be used to study the development of OPTIMA-ID: Optimising Pharmaco-Therapy and Improving Medication for Ageing with Intellectual Disability.

Dr O’Connell also published a paper this year which looked at defensive pharmacy practice. Defensive practice is prevalent across healthcare disciplines and much study has been performed on this behaviour in medicine and nursing.

However, little research has been carried out on defensive practice in pharmacy, despite its potential to increase healthcare costs, reduce quality of care and affect pharmacist job satisfaction. Research in this area is necessary to identify how this phenomenon affects the profession and to develop methods of improving pharmacy practice.

Máiréad O'Connor, Pharmacy Lead – Infectious Diseases, Mater Misericordiae University Hospital Máiréad is the Pharmacy Lead for Infectious Diseases, leading a team of 5 pharmacists in the care of over 1,600 patients with Infectious Diseases (ID) including HIV, Hepatitis C, Tuberculosis and COVID-19. As with all areas of healthcare, the onset of COVID-19 had a significant impact on the provision of services to in-patient and out-patient ID patients. As the National Isolation unit Pharmacist, Máiréad was responsible for caring for the first adult COVID-19 patients admitted to an Irish hospital and was instrumental in developing local and national COVID-19 treatment guidelines. Máiréad, along with other MMUH colleagues also participated in the development of the COVID-19 Hub for the Irish Institute of Pharmacy (IIOP).

Máiréad introduced a new procedures to ensure a high quality dispensing and clinical pharmacy service to all ID out-patients who required continuous and on-going access to essential medicines which cannot be obtained in primary care.

Máiréad is considered an expert in Infectious Diseases. In recognition of this expertise, she was asked to contribute to the Medicines Criticality Assessment Group, a subgroup of the National Public Health Emergency Team (NPHET) for COVID-19 and the HSE Guidance for the Use of Antiviral Therapy in The Clinical Management of Acute Respiratory Infection with SARS-CoV-2 (COVID-19). Máiréad, along with other MMUH colleagues also participated in the development of the COVID-19 Hub for the Irish Institute of Pharmacy (IIOP).

To minimize the impact of COVID-19 on out-patients attending the ID service, Máiréad rapidly reviewed and amended the service delivery model. Máiréad has also been heavily involved in the multidisciplinary co-ordination of resumption of routine ID out-patient services in the post COVID-19 era.

Professor Martin O’Donnell, Professor of Translational Medicine, NUI Galway Professor O’Donnell has recently been awarded funding for A Randomised Controlled Trial on Sleep Hygiene Education for Blood Pressure Reduction. Professor O’Donnell is co-Director of an MSc in Clinical Research at NUI Galway.

Profesor O’Donnell’s research focus includes epidemiology of stroke, clinical trials and systematic reviews in vascular medicine. He holds an ERC award investigating sodium intake and cardiovascular health (COSIP). He has published over 100 peer-review papers, including clinical studies, in high-impact journals, including NEJM, JAMA and Lancet.

Marie O’Halloran, Supervising Pharmacist/Dispensary Services Manager, Mater Misericordiae University Hospital As the Dispensary Services Manager, Marie was required to rapidly source large volumes of drugs, in quantities beyond what the MMUH would routinely use. This involved a multi- pronged approach; rapidly calculating projected drug requirements, liaising with drug companies to ascertain stock holdings and engaging with stakeholders to determine alternative options if drugs supply chains could not be maintained, or appeared be in jeopardy. Marie sourced a variety of medications to treat COVID-19 patients, both for current and future treatment, by horizon scanning and reviewing evolving and emerging evidence. As a national centre of excellence for many specialities, the MMUH are required to source a large number of unlicensed medications for unusual indications. Marie has had to establish new supply chains for many of these medications that previously came directly from the UK. After Brexit it was no longer possible to buy drugs directly from the UK as it became a third country, causing a risk to drug supply of more unusual or lower use unlicensed drugs. Marie extensively mitigated the risks by compiling a list of all the unlicensed drugs and suppliers used for drug supply. She then identified alternative supply chains for all drugs, by liaising with a variety of suppliers and negotiating with intermediary wholesalers and UK based companies. Where options to obtain supply were limited, she engaged with stakeholders to consider alternatives and sourced these.

Coupled with the above extraordinary events of 2020, as supervising pharmacist and Dispensary Services Manager Marie had to ensure the day to day running of the Dispensary was maintained. Marie is a team player and completes any role required to ensure that drug supply for patients is maintained.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Asst Professor Fardod O’Kelly, Consultant Paediatric & Adolescent Urological Surgeon, Beacon Hospital/University College Dublin/RCSI Mr O’Kelly returned home from the prestigious Hospital for Sick Children, Toronto (recently awarded the best children’s hospital in the world) in July 2020 to take up a post as a paediatric and adolescent urological surgeon in the private sector. He established the only dedicated paediatric urological private service in the country, and in addition to this maintained research collaborations on both sides of the Atlantic and surpassed his 70th publication soon after returning home and was invited to deliver lectures at 3 international urological meetings.

He was recently appointed to three European boards within the European Association of Urology, established an educational podcast series with the Journal of Paediatric Urology, and was appointed as a panel-writer with the Joint Committee on Intercollegiate Examinations in the UK and Ireland. He is currently working with the European Association of Urology to develop guidelines on transitional and adult congenital care for urological patients and hopes to translate this back to Ireland where no such service exists.

Elizabeth O’Neill, Clinical Nurse Specialist Vascular/Veins, Tallaght University Hospital Elizabeth established the Integrated Leg Ulcer Clinic - a Slaintecare accepted project. It is a specialist leg and leg ulcer clinic, with a goal to work collaboratively with CH07 to improve the care of Vascular Patients and Patients with leg ulcers.

The project is being led by Tallaght University Hospital. Patients are assessed, diagnosed and treated in the community.

This will allow care to be brought closer to home.

This clinic is set up to avoid patients needing to attend the hospital at all. We advise and promote Vascular Health including looking at risk factors both modifiable and non-modifiable. It is proven that prevention, early identification and self-management will result in better outcomes. Elizabeth and her team aim to give patients a better quality of life.

Since its opening the team have seen 350 patients and have had over 1100 appointments. All patients seen within 2-4 weeks.

Dr Jamie O’Sullivan, Principal Investigator and Research Lecturer, Royal College of Surgeons in Ireland During 2021, Dr O’Sullivan has worked alongside a team of scientists, collaborators and clinical colleagues at St James’s Hospital, Beaumont and RCSI to provide insights into coagulopathy associated with severe COVID-19.

To this end they have published a number of high impact publications in several journals.

This work has attracted significant international attention with high Altmetric scores, placing the work in the top 5% of outputs ever tracked by Altmetric. Following this, the team were invited to write a number of editorial pieces in the Lancet Hematology and British Journal of Haematology. In addition, Dr O’Sullivan was invited to present these findings at the leading conferences in the field including the American Society of Hematology meeting.

Recently, Dr O’Sullivan secured research funding from Irish Research Council Enterprise partnership fund to grow her research team focused on crosstalk between coagulation and cancer and she has been involved in a campaign to raise awareness of the risks of blood clots as part of a public-patient engagement.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Barry O’Sullivan, Senior Pharmacist, Mater Private Hospital, Cork/ Adjunct Clinical Lecturer, School of Pharmacy, College of Medicine and Health, University College Cork Barry is the Medication safety lead for the Hospital, as well secretary of the medication governance committee, and serves on the CPR, Falls and Hemovigilance committees. He previously chaired the Pain Management committee.

He has worked on a number of cross-functional projects as well as his day-to-day Pharmacy role. He has assisted in a number of medication safety improvement plans as well as utilised his professional finance qualifications with the Finance Department including process optimisation and Clinical service expansions.

Barry’s current focus is in Cardiology additional to working with the surgical and medical wards.

In this role he regularly delivers educational sessions for clinical colleagues. As a Senior Preceptor with APPEL, he has a keen interest in teaching and development of Student Pharmacists.

Dr Sharon O’Toole, Senior Research FellowScientist in Trinity College Dublin/ Chair of OvaCare & Medical Panel This year, Dr O’Toole and the Ovacare team were awarded the World Ovarian Cancer Day 2021 Award. Dr O’Toole has been recognised for building a strong and collaborative effort in the fight against ovarian cancer in Ireland.

Dr O’Toole was instrumental in establishing INNOVATION- the Irish National Network for Ovarian Cancer Collaboration which has brought together the medical, research and charity organisations involved in ovarian cancer in Ireland. She was part of the organising committee of the first World Ovarian Cancer Day on May 8th in 2013 and this has now become a very successful annual event.

She also sits on the board of the Irish Society for Gynaecological Oncology with a responsibility for Public and Patient Involvement (PPI).

Professor Yoshi Onuma, Professor of Interventional Cardiology, NUI Galway/Medical Director, CORRIB Research Centre Dr Onuma is Deputy Chair of the PIONEER-IV trial, currently undergoing to conduct a clinical trial of a special stent which has the potential to break new ground in the treatment of patients with heart disease.

“The hope is that this trial will simplify the treatment for patients undergoing stent implantation of diseased blood vessels, and could offer benefits to patients when coupled with a shorter duration of blood-thinning medications,” he says.

Dr Onuma, MD, PhD is a leading expert in the field of bioresorbable scaffolds. He also has extensive expertise in quantative coronary angiography (2-dimensional, 3-dimensional and bifurcation-dedicated).

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Muriel Pate, Medication Safety Specialist Pharmacist, HSE Muriel has been supporting healthcare professionals and the public throughout the Covid pandemic. This includes leading roll out of access to information to aid medication reconciliation at admission to hospital, coordinating interim clinical guidance on immunosuppression, supporting medicines management at vaccination centres and supporting HSE collaboration with community pharmacy.

This is in addition to progressing the HSE's work to reduce medication-related harm and reduce harm from VTE (blood clots).

Joan Peppard, Chief Pharmacist, Midlands Regional Hospital Tullamore Having been actively involved in the vaccine rollout in the MRHT, Joan was nominated as the Pharmacy Lead for the vaccination centres for the Dublin Mid Leinster area managing the pharmacy teams in 6 centres. She established the pharmacy systems to support the vaccination rollout in Citywest CVC working as part of the multidisciplinary team which had logistical support from the Defence Forces. Joan was actively involved in the recruitment and rollout of the pharmacy teams in the vaccination centres in the Dublin Midlands region.

Joan was also nominated as a member of workstream groups supporting the national vaccination rollout including: Large Scale Health Care Facilities for Covid-19 Vaccination of Health Care Workers, the Over seventies working group and Vaccine Process and Workflow as well as the Midlands Integrated Governance Steering Group of Health Care Worker Vaccinations and Public Vaccination Sites. Joan was involved in the beta testing and enhancement of the GS1 Trackvax dispensing software that enabled an efficient track and trace solution in the large vaccination centres.

Dr Shona Pfeiffer, Lecturer & Principle Investigator, RCSI University of Medicine & Health Sciences Dr Shona Pfeiffer leads a translational collaborative, clinically-oriented research programme focused on the development of diagnostic, prognostic and novel protective agents in the treatment of neurological disorders and diabetes mellitus. At RCSI, her team works closely with collaborators in Beaumont Hospital and the Stroke Clinical Trials Network, Ireland (SCTNI) focusing on the development of novel approaches for the diagnosis and prognosis of ischaemic stroke patients in the acute phase to better inform treatment decisions and patient outcomes.

Dr Pfeiffer is co-lead of the RCSI Student Innovation Challenge, which sees students at RCSI University of Medicine and Health Sciences work to develop ideas and innovations to solve some of the biggest challenges facing global healthcare. In 2021 she was recipient of a Student Engagement and Partnership Award and the RCSI 2021 Education Innovation Award, developed to recognise the importance of innovation in teaching and learning, as well as to promote and highlight examples of innovative educational practice in medicine and health sciences education.

Ann Pilkington, Senior Pharmacy Technician, HSE Naas General Hospital Ann had originally taken up her new role in purchasing and procurement at Naas General Hospital in 2010.

Never daunted by a challenge, Ann was aware that in the then current economic climate there would be even greater demands for pharmacy savings, smart medicines management and hard contract negotiations. With a background in hospital pharmacy Ann has brought a wealth of experience, professionalism and expertise to this new role, constantly evolving and adapting to the new challenges occurring over the years. In recent times the combination of COVID-19 and Brexit has created a unique environment in which the landscape is constantly changing and the pharmacy procurement department has needed to be highly flexible and adaptable.

Ann has also, in her spare time, trained and participated in the National Covid-19 Vaccination program, and was based in the Carlow IT site. She continues to approach patient care and safety, medication safety and economy with the same commitment that she began her career with.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Shirley Potter, Consultant Plastic and Reconstructive Surgeon, Mater Misericordiae University Hospital/Associate Clinical Professor at UCD In February of this year, Dr Potter was chosen for the Irish Cancer Society’s 2021 Clinician Research Leadership Award. Dr Potter’s interest in cancer stemmed from a close personal link which has driven her determination to improve the outcomes of people affected by the disease.

“I have had a personal encounter in that my mum has had both ovarian and colorectal cancer, and she’s still alive and amazing, and she inspires me in the work that I do,” remarks Dr Potter, who wants to contribute to reducing the burden of melanoma in future given the devastating impact it can have for the 1,300 people diagnosed with it every year in Ireland.

Professor Jochen Prehn, Director, Centre for Systems Medicine, RCSI University of Medicine & Health Sciences Professor Prehn heads up a large research team at the interface of biomedical and translational research focusing on oncology, neuroscience, and metabolic disorders. His research includes the development of computational approaches to understand development, progression and therapy resistance in colorectal cancer and brain cancers.

He recently demonstrated a direct relationship between the presence of bacteria, in particular the anaerobic bacterium Fusobacterium nucleatum, the host response to this infection, and the spread of colorectal cancer resulting in poorer outcome of patients. His research can help clinicians to identify patients at risk of poorer outcomes and make decisions on treatment options for patients whose tumours are infected with the bacterium.

His team hopes that this finding will enhance diagnostics to improve the efficacy of current treatment and help further advance the use of new therapeutics for patients infected with this bacterium. This can be achieved either by interfering with the infection itself or the host response to the infection.

Professor Karen Redmond, Consultant Thoracic & Lung Transplant Surgeon, Mater Hospital/Beacon Hospital/ Blackrock Clinic Professor Redmond co-led a specialist team at Beacon hospital to introduce a groundbreaking new procedure to treat Ireland's most common cardiac rhythm disorder atrial fibrillation. It was launched earlier this year. Beacon Hospital's Heart Rhythm Centre has become the first in Ireland to exclusively offer a hybrid staged procedure involving both an Electrophysiologist and a Thoracic Surgeon.

Professor Redmond specialises in the surgical management of patients with lung cancer, end-stage lung disease (emphysema and pulmonary fibrosis) and a range of other prevalent conditions including complex airway and pectus conditions.

Professor Redmond was the first female lung transplant surgeon to be appointed both in the UK and Ireland.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Eileen Relihan, Medication Safety Facilitator, Department of Pharmacy, St James’s Hospital Eileen is the co-founder of the Medication Safety Minute – Microlearning in Medicine. Her team developed a tool based on the principles of microlearning to support safe prescribing. It involved the compilation of fundamental learning points for the prescribing of high-risk medications as concise knowledge nuggets ‘Medication Safety Minutes’ and their communication to front-line hospital prescribers.

Along with colleagues, Eileen also co-authored a paper this year on the ‘Assessment of an electronic patient record system on discharge prescribing errors in a Tertiary University Hospital.’ This study found that a multi-component educational intervention had a small effect on improving prescribing errors and communication at discharge. However, the implementation of an electronic patient record with a discharge prescribing function significantly reduced prescribing errors and omissions at discharge.

Dr Dominic Rowley, Consultant Physician, Genitourinary Medicine, Midland Regional Hospital Portlaoise/Medical Director, LetsGetChecked Dr Rowley is a Sexual Health Specialist who is passionate about raising awareness around sexual health.

Dr Rowley carried out a survey earlier this year within his STI clinic which was able to determine a rise in cases of sexually transmitted infections. Looking at the first three months of the first lockdown compared to the previous year, he and his team noticed the increase. Dr Rowley as Medical Director with LetsGetChecked is an advocate of emphasising accessible health screening and advising patients on tracking, monitoring and improving their overall health.

Professor Patrick W Serruys , Professor of Interventional Medicine and Innovation, NUI Galway This year Professor Serruys has been involved in reporting results from the SYNTAX Extended Survival Trial, of which he is Senior Investigator. According to long-term follow-up from this study, revascularization with PCI might be a reasonable alternative to CABG surgery in elderly patients with complex coronary artery disease, including multivessel and left main disease.

Professor Serruys is a renowned expert in interventional cardiology and imaging with >4 decades of experience in clinical trials and innovation. He has pioneered several interventional procedures and devices such as BMS, DES, BRS and TAVI as well as imaging techniques including quantitative angiography, IVUS and OCT. In parallel he has developed interest for non-invasive imaging of CAD combining anatomy and functional assessments of CTA.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Richard Skelly, Specialist Registrar in Anaesthesia, St. Vincent’s University Hospital Dr Skelly has recently published guidelines on the implementation and running of a telecommunications clinic. Prior to publishing these guidelines he gained experience in the area by setting up and running the Sligo University Pain Telecommunications Clinic, which was deemed extremely successful by both practitioners and patients with 100% of patients happy to reattend. Implementation of this was found to dramatically reduce travel and in-person attendances of patients from the Sligo Pain Clinic and as such reduced their costs as well as dramatically reducing CO2 emissions related to the travel.

In addition to this work he has had an interest in patient safety and in particular, patient safety in theatre. This work has culminated in the design and production of a syringe safety mechanism. This device reduces the risk of medication errors in theatre and as such improves patient safety. Additionally, Richard has set up a Community First Responder Group in Strandhill, Co.Sligo which has taken over two years to realise due to delays caused by the pandemic.

Professor Gábor Széplaki, Head of Cardiac Electrophysiology, Mater Private Hospital/Hon. Clinical Associate Professor RCSI Led by Professor Széplaki, Mater Private Network has become the first electrophysiology centre in the UK and Ireland, and one of the first ten hospitals in the world, to implement the new SPI digital platform for quantifying the efficiencies inside the Cath Lab. This new technology is designed to reduce variability in surgical processes and enhance team performance through synchronised workflows, real-life learning and real-time analytics.

SPI digital platform enables the hospital team to deliver consistent high quality of care and improved efficiency, to reduce risk and improve patient outcomes.

Mariangela Toma, Chief II Pharmacist, HSE National Immunisation Office Mariangela joined the NIO in January 2021 at the start of the rollout of the COVID-19 Vaccination programme. She represented the NIO in the TrackVax project team supported by GS1 Ireland.

Publicly procured vaccines have been within the remit of the NIO for over 15 years, and the COVID-19 vaccines required equally high-quality management at all times. Some of the vaccination channels were new and required procedures to effectively manage the ordering and storage of the and to reduce vaccines wastage.

After an intense designing phase, TrackVax, an intuitive app, based on the barcode scanning technology, was created with the intent of tracing vaccines journey from time of dispatch from central storage to vaccination centres to the time of administration.

Throughout the intensive design, implementation, and evolution of the TrackVax App, Mariangela’s participation to the project was instrumental to ensure that the technological innovation was brought to the health sector’s service for the provision of a safer and standardised medication management and more efficient vaccine reconciliation across the 43 Central Vaccination Clinics.

Professor Oscar Traynor, Professor of Postgraduate Surgical Education at RCSI Professor Traynor has this year, been made an Honorary Fellow of the American College of Surgeons.

Spanning more than 20 years, Professor Traynor’s career in RCSI and Irish surgical training has been long and distinguished, He is widely regarded as an international expert in liver transplantation and hepatobiliary surgery as well as surgical training.

During his tenure as Dean of Post Graduate Surgical Training and Education, Professor Traynor oversaw many changes in the delivery of surgical training in Ireland, including structured operative skills training, surgical boot camp for new core trainees, the establishment of a centralised application and selection process using innovative aptitude and objective measurement techniques, the implementation of the intercollegiate surgical curriculum across all specialties and the creation of online e-learning programmes for surgical trainees.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Oliver Treacy, Senior Postdoctoral Researcher, NUI Galway Despite significant disruptions caused by the pandemic, Dr Treacy has achieved a number of significant milestones over the past 12 months. He was senior author on a high-impact publication in the prestigious journal Molecular Therapy in September 2020 concerning the efficacy of adult stem cells as a cell therapy for corneal transplantation, which already has 11 citations. In March 2021, in recognition of his achievements in a separate research area (cancer immunology), Dr Treacy was awarded the European Association for Cancer Research Young Scientist Award. In July 2021, Dr Treacy, again as senior author, published a highly accessed study on the preprint server bioRxiv concerning the role of stromal cell sialylation in the context of colorectal cancer. In June 2021, Dr Treacy was nominated by NUI Galway to submit an application to the SFI-IRC Pathway programme for outstanding early career researchers making the transition to become independent group leaders.

Alexandra Troy, Physician Associate, Beaumont General and Colorectal Surgery Alexandra is one of the first Irish trained Physician Associate (PA) graduates to be employed in Ireland. She was part of the pioneering first cohort of the RCSI Physician Associate Studies Programme and is involved in examining PA students for OSCEs and long case exams as well as being a supervisor for students when they are on clinical rotation on the hospital site. Alexandra has facilitated the PA students and has set up a number of teaching opportunities for first and second year PA class groups. She has also been involved in the RCSI Student Innovation Programme and Competition as well at the Physician Associate Graduate and Physician Associate Student Mentorship Programme.

Dr Damir Vareslija, Principal Investigator and Breast Cancer Now Senior Research Fellow, RCSI Earlier this year, Dr Vareslija and his team led a new study exploring how a new drug could be used to treat people with incurable secondary (metastatic) breast cancer which has spread to the brain.

The study is funded by Breast Cancer Now, and Dr Vareslija’s team will investigate if the drug could be used to treat secondary breast cancer in the brain.

Secondary breast cancer occurs when breast cancer cells spread from a primary tumour in the breast, through the lymphatic or blood system to other parts of the body where it becomes incurable. There are limited treatment options for people with breast cancer that has spread to the brain and a lot of drugs are unable to reach these tumours because of the brain's natural protection, meaning new treatment discoveries are urgently needed.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Sinead Walsh, Lecturer in Medical Education & Consultant Respiratory Physician , NUI Galway/University Hospital Galway During the Covid-19 pandemic, Dr Walsh was faced with a major challenge to provide sufficient and effective clinical training despite a 50% reduction in clinical placement time. She was instrumental in introducing an ‘Experiential based learning’ approach into the final year medical curriculum at NUI Galway, where students were embedded contributors to the work of clinical teams rather than observers. She has recently been appointed as Year 5 Head. She was awarded the Professor Pat McHugh award for ‘Best Consultant Teacher’ for academic year 2020 – 2021 in Galway, as voted by the final year medical students.

Dr Walsh has a special interest in interstitial lung disease (ILD) and sleep medicine. She recently obtained funding to create a unique biorepository of biological material from patients with progressive fibrosing ILD and will represent NUIG & UCHG in the international effort to identify biomarkers of disease severity and identify new treatments.

Simone Walsh, Senior Research Projects Manager, RCSI University of Medicine and Health Sciences Simone is an Irish trained nurse and certified Project Management Professional. Having worked as a research nurse for 11 years, Simone was appointed as the Senior Research Projects Manager of the RCSI Skin Wounds and Trauma (SWaT) Research Centre in September 2018. The Centre is Ireland’s only nurse-led research centre and is driving cutting-edge research in wound healing and tissue repair.

Simone established the Centre’s gold-standard research development protocol, and built the structures to launch the SWaT Research Network. She is the Centre’s lead on Industry sponsored HPRA regulated clinical investigations of medical devices, ethics, data protection and PPI. Most recently she project managed a Science Foundation Ireland Covid-19 Rapid Response award, at the height of the pandemic.

Simone is a member of the RCSI Research Ethics Committee, HRB-CRCI Public and Patient Involvement (PPI) Working Group and Irish Research Nurses and Midwives Working Group.

Dr Thomas Walther, Professor of Pharmacology, Head of Department at University College Cork, Ireland (UCC) Professor Walther’s research carried out in 2021 has found a treatment that could potentially extend the lives of kidney cancer patients. Renal cell carcinoma (RCC) is the sixth most frequently diagnosed cancer in men and the 10th in women, accounting for over 175,000 deaths annually worldwide. The five-year survival rate for patients with metastatic RCC is only about 12%. Resistance to therapy occurs in most patients, and new combinations of treatments to enhance the efficacy of current medication are urgently needed. A team of investigators led by Dr Thomas Walther, Professor in Pharmacology at UCC, and Dr Rupal Bhatt, Associate Professor, Medicine, at Harvard Medical School, have identified that the enzyme ACE2 plays an essential role in resisting current therapies.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Professional 100 Dr Dale Francis Whelehan, PhD researcher in Behaviour Science at the School of Medicine, Trinity College Dublin Surgeons were already sleep deprived before their on-call shifts and were even more sleep-deprived afterwards. This was one of the key findings from a study carried out by Dale this year focussed on the effects of being ‘on-call’; a frequent state for surgeons.

The study is unique as it is the first to attempt to control for a series of confounding variables such as experience, quality and quantity of sleep, the influence of caffeine and circadian rhythm influences. Dale has presented on 'student centred approaches to teaching and learning' in several conferences, both nationally and internationally as well as his current research exploring analysis of surgical performance with particular focus on objective assessment of the domains of medical professional practice, sleep deprivation, and cognitive biases in clinical decision making.

Professor Leonie Young, Department of Surgery, Royal College of Surgeons Ireland In October of this year it was revealed that Professor Young’s work within the field of breast cancer is investigating if certain drugs could be used to treat people with secondary breast cancer in the brain.

"People are always at the heart of the research we do and we are always trying to answer questions that are important to our patients,” she says.

There are limited treatment options for people with breast cancer that has spread to the brain and a lot of drugs are unable to reach these tumours because of the brain's natural protection, meaning new treatment discoveries are urgently needed.

Professor Leonie Young leads the Endocrine Oncology Research Group based at York House in the Royal college of Surgeons in Ireland.

Professor Dominic Zerulla, Founder, PEARlabs, University College Dublin Professor Zerulla’s spin-out company PEARlabs have just won the 'Viewers’ Choice Award' at Enterprise Ireland’s 2021 Big Ideas Showcase. The company, which is currently taking part in the UCD VentureLaunch Accelerator Programme run by NovaUCD, has a developed a novel photonic chip that has the potential to transform the understanding of processes such as cell signalling and cell proliferation in cancer and other life-threatening diseases.

This patented technology enables ultra-high spatial resolution at video rates in optical microscopy far beyond the diffraction limit of visible light.

Full prescribing information is available on www.medicines.ie Legal category: POM (S1A). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Marketing Authorisation Numbers: EU/1/16/1138/001-007

▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

IE-VNCLY-210007 | Date of Preparation: April 2021

Awards

2022

Hospital Professional

Hospital Professional Awards 2022 To mark what has been an incredibly tumultuous year, IPN Communications are thrilled to announce that the Hospital Professional Awards (HPA) will once again take to the stage in 2022.

Hospitals have faced an especially challenging year. They have risen to the occasion with aplomb. That’s why we want this year’s Awards to be the biggest yet – not only in recognition of excellence, but as applause to the teams around Ireland who helped keep the country going during the pandemic pressures.

The Awards will represent a celebration of all hospital healthcare teams who were working tirelessly on the frontline, for their incredible efforts during the Covid-19 pandemic.

Award Categories: Pharmasource Hospital Pharmacist of the Year Award Young Hospital Pharmacist of the Year Award GSK Excellence in Respiratory Initiative of the Year Award Grunenthal Advancing the Standard of Care in Pain Management Award Excellence in Haematology Award Accord Innovation in Aseptic Compounding Award GSK ViiV Infectious Diseases Project of the Year

The HPAs are the most influential and respected networking event, lauding excellence, innovation and service development; judged by key influencers including renowned respected experts.

Hospital Pharmacy Team of the Year Award

The foundation for these Awards lies in our collaboration with leading pharmaceutical companies; without their investment and support, the event would not be possible.

Novartis Neurology Neurological Innovation Award

Entry forms will be available shortly.

We look forward to welcoming you all to The O’Reilly Hall at University College Dublin on Saturday 10th September 2022 for what promises to be an unmissable night.

Galapagos Multidisciplinary Team Award

Medisource Hospital Pharmacy Technician of the Year

Sanofi Hospital Specialist Award

MSD Excellent in Oncology Award Excellence in Psychiatry Award

Date: Saturday 10th September, 2022 Venue: The O’Reilly Hall, University College Dublin - Further details to be confirmed in the next issue.

For further information contact Kelly Jo Eastwood via email: kelly-jo@ipn.ie – Tel: 0044787 654 8989

78 News

‘Cheers’ to Safe Medications Dr Barry O’ Connell, Dr Una Kennedy and Medication Safety Facilitator, Pharmacist Eileen Relihan, St James’s Hospital, Dublin

to recipients, allowing for the easy digestion of complex information.

A team at St James’s Hospital has received a ‘Cheers Award’ from the Institute for Safe Medication Practice (ISMP).

The ‘Medication Safety Minute’ is an innovative education tool that has been developed to promote the safe prescription of medication to patients. The project emerged from the review of real-world medication errors and discussions about how to optimally

communicate the learning points to prescribers in the age of information overload.

The initiative is based on the concept of ‘microlearning’ which involves the delivery of concise nuggets of information that are presented in a question and answer, two-slide format, which recipients can review and digest within one minute or less. Each week a new minute is distributed

The project is the only European initiative to be awarded a ‘Cheers Award’ at the 24th annual awards ceremony. The Cheers Awards take place each year and seek to highlight institutions and individuals that ensure that the implementation of medication safety strategies stretch far beyond a few individuals or a single department and are fully integrated into their organisation’s culture and clinical practice. The awards are hosted by the USA based Institute for Safe Medication Practices (ISMP).

The Institute for Safe Medication Practices (ISMP) is a non-profit organisation devoted entirely to preventing medication errors.

During its more than 25-year history, ISMP has helped make a difference in the lives of millions of patients and the healthcare professionals who care for them.

The Medication Safety Minute is a collaborative project undertaken

by Dr Barry O’ Connell, Dr Una Kennedy and Medication Safety Facilitator, Eileen Relihan, all of St James’s Hospital, Dublin. The project resources are currently used by 24 hospitals in Ireland and by a number of university undergraduate and postgraduate programmes. The material has also been made available as a free online access resource in the form of a digital flipbook as well as being published weekly on a dedicated Twitter page, @medsafetymin.

The awards ceremony will take place Tuesday, 7 December.

Pharmacy Role in Preventing Diabetes The role that pharmacists can play in preventing the projected rise in diabetes to 700 million people by 2045 is highlighted in a new resource released by the International Pharmaceutical Federation (FIP.) “Diabetes prevention, screening and management: A handbook for pharmacists” provides information on the wide range of pharmaceutical services that pharmacists can provide to reduce the global burden of this disease.

“It is imperative to ensure the

healthcare workforce is prepared to care for people with diabetes and those at risk. In 2019, more than half of the 463 million adults with diabetes were not aware they had it. While pharmacists are primarily trained to address health concerns through pharmacological means, they also have the necessary skills and knowledge to provide prevention and screening services,” said Paul Sinclair, chair, FIP Board of Pharmaceutical Practice.

In addition to prevention, screening and referral, the new

FIP handbook covers medicines management, non-pharmacological management and advice, and prevention and management of complications such as diabetic neuropathy and retinopathy. It also addresses barriers to providing diabetes services.

“Pharmacists are active members of the healthcare team, providing trusted advice into a community to which, more often than not, they also belong. From a diabetes care perspective, it is a key role. Advice, of course, should be based on the best available evidence. This

New Director of Healthcare Leadership The Royal College of Physicians of Ireland has announced the appointment of Professor Trevor Duffy to the role of Director of Healthcare Leadership.

This new role has been established as part of a new Strategic Framework for 2021-2024. The purpose of the role will be to lead RCPI activity in the area of healthcare delivery and professional practice, working with internal and external stakeholders to promote excellence in patient care.

As a member of the Senior Management Team, Prof Duffy will oversee existing activities in the area of healthcare policy and delivery, developing new initiatives in agreement with the Executive Board and Council.

Professor Duffy is Consultant Rheumatologist at the Connolly Hospital Blanchardstown and the Hermitage Medical Clinic and is Honorary Clinical Associate Professor at RCSI. Following specialist training in Ireland he was a Rheumatology Fellow at the Hospital Universitaire Cantonal de Geneve where he subsequently became a Chef de Clinique.

He has significant experience in healthcare strategy and leadership roles, including stints as Lead Clinical Director at Connolly Hospital; President of the IMO from 2014 to 2015 and IMO delegate to the UEMS (Union Européan des Medicins Specialists).

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

publication provides pharmacists with everything they need to know to help guide community members to make healthy choices and adopt healthy habits,” said Prof. Andrew Boulton, president, International Diabetes Federation.

This new FIP publication is part of the federation’s new Practice Transformation Programme on Non-Communicable Diseases. FIP has also produced a hub of online resources on non-communicable diseases: https://ncd.fip.org/

For high risk patient eligibility*

When statins plus ezetimibe are not enough, add Repatha® to lower LDL-C and reduce CV risk1 Repatha® (evolocumab) Brief Prescribing Information

Please refer to the Summary of Product Characteristics (SmPC) before prescribing Repatha. Pharmaceutical Form: Pre-filled pen (SureClick®) containing 140 mg of evolocumab in 1 mL solution for injection. Indication: Hypercholesterolaemia and mixed dyslipidaemia: Repatha is indicated in adults with primary hypercholesterolaemia (heterozygous familial and nonfamilial) or mixed dyslipidaemia, as an adjunct to diet: in combination with a statin or statin with other lipid lowering therapies in patients unable to reach LDLC goals with the maximum tolerated dose of a statin or; alone or in combination with other lipid-lowering therapies in patients who are statinintolerant, or for whom a statin is contraindicated. Homozygous familial hypercholesterolaemia: Repatha is indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolaemia in combination with other lipidlowering therapies. Established atherosclerotic cardiovascular disease: Repatha is indicated in adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors: in combination with the maximum tolerated dose of a statin with or without other lipid-lowering therapies or; alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated. For study results with respect to effects on LDL-C, cardiovascular events and populations studied see section 5.1 of the SmPC. Dosage and Administration: Repatha is for subcutaneous injection into the abdomen, thigh or upper arm region. Repatha is intended for patient self-administration after proper training. Prior to initiating Repatha, secondary causes of hyperlipidaemia or mixed dyslipidaemia (e.g., nephrotic

syndrome, hypothyroidism) should be excluded. Primary hypercholesterolaemia and mixed dyslipidaemia in adults: The recommended dose of Repatha is either 140 mg every two weeks or 420 mg once monthly; both doses are clinically equivalent. The safety and efficacy of Repatha in children aged less than 18 years has not been established. Homozygous familial hypercholesterolaemia in adults and adolescents aged 12 years and over: The initial recommended dose is 420 mg once monthly. After 12 weeks of treatment, dose frequency can be up titrated to 420 mg once every 2 weeks if a clinically meaningful response is not achieved. Patients on apheresis may initiate treatment with 420 mg every two weeks to correspond with their apheresis schedule. The safety and efficacy of Repatha in children aged less than 12 years has not been established. Established atherosclerotic cardiovascular disease in adults: The recommended dose of Repatha is either 140 mg every two weeks or 420 mg once monthly; both doses are clinically equivalent. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special Warnings and Precautions: Traceability: Clearly record the name and batch number of administered product to improve traceability of biological products. Hepatic impairment: In patients with moderate hepatic impairment, a reduction in total evolocumab exposure was observed that may lead to a reduced effect on LDLC reduction. Therefore, close monitoring may be warranted in these patients. Patients with severe hepatic impairment (Child-Pugh C) have not been studied. Repatha should be used with caution in patients with severe hepatic impairment. Dry natural rubber: The needle cover of the glass pre-filled pen (SureClick®) is made from dry natural rubber (a derivative of latex), which may cause severe allergic reactions. Interactions: No interaction studies have been performed. Fertility, pregnancy

and lactation: There are no or limited amount of data from the use of Repatha in pregnant women. It is unknown whether evolocumab is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded. No data on the effect of evolocumab on human fertility are available. Undesirable Effects: Adverse reactions reported in pivotal, controlled clinical studies and from spontaneous reporting: common (≥ 1/100 to < 1/10) influenza, nasopharyngitis, upper respiratory tract infection, hypersensitivity, rash, headache, nausea, back pain, arthralgia, myalgia, injection site reactions; rare (≥1/10,000 to <1/1,000) angioedema. Please consult the SmPC for a full description of undesirable effects. Pharmaceutical Precautions: Store in a refrigerator (2°C – 8°C). Do not freeze. Store the pre-filled pen (SureClick®) in the original carton in order to protect from light. If removed from the refrigerator, Repatha may be stored at room temperature (up to 25°C) in the original carton and must be used within 1 month. Legal Category: POM. Presentation, Basic Costs and Marketing Authorisation Number: Repatha pre-filled pen (SureClick®) 140 mg/1mL: Pack of 2 pre-filled pens. EU/1/15/1016/003. Price in Republic of Ireland is available on request. Marketing Authorisation Holder: Amgen Europe B.V. Minervum 7061, 4817 ZK Breda, The Netherlands. Further information is available from Amgen Ireland Limited, 21 Northwood Court, Santry, Dublin D09 TX31. Repatha is a registered trademark of Amgen Inc. Date of PI preparation: March 2021 (Ref: IE-REP-0321-00002).

* Managed Access Protocol – Repatha® https://www.hse.ie/eng/about/who/cspd/ncps/medicines-management/ pcsk9-inhibitors/hse-managed-access-protocol-repatha1.pdf 1. Repatha® (evolocumab) Amgen – Summary of Product Characteristics. https://www.medicines.ie/medicines/repatha-sureclick-33565/smpc

Amgen Ireland 21 Northwood Court Santry, Dublin 9, Ireland

© 2021 Amgen Inc. All rights reserved.

IE-REP-0421-00005. Date of preparation: May 2021

Adverse reactions/events should be reported to the Health Products Regulatory Authority (HPRA) using the available methods via www.hpra.ie. Adverse reactions/events should also be reported to Amgen Limited on +44 (0)1223 436441 or Freephone 1800 535 160.

80 HIV

Ending HIV Means Ending HIV-related Stigma Written by Stephen O'Hare, Executive Director, HIV Ireland

This year marks the 40th Anniversary of the emergence of HIV and AIDS as a global epidemic. World AIDS Day (1st Dec) provides an opportunity to reflect on the toll taken by HIV and to remember those lost to AIDS. It is also an opportunity to acknowledge key advances in prevention and treatment, and to evaluate current strategies to end new HIV transmissions once and for all.

UNAIDS, the dedicated agency leading the global effort to end AIDS as a public health threat, estimates that, since its emergence, almost 80 million people have acquired HIV with more than 36 million lives having been lost to AIDS-related illnesses in that time.

In its recent strategy statement for the period 2021 -2026, the agency highlights the impact of inequalities that drive AIDS and other pandemics, including COVID-19.

Prominent among the driving inequalities hampering efforts to end HIV is stigma. Eliminating stigma is, therefore, a key component of any viable strategy to end new HIV transmissions.

Unfortunately, the phenomenon of HIV-related stigma, its causes, and its impact, receives considerably less attention than some of the more tangible measures developed to treat and prevent HIV. Thanks to key advances in HIV medication over the years, the trajectory of the virus for those with access to effective antiretroviral treatment has dramatically changed. A person living with HIV, on effective treatment and who attains an undetectable viral load, cannot pass on HIV to a sexual partner.

This fact, confirmed in multiple major scientific studies, is written in shorthand as “U equals U”.

Put simply, when the virus is Undetectable, it is Untransmittable.

For people who are HIV negative, measures to prevent the acquisition of HIV now include highly successful medications which can be taken before or after sex. In Ireland, the rollout of the national PrEP (pre-exposure prophylaxis) programme means that anyone who meets the criteria can access the medication free of charge. PEP (post exposure prophylaxis) is similarly available free of charge as an emergency preventive measure in clinical settings. Condoms, which when used correctly provide an effective prevention option against HIV and other STIs, are also available free through the National Condom Distribution Service.

Despite these ground-breaking advances in both treatment and prevention, and the free availability of same in Ireland, experiences of HIV-related stigma persist. It persists as a barrier to inclusion for people living with HIV and as a significant obstacle to achieving an end to new HIV transmissions.

It persists among health care practitioners, policy makers, service providers, employers, family members, affected populations and wider society.

HIV-related stigma to zero by the end of the current decade. By 2020, participating Fast-Track cities were working towards ensuring 90 percent of people living with HIV are aware of their HIV status, 90 percent of those are on effective treatment and 90 percent on treatment have attained viral suppression. While many cities, including cities in Ireland, have been moderately successful in meeting or coming close to meeting these targets, the elimination of HIV-related stigma remains far more elusive.

Given the complexity of stigma and its effects on people socially, psychologically and, in some cases, legally, a multi-pronged approach is required to make meaningful progress towards ending this acutely debilitating aspect of the HIV epidemic.

Information and education to facilitate better understanding of the causes and effects of HIVrelated stigma, how to challenge attitudes, values, and beliefs, how to support people who feel stigmatized, the importance of using appropriate language and how to avoid discrimination in service provision is vital if we are to succeed in this endeavour.

As a community-based HIV and sexual health advocacy and support organisation, HIV Ireland works to reduce HIV-related stigma and improve conditions for people living with and vulnerable

Stigma is often driven by fear, misinformation, or judgment. It arises from a lack of awareness and/or empathy. It emerges because of prejudice, intolerance, and stereotyping. For people living with, or vulnerable to HIV, stigma can lead internally to feelings of shame and self-stigma, and externally to experiences of discrimination and exclusion.

Stigma is a key determinant in preventing progress on eliminating HIV around the world including deterring access to, and preventing uptake of, testing, treatment, and effective preventive measures.

As part of its commitment to ending new HIV transmissions by 2030, the Government signed the Paris Declaration in 2019, committing Ireland’s four largest cities to the FastTrack Cities global initiative. The initiative focuses on eliminating transmission of HIV and reducing

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

to acquiring HIV. This is achieved through dedicated prevention services, community, and peer support services and through the provision of evidence-based information, education and training supports for health and social care providers.

This year, in response to limitations placed on in-person education and training opportunities due to COVID-19, HIV Ireland has developed a suite of online e-learning courses for health and social care providers. The first two modules cover 1) HIV Prevention in Ireland and 2) HIV: Stigma and Discrimination. The resources are free and intended to benefit health, social and community-based care professionals working with people more vulnerable to acquiring HIV and with people living with or affected by HIV. This includes sexual health workers, health advisers, drug service providers, LGBT services, education sector, youth services, housing/homeless services, migrant services, Traveller community health projects, GPs, mental health practitioners, counsellors, social workers, nurses, and other practitioners.

More information on how to access the e-learning modules and the expected learning outcomes is available at www.hivireland.ie/elearning.

Stephen O’Hare is Executive Director of HIV Ireland.

For treatment of HIV-1

Make Doravirine a Part of Every Day DELSTRIGO® (100 mg doravirine/300 mg lamivudine/300 mg tenofovir disoproxil fumarate, equivalent to 245 mg of tenofovir disoproxil) is indicated for the treatment of adults infected with HIV-1 without past or present evidence of resistance to the NNRTI class, lamivudine, or tenofovir.1 PIFELTRO® (doravirine) is indicated, in combination with other antiretroviral medicinal products, for the treatment of adults infected with HIV-1 without past or present evidence of resistance to the NNRTI class.2 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions.

See section 4.8 of the SPC for how to report adverse reactions.

ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION Pifeltro: film-coated tablet containing 100 mg doravirine. Delstrigo: film-coated tablet containing 100 mg doravirine, 300 mg lamivudine and 300 mg tenofovir disoproxil fumarate, equivalent to 245 mg of tenofovir disoproxil. INDICATIONS Pifeltro: For use in combination with other antiretrovirals, for the treatment of HIV-1 without past or present evidence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). Delstrigo: For the treatment of HIV-1 without past or present evidence of resistance to NNRTIs, lamivudine or tenofovir. DOSAGE AND ADMINISTRATION Therapy should be initiated by a physician experienced in HIV infection management.

Pifeltro: One 100 mg tablet once daily. Delstrigo: One 100/300/245 mg tablet once daily. Pifeltro and Delstrigo: If co-administered with rifabutin or other moderate CYP3A inducers, increase doravirine dose to 100 mg twice daily (12 hours apart). Pifeltro: Elderly: No dose adjustment necessary. Renal impairment: No dose adjustment necessary. Hepatic impairment: mild to moderate: no dosage adjustment required; severe: use with caution. Delstrigo: Elderly: Special care advised. Renal impairment: estimated creatinine clearance (CrCl) ≥ 50 mL/min: no dose adjustment necessary; estimated CrCl <50 mL/min: not recommended. Hepatic impairment: mild to moderate: no adjustment required; severe hepatic: use with caution. CONTRAINDICATIONS Hypersensitivity to the active substance or excipients Co-administration with strong CYP3A inducers. PRECAUTIONS AND WARNINGS A residual risk of sexual transmission of HIV-1 cannot be excluded and precautions should be taken in accordance with national guidelines. Use with CYP3A inducers may reduce the exposure of doravirine. Autoimmune disorders (such as autoimmune hepatitis) and immune reactivation syndrome have been reported in patients treated with combination antiretroviral therapy which may require investigation and treatment. Contains lactose monohydrate. Delstrigo: Post-treatment exacerbation of HBV (including hepatic decompensation and liver failure) have been reported in patients co-infected with HIV-1 and HBV following discontinuation of lamivudine or tenofovir disproxil. Monitor patients co-infected with HIV-1 and HBV after discontinuation of Delstrigo and if appropriate initiate anti-HBV therapy. Renal impairment, including acute renal failure and Fanconi syndrome have been reported with tenofovir disoproxil. Assess estimated CrCl prior to initiation and during therapy. In patients at risk of renal dysfunction, serum phosphorus, urine glucose, and urine protein should also be assessed. Discontinue therapy if estimated CrCl declines below 50 mL/min. Avoid with concurrent or recent use of nephrotoxic medicinal products (e.g. high-dose or multiple NSAIDs). Evaluation of renal function is recommended for persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness. Assessment of bone mineral density should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms. Doravirine/lamivudine/tenofovir disoproxil must not be co-administered with other medicinal products containing lamivudine, tenofovir disoproxil, or tenofovir alafenamide or with adefovir dipivoxil. Doravirine/lamivudine/tenofovir disoproxil should not be administered with doravirine unless needed for dose adjustment (e.g. co-administered with rifabutin). Drug interactions: Refer to SmPC for full information on drug interactions. Pifeltro and Delstrigo: Doravirine is metabolized

primarily by CYP3A. Do not co-administer with strong CYP3A enzyme inducers. If co-administration with rifabutin or other moderate CYP3A inducers cannot be avoided, increase doravirine dose to 100 mg twice daily (taken 12 hours apart). Use with caution when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that have a narrow therapeutic window (e.g., midazolam, tacrolimus and sirolimus). Delstrigo: Do not administer with other antiretroviral medicinal products. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion may increase serum concentrations of lamivudine. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion via OAT1, OAT3 or MRP4 may increase serum concentrations of tenofovir. Avoid with concurrent or recent use of nephrotoxic medicinal products. Pregnancy and Lactation: Pifeltro and Delstrigo: Avoid use during pregnancy. An Antiretroviral Pregnancy Registry has been established. Breastfeeding is not recommended.

SIDE EFFECTS Refer to SmPC for complete information on side-effects. Pifeltro and Delstrigo: Common: abnormal dreams, insomnia, headache, dizziness, somnolence, nausea, diarrhoea, abdominal pain, flatulence, vomiting, rash, fatigue alanine aminotransferase increased. Uncommon: hypophosphataemia, nightmare, depression, suicidal ideation, paraesthesia, asthenia. Rare: hypomagnesaemia, blood creatine phosphokinase increased. Delstrigo: Common: cough, nasal symptoms, alopecia, muscle disorders, fever. Uncommon: neutropenia, anaemia, thrombocytopenia, pancreatitis, rhabdomyolysis, proximal renal tubulopathy (including Fanconi syndrome), aspartate aminotransferase increased. Rare: lactic acidosis, hepatitis, angioedema, myopathy, acute renal failure, renal failure, acute tubular necrosis, nephritis (including acute interstitial) and nephrogenic diabetes insipidus. Very Rare: pure red cell aplasia, peripheral neuropathy (or paraesthesia). Lactic acidosis Cases of lactic acidosis have been reported with tenofovir disoproxil alone or in combination with other antiretrovirals. Patients with predisposing factors such as patients with decompensated liver disease, or patients receiving concomitant medications known to induce lactic acidosis are at increased risk of experiencing severe lactic acidosis during tenofovir disoproxil treatment, including fatal outcomes. PACKAGE QUANTITIES Bottle of 30 tablets. Legal Category: POM. Marketing Authorisation numbers: Pifeltro: EU/1/18/1332/001. Delstrigo: EU/1/18/1333/001. Marketing Authorisation Holder: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: June 2020. © Merck Sharp & Dohme B.V., 2020. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 or from www.medicines.ie. Date of Preparation: April 2021. IB/0019.

References: 1. DELSTRIGO Summary of Product Characteristics, June 2020. 2. PIFELTRO Summary of Product Characteristics, November 2019.

Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie.

Adverse events should also be reported to MSD (Tel: 01-2998700)

Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 Ireland

IE-DOV-00022

PIFELTRO® ▼ (Doravirine) DELSTRIGO® ▼ (Doravirine/Lamivudine/Tenofovir disproxil fumarate)

82 HIV Interview

Working Together to improve HIV Care in Europe Dr Sanjay Bhagani, President of the European AIDS Clinical Society (EACS)

living longer, and experiencing more co-morbidities. It really is time to think beyond just undetectable viral load.

“Key populations are still struggling in many parts of the region, with inequalities of care affecting people who inject drugs, people in prison settings, men who have sex with men, women, children, and transgender people.

In terms of the region as a whole, I would use that well-polished phrase, ‘leaving no-one behind’.”

How has COVID-19 impacted the HIV sector in Europe?

Dr Sanjay Bhagani is President of the European AIDS Clinical Society (EACS) and an experienced consultant in infectious diseases and HIV. Below he shares his thoughts in advance of the EACS Conference 2021 and his vision for HIV care in Europe.

The theme of this year’s EACS conference is ‘crossing borders’. What does that mean to you and what do you hope it will inspire in others?

“One of the really important things that the EACS conference does is bring people together from many different countries and regions across Europe and also outside of Europe.

“While we may usually practise medicine in our specialties and within our national borders, big meetings like this highlight the importance of crossing those boundaries and learning from each other’s experience.

“An important reason for choosing the theme was to say to people: when we think about HIV care, we should think across the whole European region.

“But it is not only about national borders. We also need to think about care across sectors as well.

We realise that HIV care is not just about clinicians, scientists, community, academia or industry; it’s bringing all partners together, across those boundaries, to look after people with HIV.

“COVID-19 has really highlighted for us that care for HIV also crosses borders in terms of disease disciplines. In other words, caring for people with HIV encompasses everything, including sexual health, mental health, and co-morbidity care.

“The whole concept of the conference is that we are crossing borders on many different fronts.”

In that context, how would you describe the European HIV field at the moment and how can we improve?

“We have been aware for many years that there is inequity in HIV care across Europe, both in terms of testing and prevention services, and in terms of care for individuals. There is huge variation not only between countries, but across regions – between the north and the south, and particularly between central and eastern Europe and western Europe.

“Some differences are positive and help us to learn from each other and improve care, but some differences highlight areas we really need to tackle, including access to testing, prevention and HIV care and treatment.

“The work we do at EACS focuses on addressing these differences. Our three key themes as an organisation are: education and training; production of HIV care guidelines including co-morbidities, co-infections and opportunistic infections; and

work on standards of care.

The work we do within those streams contributes to fixing these inequities in care across our region.”

As EACS president and as a clinician, what’s your vision for the future of HIV care?

“We all have the big vision of what we would like to achieve in the next 5, 10 or 20 years, and then there are the immediate or unexpected things we need to attend to. I started my presidency at EACS during the COVID-19 pandemic and it’s been a difficult time for all of us.

“The first part of my presidency has been focused on steadying the boat. I’ve been focused on making sure that we can continue to deliver the programmes we set out to deliver.”

“The EACS conference in London (held in October past) was the first time since COVID-19 emerged that we have the opportunity to host anything close to a face-to-face event. It is also the first-ever hybrid HIV conference and a lot of work has gone into it.

“Thinking longer-term, I would like to see us move from diseasefocused care to patient-centred care. That would be my vision.

We have to stop thinking about specific diseases and start thinking about the patients in front of us.

This is particularly important in the context of HIV, where in certain parts of the region we have a population that is growing older,

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

“Because of our infectious disease backgrounds, HIV caregivers across Europe have been at the frontline of COVID-19 care over the last 18 months. It has taken a huge toll in terms of people’s resilience and the impact on their mental health.

“Having said that, we’ve seen during COVID-19 that adversity is often a driver of innovation. We’ve seen models of care emerge that will probably change the way we deliver care for years to come.

For example, in some countries, telemedicine has become a key component of the way we deliver care and I think it is here to stay.

“Another important aspect is delivering care near to the patient. Innovations like home self-testing kits for sexually transmitted infections and HIV, home management of blood pressure and diabetes – all of those things are going to become important, and the reliance on specialist centres is going to be less important.

“Perhaps most importantly, the pandemic highlighted our need for partnerships, and partnerships not just with academia in terms of research and science, but partnerships with community organisations. In the midst of the COVID pandemic, it was often the community organisations that were directly involved in providing care and support. It really highlighted the need for us all to work together.”

This feature appeared in the October edition of the Eurobulletin.

OTEZLA® can offer solutions to the challenges in this new environment

OTEZLA® has an established efficacy and safety profile for up to 5 years†1,2

No warnings regarding risk of serious infection2

No contraindications for concurrent use with live vaccination2

A short half-life of 9 hours

Minimise frequency of clinical appointments

Immunomodulatory mode of action2

No laboratory pre-screening, and no drug specific blood monitoring required2

Means that OTEZLA® is rapidly cleared from the body if administration needs to be stopped2

Confidence not compromise in immune response, down-regulation of proinflammatory cytokines and up-regulation of anti-inflammatory cytokines

Make OTEZLA® the positive choice for your psoriasis and psoriatic arthritis patients OTEZLA® (apremilast) 10mg, 20mg and 30mg film coated-tablets Brief Prescribing Information.

Refer to the Summary of Product Characteristics (SPC) before prescribing. Further information is available upon request. Presentation: 10mg, 20mg and 30mg film coated-tablets. Indications: Psoriatic arthritis: OTEZLA, alone or in combination with Disease Modifying Antirheumatic Drugs (DMARDs), is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy. Psoriasis: OTEZLA is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including ciclosporine, methotrexate or psoralen and ultraviolet-A light (PUVA). Dosage and administration: Treatment with OTEZLA should be initiated by specialists experienced in the diagnosis and treatment of psoriasis or psoriatic arthritis. The recommended dose of OTEZLA is 30mg twice daily taken orally in the AM and PM, approximately 12 hours apart, with no food restrictions. The film-coated tablets should be swallowed whole. An initial dose titration is required per the following schedule: Day 1: 10mg in the AM; Day 2: 10mg in the AM and 10 mg in the PM; Day 3: 10mg in the AM and 20mg in the PM; Day 4: 20mg in the AM and 20mg in the PM; Day 5: 20mg in the AM and 30mg in the PM; Day 6 and thereafter: 30mg twice daily in the AM and PM. No re-titration is required after initial titration. If patients miss a dose, the next dose should be taken as soon as possible. If it is close to the time for their next dose, the missed dose should not be taken and the next dose should be taken at the regular time. Patients with severe renal impairment: The dose of OTEZLA should be reduced to 30mg once daily in patients with severe renal impairment (creatinine clearance of less than 30mL per minute estimated by the Cockcroft-Gault equation). For initial dose titration in this group, it is recommended that OTEZLA is titrated using only the AM doses and the PM doses be skipped. Paediatric population: The safety and efficacy of OTEZLA in children aged 0 to 17 years have not been established. No data is available. Contraindications: Hypersensitivity to the active substance(s) or to any of the excipients. OTEZLA is contraindicated in pregnancy. Pregnancy should be excluded before treatment can be initiated. Special warnings and precautions: Diarrhoea, nausea and vomiting: Severe diarrhoea, nausea, and vomiting associated with the use of OTEZLA have been reported. Most events occurred within the first few weeks of treatment.

In some cases, patients were hospitalized. Patients 65 years of age or older may be at a higher risk of complications. Discontinuation of treatment may be necessary. Psychiatric disorders: OTEZLA is associated with an increased risk of psychiatric disorders such as insomnia and depression. Instances of suicidal ideation and behaviour, including suicide, have been observed in patients with or without history of depression. The risks and benefits of starting or continuing treatment with OTEZLA should be carefully assessed if patients report previous or existing psychiatric symptoms or if concomitant treatment with other medicinal products likely to cause psychiatric events is intended. Patients and caregivers should be instructed to notify the prescriber of any changes in behaviour or mood and of any suicidal ideation. If patients suffered from new or worsening psychiatric symptoms, or suicidal ideation or suicidal attempt is identified, it is recommended to discontinue treatment with OTEZLA. Severe renal impairment: See dosage and administration section. Underweight patients: OTEZLA may cause weight loss. Patients who are underweight at the start of treatment should have their body weight monitored regularly. In the event of unexplained and clinically significant weight loss, these patients should be evaluated by a medical practitioner and discontinuation of treatment should be considered.

Lactose content: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Interactions: Co-administration of strong cytochrome P450 3A4 (CYP3A4) enzyme inducer, rifampicin, resulted in a reduction of systemic exposure of OTEZLA, which may result in a loss of efficacy of OTEZLA. Therefore, the use of strong CYP3A4 enzyme inducers (e.g. rifampicin, phenobarbital, carbamazepine,

phenytoin and St. John’s Wort) with OTEZLA is not recommended. In clinical studies, OTEZLA has been administered concomitantly with topical therapy (including corticosteroids, coal tar shampoo and salicylic acid scalp preparations) and UVB phototherapy. OTEZLA can be co-administered with a potent CYP3A4 inhibitor such as ketoconazole, as well as with methotrexate in psoriatic arthritis patients and with oral contraceptives. Pregnancy, lactation and fertility: Women of childbearing potential should use an effective method of contraception to prevent pregnancy during treatment. OTEZLA should not be used during breast-feeding. No fertility data is available in humans. Undesirable effects: Psychiatric disorders: In clinical studies and post-marketing experience, uncommon cases of suicidal ideation and behaviour, were reported, while completed suicide was reported post-marketing. The most commonly reported adverse reactions with OTEZLA in these indications are gastrointestinal (GI) disorders including diarrhoea (15.7%) and nausea (13.9%). These GI adverse reactions generally occurred within the first 2 weeks of treatment and usually resolved within 4 weeks. Adverse reactions reported in the psoriatic arthritis and/or psoriasis clinical trial programme and post marketing experience include: very common (≥ 1/10) diarrhoea*, nausea*; common (≥1/100 to <1/10) bronchitis, upper respiratory tract infection, nasopharyngitis*, decreased appetite*, insomnia, depression, migraine*, tension headache*, headache*, cough, vomiting*, dyspepsia, frequent bowel movements, upper abdominal pain*, gastroesophageal reflux disease, back pain*, fatigue; uncommon (≥1/1,000 to <1/100) hypersensitivity, suicidal ideation and behaviour, gastrointestinal haemorrhage, rash, urticaria, weight loss; not known (cannot be estimated from the available data) angioedema. *At least one of these adverse reactions was reported as serious. Please consult the SPC for a full description of undesirable events. Pharmaceutical Precautions: Do not store above 30°C. Legal category: POM. Presentation and Marketing Authorisation Numbers: Initiation pack containing 27 film coated tablets (4 x 10mg, 4 x 20mg, 19 x 30mg) - EU/1/14/981/001; 30mg film coated tablets in a pack size of 56 tablets - EU/1/14/981/002.

Marketing Authorisation Holder: Amgen Europe B.V. Minervum 7061, 4817 ZK Breda, The Netherlands.

Further information is available from Amgen Ireland Limited, 21 Northwood Court, Santry, Dublin D09 TX31. OTEZLA is a trademark owned or licensed by Amgen Inc., its subsidiaries, or affiliates. Date of preparation: April 2020 (Ref: IE-OTZ-2000019).

Adverse reactions/events should be reported to the Health Products Regulatory Authority (HPRA) using the available methods via www.hpra.ie. Adverse events should also be reported to Amgen Limited on +44 (0)1223 436441. † Otezla met the primary endpoint of the pivotal trials in psoriasis: PASI-75 response vs placebo at 16 weeks. ESTEEM 1: 33.1% (N=562) vs 5.3% (N=282); ESTEEM 2: 28.8% (N=274) vs 5.8% (N=137), P<0.0001. OTEZLA met the primary endpoint of the pivotal trials in Psoriatic Arthritis: ACR 20 response vs placebo at 16 weeks. PALACE 1: 38% (N=168) vs 19% (N=168), P≤0.001. PALACE 2: 32% (N=162) vs 19% (N=159) P≤0.01; PALACE 3: 41% (N=167) vs 18% (N=169) P≤0.001.2 References: 1. Kavanaugh et al. Arthritis Research & Therapy 2019: 21;118. 2. OTEZLA (apremilast).

Summary of Product Characteristics.

© 2020 Amgen Inc. All rights reserved.

Amgen Ireland Ltd., 21 Northwood Court, Santry, Dublin 9 IE-OTZ-0820-00002 | Date of preparation: September 2020

84 Hepatitis C

Europe far from achieving hepatitis C elimination targets Dr Erika Duffell, European Centre for Disease Control (ECDC) speaking at the 18th European AIDS Conference (EACS 2021)

European Union states are far from reaching the global targets towards hepatitis C elimination, especially on harm reduction, testing and treatment, Dr Erika Duffell of the European Centre for Disease Control (ECDC) told the 18th European AIDS Conference (EACS 2021) recently.

In 2016, the World Health Assembly agreed global targets for elimination of viral hepatitis as a public health problem by 2030. The targets aim to eliminate viral hepatitis by reducing new viral hepatitis infections by 90% and reducing deaths due to viral hepatitis by 65% by 2030.

Dr Duffell reviewed progress on elimination of hepatitis C, the predominant hepatitis virus in the European region.

ECDC estimates that 3.9 million people were living with hepatitis C in the European Union, United Kingdom, Iceland, Liechtenstein and Norway in 2015, around 6% of the global burden of hepatitis C (71 million).

Hepatitis C prevalence in the region is highly concentrated among several key populations, notably people who inject drugs.

Estimates of prevalence among people who inject drugs range from 15 to 64% across various countries of the region. High hepatitis C prevalence has also been reported in people in prisons in some countries.

Prevalence is also high in men who have sex with men, especially those living with HIV (1-5%), and in migrants (1-17%).

Measuring progress towards elimination in the region is challenging due to lack of data collection or national targets for elimination in some countries, Dr Duffell observed. In 2020, the majority of countries in the region still lacked up-to-date estimates of how many people are living with hepatitis C. On blood safety, the region is making progress towards achieving targets for not remunerating blood donors (21 countries have achieved this target) and nucleic acid testing of blood donations (14 countries have achieved this target). But eight countries in the region were unable to report whether their blood donation systems had eliminated paid blood donation in 2016, illustrating the information gap in under-funded health systems.

Harm reduction coverage remains weak. By 2019, only three countries had achieved the target of distributing 200 syringes per drug user per year, while eleven countries had failed to achieve this level of coverage. Only nine countries reported that they had hit the target of providing opioid substitution therapy to 40% of high-risk opioid users. Only two countries – Luxembourg and Norway – had reached both these targets by 2019. Spain, Belgium and the Czech Republic were close to achieving both targets.

Data on the cascade of care remains limited. Less than half of countries in the region are able

to report hepatitis C diagnoses for 2020. Although slightly more countries are able to report how many people were treated for hepatitis C in 2020, fewer than ten can report how many treated people achieved a sustained virologic response after treatment.

Only four countries in the region – France, Ireland, Italy and Sweden – were estimated to have diagnosed more than half of people living with hepatitis C by 2020. The prevalence of undiagnosed cases is especially high in Romania and Greece. Hepatitis C prevalence in Romania may be as high as 3%.

“COVID has shown what can be done on testing at a large scale and we need to channel some of that innovation into testing for hepatitis C,” said Dr Duffell.

Although testing in harm reduction services and prisons is now routine in most European countries, testing is still not offered in prisons in several countries including Romania, Latvia and Greece.

Another site that could be critical for diagnosing new cases is also being under-utilised; in 2019, only eight countries reported that more than half of people entering drug treatment facilities were tested for hepatitis C in the previous year.

Data are also lacking on late diagnosis. Only five countries were able to supply data in 2020 on hepatitis C diagnosed at the stage of decompensated cirrhosis or hepatocellular carcinoma. These estimates varied from 5 to 27% of all diagnosed cases.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Data on changes in hepatitis C incidence and prevalence are also lacking for most countries.

Studies of incidence have been largely confined to people who inject drugs and no country in the region has evidence of a significant reduction in hepatitis C transmission among people who inject drugs between 2015 and 2019. Greece and Italy are the only countries to report marked reductions in hepatitis C antibody prevalence among people who inject drugs. In most other countries, prevalence has remained stable.

The European region is unlikely to achieve the elimination target of a 65% reduction in liver-related deaths by 2030 at the current rate of progress, according to ECDC projections. In 2015, ECDC estimates that 64,000 people with hepatitis C died of liver-related causes. To reach the 2020 target, deaths need to decline to 22,400 per year by 2030. But deaths due to liver cancer are still increasing.

Countries in the region need to make substantial investments in epidemiology and monitoring to understand their national epidemics, as well as scaling up harm reduction, testing and treatment, she concluded.

References Duffell E. How far are we from eliminating hepatitis C in Europe? 18th European AIDS Conference, London, parallel session B2, 2021.

POWER POWER REIMAGINED REIMAGINED AN INNOVATIVE TREATMENT FOR YOUR PATIENTS LIVING WITH HIV AN INNOVATIVE TREATMENT FOR YOUR PATIENTS LIVING WITH HIV POWERFUL, DURABLE EFFICACY1,2

POWERFUL, DURABLE EFFICACY1,2 HIGH BARRIER TO RESISTANCE1,2

HIGH BARRIER TO RESISTANCE1,2 TDF, TAF AND ABC FREE1-3

TDF, TAF AND ABC FREE1-3

GEMINI-1 and GEMINI-2 96-week data in treatment-naïve patients: DOVATO 86.0% (n=716) vs DTG + TDF/FTC 89.5% (n=717) (Proportion of patients with HIV-1 RNA <50 copies/mL) GEMINI-1 and GEMINI-2 96-week data in treatment-naïve patients: DOVATO 86.0% (n=716) vs DTG + TDF/FTC 89.5% (n=717) (Proportion of patients with HIV-1 RNA <50 copies/mL)

WHY USE 3 IF 2 IS ALL HE NEEDS?

DTG 50 mg + 3TC 300 mg used in the GEMINI studies.

WHY USE 3 IF 2 IS ALL HE NEEDS?

DOVATO is indicated for the treatment of HIV-1 in adults and adolescents above 12 years weighing at least 40 kg, with no known or DTG 50 mg + 3TC 300 mg used in the GEMINI studies. suspected resistance to the integrase inhibitor class, or lamivudine.

DOVATO is indicated for the treatment of HIV-1 in adults and adolescents above 12 years weighing at least 40 kg, with no known or suspected resistance to the integrase inhibitor class, or lamivudine.

Abridged Prescribing Information Dovato (dolutegravir 50mg/lamivudine 300mg) tablets See Summary of Product Characteristics (SmPC) before prescribing.

Presentation: Film-coated tablet containing dolutegravir sodium equivalent to 50 mg indicate no effects. Women of childbearing potential (WOCBP) should be counselled about Abridged Prescribing Information dolutegravir and 300 mg lamivudine debossed with “SV-137” on one face. Indication: HIV-1 the potential risk of neural tube defects including consideration of effective contraceptive Dovato (dolutegravir 50mg/lamivudine 300mg) tablets in adults & adolescents above 12 years of age weighing >40kg, with no known or suspected measures. If a woman plans pregnancy, the benefits and the risks of continuing treatment See Summary of Product Characteristics before prescribing. resistance to the integrase inhibitor class,(SmPC) or lamivudine.

Dosing: One tablet once daily with should be discussed with the patient. The safety and efficacy of a duel regime has not been pregnancy.

If a pregnancy is confirmed in the first trimester on Dovato,about the or without food.

Use an additional 50mg tablet of dolutegravir approximately 12 hours indicateinno effects. Women of childbearing potential (WOCBP) shouldwhile be counselled Presentation: Film-coated tablet containing dolutegravir sodium equivalent to 50after mg studied and risks switching to another regimen the dose of Dovato when co-administered with efavirenz, tipranavir/ritonavir, the potential risk of of continuing neural tubeDovato defectsversus including consideration of antiretroviral effective contraceptive dolutegravir and 300 mg lamivudine debossed with “SV-137”nevirapine, on one face.

Indication: HIV-1 benefits should be discussed with the patient taking the gestational age and the critical time period boosted oxcarbazepine, phenytoin, phenobarbital, inetravirine adults & (without adolescents abovePI), 12carbamazepine, years of age weighing >40kg, with no known or suspected measures. If a woman plans pregnancy, the benefits and the risks of continuing treatment St John’s Wort or rifampicin. Elderly: Limited data in 65+ yrs. Renal impairment: Not of neural tube defect development into account (see SmPC section 4.6). There have been resistance to the integrase inhibitor class, or lamivudine. Dosing: One tablet once daily with should be discussed with the patient. The safety and efficacy of a duel regime has not been recommended in patients with creatinine clearance < 30 mL/min. For patients with a reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or or without food. Use an additional 50mg tablet of dolutegravir approximately 12 hours after studied in pregnancy. If a pregnancy is confirmed in the first trimester while on Dovato, the sustained creatinine clearance between 30 and 49 mL/min see SmPC section 4.4. Hepatic post-natally to nucleoside analogues. Do not breast-feed. Side effects: See SmPC for the dose of Dovato when co-administered with efavirenz, nevirapine, tipranavir/ritonavir, benefits and risks of continuing Dovato versus switching to another antiretroviral regimen impairment: Caution in severe hepatic impairment (Child-Pugh grade C). Contraindications: full details. Headache, GI disturbance, insomnia, abnormal dreams, depression, anxiety, should be discussed with the patient taking the gestational age and the critical time period etravirine (without boosted PI), carbamazepine, oxcarbazepine, phenytoin, phenobarbital, dizziness, somnolence, rash, pruritus, alopecia, fatigue, arthralgia, myalgia, hypersensitivity, Hypersensitivity to any ingredient. Co-administration with substrates of OCT-2 with of neural tube defect development into account (see SmPC section 4.6). There have been St John’s Wort or rifampicin. Elderly: Limited data in 65+ yrs. Renal impairment: Not suicidal ideation or suicide attempt, hepatitis, blood dyscrasias, acute hepatic failure, narrow therapeutic windows, such as fampridine. Special warnings/precautions: Risk of reports of mitochondrial dysfunction in lactic HIV-negative infants exposed in utero and/or recommended in patients with creatinine clearance < 30 mL/min. For patients with a pancreatitis, angioedema, rhabdomyolysis, acidosis, peripheral neuropathy.

Elevations hypersensitivity reactions. Discontinue dolutegravir and other suspect agents immediately. post-natally to nucleoside analogues. Do not breast-feed. Side effects: See SmPC for sustained creatinine clearance between 30 andsyndrome.

49 mL/minMonitor see SmPC section 4.4. Hepatic Risks of osteonecrosis, immune reactivation LFTs in Hepatitis B/C of bilirubin, ALT, AST and CPK. MA Nr: EU/1/19/1370/001. MA holder: ViiV Healthcare BV, full details. Headache, GI disturbance, insomnia, abnormal dreams, depression, anxiety, impairment: in severe hepatic impairment (Child-Pugh grade C). Contraindications: co-infectionCaution and ensure effective Hepatitis B therapy.

Caution with metformin: monitor renal Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands. Legal Category: POM A. dizziness, somnolence, rash,August pruritus, alopecia, fatigue, arthralgia, myalgia, hypersensitivity, Hypersensitivity to anymetformin ingredient.

Co-administration substratesrequires of OCT-2 with Date of preparation of API: 2021.

Code: PI-6305.

Further information available from function and consider dose adjustment. Use with with etravirine boosted suicidal ideation 12 orRiverwalk, suicide attempt, blood dyscrasias, hepatic failure, narrow therapeutic windows, such as fampridine.

Special warnings/precautions: Risk of Citywest,hepatitis, Business Campus, Dublin 24.acute Tel: 01-4955000.

PI or increased dose of dolutegravir. Use with Mg/Al-containing antacids requires dosage GlaxoSmithKline, pancreatitis, angioedema, rhabdomyolysis, lactic acidosis, peripheral neuropathy.

Elevations hypersensitivity reactions.

Discontinue dolutegravir and other suspect agents immediately. separation. Use with calcium, multivitamins or iron also requires dosage separation if not Risks immune syndrome.

Monitor LFTs Hepatitis B/C of bilirubin, ALT, AST and CPK. MA Nr: EU/1/19/1370/001. MA holder: ViiV Healthcare BV, takenof at osteonecrosis, the same time with food.reactivation Use with cladribine or emtricitabine notinrecommended.

Adverse events should be reported directly to the Health Products Regulatory co-infection and avoid ensurechronic effective Hepatitis B therapy.

Caution metformin: monitor renal Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands. Legal Category: POM A. When possible, co-administration of sorbitol orwith other osmotic acting alcohols Authority (HPRA) on their website: www.hpra.ie. Adverse events should also be reported 2021. Code: PI-6305. Further information available from function andsection consider metformin dose adjustment.

Use with etravirine boosted Date of preparation of API:toAugust (see SmPC 4.5).

If unavoidable, consider more frequent viral requires load monitoring.

GlaxoSmithKline on 1800 244 255.

PIFertility, or increased dose of dolutegravir.

Use withfertility Mg/Al-containing requires dosage GlaxoSmithKline, 12 Riverwalk, Citywest, Business Campus, Dublin 24. Tel: 01-4955000. pregnancy and lactation: Human - no data; antacids animal fertility - studies separation. Use with calcium, multivitamins or iron also requires dosage separation if not taken at the same time with Use with cladribine or emtricitabine not recommended.

Adverse should be reported directly to the Health Products Regulatory References: 1. Cahn P et al. Jfood.

Acquir Immunde Defic Syndr.

2020;83(3):310-318.

2. van WYK J et al. Clin Infect Dis.events 2020;ciz1243:1-10 3. DOVATO Summary of Product When possible, avoid chronic co-administration of sorbitol or other osmotic acting alcohols Authority (HPRA) on their website: www.hpra.ie. Adverse events should also be reported Characteristics.

Last Accessed: October 2021. Available at: https://www.medicines.ie/medicines/dovato-50-mg-300-mg-film-coated-tablets-34871/spc. (see SmPC section 4.5). If unavoidable, consider more frequent viral load monitoring. to GlaxoSmithKline on 1800 244 255.

Fertility, pregnancy and lactation: Human fertility - no data; animal fertility - studies

References: 1. Cahn P et al.isJ Acquir Deficto Syndr.

2020;83(3):310-318.

WYK J et al. Clin Infect Dis. 2020;ciz1243:1-10 3. DOVATO Summary of Product DOVATO ownedImmunde by or licensed the ViiV Healthcare group2.ofvan companies.

Characteristics. Last Accessed: October 2021.

Available at: https://www.medicines.ie/medicines/dovato-50-mg-300-mg-film-coated-tablets-34871/spc.

Date of preparation: October 2021. PM-IE-DLL-ADVT-200002 ©2021 ViiV Healthcare group of companies or its licensor.

DOVATO is owned by or licensed to the ViiV Healthcare group of companies. ©2021 ViiV Healthcare group of companies or its licensor.

Date of preparation: October 2021. PM-IE-DLL-ADVT-200002

BIKTARVY® combines the INSTI bictegravir with FTC/TAF1 Helping people living with HIV achieve durable* treatment success regardless of baseline CD4 count or viral load:†1-4 HIGH EFFICACY‡ with 0 resistance§ through 144 weeks in treatment-naïve PLHIV2

WELL TOLERATED‖ with significantly fewer all grade treatment-related AEs vs ABC/3TC/ DTG (secondary endpoint) through 144 weeks, with similar low rates of treatment discontinuation and serious AEs in both arms#¶2

SMALL STR** with flexible daily dosing1

For healthcare professionals only. Prescribing information can be found overleaf. Material created by Gilead Sciences Ltd. Fictional patient | May 2021 UK-BVY-0062

REFERENCES: 1. BIKTARVY (BIC/FTC/TAF) Summary of Product Characteristics.

Available at: www.medicines.org.uk/emc (last accessed May 2021).

2. Orkin C, et al. European AIDS Conference (EACS) 2019, 6–9 November; Basel, Switzerland. PE3/14.

3. Wohl DA, et al. Lancet HIV. 2019; 6: e355–e363.

4. Stellbrink HJ, et al. Lancet HIV. 2019; 6: e364–e372.

5. US DHHS ARV guidelines Dec 2019 (https://bit.ly/2sNICai - Accessed April 2021).

6. Cihlar T and Fordyce M. Curr Opin Virol. 2016; 18: 50–56.

7. Trottier B, et al. J Int AIDS Soc. 2014; 17(4 Sup 3): 19765.

8. Orkin C, et al. HIV Med. 2018; 19: 18–328.

9. University of California, San Francisco (UCSF). Adherence to HIV Antiretroviral Therapy. Available from: http://hivinsite.ucsf.edu/ InSite?page=kb-03-02-09. Accessed April 2021. ®

3TC, lamivudine; ABC, abacavir; AE, adverse event; BIC, bictegravir; CI, confidence interval; DTG, dolutegravir; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; IQR, interquartile range; NRTI, nucleoside reverse transcriptase inhibitor; PLHIV, people living with HIV; STR, single-tablet regimen; TAF, tenofovir alafenamide. * Durability in HIV is defined as maintained efficacy, which is dependent on patient adherence. Adherence is impacted by tolerability and simplicity of treatment.5-9 † Median CD4 cell count (IQR) and HIV-1 RNA (IQR) at baseline for patients receiving BIKTARVY® in pooled data from Study 1489 and Study 1490 (n=634) were 442 (293–590) cells/µL (13% had CD4 count

<200 cells/µL) and 4.42 (4.00–4.88) copies/mL (19% had HIV-1 RNA >100,000 copies/mL), repectively.2 At Week 96, subgroup analyses for Study 1489 and 1490 showed that baseline CD4 count and baseline HIV-1 RNA did not significantly influence treatment outcomes.3,4 ‡ At Week 144, in Study 1489 (BIKTARVY® [n=314] vs ABC/3TC/DTG [n=315]) efficacy was 82% vs 84% (95% CI: –2.6 [–8.5–3.4]) and in Study 1490 (BIKTARVY® [n=320] vs DTG + FTC/TAF [n=325]) efficacy was 82% vs 84% (95% CI: –1.9 [–7.8–3.9]), with BIKTARVY® demonstrating non-inferior efficacy vs comparator in both trials.2 § At Week 144, in pooled data from Study 1489 and Study 1490 in treatment-naïve patients, there were 0 cases of treatment-emergent resistance in the BIKTARVY® (n=0/634), ABC/3TC/DTG (n=0/315) and DTG + FTC/TAF (n=0/325) groups.2 ‖ At Week 144, in pooled data from Study 1489 and Study 1490 in treatment-naïve patients receiving BIKTARVY®, the most frequently reported adverse reactions (≥5%) were nausea (4), headache (5) and diarrhoea (5).2 # At Week 144, in pooled data from Study 1489 and Study 1490 in treatment-naïve patients receiving BIKTARVY®, any drug-related AE was reported in 26% for BIKTARVY®, 42% for ABC/3TC/DTG and 29% for DTG + FTC/TAF. BIKTARVY® had significantly lower rates of study drug-related AEs, nausea and study-drug related nausea than DTG/ ABC/3TC (p<0.001).2 ¶ At Week 144, in pooled data from Study 1489 and Study 1490 in treatment-naïve patients, AEs leading to discontinuation were reported in 1% (n=6/634) for BIKTARVY®, 2% (n=5/315) for ABC/3TC/DTG and 2% (n=6/325) for DTG + FTC/TAF groups.2 ** Each BIKTARVY® tablet is approximately 15 mm x 8 mm.1

PRESCRIBING INFORMATION Consult the Summary of Product Characteristics (SmPC) before prescribing. bictegravir 50mg/emtricitabine 200mg/ tenofovir BIKTARVY® alafenamide 25mg film-coated tablets.

INDICATION: Treatment of adults with HIV-1 infection without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir DOSAGE: Adults: One tablet, once daily, taken orally and whole with/ without food. Elderly: No dose adjustment is required in patients ≥ 65 years. Renal impairment: Patients with estimated creatinine clearance (CrCl) ≥ 30 mL/min: No dose adjustment required. Patients with CrCl ≥ 15 mL/min and < 30 mL/min or Patients with end stage renal disease (ESRD, CrCl < 15 mL/min) who are not receiving chronic haemodialysis: Should be avoided. Patients with ESRD on chronic haemodialysis: No dose adjustment, but only use if potential benefit outweighs the potential risks. Hepatic impairment: Mild/moderate hepatic impairment: no dose adjustment required. Severe hepatic impairment: not recommended.

Paediatric population (<18 years): Safety and efficacy has not been established. Refer to SmPC for full information CONTRAINDICATIONS: Hypersensitivity to active substances / any excipients. Co-administration with rifampicin and St John’s wort. Refer to SmPC for full information.

WARNINGS/PRECAUTIONS: Should not be co-administered with other antiretroviral products. Limited safety and efficacy data in HCV coinfection. Tenofovir alafenamide is active against HBV. Co-infected HIV/HBV patients should be closely monitored for at least several months following discontinuation for symptoms of severe acute exacerbations of hepatitis.

Should not be administered simultaneously with magnesium/aluminiumcontaining antacids or iron supplements under fasted conditions. See SmPC for more information on liver disease, weight and metabolic parameters, risk of mitochondrial dysfunction following exposure in utero, immune reactivation syndrome, opportunistic infections, osteonecrosis with CART therapy or nephrotoxicity and patients with ESRD on chronic haemodialysis.

Co-administration: Biktarvy is not recommended for co-administration with atazanavir, carbamazepine, ciclosporin (IV or oral use), oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, or sucralfate. Excipients: Contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially ‘sodium free’. Refer to SmPC for full information on warnings and precautions.

INTERACTIONS: See SmPC for full list.

May 2021 UK-BVY-0062

PREGNANCY/LACTATION: Use only if potential benefit justifies the potential risk. Breast-feeding: not recommended. Refer to SmPC for full information.

DRIVING/USING MACHINERY: dizziness has been reported.

SIDE EFFECTS: Refer to SmPC for full information Common (≥1/100 to <1/10): depression, abnormal dreams, headache, dizziness, diarrhoea, nausea, fatigue. Serious adverse events: suicidal ideation, suicide attempt behaviour (particularly in patients with a pre-existing history of depression or psychiatric illness), anxiety, sleep disorders, angioedema and Stevens-Johnson syndrome.

LEGAL CATEGORY: POM. PACK: Bottle of 30 film-coated tablets.

PRICE: UK NHS List Price - £879.51; Éire/Ireland – POA. MARKETING AUTHORISATION NUMBER: Great Britain: PLGB 11972/0008 Ireland and United Kingdom (Northern Ireland: EU/1/18/1289/001 & EU/1/18/1289/002 FURTHER INFORMATION: Gilead Sciences Ltd, 280 High Holborn, London, WC1V 7EE, UK; Great Britain & Northern Ireland: +44 (0) 8000 113700, For Ireland: +353 214 825 999. E-mail: ukmedinfo@gilead.com.

Biktarvy is a trademark.

DATE OF PREPARATION: March 2021; UK-HIV-2021-03-0032.

Additional monitoring required.

Adverse events should be reported.

For Great Britain and Northern Ireland, reporting forms and information can be found at www.mhra.gov.uk/yellowcard/ or via the Yellow Card app (download from the Apple App Store or Google Play Store). Adverse events should be reported to Gilead (safety_FC@gilead.com) or +44 (0) 1223 897500.

Adverse events should be reported. For Ireland, reporting forms and information can be found at www.hpra.ie and can be reported to HPRA on +353 1 6764971. Adverse events should be reported to Gilead (safety_FC@gilead.com) or +44 (0) 1223 897500.

88 Urology

Improvement of urinary tract symptoms and quality of life in benign prostate hyperplasia patients Urology and Renal Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy - Luigi Cormio, Beppe Calò, Ugo Falagario, Giovanni Silecchia & Giuseppe Carrieri Bonomo Teaching Hospital, Andria (BAT), Italy - Luigi Cormio, Beppe Calò & Giovanni Silecchia Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), G.d’Annunzio University, Chieti, Italy Manuela Iezzi, Alessia Lamolinara, Pier Giorgio Natali & Mauro Piantelli Department of Agricultural Sciences, University of Naples, Portici, Italy - Paola Vitaglione Department of Agrotechnology and Food Science, Wageningen University, Wageningen, The Netherlands - Vincenzo Fogliano Janus Pharma S.r.l., Via Giacomo Peroni 386, 00131, Roma, Italy - Stefano Iacobelli Benign prostatic hyperplasia (BPH) affects aging men and is the most common urologic disease among elderly men.1 BPH is the consequence of the proliferation of both epithelial and stromal cells from the transition zone and periurethral prostatic areas. It typically develops after the age of 40 years, ranging in prevalence from > 50% at 60 years to as high as 90% by 85 years.2 The diagnosis of BPH is usually driven by lower urinary tract obstructive, and lower urinary tract symptoms (LUTS), i.e. urinary hesitancy, urgency, frequency, and post-void dribble. Pharmacological treatment possibilities include α-adrenergic antagonists or 5-α reductase inhibitors, however, one-third of patients with LUTS do not respond to either treatment approach3 and a fraction of responders is penalized by the occurrence of side-effects. Patients who are resistant to medical treatment, or who become resistant to treatment over time will become candidates for surgical intervention to reduce LUTS severity.

adipose deposition was associated with the severity of prostate tissue inflammation and LUTS and an approach to minimize centralized fat deposition may reduce LUTS severity in BPH patients.7 Phytocompounds in the form of plant portions or extracts are widely used in the treatment of prostate diseases.8 In this context, a large number of anti-inflammatory compounds have been identified in tomato extracts;9, 10 moreover, tomato consumption reduces inflammation by decreasing inflammatory cytokines in overweight and obese men.11, 12 Along this line of investigation, we have observed that a diet

enriched with a 10% whole tomato13 vs a tomato-free control diet increased the anti-oxidant serum activity and reduced serum levels of inflammatory biomarkers in the transgenic adenocarcinoma mouse prostate model (TRAMP) of prostate carcinogenesis, even before the appearance of cancer.14 As a result, a decrease in cancer incidence and mortality was observed. In this regard, the role of lycopene is relevant, as a lycopene-poor tomato supplement failed to duplicate these findings.15 However, the antineoplastic activity of the whole tomato preparations cannot be explained by the lycopene content alone,16,17,18 and constituents already present in

Further understanding of the causes of LUTS will guide interventions to prevent LUTS or increase sensitivity to medical treatment. To date, there are multiple theories on the cellular and molecular processes underlying the pathogenesis of BPH leading to symptomatic disease. In addition to androgens, both chronic and acute inflammation can lead to events that can cause proliferation within prostatic tissue through a variety of mechanisms, notably oxidative stress.4, 5 At present, non-steroidal anti-inflammatory drugs are used to improve urinary symptoms and flow measures, but their long-term effectiveness and safety are not known.6 BPH is also associated with obesity and related pathologies.

However, the biological pathways linking obesity and BPH are poorly understood. The centralized Figure 1

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

small amounts or newly formed during processing also contribute to their final in vivo efficacy.19 Recently, a whole tomato-based food supplement (WTBS) has been developed and registered by the Italian Health Ministry (registration n. 68843, 2018–19) with the claims “antioxidant” and”prostate health”. In a pilot study, we demonstrated that new WTFS, at the dosage of one sachet/day for 2 months, decreased LUTS in about 80% of BPH patients.20 The present phase II prospective, randomized, double-blinded, placebo-controlled study aimed to determine the efficacy and safety of the novel whole tomato-based

BE PREPARED WHEN SEIZURES STRIKE BUCCOLAM (R) is indicated for the for treatment of prolonged, convulsive seizures infants, toddlers, childreninand adolescents (from 3 children months to and <18 years).

BUCCOLAM is indicated the treatment ofacute, prolonged, acute, inconvulsive seizures infants, toddlers, adolescents (from 3 months to <18 years).

BUCCOLAM® must only be used by parents/carers where the patient has been diagnosed to have epilepsy. For infants between 3–6 months of age, treatment should be in a hospital setting where BUCCOLAM (R) must only be used by parents/carers where the patient has been diagnosed to have epilepsy. For infants between 3-6 months of age, treatment should be in a hospital setting where monitoring is monitoring is possible and resuscitation equipment is available. 1 Please consult the Buccolam® Summary of Product Characteristics (SmPC) before prescribing. ® possible and resuscitation equipment is available.

References: 1. Buccolam . Summary of Product Characteristics.

Further prescribing information is available on request from Neuraxpharm or the Summary of Product Characteristics - eMail: medinfo@neuraxpharm.com or Tel.: +353 (1) 4688 202 Marketing Authorisation Holder: Laboratories Lesvi S.L. Avinguda Joan Despi, 08970 Barcelona, Spain. Marketing Authorisation Number: EU/1/11/709/001-004 Legal Classification: POM CD. Pricing Information: POA Adverse events should be reported to: medinfo@Neuraxpharm.com - Tel: +353 (1) 4688202 or the Health Products Regulatory Authority - www.hpra.ie – e: medsafety@hpra.ie Tel +353 (1) 676 4971 Fax: +353 1 6767836 ®

1

Neuraxpharm is delighted to commence operations in Ireland Many of us will suffer mental or neurological disorders at some point in our lives.

The wellbeing of those suffering from these disorders is at the heart of what we do. This is why we investigate and develop new solutions.

Our commitment has led us to become a European leader in developing medicines for Central Nervous System disorders. We strive to support our doctors, pharmacists, nurses and the families affected.

Now that we have located in Ireland, we look forward to working as part of the Irish Healthcare System, supporting patients and healthcare professionals in reducing the impact of Central Nervous System disorders in the lives of patients.

From: Improvement of urinary tract symptoms and quality of life in benign prostate hyperplasia patients associated with consumption of a newly developed whole tomato-

90 Urology

based food supplement: a phase II prospective, randomized double-blinded, placebocontrolled study

Table 1

food supplement in reducing LUTS of patients with histologically proven BPH. Materials, methods, and patients The WTFS which is produced by a patented solvent-free process resulting in increased bioavailability of antioxidant and anti-inflammatory tomato micronutrients: carotenoids, main lycopene with increased cis-configuration, flavonoids, and ketosamines is added with a small percentage of olive polyphenols.21

Group A

Group B

P-value

Age

*65.6 ± 5.1

64.1 ± 8.2

0.468

Prostate volume (mL)

57.3 ± 7.1

59.8 ± 6.5

0.244

Prostate phlogosis (IRANI score)

2.5 ± 1.3

2.0 ± 1.2

0.182

Total PSA (ng/mL)

8.8 ± 1.5

6.6 ± 1.1

0.229

*

All values are expressed as mean ± SE

treatment, and 0.5 mL aliquots were immediately frozen and stored at − 80°C until processing.

Quantitation of total and free PSA as well as of cytokines/growth factors (IL-1, IL-6, IL-8, IL-17, IL18, Angiopoietin 2, VEGF A) were performed by a multiplex assay (Milliplex®, Merck Life Science, Milano, Italy).

inflammation, and serum PSA levels (Table 1) between treated (Group A) and control patients (Group B).

PSA was seen in placebo-treated subject (6.83 ± 1.09 vs 8.05 ± 0.96, Back to article page P = 0.114).

One patient in Group B was Free PSA concentrations were lost at follow-up; all the others not modified by the treatment Patients and methods completed the study reporting no (1.35 ± 0.24 vs 1.42 ± 0.198, side effects. Patients in Group A P = 0.70). In addition, free/total Forty consecutive patients having experienced a significant reduction PSA ratios were not significantly undergone prostate biopsy (PBX) in mean IPSS 9.05 ± 1.15 (range different before and after the at our Institution and having 16–2) and 7.15 ± 1.04 (range 14–2), WTFS treatment (17.11 ± 1.89 vs been diagnosed with BPH were two- prostate22.38 ISSN: 1479-5876 ± 2.70, Ppatient... = 0.117), and this1isof 2 of urinary tract symptomsrespectively and quality(paired of lifet-test, in benign hyperplasia Page included in a phase II prospective, Improvement The sample size was calculated tailed P < 0.001) whereas patients also true in the case of overweight/ randomized double-blinded, assuming a 20% reduction in in Group B did not (13.89 ± 6.45 vs obese patients with basal levels of placebo-controlled study. The IPSS and an 80% study power; Contact us 13.79 ± 6.29, P = 0.607). The effects total PSA > 10 ng/mL (14.65 ± 3.39 study protocol was approved based on this data, 15 patients per journals Get vs published About BMC Login of treatment onExplore the symptoms 23.20 ± 4.63, P = 0.175). by the University of Foggia group were needed. Therefore, 20 Search contributing toMenu the Contact IPSS scoreUs are Ethics Committee (Nov. 8, 2017; patients per Group were planned.

Submission enquiries: Access here and click Discussion detailed in Table 2. In particular, Registration Number 871-16) and A study flow diagram in agreement the WTFS strongly reduced both was carried out in agreement with with the CONSORT guidelines is General enquiries: info@biomedcentral.com The newly developed WTFS urination frequency (P = 0.002) the provisions of the Declaration of shown in Fig. 1 (on page 88). is a mixture of whole tomato and urgency (P < 0.0001).

As Helsinki. Written informed consent powder and a polyphenolic The primary study endpoint a consequence, a significant was obtained from all patients. extract from olives. The original improvement in life quality was was testing changes in LUTS as tomato powder was firstly used Read more on our blogs Policies Support and Contact Indications for trans-rectal assessed by the IPSS questionnaire referred by WTFS-assuming to produce food for special Home About Articles Submission Guidelines ultrasound-guided PBX were patients (P < 0.0001; Table 2). and PSA.23 IPSS is based on medical purposes (FSMP) increased serum prostate Quality of life was not affected by the answer to seven questions and investigated as adjuvant specific antigen (PSA) (≥ 4 ng/ placebo (2.32 ± 0.29 vs 2.42 ± 0.26, concerning urinary symptoms and therapy in subjects affected by mL) and/or abnormal digital rectal https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02684-3/tables/3 08/11/2021 P = 0.330). is the only questionnaire validated chronic hepatitis C. This FSMP examination. The inflammation

by WHO in the Italian language. was effective in preventing A trend toward a reduction of present in prostatic biopsies was Each question is assigned carotenoid serum depletion and total PSA levels was observed in assessed and graded according to points from 0 to 5, indicating the improving the oxidative status WTFS treated subjects (8.98 ng/ Irani’s score for both the histologic increasing severity of a particular during antiviral therapy.13 Then, mL ± 1.52 vs 6.95 ± 0.75, P = 0.065) inflammation grading (extension symptom. The total score, the anti-tumor activity of the (Fig. 2, left). Actually, this trend of inflammatory cells, range 0–3) therefore, ranges from 0 to 35 (from tomato powder was evaluated was sustained by the significant and aggressiveness (the effect asymptomatic to very symptomatic) in a transgenic mouse model of reduction of PSA concentrations of inflammatory cells on prostate and patients can be classified as prostate carcinogenesis (TRAMP).14 seen in the five patients, (2 obese, tissue, range 0–3).22 From: Improvement of urinary tractand symptoms and quality of lifemodel, in benign follows: 0–7 = mildly symptomatic; In this feedingprostate mice with 2 over1 normal-weight), 8–19 = moderately symptomatic; Patients were randomized 1:1 into the tomato powder significantly with basal levels > 10 ng/mL hyperplasia patients associated with consumption of a newly developed whole tomato20–35 = severely symptomatic. two Groups: Group A received delayed tumor progression and (18.520 ng/mL ± 2.747 vs 10.323 one oral sachet of WTFS (5 g) decreased both the incidence of ng/mL ± 2.073, P = 0.009) (Fig. 2, based II prospective, randomized double-blinded, placeboResults food supplement: a phase every 24 h dissolved in water poorly differentiated carcinoma and right). On the other hand, at the with no relation with meals, for 2 There was no difference mortality. Additionally, in agreement end of the observation period, a controlled study in terms months while Group B received trend toward an increase of total with several other reports, tomato of age, prostate volume, prostate the placebo. Placebo consisted of orange/maltodextrin. The lycopene content in the WTSF Symptoms: Pre-treatment score Post-treatment score P-value sachet consisted of 9.5 mg isomers and of 12.5 all-trans, 1.75 5-cis, 1 Incomplete emptying 1.58 ± 0.25* 1.63 ± 0.23 P = 0.577 contained in the carotenoid fraction of the product. Patients reporting 2 Frequency 1.40 ± 0.22 0.45 ± 0.18 P = 0.002 a history of hypersensitivity to tomato, inflammatory diseases of 3 Intermittency 1.55 ± 0.22 1.65 ± 0.25 P = 0.428 the urogenital tract (i.e. orchitis, epididymitis, or both), and 4 Urgency 1.16 ± 0.21 0.42 ± 0.19 P < 0.0001 malabsorption syndrome 5 Weak Stream 1.50 ± 0.22 1.70 ± 0.24 P = 0.162 were excluded.

Journal of Translational Medicine

Journal of Translational Medicine

Table 4 Effects of WTFS treatment on IPSS symptoms

Patients had to fill the International Prostate Symptom Score (IPSS) questionnaire before and after treatment. Moreover, patients’ sera were collected before and after Table 2

6 Straining

1.15 ± 0.22

1.05 ± 0.22

P = 0.163

7 Nicturia

0.80 ± 0.20

0.45 ± 0.18

P = 0.005

Quality of life

2.45 ± 0.34

1.50 ± 0.27

P < 0.0001

*

All values are expressed as mean ± SE

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Back to article page

COMBINING POWER AND CONFIDENCE AGAINST LDL-C* IN THE TREATMENT OF

HYPERCHOLESTEROLAEMIA

Rosuvastatin + Ezetimibe

Rosuvastatin + Ezetimibe

20 mg/10 mg

10 mg/10 mg

Rosuvastatin + Ezetimibe

40 mg/10 mg

Suvezen is indicated for substitution therapy in adult patients who are adequately controlled with rosuvastatin and ezetimibe given concurrently at the same dose level as in the fixed combination, but as separate products, as adjunct to diet for treatment of primary hypercholesterolaemia (heterozygous familial and nonfamilial) or homozygous familial hypercholesterolaemia1 Prescribing Information: Suvezen (rosuvastatin/ ezetimibe) film-coated tablets Please refer to the Summary of Product Characteristics (SmPC) for full prescribing details. Presentations: Suvezen 10mg/10mg, 20mg/10mg and 40mg/10mg: Each film-coated tablet contains 10mg; 20mg or 40mg of rosuvastatin (as rosuvastatin calcium) respectively, and 10mg ezetimibe. Indication: Suvezen is indicated for substitution therapy in adult patients who are adequately controlled with rosuvastatin and ezetimibe given concurrently at the same dose level as in the fixed combination, but as separate products, as adjunct to diet for treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or homozygous familial hypercholesterolaemia. Dosage and Administration: The patient should be on and continue, an appropriate lipid-lowering diet, during treatment with Suvezen. Suvezen is not suitable for initial therapy. Treatment initiation or dose adjustment, if necessary, should only be done with the monocomponents and after setting the appropriate doses the switch to the fixed dose combination of the appropriate strength is possible. Patient should use the strength corresponding to their previous treatment. The recommended dose is one Suvezen tablet daily. To be administered at any time of the day, with or without food. The tablet should be swallowed whole with a drink of water. If co-administered with bile acid sequestrant (BAS), administration of Suvezen should occur either ≥2 hours before or ≥4 hours after administration of a BAS. Special populations: Paediatric (<18 years): Safety and efficacy has not been established. Elderly (>70 years): Starting dose of 5 mg rosuvastatin is recommended. The combination is not suitable for initial therapy.

Hepatic impairment: Mild: No dosage adjustment is required. Moderate/Severe: Treatment with Suvezen is not recommended. Renal impairment: Mild: No dose adjustment is necessary. Moderate (creatinine clearance <60 ml/min): The recommended start dose is rosuvastatin 5mg. Race: The recommended start dose is rosuvastatin 5 mg for patients of Asian ancestry due to increased systemic exposure. The fixed dose combination is not suitable for initial therapy. Monocomponent preparations should be used to start the treatment or to modify the dose. Suvezen 40 mg/10 mg tablets are contraindicated in these patients. Genetic polymorphisms: In patients who are known to have specific types of genetic polymorphisms that can lead to increased rosuvastatin exposure, a lower daily dose of Suvezen is recommended. Dosage in patients with pre-disposing factors to myopathy: The recommended start dose is rosuvastatin 5mg in patients with pre-disposing factors to myopathy. Suvezen 40 mg/10 mg tablets are contraindicated in some of these patients. Concomitant therapy: The risk of myopathy (including rhabdomyolysis) is increased when Suvezen is administered concomitantly with certain medicinal products that may increase the plasma concentration of rosuvastatin (e.g. ciclosporin and certain protease inhibitors including combinations of ritonavir with atazanavir, lopinavir, and/or tipranavir). Whenever possible, alternative medications should be considered, and, if necessary, consider temporarily discontinuing Suvezen therapy. In situations where coadministration of these medicinal products with Suvezen is unavoidable, the benefit and the risk of concurrent treatment and rosuvastatin dosing adjustments should be carefully considered. Contraindications: Hypersensitivity to the active substances or excipients. Pregnancy, breast-feeding and in women of childbearing potential not using appropriate contraceptive measures. Active liver disease or any serum transaminase elevations which are unexplained, persistent or exceeding 3x the upper limit of normal (ULN). Severe renal impairment (creatinine clearance <30ml/min); myopathy or receiving concomitant ciclosporin. 40mg/10mg dose contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis; such factors include: Moderate renal impairment (creatinine clearance <60ml/min), hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate, alcohol abuse, situations where an increase in plasma levels of rosuvastatin may occur, Asian patients, concomitant use of fibrates.

Precautions and Warnings: Skeletal muscle effects: have been reported in rosuvastatin-treated patients with all doses and in particular with doses >20mg. As with other HMG-CoA reductase inhibitors, reporting rate for rhabdomyolysis is associated with use at doses >40mg. Post-marketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. If myopathy is suspected based on muscle symptoms or is confirmed by a creatine phosphokinase (CPK) level, Suvezen and any of these other agents that the patient is taking concomitantly should be immediately discontinued. All patients starting therapy with Suvezen should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness, particularly if associated with malaise or fever. Creatine kinase (CK) measurement: CK should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase. If CK levels are significantly elevated at baseline (>5x ULN) a confirmatory test should be carried out within 5 – 7 days. If the repeat test confirms a baseline CK >5x ULN, treatment should not be started. Patients with pre-disposing factors for myopathy/ rhabdomyolysis: Caution should be exercised in these patients. Risk: benefit of treatment should be considered and clinical monitoring is recommended. CK levels should be measured in these patients. Therapy should be discontinued if CK levels are markedly elevated (>5x ULN) or if muscular symptoms are severe and cause daily discomfort. If symptoms resolve and CK levels return to normal, then consideration should be given to reintroducing treatment at the lowest dose. Immune-mediated necrotising myopathy (IMNM): Clinically characterised by proximal muscle weakness and elevated serum CK, has been reported very rarely during or after treatment with statins, including rosuvastatin, despite discontinuation of statin treatment. In clinical trials an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives. Suvezen should not be used in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures). Liver effects: In controlled co-administration trials in patients receiving ezetimibe with statin, consecutive transaminase elevations ≥3x ULN have been observed. It is recommended that liver function tests be carried out prior to, and 3 months following, the initiation of treatment. Rosuvastatin should be discontinued or the dose reduced if the level of serum transaminases is >3x ULN. The reporting rate for serious events is higher at the 40mg dose. In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with rosuvastatin. Liver disease and alcohol: As with other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who consume

Single-pill combination of rosuvastatin and ezetimibe available in 3 doses**

excessive quantities of alcohol and/or have a history of liver disease. Renal effects: Proteinuria has been observed in patients treated with higher doses of rosuvastatin and was transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive renal disease. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40mg. Diabetes mellitus: Some evidence suggests that statins raise blood glucose and in some patients, at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5.6 – 6.9mmol/l, BMI >30kg/m2, raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines. Interstitial lung disease: Exceptional cases have been reported with some statins, especially with long term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected, statin therapy should be discontinued. Protease inhibitors: Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. Consideration should be given both to the benefit of lipid lowering by use of Suvezen in HIV patients receiving protease inhibitors and the potential for increased rosuvastatin plasma concentrations when initiating and up titrating rosuvastatin doses in patients treated with protease inhibitors. The concomitant use with certain protease inhibitors is not recommended unless the dose of rosuvastatin is adjusted. Fibrates: The safety and efficacy of ezetimibe administered with fibrates have not been established. If cholelithiasis is suspected in a patient receiving Suvezen and fenofibrate, gallbladder investigations are indicated and therapy should be discontinued. Anticoagulants: If Suvezen is added to warfarin, another coumarin anticoagulant, or fluindione, the International Normalised Ratio (INR) should be appropriately monitored. Fusidic acid: Suvezen must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment.

There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination. The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness. Statin therapy may be re-introduced seven days after the last dose of fusidic acid. In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of Suvezen and fusidic acid should only be considered on a case by case basis and under close medical supervision. Suvezen contains lactose monohydrate and sodium: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’. Interactions: Contraindicated combinations: Ciclosporin. Not-recommended combinations: Fibrates and other lipid-lowering products, protease inhibitors, transporter protein inhibitors and fusidic acid. Other possible interactions: Cytochrome P450 enzymes, antacids, colestyramine, anticoagulants, Vitamin K antagonists, erythromycin, oral contraceptive/hormone replacement therapy. When co-administering rosuvastatin with other medicinal products known to increase exposure to rosuvastatin, doses should be adjusted (see SmPC for full details). The maximum daily dose should be adjusted so that the expected rosuvastatin exposure would not likely exceed that of a 40mg daily dose of rosuvastatin taken without interacting medicinal products.

Fertility, Pregnancy and Breastfeeding: No clinical data are available on the use of ezetimibe during pregnancy.

Potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy. If a patient becomes pregnant during use of Suvezen, treatment should be discontinued immediately. Animal studies have shown excretion of medicinal product through breast milk. However, there are no data in humans. No clinical trial data on the effects of fertility in humans. Adverse Reactions: Adverse drug reactions previously reported with one of the individual components (ezetimibe or rosuvastatin) may be potential undesirable effects with Suvezen. Common (≥1/100 to <1/10): diabetes mellitus, headache, dizziness, constipation, nausea, abdominal pain, diarrhoea, flatulence, myalgia, ALT and/or AST increased, asthenia and fatigue. Uncommon (≥1/1,000 to <1/100): decreased appetite, paraesthesia, hot flush, hypertension, cough, dyspepsia, gastroesophageal reflux disease, nausea, dry mouth, gastritis, pruritus, rash, urticaria, arthralgia, muscle spasms, neck pain, back pain, muscular weakness, pain in extremity, ALT and/or AST increased, blood CPK increased, gamma-glutamyltransferase increased, liver function test abnormal, chest pain, pain, asthenia, oedema peripheral. Rare (≥1/10,000 to <1/1,000): thrombocytopenia, hypersensitivity reactions including angioedema, pancreatitis, increased hepatic transaminases, myopathy (including myositis), rhabdomyolysis, lupus-like syndrome and muscle rupture. Very rare (<1/10,000): polyneuropathy, memory loss, jaundice, hepatitis, arthralgia, haematuria, gynaecomastia. Not known: thrombocytopenia, hypersensitivity (including rash, urticaria, anaphylaxis and angioedema), depression, peripheral neuropathy, sleep disturbances (including insomnia and nightmares), dizziness, paraesthesia, cough, dyspnoea, diarrhoea, pancreatitis, constipation, hepatitis, cholelithiasis, cholecystitis, Stevens Johnson syndrome, erythema multiforme, immune-mediated necrotising myopathy, tendon disorders (sometimes complicated by rupture), myalgia, myopathy/rhabdomyolysis, oedema, asthenia. See SmPC for full details on adverse reactions. Legal Category: POM. Marketing Authorisation Numbers: 10mg/10mg: PA0540/193/001; 20mg/10mg: PA0540/193/002; 40mg/10mg: PA0540/193/003. Marketing Authorisation Holder: Sanofi-Aventis Ireland Ltd. T/A SANOFI, Citywest Business Campus, Dublin 24, Ireland. Further information is available from: Sanofi, 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact IEmedinfo@sanofi.com Date of Preparation: December 2020.

Reference: 1. Suvezen Summary of Product Characteristics * LDL-C: Low-density lipoprotein Cholesterol ** Suvezen is available in 3 doses in Ireland. Suvezen 10mg/10mg, 20mg/10mg and 40mg/10mg: Each film-coated tablet contains 10mg; 20mg or 40mg of rosuvastatin (as rosuvastatin calcium) respectively, and 10mg ezetimibe.

Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie; email: medsafety@hpra.ie Adverse events should also be reported to Sanofi Ireland Ltd. Tel: 01 403 5600.

Alternatively, send via email to IEPharmacovigilance@sanofi.com

MAT-IE-2101261 (v1.0) – August 2021

92 Urology Figure 2

supplementation was found to reduce the levels of circulating inflammatory/angiogenic cytokines as VEGF, TNF alpha, and IL-6 in several experimental models [24,25,26]. The patented method to produce the WTFS leads to a final product enriched in bioactive compounds, i.e. olive’s polyphenols which have been found more active than the tomato powder alone in reducing serum levels of IL-6 and VEGF in TRAMP mice.21 Serum measurement of a panel of inflammatory cytokines in the pretreatment sera did not show any significant derangement (data not shown). This does not come unexpectedly since the prostate inflammation in BPH patients is unlikely to be mirrored in circulation.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a urinary disorder that afflicts patients due to various discomforts. It is pressing and meaningful to develop novel and effective treatments because of the uncertain etiology and dismal therapeutic effect of CP/CPPS. In the absence of a standard treatment,27 the use of substances like antioxidants that may stop or potentially reverse the deleterious effects of inflammation is particularly attractive. Tomatoes and olives are the sources of complexes of micronutrients endowed with well-known strong antioxidants and anti-inflammatory activity, with properties potentially useful in protecting DNA and other cell constituents from oxidation.28, 29 Here we demonstrate that the new WTFS determines a significant improvement of urinary tract symptoms and quality of life in BPH patients, thus representing a suitable alternative option to the pharmacological treatment of this age-related pathology. Although the molecular mechanisms underlying this clinical benefit remains to be investigated, in a rat model lycopene was found to attenuate chronic prostatitis/ chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF-κB, MAPKs, and Nrf2 signaling pathways.30 Indeed, in addition to lycopene, tomatoes contain within their matrix other bioactive compounds that are responsible for the health effects associated with the constant consumption of the fruit, which cannot be accounted for solely by lycopene.18, 31 The patented WTFS production method, not only generates more bioavailable cis-lycopene and increased tomato phenolic components but produces

frus-his compounds that further increase tomato health-preserving properties.19 Thus this WTFS is likely to possess a spectrum of cooperative mechanisms. In view that the increase of the epithelial and stromal components in BPH is not paralleled by noticeable proliferation, the hyperplastic lesions have been interpreted as the result of impaired programmed cell death mechanism.32, 33 In this regard, tomato sauce has been reported to increase apoptosis in different experimental models.34, 35 Stromal cells are responsible for the androgen-mediated glandular epithelium growth. Although a defined molecular pathway has not been yet defined, tomato and lycopene have been reported to down-regulate androgen metabolism and signaling.36

cystoscopy can increase serum PSA levels fourfold, while needle biopsies and transurethral resection can temporarily increase PSA levels up to 50-fold, all as a result of increased PSA leakage into the serum. Besides, the relatively long half-life of PSA may lead to a consistent delay before serum PSA returns to a baseline level after transurethral prostatectomy, or infection [45].

On the contrary, a trend toward a reduction of total PSA levels was observed in WTFS treated patients (P = 0.096), which was sustained by the significant reduction of total PSA concentrations seen in the patients with high basal levels (> 10 ng/mL; P = 0.009).

Also, the mix of polyphenols from tomatoes and olive vegetation water can certainly contribute to the anti-inflammatory properties of the WTFS.43, 44

Although BPH and prostate cancer (PCa) share features such as hormone-dependent growth and response to treatment with anti-androgen therapy, BPH is not considered a premalignant lesion.

However, in a nationwide cohort study involving over 3 million men followed for up to 27 years, clinical BPH was associated with a two- to three-fold increased risk of PCa incidence and with a two- to eightfold increased risk of PCa mortality [46]. Because PSA determinations when properly utilized may contribute to the diagnosis and follow-up of prostate cancer,47 the effect of tomato treatment on total PSA serum levels could interfere with clinical management.

However, the determination of the percentage of free PSA and free/ total PSA ratio appears to be a helpful method for enhancing the specificity of total PSA evaluation48, 49 and WTFS does not change free PSA and free/total PSA values.

This new food supplement can modulate the total PSA concentrations even in patients with BPH. We have observed an increasing total PSA trend in the placebo group (P = 0.080), probably as the consequence of the biopsy procedure. Indeed,

The overall tomato consumption may bear harmful effects on human health such as gastroesophageal reflux disease, irritable bowel syndrome, kidney stones, and some urinary problems.50 In this context, it is worthy to be noted that, due to the preparation

Inflammation is a common histopathological finding in BPH, in absence of prostatic cancer or clinical prostatitis. It is a condition of which subclinical inflammation may be associated with a rise in serum PSA levels.37 However weak is the correlation between PSA levels and the active or chronic inflammation and no significant correlation exists between the active or chronic histopathological inflammation and IPSS.38 Also, in this regard nutritional interventions with tomato-products reduced PSA levels in subgroups of prostate patients, while lycopene supplements or extracts were found to be less effective.39,40,41,42

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

procedures, this WTFS does not contain organic acids (citric and malic acids), significant potassium/ oxalate concentration and tomato skin/seeds, responsible for these side effects.

Based on recent human experimentation51 this novel dietary supplement, which is phytosterolsfree may help to maintain prostate health and can contribute to the beneficial effect of adhering to the WCRF/AICR recommendations,52 by itself, when complemented with current treatments53 and by adopting healthy lifestyles.

Furthermore, because of its high deliverable antioxidant activity, the consumption of the WTFS can be advantageous in contrasting the unhealthy effects of the excess production of free radicals induced by a variety of risk factors, including the metabolic syndrome often associated with BPH.25, 54 Although tomatoes provide most of the dietary antioxidants in the Mediterranean-style diet, their culinary use is often associated with the consumption of carbohydrates rich meals (e.g. pasta, pizza), and high calories uptake (olive oil), thus representing a risk factor for individuals with excessive body mass, obesity, and metabolic syndrome. In this regard, the WTFS is an exemplary source of a complex of antioxidants. Furthermore, this food supplement may represent an ideal candidate to develop a variety of tomato-based enriched foods to delay the onset and/or to attenuate the course of age-related chronic degenerative disease.55, 56 Conclusions The newly developed WTFS may represent an efficient option for the treatment of symptomatic BPH patients. Unlike pharmacological treatments, this supplement is side effects free and highly accepted among patients.

References available on request

50mgs once daily

50mgs once daily

Her 10th shopping trip since the day she started BETMIGA1

Prescribing Information: Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation: Prolonged-release tablet, containing mirabegron 25mg/50mg. Indication: Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. Posology and method of administration: The recommended dose is 50 mg once daily. A lower dose of 25mg is recommended for specific patient populations (renal and hepatic impairment) as well as in specific patient populations in combination with strong CYP3A inhibitors such as itraconazole, ketoconazole, ritonavir and clarithromycin.

Renal impairment: End stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis): Not recommended. Severe renal impairment (GFR 15 to 29 mL/min/1.73 m2): Reduce dose to 25 mg. Severe renal impairment and concomitant strong CYP3A inhibitors: Not recommended. Moderate renal impairment (GFR 30 to 59 mL/min/1.73 m2): 50 mg. Moderate renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Mild renal impairment (GFR 60 to 89 mL/min/1.73 m2): 50 mg. Mild renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Hepatic impairment: Severe hepatic impairment (Child-Pugh Class C): Not recommended. Moderate hepatic impairment (Child-Pugh B): Reduce dose to 25 mg. Moderate hepatic impairment and concomitant strong CYP3A inhibitors: Not recommended. Mild hepatic impairment (Child-Pugh A): 50 mg. Mild hepatic impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. The tablet is to be taken once daily, with liquids, swallowed whole and is not to be chewed, divided, or crushed. It may be taken with or without food Contraindications: Hypersensitivity to the active substance or to any of the excipients (see the SPC for a list of excipients). Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg. Special warnings and precautions for use: Renal impairment: Betmiga has not been studied in patients with end stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis) and, therefore, it is not recommended for use in this patient population. Data are limited in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2); based on a pharmacokinetic study a dose reduction to 25 mg is recommended in this population.

This medicinal product is not recommended for use in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) concomitantly receiving strong CYP3A inhibitors. Hepatic impairment: Betmiga has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and, therefore, it is not recommended for use in this patient population. This medicinal product is not recommended for use in patients with moderate hepatic impairment (Child-Pugh B) concomitantly receiving

Date of preparation: June 2019

strong CYP3A inhibitors. Hypertension: Mirabegron can increase blood pressure. Blood pressure should be measured at baseline and periodically during treatment with mirabegron, especially in hypertensive patients. Data are limited in patients with stage 2 hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg). Patients with congenital or acquired QT prolongation: Betmiga, at therapeutic doses, has not demonstrated clinically relevant QT prolongation in clinical studies. However, since patients with a known history of QT prolongation or patients who are taking medicinal products known to prolong the QT interval were not included in these studies, the effects of mirabegron in these patients is unknown. Caution should be exercised when administering mirabegron in these patients. Patients with bladder outlet obstruction and patients taking antimuscarinic medicinal products for OAB: Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medicinal products for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with Betmiga; however, Betmiga should be administered with caution to patients with clinically significant BOO. Betmiga should also be administered with caution to patients taking antimuscarinic medicinal products for the treatment of OAB. Interactions: Pharmacokinetic interactions: Mirabegron is a substrate for CYP3A4, CYP2D6, butyrylcholinesterase, uridine diphosphoglucuronosyltransferases (UGT), the efflux transporter P-glycoprotein (P-gp) and the influx organic cation transporters (OCT) OCT1, OCT2, and OCT3. Pharmacokinetic interactions involving the potential for other medicinal products to affect mirabegron exposures: Increases in mirabegron exposure due to drug-drug interactions may be associated with increases in pulse rate. Strong CYP3A inhibitors See Posology and administration above for dose adjustments recommended during concomitant use of strong CYP3A inhibitors in patients with renal or hepatic impairment. Mirabegron exposure (AUC) was increased 1.8-fold in the presence of the strong inhibitor of CYP3A/P-gp ketoconazole. CYP2D6 inhibitors: No dose adjustment is needed for mirabegron when administered with CYP2D6 inhibitors (or in patients who are CYP2D6 poor metabolisers). Inducers: Inducers of CYP3A (such as rifampicin) or P-gp may decrease the plasma concentrations of mirabegron. No dose adjustment of mirabegron is required as this effect is not expected to be clinically relevant.

Pharmacokinetic interactions involving the potential for mirabegron to affect exposures to other medicinal products: Inhibition of CYP2D6: Moderate and time dependent inhibition of CYP2D6 by mirabegron may result in clinically relevant drug interactions. CYP2D6 activity recovers within 15 days after discontinuation of mirabegron. Caution is advised if mirabegron is co-administered with medicinal

products metabolized by CYP2D6 with a narrow therapeutic index such as thioridazine, Type 1C antiarrhythmics (e.g.flecainide, propafenone) and tricyclic antidepressants (e.g., imipramine, desipramine). Caution is also advised if mirabegron is co-administered with CYP2D6 substrates that are individually dose titrated. Inhibition of P-gp: Mirabegron is a weak inhibitor of P-gp. For patients who are initiating a combination of Betmiga and digoxin, the lowest dose for digoxin should be prescribed initially. Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect. The potential for inhibition of P-gp by mirabegron should be considered when Betmiga is combined with sensitive P-gp substrates e.g. dabigatran. Fertility, pregnancy and lactation: The effect of mirabegron on human fertility has not been established.

Betmiga is not recommended during pregnancy and in women of child-bearing potential not using contraception. Mirabegron should not be administered during breast feeding. Refer to SPC for full guidance. Driving and use of machines: Betmiga has no or negligible influence on the ability to drive and use machines.

Undesirable effects: Summary of the Safety Profile: the safety of Betmiga was evaluated in 8433 patients with OAB, of which 5648 received at least one dose of mirabegron in the phase 2/3 clinical program, and 622 patients received Betmiga for at least 1 year (365 days). In the three 12-week phase 3 double blind, placebo controlled studies, 88% of the patients completed treatment with this medicinal product, and 4% of the patients discontinued due to adverse events. Most adverse reactions were mild to moderate in severity. The most common adverse reactions reported for patients treated with Betmiga 50 mg during the three 12-week phase 3 double blind, placebo controlled studies are tachycardia and urinary tract infections.

The frequency of tachycardia was 1.2% in patients receiving Betmiga 50 mg.

Tachycardia led to discontinuation in 0.1% patients receiving Betmiga 50 mg. The frequency of urinary tract infections was 2.9% in patients receiving Betmiga 50 mg.

Urinary tract infections led to discontinuation in none of the patients receiving Betmiga 50 mg. Serious adverse reactions included atrial fibrillation (0.2%). Adverse reactions observed during the 1-year (long term) active controlled (muscarinic antagonist) study were similar in type and severity to those observed in the three 12-week phase 3 double blind, placebo controlled studies. The following adverse reactions were observed with mirabegron in the three 12-week phase 3 double blind, placebo controlled studies. The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be established from the available data) Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse events

References: 1. Freeman R, et al. Current Medical Research and Opinion 2017. https://doi.org/10.1080/03007995.2017.1419170.

are grouped by MedDRA system organ class. Infections and infestations: Common: urinary tract infection Uncommon: vaginal infection, cystitis Psychiatric disorders: Not known: Insomnia*, confusional state* Nervous system disorders: Common: headache* dizziness* Eye disorders: Rare: eyelid oedema Cardiac disorders: Common: tachycardia Uncommon: palpitation, atrial fibrillation Vascular disorders: Very rare: Hypertensive crisis* Gastrointestinal disorders: Common: nausea*, constipation*, diarrhoea* Uncommon: dyspepsia, gastritis Rare: lip oedema Skin and subcutaneous tissue disorders: Uncommon: urticaria, rash, rash macular, rash papular, pruritus Rare: leukocytoclastic vasculitis, purpura, angioedema* Musculoskeletal and connective tissue disorders: Uncommon: joint swelling Renal and urinary disorders: Rare: urinary retention* Reproductive system and breast disorders: Uncommon: vulvovaginal pruritus Investigations Uncommon: blood pressure increased, GGT increased, AST increased, ALT increased (*observed during post-marketing experience). Reporting of suspected adverse reactions: see below. Legal category: POM (S1B) Marketing Authorisation number: EU/1/12/809/003 - 25mg EU/1/12/809/010 - 50mg. Marketing Authorisation holder: Astellas Pharma Europe B.V. Sylviusweg 62, 2333 BE Leiden, The Netherlands. Further information is available from: Astellas Pharma Co., Ltd, 5 Waterside, Citywest Business Campus, Dublin 24. Phone: +3531 467 1555. Summary of Product Characteristics with full prescribing information available upon request. Job number: BET_2019_0002_IE Date of preparation of API: 27 May 2019.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance Astellas Pharma Co. Ltd Earlsfort Terrace, IRL - Dublin 2 Tel: + 353 1 467 1555 Tel: +353 1 6764971 E-mail: Irishdrugsafety@astellas.com Fax: +353 1 6762517 Website: www.hpra.ie E-mail: medsafety@hpra.ie.

Approval code: BET_2019_0004_IE

94 News

Keeping track of the COVID-19 Vaccine in the Centralised Vaccination Clinics (CVCs)

Siobhain Duggan, Director of Innovation and Healthcare, GS1 Ireland

Challenge As COVID-19 vaccines became available, Ireland’s Health Service Executive (HSE) needed an efficient and effective way of receiving, administering, tracking and reporting vaccinations across its more than 40 Centralised Vaccination Clinics (CVCs). It was important for the HSE’s National Immunisation Office (NIO) that no dose was wasted and that batches of vaccine could be tracked to the point of vaccination.

Approach The HSE in collaboration with GS1 Ireland adopted a GS1 standards-based approach for the identification and tracking of vaccines to the point of vaccination. Following an intensive design phase with the HSE project team, two software applications were developed: ScanVax and TrackVax. ScanVax was installed on over 1,000 PCs across the country to allow for the receipt of vaccines. By scanning the barcode on each of the vaccine boxes, vaccine information is then uploaded to the national vaccine administration system. This means that vaccinators can select the correct batch when administering the vaccine. TrackVax has been installed in all CVCs across the country. This allows the CVC teams to identify, label, track and report on the vaccines in their centres, allowing a much easier vaccine reconciliation process locally and nationally. Both solutions are provided by GS1 Ireland.

“The feedback on TrackVax from the Senior Management Teams and the High Level Taskforce has been really positive in terms of enabling visibility of vaccine usage and it has been recognised that TrackVax has made a significant contribution to the efficient rollout of the COVID-19 vaccinations across Ireland.”

Figure 2: ScanVax is used to record receipt of COVID-19 vaccines by scanning the barcode on the box for upload to the national vaccine administration system

Dr. Lucy Jessop, Director of Public Health, HSE National Immunisation Office

As a result of the EU’s Falsified Medicines Directive (FMD), manufacturers of prescription medicines are required to assign a two-dimensional (2D) DataMatrix barcode on the secondary package of the product, which means traceability data can be captured in one scan. The barcode has four data elements: the Global Trade Item Number® (GTIN®), batch, expiry date and serial number. Although some of the vaccines didn’t have a serial number due to a derogation for COVID-19 vaccines, which presented additional challenges in managing vaccines in the clinics.

Background Over the last 15 years, the HSE has worked with GS1 Ireland to implement traceability standards in areas such as National Haemophilia track and trace, National Instrument and Endoscope track and trace and the development of the Health Directory, which assigns

GS1 identifiers to locations, people, assets and more. These identifiers all played a role in the establishment of the national vaccine administration system as identifiers were required for the people being vaccinated and the locations where the vaccination clinics were operating. Additionally, GS1 identifiers were assigned to

“It was clear from early in the CVC design stage, that the ambitious vision for the scale of vaccination in the CVCs required a comprehensive in-CVC vaccine tracking tool to support a standardised medicines management process.

Identification and tracking of vaccine at vial level enabled vaccine stewardship. Articulating this need was crucial for the successful approval of the business case for the development and rollout of TrackVax.” Fionnuala King, Chief Pharmacist, Acute Hospitals Drug Management Programme, HSE Acute Operations

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

staff using TrackVax and in some cases to boxes of vaccines to identify smaller pack sizes.

Designing in traceability standards 1- Standardised labelling to manage dynamic expiry dates In December 2020, the HSE invited GS1 Ireland to join discussions on how to manage the change in expiry date for Figure 1: Example of label specification for the Pfizer-BioNTech vaccine

A combined force against LUTS and BPH

49% of men with LUTS report bladder and prostate symptoms1 VESOMNI treats the symptoms of both the bladder and prostate2 Abbreviated Prescribing Information - Vesomni 6 mg/0.4 mg modified release tablets. Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation: Each tablet contains a layer of 6 mg solifenacin succinate, corresponding to 4.5 mg solifenacin free base and a layer of 0.4 mg tamsulosin hydrochloride, corresponding to 0.37 mg of tamsulosin free base. Indication: Treatment of moderate to severe storage symptoms (urgency, increased micturition frequency) and voiding symptoms associated with benign prostatic hyperplasia (BPH) in men who are not adequately responding to treatment with monotherapy. Posology and method of administration: Adult males, including older people: One Vesomni tablet (6 mg/0.4 mg) once daily taken orally with or without food. The maximum daily dose is one Vesomni tablet. The tablet must be swallowed whole, intact without biting or chewing. Do not crush the tablet. Special populations (see also contraindications below): Renal impairment: Severe renal impairment (creatinine clearance ≤ 30 mL/min): Treat with caution, maximum daily dose in these patients is one Vesomni tablet.

Hepatic impairment: Moderate hepatic impairment (Child-Pugh score of 7-9): Treat with caution, maximum daily dose in these patients is one Vesomni tablet. In patients with severe hepatic impairment (Child-Pugh score > 9), the use of Vesomni is contraindicated. Concomitant treatment with moderate and strong inhibitors of CYP450 3A4: e.g. verapamil, ketoconazole, ritonavir, nelfinavir, itraconazole: Treat with caution, maximum daily dose should be limited to one Vesomni tablet.

Paediatric population: There is no relevant indication for use of Vesomni in children and adolescents.

Contraindications: Patients with hypersensitivy to the active substance(s) or to any of the excipients (see SPC). Patients undergoing haemodialysis. Patients with severe hepatic impairment. Patients with severe renal impairment who are also treated with a strong cytochrome P450 (CYP)3A4 inhibitor e.g. ketoconazole. Patients with moderate hepatic impairment who are also treated with a strong CYP3A4 inhibitor e.g. ketoconazole. Patients with severe gastrointestinal conditions (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma and patients at risk for these conditions.

Patients with a history of orthostatic hypotension. Special Warnings and Precautions for Use: Vesomni should be used with caution in patients with: severe renal impairment; risk of urinary retention; gastrointestinal obstructive disorders; risk of decreased gastrointestinal motility; hiatus hernia/ gastroesophageal reflux and/or who are concurrently taking medicinal products (such as bisphosphonates) that can cause or exacerbate oesophagitis; autonomic neuropathy. The patient should be examined in order to exclude the presence of other conditions, which can cause similar symptoms to benign prostatic hyperplasia. Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Vesomni is initiated. If a urinary tract infection is present, appropriate antibacterial therapy should be started. QT prolongation and Torsade de Pointes have been observed in patients with risk factors, such as pre-existing long QT syndrome and hypokalaemia, who are treated with solifenacin succinate. Angioedema with airway obstruction has been reported in some patients on solifenacin succinate and tamsulosin. If angioedema occurs, Vesomni should be discontinued and not restarted. Appropriate therapy and/or measures should be taken. Anaphylactic reaction has been reported in some patients treated with solifenacin succinate. In patients who develop anaphylactic reactions, Vesomni should be discontinued and appropriate therapy and/or measures should be taken. As with other alpha1-adrenoceptor antagonists, a reduction in blood pressure can occur in individual cases during treatment with tamsulosin, as a result of which, rarely, syncope can occur. Patients starting treatment with Vesomni should be cautioned to sit or lie down at the first signs of orthostatic hypotension (dizziness, weakness) until the symptoms have disappeared. The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract and glaucoma surgery in some patients on or previously treated with tamsulosin hydrochloride. IFIS may increase the risk of eye complications during and after the operation. Therefore, the initiation of therapy with Vesomni in patients for whom cataract or glaucoma surgery is scheduled is not recommended. Discontinuing treatment with Vesomni 1-2 weeks prior to cataract or glaucoma surgery is anecdotally considered helpful, but the benefit of treatment discontinuation has not been established. During pre-operative assessment, surgeons and ophthalmic teams should consider whether patients scheduled for cataract or glaucoma surgery are being or have been treated with Vesomni in order to ensure that appropriate measures will be in place to manage IFIS during surgery. Vesomni should be used with caution in combination with moderate and strong inhibitors of CYP3A4 and it should not be used in combination with strong inhibitors of CYP3A4, e.g., ketoconazole, in patients who are of the CYP2D6 poor metaboliser phenotype or who are using strong inhibitors of CYP2D6, e.g., paroxetine.

Interactions: Pharmacological interactions: Concomitant medication with other anticholinergic medicinal products may result in more pronounced therapeutic and undesirable effects. Allow approximately one week after stopping treatment with Vesomni before commencing any anticholinergic therapy. The therapeutic effect of solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Pharmacokinetic interactions: Pharmacokinetic interactions involving the potential for other medicinal products to affect Vesomni exposures: Interactions with CYP3A4 and CYP2D6 inhibitors: See Contraindications, Posology and administration and Special warnings and precautions above. Concomitant administration may lead to increased exposure to both solifenacin (ketoconazole 400 mg/day resulted in a 1.5-fold increase in Cmax and a 2.8-fold increase in AUC). and tamsulosin (ketoconazole 400 mg/day resulted in a 2.2-fold increase in Cmax and a 2.8-fold increase in AUC). Vesomni should be used with caution in combination with strong CYP3A4 inhibitors. Vesomni should not be given together with strong CYP3A4 inhibitors in patients who are also CYP2D6 poor metabolizer phenotype or who are using strong CYP2D6 inhibitors. See SPC for details of the effects of other CYP3A4 and CYP2D6 inhibitors. Inducers: Inducers of CYP3A4 (e.g. rifampicin) may decrease the plasma concentrations of solifenacin and tamsulosin. Information available for the individual active substances: Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as metoclopramide and cisapride. Solifenacin did not affect the pharmacokinetics of digoxin, or the pharmacokinetics or effect on prothrombin time of R- or S-warfarin. Co-administration of tamsulosin and other alpha1-adrenoreceptor antagonists could lead to hypotensive effects. Diclofenac and warfarin may increase the elimination rate of tamsulosin. No interactions have been seen when tamsulosin was given concurrently with atenolol, enalapril or theophylline. Fertility, pregnancy and lactation: The effect of Vesomni on fertility has not been established. Ejaculation disorders have been observed in short and long term clinical studies with tamsulosin. Events of ejaculation disorder, retrograde ejaculation and ejaculation failure have been reported in the post authorization phase.

Vesomni is not indicated for use in women. Driving and use of machines: No studies have been performed, however patients should be informed about the possible occurrence of dizziness, blurred vision, fatigue and uncommonly somnolence, which may negatively affect the ability to drive or use machines. Undesirable Effects: Summary of the safety profile: Vesomni may cause anticholinergic undesirable effects of, in general, mild to moderate severity. The most frequently reported adverse reactions during the clinical studies performed for the development of Vesomni were dry mouth (9.5%), followed by constipation (3.2%) and dyspepsia (including abdominal pain; 2.4%). Other common undesirable effects are dizziness (including vertigo; 1.4%), vision blurred (1.2%), fatigue (1.2%), and ejaculation disorder (including retrograde ejaculation; 1.5%). Acute urinary retention (0.3%, uncommon) is the most serious adverse drug reaction that has been observed during treatment with Vesomni in clinical studies. List of adverse reactions: the ‘Vesomni frequency’ below reflects adverse drug reactions that have been observed during the double-blind clinical studies performed for the development of Vesomni (based on reports of treatment-related adverse events, which have been reported by at least two patients and occurred with a frequency higher than for placebo in the double-blind studies). The ‘solifenacin frequency’ and ‘tamsulosin frequency’ below reflect adverse drug reactions (ADRs) previously reported with one of the individual components (as presented in the Summary of Product Characteristics (SmPCs) of solifenacin 5 and 10 mg and tamsulosin 0.4 mg respectively that may also occur when receiving Vesomni (some of these have not been observed during the clinical development program of Vesomni). The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). The adverse events are grouped by MedDRA system organ class preferred term (PT). Vesomni frequency: Nervous system disorders: Common: dizziness Eye disorders: Common: vision blurred Gastrointestinal disorders: Common: dry mouth, dyspepsia, constipation Skin and subcutaneous tissue disorders: Uncommon: pruritus Renal and urinary disorders: Uncommon: Urinary retention*** Reproductive system and breast disorders: Common: ejaculation disorders including retrograde ejaculation and ejaculation failure General disorders and administration site conditions: Common: fatigue Solifenacin 5mg & 10mg frequency#: Infections and infestations: Uncommon: urinary tract infection, cystitis Immune system disorders: Not known: anaphylactic reaction* Metabolism and nutrition disorders: Not known: decreased appetite*, hyperkalemia* Psychiatric disorders: Very rare: hallucination*, confusional state* Not known:

References: 1. Sexton CC, et al. BJU Int 2009; 103(Suppl 3): 12-23. 2. VESOMNI Summary of Product Characteristics.

Date of preparation: July 2019 Job code: VESOM_2019_0003_IE

delirium* Nervous system disorders: Uncommon: somnolence, dysgeusia Rare: dizziness*, headache* Eye disorders: Common: vision blurred Uncommon: dry eyes Not known: glaucoma* Cardiac disorders: Not known: palpitations*, Torsade de Pointes*, electrocardiogram QT prolongation*, atrial fibrillation*, tachycardia* Respiratory, thoracic and mediastinal disorders: Uncommon: nasal dryness Not known: dysphonia* Gastrointestinal disorders: Very common: dry mouth Common: dyspepsia, constipation, nausea, abdominal pain Uncommon: gastro-oesophageal reflux disease, dry throat Rare: vomiting*, colonic obstruction, faecal impaction, Not known: ileus*, abdominal discomfort* Hepatobiliary disorders: Not known: liver disorder*, liver function test abnormal* Skin and subcutaneous tissue disorders: Uncommon: dry skin Rare: pruritus*, rash* Very rare: urticaria*, angioedema*, erythema multiforme* Not known: exfoliative dermatitis* Musculoskeletal and connective tissue disorders: Not known: muscular weakness* Renal and urinary disorders: Uncommon: difficulty in micturition Rare: urinary retention***Not known: renal impairment* General disorders and administration site conditions: Uncommon: fatigue, perhiperal oedema Tamsulosin 0.4mg frequency#: Nervous system disorders: Common: dizziness Uncommon: headache Rare: syncope Eye disorders: Not known: vision blurred*, Intraoperative Floppy Iris Syndrome (IFIS)**, visual impairment* Cardiac disorders: Uncommon: palpitations Not known: atrial fibrillation*, arrhythmia*, tachycardia* Vascular disorders: Uncommon: orthostatic hypotension Respiratory, thoracic and mediastinal disorders: Uncommon: rhinitis Not known: dyspnoea*, epistaxis* Gastrointestinal disorders: Uncommon: constipation, nausea, diarrhea, vomiting Skin and subcutaneous tissue disorders: Uncommon: pruritus, rash, urticaria Rare: angioedema Very Rare: Stevens-Johnson syndrome Not known: erythema multiforme*, exfoliative dermatitis* Reproductive system and breast disorders: Common: ejaculation disorders including retrograde ejaculation and ejaculation failure Very rare: priapism General disorders and administration site conditions: Uncommon: asthenia. #: The ADRs from solifenacin and tamsulosin included are the ADRs listed in the summary of product characteristics of both products. *: from post-marketing reporting. Because these spontaneously reported events are from the worldwide post-marketing experience, the frequency of events and the role of solifenacin or tamsulosin and their causation cannot be reliably determined. **: from post-marketing reporting, observed during cataract and glaucoma surgery. ***: see Special warnings and precautions for use. Long-term safety of Vesomni: The profile of undesirable effects seen with treatment up to 1 year was similar to that observed in the 12-week studies. The product is well-tolerated and no specific adverse reactions have been associated with long-term use.

Description of selected adverse reactions: For urinary retention see Special warnings and precautions for use. Older people: The therapeutic indication of Vesomni, moderate to severe storage symptoms (urgency, increased micturition frequency) and voiding symptoms associated with BPH, is a disease affecting elderly men. The clinical development of Vesomni has been performed in patients 45 to 91 years of age, with an average age of 65 years. Adverse reactions in the elderly population were similar to the younger population. Reporting of suspected adverse reactions: see below. Overdose: Overdosage with the combination of solifenacin and tamsulosin can potentially result in severe anticholinergic effects plus acute hypotension. Refer to SPC for details of treatment of overdose. Legal Category: Prescription Only Medicine (SIB). Nature and contents of container: Aluminium blister packs containing 30 tablets. Product Authorisation Number: PA1241/016/001. Marketing Authorisation holder: Astellas Pharma Co. Ltd. Further information is available from: Astellas Pharma Co. Ltd, 5 Waterside, Citywest Business Campus, Naas Road, Dublin 24. Phone: +3531 467 1555. Summary of Product Characteristics with full prescribing information available upon request. Job number: VESOM_2019_0001_IE Date of preparation of API: 24 May 2019 Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance Astellas Pharma Co. Ltd Earlsfort Terrace, IRL - Dublin 2 Tel: + 353 1 467 1555 Tel: +353 1 6764971 E-mail: Irishdrugsafety@astellas.com Fax: +353 1 6762517 Website: www.hpra.ie E-mail: medsafety@hpra.ie.

96 News the Pfizer-BioNTech vaccine on removal from the Ultra-Low Temperature (ULT) freezer prior to distribution. GS1 Ireland provided a label design for the distributor and subsequently worked very closely with the HSE and system implementation partners to advise on how to “design-in” traceability standards for the national COVID-19 vaccination programme.

2- ScanVax to capture vaccine details in one scan The next challenge was how to capture the batch details of the vaccines on receipt in the vaccination clinics across Ireland. There was

COVID-19 vaccines: Gaining efficiencies in special handling processes The COVID-19 vaccines, based on the mRNA technology, are fragile and require special handling to ensure they maintain their effectiveness. For the PfizerBioNTech vaccine, on removal from the ULT freezer to storage between +2°C and +8°C, the expiry date must change and a “use before” date and time of 120 hours needed to be assigned to the product prior to distribution. This now has been increased to 31 days. For the Moderna vaccine, the expiry date changes on arrival at the vaccination centres and requires a new label “use before” for storage between +2°C and +8°C, which is assigned on receipt into TrackVax. Consider the process for the PfizerBioNTech vaccine. There is one distributor that delivers the National Cold Chain Service (NCCS) for the entire country. All vaccines arriving in Ireland are brought to a central warehouse in Dublin. Each package or box of Pfizer-BioNTech vaccines, containing 195 vials or 1,170 doses, is marked with a 2D DataMatrix barcode as part of the requirements for the EU’s FMD regulation. The boxes are stored in freezers at the designated temperature.

To prepare the vials for distribution to vaccination sites, the vials are repackaged in smaller pack sizes with the exact number needed for these sites (e.g., nursing homes). From the distribution site, the packaged vials of vaccines are transported in refrigerated vans to more than 600 locations throughout Ireland. One of the first recommendations by the GS1 Ireland team was the design of a standardised, full box and break-pack label—for the secondary packages that contain the vaccine’s unique identifier— the GTIN, its batch/lot number, and the revised expiry date and time based on the re-packaging activity—encoded in a 2D DataMatrix barcode. The “use before” date and time information was needed for the PfizerBioNTech and Moderna vaccines as their remaining shelf life reduced once stored between +2°C and +8°C.

a backlog of vaccine data that needed to be transferred, so barcode scanning was the obvious choice. One scan can automatically capture the vaccine type, batch and expiry date details related to the COVID-19 vaccines.

By early January 2021, GS1 Ireland had developed ScanVax, an app that enables the receipt of vaccines by scanning the barcode

on the vaccine boxes. The details from the barcode are then uploaded to the national vaccine administration system. This means that vaccinators can select the correct batch when administering the vaccine, thus minimising human error and greatly reducing the time required to record the vaccine details. ScanVax has been installed on more than 1,000 PCs and is used to record receipt of vaccines and upload vaccine information to the national vaccine administration system in locations across the country.

3- TrackVax for safer medication management and more efficient vaccine reconciliation The evolving situation with the pandemic meant it was a race to get people vaccinated. The HSE COVID-19 vaccination planning teams worked intensively on the design of the purpose-built CVCs. As part of this design phase, it was agreed that a standardised vial label was required, and GS1 Ireland was asked to provide the software to print these labels. This software ultimately evolved to become TrackVax, a full track and trace software to identify, label, track and report on the COVID-19 vaccines in the vaccination centres. This proved invaluable for pharmacy staff as the CVCs were extremely busy during their peak when averaging 8 clients vaccinated per minute.

The COVID-19 vaccines are received into stock in the CVC so that a full record is available for stock management. When a vial is required by vaccinators, the staff scans the box and the required number of vials are entered. TrackVax then prints a label for each vial with the key data, including a GTIN, batch and discard time, printed and encoded in a 2D DataMatrix barcode.

“We had approximately 20,000 vaccine deliveries, 4 vaccine types and 20 complicated data fields for each vaccine type. ScanVax standardised everything and meant we could capture records both accurately and quickly. Vaccine data is now seamlessly reportable for the first time in a vaccine programme in Ireland.”

Kerry Ryder, ICT General Manager, HSE National Immunisation Office

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Figure 3: Traceability of vaccines within the CVC using TrackVax

There is also the option to print syringe labels depending on the requirements of the CVC. The syringe mode is particularly helpful when approaching the end of the day to minimise the number of open vials and avoid wastage.

The vials or syringes are given to the vaccinators in the booths. There is also the option to assign a vial to a vaccination bay.

Some sites used this option when they didn’t have as many staff since it was easier to locate a vial when needed. The vaccinators like the standardised label as they can easily read the batch information and the discard time.

When the vaccinator is finished administering the vaccine, the number of doses drawn from the vial is written on the vial label and is then returned to the pharmacy so that the vial yield can be recorded in TrackVax. When in syringe mode, the tray is returned so the yield can be recorded. Each vaccine has different levels of yield. For example, for AstraZeneca the yield is typically between 11 and 12 vaccinations. For Pfizer-BioNTech the yield is between 6 and 7.

Based on this wide range, TrackVax needed to be flexible to manage the yields.

TrackVax also allows for discarded vaccines to be accounted for. The system was designed so a discard code can be assigned. This is an important reporting requirement for the NIO in relation to vaccine usage and to detect any trends related to quality issues, or if additional training is required in sites.

The system provides a live dashboard for staff so that vaccine usage can be tracked throughout the day and oversight can be kept if a vial is close to expiration.

Reconciliation of vaccines One of the challenges for staff in the early days was the reconciliation of the vaccine when using a paper-based process. CVCs use the data from TrackVax to keep a very close track of opened vials particularly as the end of the day approaches which enables an accurate forecast of the number of additional vials that will be required for the remainder of the clinic. It is the combination of vial information or doses in open vials and remaining appointments that helps them manage this process.

TrackVax has made the vaccine reconciliation process much easier to manage since a full audit trail is available and an end-of-day report is automatically generated. This report is used to complete the vaccine reconciliation and

97 “The success of the implementation of TrackVax has demonstrated the importance of traceability, not just for the COVID-19 vaccine, but for all vaccines.

It is truly exciting times for immunisation programmes which are ever changing and TrackVax will be integral to successful rollouts in the future.”

Cliona Kiersey, Chief Pharmacist, HSE National Immunisation Office

confirm that the doses dispensed match the doses administered in the national vaccine administration system. The report also summarises the vaccine usage information and includes any discarded doses. This reporting was previously done manually by staff at the end of a busy day.

As all of the CVCs started to use TrackVax, the information related to vial yield was visible at local and national levels. The HSE can follow the yields by site and by vaccine type. And, because the vials are scanned and tracked as they are used in the CVC, the accuracy and timeliness of the data enables HSE and the individual CVC to make quick decisions.

TrackVax is giving the CVCs and HSE visibility of vaccine usage and stock management: • What are current inventory levels of vaccines?

• What are the expiry dates?

• How many boxes and how many vials by vaccine type are in stock?

• How many doses have been administered in a given timeframe?

• What is the yield per vial? Are there any discarded doses?

Consider that one large CVC was experiencing a decrease in yield for the Pfizer-BioNTech vaccine. They immediately alerted the HSE’s NIO. Using TrackVax, the team was able to check the yields for other sites and quickly identified that this decline was also happening in other CVCs. Upon closer examination, the HSE deduced very quickly that it was due to the type of syringes being used. Because the HSE had this data readily available, it immediately contacted the procurement team and arranged for the appropriate syringes to be provided to the sites to optimise the yield per vial. The data from TrackVax facilitated quick decision making.

The data wouldn’t have been available using a paper-based system, and it is estimated that about 75,000 doses were saved due to this one change.

“From a medication safety perspective, the use of Trackvax across our vaccination centres really helps to standardise our workflow, ensuring vaccines are labelled clearly with all relevant details, which is so important when delivering a programme on such a big scale.

The data from Trackvax is also informing evidence-based decisions to ensure we achieve optimum yield from vaccine vials as it allows us to act quickly if any issues arise.”

Muriel Pate, Medication Safety Specialist Pharmacist, HSE Quality and Patient Safety Directorate

Throughout the roll out of the mass vaccination effort, the GS1 Ireland team has acted as an advisor to the HSE, helping to develop and put processes in place to sustain the support model. The team has also delivered onsite training as well as online training sessions as new versions of the software were rolled out and for new staff joining the CVCs. There are over 40 CVCs in Ireland and as these sites worked at full capacity, the GS1 Ireland team was busy supporting the teams on the ground.

The feedback from the CVCs is very positive, and the traceability system is making their work easier. Reconciliation of the vials at the end of the day is a very time-consuming process when working with a manual process. The excellent data quality means that the NIO has oversight of vaccine usage and accurate stock level data.

This means vaccines can be managed closely and wastage is kept to a minimum.

“Traceability is a key part of managing the vaccine process.

The use of barcodes has been very beneficial and it is evident that while it has saved time and resources, more importantly it is giving time back to clinicians while providing accurate information for decisions. Patient safety is key and TrackVax has been a real enabler in this case.”

John Swords, National Director of Procurement, HSE

Looking forward The pandemic and urgent need for mass vaccinations helped to drive the call for standardisation in how the vaccines were identified, scanned, administered and tracked.

By “designing in” GS1 standards from the start, HSE and GS1 Ireland were able to act quickly and then monitor progress over time.

TrackVax has been operational since 3 March 2021. The software has enabled the tracking and management of over 3 million vaccine doses, as of September 2021, or nearly 50% of Ireland’s vaccination programme. TrackVax has been widely accepted across CVCs and has delivered value to the HSE through medicine safety, vaccine tracking, operational efficiency and programme integrity.

The TrackVax governance team recognises TrackVax using barcode scanning right to the point of vaccination as an important foundation for the future management of vaccines across all vaccination centres, both large and small.

The use of GS1 Traceability standards enable the tracking of vaccine type, batch and expiry date in one scan. This forms a working model for how traceability can be applied to many areas of care across the HSE. While the benefits accrue during mass vaccination sites, further investigation is required to find ways to bring these benefits to smaller sites, such as nursing homes and general practitioners to enable end-to-end vaccine tracking and efficient, safe vaccine record creation through scanning barcodes at point of care. The next step is the development of a mobile app to facilitate the tracking of vaccines in the community based on a simpler version of TrackVax.

“History tells us that pandemics can last up to four years, and Ireland is now reopening society after 18 months. In order to do this, it has been critical that we have a safe and efficient vaccination programme.

TrackVax has been instrumental in enabling a high level of quality assurance and traceability of the vaccine to every citizen. At our peak we were vaccinating 8 clients per minute, we couldn’t have done that without TrackVax.” Joan Peppard, Pharmacy Vaccination lead Dublin Mid-Leinster, HSE

Thank you GS1 Ireland would like to extend a special note of thanks to all the pharmacists who were involved in the design, testing and rollout of the ScanVax and TrackVax applications. The involvement of the pharmacists and other CVC staff was pivotal to the success of this project.

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

98

Clinical Research Facility Galway secures ¤3 million funding Some ¤3 million funding has been announced for the Clinical Research Facility Galway - a Health Research Board (HRB) centre supporting clinical trials to improve health and care.

Professor Fidelma Dunne and Professor Andrew Smyth at the Clinical Research Facility Galway

The investment is part of a ¤22 million fund from the HRB for clinical research facilities located at hospital sites and supported by universities.

The Clinical Research Facility Galway is a joint initiative of NUI Galway and Saolta University Health Care Group for the promotion of clinical research and conduct of clinical trials, bringing together clinicians, researchers and academics to focus on studies aimed at understanding diseases and translating the knowledge gained into advances in patient care.

Professor Andrew Smyth, Director of the HRB Clinical Research Facility Galway and Consultant Nephrologist at Galway University Hospitals, said, "The HRBCFRG aims to improve patient care and population health through the delivery of clinical trials by providing the necessary infrastructure, physical space, facilities, expertise, specialist training and culture.

“This infrastructure funding support from the HRB puts us on the map globally in terms of the ability to manage and execute all stages of clinical trials from conception to conclusion.

“At the HRB Clinical Research Facility Galway we have the end-to-end services to guide breakthrough research including first-in-human trials, medical technology/devices, pharmaceuticals, cancer trials and much more. Our portfolio is one of the most diverse nationally, and we have both the clinical expertise and clinical trial experience to grow our own trials from the ground up.

“The HRB infrastructure funding makes this possible and is essential for growth and expansion of our clinical trials.”

The overall HRB funding package will keep Ireland at the forefront of clinical research and trials internationally while also increasing opportunities for patient participation and benefit.

Professor Fidelma Dunne, Associate Director of the HRB-CRFG and Consultant Endocrinologist with Saolta University Health Care Group,

said, “With the support of the HRB we have been able to take trials from seed stage, through discovery and design through to all stages of trial execution.

In the case of my research on gestational diabetes, this support allowed me to conceptualise and trial innovative therapies for women with this condition, as all of the necessary supports were available in Galway.”

Lipertance Launched in Ireland Servier Laboratories (Ireland) Ltd is delighted to announce that Lipertance, the combination of atorvastatin, perindopril and amlodipine1, will be available for prescription from November 2021 and is listed as a PCRS reimbursable product.

Lipertance® is the first Statin + ACEi + Calcium Channel blocker combination available in Ireland2.

Servier continue to add to their range of Single Pill Combination solutions for the management of patients with cardiovascular disease3. The arrival of Lipertance, in particular, offers greater intensification of blood pressure (BP) control for patients on a statin1. It follows the recent launch (Feb 2021) of , Lipercosyl the statin/ACEi combination of atorvastatin and perindopril4.

Like Lipercosyl®, Lipertance® controls high cholesterol and hypertension in unison1, helping patients with these cardiovascular risk factors to meet their target blood pressure5 and low-density lipoprotein cholesterol (LDL-C)6 and thereby helping to avoid cardiovascular outcomes1.

Atorvastatin has been shown to reduce concentrations of LDL-C by up to 49%7. Perindopril and amlodipine reduce BP by up to 33.7/17.1mmHg helping patients reach lower targets8. Perindopril and amlodipine’s antihypertensive effect is sustained for at least 24 hours and atorvastatin is a longacting statin, ensuring true 24hr control from a single daily dose1, 9.

Furthermore, it has been demonstrated in the large ASCOT study (n=19,259 patients) that

a combination of statin with amlodipine +/- perindopril yields a 53% relative risk reduction in fatal coronary events and non-fatal MI p<0.00011.

Should you require any further information, please contact Servier on 01 6638110, or refer to the full Summary of Product Characteristics on www.medicines.ie

Prescribing the 3 agents in a Single-Pill Combination offers patients better efficacy, tolerability and adherence10-13. Lipertance is taken as one tablet daily in the morning before breakfast.1

References on request

Lipertance® is indicated for the treatment of essential hypertension and/or stable coronary artery disease, in association with primary hypercholesterolaemia or mixed hyperlipidaemia, as substitution therapy in adult patients adequately controlled with atorvastatin, perindopril and amlodipine given concurrently at the same dose level as in the combination.1

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Toujeo® is available in two pre-filled insulin devices allowing you to choose the most suitable device for your patients

Toujeo® DoubleStar™ holds more units per pen than any other basal insulin pen on the market1-4 Shared features with Toujeo® SoloStar • Pen size • 5-second hold time5,6 • 42-day shelf life after first use1 • Same technical platform *Toujeo® DoubleStar™ is recommended for patients requiring at least 20 units of basal insulin per day1

References: 1. Toujeo® Summary of Product Characteristics.

2. Lantus® Summary of Product Characteristics.

3. Tresiba® Summary of Product Characteristics.

4. Levemir® Summary of Product Characteristics.

5. Toujeo® DoubleStarTM Package leaflet: information for the user.

6. Toujeo® SoloStar® Package leaflet: information for the user.

Prescribing Information: Toujeo® (insulin glargine 300 units/ml) Please refer to Summary of Product Characteristics (SmPC) before prescribing.

Presentation: Toujeo SoloStar and DoubleStar pre-filled pens. Each ml contains 300 units of insulin glargine. SoloStar pen contains 1.5ml (450 units) of solution for injection. DoubleStar pen contains 3ml (900 units) of solution for injection.

Indication: Treatment of diabetes mellitus in adults, adolescents and children from the age of 6 years. Dosage and Administration: Toujeo is administered subcutaneously, by injection into the abdominal wall, the deltoid or the thigh, once daily, at any time of the day, preferably at the same time every day. Injection sites must be rotated within a given injection area from one injection to the next in order to reduce the risk of lipodystrophy and cutaneous amyloidosis. The dose regimen (dose and timing) should be adjusted according to individual response. Do not administer intravenously. In type 1 diabetes mellitus, Toujeo must be combined with short-/ rapid-acting insulin to cover mealtime insulin requirements. In patients with type 2 diabetes mellitus, recommended daily starting dose is 0.2 units/kg followed by individual dose adjustments. Toujeo can also be given together with other anti-hyperglycaemic medicinal products. Switch between insulin glargine 100 units/ml and Toujeo: Insulin glargine 100 units/ml and Toujeo are not bioequivalent and are not directly interchangeable. When switching from insulin glargine 100 units/ml to Toujeo, this can be done on a unit to unit basis, but a higher Toujeo dose (approximately 10-18%) may be needed to achieve target ranges for plasma glucose levels. When switching from Toujeo to insulin glargine 100 units/ml, the dose should be reduced (approximately by 20%). Switching from other basal insulins to Toujeo: A change of dose and/or timing of the basal insulin and concomitant anti hyperglycaemic treatment may be required. Dose adjustments may also be required if the patient’s weight or lifestyle changes, the timing of insulin dose is changed or other circumstances arise that increase susceptibility to hypo- or hyperglycaemia. Toujeo must not be mixed or diluted with any other insulin or other medicinal products. Close metabolic monitoring is recommended during a switch and in the initial weeks thereafter. SoloStar 1-80 units per single injection in steps of 1 unit and DoubleStar 2-160 units in steps of 2 units.

When changing from Toujeo SoloStar to Toujeo DoubleStar, if the patient’s previous dose was an odd number then the dose must be increased or decreased by 1 unit. Toujeo DoubleStar prefilled pen is recommended for patients requiring at least 20 units per day. Special Populations: Insulin requirements may be diminished in the elderly or patients with renal or hepatic impairment.

Paediatric: When switching basal insulin to Toujeo, dose reduction of basal and bolus insulin needs to be considered on an individual basis, in order to minimise the risk of hypoglycaemia. The safety and efficacy of Toujeo in children and adolescents below 6 years of age have not been established. Contraindications: Hypersensitivity to insulin glargine or any excipients. Precautions and Warnings: Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Toujeo is not the insulin of choice for treatment of diabetic ketoacidosis. Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites

References: 1. Toujeo® Summary of Product Characteristics.

Date of preparation: August 2020 | MAT-IE-2000823 (v1.0)

with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may be considered. Hypoglycaemia: In case of insufficient glucose control or a tendency to hyper/hypoglycaemic episodes, the patient’s adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered. Particular caution should be exercised, and intensified blood glucose monitoring is advisable for patients in whom hypoglycaemic episodes might be of clinical relevance and in those where dose adjustments may be required. Warning signs of hypoglycaemia may be changed, less pronounced or absent in certain risk groups, potentially resulting in severe hypoglycaemia and loss of consciousness. Risk groups include patients in whom glycaemic control is markedly improved, hypoglycaemia develops gradually, an autonomic neuropathy is present, or who are elderly. The prolonged effect of subcutaneous insulin glargine may delay recovery from hypoglycaemia. Intercurrent illness: Requires intensified metabolic monitoring and often it is necessary to adjust the insulin dose. Insulin antibodies: administration may cause insulin antibodies to form. Use with pioglitazone: Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.

Medication errors: Insulin labels must always be checked before each injection to avoid errors between Toujeo and other insulins.

Patients must be instructed to never use a syringe to remove Toujeo from the SoloStar or DoubleStar pre-filled pen, A new sterile needle must be attached before each injection. Needles must not be re-used. Pregnancy and lactation: There is no data from exposed pregnancies in controlled clinical trials. However, there is a large amount of data on use of insulin glargine 100 units/ ml in pregnant women indicating no specific adverse effects on pregnancy and no specific malformative nor feto/neonatal toxicity.

The use of Toujeo may be considered during pregnancy, if clinically needed. Careful monitoring of glucose control is essential.

It is unknown if insulin glargine is excreted in breast milk. Interactions: Substances that affect glucose metabolism may require adjustment of insulin glargine. Adverse Reactions: Very common: Hypoglycaemia. Prolonged or severe hypoglycaemia may be life-threatening. Common: Lipohypertrophy, injection site reactions, including redness, pain, itching, hives, swelling, or inflammation.

Legal Category: POM. Marketing Authorisation Number: SoloStar 3 Pen pack: EU/1/00/133/034, DoubleStar EU/1/00/133/038.

Marketing Authorisation Holder: Sanofi Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany. Further information is available from: Medical Information, Sanofi 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact IEmedinfo@sanofi. com. Date of preparation: July 2020.

Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie; email: medsafety@hpra.ie Adverse events should also be reported to Sanofi Ireland Ltd. Tel: 01 403 5600.

Alternatively, send via email to IEPharmacovigilance@sanofi.com

100 EASD News New Diabetes Comprehensive Consensus Report

Dr Anne L. Peters, Professor of Clinical Medicine at Keck School of Medicine, University of Southern California

future technologies including beta-cell replacement and immunotherapy. Front and centre of the report is the need to address all these factors from the patient’s perspective.

Some important highlights include an algorithm to accurately diagnose T1D, since no single factor in isolation can accurately confirm the condition.

Furthermore, some 40% of individuals diagnosed with T1D as adults are initially misdiagnosed as having T2D, partly because T2D is becoming more common in younger adults due to the rising rates of obesity and physical inactivity.

A new comprehensive Consensus Report to manage type 1 diabetes (T1D) has been launched by two leading diabetes societies – the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA). The final report, launched at the online annual meeting of EASD, is also published in Diabetologia (the official journal of EASD) and Diabetes Care (the official journal of ADA).

EASD and ADA decided together that a wide-ranging document to capture best practice for T1D was needed after their successful collaboration to provide similar guidance for people with type 2 diabetes (T2D) back in 2019.

Although people with T1D represent 5-10% of all people with diabetes, this still amounts to over 25 million people worldwide.

“This new consensus statement not only brings in the advances that have been made in treating type 1 diabetes in recent years, but also covers other vital areas from a patient perspective – such as the psychosocial consequences of living with the condition, that can sometimes be neglected,” explains co-author Dr Anne L. Peters, Professor of Clinical Medicine at Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. While various other guidance has been published in the past relating to people living with T1D, a clear consensus document has been lacking, and recommendations for people with T1D are often confused with or ‘bundled in’ with those for people who have T2D.

To get a broad range of perspectives, the writing team for these new guidelines included 14 experts, with half based in the USA and half in Europe, across a range of healthcare disciplines.

The areas covered in the report are: diagnosis, goals of therapy and blood sugar targets, schedule of care, diabetes self-management education and additional behavioural considerations, glucose monitoring, insulin therapy, managing hypoglycaemia, psychosocial care, diabetic ketoacidosis, pancreas and islet cell transplantation, additional therapies, special populations (including pregnant women, older adults, and inpatient management), and developing/

Psychosocial health and living with T1D is also specifically addressed, since between 20% and 40% of people with type 1 diabetes experience diabetesrelated emotional distress (including 15% with depression).

The authors together conclude: “There are still huge gaps in our knowledge about how to prevent, diagnose and treat type 1 diabetes. We are also aware that many people with type 1 diabetes experience inequalities in treatment. We hope that this report will promote better higher quality research to determine optimal care, while helping to share best clinical practice so that all individuals with type 1 diabetes have access to the care they need.”

Risk of Stroke increases with Insulin Resistance A study of more than 100,000 people with type 2 diabetes (T2D), presented at the annual meeting of the European Association for the Study of Diabetes (EASD), held online this year, found that insulin resistance is associated with stroke.

The higher the insulin resistance, the greater the risk of stroke, the research, from Dr Alexander Zabala and colleagues at the Karolinska Institute and researchers at Gothenburg University and the National Diabetes Registry in Sweden, found.

Insulin resistance – when the body’s cells don’t respond properly to insulin and can’t easily take up glucose from blood – is a key feature of T2D and levels vary from patient to patient.

Dr Zabala used estimated glucose disposal rate (eGDR) as a measure of insulin resistance. eGDR has previously been shown to be a good proxy for insulin resistance and is calculated using a formula that factors in a patient’s waist circumference, HbA1c (average blood sugar level) and whether they have high blood pressure.

Health records were used to calculate the eGDR of 104,697 T2D patients in Sweden. The participants had an average age of 63 and 44.5% were female.

They were followed up for an average of 5.6 years, during which 4,201 (4%) had a stroke.

Analysis revealed that the higher a person’s insulin resistance, the greater their chance of having a stroke. Those with the lowest insulin resistance (the highest eGDR) were 40% less likely to have a stroke than those with the highest insulin resistance.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Age, cholesterol levels, smoking, heart conditions and other traditional risk factors for stroke were all adjusted for.

The study also found that higher insulin resistance was linked to a higher risk of death after a stroke.

Those with the lowest resistance were 28% less likely to die during the follow-up period than those with the most severe insulin resistance.

Further analysis showed high blood pressure to be more strongly linked to stroke than waist circumference or HbA1c.

EASD News 101 Management of Serious Diabetic Foot Ulcers

Reducing Risk of Type 2 Diabetes Also presented at EASD, was research which suggests that the widely used osteoporosis drug alendronate reduces the risk of type 2 diabetes.

It has been known for decades that patients with diabetes have a higher risk of fractures – suggesting a link between the blood sugar regulation and bone quality. More recently, animal studies have suggested that the modification of bone cells by osteoporosis drugs affects glucose regulation.

“Thus, we speculated that the treatment of osteoporosis might impact on the risk of type 2 diabetes,” says Dr Rikke Viggers, of Aalborg University Hospital, Aalborg, Denmark.

To find out more, Dr Viggers and colleagues compared diabetes rates among those prescribed the osteoporosis drug alendronate with those not given the treatment.

The first-line treatment for osteoporosis, alendronate and other bisphosphonates help strengthen bones and reduce the risk of a fracture.

Hospital records were used to identify all individuals with type 2 diabetes in Denmark between 2008 and 2018. Each diabetes patient was matched by age and sex with three healthy people from the population.

Prescription records were used to determine whether the participants had ever been prescribed alendronate.

Analysis revealed that those who had taken alendronate were 34 per cent less likely to have been diagnosed with type 2 diabetes than those who had never taken the drug.

Factors such as smoking, alcohol use, obesity, income and marital status were included in the analysis.

Taking alendronate for at least eight years could potentially reduce the risk by more than half (53 per cent) compared to those who have never used alendronate.

Further analysis suggested a dose-dependent effect i.e. the longer a person took the drug, the lower their odds of developing the condition.

New research presented at EASD has revealed how Belgium’s efforts to maintain a diabetic foot care programme during the Covid-19 pandemic can offer valuable lessons to the rest of the world.

“Thanks to the great efforts of diabetic foot clinics, continued availability of diabetic foot ulcer services during lockdown, although in a limited capacity, were really helpful, and may be the reason why we didn’t see late presentation and the impact on the severity of ulcers was limited to slightly larger wounds”, says lead author Dr An-Sofie Vanherwegen from Sciensano, Brussels, Belgium. “Our findings will hopefully guide diabetic foot clinics in serving their patients using innovative strategies, such as telemedicine, during the current, and eventual future, public health crises.”

It is estimated that around a quarter of all people living with diabetes worldwide will develop a foot ulcer in their lifetime.1 The ulcers develop as diabetes damages the nerves and blood supply to the feet. Without timely treatment, these ulcers are hard to heal and form the leading cause of lower limb amputations in Western countries.2 In 2005, a national diabetic foot care programme (IQED-Foot) was established in Belgium,3 that has resulted in 34 multidisciplinary diabetic foot clinics recognised by the Belgian Ministry of Health for the treatment of diabetic ulcers.

Since then, a clear decline in the lower-limb amputation rate has been noted in Belgium.4 A national lockdown in Belgium between March 14th and May 3rd 2020, placed restrictions on free movement and only urgent care was provided in hospitals.

However, diabetic foot clinics were advised by professional associations to consider all active diabetic foot problems as urgent.

To gauge the impact of the pandemic on the presentation rate and severity of diabetic foot ulcers in these clinics, researchers distributed a survey to the recognised clinics across Belgium asking about the measures they had taken during and after the lockdown to maintain their activities. A total of 24 diabetic foot clinics participated in the survey.

During the lockdown, one clinic closed, but the 23 others remained open for urgent care, whilst applying Covid-19 measures almost three-quarters (71%) of clinics selected patients based on urgency and high risk for ulceration; whilst 79% reported partially switching to remote consultations; 13 clinics (54%) reduced the frequency of consultations for patients; and half spread out patient appointments during the day to allow for physical distancing.

Between January 1st and September 30th, 2020, patient and ulcer characteristics were recorded by 22 foot clinics for 887 consecutive patients presenting with new moderate to severe diabetic foot ulcers a big enough sample for it to be representative of the picture across Belgium.

Patients were assigned to three groups based on the date of first contact with the clinic pre-lockdown (322 patients), during lockdown (93), and post-

lockdown (472) and compared to data from the same time period of the IQED-Foot data collection in 2018. No differences in patient characteristics (eg, age, gender, medical history, diabetes type and duration) were noted between the groups.

The study found that compared to the same time period in 2018, the average weekly presentation rate of patients during lockdown was substantially reduced (by almost 60% from 1.4 patients per week in 2018 to 0.6 patients per week in lockdown). However, there was no change in average patientreported delay in presentation, although patients during and after lockdown tended to present with slightly larger ulcer. No significant differences in depth, infection or loss of protective sensation were detected between the three groups.

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

102 EASD News Type 2 Diabetes Remission and Weight Loss Type 2 diabetes isn’t caused by being obese – it’s triggered by being too heavy for your body, whatever your BMI Professor Roy Taylor, of Newcastle University, Newcastle, UK

New research presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) has found that contrary to the perceived wisdom, people of normal weight with type 2 diabetes (T2D) can reverse the condition through substantial weight loss.

Eight of the 12 participants achieved remission after losing 10-15% of their body weight, despite having a BMI that fell in the normal weight range. Levels of fat in the liver and pancreas fell substantially and the activity of the insulin-producing cells in the pancreas was restored.

The finding clearly demonstrates weight loss can be beneficial in type 2 diabetes, even in those who are of normal weight, says Professor Roy Taylor, of Newcastle University, Newcastle, UK, the principal investigator on the trial.

It also supports the idea that we each have a “personal fat threshold” – a level of body fat we can cope with – and if we go above it, we will develop T2D, even if we are still of normal weight.

Professor Taylor explains, “Our previous research has shown that weight loss of 10-15% can achieve remission in people with type 2 diabetes who are overweight or obese.

“Doctors tend to assume, however, that type 2 diabetes has a different cause in those who aren’t overweight. This means that, unlike those who are overweight, those who are of normal weight aren’t usually advised to lose weight before being given diabetes drugs and insulin.

“Instead, there’s a tendency to start them on insulin and other medication at a much earlier stage.

“What we’ve shown is that if those of normal weight lose 1015% of their weight, they have a very good chance of getting rid of their diabetes.

“This should be a wake-up call to doctors and, with one in ten of the 4.5 million people with type 2 diabetes in the UK of normal weight at diagnosis, there is no time to be lost in getting the message across.”

“As a rule of thumb, your waist size should be the same now as when you were 21. If you can’t get into the same size trousers now, you are carrying too much fat and therefore at risk of developing type 2 diabetes, even if you aren’t overweight.”

Previously, the landmark Diabetes Remission Clinical Trial (DiRECT), from Glasgow and Newcastle universities, showed that an intensive weight loss programme delivered by GPs can put T2D into remission in people who are overweight.

The latest results are from the Reversal of Type 2 Diabetes upon Normalisation of Energy Intake in the Non-obese (ReTUNE) trial, which is looking at whether weight loss can also reverse the condition in people of normal weight.

Twelve men and women who had T2D and were of normal weight (average BMI of 24.5) followed a weight loss programme in which they consumed 800 calories a day (from low calorie soups and shakes) for two weeks, followed by four to six weeks in which they received support to maintain their

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

new weight. They completed up to three rounds of this diet/weight maintenance cycle until they had lost 10-15% of their body weight.

The participants underwent a range of tests at the start of the study and after each round of dieting and weight maintenance.

Their results at the end of the study were compared to those of a group of controls - people without diabetes who were matched for age, sex and BMI. Average weight fell by 8.2kg, from 69kg to 61.8kg – a reduction of 11.9%. Total body fat fell from 33.1% to 27.4%. This compares to a figure of 25.4% for the controls.

Scans showed that the average amount of fat in the liver fell from 4.4% - more than twice as high as in the controls – to 1.4%.

Fat in the pancreas fell from an average of 5.1% to 4.5%. Average levels of triglycerides (plasma TG, a measure of fat metabolism efficiency) fell dramatically from 1.6mmol/L to 1.0mmol/L – on a par with the controls.

In eight of the 12 participants (67%), diabetes went into remission, a similar proportion to previous studies involving overweight and obese participants. Remission was defined as HbA1c (average blood sugar level) of less than 48mmol/ mol and off all medication.

Professor Taylor says, “These results, while preliminary, demonstrate very clearly that diabetes is not caused by obesity but by being too heavy for your own body. It’s due to having too much fat in your liver and pancreas, whatever your BMI. “In the liver, this excess fat prevents insulin from working normally. In the pancreas, it causes the beta cells to stop producing insulin.”

Professor Taylor adds, “As a rule of thumb, your waist size should be the same now as when you were 21. If you can’t get into the same size trousers now, you are carrying too much fat and therefore at risk of developing type 2 diabetes, even if you aren’t overweight.”

EASD News 103

Men at Greater Risk Following Surgery Dr Hannes Beiglböck from the Medical University of Vienna in Austria

Female Diabetics Less Likely to receive Cardiovascular Prevention Giulia Ferrannini, MD, from the Karolinska Institutet, Stockholm, Sweden

Men who undergo bariatric (obesity) surgery are five times as likely to die within 30-days of the procedure compared to women, and their long-term mortality is almost three times higher, according to an analysis of national data from Austria spanning 10 years.

The findings, presented at Annual Meeting of the European Association for the Study of Diabetes indicate that men tend to be older and have higher rates of comorbidities (adverse health conditions) such as cardiovascular disease and type 2 diabetes at the time of surgery, highlighting a pressing need to educate men about the importance of treating obesity earlier, before they develop potentially life-threatening comorbidities.

“Surgical procedures are some of the most successful ways to help people with extreme obesity to lose weight, but they can come with complications”, says lead author Dr Hannes Beiglböck from the Medical University of Vienna in Austria. “Although the absolute risk of dying after bariatric surgery is low, the findings of our large nationwide study highlight a substantially increased mortality risk among men compared to women. Women seem more willing to look at surgical weight loss earlier in life, whereas men tend to wait until they have more comorbidities.”

To find out more, researchers retrospectively analysed medical health claim data from the Austrian state insurance (the Österreichische Gesundheitskasse) that covers around 98% of the population (around 9 million Austrians in 2018). In total, 19,901 patients (14,681 women, average age 41 years; 5,220 men, average age 42 years) who had undergone bariatric surgery (ie, sleeve gastrectomy, gastric bypass, biliopancreatic diversion, or gastric banding) between January 2010 and December 2018 were included in the analyses and followed for an average of 5 years (107,806 patient years of observation). Researchers analysed sex-specific differences in comorbidities associated with obesity (ie, type 2 diabetes, cardiovascular diseases, psychiatric disorders, and cancers) in patients who died.

Between January 2010 and April 2020, less than 2% (367/19,901; 176 men and 191 women) of bariatric surgery patients died.

Nevertheless, overall postoperative mortality rates (per year of observation) were almost three times higher among men than women (0.64% vs 0.24%) although deaths were rare in absolute terms; whilst 30-day mortality was five-fold higher in men compared to women (25 deaths, 0.5% vs 12 deaths, 0.1%).

Among those who died, cardiovascular diseases (84% of men, 80% of women) and psychiatric disorders (51% of men, 58% of women) were the most common comorbidities.

Type 2 diabetes was more common in men than women who died (43% vs 33%), and cancers were more common in women than men (41% vs 30%).

Women with type 2 diabetes and cardiovascular disease (CVD), or at high risk of developing CVD, are less likely to reach recommended treatment targets than men, according to an international study involving almost 10,000 patients with type 2 diabetes. Nevertheless, women were less likely to experience adverse CVD outcomes apart from stroke.

“Cardiovascular disease is the leading killer of women, but it has never been more preventable and treatable. The reasons why women are not receiving the same standard of treatment as men are complex and require further investigation so that women with type 2 diabetes can be treated more effectively,” says lead author Giulia Ferrannini, MD, from the Karolinska Institutet, Stockholm, Sweden.

Previous studies have suggested that type 2 diabetes is associated with a higher risk of fatal coronary heart disease, stroke and death in women than men.1 To find out more, researchers investigated whether there are gender differences in risk factor management and outcomes of patients with type 2 diabetes, who had either a previous cardiovascular event or cardiovascular risk factors.

They analysed data from 9,901 adults (46%, 4,589 women; average age 66 years) taking part in the REWIND trial a multicentre, randomised, placebo-controlled trial in 24 countries involving adults with type 2 diabetes with a wide range of cardiovascular risk2 and followed for an average of 5.4 years. Significantly fewer women than men had a history of CVD (20% vs 41%).

The researchers analysed use of cardioprotective therapies and the achievement of guidelinerecommended treatment targets at the start of the study and after two years. They also analysed the risk of individual cardiovascular outcomes including fatal/nonfatal stroke, fatal/nonfatal heart attack, cardiovascular death, death from any cause, and severe heart failure, after adjusting for several factors that could have influenced the results (including age, lipid levels, and blood pressure.

Although the majority of women and men met treatment targets for blood pressure and lowdensity lipoprotein (LDL, or bad) cholesterol at the start of the study, women were less likely to receive recommended medications, like ACE inhibitors or angiotensin receptor blockers (ARBs) for blood pressure (80% vs 83%), and statins for cholesterol-lowering (73% vs 81%). Over 2 years follow-up, women remained less likely than men to achieve LDL cholesterol treatment goals, regardless of whether they had previously had a cardiovascular event.

Nevertheless, in the REWIND trial, women were less likely than men to experience adverse cardiovascular outcomes except stroke, including a 46% reduced risk of heart attack and death from any cause and a 38% lower risk of being hospitalised for heart failure.

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

104 EASD News Reducing Dementia Risk in Type 2 Diabetics of albuminuria (a sign of kidney damage) appeared to be the strongest risk reducers.

The study is the first to investigate the links between such a broad range of risk factors and the risk of dementia, and presence of cognitive dysfunction and structural brain abnormalities in type 2 diabetes.

People with type 2 diabetes have an increased risk of dementia, but lifestyle changes such as stopping smoking and following a healthy diet, together with adherence to treatment targets such as blood sugar control, may be able to lower that excess risk, according to new research.

guideline-recommended target levels (eg, not smoking, a healthy weight, and recommended levels of blood sugar and blood pressure), compared to controls without diabetes—with a 20% lower dementia risk for each additional risk factor within the target range.

By analysing brain scans and medical information from nearly 88,000 volunteers (over 10,000 with type 2 diabetes and more than 77,000 controls, average age 57 years) in the UK Biobank database over an average of 9 years, researchers found that the risk of dementia was progressively lower in individuals with type 2 diabetes who had a higher number of risk factors within

Additionally, differences in cognitive performance and structural brain abnormalities were also progressively smaller with greater adherence to these targets. The results were replicated in the Maastricht Study, an independent population-based cohort from the Netherlands.

Maintaining recommended levels of blood sugar, being a non-smoker, and the absence

“Our findings support current risk factor treatment strategies and making lifestyle changes ”, says co-lead lead author Dr April van Gennip from Maastricht University Medical Centre in the Netherlands. “These risk factors don’t just have an impact on the risk of developing dementia—they also have an impact on brain structure and current levels of cognitive function. Moreover, they are modifiable, making them important prevention targets.”

Type 2 diabetes is not only associated with an increased risk of dementia, but also a greater risk of cognitive dysfunction and structural changes in the brain that are important risk factors for dementia. This progressive disease can start to develop 15 to 20 years before any symptoms appear, so identifying factors that might prevent the onset of dementia are important. However, the extent to which taking steps to modify risk factors in type 2 diabetes can help reduce the risk of cognitive decline is unclear.

To provide more evidence, researchers examined the incidence of dementia, and presence of cognitive dysfunction (lower performance in tasks that evaluate processing speed, memory, and the ability to control behaviour, known as executive function) and structural brain abnormalities (ie, white matter hyperintensities and total brain volume). They looked at whether these associations differed according to the number of risk factors on target (ie, not smoking, and guideline-recommended levels of blood sugar, blood pressure, body mass index, albuminuria, physical activity, and diet). The researchers adjusted the results to account for confounding factors such as age, sex, and educational attainment.

After an average follow-up of 9 years, 147 (1.4%) individuals with diabetes and 412 (0.5%) controls developed dementia.

The researchers found that when individuals with diabetes had 5 to 7 risk factors within the recommended target range, the excess risk of dementia associated with type 2 diabetes was substantially lower. Similarly, differences in processing speed, executive function, and brain volumes were progressively smaller for a higher number of risk factors on target.

Improving Blood Sugar Control New research presented at EASD, suggests that consuming a very low calorie whey protein microgel shot 15 minutes before a meal reduces postmeal blood sugar spikes and improves the body’s insulin response (which clears glucose in the blood) in people with type 2 diabetes.

Whey is one of the main proteins found in dairy products, and is known to increase the production of a gut glucagon-like peptide (GLP-1), a hormone that triggers the production of insulin, that in turn reduces the blood glucose rise after meals. However, its routine use as a natural dietary supplement has been limited by the need for a relatively high protein dose with a high caloric content, and the requirement to take it 30-60 minutes before a meal.

Now researchers have developed new ‘micelle’ technology that allows whey protein to be more rapidly available for the body so it can be taken at a lower dose (10g, 40 kcal) just 15 minutes before a meal.

The study included 26 people (14 women, average age 62 years) with well-controlled type 2 diabetes, some of whom were taking metformin (an oral diabetes medication). The participants were randomised to receive either the new low dose whey protein microgel shot (10g, 40 kcal) in 125ml of water or placebo (125ml of water), followed 15 minutes later by a pizza meal (622 kcal, 29g protein, 22.6 g fat, 72.6 g carbohydrates)—designed to produce an adequate post-meal glucose spike.

Blood samples were taken 15 minutes before the meal, when the whey protein or placebo drinks were consumed, and at regular intervals over 4 hours after the meal.

One week after their initial study visit, the participants were assigned to repeat the trial using the alternate treatment (either the whey protein microgel shot or placebo). The crossover design of the trial also means that the study was statistically well powered despite the small number of participants.

The researchers found that during the 2-hour post-meal period, glucose levels were reduced by 22% in the whey protein group compared with placebo, with a uniform reduction during late phases (between 2 and 4 hours after the meal). Additionally, both insulin response and GLP-1 responses were significantly higher (by 61% at 1 hour, and 66% at 2 hours, respectively) in the whey protein group. However, responses for both peptide-YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP) that also stimulate insulin production were similar between the whey protein shot and placebo. There were no adverse events in this study.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

News 105 HRB grant to Improve Care for Psychotic Disorders An RCSI-led PhD consortium is among those to be awarded funding as part of an investment of ¤4.5 million by the Health Research Board (HRB) under the Collaborative Doctoral Awards (CDA) 2021.

RCSI University of Medicine and Health Sciences will lead one of the three expert teams who will each receive ¤1.5 million under the scheme. The award will provide structured training for up to five PhD candidates and will fund a research programme on health and care in psychotic disorders.

The RCSI consortium, PSychosis Ireland Structured Training and Research programme (PSI-STAR) is led by Professor David Cotter with co-leads Professor Mary Cannon, RCSI, and Professor Agnes Higgins, TCD and with PPI lead, Dr Mike Watts of GROW, a community-based mental health support organisation.

PSI-STAR is a collaboration with clinicians and researchers from Maynooth University, Queens University, NUI Galway, UCD and UCC. Collaborators included HSE and Mental Health Commission partners but most critically a deep representation from Irish Patient and Family Advocacy groups including SHINE, Mental Health Reform, Mental Health Engagement and Recovery, Irish Advocacy Network and Spunout, The PSI-STAR will develop an

Professor David Cotter, Professor of Psychiatry, RCSI

all-Ireland integrated network of clinicians and researchers from the disciplines of psychiatry, nursing, social work, sociology and psychology, as well as policymakers, who will foster, support and implement findings of clinically-oriented research into psychosis care in Ireland.

“Psychotic disorders such as schizophrenia and bipolar disorder occur in about three in one hundred people. They usually start in adolescence or young adulthood and can have a devastating impact on a young person's education, family and social relationships and career,” said Professor David Cotter, Professor of Molecular Psychiatry at RCSI, Consultant Psychiatrist at Beaumont Hospital, Dublin and investigator at FutureNeuro, the SFI research centre for chronic and rare neurological diseases.

“It is critical that people are diagnosed in the early stages of psychosis, or even just before it begins, so that the best treatments and supports can be offered as soon as possible. With funding from the HRB, I am looking forward to the training and research outcomes from the PSI-STAR programme that have the potential to drive

early interventions that will potentially aid the recovery of people with psychosis.”

The PSI-STAR programme encompasses stigma reduction, improving physical health in people with psychotic disorders and empowering recovery among those admitted to hospital. It will will have extensive public, patient and family involvement, including an academic with lived experience of psychosis, to firmly embed Patient, Public and Carer Involvement (PPI) in this research.

Professor Fergal O'Brien, RCSI Deputy Vice Chancellor for Research and Innovation, said, “At RCSI, we focus on clinical and patient-centred research that address health challenges in

Ireland and internationally. The PSI-STAR programme exemplifies how world-class research can be applied in clinical settings so that those working in patientfacing roles can make meaningful early interventions to improve the lives of people with disorders such as schizophrenia and bipolar disorder.”

According to Dr Mairead O'Driscoll, Chief Executive at the HRB: “This HRB funding will equip a new generation of health and social care researchers and professionals to ensure research done in academic and clinical settings is translated into better care. This will improve the lives of people and their loved ones affected by these difficult diagnoses.”

RCSI and Locate Bio win KTI Impact Award RCSI University of Medicine and Health Sciences and Locate Bio were announced as winners of the 2021 Knowledge Transfer Ireland (KTI) Commercialisation Impact Award at the 6th annual KTI Impact Awards.

RCSI was one of only three winners to be recognised at the KTI awards, which celebrate the work of the Higher Education Innovation Offices around the country, and their role in helping transform academic research into commercial impact. KTI supports businesses to increase their competitiveness through innovation with third level research.

KTI presented the Commercialisation Impact Award in recognition of the successful licensing of three bone and cartilage regenerative technologies from Professor

Pictured at the 6th Annual Knowledge Transfer Ireland Impact Awards are (L) Alison Campbell, KTI Director, and (R) Richard Curran, Impact Awards MC

Fergal O’Brien’s research lab to Locate Bio, an innovative orthobiologics company, in 2020.

The technologies have since been granted FDA breakthrough device designation, a key milestone which will simplify its regulatory pathway.

The judges were particularly impressed by the level of support provided from the Innovation Office at RCSI in what was an unusual transfer of intellectual property (IP). Locate Bio’s use of the IP has been pivotal to recent success including the closing of a ¤12M funding round.

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

106 Diabetes

Transforming Diabetes Care in Pregnancy With Ciara Coveney Advanced Midwife Practitioner in Diabetes in Pregnancy in the National Maternity Hospital, Holles Street Dublin

A new service from The National Maternity Hospital eliminates the need for gestational diabetes patients to come to the hospital during Covid-19 and beyond.

Gestational diabetes patients, who previously had to come to the hospital every three to four weeks for the duration of their pregnancy on top of their antenatal care can now receive the care they need in the comfort of their own homes following the introduction of Gestational Diabetes Virtual Care.

With the onset of Covid-19, the hospital’s diabetes in pregnancy service needed to adapt and innovate clinical practice for women diagnosed with gestational diabetes mellitus (GDM). Women traditionally were brought into a midwifery led clinic for education, venous blood sampling and self-monitoring of blood glucose review.

Ciara Coveney, Advanced Midwife Practitioner at the hospital came together with her midwifery colleagues Hannah Rooney and Sally Byrne with the aim of providing a comprehensive midwifery led episode of care for GDM management on a virtual

platform, so that they could reduce the numbers of women attending the hospital in person, while maintaining their care standards and keep satisfactory outcomes for the GDM cohort. This innovation was supported and delivered with dietetics and the wider multi-disciplinary team network.

Speaking about the initiative, Ciara Coveney said, “This innovation provides significant cost saving to the hospital and also to the patient, whilst keeping women safe by providing their care remotely closer to the home. This digital innovation is the first of its kind and scale in diabetes and pregnancy in Ireland.

We hope it will transform care standards for women.”

The service has now been entirely transformed into a virtual telehealth service from the point of diagnosis, treatment and through to discharge. From diagnosis, women are educated on a live webinar with midwives and dietitians, and then followed up with a virtual telehealth clinic. The team sourced a blood glucose monitor, which is Bluetooth enabled and syncs to an App that auto-populates to a patient master list.

This means that for the virtual visit, all of women’s synched information is to hand and along with the electronic health record, to facilitate a comprehensive midwifery led consultation. It also allows for escalation to the Registered Advanced Midwife Practitioner for review if pharmacological treatment is needed. From there women can be referred to Endocrinology and Obstetrics within the diabetes in pregnancy specialist clinic if required. With the twinning of attend anywhere and the new remote glucose monitoring, the team aim to deliver evidencebased care on a more personal level to transform the service for women.

a ten-fold risk of developing type 2 diabetes later in life. Women who have had gestational diabetes and are also overweight are at an even higher risk. Type 2 diabetes has lifelong consequences and can lead to other chronic diseases such as heart disease and cancer.

Ciara Coveney represented her team and the project undertaken in The National Maternity Hospital during Covid-19 pandemic at the Diabetes in Pregnancy Health Care Professional webinar series organized by Diabetes Ireland in September this year.

“The trouble is, however, that new mums often put themselves last – they're struggling with fatigue and juggling family responsibilities – so when it comes to weight loss, many find it hard to stick to a low-calorie diet.

Weight Loss Research New research from the University of South Australia suggests that the popular 5:2 or intermittent fasting diet is just as effective as a conventional energy-restricting diet, enabling women greater choice and flexibility when it comes to weight loss.

The 5:2 diet allows five days of normal eating each week while substantially restricting calories over two days a week, as opposed to a typical diet that requires moderate energy restrictions daily.

Globally, one in five pregnancies are affected by gestational diabetes, with these women having

Lead researcher, UniSA's Dr Kristy Gray, says the finding will be greatly welcomed by women looking to lose weight.

“Healthy eating and regular physical activity are recommended to manage gestational diabetes, with continuous energy restriction diets – or diets that cut calories by 25-30 per cent – being the most common strategy for weight loss and diabetes prevention.

“The 5:2 diet may provide a less overwhelming option. As it only cuts calories over two days, some women may find it easier to adopt and adhere to, as opposed to a consistently low-calorie diet requiring constant management.”

The research investigated the effects of both the 5:2 diet (five days of normal eating and two days of 500 calories) and a continuous energy-restricted diet (1500 calories per day) on weight loss and diabetes risk markers in women with a previous diagnosis of gestational diabetes. Both diets restricted energy by approximately 25 percent each week.

Diabetes now affects one in 10 adults worldwide The International Diabetes Federation (IDF) has released new figures showing that 537 million adults are now living with diabetes worldwide — a rise of 16% (74 million) since the previous IDF estimates in 2019. Released in advance of World Diabetes Day on November 14th, these new findings highlight the alarming growth in the prevalence of diabetes around the world. The new figures are taken from the upcoming 10th Edition of the IDF Diabetes Atlas, which will be published on December 6th.

“As the world marks the centenary of the discovery of insulin, I wish I could report we have witnessed decisive action to turn the rising tide of diabetes.

Alas I cannot,” comments IDF President, Professor Andrew Boulton. “Diabetes is a pandemic of unprecedented magnitude. Earlier this year, the World Health Organization launched the Global Diabetes Compact and United Nations Member States adopted a Resolution that calls for urgent coordinated global action to tackle diabetes. These are significant milestones, but words must be turned into action now, and if not now, when?”

The centenary of the discovery of insulin presents a unique opportunity to reflect on the impact of diabetes and highlight the urgent need to improve access to care for the millions affected. An estimated 1 in 2 people with diabetes across the world who need insulin cannot access or afford it.

“The new data confirm diabetes as a significant global challenge to the health and wellbeing of individuals, families and countries. A lot of diabetes is hidden. Almost every time we find more recent and more accurate data, our estimates have to be revised upwards,” said Professor Dianna Magliano Co-Chair of the IDF Diabetes Atlas Committee.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

RESPIRATORY OBESITY

ELDERLY

CARDIAC

WHEN CONTROL OF NMB REVERSAL IS WHAT MATTERS

BRIDION INDICATIONS • Reversal of rocuronium (ROC) or vecuronium (VEC) induced neuromuscular block (NMB) in adults.

• For routine reversal of ROC-induced block in children and adolescents aged 2 to 17 years.1 investigated in patients receiving ROC or VEC in the ICU setting. Do not use sugammadex to reverse block induced by nonsteroidal blockers such as succinylcholine or benzylisoquinolinium compounds, or steroidal blockers other than ROC or VEC. Conditions associated with prolonged circulation time such as cardiovascular disease, old age, or oedematous state may cause longer recovery times. Be prepared for possible drug hypersensitivity reactions. This medicinal product contains up to 9.7 mg sodium per ml, equivalent to 0.5 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. OVERDOSE No dose related adverse events nor serious adverse events were reported. Sugammadex can be removed using haemodialysis with a high flux filter. INTERACTIONS Toremifene and fusidic acid may displace rocuronium or vecuronium from sugammadex and delay recovery (no clinically relevant capturing interactions are expected). Interaction of sugammadex with hormonal contraceptives may lead to a decrease in progesterone exposure equivalent to one missed daily dose of oral contraceptive (no displacement interactions are expected). In general sugammadex does not interfere with laboratory tests, with the possible exception of the serum progesterone assay where interference is observed at sugammadex plasma concentrations of 100 μg/ml plasma. In a study doses of 4 mg/kg and 16 mg/kg sugammadex resulted in maximum mean prolongations of the activated partial thromboplastin time by 17 and 22% respectively and prothrombin time by 11% and 22% respectively. These were of short duration (≤ 30 minutes). In in vitro experiments pharmacodynamic interaction was noted with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran. PREGNANCY AND LACTATION Pregnancy and Lactation: Caution in pregnant women. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sugammadex therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. The effects on human fertility have not been investigated. SIDE EFFECTS Refer to SmPC for complete information on side effects. Common (≥ 1/100 to < 1/10): Anaesthetic complications including movement of limbs or body or coughing during anaesthesia, grimacing, or suckling on the endotracheal tube, airway complication of anaesthesia, procedural hypertension and procedural complication. Uncommon (≥ 1/1,000 to < 1/100): Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers. Other less common and rarely reported side effects are listed in the SmPC. In clinical studies with subjects treated with rocuronium or vecuronium, where sugammadex was administered using a dose labelled for the depth of neuromuscular blockade, an incidence of 0.2% was observed for recurrence of neuromuscular blockade as based on neuromuscular monitoring or clinical evidence. The use of lower than recommended doses may lead to an increased risk of recurrence of neuromuscular blockade after initial reversal and is not recommended. HANDLING See SmPC for details of compatability with infusion solutions. Physical incompatibility has been reported with verapamil, ondansetron and ranitidine. PACKAGE QUANTITIES 10 vials of 2 ml, 10 vials of 5 ml.

LEGAL CATEGORY POM. Marketing Authorisation Numbers EU/1/08/466/001-002. Marketing Authorisation Holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of review of prescribing information: April 2020. © Merck Sharp and Dohme B.V., 2020. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin 18 or from www.medicines.ie. Date of preparation: July 2020. EMEA/H/C/000885/II/0036.

Reference: 1. Bridion SPC April 2020

PREDICTABLE. COMPLETE. RAPID.

Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie.

Adverse events should also be reported to MSD (Tel: 01-299 8700)

Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 Ireland

IE-XBR-00032

BRIDION® 100 MG/ML SOLUTION FOR INJECTION (Sugammadex) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics (SmPC) before prescribing. PRESENTATION Vials of 200mg (2 ml) or 500mg (5 ml). INDICATIONS Reversal of rocuronium (ROC) or vecuronium (VEC) induced neuromuscular (NM) block in adults. For routine reversal of ROC-induced block in children and adolescents aged 2 to 17 years. DOSAGE AND ADMINISTRATION I.V. as a single bolus injection administered rapidly (within 10 seconds), into an existing I.V. line, by/under the supervision of an anaesthetist. Use appropriate technique to monitor recovery of NM block. Dose depends on the level of block to be reversed, not the anaesthetic regimen. Adults: Routine reversal following ROC- or VEC-induced block: • 4 mg/kg if recovery has reached at least 1-2 post-tetanic counts (PTC). Median recovery time (T4/T1 = 0.9) ≅ 3 minutes. • 2 mg/kg if recovery has occurred up to at least T2 following ROC- or VEC-induced block. Median recovery time (T4/T1 = 0.9) ≅ 2 minutes. Median recovery time (T4/T1= 0.9) is slightly faster with ROC- than VEC-induced block. Immediate reversal of ROC-induced block: 16 mg/kg. Median recovery time (T4/T1 = 0.9) ≅ 1.5 minutes when 16 mg/kg is given 3 minutes after a bolus dose of 1.2 mg/kg ROC. Not recommended for immediate reversal of VEC-induced block.

Re-administration of sugammadex: For post-operative recurrence of block after an initial dose of 2 mg/kg or 4 mg/kg, repeat dose of 4 mg/kg is recommended. Following a second dose of sugammadex, monitor the patient closely to ascertain sustained return of neuromuscular function. Re-administration of ROC or VEC after sugammadex: Up to 4 mg/kg Sugammadex a waiting time of 5 minutes for re-use of 1.2 mg/kg ROC; 4 hours waiting time for re-use of 0.6 mg/kg ROC or 0.1 mg/kg VEC. With ROC onset of NM block may be prolonged and duration of NM block may shortened. After immediate reversal, 16 mg/kg sugammadex, a waiting time of 24 hours is recommended. See SPC for patients with mild or moderate renal impairment. Special populations: Renal impairment: For mild and moderate renal impairment use adult dose. Not recommended in severe renal impairment (including patients requiring dialysis). Elderly: Use adult dose although recovery times are slower. Obese: In obese patients, including morbidly obese patients (body mass index ≥ 40 kg/m2), adult dose based on actual body weight. Hepatic impairment: Caution in patients with severe hepatic impairment, or impairment with coagulopathy. Children and adolescents (2-17 years): 2 mg/kg for routine reversal of ROC-induced block at T2. Not recommended in other routine reversal situations. Not recommended for Immediate reversal. May be diluted for accuracy of dose. Term newborn infants and infants: Not recommended. CONTRA-INDICATIONS Hypersensitivity to sugammadex or to any excipients. PRECAUTIONS AND WARNINGS Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored following reversal of block. Should block reoccur following extubation, adequate ventilation should be provided. The use of lower than recommended doses may lead to an increased risk of neuromuscular blockade after an initial reversal and is not recommended. Caution should be exercised when considering the use of sugammadex in patients receiving anticoagulation for a pre-existing or co-morbid condition. An increased risk of bleeding cannot be excluded in patients with hereditary vitamin K dependent clotting factor deficiencies; with pre-existing coagulopathies; on coumarin derivatives and at an INR above 3.5; using coagulants who receive a dose of 16mg/ kg sugammadex. If re-administration of ROC or VEC is required in patients with mild or moderate renal impairment after routine sugammadex reversal a waiting time for re-use of 0.6 mg/kg ROC or 0.1 mg/kg VEC should be 24 hours. If a shorter waiting time is required, the ROC dose for a new NM blockade should be 1.2 mg/kg within 30 minutes after Sugammadex administration. For re-administration of ROC or VEC after immediate reversal a waiting time of 24 hours is recommended. If neuromuscular block is required before the recommended waiting time has passed, a nonsteroidal neuromuscular blocking agent should be used. The use in patients with severe renal impairment is not recommended including those requiring dialysis. If neuromuscular block is reversed, while anaesthesia is continued, additional doses of anaesthetic and/or opioid should be given as clinically indicated. Marked bradycardia with cardiac arrest have been observed within minutes after administration, closely monitor patients for hemodynamic changes during and after reversal. Treat with anti-cholinergic agents such as atropine if clinically significant bradycardia observed. Sugammadex has not been

108 News 2019/2020 with recorded age, race, sex, BMI, and socioeconomic status. 1,115 (0.25%) had COVID-19, and of these, 150 (13.5%) required mechanical ventilation. His research found that skin disease patients have higher rates of COVID-19 than the general population but appear to have less severe cases. The study also found that skin diseases and SARS-CoV-2 share upregulated genes, including IL-6, IL-1B, TNF-α, and IL-17C, and psoriasis and SARSCoV-2 share high gene expression inside the epidermal differentiation complex (EDC) locus, involved in keratinocyte differentiation and molecular physiology of psoriasis.

PUSTULAR PSORIASIS

Due to the Covid-19 pandemic, the European Society for Dermatological Research (ESDR)’s 50th Annual Meeting was held virtually (September 22 – 25, 2021). The virtual format ensured that participation would be international and collaborative without putting anyone at greater risk of contracting the virus.

IPC opened with a symposium titled “Research on SARS-CoV-2 during the COVID-19 pandemic crisis: An IPC tribute to young researchers,” which gave sincere credit and appreciation to young researchers who continued high-level research despite the COVID-19 pandemic.

The ESDR congress also included many noteworthy psoriasis presentations from both IPC councilors and experts from around the world, including a special 50-year ESDR Anniversary Lecture from IPC Chief Medical Officer Peter van de Kerkhof. Thomas Sharnitz, MD, has written a report on several of these presentations.

50 Year ESDR Anniversary Lecture IPC Chief Medical Officer, Peter van de Kerkhof, was honored as one of five ESDR 50th-anniversary speakers. These lectures were intended to reflect the history of the ESDR, with Dr van de Kerkhof speaking on Psoriasis: From empirical to pathogenesis-based treatment of psoriasis, covering the history of research and noteworthy discoveries from 1970 – present.

The lecture was concluded with Dr van de Kerkhof describing the critical shift over 50 years from categorizing psoriasis as a ‘skin-only disease’ to a vital recognition of its systemic inflammatory nature.

IPC SYMPOSIUM: RESEARCH ON SARSCOV-2 DURING THE COVID-19 PANDEMIC CRISIS: AN IPC TRIBUTE TO YOUNG RESEARCHERS Dr Paul Bastard presented, Autoantibodies to type I IFNs in patient with life threatening COVID-19, where he discussed which epidemiologic risk factors increase the threat of life-threatening COVID-19, such as age and male sex, however substantial interindividual variability remains. Dr. Bastard details his

study, conducted together with The COVID Human Genetic Effort. Over 10,000 patients with asymptomatic/mild and severe/critical COVID-19 focusing on Type 1 interferons (IFNs), which trigger potent anti-viral responses and are implicated in other severe infections. The research discovered that type 1 IFNs appear to be essential for protective immunity against SARS-CoV-2; inborn errors or autoantibodies to type 1 IFNs place individuals at risk for life-threatening/critical COVID-19 and that autoantibodies neutralizing type 1 IFNs underlie at least 15% of critical COVID-19 cases, > 20% of cases in patients older than 80 years old, and > 20% in patients who died of COVID-19.

Dr Zijun Wang presented B-cell responses to SARS-CoV-2 in the setting of COVID-19 infection and vaccination, which discussed a study on a group of convalescent individuals, looking at polyclonal and monoclonal B-cell and antibody responses to SARS-CoV-2 postinfection. The study found that approximately 10% of convalescent patients were hospitalized for SARS-CoV-2 infection. Regardless of vaccination status, neutralizing antibody titers remain relatively unchanged between 6 and 12 months after infection. However, vaccination boosts these significantly and immensely.

IPC Councilor Satveer Mahil presented COVID-19 infection in psoriasis patients: Lessons from real-life registries and discussed data collected from PsoProtect and PsoProtectMe, international registries for healthcare providers and patients to report outcomes of COVID-19 in individuals with psoriasis. Their data found that most cases reported fully recovered from infection and that biologic monotherapy is associated with a reduced risk of hospitalization. The COVID-19 pandemic may cause non-adherence and worsening psoriasis, which is associated with poor mental health, driven primarily by concerns about immunosuppressant risks of COVID-19.

Dr Matthew Patrick presented, Interactions between skin inflammatory diseases and COVID-19: Lessons from genomic epidemiology studies, discussing an extensive study (n > 435,000) across encounters in

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

IPC Chief Medical Officer Dr Peter van de Kerkhof presented Discovery: Understanding of generalized pustular psoriasis from bench to bedside, where he discussed that generalized pustular psoriasis (GPP) is phenotypically, genetically, and clinically distinct from plaque psoriasis, and much evidence supports the central role of the IL-36 pathway in GPP pathophysiology. Further research to explicate the GPP pathogenesis could produce effective treatment options.

IPC Councilor Dr Jörg Prinz presented Innovations in generalized pustular psoriasis treatment, where he discussed the development of two IL-36R antibody antagonists IFN-Ω currently in clinical trials: imsidolimab and spesolimab. Studies have found IL-36 is a key cytokine in generalized pustular psoriasis (GPP). Blockade of the IL-36 receptor signaling, central to the pathogenesis of GPP, is a novel, targeted therapeutic approach. Early data suggest promising results for both imsidolimab and spesolimab in treating GPP independent of IL-36RN mutation status.

IPC Councilor Dr Siwe Eng Choon presented Impact of generalized pustular psoriasis: Disease burden and unmet needs, where she discussed that, although generalized pustular psoriasis (GPP) is rare, it is potentially life-threatening and has huge impacts on physical and mental health. Unfortunately, we lack high-quality evidence to guide the treatment of GPP, and treatment often provides an inadequate response.

OTHER Dr Lajos Kemeny presented on Mesenchymal stromal cell therapy for psoriasis. Dr Kemeny explained that Mesenchymal stromal/stem cells (MSCs) are highly immunomodulatory and can be harvested and systemically administered to patients who autoimmune diseases. MSC therapy offers a promising future option for patients with recalcitrant or severe psoriasis, and trials are underway to further study and perfect this technique for use in psoriasis.

Dr Frank Behrens presented, Detection and management of psoriatic arthritis: Spot the signs, act fast, and discussed the importance of early detection of psoriatic arthritis (PsA) to slow progression and joint damage. Screening for joint stiffness, edema, nail changes, and resting pain can be early clues. Future serum biomarkers may assist in early detection, and IL-23 inhibition shows great promise in treating PsA, including in those who failed other therapies.

NEW INDICATION IN PsA

DEMONSTRABLE JOINT EFFICACY

COMPLETE SKIN CLEARANCE

PROVEN DURABILITY*

Sustained joint symptom relief proven for 2 years in PsA1

Fast2,3 and sustained complete clearance proven for 2 years in PsA1

Most patients who started on TREMFYA® stayed on TREMFYA® long-term1,4,5

Durability*, also known as patient retention or drug survival is a combination of efficacy, safety, tolerability and patient satisfaction or preference.

DISCOVER-2 was a Phase 3, double-blind, multi-centre, placebo-controlled study that evaluated the efficacy and safety of TREMFYA® in bio-naïve patients with active PsA.1 Tremfya▼ 100 mg solution for injection in pre-filled pen PRESCRIBING INFORMATION. ACTIVE INGREDIENT(S): Guselkumab. Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATION(S): Treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. Treatment of active psoriatic arthritis in adult patients, alone or in combination with methotrexate, who have had an inadequate response or have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy. DOSAGE & ADMINISTRATION: For use under guidance/supervision of physician experienced in diagnosis and treatment of conditions for which Tremfya is indicated.

Subcutaneous injection. Avoid areas showing psoriasis. Adults: For both indications, 100 mg at weeks 0 and 4, followed by maintenance dose every 8 weeks. In the case of psoriatic arthritis, for patients at high risk for joint damage according to clinical judgement, consider a dose of 100 mg every 4 weeks. Consider discontinuation if no response after 16 weeks of treatment for plaque psoriasis and 24 weeks for psoriatic arthritis. Children: No data available in children/adolescents <18 years. Elderly: No dose adjustment required, limited information in subjects aged ≥ 65 years, very limited information > 75 years. Renal & Hepatic impairment: Not studied. CONTRAINDICATIONS: Serious hypersensitivity to active substance or excipients; clinically important, active infection. SPECIAL WARNINGS & PRECAUTIONS: Infections: Potential to increase risk. If signs/symptoms of clinically important chronic/ acute infection occur, monitor closely and discontinue Tremfya until resolved. Tuberculosis: Evaluate patients for TB pre-treatment; monitor for signs/symptoms of active TB during and after treatment. Consider anti-TB therapy prior to Tremfya if past history of latent/active TB and adequate treatment course not confirmed. Serious hypersensitivity reaction: Includes anaphylaxis. Some serious hypersensitivity reactions occurred several days after treatment and included urticaria and dyspnoea. If occurs, discontinue Tremfya immediately and initiate appropriate therapy. Hepatic Transaminase Elevations: An increased incidence of liver enzyme elevations has been observed in patients treated with Tremfya q4w compared to patients treated with Tremfya q8w or placebo. When prescribing Tremfya q4w in psoriatic arthritis, consider evaluating liver enzymes at baseline and thereafter according to routine patient management. If increases in ALT or AST are observed and drug-induced liver injury is suspected, Tremfya should be temporarily interrupted until this diagnosis is excluded. Immunisations: Consider completing all appropriate immunisations prior to Tremfya. Do not use live vaccines concurrently with Tremfya; no data available; before

live vaccination, withhold Tremfya for at least 12 weeks and resume at least 2 weeks after vaccination. SIDE EFFECTS: Very common: Respiratory tract infection. Common: headache, diarrhoea, arthralgia, injection site reactions, transaminases increased. Other side effects: hypersensitivity, anaphylaxis, rash, herpes simplex infections, neutrophil count decreased.

Refer to SmPC for other side effects. LEGAL CATEGORY: Prescription Only Medicine (POM).

PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S): Pre-filled pen, x1, EU/1/17/1234/002. MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. FURTHER INFORMATION IS AVAILABLE FROM: Janssen Sciences Ireland UC, Barnahely, Ringaskiddy, IRL - Co. Cork, P43 FA46.

Prescribing information last revised: November 2020.

Adverse events should be reported. ▼ This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Healthcare professionals are asked to report any suspected adverse events via: HPRA Pharmacovigilance Website: www.hpra.ie.

Adverse events should also be reported to Janssen Sciences Ireland UC on 1800 709 122 or at dsafety@its.jnj.com.

References: 1. McInnes IB, et al. Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19-Subunit of Interleukin-23, Through 2 Years: Results from a Phase 3, Randomized, Double-blind, Placebo-controlled Study Conducted in Biologic-naïve Patients with Active Psoriatic Arthritis. Presented at Innovations in Dermatology Conference, March 16-20, 2021. Online. 2. Blauvelt A et al. J Am Acad Dermatol 2017;76(3):405–417. 3. Mease PJ, et al. Lancet 2020;395:1126-1136. 4. McInnes IB, Rahman P, Gottlieb AB, Hsia EC, Kollmeier AP, Chakravarty SD, et al. Efficacy and safety of guselkumab, an interleukin-23p19-specific monoclonal antibody, through 1 year in biologic-naive psoriatic arthritis patients. Arthritis Rheumatol 2021. Apr;73(4):604-616. 5. Ritchlin CT, Helliwell PS, Boehncke W- H, et al.

Guselkumab, an inhibitor of the IL- 23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic- naïve or TNFα inhibitor- experienced. RMD Open 2021;7:e001457. © Janssen-Cilag Limited 2021

CP-245976 | Date of Preparation: August 2021

110 Clinical Profile

European Commission (EC) Approval for RINVOQ® Professor Alan Irvine, Professor of Dermatology, Trinity College Dublin a 75 percent improvement in the Eczema Area and Severity Index (EASI 75) and validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear) at week 16.1 “As a dermatologist researching and treating atopic dermatitis for more than 25 years, I’ve seen first-hand the debilitating impact this disease can have on a person’s daily life,” said Professor Alan Irvine, Professor of Dermatology, Trinity College Dublin, Ireland, and upadacitinib clinical study investigator.

“Clinicians need more tools to help them treat and manage this complex disease. The degree and early onset of skin clearance and itch relief in the upadacitinib Phase 3 clinical studies are very encouraging. The outcomes have the potential to advance treatment goals for patients with moderate to severe atopic dermatitis.”

AbbVie has announced the European Commission (EC) approved upadacitinib, an oral, selective and reversible JAK inhibitor, for the treatment of moderate to severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy.1 The recommended dose of upadacitinib for atopic dermatitis in adults is 15 mg or 30 mg once daily based on individual patient presentation, and 15 mg once daily for adolescents (12-17 years of age) and adults 65 years and older.1 Upadacitinib can be used with or without topical corticosteroids (TCS).1 “Discovering, developing, and delivering medicines that have a remarkable impact on patients’ lives is a complex endeavour that takes time, expertise, and

unwavering innovation,” said Andres Rodrigo, General Manager, AbbVie Ireland. “This approval is a significant milestone for AbbVie in our pursuit to help alleviate the burden of unrelenting itch and rash that many of these patients struggle with in daily life, despite available treatment options.”

The EC approval is supported by data from one of the largest registrational Phase 3 programmes in atopic dermatitis with more than 2,500 adults and adolescents with moderate to severe disease.1 These studies evaluated the efficacy and safety of upadacitinib monotherapy (Measure Up 1 [MU1] and Measure Up 2 [MU2]) and with topical corticosteroids (AD Up [AU]) compared to placebo.1 In all three studies, the coprimary endpoints were at least

Highlights From the Global Phase 3 Atopic Dermatitis Clinical Trial Programme1 Across the Phase 3 studies, all primary and secondary endpoints were met with 15 mg and 30 mg doses of upadacitinib compared to placebo. Highlights include: • Significantly more patients achieved EASI 75 at week 16 in the upadacitinib 15 mg group (MU1: 70%; MU2: 60%; AU: 65%) and the upadacitinib 30 mg group (MU1: 80%; MU2: 73%; AU: 77%), compared to placebo (MU1: 16%; MU2: 13%; AU: 26%).

• Significantly more patients achieved vIGA-AD 0/1 at week 16 in the upadacitinib 15 mg group (MU1: 48%; MU2: 39%; AU: 31%) and the upadacitinib 30 mg group (MU1: 62%;

Hundreds join #MarchForMaternity at Dáil Last month, hundreds of parents, pregnant people and supporters gathered outside the Dáil for #MarchForMaternity.

A long scroll, containing stories of peoples experiences of being pregnant and giving birth was unrolled and held up by women politicians from all parties and members of the #BetterMaternityCare campaign group.

Large signs were held up calling on Stephen Donnelly to honor his commitment to end partner restrictions in maternity care.

The #BetterMaternityCare campaign, supported by Uplift who organised the rally, is calling for the Health Minister to meet with to discuss the ongoing impacts of the restrictions and his commitment to end the exclusion of partners from full labour and emergency care.

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

MU2: 52%; AU: 59%) compared to placebo (MU1: 8%; MU2: 5%; AU: 11%).

• Significantly more patients achieved clinically meaningful itch reduction (improvement in Worst Pruritus NRS ≥4) in the upadacitinib 15 mg group (MU1: 52%; MU2: 42%; AU: 52%) and the upadacitinib 30 mg group (MU1: 60%; MU2: 60%; AU: 64%) compared to placebo (MU1: 12%; MU2: 9%; AU: 15%) at week 16.

• Clinically meaningful itch reduction (improvement in Worst Pruritus NRS ≥4) and skin clearance (EASI 75) were observed as early as week 1 and week 2, respectively, in patients treated with either dose of upadacitinib compared to those treated with placebo.

The most commonly reported adverse reactions (≥2% of patients) with upadacitinib 15 mg or 30 mg were upper respiratory tract infection (25.4%), acne (15.1%), herpes simplex (8.4%), headache (6.3%), cough (3.2%), folliculitis (3.2%), abdominal pain (2.9%), nausea (2.7%), neutropenia (2,3%), pyrexia (2.1%), influenza (2.1%) and increased blood creatine phosphokinase (CPK; 5.5%).1 The most common serious adverse reactions were serious infections (<1.0%).1 The Marketing Authorisation means that upadacitinib is approved in all member states of the European Union, as well as Iceland, Liechtenstein, Norway and Northern Ireland.

Upadacitinib is already approved for the treatment of moderate to severe atopic dermatitis in Russia, Saudi Arabia, United Arab Emirates, New Zealand and Chile, and is currently under review in the U.S. by the Food and Drug Administration (FDA).

References available on request

Clinical R&D 111 ASTELLAS’ AND PFIZER’S XTANDI® (ENZALUTAMIDE) REDUCED RISK OF DEATH BY 34% IN MEN WITH METASTATIC HORMONE-SENSITIVE PROSTATE CANCER

double-blind, placebo-controlled trial compared XTANDI plus androgen deprivation therapy (ADT) versus placebo plus ADT in men with mHSPC and OS was a key secondary endpoint.

Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) and Pfizer Inc. (NYSE: PFE) announced ahead of the European Society for Medical Oncology (ESMO) Congress 2021 that XTANDI® (enzalutamide) improved overall survival (OS) in the ARCHES study in men with metastatic hormonesensitive prostate cancer (mHSPC, also known as metastatic castration-sensitive prostate cancer). The Phase 3, randomized,

In the study, XTANDI plus ADT reduced the risk of death by 34% (n=1,150; hazard ratio [HR]=0.66; [95% confidence interval [CI]: 0.53-0.81]; p<0.0001) compared to placebo plus ADT. Median OS, which represents the time from randomization to death due to any cause, was not reached in either treatment group. The safety profile in both study arms was consistent with findings from the primary analysis.

Results from the final analysis of the ARCHES trial will be presented virtually at ESMO by Andrew Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer Biology, and Director of Research in the Duke Cancer Institute’s Center for Prostate and Urologic Cancers in Durham, North Carolina, U.S. (Abstract LBA25; September 18, 14:20 CEST).

The primary results from the ARCHES trial were published in the Journal of Clinical Oncology in 2019. The study met its primary endpoint of radiographic progression-free survival (rPFS) as assessed by independent central review, finding that treatment with XTANDI plus ADT demonstrated a 61% reduction in the risk of radiographic disease progression or death compared with ADT alone in men with mHSPC (HR=0.39; [95% CI: 0.30-0.50]; p<0.001).

The median follow-up time was 14.4 months. Median rPFS was not reached (NR) with XTANDI plus ADT (95% CI: NR to NR) versus 19.0 months (95% CI: 16.6-22.2 months) with placebo plus ADT. At the time of the primary analysis, OS data were not mature.



TREMFYA® (GUSELKUMAB), APPROVED FOR REIMBURSEMENT IN IRELAND The Janssen Pharmaceutical Companies of Johnson & Johnson have announced that TREMFYA® (guselkumab), a first-in-class treatment for adult patients with active psoriatic arthritis (PsA) who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy has been granted reimbursement in Ireland.



Vimovo® is indicated in adults for the symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, in patients who are at risk for developing non-steroidal anti-inflammatory drug (NSAID) -associated gastric and/or duodenal ulcers and where treatment with lower doses of naproxen or of other NSAIDs is not considered sufficient.1

Guselkumab is the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of interleukin (IL)-23 and inhibits its interaction with the IL-23 receptor. It is already approved for the treatment of patients with moderate to severe plaque psoriasis. IL-23 is an important driver of the progression of inflammatory diseases including psoriasis and PsA, among others.

Reference: 1. Vimovo Summary of Product Characteristics.

Legal classification: POM. Marketing Authorisation number, pack sizes: PA 2242/014/001, 60 packs. Marketing Authorisation Holder: Grünenthal Pharma Ltd, 4045 Kingswood Road, Citywest Business Park, Citywest, Co. Dublin, Ireland. Further information is available upon request from Grünenthal Pharma Ltd, 4045 Kingswood Road, Citywest Business Park, Citywest, Co Dublin. M-VMO-IE-09-21-0004 – September 2021

The approval for this new indication was based on results from the DISCOVER-1 and DISCOVER-2 Phase 3 clinical studies, which assessed safety and efficacy of guselkumab 100 mg q4w and q8w in adult patients with active PsA. DISCOVER-1 evaluated 381 participants with active PsA who had an inadequate response to standard therapies, including participants (~30

percent) previously treated with anti-tumour necrosis factor (TNF) alpha biologics.8 DISCOVER-2 included 739 patients who were biologic-naïve only and had an inadequate response to standard therapies. Data from these studies was published earlier this year in The Lancet (24-weeks; DISCOVER-1, DISCOVER 2).

The published results show that in both studies, at week 24, adult patients with active PsA achieved statistical significance in the primary endpoint of American College of Rheumatology (ACR) 20 percent improvement (ACR20) response (DISCOVER-1: p<0.001; DISCOVER-2: p<0.001) in both q4w and q8w guselkumab groups (DISCOVER-1: n=255; DISCOVER-2: n=493) vs the placebo groups (DISCOVER-1: n=126; DISCOVER-2: n= 246).

In addition, significant improvements in quality of life scores (36-item short-form [SF36] physical component summary) were observed in the guselkumab groups vs the placebo groups in DISCOVER-1 (p<0.001 for both doses); in DISCOVER-2, significant improvements were observed in the q4w guselkumab group vs placebo group (p=0.0056 [q8w, p=0.068]).

In DISCOVER 2, inhibition of structural damage progression was measured radiographically and expressed as the mean change from baseline in the total modified van der HeijdeSharp (vdH-S) score. At week 24, the guselkumab q4w group demonstrated statistically significantly less radiographic progression (p=0.006) and the guselkumab q8w group showed numerically less progression than placebo (p=0.068). At week 52, the mean change from baseline in total modified vdH-S score was similar in the guselkumab q8w and q4w groups (mean scores of 0.97 and 1.07 respectively).

In addition, higher Psoriasis Area and Severity Index 75 percent improvement (PASI 75), PASI 90 and PASI 100 response rates were observed in the q4w and q8w guselkumab groups vs the placebo groups (in DISCOVER-1, all unadjusted p<0.001 with PASI 100 being p=0.0005 and in DISCOVER-2, all unadjusted p<0.001).

In both studies, guselkumab was well-tolerated, and observed adverse events (AEs) were generally consistent with previous studies of guselkumab and current prescribing information.

HOSPITALPROFESSIONALNEWS.IE | HPN • DECEMBER - PROFESSIONAL 100 ISSUE - 2021

112 Clinical R&D LEO PHARMA PRESENTS NEW ADTRALZA® (TRALOKINUMAB) DATA



LEO Pharma A/S, a global leader in medical dermatology, has announced results showing that after two years of continuous treatment with Adtralza, adult patients with moderate-to-severe atopic dermatitis maintained improvements in signs and symptoms, itch severity and sleep interference.1 Findings were shared as an oral presentation during the European Academy of Dermatology and Venereology (EADV) Congress 2021.

The interim analysis investigated continued treatment with Adtralza as well as the ability to regain response after pausing and reinitiating Adtralza.1 Long-term efficacy outcomes were assessed in patients (n=345) who had received two years of treatment with Adtralza, including the full 52 weeks in the pivotal Phase 3 parent trials (ECZTRA 1 and 2) and 56 weeks in the ECZTEND trial.1 Patients were split into three cohorts based on the length of time between their last dose of Adtralza in the parent trial and their first dose in ECZTEND. Continuous treatment was defined as ≤5 weeks between the last dose in the parent trial and the first dose in ECZTEND (n=126), interrupted treatment was defined as 6-15 weeks (n=133), and >15 weeks (n=86) was considered a full washout of treatment.1 Patients who received continuous treatment with Adtralza over two years reported a high level of long-term control in atopic dermatitis signs and symptoms, as demonstrated by a median Eczema Area and Severity Index score (EASI) improvement from parent trial baseline of 92.7%.1 Maintenance of improvements in patient-reported outcomes, including pruritus (itch) severity and sleep interference, were demonstrated at two years as well. Itch severity and sleep interference were reported using a Numeric Rating Scale (NRS) of 0-10. Patients who received continuous treatment reported improvements in itch severity, with worst weekly NRS score for median pruritus, shifting from severe itch (8.1 out of 10) at parent trial baseline to mild itch (3 out of 10) following two years of treatment.1 These patients also reported improvement in median sleep interference, from severe sleep interference (7.3 out of 10) at parent trial baseline to mild sleep interference (1 out of 10)

in ECZTEND.1 During the parent trials, patients recorded their daily itch and sleep interference, and weekly averages of scores were used. During ECZTEND, worst itch severity and sleep interference of the previous week were reported.

A decline in the median EASI percentage was observed in the washout cohort within the period without treatment. After one year of treatment in the parent trial, results showed a median EASI percent improvement of 86.9% compared to baseline.

Following the washout of treatment (>15 weeks), median EASI percent improvement (vs. parent trial baseline) declined to 68.6%. A median EASI percent improvement equivalent to response at one year in the parent trials was regained within 12 weeks from treatment re-initiation with tralokinumab in ECZTEND.1 The safety of Adtralza treatment was also assessed in this interim analysis and results were consistent with the initial placebocontrolled treatment periods of the parent trials.1 Additionally, LEO Pharma is presenting a post-hoc analysis that evaluated predictors of maintained response with Adtralza dosing every four weeks as a late-breaking oral presentation.2 An interim analysis of COVID-19 cases and SARS-CoV-2 vaccinations during treatment with Adtralza in patients with moderate-tosevere atopic dermatitis enrolled in the ECZTEND trial will also be presented as an e-poster.3 NEW APPOINTMENT AT MATER PRIVATE NETWORK Mater Private Network has appointed Garry McCabe as Group Chief People Officer. Garry

has over twenty years’ experience in Strategic Human Resources and Industrial Relations and holds a Bachelors in Business Studies degree from UCD, specialising in Human Resources Management.

He began his Industrial Relations / Human Resources career in Tayto before moving within the C&C Group to the Soft Drinks Division.

Working with Kuehne + Nagel, the world’s leading Freight & Logistics company, since 2007, Garry has successfully experienced both Human Resources and Commercial Leadership roles, delivering exceptional profitable growth during his tenure.

Speaking about his appointment, John Hurley, Chief Executive, Mater Private Network, said “We are delighted to welcome Garry to our senior leadership team. He brings a wealth of experience to our organisation, having led the HR function in a number of leading Irish and global companies. We look forward to having the benefit of his expertise as we work to consolidate our position as the leading private hospital group and one of the top ten most trusted companies in Ireland*.”

HSE APPROVAL TO REIMBURSE ZOLGENSMA Following the first joint agreement on the price of a drug between Belgium, Ireland and the Netherlands, the HSE has decided to approve the gene therapy drug Zolgensma (onasemnogene abeparvovec) for reimbursement in the treatment of Spinal Muscular Atrophy (SMA) for patients who meet the specified criteria.

The Minister for Health, Stephen Donnelly, TD has welcomed the HSEs decision, which represents a very significant development

for the State as it is the first time Ireland has agreed to fund a drug for rare diseases in partnership with other countries in the BeNeLuxA Initiative.

The BeNeLuxA Initiative is a partnership approach to pharmaceutical policy with Belgium, the Netherlands, Luxembourg and Austria that aims to secure sustainable access to high quality and affordable medicines in the participating countries. Ireland became a member of the BeNeLuxA Initiative in June 2018, alongside existing members Belgium, the Netherlands, Luxembourg and Austria.

SMA is a rare, genetic neuromuscular condition causing progressive muscle wasting and weakness leading to loss of movement. This may affect walking and upper body movement, breathing and swallowing.

The new innovative gene therapy treatment Zolgensma was granted EU marketing authorisation for treating SMA in May 2020. The joint process for Zolgensma consisted of a Health Technology Assessment, followed by a price negotiation which commenced in July 2021. Considerable engagement and negotiation with the manufacturer Novartis Gene Therapies has allowed Belgium, Ireland and the Netherlands to jointly reach an agreement on the price of a drug for the first time.

Speaking today, Minister Donnelly said: "The reimbursement of Zolgensma by the HSE represents a great achievement in ensuring access to this gene therapy for two groups of young SMA patients. This is a welcome decision for their families, carers and friends.

"The success of the joint process for Zolgensma represents a tangible output of the BeNeLuxA partnership and I look forward to more successes like this in the future. I wish to take the opportunity to recognise and thank the HSE and the National Centre for Pharmacoeconomics for their significant role in this process."

Garry McCabe, Mater Private Network, Group Chief People Officer

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

HSE Chief Executive Officer Paul Reid said: _"_The HSE, as its standard, engages in commercial negotiations with drug manufacturers to ensure we obtain the best possible value for new medicines. This enables the HSE to reimburse as many medicines as possible, for as many patients as possible, within its resources.

▼

CAR-T Cell Therapy

I AM KYMRIAH Kymriah is indicated for the treatment of: 1 – Paediatric and young adult patients up to and including 25 years of age with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse.

– Adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

Further information is available upon request by contacting Novartis Ireland Ltd. on 01 260 1255 Full prescribing information available via the Kymriah SmPC at www.medicines.ie Reference: 1. Kymriah [summary of product characteristics] https://www.medicines.ie/medicines/kymriah-1-2-x-106-6-x-108-cells-dispersion-for-infusion-34945/spc ▼This medicinal product is subject to additional monitoring. Reporting suspected adverse reactions of the medicinal product is important to Novartis and the HPRA. It allows continued monitoring of the benefit/risk profile of the medicinal product. All suspected adverse reactions should be reported via HPRA Pharmacovigilance, website www.hpra.ie. Adverse events could also be reported to Novartis preferably via www.report.novartis.com or by email: drugsafety.dublin@novartis.com or by calling 01 2080 612.

Novartis Ireland Ltd., The Vista Building, Elm Park Business Pk., Merrion Road, Dublin 4, D04 A9N6

POM

7 April 2021 | 115416

114 Clinical R&D "HSE decisions on which medicines are reimbursed by the taxpayer must be made on objective, scientific and economic grounds. Providing funding for new high-cost innovative medicines alongside the many demands of the health service presents a continual challenge and the BeNeLuxA engagement with international colleagues aims to collectively address this challenge.

"This is the first time that Belgium, Ireland and the Netherlands have jointly conducted such a negotiation and reached an agreement on the price of a medicine. From today, the HSE will provide reimbursement of Zolgensma for a subgroup of patients who meet the specified criteria on which the BeNeLuxA assessment and negotiation was based."

OPENING OF NEW LIMERICK MANUFACTURING PLANT Edwards Lifesciences Corporation has recently celebrated the opening of its new manufacturing center in Castletroy, Limerick City, and announced its intention to increase its workforce to 850 employees in the coming years.

This represents the creation of 250 additional jobs compared to what was initially announced at the groundbreaking in 2019.

Edwards established operations in Ireland in 2018 at a facility in the Shannon Freezone and already employs 250 people in the region.

The new purpose-built facility will focus on the manufacture of breakthrough innovative therapies and life-saving medical technologies for patients suffering from heart valve disease.

“Our announcement illustrates the continued growth of our company

globally and demonstrates our confidence to the Mid-West of Ireland. By expanding our presence in the area, we aim to create a hub for Europe and bring us closer to the patients in the region who will receive these life-saving therapies.” says Michael A. Mussallem, Chairman and Chief Executive Officer of Edwards Lifesciences.

Employees at the plant will manufacture transcatheter therapies to repair or replace damaged heart valves, enabling patients to live longer, healthier lives.

“Our teams are dedicated to patients and work with passion.

We look forward to welcoming new members to join us in our mission to save and improve the lives of thousands of people around the world”, continues Michael A. Mussallem.

Tánaiste and Minister for Enterprise, Trade and Employment, Leo Varadkar said, “It’s great to be back in Limerick to officially open this fantastic new facility for Edwards Lifesciences. It will employ 250 more people than initially estimated, bringing the total new jobs being created to 850. It’s an enormous vote of confidence in the Mid-West region and the talent, skills and experience on offer here. Congratulations to the team involved and the very best of luck with this remarkable expansion.”

CEO of IDA Ireland, Martin Shanahan, added, “An investment of this scale by Edwards Lifesciences, a global leader in its field, is terrific news for the Mid-West Region and indeed for Ireland. It demonstrates the company’s commitment to the

region and its ambitions for its operations here. IDA Ireland remains committed to winning jobs and investment in regional locations. I wish to congratulate Edwards Lifesciences on this significant expansion and assure the company of IDA Ireland’s continued support.”

HSE APPROVES REIMBURSEMENT OF AJOVY® (FREMANEZUMAB) IN MIGRAINE



Teva Pharmaceuticals Ireland is delighted to announce the approval of AJOVY® (fremanezumab) 225mg pre-filled syringe for prescription under the High Tech Drug Payments Scheme, from October 1st 2021.



AJOVY is indicated for the prophylaxis of migraine in adults who have at least four migraine days per month1. From October 1st 2021, AJOVY® is reimbursed, under High Tech arrangements, for the prophylaxis of chronic migraine in adults who have failed three or more migraine-preventive treatments. Ajovy® offers the flexibility of monthly dosing (225 mg once monthly), or quarterly dosing (675 mg every three months)1 and is the only antiCGRP with the additional benefit of switching between the two.1 Between 12-15% of Irish people suffer from migraine – this means that roughly half a million people suffer from migraine in Ireland2.

Migraine has an impact on almost every aspect of a patient’s life – a survey3 carried out amongst 265 adult Migraine sufferers in Ireland revealed: - 53% of migraine suffers said that their partner is impacted3 - 57% said migraines impacted the ability to provide unconditional support to their children3 - 41% of people with migraine said it impacted on the career.3 Dr Martin Ruttledge, Consultant

DECEMBER - PROFESSIONAL 100 ISSUE - 2021 • HPN | HOSPITALPROFESSIONALNEWS.IE

Neurologist, Beaumont hospital said: "There are approximately one million people in Ireland who experience some level of migraine, a sometimes underestimated and misunderstood complex neurological disorder. The financial and societal burden of migraine is significant. It is the third most common disease in the world and is ranked as the second most disabling non-fatal medical condition in women by the World Health Organization (WHO). People living with more chronic forms of migraine may be very disabled and frequently struggle to maintain a reasonable quality of life. The approval of fremanezumab (Ajovy) by the HSE is very much welcomed by the many patients who suffer from migraine and is a significant addition to the treatment options available to Neurologists and Headache Specialists who treat migraine."

Clodagh Kevans, Director, Specialty Medicines Ireland said: “On behalf of Teva Pharmaceuticals Ireland, we are delighted to announce that the HSE has approved the use of AJOVY® (fremanezumab) for the prophylaxis of chronic migraine in adults who have failed three or more migrainepreventive treatments. With over half a million people in Ireland suffering migraines, combined with the hugely disabling effects of migraines, this news represents a major step forward in offering migraine sufferers a much needed, and much anticipated, treatment option. At Teva we are committed to supporting people affected by migraine, and giving their treating healthcare professional, innovative treatment options.”



More information on AJOVY® (fremanezumab) can be found at Ajovy.ie

3 in 1 solution

Helping to Combat Cardiovascular Disease1

NEW The 1st Statin, ACEi & CCB

combination in Ireland2

Controlling High Cholesterol and Hypertension in unison1 Lipertance® (Atorvastatin,perindopril,amlodipine): Abbreviated Prescribing Information: Please refer to the Summary of Product Characteristics before prescribing. COMPOSITION*: Lipertance 10mg/5mg/5mg, 20mg/5mg/5mg, 20mg/10mg/5mg, 20mg/10mg/10mg, 40mg/10mg/10mg film-coated tablets contain 10 mg atorvastatin (ator)/5 mg perindopril arginine (per)/5 mg amlodipine (amlo), 20mg ator/5 mg per/5 mg amlo, 20mg ator/10 mg per/5 mg amlo, 20mg ator/10 mg per/10 mg amlo, 40mg ator/10 mg per/10 mg amlo. Contains lactose as excipient. INDICATIONS*: Substitution therapy for treatment of essential hypertension and/or stable coronary artery disease, in association with primary hypercholesterolaemia or mixed hyperlipidaemia, in adult patients adequately controlled with atorvastatin, perindopril and amlodipine given concurrently at the same dose level. DOSAGE AND ADMINISTRATION*: One tablet once daily before a meal in the morning. Lipertance is not suitable for initial therapy. If a change of posology is required, the dose could be modified or individual titration with free combination may be considered. Co-administration: with elbasvir/grazoprevir or letermovir, the dose of atorvastatin should not exceed 20 mg/day. Lipertance not recommended when letermovir co-administered with ciclosporin. Elderly and patients with renal failure: frequent monitoring of creatinine and potassium. Clcr < 60 ml/min: not suitable. Hepatic impairment: should be used with caution. Lipertance is contraindicated in patients with active liver disease. Children and adolescents: should not be used. CONTRAINDICATIONS*: Hypersensitivity to the active substances or to any other ACE inhibitor or dihydropyridine derivatives or statin or to any of the excipients, active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal, during pregnancy, while breast-feeding and in women of child-bearing potential not using appropriate contraceptive measures (see section PREGNANCY* and BREASTFEEDING*), concomitant use with the hepatitis C antivirals glecaprevir/pibrentasvir, severe hypotension, shock (including cardiogenic shock), obstruction of the outflow tract of the left ventricle (e.g., hypertrophic obstructive cardiomyopathy and high grade aortic stenosis), haemodynamically unstable heart failure after acute myocardial infarction, history of angioedema (Quincke’s oedema) associated with previous ACE inhibitor therapy, hereditary or idiopathic angioedema, concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73m²) (see section INTERACTIONS*), concomitant use with sacubitril/valsartan (see WARNING* and INTERACTIONS*), extracorporeal treatments leading to contact of blood with negatively charged surfaces (see INTERACTIONS*), significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney (see WARNINGS*). WARNINGS*: Special warnings and precaution for use: Liver effects: liver function tests should be performed periodically and in case of transaminase levels increased, the patient should be monitored until resolution. Stop treatment if jaundice or marked elevations of hepatic enzymes (serum transaminases exceeding 3 times the upper limit of normal) and in patients with active liver disease. Use with caution in patients with hepatic impairment, who consume alcohol and/or have history of liver disease. Skeletal muscle effects: stop treatment if elevation of CK levels > 10 x ULN or muscular symptoms with elevation of CK level > 5 x ULN occur, or if rhabdomyolysis is suspected. Caution should be exercice when Lipertance is used with certain medicinal products that may increase the plasma concentration of atorvastatin and then the risk of rhabdomyolysis such as potent inhibitors of CYP3A4 or transport proteins (e.g ciclosporine, ketoconazole, letermovir, ritonavir…). Increased risk of myopathy with concomitant use of gemfibrozil and other fibric acid derivatives, antivirals for the treatment of hepatitis C, erythromycin, niacin and ezetimibe. Co-administration with systemic fusidic acid or within 7 days of stopping the treatment is not recommended. If use essential, Lipertance should be discontinued during fusidic acid treatment. Interstitial lung disease: if suspected, treatment should be discontinued. Diabetes Mellitus: In diabetic patients, glycaemic control should be closely monitored during first month of treatment. Patients with cardiac failure: use with caution. Hypotension: monitor blood pressure, renal function and potassium in patients at high risk of symptomatic hypotension (volume depleted or who have severe renin-dependent hypertension) or with symptomatic heart failure (with our without renal insufficiency), or with ischaemic heart or cerebrovascular disease. A transient hypotensive response is not a contraindication to further doses once the blood pressure has increased after volume expansion. Aortic and mitral valve stenosis/hypertrophic cardiomyopathy: use with caution and see CONTRAINDICATIONS. Kidney transplantation: no experience in case of recent transplantation.

Renovascular hypertension: Increased risk of hypotension and renal insufficiency in patient with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Diuretics may be a contributory factor. Loss of renal function may occur (minor changes in serum creatinine) even in patients with unilateral renal artery stenosis. Renal impairment: monitor potassium and creatinine; individual dose titration with the monocomponents recommended if Clcr < 60 ml/min. In patients with renal artery stenosis, blood urea and creatinine may increase; with renovascular hypertension, risk of severe hypotension and renal insufficiency. Amlodipine may be used at normal doses in patients with renal failure. Amlodipine is not dialysable. Haemodialysis patients: use with caution.

Hypersensitivity/Angioedema: stop treatment and monitor until complete resolution of symptoms. Angioedema associated with laryngeal oedema may be fatal. Combination with sacubitril/valsartan (contraindicated due to the increased risk of angioedema). Sacubitril/ valsartan must not be initiated until 36 hours after taking the last dose of perindopril therapy. Perindopril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan. Concomitant use of other NEP inhibitors (e.g. racecadotril) and ACE inhibitors may also increase the risk of angioedema. Concomitant use of mTOR inhibitors: Increased risk for angioedema. Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis: rarely, patients have experienced life-threatening anaphylactoid reactions, temporarily withhold treatment prior to exams. Anaphylactoid reactions during desensitisation: temporarily withhold treatment prior to exams. These reactions reappeared upon inadvertent rechallenge. Neutropenia/agranulocytosis/thrombocytopenia/anaemia: extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treated with allopurinol or procainamide, periodic monitor of white blood cell counts advised. Race: perindopril may be less effective and cause a higher rate of angioedema than in non-black. Cough: resolves after discontinuation. Surgery/Anaesthesia: stop treatment one day prior to surgery. Hyperkaliemia: frequent monitoring of blood potassium if renal insufficiency, worsening of renal function, age (>70 years), diabetes mellitus, dehydration, acute cardiac decompensation, metabolic acidosis, and concomitant use of potassium-sparing diuretics and potassium salts or supplements. Combination with lithium. not recommended Dual blockade of the renin-angiotensin-aldosterone system (RAAS): concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS is therefore not recommended. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Primary aldosteronism: Use not recommended in patients with primary hyperaldosteronism (not responding to drugs acting through inhibition of reninangiotensin system). Galactose intolerance/glucose- galactose malabsorption/total lactase deficiency: should not be taken. Sodium: ‘sodium-free’. INTERACTIONS*: Contraindicated: Aliskiren (in diabetic and impaired renal patients), Extracorporeal treatments, Sacubitril/valsartan, Glecaprevir/pibrentasvir. Not recommended: CYP3A4 inhibitors, aliskiren, concomitant therapy with ACE inhibitor and angiotensin-receptor blocker, estramustine, lithium, Co-trimoxazole (trimethoprim/sulfamethoxazole), potassium- sparing diuretics (e.g. triamterene, amiloride, eplerenone, spironolactone), potassium salts, dantrolene (infusion), grapefruit or grapefruit juice. Precautions: CYP3A4 inducers, digoxin, ezetimibe, fusidic acid, gemfibrozil / fibric acid derivatives, transport inhibitors, warfarin, antidiabetic agents (insulins, oral hypoglycaemic agents), baclofen, non-steroidal anti- inflammatory medicinal products (NSAIDs) (including aspirin ≥ 3 g/day), racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus), colchicine, colestipol, oral contraceptives, gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin), sympathomimetics, tricyclicantidepressants/antipsychotics/anesthetics, gold, digoxin, atorvastatin, warfarin or ciclosporine, tacrolimus, antihypertensive agents and vasodilators. PREGNANCY AND BREASTFEEDING*: Lipertance is contraindicated during pregnancy and lactation. FERTILITY*: Reversible biochemical changes of spermatozoa in some patients treated by calcium channel blockers. DRIVE AND USE MACHINES*: May be impaired if dizziness, headache, fatigue, weariness or nausea. Caution is recommended especially at the start of treatment. UNDESIRABLE EFFECTS*: Very common: Oedema. Common: nasopharyngitis, hypersensitivity, hyperglycaemia, somnolence, dizziness, headache, dysgeusia, paraesthesia, vertigo, visual impairment, diplopia, tinnitus, palpitations, hypotension (and effects related to hypotension), flushing, pharyngolaryngeal pain, epistaxis , cough , dyspnoea, nausea, vomiting, abdominal pain upper and lower, dyspepsia, diarrhoea, constipation, change of bowel habit, flatulence, rash, pruritus, joint swelling, ankle swelling, pain in extremity, arthralgia, muscle spasms, myalgia, back pain, asthenia, fatigue, liver function test abnormal, blood creatine kinase increased. Uncommon: Rhinitis, eosinophilia, hypoglycaemia, hyponatraemia, hyperkalaemia reversible on discontinuation, anorexia, insomnia, mood altered (including anxiety), sleep disorder, depression, nightmares, tremor, syncope, hypoaesthesia, amnesia, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), vision blurred, tachycardia, vasculitis, bronchospasm, dry mouth, pancreatitis, eructation, hepatitis either cytolytic or cholestatic, urticaria, purpura, skin discolouration, hyperhidrosis, exanthema, alopecia, angioedema, pemphigoid, photosensitivity reactions, neck pain, muscle fatigue, micturition disorder, nocturia, pollakiuria, renal failure, erectile dysfunction, gynecomastia, chest pain, pain, malaise, oedema peripheral, pyrexia, blood urea increased, blood creatinine increased, weight increase, white blood cells urine positive, weight decrease, fall. Rare: Thrombocytopenia, confusional state, neuropathy peripheral, cholestasis, psoriasis aggravation, stevens-johnson syndrome, toxic epidermal necrolysis, erythema multiforme, myopathy, myositis, rhabdomyolysis, muscle rupture, tendinopathy sometimes complicated by rupture, hepatic enzymes increased, blood bilirubin increased. Very rare: Leucopenia/neutropenia, agranulocytosis or pancytopenia, haemolytic anaemia in patients with a congenital deficiency of g-6pdh, haemoglobin decreased and haematocrit decreased, anaphylaxis, hypertonia, hearing loss, myocardial infarction secondary to excessive hypotension in high-risk patients, angina pectoris, stroke possible secondary to excessive hypotension in high-risk patients, eosinophilic pneumonia, gastritis, gingival hyperplasia, jaundice, hepatic failure, exfoliative dermatitis, lupus-like syndrome, renal failure acute. Not known: immune-mediated necrotizing myopathy, extrapyramidal disorder (extrapyramidal syndrome), Raynaud’s phenomenon. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be considered as a very rare complication associated with ACE inhibitor therapy. OVERDOSE*. PROPERTIES*: Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase. Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (Angiotensin Converting Enzyme ACE). Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. PRESENTATION*: Box of 30 film-coated tablets for Lipertance 10mg/5mg/5mg, 20mg/5mg/5mg, 20mg/10mg/5mg, 20mg/10mg/10mg, 40mg/10mg/10mg.

FOR BOTH LIPERTANCE AND LIPERCOSYL: MARKETING AUTHORISATION HOLDER Les Laboratoires Servier, 50 rue Carnot, 92284 Suresnes cedex France. www.servier.com. Marketing Authorisation number: PA0568/028/001-005 (LPT) PA0568/032/001-006 (LPC). Legal Classification for Supply: Lipertance and Lipercosyl POM. Further information available from: Servier Laboratories (Ireland) Ltd. Second Floor, 19 Lr. George’s Street, Dun Laoghaire, Co. Dublin A96 ER84, Ireland. Tel (01) 6638110, www.servier.ie. *For complete information, please refer to the Summary of Product Characteristics available on medicines.ie.

Date of last revision of text: June 2021 (Date of last approved SmPC: August 2021). 2122 C1 LPT.LPC Press ad CBU. Date of Preparation September 2021 1. Lipertance SmPC, August 2021 2. IMS Data, C11A Monthly Sales, June 2021. ACEi = Angiotensin-converting-enzyme inhibitors; CCB= Calcium channel blocker.

N EW N ew

Sc t ien tifically S

1714

ud ied

ud ied

+

The TheEvolution Evolutionof of Precision Precision Science Science

Sc t ien tifically S

Contains a unique combination of two clinically

Contains a unique combination of two clinically researched researched synergetic strains. individual strains with two different modes of action both targeting key mechanisms in IBS Calcium: Contributes to the normal function of digestive enzymes Pantothenic Acid, Vitamin B6: Contribute to the reduction of tiredness and fatigue.

TM

Group