HPN 2023 November

HOSPITAL PROFESSIONAL NEWS IRELAND

HPN November 2023 Issue 114 HOSPITALPROFESSIONALNEWS.IE

Ireland’s Dedicated Hospital Professional Publication

IN THIS ISSUE: NEWS: Medicine Suppliers Call for Action Page 5

Caring for Life, Every Step of the Way At Fresenius Kabi we offer a diverse range of products to meet various healthcare needs. Contact your Fresenius Kabi representative for further information.

Our broad portfolio of healthcare products includes the following: Products

Providing

Enteral

Supporting Patient Recovery

Parenteral

Nutrition for the Critically ill

IV Drugs Oncology

Established Cytotoxics & other IV Drugs

IV Solutions

Rehydration & diluents for IV Drug administration

Biosimilars

Used in some Chronic Conditions

Colloids

Volume Replacement

Medical Devices

Reliable Drug Delivery

Fresenius Kabi Limited - Fresenius Kabi Ireland, Unit 3B Fingal Bay, Balbriggan, Co. Dublin, Ireland T: +353 (0)1 8413030 | F: +353 (0)1 8496949 | E: FK-enquiries.Ireland@fresenius-kabi.com | www.fresenius-kabi.com/ie/ Job Code: IE-FK-NPR-2300172 Date of Prep: September 2023

This Publication is for Healthcare Professionals Only

REPORT: First Pharmacy Workforce Report Page 6 PHARMACY: Antimicrobial Prevalence Survey Page 14 FEATURE: Cost-Effectiveness of HCL in Ireland Page 24 CONFERENCE: International Women’s Symposium Page 36 CPD: Giant Cell Arteritis Page 41 MEN'S HEALTH FOCUS: Talking Weight Management Page 46

Transforming lives

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• Over 7 million patient-years’ experience across indications – and counting2 ABBREVIATED PRESCRIBING INFORMATION Enbrel® etanercept Before prescribing Enbrel® please refer to full Summary of Product Characteristics (SmPC). Presentation: Enbrel Pre-filled Syringe: Enbrel 25 mg and 50 mg solution for injection in pre-filled syringe. Each pre-filled syringe contains either 25 mg or 50 mg etanercept. Enbrel Pre-filled Pen (MYCLIC®): Enbrel 25mg and 50 mg solution for injection in pre-filled pen. Each pre-filled pen contains either 25mg or 50 mg etanercept. Enbrel Powder: Enbrel 25 mg powder and solvent for solution for injection. Each vial contains 25 mg etanercept and each pre-filled syringe contains 1 ml water for injections. Enbrel Paediatric: Enbrel 10 mg powder and solvent for solution for injection for paediatric use. Each vial contains 10 mg etanercept and each pre-filled syringe contains 1 ml water for injections. Uses: Adults: Moderate to severe active rheumatoid arthritis (RA), in combination with methotrexate, when response to disease-modifying anti-rheumatic drugs DMARDs, including methotrexate (unless contraindicated), has been inadequate. Enbrel can be given as monotherapy in the case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. Severe, active and progressive RA without prior methotrexate treatment. Enbrel alone or with methotrexate has been shown to reduce the rate of progression of joint damage measured by X-ray and to improve physical function. Patients with moderate to severe plaque psoriasis (PP) who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including ciclosporine, methotrexate or PUVA. Active and progressive psoriatic arthritis (PsA) when response to DMARDs has been inadequate. Enbrel has been shown to improve physical function in PsA patients, and to reduce the progression rate of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of PsA. Severe active ankylosing spondylitis (AS) when response to conventional therapy has been inadequate. Nonradiographic axial spondyloarthritis (nr-axSpA).Treatment of adults with severe non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs). Children aged 2-17 years: Juvenile idiopathic arthritis (JIA). Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis from the age of 2 years when inadequate response to, or intolerant of methotrexate. Psoriatic arthritis from the age of 12 years when inadequate response to, or intolerant of methotrexate.

Enthesitis-related arthritis from the age of 12 years when inadequate response to, or intolerant of, conventional therapy. Children aged 6-17 years: CChronic severe psoriasis when inadequately controlled by, or intolerant to, other systemic therapies or phototherapies.

Dosage: By subcutaneous injection. Adults: RA – 25 mg twice weekly or 50 mg once weekly PP - 25 mg twice weekly or 50 mg once weekly for up to 24 weeks, or 50 mg twice weekly for up to 12 weeks followed by 25 mg twice weekly or 50 mg once weekly for a further 12 weeks if needed. Continuous therapy may be appropriate for some adult patients. Discontinue if no response after 12 weeks. For re-treatment: 25 mg twice weekly or 50 mg once weekly for up to 24 weeks. AS, nr-axSpA and PsA – 25 mg twice weekly or 50 mg once weekly. Children aged 2-17 years: JIA – 0.4 mg/kg (maximum per dose 25 mg) twice weekly with an interval of 3 – 4 days or 0.8 mg/ kg (maximum per dose 50 mg) once weekly. Discontinuation of treatment should be considered in patients who show no response after 4 months. Children aged 6-17 years: Plaque psoriasis in children aged 6-17 years – 0.8 mg/kg (maximum per dose 50 mg) once weekly for up to 24 weeks. Discontinue if no response after 12 weeks. For re-treatment: 0.8 mg/kg (maximum per dose 50 mg) once weekly for up to 24 weeks.

Contra-indications: Hypersensitivity to any of the ingredients, sepsis or risk of sepsis, active infections. Warnings and Precautions: In order to improve the traceability of biological medicinal products, the brand name and batch number of the administered product should be clearly recorded (or stated) in the patient file.

Enbrel should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of RA, JIA, PsA, AS, PP or Paediatric PP. Patients treated with Enbrel should be given the Patient Card. Use carefully in patients predisposed to, or with history of, infection due to underlying diseases other than RA (e.g. advanced or poorly controlled diabetes) or with history of blood dyscrasias, pre-existing or predisposition to demyelinating disease or congestive heart failure (CHF). There have been rare (< 0.1%) reports of new onset CHF, including CHF in patients without known pre existing cardiovascular disease, including patients under 50 years of age. Cases of active tuberculosis have been reported, therefore all patients should be evaluated for both active and inactive TB prior to being treated with Enbrel. If active TB is diagnosed, Enbrel should not be initiated. Caution should be used when administering Enbrel to patients previously infected with hepatitis B and there have been reports of worsening hepatitis C in patients receiving Enbrel. Use with caution in patients with a history of hepatitis C. Whether treatment with Enbrel might influence the development and course of active and/or chronic infections is unknown. Concurrent administration of Enbrel and anakinra has been associated with increased risk of serious infections and neutropenia, and is therefore not recommended. In clinical studies, concurrent administration of abatacept and Enbrel resulted in increased incidences of serious adverse events, and is therefore not recommended. Use caution when considering combination therapy with DMARDs other than methotrexate. Reports of various malignancies have been received in the post-marketing period, therefore with current knowledge, a possible risk for the development of lymphomas, leukaemia or other haematopoietic or solid malignancies in patients treated with a TNF-antagonist cannot be excluded. Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age) in the post marketing setting. Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF-antagonists, including Enbrel. Post-marketing cases of Merkel cell carcinoma have been reported very infrequently REFERENCES 1. Scott LJ. Drugs. 2014;74:1379-1410. 2. Pfizer Data on File. March 2020.

PP-ENB-IRL-0285 | Date of preparation: September 2023

For more information on ENBREL and access to downloadable resources for your ENBREL patients, scan the QR code.

in patients treated with Enbrel. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Enbrel has not been studied in combination with other systemic therapies or phototherapy for the treatment of psoriasis. Monitor closely if patient develops new infection during treatment. Discontinue treatment if serious infection or allergic reaction develops or if blood dyscrasias are confirmed. Caution should be used in patients who have moderate to severe alcoholic hepatitis and Enbrel should not be used in patients for the treatment of alcoholic hepatitis. Discontinue temporarily if significantly exposed to varicella virus. Live vaccines should not be given concurrently with Enbrel. Paediatric patients should have received all vaccines recommended in current immunization guidelines prior to starting Enbrel.

Treatment with Enbrel may result in the formation of autoantibodies. Enbrel is not recommended for use in patients with Wegener’s granulomatosis. There have been reports of hypoglycaemia in Enbrel patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients. There have been reports of Inflammatory Bowel Disease (IBD) and uveitis in JIA patients being treated with Enbrel. Caution should be exercised when treating the elderly and with particular attention to occurrence of infections.

Pregnancy & Lactation: Enbrel is not recommended in pregnant or breast-feeding women. Enbrel should only be used during pregnancy if clearly needed. The administration of live vaccines (e.g., BCG) to a breastfed infant when the mother is receiving etanercept could be considered 16 weeks after stopping breast-feeding (or at an earlier timepoint if the infant etanercept serum levels are undetectable).

Undesirable Effects: Adults: TThe most commonly reported adverse reactions are injection site reactions, infections, headache, allergic reactions, development of autoantibodies, itching, and fever. See SmPC for less commonly reported side effects. TNF-antagonists, such as Enbrel, affect the immune system and their use may affect the body’s defences against infection and cancer. Serious infections affect fewer than 1 in 100 patients treated with Enbrel. Reports have included fatal and life threatening infections and bacterial sepsis. Various malignancies have also been reported with use of Enbrel, including cancers of the breast, lung, skin and lymphatic system (lymphoma).

Serious infections and other adverse events such as uncommon reports of: thrombocytopenia, systemic vasculitis, uveitis and scleritis, elevated liver enzymes, worsening of CHF, inflammatory bowel disease, rare reports of tuberculosis, opportunistic infections, anaemia, leucopoenia, neutropenia, pancytopenia, seizures, heart failure, autoimmune hepatitis, Steven Johnson’s syndrome, anaphylaxis, interstitial lung disease, lichenoid reactions and very rare reports of: toxic epidermal necrolysis and aplastic anaemia have been reported. Reactivation of hepatitis B (a liver infection) and worsening of symptoms of dermatomyositis have also been reported. Central and peripheral demyelinating events have been seen rarely with Enbrel use. There have been rare reports of lupus, lupus-related conditions, and vasculitis. Rate of new malignancies was similar to that expected for the population studied. Fatalities associated with serious infections, pancytopenia, aplastic anaemia and interstitial lung disease have also been reported.

Paediatrics: Generally as for adults, except the following were more common: headaches, nausea, vomiting and abdominal pain. In addition the following were reported as severe events: varicella, appendicitis, gastroenteritis, depression/personality disorder, cutaneous ulcer, oesophagitis/gastritis, group A streptococcal septic shock, type I diabetes mellitus and soft tissue and post-operative wound infection. See section 4.8 of the SmPC for how to report adverse reactions.

Package Quantities: Enbrel Pre-filled Syringe: Each carton contains 4 pre-filled syringes containing either 25 mg or 50 mg of Enbrel and 4 alcohol swabs. Enbrel Pre-filled Pen (MYCLIC): Each carton contains 4 pre-filled pens containing either 25mg or 50 mg of Enbrel and 4 alcohol swabs. Enbrel Powder: Each carton contains 4 vials of Enbrel 25 mg powder, 4 pre-filled syringes of water for injections, 4 needles, 4 vial adaptors and 8 alcohol swabs. Enbrel Paediatric (10 mg): Each carton contains 4 vials of Enbrel 10 mg powder, 4 prefilled syringes of water for injections, 4 needles, 4 vial adaptors and 8 alcohol swabs.

European Marketing Authorisation Numbers: Enbrel Pre-filled Syringe 25 mg: EU/1/99/126/013 Enbrel Pre-filled Syringe 50 mg: EU/1/99/126/017 Enbrel Prefilled Pen (MYCLIC) 25 mg: EU/1/99/126/023 Enbrel Pre-filled Pen (MYCLIC) 50 mg: EU/1/99/126/020 Enbrel Powder 25 mg: EU/1/99/126/003 Enbrel Paediatric 10 mg: EU/1/99/126/022.

Legal Category: S1A European Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

For full prescribing information see the Summary of Product Characteristics.

For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 467 6500.

API Reference Number: EN 137_0.

Pfleet number: 2022-0078193, 2022-0080082, 2022-0079879, 2022-0078596, 2022-0078595, 2022-0078594, 2022-0078593.

Date of Prescribing Information: July 2023.

November Issue Issue 114

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Contents

Foreword

First Pharmacy Workforce Report Published by PSI P6

Editor As Hospital Professional News was going to press, the Minister for Health Stephen Donnelly, Minister for Public Health, Wellbeing and the National Drugs Strategy, Hildegarde Naughton, and Minister for Mental Health and Older People, Mary Butler, announced a ¤22.5 billion health budget that will facilitate the continued delivery and expansion of quality, affordable healthcare services.

Advancing Biophotonics Science P8 Asthma Society launched pre-budget submission P10

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The significant allocation includes a Health Resilience Fund which will support service delivery in response to high inflation and increased patient demand among an expanding and ageing population.

Staff shortages fuelling abuse against Doctors P12

Budget 2024 also contains several health promotion and prevention measures through Healthy Ireland as well as funding for the continued implementation of the National Drugs Strategy.

Accreditation for St Vincent’s University Hospital P20 University of Galway Partners with NBCRI P23

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Marking World COPD Day in Ireland P32

The December issue of HPN will carry more in-depth coverage of Budget 2024 including comment and opinion from industry leaders.

REGULARS

CPD: Giant Cell Arteritis P41

In other news, Medicines for Ireland (MFI) are highlighting the role of inflation, rising energy and transport costs, and persistent global supply chain disruptions which have combined to create a real and serious risk of medicine shortages in the year ahead. The critical issue of medicine shortages has received significant public and political attention in Ireland and across the EU.

20

Men’s Health: BRCA Gene P45 Men’s Health: Erectile Dysfunction P48

The concern surrounding the possible shortages of medicines in Ireland is caused by growing and multifaceted challenges and there is no basis to assume this matter is temporary or will resolve autonomously.

Men’s Health: Penile Cancer P53 Clinical R&D: P80 Hospital Professional News is a publication for Hospital Professionals and Professional educational bodies only.

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 or 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 EDITOR Kelly Jo Eastwood EDITORIAL danielle@hospitalprofessionalnews.ie ACCOUNTS Fiona Bothwell cs.ipn@btconnect.com

The 2024 Health Budget will see spending on Mental Health rise to almost ¤1.3 billion. This is the fourth consecutive year that an increase has been provided to support mental health services, and highlights in real terms the importance this government places on the mental health of those living in Ireland.

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SALES EXECUTIVE Avril Boyd avril@hospitalprofessionalnews.ie SALES & TRAINING MANAGER Sibongile Mude s.mude@hospitalprofessionalnews.ie CONTRIBUTORS COPD Support Ireland Dr Rachel Clarke Dr Mark Doherty Dr Tom Wall Professor Richard Conway Bernie Carter Dr Kate McCann Professor Asif Muneer Dr Harriet Treacy Professor Carel Le Roux Professor Brendan Kelly HSE Community Antimicrobial Pharmacist Group Dr Jonathan Briody Liam Manning Dr Sally Griffiths Dr David Breen Michèle Bourke

DESIGN DIRECTOR Ian Stoddart Design HOSPITALPROFESSIONALNEWS.IE

@HospitalProNews HospitalProfessionalNews

Commenting on MFI’s Pre-Budget Submission, Chairperson Padraic O’Brien said, “Our primary objective at MFI continues to be centred on assisting Government to maintain sustainable market conditions, thus safeguarding continued access to cost-effective treatments for patients in Ireland.”

Turn to page 5 for the full story.

Our Special Focus this month is on Men’s Health with some excellent articles including the Management of Penile Cancer on page 53, authored by Professor Asif Muneer and Professor Brendan Kelly discussing Mindfulness and Mental Health Promotion on page 56.

Professor Carel Le Roux and Dr Harriet Treacy unlock men’s health with their article entitled, ‘The Vital Role in Managing the Disease of Obesity’ on page 54.

I hope you enjoy the issue.

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

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News

Innovating for Life Eimear O’Leary, IPHA’s Director of Communications and Advocacy

documenting how innovating in new medicines today can provide Irish patients with a healthy and happy future.

The Irish Pharmaceutical Healthcare Association (IPHA), which represents the international research-based biopharmaceutical industry, has launched new films

The films are part of Innovate For Life, the industry’s digital campaign demonstrating the social and economic value of medicines innovation. This is the fifth cycle of the campaign which is aimed at raising awareness of how the biopharmaceutical industry is constantly striving to find new

technologies and treatments to improve the lives of patients today and into the future.

expert contributions from clinicians, patient advocates, researchers and scientists.

The films this year use both animation and Talking Heads to tell the story of how patient’s lives will be positively affected in the future due to breakthrough in medicines development today. The animation is created by Dublin based illustrator Dermot Flynn.

Eimear O’Leary, IPHA’s Director of Communications and Advocacy, said: “Innovate For Life is aimed at everyone who is curious about the future of innovation and of where science and technology can lead us. Researchers and scientists globally, and here in Ireland, are constantly looking at how we can extend lives and provide people with happy and healthy futures. Innovation in medicines development is galloping ahead, in a constantly changing landscape.

For this year’s campaign we want to show what is possible in the future due to work underway today. We are living in a golden era of innovation which will benefit us all tomorrow. We are very grateful to the film’s six-member cast who shared their personal stories and their hopes for the future.”

The campaign features three international biopharmaceutical companies with a strong presence in Ireland – Amgen, MSD and Gilead. The Hero film is fully animated, telling the story of how one man’s life, and that of his mother, daughter and extended family, has been positively impacted by advances in science.

This is complimented by a series of short documentary-style Talking Heads films featuring

Hospital Pharmacy Role in Patient Safety WHO World Patient Safety Day, observed annually on 17 September, aims to raise global awareness about patient safety and calls for solidarity and united action by all countries and international partners to reduce harm to patients.

Hospital pharmacists serve as an integral part of all patient care teams. Thus, hospital pharmacists should ensure that patients and carers are offered information about their clinical medication management options, and especially about the use of their medicines, in a language they can understand.

The European Association of Hospital Pharmacists has participated this year in several initiatives to celebrate World Patient Safety Day. An awareness campaign has been launched with GS1, the International Alliance of Patients’ Organizations, International Society for Quality in Healthcare, and the International Hospital Federation. In addition, EAHP has co-hosted and moderated with the European Health Management Association a webinar on “Engaging Patients for Patient Safety: Educating and Reporting Medication Harm in Hospitals.” EAHP’s mission is to ensure the continuous improvement of care and outcomes for patients in the hospital setting.

EAHP President Andras Süle stated, “Healthcare professionals can rely on hospital pharmacists to provide adequate information to patients regarding their medication. We strongly call on all national governments and health system providers to guarantee an adequate number of hospital pharmacists and the full utilisation of the pharmaceutical expertise and pharmacy services to improve concordance and clinical pharmacy services.”

All Ireland Pharmacy Conference The 10th All Ireland Pharmacy Conference (AIPC) will be held at Ballymascanlon House Hotel, Dundalk on 6th and 7th November 2023.

The theme for this year’s conference is ‘Creating Momentum & Building Capacity’ This conference is jointly coordinated by the Northern Ireland Centre for Pharmacy Learning and Development and the Irish Institute of Pharmacy. Its focus is to share good practice in pharmaceutical care and practice development across the primary and secondary care sectors.

Pharmacists, technicians and qualified assistants are encouraged to exchange ideas for pharmaceutical service development in the Republic of Ireland and Northern Ireland.

On the evening of Monday 6th November, the conference dinner will take place at 8.00pm and provides an opportunity to network with colleagues. The main conference proceedings will start at 9.30am on Tuesday 7th November and will involve parallel oral sessions and poster presentations.

Visit www.allirelandpharmacyconference.com for full details.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

News

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Medicine Suppliers Call for Action Medicines for Ireland (MFI) are highlighting the role of inflation, rising energy and transport costs, and persistent global supply chain disruptions which have combined to create a real and serious risk of medicine shortages in the year ahead.

The critical issue of medicine shortages has received significant public and political attention in Ireland and across the EU. The concern surrounding the possible shortages of medicines in Ireland is caused by growing and multifaceted challenges and there is no basis to assume this matter is temporary or will resolve autonomously.

The Medicines for Ireland PreBudget Submission 2024 sets out recommendations to tackle and prevent any potential shortages.

These include the development of a flexible Pricing Mechanism to safeguard against the risk of medicine shortages; exploring the

possibility of the establishment of a National Medicines Reserve; and effective preparatory measure to facilitate implementation of the EU Pharmaceutical Package.

Commenting on MFI’s Pre-Budget Submission, Chairperson Padraic O’Brien said, “Our primary objective at MFI continues to be centred on assisting Government to maintain sustainable market conditions, thus safeguarding continued access to cost-effective treatments for patients in Ireland.

“The volume of generic medicines used in Ireland has increased by 70% since 2012, accounting for 57 per cent of all prescribed medicines compared with just 33 per cent 10 years ago.

The increased use of generic medicines has yielded hundreds of millions in savings for the state however, Ireland remains far short of the European average for generic usage, which is 70%”

Furthermore, he added, “As a small market Ireland is more likely to be badly impacted by inflationary pressure and as costs continue to rise, market conditions will become increasingly unviable for companies supplying generic medicines to Irish hospitals and pharmacies. Additionally, in some cases, our reimbursement prices for certain medicines are too low compared to other EU countries and price adjustments in Ireland are historically downward only.

This adds to unsustainable market conditions for suppliers”.

Expanding further on the prebudget submission, Mr O’Brien explained “There are many untapped areas of reform within the medicine pricing and reimbursement system in Ireland that can deliver further value for patients and the state, and MFI can help deliver these changes quickly. Failing to address the high cost of medicines, with more sustainable generic or biosimilar options will ensure that funding constraints remain a millstone around the neck of an already overstretched healthcare system in Ireland.”

A recent MFI member survey found that all member companies expect to see increases in the cost of manufacturing and procurement in the next 12 months with 90% stating that they think potential medicines shortages will have a negative impact on patient health in Ireland.

“We are at the halfway stage of the current framework agreement on the supply and pricing of medicines. As a solution focused organisation, we look forward to transformative engagement with the HSE and the Government on the next agreement in order to satisfy the needs of patients, Government and industry.”

Beacon First in Pioneering new Treatment Beacon Hospital has announced completion of its first ablation case performed using the Medtronic Affera™ Mapping and Ablation System. The surgery was performed by Professor Jonathan Lyne, Consultant Cardiologist and Electrophysiologist along with Beacon Hospital’s Cath Lab team.

As well as being the first hospital in Ireland and the UK to perform the pioneering treatment, Beacon

Professor Jonathan Lyne, Consultant Cardiologist and Electrophysiologist along with Beacon Hospital’s Cath Lab team

Hospital is among the first five hospitals worldwide to carry out the procedure.

One in four people over the age of 50 are at risk of developing atrial fibrillation (AF), the most common atrial arrhythmia (fast, abnormal heart rhythms). It occurs more frequently in those with underlying heart disease. Without early intervention, AF can progress and is associated with a higher rate of cardiovascular admissions, heart failure hospitalisation, and mortality, along with a reduced quality of life.

The new technology maps and ablates (removes) atrial

Professor Jonathan Lyne, Consultant Cardiologist and Electrophysiologist

arrhythmias and provides realtime feedback through its intuitive mapping and navigation software.

Michael Cullen, CEO of Beacon Hospital said: “We are proud to provide this new treatment option to our patients and be the first in Ireland and the UK to do so.

With world-leading technology, treatments and consultants, we’re committed to providing the very best care and outcomes for our cardiac patients.”

Prof. Jonathan Lyne, Consultant Cardiologist and Electrophysiologist at Beacon Hospital said, “The first procedures went very well, and our patients are now recovering.

As atrial fibrillation is the most common arrhythmia present in patients, this new procedure is a game changer for our team as it allows for more flexibility during an ablation procedure.”

The Affera™ Mapping and Ablation System includes the Sphere-9™ Catheter and the Affera™ Prism-1 Mapping Software.

Studies to date show that treatment with the Sphere-9 Catheter provided 85% one-year freedom from recurrence of atrial arrhythmias. In all paroxysmal and persistent AF patients who underwent an ablation, 78% of both cohorts remained free from all atrial arrhythmias at the conclusion of the study. The study achieved its primary safety endpoint of 0.6%, including zero incidences of atrio-esophageal fistula, coronary spasm, pulmonary vein stenosis, and phrenic nerve injury.

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

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News

First of its Kind Pharmacy Report Katherine Morrow, PSI President, Secretary General Robert Watt and Joanne Kissane, PSI Registrar and Chief Officer, PSI

The first report of its kind in Ireland examining the emerging risks to the future availability of pharmacists in patient-facing settings has been launched in the Department of Health by Secretary General Robert Watt.

The Workforce Intelligence Report* commissioned by the PSI -the Pharmacy Regulator, examines the current challenges to the recruitment and retention of pharmacists in community and hospital settings and provides, for the first time, baseline data on emerging risks specific to this cohort.

Its aim is to provide for a sustainable supply of pharmacists to meet current and future needs in patient- facing settings, and to enable pharmacy to play a full role in the development of the future integrated healthcare system.

High levels of administration, limited career progression opportunities, gaps in professional leadership, challenging working conditions, slow progress in technology and eHealth, and the importance of agreeing the future role for pharmacists within the integrated health system were among the key issues highlighted.

An important consideration of the report were the findings of a PSI workforce survey** measuring the sentiment of over 1,200 pharmacists. This was conducted in November 2022, in the aftermath of the COVID-19 pandemic; a period during which all sections of society, and in particular, healthcare, were under immense pressure. It provides a snapshot of pharmacists’ outlook at that time.

The survey also found that although over half of community and three-quarters of hospital

pharmacists enjoyed their roles, stress was a common feature for both- community pharmacists (93%) and hospital pharmacists (75%). Furthermore, while over 90% of respondents indicated that they had capacity for an increased scope of practice, respondents also spoke of a high administrative workload, absorbing time that could be better spent on clinical tasks. In addition, only one out of every five pharmacists that responded to the survey felt valued by the health system. Over a third cited technology developments and innovations, including electronic prescribing, as one of the most important areas where progress is needed to improve pharmacy workload and enable increased capacity for pharmacists to engage with patients.

The report contains six key recommendations with a series of actions, highlighting that a multiagency stakeholder response is required to address the complex issue of workforce planning.

• Strategic Workforce Planning – Actions include the establishment of a multiagency group focused on national workforce planning; the production of an annual workforce pharmacy survey report; mandatory workforce survey for all pharmacists.

• Leadership of and for the Profession – Actions include considering the appointment of a Chief Pharmaceutical Officer; assessing the feasibility of a professional leadership body; setting and implementing a plan for the vision and role of pharmacy as part of future integrated healthcare; and developing a national strategy for the future role of pharmacy technicians.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

• Innovation and Technology Priority areas are the design and development of national eHealth projects with pharmacy involvement; introducing changes to reimbursement and regulatory processes that facilitate digital solutions to reduce the administrative burden associated with manual paper-based activities.

• Attracting and Recruiting Pharmacists - Actions include ensuring there are enough students being trained to meet demand; conducting an annual sentiment survey of student experiences; streamlining the recognition process for pharmacists from non-EEA countries who wish to practise in Ireland.

• Career Sustainability and Progression- Key items include access to dedicated leadership and governance training to support career progression; development and recognition of advanced and specialist practice.

• Working conditions - Actions include the establishment of a forum for community pharmacist employers and employees regarding best practice in relation to working conditions; expansion and promotion of a range of workplace health and wellbeing resources.

The report’s findings and recommendations will form the basis for providing a pharmacy perspective on national strategic workforce planning initiatives led by the Department of Health.

There are now over 7,200 registered pharmacists in Ireland, the highest number ever, with over 5,800 employed in community and hospital settings. However, the report notes that despite the increase, there are emerging risks to the continued supply of pharmacists, specifically in these settings. This aligns with trends globally and nationally for many health and social care professions.

PSI Registrar and Chief Officer, Joanne Kissane, says: “We are pleased to present this report,

which we regard as a milestone for pharmacy workforce planning in Ireland. The challenges facing pharmacy are not unique to Ireland. Global trends correlated in the report show these challenges can be attributed to our ageing population and complex health conditions, combined with challenges in recruiting and retaining pharmacists. In that context, the report is an important first step in gathering robust data and insights into the pharmacy workforce in Ireland, setting out a series of recommendations underpinned by evidence-based research.

“This work was undertaken with the objective of ensuring that we have a sufficient supply of trained pharmacists equipped to provide high-quality, safe, and effective services to the public.

It is about ensuring improved patient outcomes and enhancing the healthcare system overall.

It is our intention that we will continue to build upon the findings presented here today and continue to contribute data and insights about the pharmacy workforce to nationally led strategic workforce planning and modelling.

“We recognise that the number of registered pharmacists continues to grow year on year, which is an extremely positive development.

However, it is also important that we acknowledge the issues that have been raised by pharmacists, pharmacy students, and others, and take appropriate action, along with our colleagues in the Department of Health and other health and pharmacy stakeholders, to safeguard the future sustainability of the workforce to meet patient needs and play a full role in the development of the future integrated health system.

“Trends show that Ireland’s population growth will continue to impact healthcare provision in general, including access to treatment. The need to plan for the right care, by the right healthcare professional, in the right place, and at the right time has become more pertinent. Planning for the role that pharmacists will play in the health system is vital and can be realised by putting the necessary structures and policies in place.

“Safeguarding the supply of pharmacists for patient-facing settings is critically important, most particularly in the context of ensuring continued patient and public trust in pharmacy services and assuring high quality of care is provided.”

News

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Changing the Landscape of Cancer Research Minister Simon Harris, Minister for Further and Higher Education, Research, Innovation and Science of Ireland recently opened the AllIsland Cancer Research Institute (AICRI) Showcase – Vision and Progress event at the Herbert Park Hotel, Dublin. The purpose of this event was to highlight the achievements of AICRI (www.aicri.org) over the past year, to share its future plans and engage with a range of stakeholders from academia, industry, the clinic and those with a lived experience of cancer. It brings together the cancer research community on the island of Ireland to discuss its strategy going forward and show how AICRI can align with cancer care and cancer research at a national level in Ireland and Northern Ireland. It will explore future opportunities that can benefit those involved in cancer research across the island and help strengthen North-South relationships and develop new ones.

AICRI is a rapidly emerging virtual institute which is creating an overarching framework for cancer research across the island of Ireland. Since October 2020, AICRI has brought together ten academic institutions and multiple other stakeholders from the healthcare sector, cancer patients, cancer charities, industry partners and government agencies. It has a broad research programme from cancer prevention to cancer diagnosis and treatment to survivorship and quality of life.

In March 2022, AICRI received its foundation stone funding when it was awarded ¤4 million from the Shared Island Fund as a Strand III (Partnerships of Scale) award under the first round of the HEA North-South Research Programme. The Higher Education Authority (HEA) administers the North-South Research Programme on behalf of the Department of Further and Higher Education, Research, Innovation and Science.

AICRI and cancer research on the island of Ireland has benefited immensely from the North-South Research Programme, accounting for almost ¤13 million and one third of all funding under this groundbreaking scheme.

The ¤4 million award to AICRI allows for the creation of an AllIsland Doctoral and Post-Doctoral Research Training Programme in Precision Cancer Medicine AICRIstart (www.aicri.org/aicristart) The AICRIstart programme, led

by Prof. William Gallagher at

Professor William Gallagher - UCD and AICRI, with Minister Simon Harris and Professor Mark Lawler - QUB and AICRI University College Dublin and Prof.

Mark Lawler at Queen’s University Belfast, trains ten doctoral students and ten post-doctoral fellows with significant expertise in precision cancer medicine. By bringing together ten academic institutions on the island of Ireland (UCD, TCD, RCSI, TU Dublin, DCU, QUB, UU, UoG, UL and UCC) in this foundational initiative, AICRIstart will catalyse a unique all-island network of excellence in cancer research.

Commenting on the AICRI Showcase Vision and Progress event, Professor William Gallagher, Professor of Cancer Biology at University College Dublin and Co-Lead of AICRI said, “AICRI is building an overarching framework for cancer research both in Ireland and Northern Ireland. It is about creating a community, an attractive ecosystem to carry out world leading cancer research for the benefit of patients and wider public.”

Two other major cross-border cancer research awards (each ¤4 million) were funded under Strand II of the HEA NorthSouth Research Programme, one relating to digital health (led

by Prof. Aedin Culhane at UL and Professor Mark Lawler at

QUB) and the other relating to liquid biopsies (led by Professor Lorraine O’Driscoll at TCD and Professor Paul Mullen at QUB).

Professor Mark Lawler, Professor of Digital Health at QUB and co-lead of the Strand II eHealth Hub for Cancer project, presented findings of a recent landmark study led by Queen’s University Belfast which has shown how precision medicine can be a cheaper and more efficient way to treat cancer.

Professor Lawler explains, “This landmark study highlights how precision medicine can deliver affordable care for cancer patients. Moving towards a precision oncology Companion Diagnostic (CDx)-guided approach can deliver health benefits at a potentially affordable cost, including in the development phase, lowering expensive clinical trial attrition rates and sparing patients from those treatments that are ineffective and may have significant side effects. If we don’t deploy a CDx-guided approach we are missing a huge opportunity to deliver the best, most affordable care to our patients.”

Several additional Strand I Awards (¤200,000 each) covering different cancer research projects working at a North-South level were also supported under this initial round

of funding of the HEA NorthSouth Research Programme, and are collectively profiled today at the AICRI Showcase Vision and Progress event. The projects presented show what can be achieved through cross-border collaboration and help to further strengthens the island’s reputation for research excellence and innovation in the cancer space.

They also highlight the importance of funding secured through the Shared Island Fund and how this funding can help researchers on our island to work collaboratively and contribute to addressing global challenges such as cancer.

The long-term aim of AICRI is to build towards a fully integrated, large-scale Co-Centre, which unites cancer research across the entire island, as well as connects East-West into mainland Britain, the EU and the US. On 26th September 2023 AICRI co-hosted with the National Cancer Control Programme (NCCP) a very successful EU Cancer Mission Day – Ireland in Dublin, where Ireland’s current and future participation in the EU Cancer Mission and EU Beating Cancer Plan was discussed. AICRI is currently collaborating with the NCCP in establishing a National Cancer Mission Hub in Ireland through the EU funded ECHoS project.

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

8

News

Research Award for Advancing Biophotonics Science Professor Stefan Andersson-Engels

photosensitizing agent for the treatment of non–melanoma skin cancer is currently one of the first lines of treatment at most skin cancer clinics around the world.

Welcoming the announcement, Deputy Director General of Science Foundation Ireland, Dr Ciarán Seoighe, said: “Recruiting and retaining world-leading scientific talent to Ireland is a key priority for SFI in partnership with our higher education institutions.

Professor Andersson-Engels’ exceptional international track record will help to drive Ireland’s position at the forefront of photonics research. His work will contribute to improving the health and wellbeing of people by the invention and application of new technologies, as well as boosting industry engagement.

We wish him every success with his research programme."

Professor Stefan AnderssonEngels has been awarded ¤5.3 million through the SFI Research Professorship Programme, which will underpin the Biophotonics Group at Tyndall National Institute for the next five years. The funding will be used to advance the fundamental understanding of biophotonics science, the application of light-based technologies to life sciences and medicine.

This award will foster the development of new diagnostic and guidance tools to meet proven clinical needs. These will be implemented in the clinical setting of neonatology, neurosurgery, orthopaedics, and the GI tract, as well as oral cancer screening, and will be guided by 20 clinical and pre-clinical collaborators.

The objectives of the award are to provide better healthcare and outcomes for patients, and to grow economic activity through the commercialisation of the resulting technologies. This will be achieved through partnerships with existing MedTech companies.

Professor Andersson-Engels and his team have already created two start-up companies since the formation of the Biophotonics Group in 2016, one of which was in partnership with the National Cancer Centre in the Netherlands.

The team has also transferred technologies to companies in the areas of cancer boundary detection and the monitoring of babies during childbirth.

The objective of Professor Andersson-Engels’ project is to use the unique properties of light, a safe, non-invasive method for humans that can accurately detect specific cells, for diagnostic purposes such as gastrointestinal diagnostics for malignancies and inflammatory bowel diseases, in-vivo oral cancer delineation and diagnosis.

As light can only penetrate short distances into tissue, Professor Andersson-Engels will seek to address this challenge, and aim to facilitate light-based diagnostics and therapy deep inside the body, permitting use for many more diseases.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

Commenting on the award, Professor Andersson-Engels said, “I am delighted to be continuing our important work with the talented team across Tyndall, UCC, and IPIC. With the medical devices sector in Ireland recognised as one of the five emerging global hubs, it is an exciting time for the Biophotonics Group to forge close collaborations with companies, clinicians and research centres for the faster development and deployment of more accurate, less invasive diagnostic treatment methods for cancer and other diseases.”

Professor Andersson-Engels has an impressive track record, receiving several prizes for his research achievements, and his work on the development and commercialisation of technology has been critical to ensuring that patients will benefit from the results of scientific research. His pioneering work in the area of ALA-PDT (Photodynamic therapy) using the topical application of aminolevulinic acid (ALA), a

Surgical Oncologist, Head of Medical Affairs and Research, Centre for Early Cancer Detection at The Netherlands Cancer Institute, Professor Theo Ruers added, “We at The Netherlands Cancer Institute, have established a very strong and fruitful collaboration with the Biophotonics@Tyndall team over the last few years throughout the first phase of the Professorship Award. Our complementary skill sets have led to a spin-off company, multiple publications, and patents as well as collectively attracting EU and Health Holland funding. This collaboration is a win-win for both parties, and we expect the coming phase to be even more productive and impactful.”

Director of IPIC, the SFI Research Centre for Photonics, Professor Paul Townsend concluded, “This award further strengthens IPIC’s outstanding research team by providing the scientific vision and knowledge to steer existing photonic device integration towards innovative new applications in the biomedical areas. Furthermore, by continuing this world-class biophotonics research programme at IPIC and Tyndall, we can underpin strong collaborative partnerships with other Science Foundation Ireland Research Centres, such as APC, through projects that will present huge opportunities at a global level and again raise Ireland’s research credentials in the biomedical space.”

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IE-RNQG-230034 | August 2023

10 News

Cost Cannot be a Barrier to Life-Saving Medication Consultant in Respiratory Medicine at St. Vincent's Hospital and Medical Director of the Asthma Society, Professor Marcus Butler

“In Ireland, someone visits the Emergency Department due to asthma every four minutes.

Tragically, every five days, a family in Ireland loses a loved one due to asthma. If patients are unable to take their medications as prescribed, they are at risk of an asthma attack.

The Asthma Society of Ireland, now in its 50th year of impact, has released its 2024 pre-budget submission, with seven budgetary asks focused on preventing asthma deaths in Ireland, improving the quality of life for 380,000 people in Ireland with asthma, and reducing the cost of asthma to both the State and the individual.

The Asthma Society’s Seven Pre-Budget asks include: 1. Universal Subsidisation of Asthma Medications 2. Invest in severe asthma medication 3. Extend the current Asthma Management Programme to all people with asthma 4. Increase Capacity in our Healthcare System: Recruit Respiratory Specialists 5. Improve Air Quality in our Homes and Communities 6. Disincentivise smoking and e-cigarettes through taxation 7. Restore pay parity within the Community and Voluntary Sector As a priority, the Asthma Society is calling on Minister for Health Stephen Donnelly to make a substantive move towards universal subsidisation of asthma medication in this year’s Budget by making ‘combination’ inhalers free to people with asthma.

International research has found that these relatively new ‘combination inhalers’, taken daily to keep future asthma symptoms at bay, reduce the risk of asthma attacks and unscheduled GP and hospital visits.

Speaking about the need for affordable asthma medication, CEO of the Asthma Society of Ireland, Eilís Ní Chaithnía, said, “Asthma medications, when used properly, are a reliable and costeffective way of managing asthma, saving lives and substantially reducing the demands on our overwhelmed healthcare system.

While we warmly welcome the expansion of free GP visits for children under 8, our service users – people with asthma and their loved ones – were already reporting difficulty in securing appointments. With the increased risk of viral infection over recent years, and climate change posing an immediate threat to lung health, it is crucial that people can take their asthma medication as prescribed. Medications that reduce the inflammation in the lungs caused by asthma, as combination inhalers do, are the best way to protect against asthma emergencies and fatalities.

“We hope to see Budget 2024 make positive changes for people with asthma in Ireland. Given the financial pressures facing people across the country, it has never been more crucial to prioritise the affordability of asthma medications.

“Covering the substantial cost of their asthma medications has always been a worry for our members, especially because it tends to run in families. However, a 2023 survey of 1,294 people with asthma in Ireland revealed the concerning decisions people with asthma and their loved ones have been forced to make during the cost-of-living crisis. Despite 96% of those surveyed being prescribed asthma medications, 45% have had to forego them in the prior three months due to financial constraints.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

“Ireland has one of the highest hospitalisation rates for asthma in the EU. It also has one of the highest prevalences of asthma in the world. Therefore, it is crucial to ensure people have access to asthma medications, regardless of their financial circumstances, so they can manage their condition effectively. The Asthma Society, now in its 50th year, has been advocating for asthma medications to be included free of charge on the Long Term Illness Scheme for decades.

“The Asthma Society is urging Minister Donnelly to demonstrate his commitment to the health and lives of the nearly 400,000 people with asthma in Ireland and their families by making combination inhalers free of charge in Budget 2024.”

Speaking of best practice in asthma control Consultant in Respiratory Medicine at St. Vincent's Hospital and Medical Director of the Asthma Society, Professor Marcus Butler, said, “Asthma attacks can occur when a patient's asthma is not well controlled, which may be due to not taking their controller medication as prescribed, not using their inhaler correctly, or an indication that their treatment needs to be reviewed.

An asthma combination inhaler contains two types of medication recommended by national and international guidelines as best practice for asthma management.

Using this type of inhaler has proven to reduce asthma symptoms and reduce the cost of asthma to both the person and the State. Combination inhalers, however, are more expensive which can affect medication adherence. the cost is a clear barrier, with each combination inhaler costing anything up to ¤80 per inhaler. Some form of improved prescription assistance

program to help those excluded from fundamental asthma therapy is just and reasonable.

In the current cost of living crisis and a healthcare system recovering from the pressure of the COVID-19 pandemic, subsidising asthma medication makes sense. Cost cannot be a barrier to life-saving medication.

Asthma is estimated to cost the State ¤472 million annually due to hospitalisations, GP visits, and practice nurse consultations.

Increased use of combination inhalers as recommended by national and international expert bodies not only increases the quality of life for people with asthma, but it reduces the cost of asthma on the State through hospitalisation and productivity improvements.

Cost cannot be a barrier to life-saving medication. We urgently need universal subsidisation of asthma medication which would sit best within the Long-Term Illness (LTI) Scheme if not a more bespoke prescription assistance model.”

The Asthma Society also urges the Government to use Budget 2024 as an opportunity to encourage asthma-friendly communities by disincentivising smoking and e-cigarette use and by removing asthma triggers from our air and homes. Professor Marcus Butler continued - “Rising use of e-cigarettes, particularly among young people, is a deep concern within the asthma community. Research shows that e-cigarette use and passive exposure to their aerosols negatively impact respiratory health among adolescents and are shown to be an asthma trigger.

The Asthma Society are calling on the Government to tax e-cigarettes and vapes to other tobacco products, as recommended by the World Health Organisation (WHO). The Asthma Society is also calling for asthma triggers to be removed from our air both inside and outside our homes through measures that will reduce pollution from transport and smoky fuels, increase retrofitting of homes for people with asthma and improve our electricity grid.”

He concluded, “When the basics of asthma care are done well, there are long-lasting benefits to the person and the wider health system. With that in mind, the Asthma Society’s 2024 Pre-Budget Submission is calling for targeted investment that will radically reduce the long-term direct and indirect costs of asthma.”

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12 News

Staff Shortages Fuelling Abuse against Doctors Three in five doctors (60%) have experienced or witnessed verbal or physical abuse from patients or their relatives within the past 12 months, with 37% saying the incidents resulted from staff shortages and 39% saying it was due to the referral waiting list.

As the world's leading protection organisation, representing over 300,000 healthcare professionals, MPS is calling upon the Government, Garda, and HSE employers to take "every possible step" to address this issue.

In the Medical Protection Society (MPS) survey of nearly 900 doctors in Ireland, 86% of those who have experienced or witnessed abuse in the past 12 months said it negatively affected their mental health, and over a quarter (26%) said an increase in abuse and intimidation from patients has made them reconsider their career in healthcare.

Dr James Thorpe, Deputy Medical Director at MPS, said, "While long referral waiting lists and staff shortages understandably cause stress to patients and their families, healthcare professionals are doing their best under challenging circumstances.

While most patients are respectful, it is troubling that so many healthcare workers face aggression and intimidation.

A quarter of doctors (25%) also feel that abuse against healthcare professionals is not taken seriously by the Garda.

"Experiencing and witnessing abuse can have profound effects on the mental health of healthcare professionals, which

can be detrimental to both the individual and to patient care.

It can also result in healthcare staff needing time off work or even contemplating leaving the healthcare profession altogether.

“Healthcare professionals whether working in primary care, HSE or private clinics – must feel their safety is a priority and be encouraged to report all abusive behaviour.

“All healthcare settings should provide an appropriate forum where those who witness or experience any kind of abuse from patients can talk about it and seek appropriate wellbeing support. Peer support networks can also help to foster a supportive environment where experiences can be shared and reflected on, and staff should be

offered practical advice on deescalation techniques.

“The Garda could also consider how they can support healthcare settings, for example, by encouraging reporting of abuse and better communicating to the public the consequences of abuse.

“More broadly, there is a need for research to ascertain the additional training needs for HSE staff for dealing with conflict and protecting themselves from violence.

“The Irish Government, Garda, and HSE must take every possible step to address this issue and help raise awareness of the importance of treating all healthcare workers respectfully. Failure to act may result in the loss of many more skilled and dedicated staff at a time when the profession can least afford it."

Annual White Coat Ceremonies More than 850 students took part in White Coat Ceremonies at RCSI University of Medicine and Health Sciences yesterday, 3 October 2023.

ATT students Shaun McElroy, Liorah Smith, Harresh Suntharam, Ella Carr and Mark Conlon celebrate at their White Coat Ceremony

The White Coat Ceremony is a traditional event in the academic calendar that originated in RCSI during the 1990s as a result of a Students’ Union request for an occasion to acknowledge the introduction of students into the Anatomy Room. It has since progressed to a formal, inter-professional event to recognise professionalism for all our new students of medicine, physiotherapy, pharmacy, physician associates studies and advanced therapeutic technologies.

Professor Hannah McGee, Deputy Vice Chancellor for Academic Affairs, welcomed students by saying: "I am delighted to have all of you joining us here this evening as we celebrate the beginning of your student journey at RCSI. This evening you will hear from senior faculty and from Student Union representatives and student speakers; we hope these talks will inspire you as you begin your RCSI student journey.”

The students were also addressed

by Vice Chancellor and Registrar Professor Cathal Kelly, Professor Denis Harkin, Head of the Centre

for Professionalism in Medicine and Health Sciences; Professor Clive Lee, Professor of Anatomy; and Professor Celine Marmion, Deputy Dean for Student Engagement, all of whom offered their best wishes and advice to the students as they embark on their health sciences studies.

Precious trust Professor Harkin told the students: "You will wear your white coat as you train in anatomy, in the laboratory when doing

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

experiments and research, and in your clinical training... It is regarded as an emblem of the precious trust which is placed in us by both patients and the public, a trust we must earn and protect."

During the ceremony, Connor Lenihan, President of the RCSI Students' Union, and Megan Cronin, Events Officer, along with other student representatives, reflected on their experiences since their own White Coat

Ceremonies and shared stories and advice with the group.

The students were then addressed

by Professor Laura Viani, RCSI President, who led them in declaring their commitment to professionalism, mirroring the declaration recited by graduands on conferring day. The declaration signals the responsibilities they must begin to undertake as future healthcare professionals and scientists from the start of their academic training.

News 13

Budget 2024: ¤22.5 billion to facilitate the continued delivery and expansion of quality, affordable healthcare services As Hospital Professional News was going to press, the Minister for Health Stephen Donnelly, Minister for Public Health, Wellbeing and the National Drugs Strategy, Hildegarde Naughton, and Minister for Mental Health and Older People, Mary Butler, announced a ¤22.5 billion health budget that will facilitate the continued delivery and expansion of quality, affordable healthcare services.

The significant allocation includes a Health Resilience Fund which will support service delivery in response to high inflation and increased patient demand among an expanding and ageing population.

Budget 2024 will provide: • ¤500 million to tackle waiting lists, including opening, and staffing six new surgical hubs • expansion of the free contraception scheme to include women aged 17 – 31 • increased funding for mental health, including additional staff for Child and Adolescent Mental Health Services (CAMHS) teams • increased funding for digital health • the first full-year programme of publicly-funded Assisted Human Reproduction services including in vitro fertilisation (IVF) • ¤36.3 million package of surge measures to respond to periods of heightened demand across acute and community services

in-patient charges, the expansion of eligibility for GP visit cards, reduction of the monthly Drug Payment Scheme threshold and the introduction of the free contraception scheme. I’m pleased to confirm that no person will age out of this scheme as the age limit is now being extended from 30 to 31.

"However, we must keep moving forward. The 2024 Health budget is reflective of our expanding and ageing population and the increased impact this has on healthcare resources.

"It will allow us to further expand capacity, including opening and staffing six new surgical hubs, as part of a generous package to tackle waiting lists. I am also allocating ¤36.3 million to a package of surge measures to ensure our health service can respond to times of increased demand for urgent and emergency care.

"As we move towards the regionalisation of our health service, my priority is ensuring that we continue to respond to the health needs of our population, by delivering a quality, equitable service for all."

Budget 2024 also contains several health promotion and prevention measures through Healthy Ireland as well as funding for the continued implementation of the National Drugs Strategy.

Minister Naughton said, "The health of the population depends

not just on the delivery of quality healthcare, but also on the promotion of healthy lifestyles which help maximise our wellbeing. A key vehicle for achieving this is our Healthy Ireland Programme. Our budget for the fund in 2023 was just over ¤14 million, and I am delighted to announce today that I have secured an additional ¤2.3 million for 2024, bringing the total to some ¤16.5 million. This represents an increase of 16%.

"Separately, I am particularly pleased to announce that I have secured funding to develop new walking trails in communities, building on the success of the GAA Walking Tracks initiative which I announced earlier this year. I have also secured funding to develop facilities to support outdoor swimming. Some ¤1 million will be provided for these initiatives."

Minister Naughton added, "Since my appointment to the Department of Health just nine months ago I have met with people who use drugs, some of whom are living with addiction, their family members, loved ones and interest groups from right across the country. One key message I have received is that we need to change how we think about and tackle drug misuse and addiction here in Ireland.

"This year I have already ensured that core funding for our Drug and Alcohol Taskforces and Section 39 organisations increased by ¤3.5 million. In addition, I provided

¤1.5 million in funding for the first time ever towards a drug and alcohol awareness programme.

Preventative education is paramount in our fight against the misuse of drugs in Ireland.

"For 2024, we will deliver groundbreaking services never before provided. They include Dual Diagnosis hubs which will support the recovery of young people with drug dependency and mental health issues, and dedicated funding for services for people on the road to recovery from drug and alcohol addiction, to support their integration into everyday life through housing, employment, education and other supports.

"It is important to note that in the last two years alone funding for our Drug and Alcohol Taskforces has increased by almost ¤10 million. I am keen that we continue to build on this so as to ensure the fantastic care that is provided from within the community is supported. In total next year the State will invest in excess of ¤145 million on drug and alcohol addiction services."

The 2024 Health Budget will see spending on Mental Health rise to almost ¤1.3 billion. This is the fourth consecutive year that an increase has been provided to support mental health services, and highlights in real terms the importance this government places on the mental health of those living in Ireland.

Announcing the measures, Minister Donnelly said, "Patients must always be at the core of healthcare delivery, and I’m determined that Budget 2024 funding will continue to deliver targeted investment that provides patients with the right care in the right place and at the right time.

"It allows us to build on the progress of the past three years which have led to significantly reduced costs and increased capacity in our healthcare service.

This record investment has provided more than 22,000 health and social care staff and more than 1,000 permanent beds since 2020.

"We’ve implemented several initiatives that remove cost as a barrier to healthcare including the abolition of all public hospital

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

14 News

Budget 2024: Delays and Deterioration in patients’ Outcomes result of no New Funding for New Innovative Medicines IPHA Chief Executive, Oliver O'Connor

“New medicines are not ‘nice to have’, they are essential for the practice of medicine and improving standards of care for patients. Our goal is a continuous, steady flow of new medicines, integrating innovation into care pathways so that Ireland will follow the best standards of care.”

Commenting on the absence of any funding for new medicines in Budget 2024, the Irish Pharmaceutical Healthcare Association has said, “In 2024 our member companies plan to launch new medicines across many types of cancers, cardiovascular diseases, HIV, auto-immune diseases, dermatology, kidney disease, musculoskeletal diseases for children and more. These new medicines include the continuous development and extension of existing treatments for diseases such as cancer.

“Without new treatment options, Irish patients will have lower standards of care, disappointed hopes and greater disease progression.

“The Budget decision appears to mean that the availability of these new medicines depends on other new savings being realised in-year by the HSE over and above the savings being delivered by IPHA members. This is not a good basis to plan for new treatments. It will lead to delays, uncertainty and backlogs, as before. In short, it risks avoidable deterioration in the conditions of many patients, adults and children included.”

Budget 2024 has effectively interrupted the normal flow of new Exchequer funding for new medicines.

Despite the absence of allocated new Exchequer funding, the Ministers for Health and Public Expenditure and Reform need to

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

make it explicitly clear to the HSE that it can continue to approve and reimburse new medicines from next January onwards.

IPHA Chief Executive, Oliver O’Connor said, “New medicines are not ‘nice to have’, they are essential for the practice of medicine and improving standards of care for patients. Our goal is a continuous, steady flow of new medicines, integrating innovation into care pathways so that Ireland will follow the best standards of care.”

“IPHA member companies are already providing savings headroom to fund these new medicines. They have implemented a range of price cuts and rebates under the 2021 Framework Agreement for the Supply and Pricing of Medicines.

Just two years into this four-year Agreement, IPHA members have delivered ¤400 million in savings to the HSE. This is more than what was expected. It compares with the overall saving of between ¤600-¤700 million anticipated by the Minister for Health over the four-year period.

Over the past three Budgets, we acknowledge that the Government had made a clear statement that they value the provision of new medicines innovation continually to patients by allocating almost ¤100 million, enabling access to over 120 new medicines or line extensions.

Public spending on medicines directly impacts patient care.

Access to these newly-available medicines has had a positive impact on the lives of thousands of Irish patients suffering from many different diseases.

Spending on medicines accounts for 15% of the overall health budget*, a normal level within Europe. On a per capita basis, Ireland’s health spending is not at all out of line, being 9th in the EU**.

Across all health spending, new medicines expenditure is among the most robustly assessed.

Budget-impact medicines go through a strict evaluation process to determine if they will improve efficiency and standards of care before being made directly available to Irish patients.

Michael O’Connell, President of IPHA, said we cannot repeat the stop-start funding for new medicines experienced in the past: “Four years ago, the Government allocated no funding for new medicines in Budget 2020.

This resulted in a backlog of medicines, causing uncertainty and unpredictability. It also meant that Budget 2021 required an over-allocation of funding to deal with the backlog of medicines which had built up in the system.

The backlog and delays were clearly bad for standards of care for patients and very frustrating for clinicians and all involved.

“Earlier this year IPHA welcomed Minister Donnelly’s decision to publish the Mazars report and to establish a Working Group to review and improve the reimbursement system for new medicines. As an Association we have engaged fully with this process and will continue to collaborate and engage to improve the current system. However, without an assurance by the Government of an uninterrupted flow of new medicines in 2024, the recommendations of the Mazars report, when implemented, will still fail to deliver the latest treatments to Irish patients. The Ministers for Public Expenditure and Reform and Health have it in their hands to avoid this, we urge them to act”, said Mr. O’Connell.

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Presentation: Vial containing 100 mg of infliximab powder for concentrate for solution for infusion.

Indications: Rheumatoid arthritis (RA) In combination with methotrexate (MTX) in adult patients with active RA with inadequate response to diseasemodifying antirheumatic drugs (DMARDs), including MTX; or adult patients with severe, active and progressive RA not previously treated with MTX or other DMARDs. Adult Crohn’s disease (CD): Moderately to severely active CD in patients who have not responded to a full and adequate course of corticosteroid and/ or immunosuppressant, or who are intolerant to or have contraindications for such therapies; or fistulising, active CD in patients who have not responded to a full and adequate course of conventional treatment (including antibiotics, drainage and immunosuppressive therapy). Paediatric CD: Severe, active CD in patients aged 6 to 17 years who have not responded to conventional therapy including corticosteroid, immunomodulator and primary nutrition therapy, or are intolerant to or have contraindications for such therapies. Ulcerative colitis (UC): Adult patients with moderately to severely active UC, and patients aged 6 to 17 years with severely active UC, who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or are intolerant to, or have contraindications for such therapies. Ankylosing spondylitis (AS): Adult patients with severe active AS who have responded inadequately to conventional therapy. Psoriatic arthritis (PsA): Adult patients with active and progressive PsA with inadequate response to previous DMARDs, in combination with MTX or alone in patients who are intolerant to, or have contraindications for MTX. Psoriasis (PsO): Adult patients with moderate to severe plaque PsO who failed to respond to, or have a contraindication to, or are intolerant to systemic therapy including cyclosporine, MTX or psoralen ultraviolet A (PUVA).

Dosage & Administration: All doses to be administered as an intravenous infusion over 2 hours initially and monitor post-infusion for at least 1-2 hours for infusion-related reactions. RA: 3 mg/kg repeated 2 and 6 weeks after initiation, then every 8 weeks; must be given concomitantly with MTX. Moderately to severely active CD: 5 mg/kg repeated 2 weeks after initiation. If no response after 2 doses, no additional dose should be given. In responding patients either: Maintenance dose of 5 mg/kg at 6 weeks after initiation, then every 8 weeks, or: Re-administration of 5 mg/kg if signs and symptoms recur. Fistulising, active CD: 5 mg/kg repeated 2 and 6 weeks after initiation. If no response after 3 doses, no additional dose should be given. In responding patients either: Maintenance dose of 5 mg/kg every 8 weeks, or: Re-administration of 5 mg/kg if signs and symptoms recur, then every 8 weeks. UC: 5 mg/kg repeated 2 and 6 weeks after initiation, then every 8 weeks. AS: 5 mg/kg repeated 2 and 6 weeks after initiation, then every 6 to 8 weeks. If no response by 6 weeks, no additional dose should be given. PsA: 5 mg/kg repeated at 2 and 6 weeks after initiation, then every 8 weeks. PsO: 5 mg/kg repeated 2 and 6 weeks after initiation, then every 8 weeks.

If no response after 14 weeks, no additional dose should be given. Paediatric CD (6 to 17 years): 5 mg/kg repeated 2 and 6 weeks later, then every 8 weeks. Data do not support further treatment in children and adolescents not responding within first 10 weeks. Paediatric UC (6 to 17 years): 5 mg/kg repeated at 2 and 6 weeks, then every 8 weeks. Data do not support further treatment in patients not responding within first 8 weeks. Elderly patients: Specific studies have not been conducted. No major age-related differences in clearance or volume of distribution observed in clinical studies. No dose adjustments required.

Contraindications: Hypersensitivity to infliximab, to other murine proteins, or to any excipients. Tuberculosis (TB) or other severe infections such as sepsis, abscesses, and opportunistic infections. Moderate or severe heart failure (NYHA class III/IV).

Warnings and Precautions: Caution in patients with or at risk of infusion reactions and hypersensitivity. Do not administer in patients with bacterial infections, invasive fungal, viral or other opportunistic infections. Monitor closely for infections, including TB, before, during and for six months post-treatment.

Evaluate and screen for latent and active TB prior to initiation of therapy. Do not use in patients with active TB. In patients with latent TB, treatment with anti-TB therapy must be started before initiation of infliximab, and in accordance with local recommendations. Consult a physician with expertise in treatment of TB. Patients with fistulising CD with acute suppurative fistulas must not initiate therapy until source of infection, specifically abscess, is excluded. Test for Hepatitis B (HBV) infection before initiating treatment. For patients who test positive, consult a physician with expertise in treatment of HBV. Closely monitor carriers of HBV for signs and symptoms of active HBV infection during and after therapy. In patients with HBV reactivation, stop infliximab and initiate effective antiviral therapy with supportive treatment. Symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or ALT elevations ≥5 times the upper limit of normal develop(s), stop infliximab and initiate thorough investigation. Concurrent administration of infliximab with anakinra, abatacept or other biologic therapeutics is not recommended due to increased risk of serious infections and/or other potential pharmacological interactions. Patients should be monitored carefully when switching from one biologic to another as overlapping biological activity may further increase risks. Patients should be brought up to date with all vaccinations in agreement with current vaccination guidelines prior to initiating infliximab. Live vaccines or therapeutic infectious agents should not be used concurrently with infliximab due to risk of clinical infections, including disseminated infections. For infants exposed in utero to infliximab, a 12 month waiting period following birth is recommended before administration of live vaccines (e.g BCG). If a patient develops symptoms suggestive of lupus-like syndrome following treatment with infliximab and is positive for antibodies against double-stranded DNA, discontinue infliximab treatment. In patients with pre-existing or recent onset of demyelinating disorders (including multiple sclerosis and Guillain-Barré syndrome), the risk/benefit of anti-TNF treatment should be carefully considered before initiation of infliximab. Discontinuation of infliximab should be considered if these disorders develop. Caution should be exercised

in considering treatment of patients with increased risk for malignancy or when considering treatment in patients that develop a dysplasia or a malignancy or with previous history of malignancy. Caution should also be exercised in patients with psoriasis and a medical history of extensive immunosuppressant therapy or prolonged PUVA treatment. Potential risk of development of hepatosplenic T-cell lymphoma (HSTCL) when used in combination with AZA or 6-MP, especially in adolescents and young adult males with CD or UC. Periodic skin examination is recommended, particularly for patients with risk factors for skin cancer.

Patients with UC who are at increased risk for, or have prior history of, dysplasia or colon carcinoma should be screened for dysplasia (including colonoscopy and biopsies) at regular intervals before therapy and throughout their disease course. Use with caution and monitor closely in mild heart failure (NYHA class I/II).

Discontinue infliximab in patients who develop new or worsening symptoms of heart failure. Patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias. Discontinuation of infliximab should be considered in patients with confirmed significant haematologic abnormalities. For patients who require surgery, the long half-life of infliximab should be taken into account and patients should be closely monitored for infections. Special populations: Particular attention should be paid to risk of infections when treating elderly and paediatric patients. If possible, comply with current vaccination guidelines prior to initiating infliximab, except for live vaccines. Sodium content: Inflectra is essentially “sodium-free”, however as it is diluted in sodium chloride, this should be taken into consideration for patients on a controlled sodium diet. Women of childbearing potential: Should consider using adequate contraception to prevent pregnancy during and for at least 6 months after infliximab treatment. Pregnancy: Should only be used during pregnancy if clearly needed. Infliximab crosses the placenta and has been detected in serum of infants up to 12 months following birth. After in utero exposure to infliximab, infants may be at increased risk of infection, including serious disseminated infection that can become fatal. Administration of live vaccines (e.g.

BCG) to infants exposed to infliximab in utero is not recommended for 12 months after birth. If infant infliximab levels are undetectable or administration was limited to first trimester of pregnancy, live vaccine administration might be considered at an earlier timepoint if there is clear clinical benefit for the individual infant. Breast feeding: Infliximab has been detected at low levels in human breast milk (≤5% of maternal serum levels), and in infant serum after exposure via breast milk. Infliximab could be considered for use during breast-feeding, but administration of live vaccines to a breastfed infant when the mother is receiving infliximab is not recommended unless infliximab serum levels are undectable.

Undesirable effects: Viral infection (e.g. influenza, herpes virus infection), bacterial infection (e.g. sepsis, cellulitis, abscess), TB, fungal infection (e.g. candidiasis), meningitis, opportunistic infection, parasitic infection, hepatitis B reactivation, vaccine breakthrough infection, lymphoma, non-Hodgkin’s lymphoma, Hodgkin’s disease, leukaemia, melanoma, cervical cancer, hepatosplenic T-cell lymphoma, Merkel cell carcinoma, Kaposi’s sarcoma, neutropenia, leucopenia, anaemia, lymphadenopathy, thrombocytopenia, lymphopenia, lymphocytosis, agranulocytosis, thrombotic thrombocytopenic purpura, pancytopenia, haemolytic anaemia, idiopathic thrombocytopenic purpura, allergic respiratory symptom, anaphylactic reaction/shock, lupus-like syndrome, serum sickness or serum sickness-like reaction, vasculitis, sarcoid-like reaction, dyslipidaemia, depression, insomnia, amnesia, agitation, confusion, somnolence, nervousness, apathy, headache, vertigo, dizziness, hypoaesthesia, paraesthesia, seizure, neuropathy, transverse myelitis, central/peripheral demyelinating disorders, cerebrovascular accidents in close temporal association with infusion, conjunctivitis, keratitis, periorbital oedema, hordeolum, endophthalmitis, transient visual loss, tachycardia, palpitation, cardiac failure, arrhythmia, syncope, bradycardia, cyanosis, pericardial effusion, myocardial ischaemia/ infarction, hypotension, hypertension, ecchymosis, hot flush, flushing, peripheral ischaemia, thrombophlebitis, haematoma, circulatory failure, petechia, vasospasm, upper respiratory tract infection, sinusitis, lower respiratory tract infection, dyspnoea, epistaxis, pulmonary oedema, bronchospasm, pleurisy, pleural effusion, interstitial lung disease, abdominal pain, nausea, gastrointestinal haemorrhage, diarrhoea, dyspepsia, gastroesophageal reflux, constipation, intestinal perforation/stenosis, diverticulitis, pancreatitis, cheilitis, hepatic function abnormal, transaminases increased, hepatitis, hepatocellular damage, cholecystitis, autoimmune hepatitis, jaundice, liver failure, psoriasis (new onset or worsening), urticaria, rash, pruritus, hyperhidrosis, dry skin, fungal dermatitis, eczema, alopecia, bullous eruption, onychomycosis, seborrhoea, rosacea, skin papilloma, hyperkeratosis, abnormal skin pigmentation, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, furunculosis, linear IgA bullous dermatosis, acute generalised exanthematous pustulosis, lichenoid reactions, worsening of symptoms of dermatomyositis, arthralgia, myalgia, back pain, urinary tract infection, pyelonephritis, vaginitis, infusion-related reaction, pain, chest pain, fatigue, fever, injection site reaction, chills, oedema, impaired healing, granulomatous lesion, autoantibody positive, complement factor abnormal.

For a complete list of undesirable effects please refer to the Summary of Product Characteristics.

Legal category: POM; S1A. Marketing Authorisation Number: EU/1/13/854/001, EU/1/13/854/002, EU/1/13/854/003, EU/1/13/854/004, EU/1/13/854/005.

Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

Last Revised: April 2022.

Ref: IF 7_1 IE. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 467 6500.

1. Gheorghe C, et al. J Drug Assess 2019;8:129-34. 2. Jørgensen KK, et al. Lancet 2017;389:2304-16.

3. INFLECTRA® Summary of Product Characteristics. 4. Schwartzman S, Morgan Jr, GJ. Arthritis Res Ther 2004;6:S19-23.

PP-IFA-IRL-0162 | Date of Preparation: September 2023

16 Musculoskeletal

Priorities for rheumatic and musculoskeletal disease research in Ireland Written by Emma R. Dorris1, Stacey Grealis2, Karmen Kegl3, Norelee Kennedy4, Louise Larkin5, Brian Lynch6, Ailis Moran7, Justine O’Brien7, Stephanie Skeffington8, Kayleigh Slater7, Rebecca Ward7 and Allison Willett9 University College Dublin, Belfield, Dublin 2Mayo, Ireland 3Dublin, Ireland 4Discipline of Physiotherapy, School of Allied Health, Faculty of Education and Health Sciences, University of Limerick and Health Research Institute (HRI), University of Limerick, Limerick 5Health Research Institute (HRI), University of Limerick, Limerick 6Arthritis Ireland 7UCD School of Biomolecular and Biomedical Science, University College Dublin 8Tipperary, Ireland 9UCD College of Social Sciences & Law, University College Dublin 1

In Ireland, there has been a dedicated effort to engage a wider variety of stakeholders and the general public in all aspects of health research.1 The Irish government releases national research priority areas. Recently, they have initiated a programme to incorporate public views on research.2 There is increasing recognition of the historical bias in the research agenda and knockon evidence disbalance.3 These developments acknowledge gaps and uncertainty in the evidence base. Acknowledging this uncertainty, recognises that the judgement involved in assessing incomplete bodies of evidence are not solely dictated by scientific reasoning. Thus, the values and knowledge of “non-experts” can have a valid role in the decisions around research priorities.

Whereas national level prioritisation of research is useful in selecting general areas of focus nationally, it does not identify what research should be undertaken within these areas. Research in rheumatic and musculoskeletal disease (RMD) spans broad and diverse areas, with research priorities largely driven by individual researcher/research group interests and expertise.

Research priorities are also driven by the research funding landscape, for example where a funding body launches a funding call targeted at a specific condition or topic.

This traditional approach to the identification of research priorities and subsequently the research conducted may lack input from key stakeholders including people living with RMDs, carers, and healthcare professionals. Thus, in some cases the research priorities of people living with RMDs and other relevant stakeholders, have not been explored.

Seeking stakeholder perspectives is critical to informing research priorities to focus research resources in key areas. The involvement of public and patient

involvement (PPI) partners can also inform such research priorities from a unique perspective. A comprehensive and cohesive research prioritisation programme has not been defined within Ireland beyond the governmental context.

The current approach poses challenges given the competitive nature of attaining funding to support research projects. The lack of a strategic approach to the conduct of research in RMDs within the Ireland also acts as a barrier to engagement and collaboration between the RMD academic and research community.

Priority setting partnerships provide a valuable means of identifying research priorities.

Such prioritisation can serve to aid organisations such as charitable groups work with funding agencies to develop themed calls linked to the priorities. The overall connectivity across the research-patient-health ecosystem possible through the research priority setting (RPS) approach provides confidence in the value of the research undertaken. The RPS priorities can result in new funding for research and also lead to new relationships developing that benefits the overall research ecosystem.4 At a policy level, prioritisation exercises add value to the decision-making process by bridging the gap between the public/patient and the academic community leading to research that has greater overall societal impact.

Here, we present the process and results from a national RPS for arthritis and rheumatic disease research in Ireland. The project was undertaken by a multidisciplinary team of researchers and people living with rheumatic diseases following a deliberative decision-making model. The output of this RPS is designed to facilitate more socially, economically, and clinically impactful decisions about arthritis and RMD research in Ireland.

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Methods Statement of ethics This study was granted exemption from full ethical review by the University College Dublin Human Research Ethics Committee— Sciences (LS-E-20-38-Dorris).

Anonymous surveys were used and no identifiable data was collected. Digital informed consent was obtained as part of the survey (Additional file 2).

Public and patient involvement PPI contributors were full partners in this study, involved from conception, throughout design and conduct of the study, and in the analysis, preparation and revision of the manuscript.

Governance and team The initiative was developed by one of the authors (ED) after consultation with peers, patient insight partners and Arthritis Ireland, Irelands national and largest charity dedicated to supporting people with arthritis, rheumatic diseases, and musculoskeletal disorders. The Arthritis Ireland Research Working Group acted as the governance committee. This consisted of two senior members of Arthritis Ireland, a patient member of Arthritis Ireland, the Chairs of Rheumatology at two major Irish Universities, consultant rheumatologists, a research scientist, and a professor in physiotherapy and vice president for research at an Irish University.

The project team consisted of a research scientist with experience in RPS. There were three patient insight partners, all of whom had previous PPI experience, and all of whom had personal experience in different RMD areas and were located in different geographical locations within Ireland. The remaining team comprised two academic physiotherapists: a postdoctoral researcher with

experience in mixed methods and a professor of physiotherapy with significant experience in research policy.

Process framework Viergever et al.’s checklist for health research priority setting was used to plan the RPS process.5 Situational analysis and development of scope The scope of the research prioritisation was defined via situational analysis of the Irish research context. This consisted of an analysis of peer reviewed and grey literature related to how research decisions are currently made in Ireland; who makes research decisions in Ireland; Who are the influential actors in research decision making; What policy and procedural documents are in place for decision making in RMD research in Ireland; and whether there is scope for improvement in research decision making practices. We used online search engines including PubMed and Google Scholar, organizational databases including Lenus Irish Health Repository and the Houses of the Oireachtas Library Digital Collections.

We analysed if there was a need for research priority setting for arthritis and rheumatic diseases in Ireland, and if so, what was the best way to approach it.

This refined the prioritisation into five key areas: 1. The problem: research to measure the size of the health problem associated with RMDs in Ireland; 2. The cause: research to understand the causal agents and determinants of RMD and RMD-related health issues; 3. Solutions: research into what new interventions, tools, medicines, therapeutics are needed; 4. Policy & Practice: research to translate new interventions into policy and practice and understanding the barriers to delivering known interventions; 5. Health Impact:

17 research to monitor and evaluate the effectiveness or health impact of an interventions or programmes.

Design workshop This phase was aimed at defining the selection and analysis criteria for RPS. In later steps we used surveys to gather information.

We needed to know if (1) different stakeholders understood research prioritisation differently and (2) how to define if we had successfully captured enough information in these surveys.

related not just to prevalence, but to a more diverse interpretation including social, psychological and economic costs of RMD. If we did not receive a diversity of interpretation in the survey data at the interim analysis, the design of the survey and its dissemination would be reviewed.

Identification of research topics: survey design

We held a workshop with mixed stakeholder attendees including people living with rheumatic diseases, family members, junior doctors, consultant rheumatologists, allied health care professionals, researchers, and charity advocates.

A survey was designed for people to submit what topics/ areas they thought needed to be researched to improve quality of life for people living with RMD in Ireland. The survey can be found in supporting materials. The survey was completed anonymously. It stated explicitly on the survey that “by participating in this survey you consent to the use of your anonymous data”.

The workshop used a banquet style layout with a facilitator and a note taker at each table. The tables consisted of mixed stakeholders.

All facilitators were briefed in advance and had a facilitators guide to direct the workshop. The tables were covered in white paper tablecloths, which attendees were encouraged to write on should they wish to leave any additional thoughts or feedback.

The survey was reviewed and revised for clarity by a communications specialist, two people for whom English was not their first language, representatives of the key audience for the survey including people living with RMD (n = 4), family members (n = 2), clinicians (n = 3), allied health care professionals (n = 2), charity advocates (n = 2), and researchers (n = 2).

The workshop used two main techniques: Mind Mapping and MoSCoW. Mind Mapping allowed attendees to deconstruct complex topics into a graphical representation of constituent subtopics and related themes.

MoSCoW is an acronym derived from four prioritization categories (Must have, Should have, Could have, and Won't have). The workshop was designed to generate ideas using the mind map technique, and to use MoSCoW to narrow the scope. This combined method produced a strategy for the RPS, with all stakeholders agreeing on a single, clear set of deliverables for each stage of a project in a transparent way.

The survey was divided into two sections. Section one collected demographic information and section two collected the research questions the respondent would you like to see answered by RMD research. The survey collected the following demographic data on respondents: stakeholder category, age band, sex, ethnic/ cultural background, province of Ireland lived in, and community.

The design workshop facilitated better understanding of what was expected of the priority setting exercise from different stakeholder, which allowed better design of the survey to meet these expectations.

The design workshop also informed the analysis phase.

There were particular themes of research that the workshop anticipated should be reflected in the survey responses if the survey was conducted effectively and survey dissemination reached the intended diverse stakeholders.

These acted as performance indicators for the survey. For example, under the key area “The Problem: Research to measure the size of the health problem in Ireland”; through the workshop we anticipated input on questions

in each email. The survey was also advertised on social media.

No incentives were offered for completion. Unique survey respondents were measured via IP address. Cookies were not used.

Survey analysis An IP check was performed to identify potential duplicate entries.

No duplicate entries were identified.

All surveys, including incomplete surveys, were analysed.

There were 2185 research questions submitted by 545 respondents to the survey. Many people will ask a similar question in different ways. Thus, the submitted questions were analysed and grouped into themes.

Scope Every submitted question was assessed to determine if it was within scope of the RSP. Respondents had been asked not to refer to specific RMDs in their responses. The responses should relate to arthritis and RMD research generally. If a respondent had simply answered with a condition that answer is out of scope.

Real Examples: • “Fibromyalgia” • > Out of scope • “Are symptoms attributed to fibromyalgia in people with Psoriatic Arthritis really a distinct entity or should they be considered part of the diagnosis of Psoriatic Arthritis?”

• > In scope. Classed as Impact of co-morbidities on diagnosis.

Data quality expectations

There were five subsections in section two, and respondents could submit up to three questions in each subsection. The survey was only available in English.

There was a mechanism to request a paper version of the survey and request assistance to help complete the survey via phone, email or post. The eSurvey was conducted using the Survey Monkey platform.

The submitted questions were compared with the criteria identified during the design workshop to determine if the expected diversity of submissions was achieved. The demographic data was also assessed to determine if a diverse group of respondents had been reached and if different communities, geographies and stakeholder types had been reached.

The survey was publicly available for anyone to complete. It was launched on the 06 April 2020 and open for six weeks. It was available on the Arthritis Ireland (Irish National RMD charity) website. It was sent to Irish professional organizations for rheumatologists, physiotherapists, nurses and other health care professionals. It was sent out to researchers investigating different aspects of rheumatic diseases in Universities across Ireland by email. Two reminder emails were sent, to encourage participation.

The survey link was included

Grouping The aim is to group similar questions together to identify the unique questions/areas. This was done by independent researchers, not in the field of rheumatic disease, to reduce potential bias in interpretation. All topics were analysed by two separate researchers, who had to agree that the questions, or topics, should be grouped together. Any disparity between the two researchers were brought to a third researcher and discussed for consensus.

A member of the project team

reviewed the research themes and analysis. The project them as a whole then reviewed and agreed upon all the thematic grouping of the submitted questions. This reduced the list down to thirtyeight major research themes.

Research topic ranking (prioritisation) survey A voluntary open survey hosted on the survey monkey platform was designed. This consisted of two pages. The first page gave information and instructions about the study. Page two consisted of two questions: Question one was “Choose and rank your top ten most important research questions from the list below. With 1 being the most important, 2 the second most important and so on.”

Question two was a free text space that asked, “Is there anything else you would like to tell us?”.

Two versions of the survey were used. Both were worded the same. However, feedback on the first survey, which used ranking dropdown as the answer method, was that it was cumbersome to complete on certain mobile devices. Thus, survey version two had a mobile-friendlier interface by using a matrix format, with the 38 questions to be ranked as row items and the ranking options of 1st Priority, 2nd Priority, 3rd Priority……., 10th Priority, NOT a top priority for me or N/A as the column choices. The matrix version, survey version two, did not automatically prevent more than one question being given a first priority rank.

The survey was publicly available for anyone to complete. It was launched on the 11 November 2020 and open for twelve weeks.

It was disseminated via the same channels as the previous survey.

No incentives were offered for completion. Unique survey respondents were measured via IP address. Cookies were not used. Demographic data was not collected for this survey.

Analysis of the ranking survey Each rank was given a weighted score (see page 18).

When data from survey version two was being recoded with the weighted scores, cases where more than one question had been given the same ranking were adjusted. For example, if a respondent gave three questions a first priority, each of these questions would be given a score of 8, and subsequent rankings adjusted (the second priority a score of 7, the third a score of 6 and so on). No one respondent could give a combined score of > 55 in total. This prevented skewing of the results by any one individual. The scores for each

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18 Musculoskeletal Priority rank

1st

2nd

3rd

4th

5th

6th

7th

8th

9th

10th

Weighted score

10

9

8

7

6

5

4

3

2

1

of the thirty-eight questions were summed to determine a ranking of the research topics by priority.

Internal validity check between survey versions There was n = 272 respondents to survey version one and n = 192 respondents to survey version two.

An IP check was performed to identify potential duplicate entries.

No duplicate entries were identified.

All surveys, including incomplete surveys, were analysed. Surveys were checked for duplicate entries.

None were observed.

The rankings of each version were compared to each other and to the final/overall ranking. If the format did not make an impact, we would expect there to be similar rankings. There was good internal consistency between the versions. Overall, the consistency between versions was very strong, particularly within the top 10 (Additional file 1: Fig. S1).

Top 20 identified research topics: analysis of the literature A search of peer-reviewed original research, systematic review, and evidence synthesis literature was performed using online search engines including PubMed and Google Scholar. Grey literature was not included. Literature was searched for inclusion of Irish subjects or data within the study population. Most research is condition-specific, and therefore the search included articles related to “arthritis” “rheumatic disease” “RMD” “rheumatic and musculoskeletal Disease” and “rheumatology”. The search was not time-bound. Sample references are all within 15 years of the search. The aim was to identify recent literature (or lack thereof) to determine that the top 20 ranked research questions had indeed not yet been answered yet from 1. an Irish Perspective and 2.

An international perspective.

That could be a well cited, high impact publication in the field that says "more research is required" or a systematic review or similar (Fig. 1).

Figure 1

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Ranking Table

19

Results Research topic submission survey There were 545 respondents to the survey. There were 2185 topics submitted, of which 160 were determined to be out of scope. 22/545 (4%) of respondents provided partial demographic details and did not submit any research topics.

One respondent did not submit any data. We had representation from the four provinces of Ireland (Leinster 48.07%, Munster 23.36%, Connacht 21.43%, and Ulster 5.02%). Compared to the population of the provinces, Connacht is overrepresented and Leinster is underrepresented in our dataset.6 We had representation from all community types (urban (28.96%), suburban (27.41%), rural (42.28%) and island (< 1%)).

Men (n = 96) were relatively underrepresented in the sample compared to women (n = 416).

The ethnic/cultural background of the sample was predominately white Irish (n = 479). The Irish population is also predominantly white Irish (82.2% 2016 census data7). However, compared to the proportional representation in the general population, Traveller and Asian communities are underrepresented in our data by approximately half, and Black/ Black-Irish is underrepresented at approximately one quarter of what we would have expected to be reflective of the general population.7 Interim analysis identified a total lack of representation from the Traveller community. In response, we proactively engaged with Pavee Point, the Traveller and Roma centre, to increase engagement.

The themes of research that the workshop anticipated should be reflected in the survey

responses if the survey was conducted effectively and survey dissemination reached the intended diverse stakeholders were present in the data. Pattern and topic analysis grouped the submitted topics into 38 RMD research topics of priority for Ireland.

Ranking survey There were 460 respondents to the ranking survey. The results of priority ranking and distribution of the weighted scores can be found in Fig. 2. The median weighted score for the 38 questions being prioritised is 560 and the mean score is 619.66 (95% CI: 536.92–702.40). The top 10 ranked research priorities have scores ranging from 1352–785, with priorities ranked 11–20 ranging from 709–584, and remaining topics scoring between 508–207.

Evidence uncertainty in top ranked research priorities A literature search of the top ranked research priorities demonstrated there was evidence uncertainty for all top priorities.

Of the top 20 priorities, 15 had either no studies or only smallscale studies published from an Irish-specific perspective. Further literature was available from an international perspective, however, literature relating to the impact of national government policy, the impact of RMD on employment, careers, and schooling and the impact of clear communication about treatment and management tended to be regionally restricted or largely underrepresented in more recent literature.

Discussion Here we identified the top research priorities for arthritis and RMD research in Ireland. Of note is the scope of the priorities identified.

In addition to clinical and health

services-related priorities, there was focus on self-management factors, such as diet and exercise, and secondary impacts such as pain and mental health.

The identification of RMD research priorities presents an excellent opportunity for a more cohesive and focussed research strategy within the Irish context.

Stakeholders now have a definitive list of research topics which are deemed of significant importance to the RMD community. This should guide the research strategy of research groups, harnessing the expertise of the academic and PPI research community to examine specific topics. This targeted approach can facilitate increased collaboration and lead to enhanced research outputs and impacts to the key areas identified in this prioritisation. A focussed approach to research has the potential to impact beyond research, by highlighting key issues and increasing the depth and breadth of research on prioritised topics.8 There will be scope to influence healthcare policy and delivery with a more robust body of research evidence, thereby enhancing the health outcomes of people with RMDs. Health research charities provide significant funding for research.9 The identification of national research priorities can help to guide charities in the direction of what research to fund. It can also be very useful in the development of research strategies and fundraising as it gives a truer sense of the needs and challenges of the community as a whole.10 The priorities identified here have been used by the national Irish RMD charity Arthritis Ireland in their latest funding call.11 They are also being used to inform their research strategy. Having an

Figure 2

evidence-based, transparent set of priorities identified by the community the charity represents can greatly assist in communicating clear needs and goals to potential donors.

RMDs are complex conditions with a wide impact on peoples’ lives.

There are no easy answers when it comes to understanding their related impact on social issues, healthcare, and quality of life.

While this RSP was undertaken in Ireland, given the evidence uncertainty present for the top 20 priorities it is reasonable that the findings of this study are relevant to groups in other countries considering undertaking an RSP. Conclusion Research funded in response to these co-created research priorities should have increased relevance and impact. As the priorities were developed together with all stakeholders who have an interest in improving the quality of life for people living with RMDs, there is shared ownership. This provides a strong foundation to continue the process of collaboration between people living with RMDs, advocating for RMDs, researchers and healthcare professionals.

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

20 News

Accreditation for St Vincent’s University Hospital Pictured are Prof Emir Hoti alongside members of the Surgical Fellow Team, who have played a pivotal role in this accomplishment

maintain, as established by the European Board of Surgery.

St. Vincent’s University Hospital’s Hepatobiliary, Transplant, and Liver Services Directorate have proudly announced the recent accreditation from the European Board of Surgery (EBS) for Training in Multi-Organ Procurement and Liver Transplantation. This significant achievement highlights the exceptional commitment to

excellence in healthcare that our institution upholds.

The European Board of Surgery Accreditation (EBS) is a prestigious recognition bestowed upon our hospital’s Multi-Organ and Liver Transplant Team. It serves as a testament to the high standards of quality and safety that our surgical services and training consistently

Professor Emir Hoti, Director of the National Liver Transplant Programme at St. Vincent’s University Hospital expressed his pride, saying, “Achieving this prestigious EBS accreditation is a testament to our unwavering commitment to providing the highest quality care to our patients.

We are proud of this achievement and the impact it will have on advancing healthcare standards.”

This accreditation represents a milestone in their continuous pursuit of excellence in patient care and surgical expertise. It offers numerous advantages, all of which ultimately benefit our

patients, who are at the core of St Vincent Hospital’s mission: 1. International Recognition: The EBS accreditation places St. Vincent’s University Hospital on an international stage, showcasing our dedication to delivering world-class healthcare services.

2. Quality Assurance: Meeting the rigorous standards set by the European Board of Surgery reaffirms our commitment to delivering safe, high-quality care to our patients.

3. Improved Patient Outcomes: The accreditation signifies our unwavering dedication to improving patient outcomes, ensuring that our patients receive the best possible care.

4. Professional Development: The accreditation process has provided our team with significant opportunities for professional growth and development, further enhancing our ability to serve our patients effectively.

Pharmacy must Mitigate to Climate Change Calls for climate change action in pharmacy are made by FIP in a new Statement of Policy published recently. The new policy, on environmental sustainability within pharmacy, expands on a 2016 FIP statement on the importance of reducing the environmental impact of pharmaceuticals and related activities. It makes clear that environmental sustainability includes both mitigation measures, such as reducing pharmaceutical pollution and greenhouse gas emissions, as well as adaptation measures to climate change.

“Pharmacy professionals have an ethical responsibility to mitigate climate and pollution risks to health throughout the pharmaceutical supply chain and across the spectrum of medication management. For example, optimised medicines management can mitigate the environmental footprint of health care within clinically appropriate deprescribing. However, the profession must now also address climate adaptation to allow for the sustainability of pharmacy services in rapidly changing environments,” said Shellyza Moledina Sajwani, co-chair of FIP’s policy committee that developed the statement.

For different sectors of the profession — pharmacy associations, hospital, community, regulation, industry, procurement, academia, public and population health, military and emergency services — the new policy statement makes a number of recommendations under the headings of mitigation and adaptation.

For example, under mitigation, the federation says that regulators should collaborate with other stakeholders to build standardised data collection at national level about greenhouse gas emissions and waste from all sectors of pharmacy while creating objectives to reduce the environmental impact of medicines across their lifecycle. And under adaptation, it says that community pharmacists should update their disaster plans for emergencies and provide regular training or drills on disaster plan procedures relevant to worsening natural disasters and extreme weather events.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

Abstract 21

Hypertension and Chronic Kidney Disease Prevalence, Awareness, Treatment and Control of Hypertension in Older Adults with Chronic Kidney Disease Written by Mohammed Alamin1, Hamidi Miri1, Mary Byrne1, Robert Gilligan1, Leonard Browne1, Donal Sexton3, Austin Stack2 1

University of LImerick, School of Medicine, Limerick

2

University of Limerick, Health Research Institute, Limerick; University Hospital Limerick, Department of Nephrology, Limerick

Trinity College Dublin, School of Medicine, Dublin; Trinity College Dublin, Department of Medical Gerontology, School of Medicine, Dublin; Trinity College Dublin, Trinity Health Kidney Centre, Dublin, Ireland 3

Background and Aims

sample weights, and multivariable logistic regression explored associations of demographic, clinical and behavioural characteristics with control of hypertension. Associations were expressed using adjusted odds ratios (OR) with 95% confidence intervals (CIs). Analyses were conducted in Stata and R.

CKD. The weighted prevalence of hypertension was significantly higher in participants with CKD than without CKD (81.8% versus 59.8% respectively, P<0.001).

Among those with CKD and hypertension, 70.8% (95% CI: 66.5-74.7) were aware of hypertension, and 83.4% (95% CI 79.9-86.5) were treated with antihypertensive medication.

Despite higher levels of awareness and treatment of hypertension in those with CKD, only 50.4% (95% CI 45.4-55.5) of treated subjects had BP <140/90 mmHg. BP control was similarly poor for non-CKD participants at 49.4% (95%CI: 46.9-51.8). The most commonly used medications among treated CKD participants were β-blockers 41.8% (95% CI 36.7-47.1), angiotensin-converting enzyme inhibitors 34.0% (95% CI 29.2-39.2), and angiotensin receptor blockers 33.7% (95% CI: 28.9-38.8). Over half [54.8% (95% CI: 49.5-60.0)] of CKD

participants were treated with ≥ 2 antihypertensive medications.

In multivariable analysis, the likelihood of BP control (<140/90 mmHg) was lower for older CKD patients [OR: 0.94 (95% CI: 0.900.98) per 1 year increase in age], greater for those on combination therapy [OR: 1.87 (95%CI: 1.133.1)] and for those with history of cardiovascular disease [OR: 2.33 (95%CI: 1.43-3.82)].

Conclusion Despite established evidence that control of hypertension can slow the progression of CKD and reduce cardiovascular complications, our results indicate that the prevalence of hypertension in older adults with CKD is high and the control of hypertension is poor and worsens with advancing age. Approximately, one third of participants with CKD were unaware of their hypertensive status and approximately one fifth of participants were untreated.

Hypertension is a well-known modifiable risk factor for chronic kidney disease (CKD) yet effective management remains a challenge.

Data on hypertension awareness, treatment and control among CKD patients in Ireland is limited.

Therefore, the objective of this study was to determine theFigure 1: Comparisons of weighted prevalence (95% Confidence Results prevalence, extent of awareness, Figure 1: Comparisons of weighted prevalence (95% Confidence intervals) of hypertension, awareness, treatment, andConfidence ... treatment and control of intervals) ofFigure hypertension, awareness, treatment, and control of blood pressure among 1: Comparisons of weighted prevalence (95% There were 639/5,356 participants hypertension among older adults participants with and without Chronic Kidney Disease (CKD). intervals) of hypertension, awareness, treatment, and ...

[13.3% (95%CI: 12.3-14.4)] with with CKD in the Irish population.

Method We utilised cross sectional data from the first wave of The Irish Longitudinal Study on Ageing (TILDA) conducted between 2009 and 2011. Participants aged 50 years or more with complete measurements on serum creatinine and blood pressure (BP) were included (n = 5, 356). CKD was defined as eGFR <60ml/ min/1.72m2. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or selfreported use of antihypertensive medication. Participants’ awareness and treatment of hypertension were defined using self-report and hypertension control was evaluated as systolic/diastolic blood pressure <140/90 mmHg. We determined the weighted prevalence of hypertension, awareness, treatment, and control using

Nephrol Dial Transplant, Volume 38, Issue Supplement_1, June 2023, gfad063c_6749, https://doi.org/10.1093/ndt/gfad063c_6749 The content of this slide may be subject to copyright: please see the slide notes for details.

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

22 Diabetes

Ground-breaking Survey into Living with Diabetes Diabetes Ireland launched the results of the first-ever survey highlighting the lived experience of people with diabetes in Ireland.

An anonymous online survey of adults with diabetes or parents/ carers of children with diabetes was conducted between 16 January and 5 February 2023 via social media and standard online communication to ask about experiences of living with diabetes in Ireland. 517 people completed all sections of the survey: 230 adults with type 1 diabetes, 155 with type 2 diabetes and 12 with other types of diabetes, and 120 parents/carers.

Amongst adults, 37% reported they were already living with diabetes-related complications and comorbidities. Most commonly these were hypertension (high blood pressure - 23%), diabetes retinopathy (23%), hypothyroidism (17%) and mental health-related issues (14%). During their lifespan living with diabetes, both adults & children living with type 1 diabetes had experienced severe complications: 40% had experienced DKA, mainly at the time of diagnosis, which should be avoidable if diabetes symptoms were recognised early; and 45% of adults experienced at least one episode of severe hypoglycaemia – a critically low glucose level, which usually comes with unconsciousness and requires third party help and possible hospitalisation.

In terms of their ongoing care, the majority of respondents were cared for in the public system but 20% of people with type 1 diabetes and 46% of those with type 2 diabetes pay privately for diabetes care. Only 13% of adult respondents had no review appointment with their healthcare provider in 2022 with a further 29% having only one appointment. However, all children with type 1 diabetes had at least 2 or more appointments in the same period, with 67% of them having 3 appointments or more.

Overall, respondents expressed satisfaction with their diabetes care, but many highlighted the lack of time given to them by their diabetes healthcare provider and felt the appointments were rushed.

The vast majority of respondents (88%) are under the Long-Term Illness Scheme, giving them access to free diabetes related medications and technologies plus free high blood pressure and high cholesterol medications.

Interestingly, when comparing Dublin with the rest of the country, there were a number of noticeable differences in people’s daily experience of living with diabetes.

More often, people with type 1 diabetes pay privately for their diabetes care if they live outside of Dublin (19% vs. 10%). Among people with type 2 diabetes, those from outside of Dublin were usually receiving their care in general practices (75% vs. 55%).

People from Dublin more often were treated in outpatient diabetes hospital clinics (27% vs. 20%) or attended diabetes clinics privately (13% vs. 5%).

Among adults living with type 1 diabetes, those living outside Dublin were more often diagnosed with diabetes related complications or comorbidities (41% vs. 35%). Among people with type 2 diabetes, those living outside Dublin more often had increased occurrence of diabetes-related complications or comorbidities (48% vs. 20%), mainly hypertension (40% vs.

18%) and mental health related issues (24% vs. 15%).

hear from people with diabetes about difficulties in accessing diabetes care services and new technologies across the country. However, we had no real data on this, so we decided to undertake this survey and provide an opportunity for people with diabetes to share their experience of accessing services and living daily with the condition. This survey is the first of its kind in Ireland, and in the absence of a National Diabetes Register and Clinical Audit, it provides very detailed information about experiencing diabetes care by those affected by diabetes in Ireland.”

Alongside the release of the survey findings, Diabetes Ireland is also launching its Pre-Budget Submission 2024 calling on the Minister for Health to set up a Taskforce, similar to the Cancer Strategy Taskforce to develop a 10-year National Diabetes Strategy to improve and standardise the delivery of care, access to diabetes services to improve the quality of life of more than 300,000 people living with diabetes in Ireland.

challenge for the government and the Health Service Executive.

The high cost of diabetes is mainly caused by the treatment of complications, many of which could be avoided with earlier detection, greater awareness of symptoms, better access to newer treatments and diabetes technologies, multidisciplinary teams, including psychologists, and regular diabetes review appointments. Despite the positive ongoing work of the HSE and Sláintecare, there are still many gaps in current diabetes services, as highlighted by this survey, that need to be tackled strategically in order to provide optimum diabetes care to everyone in need.

Therefore, to improve diabetes care, we need to collectively act now and decide what future care for people with diabetes will look like. “The Cross Parliamentary Group on Diabetes agree that it is time to set up a diabetes taskforce of relevant stakeholders to develop a 10-year National Diabetes Strategy that provides vision, leadership, direction, goals, and priorities, as well as identifying and securing the future funding required to provide optimum care for every person living with diabetes in Ireland. We know this will take some time, but we need to be very forward thinking

Overall, the rates of technology Cormac Devlin TD, Chairperson usage (CGM) were very high and of the Cross Parliamentary Group there were no differences between on Diabetes said: “The economic Dublin and the rest of the country burden of diabetes on the Irish with insulin pump usage also healthcare system is now a major been similar. However, in openended responses many people referenced very long waiting LIVING lists and difficulties in accessing WITH DIABET ACCES ES IN IR SING A diabetes-related technology, ELAND ND USI : FIND NG DIA INGS FR THE N BETES EED FO OM TH mainly insulin pump therapy, as HEALT R A 10 E SURV H SERV -YEAR EY ON NATIO ICES B EXPER W NAL D Di Y PEO hy? well as difficulties D: chro abetes can be IENCIN IABETE LAN PLE W IRE IN E S STRA G, nic cond a relent ITH DIA DIABETES CAR TEGY le iti ss on BETES IN IREL 4their families. , affecting pe and burdenso 202 in accessing N .

SIO A MIS ND m It’s estim ople of e people al PRE-BUDGET SUB at the l liv ed ag and e ent es that ap with di ernm and on the Gov abetes prox. 30 calls Pe nd specialist Irela op To in Irela le have gether 0,000 How? ity, Diabetes nd. inclu with he to lf2024 da ily (edes: diabetes commun and academ .g. adapimprse althca re that Budget anagss ovemacce On behalf of the re prof to t to nu e diab ics and Health to ensu Stra ect tegy multidisciplinary essiona etes inj etes trithan Department of insuli people conduc tional 300,000 ls, rese ear National Diab advice, living wi ofecmore ted a su 365 da beinn,gch THE SU archer k glucos develop a 10-Y take m th diab rvey to ys a ye - Living s, ), health and well a Taskforce to RV e (QoL up le] le ed life set EY etes we ligib of ask ab ve to ar ici s ity Neg with di ls etc.) nes, 1) Cost team members ds [Cos, t:with no br out: To se frien abetes ices, improve qual and 7 days rs TO serv for loye lfM ), care ea O emp an m etes (CGM rs, since di L anage itoring ks or ho a week agemen accegluc delivery of diab ose mon their di , lidays. their families, care agnosis t ss nd, us of Irela to in inuo di Di cont abet health abetes abetes on] diabetes milli es we t: €5 multid (e.g. dietitians, any form of a ca [Cos to ca s. ss people living with re ll, eline re acce guid re pr is receive ove - Diab nal ciplinar gular ofessi etes ch d of €5 m to impr onal su nal and internatio educat y team eck-up 2) Investment pport, mmended by natio s (MDT ion, an - Appo s intmen nual re ), diab 1 diabetes as reco podiatrists, their lif ts in 20 etes views, people with Type We aske estyle 22. treatm and ne d adult from co ent th eds an s living parent m at pl ic su d wi s of ch psychologists etc). ations keeps its th diab ildren We ofte , are ab them sa etes (a Peop wi Charity

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NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

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23 in our approach to dealing with diabetes long into the future and the immediate setting up of a Taskforce will help us achieve it.” – added Mr Devlin.

Diabetes Ireland, alongside the HSE National Clinical Programme, is also calling for additional funding

of ¤5m to enable more equitable access to continuous glucose monitoring (CGM) for people with type 1 diabetes. Professor Derek O’Keeffe, National Clinical Programme for Diabetes Lead said: “In line with international best practice, the National

Clinical Programme for Diabetes is requesting a broadening of the criteria for the provision of a form of CGM to all individuals living with Type 1 diabetes in Ireland. Bearing in mind that many people already use CGM in Ireland, securing ¤5 million by the Government in the

Budget 2024 will facilitate more equitable access and reduce disparities for those living with type 1 diabetes who have not availed of this technology yet, will help them improve their diabetes management, outcomes and quality of life.”

News

University of Galway in New Research Partnership University of Galway has announced a new partnership with the National Breast Cancer Research Institute (NBCRI) with the charity committing a ¤2 million research investment fund over two years.

The collaboration builds on a longstanding relationship between NBCRI and the University, which dates back to the 1990s and has involved support for numerous projects and developments in breast cancer research.

President of University of Galway Professor Ciarán Ó hÓgartaigh with Professor Michael Kerin, Director of Research at National Breast Cancer Research Institute and Professor of Surgery at University of Galway and Kelsey Bruce, researcher at University of Galway, to announce the new NBCRI-University of Galway partnership and ¤2m research funding. Credit – Andrew Downes, XPOSURE

One in 7 Irish women will be diagnosed with breast cancer in their lifetime and there are 3,507 breast cancer diagnoses every year - a figure which is set to continue to increase.

Thanks to advances in research and healthcare, the survival rate of breast cancer patients has gone from 50% to 88% over the last 40 years.

The NBCRI-University of Galway partnership runs until October 2025 and sees the charity committing almost ¤2 million for a variety of research activity and projects led by Professor Michael Kerin; Professor Aoife Lowery; Dr Róisín Dwyer; and Dr Nicola Miller.

They include: • translational research related to metastatic breast cancer; genetics to predict risk and treatment response; and biomarker discovery • development of the Cancer Biobank, housing tissue and blood samples crucial to research • clinical research focused on cardio-oncology and how cancer therapy affects the heart; breast cancer imaging; and women’s health, including post treatment support and rehab

Since its foundation in 1989, the NBCRI has strived to increase awareness, improve access to treatment and conduct internationally significant research into breast cancer. A significant part of that work has been in partnership with University of Galway. The new partnership provides an opportunity to expand this key relationship with increased investment in the breast cancer research programme as the charity and academia work together to achieve better outcomes for patients.

Speaking about the partnership NBCRI Director of Research and Professor of Surgery at University of Galway, Professor Michael Kerin, said, “The advancement of research and healthcare for people diagnosed with cancer is remarkable. Day-in, day-out, we see patients and their loved ones in our clinics who reap the rewards. We need to increase the pace of those advancements in

cancer treatment, care, quality of life and cures, by ensuring our patients can access a fit-forpurpose cancer centre that is underpinned by quality research, education and clinical trials.

“I would like to thank the NBCRI Board and its Chairperson, Caroline Loughnane, for their leadership and commitment to advancing breast cancer research to improve outcomes for patients.

A commitment of this scale is testament to the value that the NBCRI charity places on research at the University of Galway and how it can be the catalyst for improvements in care and the lives of our patients and their families, as well as a lasting global impact on research.”

Governed by a voluntary board, NBCRI is funded almost entirely by public donations from fundraising events held nationwide, which all help to keep the charity “in the pink” to fund research. The charity is one of the

driving forces in the development of a major new cancer centre in the west of Ireland.

Among many initiatives over the years of partnership with the University, NBCRI has supported major capital developments providing research and patient facilities for breast cancer research, including the Symptomatic Breast Unit and the Lambe Institute for Translational Research on the grounds of Galway University Hospital. In addition, NBCRI has been at the forefront of developing many of the key leaders in academic surgery and science including taking part in important national research initiatives such as Precision Oncology Ireland. The charity has also supported more than 40 full-time postgraduate places and more than 100 undergraduate medicine and science students as part of the University of Galway School of Medicine summer research programme.

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

24 Diabetes

The cost-effectiveness of HCL in Ireland: closing the loop on a revolutionary new therapy Written by Dr Jonathan Briody, Health Economist & Liam Manning, Medical Student, RCSI University of Medicine and Health Sciences

"Although HCL offers significant advantages, its cost cannot be overlooked. To conclusively assess the value of HCL therapy in Ireland, a national analysis that reflects the costs and outcomes in this setting is urgently required."

Dr Jonathan Briody is a health economist conducting an economic evaluation of intervention in, and prevention of, diabetes at RCSI University of Medicine and Health Sciences. With Professor Seamus Sreenan, he was awarded the Irish Endocrine Society Student Research Bursary to encourage promising students to pursue careers in endocrinology. He is supporting Liam Manning as part of this award.

Liam Manning is a medical student in RCSI. He is also collecting and analysing information on patients with diabetes. As the Irish Endocrine Society student award recipient Liam is participating in a research project at Connolly Hospital under the guidance of Professor Seamus Sreenan and Dr Jonathan Briody. He would like to thank the Irish Endocrine Society for their support.

Type 1 Diabetes in Ireland:

such as heart disease, renal disease, blindness, and many more. This greatly affects a patient’s quality of life and can be very costly to treat (1).

Diabetes Mellitus (DM) describes a group of metabolic diseases characterised by hyperglycaemia.

Once known as juvenile onset diabetes, type 1 diabetes mellitus (T1DM) involves an absolute insulin deficiency caused by the autoimmune destruction of beta cells in the pancreas. Type 2 diabetes mellitus (T2DM) involves a relative insulin deficiency caused by an acquired resistance to insulin, insufficient insulin production by beta cells or, both.

While both T1DM and T2DM are characterised by hyperglycaemia, these diseases have different pathophysiology, risk factors and treatments.

T1DM affects about 20,000 people in Ireland, or 0.4% of the total Irish population. T1DM is a chronic condition that will affect an individual for the rest of their life. It typically develops during childhood or adolescence so the negative impact of hyperglycaemia can compound over one’s lifetime to produce severe complications

Intervention in Type 1 Diabetes: It is essential that people with T1DM maintain their blood glucose to reduce the risk of short and long-term complications. HbA1c and time in range are the current metrics by which clinicians monitor a patients glycaemic control. It is recommended that patients achieve a HbA1c of 53mmol/mol or lower and 70%, or higher, time in range (3.9mmol/L-10mmol/L).

Many factors influence how much insulin a patient needs such as emotional stress, exercise, diet, how well they sleep, and many medications. As a result, many patients fail to meet their therapeutic targets (2).

T1DM is sometimes referred to as insulin-dependent diabetes because the only treatment is exogenous insulin. Before the preparation of recombinant DNA

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

human insulin in 1978 by David Goeddel and his colleagues, insulin was obtained from cows and pigs. While animal insulins still exist in clinical practice today, the recombinant form is the dominant one in today’s market. While the types of insulin that clinicians have at their disposal has changed a lot over the years, the methods of delivery have remained relatively constant. Many patients with diabetes still rely on subcutaneous insulin infusions via needles or syringes. The modern option of a continuous subcutaneous insulin infusion (CSII) uses an insulin pump to constantly administer a preprogrammed dose of insulin which can be adapted to different doses depending on the time of day or activity of the patient.

These have significantly improved glycaemic control in patients using the technology. However, these devices still require the patient to monitor many factors which can affect the amount of insulin they will require such as their blood glucose, food intake, exercise, sleep, any potential illness and more. The patient must then incorporate all this information to predict how much insulin they need to maintain blood glucose within range. Unsurprisingly, this system leads to hyperglycemia, hypoglycemia, mental stress, reduced sleep, and an overall reduction in quality of life. Hybrid closed-loop insulin pumps promise

a breakthrough in diabetes care to address these issues and facilitate a reduction in the morbidity associated with T1DM. A revolution in T1DM: The hybrid closed-loop systems represent a paradigm shift in the management of T1DM. Often referred to as an artificial pancreas, such systems have an unprecedented ability to influence blood glucose levels based on real time blood glucose information. The hybrid closed loop systems involve three components: a CGM, an insulin pump and an algorithm within the pump. These work together to maintain normoglycaemia. The CGM monitors blood glucose and communicates this information to the algorithm. The algorithm notes the current blood glucose, whether it is trending upwards, downwards or remaining steady, and the target blood glucose. This informs the pump about how much insulin to deliver to the patient.

These systems are referred to as “hybrid” because the patient must still count carbohydrate intake and manually enter this into the insulin pump. The closed loop system has allowed for improved glycemic control by reducing insulin infusion in anticipation of a hypoglycemic event and increasing insulin infusion to treat or prevent hyperglycemia.

25 trade-off across competing needs, allocating resources to maximise the expected overall benefits from the health system and, thus, the health gain for the population.

Notionally, the Irish healthcare service offers insulin pumps and consumable products through the HSE's Community Funded Schemes and the long-term illness scheme. Public hospitals also provide free training on the usage of such pumps. However, the qualifying criteria for meeting access to such pumps are not transparent, and waitlists are long.

This may explain why uptakes are so low, almost 77% less than the international average, according to Diabetes Ireland. Additionally, the National Clinical Guidelines (NCG) for Adults with T1DM recently reported that more than two-thirds of the Irish population does not have access to pump therapy as a treatment option.

The benefits of HCL By responding to the individual patient’s insulin requirements in the moment, closed loop systems are improving glycemic control, preventing acute complications such as hypoglycemia and generating psychosocial benefits.

A meta-analysis which examined 32 studies showed that closed loop systems significantly improve time spent in the therapeutic range (3.9mmol/L to 10mmol/L) by 9.6%.

This translated to an additional 140 minutes in range over a 24-hour period (3). Closed loop systems have also been shown to significantly reduce the amount of time spent hypoglycemic (<3.9mmol/L) by 1.5% (3).

Importantly, most of these benefits came during the night, when patients are unable to respond to milder changes in their blood glucose. Average blood glucose overnight dropped by 0.81mmol/L and 0.48mmol/L during the day. This was reflective of the reduction in HbA1c improvement of 3mmol/mol. A recent study in England also found a benefit to HCL use on HbA1c, time in range, and the proportion of patients who achieved >70% time in range. Furthermore, 94.7% of the participants reported HCL had a positive impact on their quality of life.

Glycaemic variability has been suggested to predict diabetic complications, independent of HbA1c levels in patients with T2DM and may play a role in the development of microvascular complications in those with T1DM (4). Closed loop systems

repeatedly lower glucose variability when compared to controls (5).

Closed loop systems provide psychosocial benefits in the form of less anxiety, improved sleep, and less fear of hypoglycaemia, particularly in the context of exercise (6). Closed loop systems are improving the quality of life of those with T1DM and helping patients obtain blood glucose readings which should protect them from some of the complications of the disease.

The costs of HCL:

choices have implications for the health of all users of the healthcare system. Funding one area of care will necessarily provide fewer resources for another because healthcare systems must allocate resources across a broad range of needs. For example, introducing a new treatment that reduces the disease burden of diabetes in adults could inadvertently lead to higher rates of mortality and morbidity in newborns as fewer funds are available for neonatal services.

The Cost-Effectiveness of HCL in Ireland:

Health economics provides national decision-makers with the tools to make informed choices that maximise the well-being of all users of a healthcare system in the population. Particularly, health economics recognises the opportunity cost of a choice. As described above, for health care resources, this is the value of the best alternative that is necessarily forgone when finite resources require a funding decision between several mutually exclusive options.

Simply put, allocating the health budget to hiring neonatal nurses is impossible when it has already been spent on a new diabetes medication. Reflecting this, decisions on national investments in new healthcare technologies are typically guided by a costeffectiveness analysis in Ireland.

Health care is more than the provision of medical services to those who need them. In a system with finite resources, it is necessary to make decisions on which services to provide, who to provide these services to, and how to pay for them. Such

Cost-effectiveness analysis compares the costs and benefits of competing healthcare interventions which aim to achieve the same outcome. In the context of constrained healthcare budgets, such an analysis allows decision-makers to prioritise and

The costs associated with HCL are undeniably higher than multiple insulin injections or even continuous subcutaneous insulin infusion. The pump is costly and requires associated consumables and training, while the lifetime of between four to eight years necessitates relatively frequent replacement over the disease's time horizon. However, such initial costs may be partially or wholly offset by significant cost savings in the long run due to reduced insulin requirements, improved clinical outcomes and the reduced diabetes-related complications - such as hypoglycaemia and long-term disease - that come with improved glycaemic control.

The allocation of healthcare resources must be fair, efficient and transparent. While HCL therapy suggests significant potential for improving health outcomes, it is also costly, and the healthcare system can only reduce health inequalities by investing in interventions that deliver value for money while enhancing the quality of care. By applying a cost-effectiveness analysis to the widespread and transparent uptake of HCL therapy in T1DM, the system can ensure that it achieves the best possible health outcomes for the people of Ireland.

To evaluate the long-term costeffectiveness in Ireland, an analysis must be performed over a lifetime horizon and from the healthcare payer's perspective (the HSE).

Clinical input data should be sourced from the critical trials that resulted in the introduction of such pumps to Ireland. Disutilities associated with diabetes-related complications can be sourced from the published literature.

Costs can be based on list prices and include direct costs and consumables, such as the pump, cannula, reservoir, sensors, insulin, blood glucose monitoring, diabetes complications, hospital visits, and pump training. Where necessary, national demographics and characteristics can be drawn from Irish patient cohort studies.

Improvements in quality-adjusted life years (QALYs) relative to the current standard of care and total lifetime costs can be assessed.

An incremental cost-effectiveness ratio (ICER) per QALY gained can be calculated and compared to standard of care. Sensitivity analysis can demonstrate the

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

26 Diabetes robustness of any such ICER values to various ranges of clinical effectiveness (glycemic control) and the quality-of-life benefit and costs associated with this new technology.

Such analysis has already been conducted in the UK and Europe. For example, HCL versus continuous subcutaneous insulin infusion yielded an ICER of ¤14,000 per QALY gained in Sweden. In the UK, a comparison to continuous subcutaneous insulin infusion yielded an ICER of ¤25,000 per QALY gained.

In the Netherlands, HCL versus multiple daily injections with intermittently scanned glucose monitoring resulted in an ICER of EUR 6,133 per QALY gained. These are well below the threshold of ¤45,000 per QALY gained, at which an intervention is usually considered cost-effective in Ireland and recommended for reimbursement. However, these estimates are based on assumptions and data from other settings and do not reflect Ireland's actual costs and outcomes. Therefore, a national analysis is necessary to answer the question once and for all: is HCL therapy a cost-effective use of Irish healthcare resources?

References available on request Acknowledgement: This research is funded by the Irish Research Council and Diabetes Ireland under the Enterprise Partnership Scheme – Postdoctoral Fellowships Project ID: EPSPD/2022/165

News

New Chair in Early Brain Injury and Cerebral Palsy Pictured (l-r): Rachel Byrne, Executive Director, Cerebral Palsy Foundation; Professor Deirdre Murray, the Cerebral Palsy Foundation Chair, UCC; and Lily Collison, Board Member and Advocate, Cerebral Palsy Foundation Image credit: Fennell Photography

On World Cerebral Palsy Day, University College Cork (UCC) has announced the appointment of Professor Deirdre Murray as the new Chair in Early Brain Injury and Cerebral Palsy, as part of a new programme of excellence to revolutionise the delivery of cerebral palsy care in Ireland.

In May, the Cerebral Palsy Foundation (CPF) announced UCC as one of three new clinical and research hubs, which will help establish Ireland as an international leader in Cerebral Palsy (CP) care and research.

As part of the programme, CPF is investing ¤1.6 million to advance research in early brain injury and

cerebral palsy at the Irish Centre for Maternal and Child Health Research (INFANT), UCC. A UCC alumnus, Professor Murray graduated from UCC in 1995 before completing paediatric training in Paediatric Intensive Care Medicine in Bristol Royal Hospital for Sick Children, and later working as a Paediatric Intensive care Fellow in the Royal Children’s Hospital, Melbourne.

In 2012 she was awarded a prestigious Health Research Board Clinician Scientist Award for the BiHiVE study, an ongoing project focusing on the discovery and validation of biomarkers in neonatal brain injury.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

A Consultant Paediatrician, Paediatric Research Lead at INFANT and Professor of Paediatrics, in UCC’s Department of Paediatrics and Child Health, Deirdre’s research is focused on early brain injury and the development of new ways to predict and assess neurocognitive outcome in children.

Professor Geraldine Boylan, Director of INFANT, said, “Congratulations to Professor Deirdre Murray on her welldeserved appointment as Chair in Early Brain Injury and Cerebral Palsy at UCC. Professor Murray’s expertise in this important leadership role will allow us to focus our early brain injury research on early detection and interventions for cerebral palsy.

We are immensely grateful to the Cerebral Palsy Foundation for this strategic funding which also highlights our growing partnership and joint commitment to effect positive change for people with cerebral palsy.”

Professor Deirdre Murray said: “I am very honoured to assume the role of Chair in Early Brain Injury and Cerebral Palsy. This signifies an important step forward and I am committed to leading our research efforts at INFANT in partnership with the Cerebral Palsy Foundation, to make Ireland a leading country for research into early brain injury and more importantly to improve health outcomes for children with cerebral palsy and their families.”

Currently the most common lifelong physical disability acquired during childhood, cerebral palsy is diagnosed in approximately 150 children each year in Ireland.

Early diagnosis in babies can lead to much better outcomes.

The Cerebral Palsy Foundation’s partnership with UCC will enable researchers at INFANT to generate critical knowledge that will transform outcomes for children with Cerebral Palsy.

Smoking Cessation 27

Smoking cessa�on: An Essen�al but Under-U�lised Pillar of Irish Healthcare

Writen by Dr S Griffiths, Dr D Breen, Department of Respiratory Medicine, Galway University

Smoking cessation: An Essential but Under-Utilised Abstract: Pillar of Irish Smoking Healthcare remains the single leading cause of preventable disease, disability and death worldwide

Irish adults are ac�veofsmokers, and recent years Galway have seenUniversity an upwardHospital trend of young pe Written by Dr S Griffiths, 18% Dr DofBreen, Department Respiratory Medicine,

developing a nico�ne addic�on, in part due to the rise in popularity of electronic nico�ne delive Abstract: Smoking remains the single Smoking leading cause of preventable disease, disabilitycomponent and death worldwide.

(ENDS). cessa�on services are an essen�al of tobaccoCurrently control,18% and of play a ke Irish adults are active smokers,mee�ng and recent years have seen an upward trend of young people developing a nicotine addiction, the goal of a Tobacco-Free Ireland. in part due to the rise in popularity of electronic nicotine delivery systems (ENDS). Smoking cessation services are an essential In this paper we will analyse current prevalence and trends in smoking habits in Ireland, and disc component of tobacco control, and play a key role in meeting the goal of a Tobacco-Free Ireland. of ENDS in the market, par�cularly the impact on Irish teenagers and poten�al legisla�on to tack In this paper we will analyse current prevalence and trends in smoking habits in Ireland, and discuss the impact of ENDS in challenge. We aim to iden�fy successful smoking cessa�on frameworks worldwide and discuss t the market, particularly the impact on Irish teenagers and potential legislation to tackle this novel challenge. We aim to identify the pa�ent and the system.

A localtoaudit conducted in Galway University pr successful smoking cessationboth frameworks worldwide andhealth discuss the benefits both the patient and the health system. Hospital A local audit conducted in Galway University insight into current cessation practise methods and we have into current Hospital smokingprovides cessa�on prac�se and wesmoking have iden�fied poten�al to improve loc identified potential methods towill improve local willSmoking review theGuideline National Stop Guideline 2022, in particular review thesystems.

Na�onalWe Stop 2022,Smoking in par�cular it’s applica�on to the hospita it’s application to the hospital setting and discuss the need for increased training among all healthcare staff in smoking discuss the need for increased training among all healthcare staff in smoking cessa�on provision cessation provision.

Mee�ng the goal of being tobacco-free by 2025 is dependent on accelera�ng progress with smo Meeting the goal of being tobacco-free by 2025 is dependent on accelerating progress with smoking cessation in Ireland, in Ireland, and this paper aims to iden�fy current challenges to Irish smoking habits and iden�fy and this paper aims to identify current challenges to Irish smoking habits and identify an effective approach to improving our smoking cessation services. approach to improving our smoking cessa�on services.

Introduc�on:

term illness and chronic health problems, compared with 27% of Tobacco use is the leading cause Tobacco use is4 the cause of preventable death, disease and disability worldwide. (1) The never smokers.

Year leading on year, the of preventable death, disease HI Survey identifies 25–34-yearOrganisa�on (WHO) describes current tobacco usage worldwide as a global epidemic. The Healt and disability worldwide.1 The olds as the age group most likely World Health Organisation (WHO) Report to smoke, and(HI) the proportion 2022 reports that 18% of the popula�on of Ireland are current smokers. There has b describes current tobacco usage of smokers in this group has worldwide as a global epidemic. significant shi� in demographics in Ireland with the Central Sta�s�cs Office publishing data for th experienced a 4-point increase The Healthy Ireland Report 2022 to 24%, significantly higher than 2022, showing the 4largest 12-month increase in the popula�on of Ireland since 2008, in part acc (HI) reports that 18% of the the national average. Smoking population of Ireland are current 15-year high immigrant prevalence byin age and gender arrivals (2). These demographic shi�s will have a major impact on smo smokers. There has been a is illustrated in Figure 1 and of significant shift in demographics prevalence; for example note highlights the persistentthe rapid increase in Ukrainian na�onals to Ireland will ul�mately result in Ireland with the Central high smoking rates within young Statistics Office publishing data in overall smoking numbers; it was es�mated that in 2022, 27.4% of the Ukrainian adult popula� adults, particularly males, and the for the year ending 2022, showing (3). decrease in smoking prevalence the largest 12-month increase in among older adults.

Dr Sally Griffiths Dr David Breen the population of Ireland since 2008, in part accounted for by a Current and trends in smoking habits: The useprevalence of electronic nicotine 15-year high in immigrant arrivals.2 delivery systems (ENDS), often before Éireann,use, and proposes variable, strict health regulatoryeffects The HI survey also reflects data onwithout long aterm of Dáil tobacco repor�ng that These demographic shifts will referred to as e-cigarettes or WHO framework, to introduce a regulatory framework and at present there have a major impact on smoking ‘vapes’ prevalent, and 39%isofincreasingly ex-smokers suffer from long-term illness and chronic health problems, wit for the retail sale of ENDS, compared termed is no definitive research on the prevalence; for example the rapid with a major expansion of this ‘nicotine inhaling products’.

These long-term impacts of ENDS use, increase in Ukrainian nationals smokers.

Year ontheyear, market in(4) Ireland over past the HI Survey iden�fies 25–34-year-olds as the age group most likely t measures focus on reducing access or second-hand exposure. As the to Ireland will ultimately result in two decades. Overall, 6% of the to ENDS for children by restricting of ENDS grows, there ais 4-point thepopulation propor�on of smokers in thispopularity group has experienced increase to 24%, significantly an increase in overall smoking reported using ENDS the sale of these products, and concern about their use in younger numbers; it was estimated that in na�onal regularly,average. with the highest use (4) Smoking prevalence by age and(Tobacco gender isplans illustrated inadvertisement Figure 1 and of note to prohibit people. The Public Health 2022, 27.4% of the Ukrainian adult reported in those under the age of ENDS around schools and on in smoki Products and Nicotine Inhaling 4 population smoked.3 persistent high smoking rates within young adults, par�cularly males, and the decrease of 25 (11%). ENDS are highly Products) Bill 2023 is currently public transport.

Current prevalence and trends in among older adults. smoking habits: Introduction:

The HI survey also reflects WHO data on long term health effects of tobacco use, reporting that 32% of smokers and 39% of ex-smokers suffer from long-

Figure 1: Data from the Healthy Ireland Report 2022 on prevalence of smoking by age and gender4

Figure 1: Data from the Healthy Ireland Report 2022 on prevalence of smoking by age 2023 and gende | HPN • NOVEMBER HOSPITALPROFESSIONALNEWS.IE

the iden�fica�on and treatment of tobacco addic�on across all healthcare se�ngs. Healthy Ireland reports that 29% of smokers are either trying to quit or are ac�vely planning a stop date. (4) However, only 18% of who saw their GP over a 12-month period discussed methods of smoking cessa�on, a decline of 50% 28 smokers compared to data from 2019. (4)

Smoking Cessation

The NSSG recommends that all healthcare professionals ask and document an individual’s smoking behaviours, and, inSchools turn advise smokers about for thediagnosis harms of to smoking the benefits The European Projectall onac�ve Lung Clinic, a service smokingand cessation services. A Alcohol and other Drugs (ESPAD) standardised smoking cessation and treatment of patients with of cessa�on.

Healthcare professionals should discuss the individual treatment needs Ireland 2019 Report5 provides proforma was implemented on a suspected lung cancer. A recent information about substance pilot ward as part of the admission analysis highlights the benefit and preferences, and advise that making an unsupported quit atempt is less use among Irish teenagers bundle, aiming to document to overall survival of stopping effec�ve than using recommended supports. is supported bystatus WHO attending secondary school, smoking ondata admission smoking at any time for aThis patient 9, 10 and reported that the decline to hospital and encourage with lung cancer. which demonstrates that brief advice from health professionals can increase brief in smoking has halted in Irish advice, and, in addition, all Effective smoking qui�ng while intensive advice increases the chance of referred teenagers for thesuccess first time by in up to 30%, identified smokers were cessation framework 25 years.

This correlated with a to smoking cessation services qui�ng by 84%.

higher prevalence of e-cigarette with their consent. These simple There is precedent for the use among Irish teenagers than interventions including the implementation of smoking The NSSGwith iden�fies about smoking behaviour and introduction offering advice to quit smoking tobacco, 39% of askingcessation of a standardised frameworks within 15- to 16-year-olds reporting approach to identification of healthcare settings, as evidenced as a key element of health behaviour change that should be u�lised by having used ENDS, compared smoking status and an optby the success of the Ottawa with 32% smoking tobacco. out referral of active to smokers healthcare professionals inModel theirforday-to-day prac�ce. Some�mes referred as a Smoking Cessation There are concerns about the to smoking cessation services (OMSC) which was first developed ‘teachable moment’, these conversa�ons aim to mo�vate individuals to adopt potential role of ENDS providing significantly improved practice. in the early 1990s. The OMSC new routes nicotinehealth addiction, This project was supported risk into reducing behaviours.

The 5evidence-based A’s model (figure 2), recommended by by is a validated, with 68% of adolescents in a encouragement of nursing staff process to embed comprehensive the reporting Centre for Control (CDC) and WHO, summarises thetheac�vi�es that a and 2019 study theyDisease had during daily safety-pause, smoking cessation treatments never used tobacco prior to first a poster campaign on the pilot healthcare provider can do within 3-5 Figure 2: Adapted from Centre and support as minutes an integralduring aspect a consulta�on. Mul�ple Figure 2: Adapted from Centre for use of e-cigarettes.6 ward. During the pilot programme, for Disease Control Best Practise of routine patient care. Since its studies have shown the benefits of a brief interven�on program, delivered by smoking documentation rate Disease Best Practise Users UsersControl Guide - Cessation in Tobacco inception the OMSC has continued In the adolescent population, increased difference to 85.7%, and 95% of Prevention and Control 2014 to trained, expand. Inwith 2020 athe OMSC had significant staffare who arecited appropriately sta�s�cally in e-cigarettes rarely as a tobacco users were referred to Guide - Cessation in Tobacco been implemented in over 500 smoking cessation technique, with smoking cessa�on and con�nued abs�nence.

(14) local smoking cessation services, outpatient, inpatient and primary only 3% of adolescents reporting Prevention and Control 2014 a significant improvement from the care sites across Canada. A quitting smoking as the reason reported pre-intervention results 2015 study reported that 35% of for first using e-cigarettes.6 This patients who received the OMSC contrasts with the high ENDS HSE National Stop Smoking health behaviours. The 5 A’s interventions were smoke-free at 6 use as a smoking cessation tool Guideline model (figure 2), recommended months, and had a 40% reduction in adults; the HSE National Stop by the Centre for Disease Control In Ireland, the HSE implemented in risk of death over 2 years.11 Smoking Guideline reports 38% of (CDC) and WHO, summarises the the National Stop Smoking people choosing e-cigarettes as a In 2017, the OMSC was adapted activities that a healthcare provider Guideline (NSSG) in 20227 aimed quit smoking aid in 2019.7 in the Greater Manchester Area can do within 3-5 minutes during at improving the identification and in the UK as the CURE project; a a consultation. Multiple studies Tackling tobacco use treatment of tobacco addiction comprehensive secondary care have shown the benefits of a brief across all healthcare settings.

Tackling tobacco use has become treatment program for tobacco intervention program, delivered by Healthy Ireland reports that 29% a priority for government policy addiction. The CURE project has staff who are appropriately trained, of smokers are either trying to makers worldwide. In 2008 the been shown to be cost-effective, with a statistically significant quit or are actively planning a WHO implemented the MPOWER with a highly significant return on difference in smoking cessation stop date.4 However, only 18% of policy as a worldwide tobacco investment.12 The CURE project and continued abstinence.14 smokers who saw their GP over control strategy, aiming to assist in estimates a 50% reduction in a 12-month period discussed the country-level implementation The British Thoracic Society readmissions at 30-days (3,273 methods of smoking cessation, a of effective interventions to reduce (BTS) and the National Institute admissions), and a reduction in decline of 50% compared to data the demand for tobacco. for Health and Care Excellence re-admissions at 1 year from from 2019.4 (NICE) recommend that all frontline 38.4% to 26.7%.

This project is In 2004, Ireland became the first healthcare staff should receive The NSSG recommends that estimated to save 30,880 bed days country to pass a smoke-free training to identify smoking status all healthcare professionals ask per year in the Greater Manchester law8, and furthermore in 2021 and to offer very brief advice, as and document an individual’s Area.

Furthermore, it has been was recognised by the WHO as a well as the local referral process smoking behaviours, and, in turn proven to deliver high-quality care global leader in tobacco control. for behavioural support.15,16 advise all active smokers about for patients by providing access to The Department of Health has set the harms of smoking and the highly effective interventions and the goal of being tobacco-free Additional options for behavioural benefits of cessation. Healthcare providing individualised smoking by 2025, defined as a smoking support include individual or professionals should discuss cessation treatment.13 The success prevalence of less than or equal group counselling, telephone or the individual treatment needs of the CURE project has led to a to 5%. However, as the HI Survey text-message support. Currently, and preferences, and advise commitment from the NHS that shows, ongoing improvements behavioural support is available that making an unsupported quit by 2023/24 all active smokers in smoking cessation policy and through specialist smoking attempt is less effective than using admitted to hospital will be offered practise are required to maintain cessation officers, both in hospital recommended supports.

This is NHS-funded tobacco treatment progress towards this goal. and community-based facilities, supported by WHO data which services, based on the successful who can also provide prescription demonstrates that brief advice As demonstrated in the HI and favourable results from the for NRT if required. Novel methods from health professionals can Survey 2022, a large proportion OMSC and CURE models. of delivering counselling for increase quitting success by up of smokers suffer from chronic smoking cessation have been Local data to 30%, while intensive advice illness (4) which in turn often developed including the digital increases the chance of quitting results in hospital admissions and In Galway University Hospital we counselling service ‘Florence’, an by 84%. prolonged inpatient stays. This conducted a review of current artificial intelligence bot developed was demonstrated in a 2016 study smoking prevalence and smoking by the WHO. Florence is a 24/7 The NSSG identifies asking about which attributed 309,117 bedcessation services. An initial virtual health worker, capable of smoking behaviour and offering days to smoking related illnesses. chart review revealed that 19.7% providing brief conversations by advice to quit as a key element The HSE recommends that each of audited patients were active voice or text, and can signpost of health behaviour change that patient encounter in the hospital smokers; overall in line with the patients to other digital cessation should be utilised by healthcare setting is used as a valuable national data. However, initially, programmes in their country, and professionals in their day-to-day opportunity for a brief intervention only 64.4% of patients had can found at https://www.who. practice. Sometimes referred to to discuss smoking cessation. smoking status documented, and int/campaigns/Florence. This as a ‘teachable moment’, these only 13% received brief advice, technology was developed in 2021, conversations aim to motivate In our service, this is particularly applicable in the Rapid Access primarily aimed at overcoming the with the same percentage referred individuals to adopt risk reducing

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

Figure 3: Stop Smoking medications recommended by the HSE National Clinical Guideline

29

Figure 3: Stop Smoking medications recommended by the HSE National Clinical Guideline

barriers arising from the COVID-19 pandemic such as easy access to smoking cessation services. The HSE has also developed a digital cessation service, and offers a 28-day plan including personalised daily support via email and text message through the QUIT.ie website, with a personalised web page to track progress.

For patients who wish to use pharmacological therapy in combination with behavioural supports, the NSSG recommends that combination NRT treatment or NRT monotherapy should be prescribed. NRT is available in

multiple forms and prescription can be tailored to the patient’s preference (figure 3). A recent Cochrane review confirmed the effectiveness of NRT in smoking cessation.17 Conclusion The development of an effective smoking cessation framework in the hospital setting has been proven by the Ottawa Model (Canada) and the CURE project (UK) to be a cost-effective intervention, which benefits patients at any stage of a disease course, and in addition

can equal the benefit of costly pharmacological or surgical interventions. Recent data indicates a slowdown in the momentum towards the target of a tobacco-free Ireland by 2025.

Meeting this goal is dependent on accelerating progress with smoking cessation programs across all healthcare settings.

Additional challenges are also appearing, for example, the smoking habits of Irish people are evolving with the increasing popularity of e-cigarettes and this will require the adaptation of current smoking cessation practise and legislation to tackle

these changes particularly amongst younger people.

Providing standardised clinical care to patients in healthcare is challenging, due to the diversity in environments of care and patient presentations. However, there is an opportunity during all patient encounters to provide a brief intervention and in turn direct patients to appropriate smoking cessation treatments.

Improvements in smoking cessation services in Ireland are dependent on adequate access to behavioural and pharmacological supports for all patients, irrespective of chronic illness or socioeconomic status.

At present, we risk reversing the gains which have been made to date in Ireland towards the goal of a tobacco-free nation. The impact of the COVID-19 pandemic, novel nicotine delivery systems, and the rise of tobacco addiction among young people cannot be underestimated, and additional funding and training of healthcare professionals is required for smoking cessation services to maintain momentum in tackling tobacco addiction in Ireland.

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

30 Liver Cancer

Liver Cancer in Ireland Written by: Michèle Bourke, Hepatocellular Carcinoma Advanced Nurse Practitioner, St. Vincent’s University Hospital

Introduction Primary liver cancer is among the top five causes of cancer related death worldwide. 905,700 people were diagnosed with liver cancer worldwide in 2020. 830,200 people died with liver cancer globally in the same year. There is estimated to be a 55% rise in the number of new diagnoses and deaths from liver cancer by 2040.1 October is Liver Cancer Awareness month. Raising public awareness is vital in improving outcomes for patients with liver cancer. Not only because it is a major health problem itself, but it is also associated with liver disease and cirrhosis. Prevention and early detection of primary liver cancer through public health measures, surveillance programmes, education and health promotion are key in the battle against this disease.

Background There are 2 main types of primary liver cancer, hepatocellular carcinoma (HCC) originating in hepatocytes, and cholangiocarcinoma (CCA) forming in the cells of the biliary tree. HCC is the most prominent type, accounting for approximately 90% of cases worldwide. HCC generally occurs on a background of liver cirrhosis, therefore the most common risk factor is chronic liver disease.

This article will focus on HCC. Liver cirrhosis is a chronic disease due to constant liver damage from a recurring insult e.g. excess fat in the liver, viral hepatitis, alcohol abuse, haemochromatosis, plus other aetiologies. Over time, as hepatocytes are in a constant state

of injury and repair, mutations develop in the cells leading to carcinogenesis and the formation of HCC. Patients with liver cirrhosis have a 1– 8% cumulative annual risk of developing HCC, therefore liver cirrhosis and HCC tend to be managed simultaneously by Hepatologists, in conjunction with Hepatopancreaticobiliary Surgeons, Interventional Radiologists, Oncologists and Specialist Nurses.

Diagnosis and Staging HCC is one of the few cancers which can be diagnosed radiologically if the patient has liver cirrhosis, or chronic hepatitis B virus (HBV) in the absence of cirrhosis. The Liver Imaging Reporting and Data System (LI-RADS) classification is widely used to guide non-invasive diagnosis of HCC. LI-RADS category LR-1 is considered a definitely benign lesion, whereas LR-5 is consistent with definite HCC.2 If a patient does not have cirrhosis or chronic HBV, or a LI-RADS classification of LR-M (definite or probable malignancy, not specific for HCC), a histopathological diagnosis is required.

Liver cancer can be staged with various systems. The staging of HCC and its treatment algorithm differ from that of other cancers, as the background liver disease and level of liver function is a major determining factor in treatment selection. A patient may have a small cancer which would ordinarily be considered for curative resection in an organ without a synchronous pathology e.g. breast. However, when a patient has dual pathologies like HCC and liver cirrhosis, the level of

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

liver dysfunction from the chronic liver disease will increase the mortality risk from interventions like surgery. Conservative management with a life prolonging treatment plan may become the clinical pathway of choice then, regardless of the small cancer size.

There are validated scores available in the literature to assess the level of liver dysfunction and risk of mortality for patients with cirrhosis based on their clinical data. These include the Model for End Stage Liver Disease (MELD) score, which predicts the 3-month mortality risk for patients with liver cirrhosis. As well as, the Child Turcotte Pugh (CTP) score, which stratifies the severity of liver disease and predicts surgical mortality for patients with liver cirrhosis. For HCC management, the Barcelona Clinic Liver Cancer (BCLC) Staging Classification is a widely accepted treatment algorithm which stages the cancer and guides clinicians to appropriate treatment modalities considering both HCC burden and extent of the background liver disease determined by the CTP score.3 The MELD, CTP and BCLC are internationally recognised and recommended for use in the management of HCC and can provide prognostic information for these patients.

Treatment All patients with a new diagnosis of liver cancer should have their case discussed at a specialist liver cancer multidisciplinary team meeting (MDM) with an expert consensus decision made regarding recommended treatment.4,5 The specialist liver cancer MDM in St Vincent’s University Hospital (SVUH) is an example of this. Treatment for HCC can be divided into 2 categories, those with curative intent and those which are life prolonging.

Surgical options include liver resection and liver transplantation.

Surgical resection removes the part of the liver affected by the cancer. Factors affecting consideration for resection include tumour size, location, vascular invasion, presence of metastases and level of background liver function. Liver Transplant involves the removal of the patient’s native liver and replacing it with a new healthy donor liver. Strict criteria must be met before a patient is considered for a liver transplant.

If deemed appropriate, they then undergo a period of assessment to ensure their suitability for this type of major surgery. Both surgical treatments are curative in nature, however liver transplantation is considered superior as it not only removes the existing liver cancer, but also the background liver cirrhosis which caused it, and is a continued risk factor for further HCC development.

Non-surgical options include thermal ablation (curative intent), transarterial chemoembolisation (TACE), selective internal radiation therapy (SIRT) and systemic therapy, both of which are noncurative in nature. Thermal ablation uses extreme temperature (heat or cold) to ablate the liver cancer and is used to treat lesions ≤3cm in size. TACE works by injecting chemotherapy directly into the blood supply feeding the HCC as well as blocking off the arterial blood supply to it. SIRT is similar to TACE, however radiation is injected into the liver this time, which damages the cancer cells internally. Systemic therapy is used for patients who have advanced liver cancer with preserved liver function. Immunotherapy (IV) and tyrosine kinase inhibitors (oral) are used for this type of treatment.

For patients with deranged liver function and / or poor performance status, best supportive care and palliation is the treatment of choice regardless of the liver cancer burden.

SVUH is the only centre nationally equipped to offer the full array of approved treatment modalities here in Ireland.

Health promotion The National Cancer Registry of Ireland described a 300% increase in the number of liver cancer cases in Ireland in the last decade.6 In 2018, they reported 285 new cases of primary liver cancer per year in Ireland, with 290 deaths from primary liver cancer here per year.7 While primary liver cancer is a major burden globally, awareness of liver cancer is limited in this country. When I ask members of the general public about liver cancer, they describe secondary liver cancer or metastases to the liver from another primary malignancy originating elsewhere in the body. Their knowledge is lacking about primary liver cancer,

31 the development of primary liver cancer.4,5 Although the evidence is not strong for the use of tumour markers as part of the surveillance protocol, the measurement of alphafetoprotein (AFP) level in blood may assist in early detection of primary liver cancer.

Conclusion Primary liver cancer rates are increasing in Ireland. HCC is the most common type of primary liver cancer and usually occurs on a background of liver cirrhosis.

Surveillance for HCC should be offered to all patients who qualify for it. A specialist MDT should provide recommendations for management of anyone diagnosed with liver cancer. However, prevention is better than cure!

Steps need to be taken in at risk groups to prevent the development of significant liver fibrosis, cirrhosis and primary liver cancer. If you would like any further information, the Irish Liver Foundation (www. liverfoundation.ie) and the Irish Cancer Society (www.cancer.ie) have excellent information pages dedicated to primary liver cancer.

References its causes, surveillance options, treatments and outcomes. This liver cancer awareness month we hope to shine a light on liver disease and its associated cancer here in Ireland.

Primary prevention While improvements in cancer care are always welcome, prevention is better than cure! Prevention of primary liver cancer requires awareness of the risk factors for its development, mainly chronic liver disease. Globally viral hepatitis is the leading cause of liver cirrhosis, however fatty liver and alcohol excess are the leading risk factors in the western world.

A fibroscan is a quick and easy, non-invasive test used to identify the presence of fat and inflammation or scarring in the liver. Liver specific blood tests can be used to calculate scores to predict liver dysfunction.

These tests, coupled with a comprehensive health history and physical assessment can make a diagnosis of liver disease and cirrhosis, prompting a surveillance protocol for liver cancer.

Viral Hepatitis Strategies to tackle viral hepatitis associated HCC include vaccination against HBV. Universal vaccination programmes for newborn babies in Asia are associated with significant decreases in HCC incidence there.

In Ireland, the HBV vaccine is now given to children as part of the 6 in 1 vaccine at 2, 4 and 6 months of age.

Additional strategies involve antiviral therapy for those with HBV and hepatitis C virus (HCV). Treatment for HBV will keep the virus under control.

New treatments for HCV can eradicate the virus altogether.

Both treatments aim to prevent the development of significant fibrosis or cirrhosis in the liver.

Antiviral therapies have shown to significantly reduce HCC risk.

However, patients who have already developed cirrhosis will have a persistent risk for HCC development.

Non-alcoholic fatty liver disease (NAFLD) The Health Service Executive (HSE) recently reported that Ireland has one of the highest levels of obesity in Europe.8 Obesity is linked with many chronic illnesses including NAFLD and liver cirrhosis. It is associated with a 1.5 – 4.5 times higher risk of HCC, contributing to nearly 10% of all HCC incidence worldwide.

NAFLD is currently the fastest growing cause of HCC in liver transplant candidates and is the leading cause of HCC in the absence of liver cirrhosis.4 Weight loss and increased physical activity improves outcomes for patients with NAFLD, reducing the progression to cirrhosis.

Alcohol Alcohol Action Ireland and the UCC School of Public Health attribute the number 1 cause of alcohol related deaths in Ireland to liver cancer and liver cirrhosis. The International Agency for Research on Cancer classify alcohol as a group 1 carcinogen. There is a proven link between alcohol and several types of cancer. While it is important to note that there is no safe level of alcohol consumption, low risk drinking guidelines are available recommending less than 11 standard drinks per week for women and 17 standard drinks per week for men. It is hoped that the Public Health (Alcohol) Act 2018 will help to reduce alcohol use and subsequent harms in Ireland.

Smoking Smoking is associated with risk for many cancers, but specifically a 20%-86% increased risk for HCC.4 Quitting smoking can return this risk almost to baseline after 30 years of cessation. The HSE provide resources and programmes to assist in smoking cessation.

Surveillance Once a diagnosis of liver cirrhosis has been made or a patient has chronic HBV in the absence of cirrhosis, regular surveillance for primary liver cancer is recommended the world over, in the form of an ultrasound liver every 6 months, to assess for

1. Rumgay et al. (2022) ‘Global burden of primary liver cancer in 2020 and predictions to 2040’, Journal of Hepatology, 77, pp. 15981606.

2. LI-RADS (2023) Available online at: LI-RADS | Radiology Reference Article | Radiopaedia.org Accessed on 08/08/2023.

3. Reig et al. (2022) ‘BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update’, Journal of Hepatology, 76(3), pp.681-693.

4. AASLD (2023) ‘AASLD Practice Guidance on Prevention, Diagnosis, and Treatment of Hepatocellular Carcinoma’, Hepatology, Available online at: AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma - PubMed (nih.gov) Accessed on 14/06/2023.

5. EASL (2018) ‘EASL Clinical Practice Guidelines: Management of Hepatocellular Carcinoma’, Journal of Hepatology, 69(1), pp. 182-236 6. National Cancer Registry Ireland (2016) Cancer Trends. Available online at: https://www.ncri.ie/ sites/ncri/files/pubs/Liver%20 trendsDecember2016_0.pdf Accessed on 08/08/2023.

7. National Cancer Registry Ireland (2018) Cancer Factsheet Liver.

Available online at: Factsheet liver. pdf (ncri.ie) Accessed on 08/08/2023.

8. HSE (2020) A healthy weight for Ireland Obesity policy and action plan. Available online at: ccbd6325268b48da80b8a9e5421a9eae. pdf (www.gov.ie)

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

32 COPD

Marking World COPD Day in Ireland Written by COPD Support Ireland World COPD Day is almost upon us once again, when on Nov 15th we will once more recognise the reach that this progressive disease has. However, although there are an estimated 380,000 people living with COPD in Ireland, it is thought that approximately 270,000 of these are unaware that they may have this serious and progressive lung condition.

COPD Support Ireland has been working tirelessly for several years now to raise the profile of the condition that is COPD so that more people are aware of what it actually is, if they or a loved one may have the symptoms of it and what assistance is available to help them to live their lives with this disease.

Though Covid slowed down the work that we could do we are now back stronger than ever and in the process of opening new COPD support groups all over the country. These support groups are made up of people who are living with a diagnosis of COPD and who wish to keep themselves active to ensure they are living their best life. Specifically designed exercise classes are run in each of these groups weekly with a fully qualified trainer and the physical, social, and emotional wellbeing that members get from being a part of these groups is hugely beneficial to their overall wellbeing.

"Living with a debilitating condition can be a lonely and very worrying place to be. Depression is not uncommon. Having a community of fellow sufferers to meet up with once a week (or more) provides an immeasurable sense of belonging and solidarity. Exchanging stories, “chewing the beef”, having a good laugh, and just providing each other with simple words of encouragement and care go a long, long way to boosting one’s confidence and self-esteem."

- Wexford COPD Support & Exercise Group Member.

We would encourage anyone who has been diagnosed with COPD to contact us to see if we have a local support group near them. We also welcome referrals from healthcare professionals which can be made on an electronic referral form hosted on our website www.copd. ie in the Healthcare Professionals section or on a printed version that can be requested via info@copd.ie Membership is free and we can have you signed up in no time!

We are establishing new groups all the time so if we don’t have one in your area yet then don’t worry it may be on its way to you soon.

In the meantime, we have online exercise classes which COPD patients can join to ensure that they are not missing out on regular exercise which is so important for those living with COPD. As well as exercise classes our groups offer social events and a network of members who are always ready to help or offer advice on how they deal with the impacts of COPD on their lives.

This type of backup can be hugely beneficial to someone living with COPD, who may be experiencing a decline in their ability to perform activities of daily living following an exacerbation of their condition.

"Since I joined COPD Support Ireland approximately six years ago it has benefited me in more ways than one. I was prone to chest infections and had to take antibiotics and steroids on a regular basis. I find both the breathing and general exercising each week has helped me greatly. The social side of meeting up on a weekly basis has proved to be great asset to us all as well. A lot of our members live alone, and they look forward to meeting up each week and

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

find the regular exercise routine a great asset to their everyday life."

- Limerick COPD Support & Exercise Group Member.

The growth of COPD Support Ireland has been made possible by the tireless work of our members who run their support groups with the backup of our staff. This year we are delighted to have been supported by the National Clinical Programme, Respiratory in receiving funding from the HSE Enhanced Community Care Programme which has allowed for us to establish 18 additional support and exercise groups and provide services for more people living with COPD in Ireland.

Being able to provide these invaluable services to COPD patients is hugely important to us and drives the work that we do. With an estimated 130,000 people diagnosed with COPD and almost double that estimated to be undiagnosed, there is still a lot of work to be done to ensure that everyone living with this chronic lung disease is receiving the support they need and want.

For World COPD Day this year we are joining an international network of COPD professionals and organisations to participate

in the Global Big Baton Pass challenge. This will take place on World COPD Day, Nov 15th, 2023.

On that day we will be asking people to do whatever exercise they can, to record it and let us know what you have achieved. It may be walking a few more steps than normal, a walk around your house or to the local shop. For the more adventurous of you it might be a bike ride, a swim, a hike, some gardening or just walking the dog. You might want to do a group activity with your work colleagues such as a lunchtime walk, run or indoor step challenge (it is Ireland in November after all!). Whatever it is we would love for you to let us know so we can add it to Irelands’ national total of activity for the day.

On this global stage, we would love to show how dedicated Irish people are to raising the profile of COPD and as the Virtual Baton passes through Ireland, we will be live broadcasting from COPD Support Ireland’s World COPD Day HQ, sharing the work that we do and highlighting the work that all health professionals in Ireland do for those living with COPD. Further details on how you can register your activity for the day can be found on www.copd.ie or you can contact admin@copd.ie or phone: 083 4095250.

Striving for a life uninterrupted

IT KEEPS GOING SO THEY CAN TOO*1,2 For COPD patients on treatment with ICS/LABA or LAMA/LABA and at risk of an exacerbation**1 TRELEGY Ellipta shows superiority vs. non-Ellipta Multiple Inhaler Triple Therapy in a randomized real-world trial in everyday practice3

Find out more here:

* Patients with moderate-to-severe COPD not adequately treated by a combination of ICS/LABA, or LAMA/LABA.1 ** A worsening of symptoms or a history of exacerbations treated with antibiotics or oral corticosteroids in the past 12 months.

www.trelegy.ie

ICS, inhaled corticosteroid; LABA, long-acting ß2-agonist; LAMA, long-acting muscarinic antagonist Safety information TRELEGY Ellipta is generally well tolerated. Common adverse reactions include: headache, nasopharyngitis, influenza, upper respiratory tract infection, pneumonia, back pain, rhinitis, cough, pharyngitis and arthralgia.1 In common with other corticosteroid-containing medicines, there is an increased risk of pneumonia in patients with COPD receiving TRELEGY Ellipta.1 TRELEGY Ellipta should be used with caution in patients with unstable or life-threatening cardiovascular disease.1 TRELEGY Ellipta is generally well tolerated. Common adverse reactions include: pneumonia, upper respiratory tract infection, bronchitis, pharyngitis, rhinitis, sinusitis, influenza, nasopharyngitis, candidiasis of mouth and throat, urinary tract infection, headache, cough, oropharyngeal pain, constipation, arthralgia, back pain.1

References: 1. TRELEGY Ellipta SmPC, 2023. Available at www.medicines.ie. Accessed June 2023. 2. Lipson DA et al. Am J Respir Crit Care Med 2017; 196:438–446. 3. Halpin DMG;ERJ Open Research;2021;7;1-11.

Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol [as trifenatate]) Prescribing information. or request a visit from a GSK representative Please consult the full Summary of Product Characteristics (SmPC) before prescribing.

Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol [as trifenatate]) inhalation powder. Each single inhalation of fluticasone furoate (FF) 100 micrograms (mcg), umeclidinium bromide (UMEC) 62.5 micrograms and vilanterol as trifenatate (VI) 25 mcg provides a delivered dose of 92 mcg FF, 55 mcg UMEC and 22 mcg VI. Indications: Maintenance treatment in adult patients with moderate to severe COPD who are not adequately treated by a combination of an inhaled corticosteroid (ICS) and a long-acting ß2-agonist (LABA) or a combination of a LABA and a long acting muscarinic antagonist. Dosage and administration: One inhalation once daily at the same time each day. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate & magnesium stearate). Precautions: Paradoxical bronchospasm, unstable or life-threatening cardiovascular disease or heart rhythm abnormalities, convulsive disorders or thyrotoxicosis, pulmonary tuberculosis or patients with chronic or untreated infections, narrow-angle glaucoma, urinary retention, risk factors for urinary retention, hypokalaemia, patients predisposed to low levels of serum potassium, diabetes mellitus. In patients with moderate to severe hepatic impairment patients should be monitored for systemic corticosteroid-related adverse reactions. Eye symptoms such as blurred vision may be due to underlying serious conditions such as cataract, glaucoma or central serous chorioretinopathy (CSCR); consider referral to ophthalmologist.

Increased incidence of pneumonia has been observed in patients with COPD receiving inhaled corticosteroids. Risk factors for pneumonia include: current smokers, old age, patients with a history of prior pneumonia, patients with a low body mass index and severe COPD. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Trelegy. Acute symptoms: Not for acute symptoms, use short-acting inhaled bronchodilator. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases. Therapy should not be abruptly stopped without physician supervision due to risk of symptom recurrence. Systemic effects: Systemic effects of ICSs may occur, particularly at high doses for long periods, but much less likely than with oral corticosteroids. Interactions with other medicinal products: Caution should be exercised with concurrent use of ß-blockers. Caution is advised when co-administering with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, cobicistat-containing products), hypokalaemic treatments or non-potassium-sparing diuretics. Co-administration with other long-acting muscarinic antagonists or long acting ß2-adrenergic agonists is not recommended. Pregnancy and breast-feeding: Experience limited. Balance risks against benefits. Side effects: Common (≥1/100 to <1/10): pneumonia, upper respiratory tract infection, bronchitis, pharyngitis, rhinitis, sinusitis, influenza, nasopharyngitis, candidiasis of mouth and throat, urinary tract infection, headache, cough, oropharyngeal pain, arthralgia, back pain. Uncommon (≥1/1,000 to <1/100): viral respiratory tract infection, dysgeusia, vision blurred, glaucoma, eye pain, supraventricular tachyarrhythmia, tachycardia, atrial fibrillation, dysphonia, dry mouth, fractures. Rare (≥1/10,000 to <1/1,000): Hypersensitivity reactions, including anaphylaxis, angioedema, urticaria, and rash, intraocular pressure increased, urinary retention, dysuria. Marketing Authorisation (MA) Holder: GlaxoSmithKline Trading Services Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.

MA No. [EU/1/17/1236/002]. Legal category: POM B. Last date of revision: February 2023. Code: PI-6725. Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Campus, Dublin 24. Tel: 01-4955000.

Adverse events should be reported directly to the Health Products Regulatory Authority (HPRA) on their website: www.hpra.ie.

Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

TRELEGY Ellipta was developed in collaboration with ©2023 GSK Group of Companies or its licensor Trademarks are owned by or licensed to the GSK Group of Companies PM-IE-FVU-ADVT-230001 | June 2023

34 Lung Cancer

Neoadjuvant Immunochemotherapy for Resectable Lung Cancer Written by Dr Rachel Clarke, Oncology SPR, Dr Mark Doherty, Consultant Oncologist, St Vincent’s University Hospital

Dr Rachel Clarke

Dr Mark Doherty

Immune checkpoint inhibitors have improved the outlook of metastatic non-small cell lung cancer (NSCLC) for many patients, with average survival times measured in years and over 25% of patients alive after 5 years.1 Given this success in advanced incurable disease, there has been a natural focus on its potential benefits in early stage lung cancer to improve the chances of cure. Several years ago, studies of neoadjuvant (preoperative) chemotherapy in resectable NSCLC showed only modest benefit.2 Apart from concerns regarding is efficacy, there was worry among thoracic oncologists and surgeons alike, that immunotherapy given prior to surgery would impact on surgical outcomes. This was disproven by retrospective data from the American National Cancer Registry suggesting similar surgical outcomes in patients treated with chemotherapy or immunotherapy in the neoadjuvant setting.3 Recently prospective trials have confirmed a benefit to this approach without a negative impact on surgery in what will become a new standard of care for selected patient groups.

of 22 patients with resectable NSCLC, in which 45% of patients achieved major pathological responses.4 Other studies for example the LCMC-3 study, have evaluated atezolizumab in the neoadjuvant setting, giving two cycles prior to surgery with 20% rate of major pathological response.5 These studies and others looking at neoadjuvant immunotherapy showed improved outcomes including endpoints of overall response rate (ORR), disease free survival (DFS) and major pathological response (MPR), defined as <10% residual viable tumour after neo-adjuvant treatment.6 The NEOSTAR study compared neoadjuvant nivolumab with or without ipilimumab.7 This study met its primary endpoint, with improvement in MPR (38.1% vs 21.7%), as well as secondary endpoints of pathologic complete response (pCR; 28.6% vs 8.7%) and ORR (21.7% vs 19%) for the dual checkpoint inhibitor arm.

The first prospective trial in 2018 studied the feasibility of giving two doses of neo-adjuvant Nivolumab in a small sample

Overall, studies looking at combination immunochemotherapy appear more favourable compared with neoadjuvant immunotherapy alone. Three single arm phase 2 studies have been completed, in Spain, Switzerland and China, all studying the use of immune checkpoint inhibitors in combination with chemotherapy

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

in the neoadjuvant setting. The NADIM II Trial enrolled 46 patients, 41 of whom underwent surgical resection and of these, 63% had pCR with no residual viable tumour in the resection specimen, and 83% had MPR.8 A Chinese trial of 30 patients with stage IIIa NSCLC who received toripalimab with chemotherapy reported pCR in 45.5% of patients and MPR in 60.6%.9 The Swiss cooperative group for Cancer Research (SAKK) trial of 67 patients reported MPR in 62% and pCR in 19%.10 In all of these trials, there was no impact on surgical complication rates. It is clear based on these results that a neoadjuvant approach results in major pathologic responses without jeopardising the safety or feasibility of surgery.

Recently the U.S Food and Drug Administration (FDA) approved neoadjuvant nivolumab in combination with chemotherapy in operable NSCLC based on evidence from the phase 3 study Checkmate 813 study. This trial enrolled 505 patients in a 1:1 ratio to receive nivolumab with platinum chemotherapy vs chemotherapy alone for 3 cycles in stage IB to IIIA disease.11 The median event-free survival was 31.6 months with nivolumab plus chemotherapy and 20.8 months with chemotherapy alone regardless of PDL-1 score. It cited percentage of patients with a pCR was 24% versus 2.2% in the chemotherapy alone arm. The addition of immunotherapy did not negatively delay or impede surgery with a slightly higher proportion of the patients in the experimental arm successfully getting to resection (83% vs 75% in control arm).

Following this, results from the AEGEAN study were presented earlier this year. This was a randomized trial where 802 patients with resectable NSCLC, irrespective of PD-L1 expression were assigned to receive neoadjuvant platinum based chemotherapy with either durvalumab or placebo for 4 cycles. Following surgery patients continued on either durvalumab or placebo for a year. In total 77.6%

of the treatment arm vs 76.7% of patients in placebo arm underwent surgery. The experimental group had a pCR rate of 17.2% vs 4.3% of the placebo group. After a median follow-up of 11.7 months, median event free survival (EFS) was not reached in the durvalumab arm vs 25.9 months in the placebo arm. Neither trial has yet been able to report mature survival outcomes and the gold standard of an overall survival analysis is awaited.

Despite the evidence above there are still multiple uncertainties surrounding neoadjuvant treatment in resectable NSCLC. Many of the trials discussed have had different end points (eg. MPR, pCR, median EFS and PFS) as well as different inclusion criteria in terms of staging. Another concern is the potential risk of nodal immune flare which may lead to patients being deemed unresectable due to nodal progression which may only be an immunotherapy treatment response. This phenomenon was observed in the NEOSTAR trial where some patients had observed stable disease or progressive nodal disease on imaging but pathologically were non caseating granulomas. Another unresolved issue is the optimal sequencing of treatment between neo-adjuvant, peri-operative or adjuvant. Both preclinical models and research in other tumour types have shown increased antitumour activity of immunotherapy in the neoadjuvant setting, but there is no current evidence that this translates into clinical benefit. Another question left unresolved is whether patients should have postoperative treatment after neoadjuvant immunochemotherapy, and whether we can move towards de-escalation of therapy. In these circumstances we could consider the utility of circulating tumour DNA testing although this is relatively unsupported at present.

We are finally seeing the promise of immunotherapy translating into better curative treatment strategies for patients with lung cancer. Of course, there are still challenges to address due to the heterogeneity of patient factors (eg clinical stage, pathological alterations) as well as

35 IONESCO). J Immunother Cancer.

2022;10(10):e005636. doi:10.1136/ jitc-2022-005636

the optimal use and sequencing of diverse treatment strategies, but we expect that the importance of using immune checkpoint inhibitors in early stage lung cancer will continue to rise.

doi:10.1016/j.jtho.2021.05.001 2.

References 1.

Herbst RS, Garon EB, Kim DW, et al. Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed DeathLigand 1-Positive Advanced NSCLC. J Thorac Oncol.

2021;16(10):1718-1732.

3.

NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-smallcell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet.

2014;383(9928):1561-1571 Mathey-Andrews C, McCarthy M, Potter AL, et al. Safety and feasibility of minimally invasive lobectomy after neoadjuvant immunotherapy for non-small cell lung cancer. J Thorac Cardiovasc Surg. 2023;166(2):347-355.e2. doi:10.1016/j.jtcvs.2022.12.006

4.

Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 2018;378(21):1976-1986.

5.

Carbone D, Lee J, Kris M, et al.

OA06.06 Clinical/biomarker data for neoadjuvant atezolizumab in resectable stage IB-IIIB NSCLC: primary analysis in the LCMC3 study. J Thorac Oncol.

2021;16(suppl 3):S115-S116.

6.

Wislez M, Mazieres J, Lavole A, et al. Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601

7.

Cascone, T., William, W.N., Weissferdt, A. et al. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial.

Nat Med 27, 504–514 (2021). https://doi.org/10.1038/s41591020-01224-2

8.

Provencio M, Nadal E, Insa A, et al. Neoadjuvant chemotherapy and nivolumab in resectable nonsmall-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020;21(11):14131422. doi:10.1016/S14702045(20)30453-8

9.

Zhao ZR, Yang CP, Chen S, et al. Phase 2 trial of neoadjuvant toripalimab with chemotherapy for resectable stage III non-small-cell lung cancer. Oncoimmunology.

2021;10(1):1996000. Published 2021 Oct 25. doi:10.1080/216240 2X.2021.1996000

10. Rothschild SI, Zippelius A, Eboulet EI, et al. SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial. J Clin Oncol. 2021;39(26):2872-2880. doi:10.1200/JCO.21.00276 11. Forde PM, Spicer J, Lu S, et al.

Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022;386(21):1973-1985. doi:10.1056/NEJMoa2202170

News

Consultants Question Waiting List Claim The Irish Hospital Consultants Association (IHCA) has questioned claims by the Department of Health that the Government’s Waiting List Action Plan is running ‘ahead of target’.

It follows the release of the latest National Treatment Purchase Fund (NTPF) figures which confirm that 896,700 people were on some form of hospital waiting list at the end of August.

The ¤443 million Action Plan set a target to reduce waiting lists for outpatient appointments and inpatient and day case treatment by 10% (-69,000) by the end of the year, compared with the number waiting at the start of 2023.

However, eight months into 2023 and instead of an expected reduction of around 45,500 people, the latest NTPF figures confirm that almost 18,200 additional people have in fact been added to

these three main waiting lists – a 63,700 shortfall.

While the number of patients treated or removed from the waiting lists may be above target, additions to waiting lists in the same period have been much higher than projected. This means there has been no net reduction so far this year, with waiting lists increasing by around 3% since January.

Despite separate data confirming 49,500 patients were removed from hospital waiting lists without any treatment in the first six months of 2023 through NTPF ‘validation’, the Government is still significantly behind the 10% reduction target contained in its Action Plan.

The Association, which holds its Annual Conference in Dublin later this month, welcomed the reductions achieved since this time last year, but put into context

that August 2022 had seen the highest ever number of people on NTPF waiting lists – a total of 910,073.

Commenting on the waiting lists, IHCA President Professor Robert Landers, said, “The stark reality is that there are over 896,000 people on some form of NTPF waiting list, which is up more than 26,600 (3%) this year alone. When the additional 250,000 waiting for essential hospital diagnostic scans are included, the number of people awaiting hospital care is over 1.1 million – or one-fifth of the population.

“While it is important to know how many people are waiting longer than the Sláintecare maximum wait times, and we welcome any small gains in these wait times, it is equally important to acknowledge that waiting lists have significantly deteriorated rather than improved

since the Sláintecare report’s publication in May 2017. In fact, the number of people on NTPF waiting list has increased by over 313,000 (+54%) since Sláintecare.

“This is why the IHCA is urging the Government to commit the estimated ¤4 billion in capital funding in October’s Budget to build and open essential additional hospital beds, theatres, diagnostics and other facilities already announced by the Minister for Health in order to cut waiting lists.

“The Government also needs to address the very obvious shortages of Consultants in our public hospitals, given that a record 933 permanent Consultant posts are vacant or filled on a temporary basis, and the fact that Ireland continues to have the lowest number of medical specialists on a population basis in Europe.”

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

36 News

Pivotal Role for Viatris at International Women’s Symposium The International Canoe Federation’s (ICF) Women’s Paddlesports Symposium, hosted

by Canoeing Ireland concluded with participants from 34 countries agreeing to actions to create equity in sport. The two-day inaugural Symposium was held on September 26th-27th.

The two-day inaugural Symposium attracted prominent speakers such as International Olympic Committee (IOC) President Thomas Bach, ICF President Thomas Konietzko, Sport Ireland CEO Dr. Una May, Minister for Sport Thomas Byrne T.D., and former private secretary to Nelson Mandela, Zelda la Grange.

Panel discussions and facilitated breakout workshops provided leadership and coaching tools to the over 100 participants, underpinned by the strength of the community as a catalyst for change. Global healthcare company Viatris partnered with Symposium organisers as part of their commitment to gender equity as a driver of building healthier communities.

Minister for Sport Thomas Byrne T.D. reinforced the importance and urgency of increasing female participation in leadership roles, "I was delighted to officially open the inaugural ICF 2023 Women's Symposium. It is a great honour for Ireland to host this symposium which has brought together international delegates representing 34 nations.

Keynote speaker Zelda la Grange, former private secretary to Nelson Mandela - Copyright Canoeing Ireland/Matt Browne@Sportsfile

decision-making level in sport.

I want to commend Canoeing Ireland and everyone involved in organising this symposium."

Event sponsor Viatris assumed an active role in the two-day event, with Melissa Fisher, Country Manager, Ireland Commercial and paddlesports enthusiast drawing on her experience from corporate life to encourage dialogue and share learnings and tangible tools.

“As Sport Minister, I want to see the gender participation gap eliminated wherever it exists, be it on the court, on the pitch, on the water and in the boardrooms too. I welcomed the opportunity to reiterate my total commitment to seeing a minimum of 40% gender balance on the national boards of publicly-funded sporting organisations by the end of this year. I have been fully clear that failure to achieve the 40% target will result in serious funding implications for sporting organisations. It is so important that young girls see women at the

Sport Ireland Chief Executive Dr. Una May - Copyright Canoeing Ireland/Matt Browne@Sportsfile

Viatris Team (L-R) Tilde Pihl, Niamh Brennan, Muireann Byrne, Melissa Fisher - Copyright Viatris

She commented, “I am passionate about female empowerment. At Viatris we are also on a journey to increase women’s representation globally in senior management to at least 35% by the end of 2027.

Whether we are on the water or in the workplace, we deal with similar challenges and aspirations when it comes to encouraging female participation. I come away from these past two days with renewed confidence that while changing patterns can be difficult, change is definitely afoot.

Participants at the inaugural ICF Women’s International Paddlesports Symposium - Copyright Canoeing Ireland/Matt Browne@Sportsfile

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

“We heard from IOC President Thomas Bach that the Paris 2024 Olympics will be the first Olympics in history to achieve gender parity. More and more women are feeling empowered to reach their full potential and it’s up to each individual to harness this energy for future generations of female leaders.”

Empowering people worldwide to live healthier at every stage of life

With 1,600 people working across five sites in Ireland, Viatris provides access to medicines, develops innovative solutions and improves healthcare for patients.

Viatris Newenham Court, Malahide Road, Dublin 17, Dublin, Ireland.

Viatris.ie Job Code: CC-2023-001 Date of Preparation: July 2023 www.viatris.ie

38 Obstetrics

, Wrong time: Improving of Obstetric Emergencies Wrong place,Management Wrong time: Improving Management of Obstetric Emergencies etric Settings

in Non-Obstetric Settings

Wrong place, Wrong time: Improving Management Written by Dr Tom Wall, Specialist Anaesthesiology Trainee. of Obstetric Emergencies in Non-Obstetric Settings

om Wall, Specialist Anaesthesiology Trainee.

ne is a time sensitive, unpredictable challenge for patients and practitioners. to obstetric practice focus on the timely management of common emergency re relatively unique to this patient population. In line with international practices, Obstetric medicine is a time sensitive, unpredictable challenge for patients and practitioners. ne is highly centralised in Dublin1,2. However, patients present as unscheduled Written by Dr Tom Wall, Specialist Anaesthesiology Trainee Skillsets unique to obstetric practice focusthese on the timely management of common emergency settings that do not routinely provide obstetric care.

In our hospital, entationsscenarios highlighted patient safety issues,which we addressed in this Quality that are relatively unique to this patient population. In line with international practices, QI) project 1,2

obstetric medicine is highly centralised in Dublin . However, patients present as unscheduled

Obstetric medicine a time ersity Hospital (TUH), several is presentations of female is emergencies to settings that Scenario: do not27-year-old routinely provide obstetric care. In our hospital, these sensitive, unpredictable ts in extremis highlighted a critical medication brought in by ambulance in challenge for patients and nsider theemergency scenario presented on the right. presentations highlighted safety issues,which we addressed in this Quality severe shock.patient She is day 1-post practitioners. Skillsets unique

to obstetric practice focusproject uncomplicated vaginal delivery -partumImprovement haemorrhage (PPH) (QI) presenting to on the timely management of having discharged herself this eral necessary uterotonics were not common emergency scenarios and is clearly ilable forIn use, a working group was University Hospitalmorning (TUH), several presentations of thatTallaght are relatively unique to haemorrhaging PV. valuate the preparedness thishospitals patient population.

In for line obstetric patients in extremis highlighted a critical medication with international practices, t’semergency presentations.

Consider, in your institution;

safety issue.

Consider presented on the right. we felt PPH and Pre-Eclampsia(PET) werethe 2 scenario centralised in Dublin.1,2 However, - Do you know where patients present as unscheduled encies, whcih require specific your uterotonics are emergencies settings that do Following aAdditionally, post-partum haemorrhage (PPH) presenting to pies and thus attention.to stored? not routinely provide obstetric rgenciesTUH, are unique to the obstetric several not - What are thewere doses and care. In where our hospital, these necessary uterotonics often present in thepresentations post-partum period, and emergency contraindications of immediately for use, a working group was tetric settings like ours highlighted patientavailable safety carboprost? obstetric medicine is highly

toinnovations evaluate for - Howpreparedness is ergometrine policiesestablished and even low-tech likethe hospitals Quality Improvement (QI) project given and when in PPH? ck), requires a significant QI framework to obstetric patient’semergency presentations.

In Tallaght University Hospital d initiatives lead to actual implementation.

(TUH), several presentations of ementation is highlighted for readers. obstetric patientsbelow in extremis

wed: ty ith

ped

em ied

issues,which we addressed in this

Scenario: 27-year-old female is brought in by ambulance in severe shock. She is day 1-post uncomplicated vaginal delivery having discharged herself this morning and is clearly haemorrhaging PV. Consider, in your institution;

Examining this, we felt PPH and Pre-Eclampsia(PET) were 2 - Do you know where highlighted a critical medication obstetric whcih require specific safety issue. emergencies, Consider the scenario your uterotonics are presented on the right. pharmacotherapies and thus attention.

Additionally, Examining this, we felt PPH post-partum period, and thus to implementation is highlighted stored? to Following a post-partum non-obstetric settings like ours. below for readers. and Pre-Eclampsia(PET) were Solution Postwhilstthese emergencies are2 obstetric uniqueemergencies, to the obstetric haemorrhage (PPH) presenting What are the doses and whcih • Drugs & Therpeutics identified Implemenation Developing local policies and We developed local guidelines to TUH, where several necessary Committee population, they often present in the post-partum period, and require specific pharmacotherapies even low-tech innovations like and information • Guildlances for management • Nursing stock check • Theatre Simulation contraindications ofsheets to guide uterotonics were not immediately • Site specific information: NCDH Induction presenation • Pharmacy technician final attention. •Additionally, and thus ours, (a drug pack), requires a practioners, often unfamiliar available for use, a working group thus to non-obstetric settings like ours Door codes, bleeps, stock implementation • Working group re-review carboprost? whilstthese emergencies are location . significant QI framework to ensure with pregnant patients, on the was established to evaluate the • Yearly code&bleep • Single pack - all in 1 place verification population, ideas and initiatives lead to management of PET and PPH. hospitals preparedness for obstetric unique to the obstetric is ergometrine Developing local policies and even likeimplementation. OurHow patient’semergency presentations. they often low-tech present in theinnovations actual path These guidelines, located within Implementation

-

ours, (a drug pack), requires a significant QI framework to ensure ideas and initiatives lead to actual implementation.

Our path to implementation is highlighted below for readers.

given and when in PPH?

Figure 1 QI development Journey:

lopmentIdea Journey: Idea to Implementation to Implementation

• Critical incidents reviewed: • Medication availability • Practioner comfort with patient population • Working group developed

Solution identified • Guildlances for management • Site specific information: Door codes, bleeps, stock location .

• Single pack - all in 1 place

• Drugs & Therpeutics Committee • Theatre Simulation • Pharmacy technician final implementation

Problem identified

Figure 1 QI development Journey: Idea to Implementation NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

Implementation

PostImplemenation • Nursing stock check • NCDH Induction presenation • Working group re-review • Yearly code&bleep verification

39

protocol to prompt practitioners

Figure 2 2 Obstetric Haemorrhage Figure Obstetric HaemorrhagetoPack Guidelines recognise the need for Pack Guidelines

early escalation of care. These guidelines now accompany emergency drug packs made available in our emergency department (ED) and theatre.

information about these packs in the induction booklet ensures new trainees are aware of their availability from day 1.

improving uterine tone in the case of PPH, can be devastating.

Correspondents:

We developed often unfamiliar with the drug packs, includelocal local guidelines and information sheets to guide practioners,tom.wall2@hse.ie Finally, we believe all Model 4 contact numbers, bleeps, door This project had a large pregnant patients, on the management of PET andnon-obstetric PPH. These guidelines, located within theworking drug hospitals, and codes, additional pack locations group, with direction from Dr Model 4 sites with obstetrics but as well as clinical advice on Ciara-Jean Murphy, Consultant packs, include local contact numbers, bleeps, codes, additional pack locations as well as clinical Additionally, we conducted a doorwhere obstetrics is not managed drug dosing information and Anaesthesiologist, and significant in the general theatre complex, theatre simulation to educate administration. We chose to advice on drug dosing information and administration. chose to highlightinput how from practitioners Mary Coyle, Critical seek should We consider the introduction nursing and anaesthesia staff on highlight how practitioners Care & Anaesthesia Lead of these pack to their emergency the availability of these packs and seek specialistadvice, advice, escalate specialist escalatehighlight management to theatre,department and activate the massivePharmacist, transfusion protocol to amongst others. and theatre. Delays to specific management management to theatre, and activate the massive transfusion priorities.

The inclusion of management, especially delays in References available on request prompt practitioners to recognise the need for early escalation of care. These guidelines now accompany emergency drug packs made available in our emergency department (ED) and theatre.

News

Additionally, we conducted a theatre simulation to educate nursing and anaesthesia staff on the availability of these packs and highlight specific priorities.

Theprogramme inclusion of information BowelScreen announces agemanagement extension to its about these packs in the induction booklet ensures new trainees are aware of their availability from day 1.

BowelScreen, the HSE’s Stephen Donnelly, Minister for Health says, “The latest expansion national bowel cancer screening of the HSE’s BowelScreen programme has begun lowering Programme is another important its age range to invite men and References milestone in the Government’s women aged from 59 to take National Cancer Strategy, and I the free at-home test. Bowel 1/ Dagwas Moster et al, Neonatal mortality rates in aged would encourage everyone screening previously available betweenunits 59 and 69 to register to to those aged 60-69, now small its communities with maternity compared take the free at-home screening 59 – 69. When our expansion is with those having units, British kit. test using the BowelScreen complete, everyone aged larger 55-74 maternity willJournal be invitedofforObstetrics screening. and Gynaecology,Volume 108, “Bowel cancer is the second most common of all cancers in men Around people are Issue2,600 9,2001. and the third most common of diagnosed with bowel cancer in all cancers in women in Ireland Ireland every year. Bowel cancer 2/ second Van Den Berg, L.M.ofet of shows acutethat a and recent research is the most common all al. Centralisation fear of finding something wrong cancers in men and the third most obstetric care in the Netherlands: a qualitative study is the most common reason common of all cancers in women for not taking part with in the test. to explore the experiences of stakeholders in Ireland.

Screening offers a chance for in organisation of care.

BMC Health Serv earlier detection and often means Thisadaptations expansion is outlined in the treatment is more effective than National Cancer Strategy 2017Res 21, 2021. with a later diagnosis and could 2026 and in the Programme for save your life.”

Government: Our shared future

3/ which Høghcommits S, Thellesen L, Bergholt T, Rom AL, Johansen 2020, to extending Professor Pádraic Mac Mathuna, bowel screening to everyone aged Clinical Director and BowelScreen, M, Sorensen JL. How often will midwives 55-74 years. Research shows that says: “We are working towards experience theobstetricians maximum benefit of screeningobstetric full age emergencies expansion, whileor willhigh-risk be achieved when bowel maintaining the high-quality deliveries: a national cross-sectional study. screening is available to those screening service we offer our BMJ Open.

2021 aged 55-74. existing eligible participants.

Finally, we believe all Model 4 non-obstetric hospitals, and Model 4 sites with obstetrics but where obstetrics is not managed in the general theatre complex, should consider the introduction of these pack to their emergency department and theatre. Delays to management, especially delays primary goal of BowelScreen bettercase outcome. in“The improving uterine tone toina the of Every PPH, can is to reduce mortality from bowel year around 3,000 people have cancer in people in Ireland. It be devastating. pre-cancerous growths (known aims to detect bowel cancer as early as possible when there are no symptoms; and to identify and remove abnormal tissue growths, called adenomas or polyps, which could develop into cancer if left untreated. This greatly reduces the risk of future bowel cancer development.

as polyps) removed through BowelScreen. These are all potential cancers prevented.”

Correspondents: tom.wall2@hse.ie

There will be a period of time

This project had a large working group, with between commencing extension and some people aged 59 direction from Dr Ciara-Jean Murphy, Consultant receiving their invitation to take part in screening.

BowelScreen Anaesthesiologist, and significant input from Mary issues invitations in two-yearly “If cancer is diagnosed through cycles, meaning thatPharmacist, some people Coyle, Critical & Anaesthesia Lead BowelScreen testingCare it is more may not get an invitation until they likely to be found at an early amongst others.may lead stage when treatment are 61.

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

HIT BACK AGAINST CROHN’S DISEASE WITH RINVOQ®▼ (upadacitinib)

PRESCRIBING INFORMATION (PI). RINVOQ®▼ ▼ (upadacitinib) 15 mg prolonged release tablets; 30mg prolonged-release tablets; 45 mg prolonged-release tablets. Refer to Summary of Product Characteristics (SmPC) for full prescribing information. PRESENTATION: Each tablet contains upadacitinib hemihydrate, equivalent to 15mg of upadacitinib in the 15mg tablet, 30mg in the 30mg tablet and 45mg in the 45mg tablet.

INDICATION: Treatment of moderate to severe active rheumatoid arthritis (RA) and active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more diseasemodifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Treatment of active non-radiographic axial spondyloarthritis (nr-axSpA) in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs). Treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy.

Treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy. Treatment of adult patients with moderately to severely active ulcerative colitis (UC) or moderately to severely active Crohn’s disease (CD) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent. DOSAGE AND ADMINISTRATION: Intended for use under guidance and supervision of a physician experienced in diagnosis and treatment of conditions for which upadacitinib is indicated. Dosage: RA, PsA, AS, and nr-axSpA: Recommended oral dose is 15mg once daily. Consideration should be given to discontinuing treatment in patients with AS and nr-axSpA who have shown no clinical response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. AD: Adults: Recommended oral dose is 15 mg or 30 mg once daily based on individual patient presentation (see SmPC for details). A dose of 15 mg is recommended for patients at higher risk of venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy. The lowest effective dose to maintain response should be used. For patients ≥ 65 years of age, the recommended dose is 15mg once daily. Adolescents from 12 to 17 years weighing at least 30 kg: Recommended oral dose is 15mg once daily. Consideration should be given to discontinuing upadacitinib treatment in any patient who shows no evidence of therapeutic benefit after 12 weeks of treatment. UC: Induction; Recommended oral dose is 45mg once daily for 8 weeks. For patients who do not achieve therapeutic benefit by week 8, 45mg once daily may be continued for an additional 8 weeks. Discontinue treatment in patients with no evidence of therapeutic benefit by week 16. Maintenance; Recommended oral dose is 15mg or 30mg once daily based on individual patient presentation (see SmPC for details). A dose of 15 mg is recommended for patients at higher risk of VTE, MACE and malignancy. The lowest effective dose to maintain response should be used. Patients ≥ 65 years of age: recommended dose is 15 mg once daily. In patients who have responded to treatment with upadacitinib, corticosteroids may be reduced and/or discontinued in accordance with standard of care. For patients with UC receiving strong inhibitors of cytochrome P450 (CYP) 3A4 the recommended induction dose is 30 mg once daily and maintenance dose is 15 mg once daily. CD: Induction; Recommended oral dose is 45mg once daily for 12 weeks. For patients who have not achieved adequate therapeutic benefit after the initial 12-week induction, 30mg once daily may be considered. For these patients, upadacitinib should be discontinued if there is no evidence of therapeutic benefit after 24 weeks of treatment. Maintenance; Recommended oral dose is 15mg or 30mg once daily based on individual patient presentation (see SmPC for details). A dose of 15mg once daily is recommended for patients at higher risk of VTE, MACE and malignancy. The lowest effective dose to maintain response should be used. Patients ≥ 65 years of age: recommended dose is 15 mg once daily. In patients who have responded to treatment with upadacitinib, corticosteroids may be reduced and/or discontinued in accordance with standard of care. For patients with CD receiving strong inhibitors of cytochrome P450 (CYP) 3A4 the recommended induction dose is 30 mg once daily and maintenance dose is 15 mg once daily. (see SmPC for more details). Special Populations: Elderly: Upadacitinib should only be used in patients ≥65 years if no suitable treatment alternatives are available. For AD patients ≥ 65 years of age, a dose higher than 15mg once daily is not recommended. For RA, PsA, AS and nraxSpA there are limited data for patients 75 years of age and older. For UC and CD maintenance therapy, a dose higher than 15 mg once daily is not recommended in patients ≥ 65 years of age. For UC and CD patients ≥ 75 years of age the safety and efficacy of upadacitinib has not been established. Renal: No dose adjustment required in mild-moderate renal impairment. Patients with severe renal impairment should use upadacitinib with caution (See SmPC for dose adjustments). Upadacitinib has not been studied in subjects with end stage renal disease and is therefore not recommended for use in these patients. Hepatic impairment: No dose adjustment is required in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Should not be used in patients with severe (Child Pugh C) hepatic impairment. Paediatric Population: Safety and efficacy in RA, AS, PsA, nr-axSpA, UC and CD in children and adolescents aged 0 to 18 years and in AD in children under 12 years of age has not been established. No clinical exposure data are available in AD adolescents < 40 kg.

CONTRAINDICATIONS: Hypersensitivity to active substance or excipients. Active tuberculosis (TB) or active serious infections. Severe hepatic impairment. Pregnancy. SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details. Upadacitinib should only be used if no suitable treatment alternatives are available in patients: 65 years of age and older; with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers) or with malignancy risk factors (e.g. current malignancy or history of malignancy). Immunosuppression: Combination use, with immunosuppressants e.g. azathioprine, 6-mercaptopurine, ciclosporin, tacrolimus, and biologic DMARDs or other JAK inhibitors has not been evaluated in clinical studies and is not recommended as the risk of additive immunosuppression cannot be excluded.

Serious infections: Serious and fatal infections have been reported. Caution when treating patients ≥65 years.

Frequently reported – pneumonia and cellulitis. Bacterial meningitis and sepsis have been reported.

Opportunistic infections reported – TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis. Do not initiate treatment in patients with active, serious infection, including localised infections.

Consider the risk/benefit of treatment in patients with: chronic or recurrent infection, history of serious or opportunistic infection, those exposed to TB, those who have resided or travelled in areas of endemic TB or endemic mycoses, those with underlying conditions that may pre-dispose patients to infection, those with

diabetes. Closely monitor patients for signs and symptoms of infection during and after treatment. Interrupt treatment if the patient develops a serious/opportunistic infection. If infection is controlled, resume treatment following risk/benefit consideration. A higher rate of serious infections was observed with upadacitinib 30mg compared to upadacitinib 15mg. Tuberculosis: Pre-screen patients for active or latent TB. RINVOQ should not be given to patients with active TB. Consider anti-TB therapy in patients with previously untreated latent TB or in patients with risk factors for TB infection. Consult with a physician with experience in TB therapy to assess whether initiating anti-TB therapy is appropriate for an individual patient. Monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy. Viral reactivation: Cases of herpes virus reactivation have been reported e.g. herpes zoster. If herpes zoster is reactivated, consider interruption of upadacitinib therapy until the episode resolves. Screen for viral hepatitis and monitor regularly for reactivation before starting and during therapy with upadacitinib. Patients, positive for hepatitis C antibody/hepatitis C virus RNA and hepatitis B surface antigen/hepatitis B virus DNA were excluded from clinical studies. If hepatitis B virus DNA is detected while receiving RINVOQ, a liver specialist should be consulted. Vaccination: Use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations prior to starting therapy, in agreement with current immunisation guidelines.

Malignancy: Lymphoma, NMSCs and other malignancies have been reported in patients receiving JAK inhibitors, including upadacitinib. There is a higher rate of malignancies and NMSCs with upadacitinib 30mg compared to 15mg. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. See SmPC for full details. Haematological abnormalities: Do not start therapy if Absolute Neutrophil Count <1 x 109 cells/L, Absolute Lymphocyte Count <0.5 x 109 cells/L and Hb <8 g/dL. Monitor patients and temporarily stop therapy if abnormal haematological parameters as specified are detected during routine patient management. Gastrointestinal perforations: Events of diverticulitis and gastrointestinal perforations have been reported. Use with caution in patients who may be at risk for gastrointestinal perforation (e.g., patients with diverticular disease, a history of diverticulitis, or who are taking non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or opioids). Patients with active Crohn’s disease are at increased risk for developing intestinal perforation. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation. Major adverse cardiovascular events: Events of MACE were observed in clinical studies of upadacitinib (See SmPC for full details). Lipids: Monitor total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) at 12 weeks and thereafter according to international guidelines for hyperlipidaemia. Elevated LDL in clinical trials decreased to pre-treatment levels in response to statin therapy, although evidence is limited. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Hepatic transaminase elevations: Monitor liver enzymes at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. In such cases therapy should be interrupted until this diagnosis is excluded.

Venous thromboembolism: Deep vein thrombosis (DVT) and pulmonary embolism (PE) were observed in clinical trials for upadacitinib. Use therapy with caution in patients with known VTE risk factors other than cardiovascular or malignancy risk factors. Risk factors include previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, and inherited coagulation disorder.

Patients should be re-evaluated periodically during upadacitinib treatment to assess for changes in VTE risk and treatment should be discontinued in patients with suspected VTE. Hypersensitivity: Anaphylaxis and angioedema have been reported in patients receiving upadacitinib. Discontinue treatment and institute appropriate therapy if significant hypersensitivity occurs. INTERACTIONS: Upadacitinib is metabolised mainly

by CYP3A4 and plasma exposures may be affected by CYP3A4 inhibitors or inducers. Upadacitinib 15 mg once daily should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors.

Upadacitinib 30 mg once daily dose is not recommended for patients with atopic dermatitis receiving chronic treatment with strong CYP3A4 inhibitors. For patients with ulcerative colitis or Crohn’s disease using strong CYP3A4 inhibitors, the recommended induction dose is 30 mg once daily and the recommended maintenance dose is 15 mg once daily (see Dosage and Administration). Avoid food and drink containing grapefruit during treatment with upadacitinib. See SmPC for full details. FERTILITY, PREGNANCY AND LACTATION: Upadacitinib is contraindicated during pregnancy. Women of childbearing potential should be advised to use effective contraception during treatment and for 4 weeks following the final dose of upadacitinib. Female paediatric patients and/or their parents/caregivers should be informed about the need to contact the treating physician once the patient experiences menarche while taking upadacitinib. Upadacitinib should not be used during breast-feeding. The effect of upadacitinib on human fertility has not been evaluated. ADVERSE REACTIONS: Refer to SmPC for full details on adverse reactions. Very common adverse reactions (≥1/10): upper respiratory tract infections, acne. Common adverse reactions (≥1/100 to <1/10): bronchitis, herpes zoster, herpes simplex, folliculitis, influenza, urinary tract infection, pneumonia, non-melanoma skin cancer, anaemia, neutropaenia, lymphopaenia, urticaria, hypercholesterolaemia, hyperlipidaemia, cough, abdominal pain, nausea, rash, fatigue, pyrexia, increased blood CPK/ALT/AST, increased weight and headache. ▼ 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.

LEGAL CLASSIFICATION: POM (S1A). MARKETING AUTHORISATION NUMBER/ PRESENTATION: EU/1/19/1404/001: RINVOQ 15 mg prolonged-release tablets in cartons of 28 tablets; EU/1/19/1404/006: RINVOQ 30 mg prolonged-release tablets in cartons of 28 tablets; EU/1/19/1404/010: RINVOQ 45 mg prolonged-release tablets in cartons of 28 tablets. 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. DATE OF REVISION: April 2023. PI-1404-010.

IE-RNQG-230025 | July 2023

CPD 102: ARTERITIS Continuing Professional Development

CPD 60 Second Summary Giant cell arteritis (GCA) is the most common form of systemic vasculitis. Its incidence demonstrates a strong association with aging.

GCA will affect 1 in 100 women and 1 in 200 men in Ireland in their lifetime.

Characteristic symptoms include temporal headache, jaw pain, and systemic features.

Devastating irreversible ischaemic complications such as vision loss and stroke may occur at disease onset. In the longer term, complications such as aortic aneurysms may occur. Inflammatory markers (ESR and CRP) are generally elevated, but not always markedly so.

Temporal artery biopsy remains the gold standard for diagnosis but has poor sensitivity. The utility of temporal artery ultrasound and other imaging techniques has progressed in recent years.

Glucocorticoids remain an indispensable part of the treatment algorithm but are associated with a multitude of treatment related adverse events. The biologic agent tocilizumab has emerged as a key part of GCA treatment, facilitating lower cumulative glucocorticoid doses and reducing flare rates.

The majority of people with GCA should now be initiated on combination treatment in order to minimise treatment related complications and improve long term outcomes.

Uncertainties remain but significant progress has been made in GCA management in recent years.

41

AUTHOR: Professor Richard Conway, Consultant Rheumatologist, St. James Hospital; Clinical Associate Professor, Trinity College Dublin Richard Conway graduated from the Royal College of Surgeons in Ireland in 2006. He completed rheumatology and general internal medicine training in Ireland in 2014, and a PhD in giant cell arteritis at University College Dublin in 2017. He is currently a consultant rheumatologist and physician at St. James’s Hospital and a clinical associate professor at Trinity College Dublin. He is the author of more than 150 peer-reviewed publications and 3 book chapters. His research interests include interstitial lung disease in systemic rheumatic diseases and systemic vasculitis.

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.

Giant Cell Arteritis Introduction

Clinical Presentation

Giant cell arteritis (GCA) is a systemic inflammatory rheumatic disease. It is the commonest form of systemic vasculitis in Ireland.

It has a striking age predilection, virtually never occurring prior to age 50 and becoming more common until a peak in the 70’s with a plateau thereafter.

GCA demonstrates a marked geographic preponderance being strikingly more common in Northern European populations than in other parts of the world.

This association seems to be genetically based rather than due to physical location with emigrant populations maintaining the risk of their ancestral origin. The lifetime risk of GCA in populations similar to Ireland is 1% in women and 0.5% in men – this is not a rare condition.1 The cause of GCA is unknown; the marked age association suggests a key role for immunosenescence. It is hypothesised that a particular individual’s immune system may be primed, by aging and/or other factors, to develop GCA, and then a subsequent second hit triggers the disease. The nature of this trigger has been elusive, and this may reflect the fact that there is no specific trigger; rather it may be the case that anything that stimulates the immune system can act in this role, this would correlate with the wide variety of infectious agents mooted as triggers, and indeed with the more controversial association with vaccines.

GCA may present with a variety of different clinical phenotypes (Figure 1). In the past the focus has predominantly been on the classic cranial GCA phenotype with limited recognition of other potential presentations. The phenotypes may overlap with patients presenting with features of more than one simultaneously or in succession.

Cranial GCA typically presents with unilateral or bilateral temporal headache. Headache is of course one of the most common clinical presentations and there is a wide differential. Scalp, and more specifically focal temporal artery tenderness is frequently present. The most specific clinical feature of cranial GCA is jaw claudication. Jaw claudication present similarly to intermittent claudication in the legs. There is, at least initially, no pain at rest, pain develops with use (typical chewing), to the extent that it frequently limits eating. Cessation of the provoking chewing activity will lead to symptom resolution and the ability to resume chewing until pain subsequently returns.

This process is the basis for the “chewing gum test” in GCA, where the patient is offered gum, the chewing of which can precipitate claudication. Visual complications are the most feared outcome in cranial GCA. Unfortunately they remain common, affecting 20% of patients. Our treatment

approach in GCA has proven very effective in preventing ischaemic complications once the diagnosis has been made, but unfortunately can have little impact in the development of these prior to diagnosis, and this now represents the vast majority of visual issues we see in GCA. Anterior ischaemic optic neuropathy is the most common permanent visual manifestation in GCA and unfortunately almost always results in irreversible blindness in the affected eye. If prompt intervention is not taken, this may spread to effect the contralateral eye with devastating results. In some patients this permanent vision loss can be preceded by amaurosis fugax or other temporary vision loss type events, and recognition and intervention at this point may prevent permanent vision loss. Other less common visual manifestations may occur, including diplopia due to cranial nerve palsies, or homonymous hemianopia due to stroke.

Polymyalgia rheumatica (PMR) is another rheumatic disease entity characterised by bilateral proximal arm and leg, as well as neck, stiffness with early morning predominance. While it is still debated, PMR and GCA are likely two ends of the spectrum of a single disease process. This is supported by shared pathogenic mechanisms, demographic associations, treatment responses, and particularly by the frequent co-occurrence of the two – 50%

42

CPD 102: ARTERITIS

of stroke in GCA is particularly of GCA patients have polymyalgic Clinical Examination symptoms, while 10-30% of pronounced at the time of onset The clinical findings in GCA people with PMR will ultimately and decreases significantly vary widely both based on the develop GCA. All patients following the institution of phenotype but also between presenting with PMR should treatment but with a small residual individual patients. Patients have a clinical assessment for increase in risk compared to the may look extremely unwell with GCA including examination of the general population. In GCA the marked cachexia, but at the same temporal arteries and for large usual frequency pattern of stroke time may look entirely healthy. vessel arterial bruits. If the history is reversed with a 3:1 ratio of Temporal arteries can be swollen, or examination raise concern for posterior circulation to anterior nodular, apulsatile, and tender – GCA, further investigation with circulation stroke. There may but can also be normal. In more imaging and/or temporal artery be minimal other symptoms of prolonged disease, temporalis biopsy should be pursued. There GCA and a high level of clinical muscle wasting may be noted. are two main scenarios in which suspicion in posterior circulation Occipital arteries are more difficult GCA occurs in the context of stroke is warranted, especially to palpate but tenderness may be apparent PMR. The first of these in the presence of any atypical elicited in the occipital notch – this is when de novo GCA develops features. In such cases, a is important to assess as isolated as a progression of existing PMR careful clinical examination is occipital artery involvement may disease. The second is when what the most useful tool, and may occur. Arterial bruits should be appears to be PMR was in fact be complemented by checking sought by auscultation in the always GCA. This occurs due to inflammatory markers or vascular carotid, subclavian, and axillary the fact that involvement of the imaging. arteries in particular. Reduced or subclavian and axillary arteries asymmetric pulses, and blood ecreases in significantly the institution of treatment but with a small residual increase in risk GCA can following closely mimic PMR The final common GCA phenotype pressure differences between ompared shoulder to the general population.

In GCA the usual frequency of stroke is reversed with a symptoms in particular. is perhaps thepattern most challenging. the limbs may be seen with large clues to the presence of GCA 1 ratio ofThe posterior circulation to anterior circulation stroke.

There may be minimal other This is the patient who presents vessel disease. Fundoscopic can level be from arterialsuspicion withinexclusively constitutional ymptomsin ofthis GCAsetting and a high of clinical posterior circulation stroke is warranted, exam should be performed in bruits (but need to be assessed for symptoms.

These may represent specially in the presence of any atypical features. In such cases, a careful clinical examination the anyis patient with visual symptoms prior to glucocorticoid treatment), some combination fever, or vascular searching ost useful tool, and may be complemented by checking inflammatory of markers imaging. for anterior ischaemic imaging findings (again need to weight loss, and anorexia. It may optic neuropathy. In addition those be priorGCA to glucocorticoids), are the most alsochallenging. present exclusively a who presents he final common phenotype is perhaps This is thewith patient with diplopia warrant a thorough a sustained failure of tapering in “pyrexia of unknown origin” orof fever, neurologic ith exclusively constitutional symptoms. These may represent some combination weight eye exam for cranial PMR. Doses of glucocorticoids witharaised inflammatory ss, and anorexia.

It mayPMR also are present exclusively with “pyrexia of unknownmarkers origin” or withnerve raisedpalsies. used to treat significantly of unknown cause. This group flammatory markers of unknown cause. This group of patients frequently have extensive Laboratory Investigations lower than required in GCA of patients frequently have vestigatory prior their ultimate diagnosis.

A thorough clinical assessment andprocess will lead to atotemporary extensive investigatory process may reveal GCAin is a systemic inflammatory but never ther signssymptom of GCA atamelioration initial presentation and it is a prior diagnosis which shoulddiagnosis. always be considered to their ultimate rheumatic disease. As such acute disease,forleading to uch cases.fully It is control not infrequent cross-sectional imaging, such as CT or PET, to identify vascular A thorough clinical assessment phase reactants / inflammatory frequent relapses relatively high unsuspected flammation consistent withon GCA in previously cases. may reveal other signs of GCA markers are characteristically but glucocorticoid doses. at initial presentation and it is a not invariably elevated. Erythrocyte diagnosis which should always Stroke may also occur as an sedimentation rate (ESR) is the be considered in such cases. It is ischaemic complication in GCA. traditional diagnostic test in GCA not infrequent for cross-sectional 1-6% of patients with GCA present but actually, C-reactive protein imaging, such as CT or PET, to withclinical stroke,phenotypes and the risk of stroke (CRP) is the more useful test gure 1: GCA identify vascular inflammation is increased in patients with known overall. CRP is elevated in 95% consistent with GCA in previously GCA with a Hazard Ratio (HR) of patients with GCA. ESR can be unsuspected cases. of 1.28-2.21 The increased risk normal in up to 20% of patients with untreated GCA. An important pitfall to avoid is being misled by the extent of the inflammatory marker elevation. While it sometimes occurs, GCA does not necessarily need to be associated with very high inflammatory markers, lesser elevations are also significant in the appropriate clinical scenario.

Figure 1: GCA clinical phenotypes

Fibrinogen is another potentially useful acute phase reactant and biomarker in GCA, however its widespread utilisation is limited due to cost implications.2 Patients can also have elevated platelets as an acute phase response, as well as reduced haemoglobin and albumin as negative acute phase reactants.

In terms of monitoring, while all of the above acute phase reactants may be elevated, for the individual patient it is likely that one or the other more closely reflects their disease activity. This will most frequently be the CRP, but for some patients ESR, fibrinogen, or even platelets may be more closely related to their symptoms.

It is useful to check all available and practical markers at first presentation, and then to choose to monitor the best marker of the patient’s disease longitudinally.

Imaging and Biopsy Temporal artery biopsy is the traditional gold standard investigation in GCA. It has a very high specificity for vasculitis.

However, while most cases of vasculitis affecting the temporal artery will be due to GCA, other vasculitidies including ANCA-associated vasculitis and Takayasu arteritis can involve this artery. Sensitivity is where temporal artery biopsy falls down, being negative in 50-70% of patients who really do have GCA. This is due to a variety of reasons including technical issues, skip lesions, and GCA phenotypes which do not involve the temporal arteries. Temporal artery biopsy can be challenging to obtain due to logistic issues, and is associated with potential complications given the invasive nature of the procedure.

Vascular ultrasound is a more recent innovation, offering a non-invasive way of assessing the temporal artery structure.

Procedurally at least the temporal artery, and often other arteries such as the axillary artery, are imaged.

Its widespread adoption has not occurred yet, mainly due to issues over training, expertise, resources, and equipment. Ultrasound has a similar sensitivity to biopsy of around 50% but a higher false positive rate of 20-30%. Many other conditions can result in this positivity including atherosclerosis, migraine, and malignancy.

43 Figure 2: Glucocorticoid Monotherapy Treatment Regime in GCA. A substantial proportion of patients with GCA have involvement of the aorta and its branches, some of these in the absence of temporal artery involvement. In this setting CT angiogram, MR angiogram, or PET imaging of the large arteries may be diagnostic. The choice between these modalities depends on availability and expertise at individual centres.

Figure 2: Glucocorticoid Monotherapy Treatment Regime in GCA

New GCA

Treatment Glucocorticoids were first used Ischaemic No ischaemic to treat GCA in 1949, and have Manifestations manifestations been the mainstay of treatment since that time. Glucocorticoids rapidly improve symptoms and reduce subsequent ischaemic complications. The glucocorticoid experience in GCA however is diabetes mellitus, and cataracts, marred by troublesome adverse among others, are commonly events, and frequent relapses Consider initial IV 40mg seen. Preventable glucocorticoid on reducing the dose. Despite related complications should methylprednisolone prednisolone the extensive experience with be ameliorated with prophylaxis 1G daily for 3 days daily for 1 month glucocorticoids in GCA, we for glucocorticoid induced have little evidence to guide osteoporosis (generally a optimum treatment regimens, bisphosphonate and calcium/ and physicians adopt different vitamin D) and peptic ulcer disease. approaches. Given the potentially It is evident from the associated devastating nature of GCA adverse event rate that Decrease by 5mg and likewise the severity of 60mg glucocorticoid monotherapy is not glucocorticoid related adverse prednisolone an ideal approach. The search for prednisolone events, these patients are best every 2 weeks glucocorticoid sparing agents in managed in a specialist centre daily for 1 month GCA was until recently dominated until 20mg daily and the following discussion of by disappointment with multiple my personal treatment approach agents demonstrating no efficacy. is for information purposes Methotrexate was traditionally rather than any expectation used in GCA but it is at best that non-GCA specialist beneficial for a limited number physicians should undertake this of patients.4 The anti-tumour alone, Figure 2. If patients are 40mg Decrease by necrosis factor alpha agents hospitalised with vision loss or prednisolone 2.5mg every 2 which have revolutionised other stroke, IV methylprednisolone areas of rheumatology are entirely daily for 2 weeks weeks until 10mg at daily doses of 500-1000mg is ineffective in GCA. administered for 3 days prior to the oral dosing described below.

This state changed in 2017 when The majority of GCA patients are the GiACTA randomised controlled managed sufficiently with initial trial demonstrated dramatic oral glucocorticoids. Patients efficacy for the interleukin-6 with ischaemic symptoms blocking monoclonal antibody (vision loss, stroke, jaw or limb tocilizumab. This followed on Decrease by 1mg claudication) are typically initiated from an earlier smaller trial monthly until off on prednisolone 60mg daily, also demonstrating efficacy.5, 6 with those with no ischaemic The benefit of tocilizumab symptoms commenced on 40mg demonstrated in the GiACTA trial is daily. Glucocorticoids are weight among the most pronounced seen based drugs and consideration in any medication intervention trial of adjustment of dosing in light of in rheumatic diseases. While the and thereafter by 1mg a month. other relapses will respond to body weight and comorbidities exact role of tocilizumab in GCA Relapses requiring dose escalation an increase of approximately is prudent. The initial treatment remains to be fully defined, it is are common in GCA and should 20% of the prednisolone dose. dose is generally continued for 1 likely beneficial for the majority of be dealt with promptly asadverse delay Due to the that high doses involved is evident from the associated event rate glucocorticoid monotherapy is not an ideal month following which It tapering patients at initial diagnosis, and results in both potential damage glucocorticoid related adverse commences. Those onapproach. a 60mg certainly all relapsing patients, in The search for glucocorticoid sparing agents in GCA was until recently dominated by and greater difficulty recapturing events are seen in more than 90% dose are reduced to 40mg initially. the absence of contraindications, 3 disappointment with multiple agents noGCA. efficacy. traditionally disease control.

Recurrence of demonstrating of people with Many Methotrexate of these From 40mg prednisolone is Figure was 3. If tocilizumab is utilised ischaemic complications may are associated with significant tapered by 5mg every 2used weeks the glucocorticoid reduction can in GCA but it is at best beneficial for a limited number of patients (4). The anti-tumour necrosis necessitate a return to the initial morbidity and indeed mortality; until 20mg daily, then by 2.5mg be accelerated in line with the factor which have revolutionised othersepsis, areashypertension, of rheumatologystudy areprotocol entirelyfrom ineffective high prednisolone doses.

Most fractures, the GiACTAin every 2 weeks until 10mg daily,alpha agents

GCA.

44 CPD 102: ARTERITIS Suggested GCA treatment Algorithm Figure 3: Suggested GCA treatment Algorithm New GCA

Contraindicaitons to Tocilizumab or Patient Preference Not to Have Tocilizumab

No

Yes

Glucocorticoid + Tocilizumab

Glucocorticoid Monotherapy

Relapse

Relapse

Yes

Consider Alternative Agents

No

Yes

condition, and our experience with tocilizumab in rheumatoid arthritis, my own current practice is to recommend continuation of tocilizumab long-term. The mode of action of tocilizumab results in normalisation of CRP and ESR, which may be discordant with the clinical state of the patient. The consequence of this is that they will generally remain artificially low even in the presence of GCA relapse, or indeed other intercurrent events such as infections. Therefore considered clinical assessment becomes even mroe essential in tocilizumab treated GCA patients.

No

Reconsider Tocilizumab Consider Alternative Agents

Trials of multiple other agents are ongoing with promising early data and it is hoped that our treatment armamentarium will further expand in the near future.

The agents being studied include the T-cell modulator abatacept, IL-17 inhibitor secukinumab, IL-23 inhibitor guselkumab, IL-12/23 inhibitor ustekinumab, GM-CSF inhibitor mavrilimumab, and JAK inhibitor upadacitinib.7, 8 Summary GCA is a relatively common and potentially devastating condition.

Prompt diagnosis and treatment can avert the immediate risks of vision loss and stroke. In the longer term, the aim is minimisation of treatment related adverse events while maintaining disease control. Glucocorticoids remain a central pillar of treatment but most patients benefit from initial combination treatment incorporating tocilizumab.

trial –other this can be approximated – however this association is subcutaneous injection weekly multiple agents are ongoing with promising early data and it is hoped that our by tapering twice as quickly as weak. Glucocorticoids have a for the first year. After 1 year in outlined in Figure 2. Tocilizumab significantin impact both future. remission, someagents patients will t armamentarium will furthermore expand theonnear The being studied include is a biologic disease-modifying infections overall and diverticulitis, be able to increase their dosing modulator abatacept, secukinumab, IL-23toinhibitor IL-12/23 antirheumatic drug. The main IL-17 inhibitor so when the choice is between interval every second guselkumab, week with concern with these agents is these two options tocilizumab no relapse. The need for long-term ustekinumab, inhibitor mavrilimumab, and JAK inhibitor upadacitinib (7, 8). infectious risk. GM-CSF Tocilizumab has an is generally preferable from treatment with tocilizumab remains association with diverticulitis and increased diverticular perforation

an adverse event viewpoint.

Tocilizumab is administered by

to be clarified, however given that giant cell arteritis is a long-term

References available on request

y

elatively common and potentially devastating condition. Prompt diagnosis and treatment the immediate risks of vision loss and stroke. In the longer term, the aim is minimisation of

BRCA

45

BRCA Gene in Men’s Health BRCA stands for BReast CAncer gene. BRCA1 and BRCA2 are tumour suppressor genes which means that they stop the cells in our body from growing and dividing out of control and becoming cancer. People who inherit harmful variants in one of these genes have increased risks of several cancers—most notably breast and ovarian cancer, but also several additional types of cancer. People who have inherited a harmful variant in BRCA1 and BRCA2 also tend to develop cancer at younger ages than people who do not have such a variant.

A lot of people still think that this is a ‘Female or Woman’s’ gene, but the truth is that a BRCA1 or BRCA2 alteration/fault can be inherited from a person’s mother or father. If you carry a genetic alteration, each of your children (male or female), and each of your siblings (male or female) have a 50% (1 in 2) risk of inheriting the same alteration.

Faulty BRCA1 and BRCA2 genes are rare. Around 1 in every 400 people have a faulty BRCA1 or BRCA2 gene. Men who have inherited a fault in their BRCA1 or BRCA2 gene also have a higher risk of developing certain types of cancers, including prostate, pancreatic, and even breast cancers.

While breast cancer is rare in men, it can happen. The average male has a 0.1 percent lifetime risk of developing breast cancer, but in men with BRCA alterations, the risk is much higher: 1 to 5 percent lifetime risk for men with BRCA1 alterations and 5 to 10 percent lifetime risk for men with BRCA2 alterations.

However, most men are probably more worried about prostate cancer than breast cancer, with good reason: the lifetime risk for prostate cancer for an average male is 14 percent. In Ireland, after non-melanoma skin cancer, prostate cancer is the most common cancer in men. It accounts for almost one-third of all invasive cancers in men. 1:8 Irish men will develop prostate cancer (to the age of 75) and 1:6 in their life time. An average of 3,941 men are diagnosed each year in Ireland with prostate cancer and 554 deaths occur due to prostate cancer. However, the 5 year survival rate for prostate cancer is increasing all the time and it is now up to 93%!

For men with BRCA1/2 alterations, the risk of developing prostate cancer is higher than for the general public and if prostate cancer does develop, it may be more aggressive. The risk is higher for people born male with

Written by Bernie Carter, Assistant Director of Nursing Services, Marie Keating Foundation

an alteration in the BRCA2 gene than in the BRCA1. Men who carry a BRCA2 alteration have a 27% risk of developing prostate cancer by the time they are 80 years old, more than double the rate compared to non-carriers and may be diagnosed at a younger age.

Men with BRCA alterations are also at increased risk for pancreatic cancer: 2 to 3 percent lifetime risk for those with BRCA1 alterations and 3 to 5 percent lifetime risk for those with BRCA2 alterations, compared to just 1 percent lifetime risk in the general population.

Unfortunately, there's currently no reliable screening test for prostate cancer. Some research suggests that perhaps annual PSA tests for prostate cancer may benefit men who carry the faulty BRCA2 gene.

BRCA2 mutations are also associated with a higher risk of melanoma in males.

BRCA: The Breast Cancer Gene - BRCA Mutations & Risks (nationalbreastcancer.org)

Talk to your GP if you think you could have inherited any of these faulty genes or if you have a strong family history of cancer especially breast, ovarian and or prostate cancer. A strong family history of cancer means multiple close family members on the same side of the family who have the same cancer or related cancer types.

Predictive genetic tests for cancer risk genes - NHS (www.nhs.uk) BRCA Gene Mutations: Cancer Risk and Genetic Testing Fact Sheet - NCI What Men Need to Know About BRCA and Other Gene Mutations | Breast Cancer Research Foundation (bcrf.org)

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

Obesity

46

Let’s Talk Weight Management Written by Dr Kate McCann, Lifestyle Medicine Physician

As we roll into November, there will be multiple media campaigns reminding men to get themselves checked. It is very likely that as part of those health checks, the patient will be asked to get on the scale. How many men will be told that they should take steps to reduce their weight? And more importantly, how many men will be offered supports to lose the weight? Statistically, probably not as many that need it.

It is important to talk about weight during Men’s Health Awareness Month. In Ireland, men are more likely to be above a healthy weight or obese compared to women. 43% of men versus 31% of women are above a healthy weight. 25% of men versus 22% of women are obese. If we break this down by age, 65% of those aged 15-24 are a healthy weight, but this dramatically decreases to only 35% by age 24, and then only fewer than 20% of men are a healthy weight by age 64. Obesity in 51- 64 year old Irish men has risen 42%. . A NIHR study found that the likelihood of men returning to healthy weight was only 1: 210 compared to 1:124 in women.

Studies also show that not only are men more likely to be above a healthy weight, but that men are more likely than women to need the supports to lost weight.

In the current climate, it is simply impossible to discuss obesity and weight management without talking about pharmaceutical

treatment options. In this context, though, what has the option of GLP-1a medications (liraglutide, semaglutide), meant for men?

I’m not sure enough people are asking that very good question.

In September, there was a UK documentary about “skinny jabs.”

There were many criticisms that could be – and should be - levelled at that particular programme, but let’s just focus on that the show only featured women’s experience with obesity and treatment.

Now, I will be the first to argue that women’s voices need to be heard. But in this case, the documentary subtly perpetuated many unhelpful biases, including that not only the myth that weight is predominantly a body image problem but that weight is more of a problem for women. Like the ads for weight loss programmes that feature images of women, it is based on solid market research: women more consistently report that they are actively trying to lose weight than men. We should be discussing treatment options equally with our male patients.

It is challenging the outdated ideas surrounding obesity - for example, that treatment is just a matter of the outdated mantra “Eat Less, Move More”. We know now that obesity is a complex, chronic, recurring, and progressive disease. While evidence-based lifestyle intervention is an essential part in both obesity prevention and management, patients may need far more. Evidence-based

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

lifestyle interventions should consider the patient’s goals, and target sustainable, long-term changes. It may require input from dietitians, physiotherapists, and psychologists. Patients who have metabolic or hormonal factors including hypothyroidism, PCOS, hypotestosteronism – may also need that addressed with expert endocrinology input. Options such as GLP-1 analogues or referral to tertiary level, multi-disciplinary bariatric services should also be discussed where indicated.

Patients deserve these informed conversations about their evidence-based and safe options.

And if patients are not offered these conversations from their doctor, with knowledge and empathy, then the information and offers of help will come from elsewhere. While GLP-1a medications sourced from online virtual consultation services may be effective at moving numbers on the scale, that is not the end in itself. We need to treat obesity as the complex disease it is that deserves whole patient care. Guidance on incorporating physical activity to maintain bone health, mental health, and reduce blood pressure is important -- independent to any effect on weight loss. Addressing any unhealthy drinking or any underlying trauma that has led to comfort eating patterns is important. Addressing potential obstructive sleep apnoea is essential to reduce cardiovascular risk factors and improve mental health. Nutrition input is key: reducing risk of complications from obesity requires not just eating less, but eating a diet that will reduce risk of complications from obesity, such as heart disease, stroke, and colon cancer.

These obesity-related complications should be highlighted in relation to men’s health. In Europe, about 11% of colorectal cancers are associated with being above a healthy weight or obesity; this data suggests that obesity is associated with between 30%-70% increased risk of colon cancer in men, an association that is not seen in women. In regards to fertility, up to 50% of couples who present with subfertility will have a contributing male factor. Obesity

in men is associated with erectile dysfunction, hypotestosteronism, secondary hypogonadism, and low sperm count. In regards to cardiovascular disease, metaanalyses have demonstrated that for each 10 kg increase in body weight, there is an associated 12% increase in the risk of coronary artery disease. For each 1kg/ m2 increase in BMI, the risk of ischaemic stroke increases 4% and the risk of haemorrhagic stroke increases by 6%. For men, an increased waist circumference is associated with a five-fold risk of diabetes, compared to a three-fold risk of diabetes in women with an increased waist circumference.

Reducing these risks is why we need to have discussions with our patients about the disease of obesity and treatment. Based on multiple studies, HIQA has recommended that surgery is safe and the most effective treatment for type 2 diabetes; not only do patients go into remission but surgery also reduces the risks of diabetic complications, including kidney disease. The results of the SELECT trial were published this past August. This trial was important because it measured the impact of semaglutide not on weight but on reducing the incidence of myocardial infarction, heart failure, peripheral vascular disease, and stroke over a 5 year period in a predominantly male cohort.

While the ability to prescribe and dispense these drugs is currently impacted by a long waiting lists for bariatric services, limited access to necessary multidisciplinary supports, restrictive reimbursement schemes, prohibitive drug prices, and a global drug shortage, it is still worth considering and having the discussion about treatment options with patients.

We need to talk about the options with patients because the consequence of all of this, coupled with weight stigma and environmental factors that contribute to the perpetuation of our current obesity crisis – including urbanisation, sedentary lifestyle, socio-economic factors, diets high in ultra-processed foods -- has created situations in which many patients feel pushed into unsafe or desperate

47

choices. Top of the list of unsafe options for patients include medical tourism for bariatric procedures. Too many health professionals, unfortunately, who will read this article will already have come across a patient with complications from an ill-advised surgery abroad. Problems with surgery abroad include out-of-date procedures, such as the fitting of a gastric band or balloon, which is not a recommended treatment for obesity (Up to 40% of patients will have to have these removed.)

For those who have had gastric sleeve or gastric bypass done abroad, complications include not just peri-operative risks such as complications from anaesthesia, VTE, or infection, but long term complications due to lack of standard pre-operative and post-operative care, including addiction, self-harm, malnutrition, vitamin deficiencies, and dumping syndrome. Conversely, we also should be having conversations with patients who are excellent candidates for medications or surgery but a reluctant to be referred to safe, expert bariatric programmes due to the misinformation about side-effects, the procedures, or fears of complications.

Throughout this article, the term “men” has been used inclusively, but I think that most healthcare professionals will read it as referring to cisgender men. It is

important to highlight that there are groups of men with increased risk. There is an overall increased risk of obesity among transgender men. Men who identify as gay are less likely to be above a healthy weight or have obesity, but seven times more likely to report binge eating, and in a UK study, 42% of men with eating disorders identify as gay. In regards to MSM (men

who have sex with men) who are living with HIV, complications from some of the anti-retroviral agents may include lipodystrophy and insulin resistance.

Overall, as we roll into November, it is helpful to remember that we are advocating for men to schedule their health checks because men are around 32% less likely than

women to seek a healthcare appointment when needed. In this context, when we do see men in in our clinical practice, it is a good time to Make Every Contact Count and, where appropriate, have supportive, compassionate, and informed conversations around maintaining a healthy weight and obesity as a complex disease with safe treatment options.

Men's Health News

Reform is Needed – Says IMO The Irish Medical Organisation (IMO) has warned that radical reform is now the only viable option for a health system that has been chronically under-funded and under-resourced for decades.

The IMO launched its pre-Budget submission in Dublin recently. It said it was imperative that the Government focus on two key areas in next month’s Budget: • Health service capacity: there has been little or no increase in capacity across our health system despite rising demand from a growing and ageing

population. This is the key driver of Emergency Department overcrowding.

• Medical workforce planning: poor medical workforce planning has left us with an on-going shortage of medical specialists and extensive waiting lists for hospital care Dr John Cannon, President of the IMO, said, “This year, the Government has the chance to do what successive governments have failed to do for decades: implement radical reform of our health system for the good of patients.

“This is the only viable option for a service that has been chronically under-funded and under-resourced for generations.

We cannot accept another Budget which does not adequately address our significant capacity issues. We need substantial investment in capacity right across our health system including 5,000 acute hospital beds, supports for investment in GP infrastructure, short and longterm care for our older population and a plan to fully digitalise our health service.

“We need urgent investment in our medical workforce.

Workforce planning requires a clear implementation plan that not only aligns the number of training places with future demand but addresses working conditions and the ongoing issues of recruitment and retention.

“Time and again we see examples of the Government failing to follow through on recommendations that are urgently needed across the board.

We cannot postpone meaningful reform any longer.”

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

Erectile Dysfunction

48

Relationship Between Age, Comorbidity, and the Prevalence of Erectile Dysfunction Written by Francesco Pellegrinoa b, Daniel D. Sjoberga, Amy L. Tina, Nicole E. Benfantea, Alberto Brigantib, Francesco Montorsib, James A. Easthamc, John P. Mulhallc, Andrew J. Vickersa a

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

b c

Division of Oncology/Unit of Urology, IRCCS San Raffaele Hospital, Urological Research Institute, Milan, Italy

Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Erectile dysfunction (ED) is defined as the persistent inability to obtain or maintain an erection that is sufficient to allow satisfactory sexual intercourse.1 ED has important implications for the quality of life and psychosocial health of men and their partners.2, 3 Age is a well-known risk factor for ED, and several studies have reported on the prevalence of ED with advancing age.2, 4, 5, 6, 7 Remarkably, all of these studies reported on ED prevalence using crude categories, such as 10-yr age intervals. This is problematic since there may be important variations within these groups. For instance, 50-yr-old men may not have the same ED risk as 59-yr-old men, but are treated the same in a paper reporting ED among men aged 50–59 yr. Moreover, all the studies used mixed populations of participants both with and without other risk factors for ED, such as obesity, hypertension, and

diabetes.8 Hence, the risks given reflect the respective combined distribution of comorbidities in the cohorts studied. For example, when the authors of the Cologne study4 report an ED prevalence of 34% for men aged 60–69 yr, what they mean is that in any group of 100 men in their 60s with the same distribution of comorbidities as 60-yr-old men in the Cologne study, 34 will have ED. Similarly, the Massachusetts Male Aging Study2 reported at least minor ED in 50% of men aged 50–54 yr, but again this is true only for groups of men with a similar level of comorbidity as in that study.

In this context, our aim was to understand how the risk of patientreported ED varies according to age, alone and together with the presence of other risk factors for this condition.

At Memorial Sloan Kettering Cancer Center (MSKCC, New York, NY, USA), sexual status

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

surveys are used as part of routine care in the evaluation of patients with prostate cancer. This provides us with a large database of patients that can be used to describe the prevalence of ED by age with far more granularity on age and comorbidity status than prior studies, permitting us to take into account the effect of comorbidities separately. Because ED is a marker of endothelial dysfunction,9 our results provide insight into how this varies by age and comorbidities.

Patients and methods Study population In this cross-sectional study, after obtaining institutional review board approval (reference 17-629), we used a prospective database of 19 601 patients with a diagnosis of prostate cancer referred to MSKCC between 2007 and 2021 who completed ED questionnaires at their first visit. We excluded

patients who had undergone previous prostate cancer therapy or surgery for ED. This resulted in a final population of 17,250 men.

Erectile function assessment Erectile function was evaluated in our population using the patientreported erectile function domain score of the International Index of Erectile Function (IIEF), which comprises questions 1–5 and 15 of the IIEF questionnaire (IIEFEF) and is routinely used as a standalone instrument for this purpose.10 We used the MSKCC modification of the IIEF-EF, which incorporates a wider range of sexual behaviors compared to the original IIEF-EF.10 We defined patients affected by ED as those with an IIEF-EF score ≤24.11 Comorbidity assessment Age, diabetes, dyslipidemia, hypertension, obesity, cardiovascular disease (CVD),

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The First & Only Oral ADT Tablet not to size.

ABBREVIATED PRESCRIBING INFORMATION Please refer to the Summary of Product Characteristics (SmPC) before prescribing ▼Orgovyx 120 mg film-coated tablets Presentation: Each tablet contains 120mg of relugolix. Indications: For the treatment of adult patients with advanced hormone-sensitive prostate cancer.

Dosage and Administration: Treatment with Orgovyx should be initiated and supervised by specialist physicians experienced in the medical treatment of prostate cancer. Treatment should be initiated with a loading dose of 360 mg (three tablets) on the first day, followed by a 120 mg (one tablet) dose taken once daily at approximately the same time each day. Because relugolix does not induce an increase in testosterone concentrations, it is not necessary to add an anti-androgen as surge protection at initiation of therapy. Dose modification for use with P-gp inhibitors Coadministration of Orgovyx with oral Pglycoprotein (P-gp) inhibitors must be avoided.

If co-administration is unavoidable, Orgovyx should be taken first and dosing should be separated by at least 6 hours. Treatment with Orgovyx may be interrupted for up to 2 weeks if a short course of treatment with a P-gp inhibitor is required. Dose modification for use with combined P-gp and strong CYP3A inducers Co-administration of Orgovyx with combined P-gp and strong cytochrome P450 (CYP) 3A inducers must be avoided. If co-administration is unavoidable, the dose of Orgovyx must be increased to 240 mg once daily. After discontinuation of the combined P-gp and strong CYP3A inducer, the recommended 120 mg dose of Orgovyx once daily must be resumed. Missed doses If a dose is missed, Orgovyx must be taken as soon as the patient remembers. If the dose was missed by more than 12 hours, the missed dose must not be taken and regular dosing schedule should be resumed the following day.

If treatment is interrupted for over 7 days, Orgovyx must be restarted with a loading dose of 360 mg on the first day, followed with a dose of 120 mg once daily. Elderly No dose adjustment is required. Renal impairment No dose adjustment in patients with mild, or moderate renal impairment is required. Caution is warranted in patients with severe renal impairment. Hepatic impairment No dose adjustment in patients

with mild or moderate hepatic impairment is required. Paediatric population There is no relevant use of Orgovyx in children and adolescents under 18 years of age for the indication of treatment of advanced hormone sensitive prostate cancer. Method of administration Oral use. Orgovyx can be taken with or without food. Tablets should be taken with some liquid as needed and swallowed whole. Contraindications: Hypersensitivity to the active substance or to any of the excipients, see SmPC for further details.Warnings and Precautions: Effect on QT/QTc interval prolongation 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 Orgovyx.

A thorough QT/QTc study showed that there was no intrinsic effect of relugolix on prolongation of the QTc interval. Cardiovascular disease Cardiovascular disease such as myocardial infarction and stroke has been reported in patients with androgen deprivation therapy. Therefore, all cardiovascular risk factors should be taken into account. Changes in bone density Long-term suppression of testosterone in men who have had orchiectomy or who have been treated with a GnRH receptor agonist or GnRH antagonist is associated with decreased bone density, which, in patients with additional risk factors, may lead to osteoporosis and increased risk of bone fracture.

Hepatic impairment Patients with known or suspected hepatic disorder have not been included in long-term clinical trials with relugolix. Mild, transient increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been observed but were not accompanied by an increase in bilirubin or associated with clinical symptoms.

Monitoring of liver function in patients with known or suspected hepatic disorder is advised during treatment. The pharmacokinetics of relugolix in patients with severe hepatic impairment has not been evaluated. Severe renal impairment Exposure to relugolix in patients with severe renal impairment may be increased by up to 2 fold.

Because a lower dose of relugolix is not available, caution in patients with severe renal impairment is warranted upon administration of a 120 mg dose of relugolix

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

once daily. The amount of relugolix removed by haemodialysis is unknown. Prostatespecific antigen (PSA) monitoring The effect of Orgovyx should be monitored by clinical parameters and prostate-specific antigen (PSA) serum levels. Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’. Fertility, Pregnancy and Lactation: This medicinal product is not indicated in women of childbearing potential. It is not to be used in women who are, or may be, pregnant or breast-feeding. Effective contraception must be used during treatment and for 2 weeks after the last dose of Orgovyx. Orgovyx may impair fertility in males of reproductive potential. Refer to SmPC. Adverse events include: Adverse events which could be considered serious include; Common: Anaemia, Hypertension, Glucose increased Rare: Myocardial infarction. Unknown: QT prolonged. Other Very Common adverse events: Diarrhoea (inc colitis), Musculoskeletal pain (inc arthritis), Hot flush, Constipation, Fatigue. Other Common adverse events: Gynaecomastia, Insomnia, Depression, Dizziness, Headache, Nausea, Hyperhidrosis, Rash, Libido decreased, Weight increased, Triglyceride increased, Blood cholesterol increased. Other Uncommon adverse events: Osteoporosis/osteopenia, Aspartate aminotransferase increased, Alanine aminotransferase increased. Shelf Life: 36 months. Pack size: 30 and 90 (3 packs of 30) film-coated tablets. Marketing Authorisation Holder (MAH): Accord Healthcare S.L.U., World Trade Center, Moll de Barcelona, s/n, Edifici Est 6ª planta, 08039 Barcelona, Spain.MA Number: EU/1/22/1642/001, EU/1/22/1642/002. Legal Category: POM. Full prescribing information including the SmPC, is available on request from Accord Healthcare 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: April 2023 IE-02042 ADT: Androgen Deprivation Therapy. * 1. ORGOVYX® Summary of Product Characteristics.

2. Fragkoulis C, et al. Arab J Urol. 2021;19(4):460–463.

3. Shore ND, Saad F, Cookson MS, et al. N Engl J Med. 2020;382(4):2187–2196.

June 2023. IE-02064

Erectile Dysfunction

50

lower urinary tract symptoms/ benign prostatic hyperplasia (LUTS/BPH), and depression/ anxiety were considered as ED risk factors for the present study.

These are some of the ED risk factors reported by the American Urological Association12 and European Association of Urology guidelines,8 and associations between these risk factors and ED have been extensively studied.13, 14, 15, 16, 17, 18 Metabolic syndrome,19 sleep apnea,20 and smoking21 were not included because of inconsistent clinical recording of these risk factors. All risk factors were obtained from the medical history as documented by the physician who evaluated each patient. Dyslipidemia was defined as elevated total cholesterol, low-density lipoprotein cholesterol, or triglyceride levels, or low levels of high-density lipoprotein cholesterol. We defined patients as having CVD if they had a history of coronary artery disease, other heart diseases (eg, rhythm

problems, cardiomyopathy, and heart valve diseases), or vascular disease (eg, peripheral vascular disease, stroke, transient ischemic attack, and carotid stenosis), but excluded hypertension and dyslipidemia, as these were considered separately. All risk factors except for age were considered as dichotomous variables (eg, diabetes: yes vs no).

Statistical models To estimate the prevalence of ED due to the selected risk factors in our population, we first evaluated whether or not the association between age and ED risk was linear. We used restricted cubic splines for age with four knots placed at the 5th, 35th, 65th, and 95th percentiles, corresponding to 49.6, 60.2, 66.7, and 76.8 yr.22 There was strong evidence of a nonlinear relationship between age and the logarithmic odds of ED (p < 0.001), and therefore the nonlinear terms were retained.

To assess further how we should

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

build our model, we evaluated wherever there was interaction between age and each of the other risk factors. We saw no evidence of interaction, with p ≥ 0.5 for all the risk factors except for diabetes (p = 0.2) and LUTS/ BPH (p = 0.09). Interaction terms were therefore not considered.

The predictors included in the final model were age as a nonlinear term and diabetes, dyslipidemia, hypertension, obesity, CVD, LUTS/ BPH, and depression/anxiety as binary terms (yes vs no).

To investigate how ED varies according to age and the presence of other risk factors, we converted the coefficient for each risk factor from the multivariable logistic regression model to an integer score. Then we plotted ED prevalence against age and the aggregate risk score obtained by summing the risk factor scores for each combination of possible comorbidities using two different methods. First, we

used a line plot representing ED risk by age for men with different aggregate scores (0 = absence of risk factors; 10 = patients with, eg, LUTS/BPH and CVD; 20 = patients with, eg, LUTS/ BPH, CVD, hypertension, and obesity; 30 = patients with, eg, depression/anxiety, diabetes, and CVD; and 45 = patients with all six risk factors). Second, we used a heatmap to represent ED prevalence by age and risk factors in a more granular way.

As some urologists use an IIEFEF score <26 to define ED,24 we repeated all of the analyses using this cutoff. Finally, we plotted the prevalence of moderate ED (IIEF-EF score <17) and severe ED (IIEF-EF score <11) using the same approach. All tests were two-sided with a significance level of 0.05. Statistical analyses were performed using R v4.0.2 statistical software (R Foundation for Statical Computing, Vienna, Austria).

51

Fig 1: Prevalence of erectile dysfunction (ED; International Index of Erectile Function erectile function domain score ≤24) by age for patients with different aggregate risk scores (0, 10, 20, 30, and 45). To obtain the aggregate score for a patient with specific risk factors, add the risk factor scores in the table. CVD = cardiovascular disease; LUTS/BPH = lower urinary tract symptoms/benign prostatic hyperplasia

Fig 2: Prevalence of erectile dysfunction (ED; International Index of Erectile Function erectile function domain score ≤24) by age and aggregate risk factor score. Black curves denote ED risk (from 10% to 90%). To obtain the aggregate score for a patient with specific risk factors, add the risk factor scores in the table. CVD = cardiovascular disease; LUTS/BPH = lower urinary tract symptoms/benign prostatic hyperplasia

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

Erectile Dysfunction

52

approaches. The authors of the Massachusetts study reported ED prevalence of 70% for 70-yr-old men, whereas we found that risk varies from 55% for healthy men to >80% for men with numerous comorbidities.

Results Approximately half of the study population was affected by ED (51%). All comorbidity risk factors were more frequent in the group of patients with ED, and approximately two-thirds of the men with ED had at least two concomitant risk factors.

The intercept for our model was zero. All of the risk factors except for dyslipidemia were significantly associated with ED. Diabetes emerged as the strongest risk factor for ED (odds radio 2.01, 95% confidence interval 1.81– 2.24). To ease interpretation, we converted the coefficients from the multivariable model to integer scores using the standard approach of dividing by the smallest coefficient.23 We then multiplied by a factor of three and rounded the results to integer numbers.

The prevalence of ED by age and aggregate risk factor scores is shown in Fig. 1, Fig. 2 for specific combinations of age and comorbidities. The data can also be serve as a visualization of endothelial function in aging males.

Aggregate risk scores calculated by summing the risk factor scores were used to plot the prevalence of ED for specific combinations of age and various comorbidities.

ED prevalence ranged between 10% and 78% for men without comorbidities as age increased from 40 to 80 yr (Fig. 1). At a specific patient age, ED risk greatly increases with the presence of additional risk factors. However, a given relative increase in the odds of ED has differential effects on the absolute risk, depending on the baseline risk. Hence, the effect of comorbidities on the absolute risk of ED was higher for young patients than for older patients. For instance, for a 40-yr-old man the risk of ED increases from 10% to 44% (an increase of 34%) if all the risk factors are present, whereas for an 80-yr-old patient this increase is approximately 18% (from 78% to 96%). The prevalence of ED for 50-yr-old and 75 yr-old men

was 20% and 68%, respectively, for healthy men, but 41% and 85%, respectively, for men with concomitant hypertension, obesity, and diabetes. Finally, the data show that healthy older men have the same risk of ED as younger patients who have several comorbidities. For instance, a 50-yr-old man with diabetes, obesity, and hypertension has the same risk of ED as a 65-yr-old man without comorbidities.

Discussion We used a large database to estimate the prevalence of patientreported ED for specific ages and combinations of comorbid conditions. A particular advantage of our approach is that we provide estimates for men at specific ages rather than for men in 5–10-yr age intervals. This contrasts with previous studies on age and ED.2, 4, 5, 6, 7 By categorizing age in 5–10-yr ranges, authors overestimate ED risk for younger men and underestimate it for older men in each group. For example, the average risk of ED among healthy men aged 50–59 yr in our study was ∼28%, but this varied over an approximately 1.75-fold range, from 20% risk at age 50 yr to 35% risk at age 59 yr.

A second advantage of our approach is that we provide estimates for specific combinations of comorbidities rather than for men with the average comorbidity. Prior studies that explored the relationship between age and ED2, 4, 5, 7 reported ED risk for mixed cohorts of patients both with and without comorbidities (eg, hypertension, cardiovascular disease, diabetes).

Their results therefore correspond to the average ED prevalence in the general population and not to the ED risk due to age alone.

Comparison of ED prevalence between studies is difficult owing to differences in study design, ED definitions, and the methods used to diagnose ED. However, the Massachusetts Male Aging Study2 provides an opportunity to compare the methodological

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Our more granular approach allows a better understanding of how ED, and hence endothelial dysfunction in general, changes in the aging male. Previous analyses hypothesized that ED is a harbinger of CVD, suggesting that ED pathology may be the first manifestation of endothelial dysfunction.9, 13, 25, 26 We were able to find only one study that reported the prevalence of ED among men without concomitant diseases. Nicolosi et al.6 interviewed 2412 men across four countries (Brazil, Italy, Japan, and Malaysia) and reported results comparable to ours (eg, ED prevalence of 7.8% for healthy men aged 40–44 yr).

However, their study had two main limitations. They reported probabilities for age groups comprising 5-yr increments.

Furthermore, in contrast to our use of the validated IIEF-EF instrument, the authors assessed erectile function using the response to a single question (“How would you describe yourself?”) with four possible answers (“always, usually, sometimes or never able to get and keep an erection good enough for sexual intercourse”), which is not validated.

Numerous other studies have shown an association between ED and the comorbidities considered here.13, 14, 15, 16, 17, 18 Nevertheless, our study is the first to estimate the prevalence of ED in the presence of specific comorbidities.

However, we evaluated only some of the risk factors associated with ED, and therefore further studies should assess the degree to which other risk factors such as cigarette smoking,21 metabolic syndrome,19 and obstructive sleep apnea20 are independently associated with ED. The population in our study presents a potential limitation.

We evaluated patients with prostate cancer before they received definitive therapy. Cancer screening, as reported in a recent study,27 is associated with a lower hazard of all-cause mortality after accounting for other risk factors.

The most convincing explanation for this effect is that nonadherence to protocol screening could be a marker for a general behavioral profile involving an unhealthy lifestyle and nonadherence to

medical tests and treatments, and consequently a higher risk of mortality; moreover, patients who have short life expectancy because of other diseases should not be screened nor present for treatment of prostate cancer.28 We previously showed that patients who undergo radical prostatectomy have life expectancy equivalent to that for men from the general population who are 3 yr younger.29 Correcting for this effect would shift the curves in Figure 1 to the left: for instance, a 60-yr-old man with obesity and hypertension (aggregate score 10) would have ED risk of 50% rather than the 44% calculated with the original model. Supplementary Table 6 reports the risk of ED by age according to this correction.

Nevertheless, further studies should confirm our findings in a population of patients without prostate cancer.

Another potential limitation of this study is that we included comorbidities in our model as binary variables (eg, hypertension yes vs no) obtained from the patient’s medical history and not defined using predefined cutoffs. Moreover, patients with uncontrolled comorbidities were not distinguished from those with comorbidities well controlled with specific therapies. Finally, we did not consider the risk factor duration. However, all of these pathologies have different severity levels. It is likely, for example, that the risk of ED is very different between men with severe and mild cases of hypertension, ands between men with controlled and uncontrolled hypertension and patients affected by hypertension for a different length of time.

Similarly, dyslipidemia, which was not associated with ED in our analyses despite being a well-known risk factor,2, 19 would probably emerge as a predictor if lipid status was used as a continuous variable instead of a categorical classification. There is room for future studies to further refine our approach by considering the severity of comorbidities and their treatments.

Conclusions Our results allow a better understanding of how the risk of ED, and endothelial function in general, changes with age and comorbidities. Further research should evaluate the impact of other risk factors not considered in the present study and take risk factor severity into account.

References available on request

Penile Cancer

53

Management of Penile Cancer Penile cancer is a rare male genital cancer which presents in older men in the 6th or 7th decades. However, the disease is not limited to the older population and younger men with risk factors can also develop penile cancer.

Some of the highest reported incidence is in South America and parts of Africa where neonatal circumcision is not commonly practiced. North America and Europe have a low incidence and there are very few cases in countries where religious or ritual neonatal circumcision is practiced.

The incidence of penile cancer in the United Kingdom (UK) is between 1.5 to 2.5 per 100,000 men with between 6-700 cases per annum. Significant regional variation exists with areas of greater socio-economic deprivation suffering the highest incidence. From 2013-2017 in England, incidence rates in males were 52% higher in the most deprived quintile compared with the least.

Risk Factors for Penile Cancer There are several risk factors associated with the development of penile cancer. The accepted risk factors include phimosis (nonretractile foreskin), high risk HPV16 and 18 infection and lichen sclerosus which is a chronic inflammatory disease affecting the foreskin. Additional risk factors include poor genital hygiene, smoking, obesity and exposure to ultraviolet light A (PUVA).

Lichen sclerosus can be manged using topical steroid treatment but failure to respond should be followed by a circumcision. The chronic inflammation can lead to the development of differentiated PeIN which is the non-invasive pre-malignant phase. With HPV associated pre-malignant disease, undifferentiated PeIN can develop before invasive disease and in some cases both differentiated and undifferentiated PeIN may co-exist. The implementation of gender neutral vaccination programmes using the nanovalent HPV vaccine will eventually reduce the incidence of HPV related cancers which also include head and neck cancers, vulval and anal cancer.

Anatomy of the penis The penis compromises a shaft which is formed from 3 cylinders, corpus cavenosum of which there are two and contain the vascular smooth muscle surrounded by the tunica albuginea. The third component is the corpus spongiosum surrounding the urethra. The head of the penis is the glans and this is normally covered by the prepuce which has an inner mucosal layer. The neurovascular bundle runs on the dorsal aspect of the shaft of the penis and is covered by the Bucks fascia.

Penile Cancer Pathology Squamous cell carcinoma accounts for greater than 95% of cases and most commonly affects the glans and/or inner foreskin.

The squamous cell cancer has several subtypes with the sarcomatoid subtype being very aggressive. Rarer pathological subtypes include mucosal melanoma and sarcoma. The treatment of the primary lesion is standard for all the subtypes and is mainly directed by the extent of invasion into the proximal penis. Commonly the tumours are limited to the foreskin or glans penis and these are staged as T1 and T2 tumours. However, more extensive invasion into the corpus cavernosum requires more extensive surgery to ensure clear margins and these are staged as T3.

The lymphatic drainage from the penis is predictable and initially drains to the inguinal lymph nodes bilaterally. The involvement of the inguinal lymph nodes is the most important prognostic indicator for patients with penile cancer.

Management of the primary lesion The management of premalignant disease is primarily by offering a circumcision and adjuvant topical chemotherapy such as 5-FU or immunotherapy such as imiquimod can be used for refractory areas of disease.

Where available CO2 laser can also be effective. In some cases with extensive glans involvement which persists, glans resurfacing can be performed. This is a surgical procedure which excises

Professor Asif Muneer MD FRCS(Urol), Consultant Urological Surgeon and Andrologist - Clinical Lead Urology, NIHR Biomedical Research Centre UCLH Professor of Urology and Surgical Andrology, Department of Surgical Biotechnology, UCL

the glans epithelium and replaces the defect with a split skin graft.

Circumcision can also be used to excise tumours on the foreskin and wide local excision of small volume glans lesions is also an option.

Surgical techniques are aimed to preserve as much penis as possible so that patients can void standing up and have enough length for penetrative intercourse.

Where lesions are invading the glans penis, a glansectomy (removal of the glans cap) with reconstruction of the neoglans using a split skin graft is now a standard of care with low recurrence rates of less than 10%.

If there is invasion into the corpus cavernosum then a partial penectomy is required or for more extensive lesions, a subtotal or total penectomy. For patients who are motivated and have a good performance status, reconstruction of a neophallus using a free flap can be offered following a subtotal or total penectomy.

Management of Inguinal Lymph Nodes As mentioned already the most important prognostic indicator is the presence of metastatic disease in the inguinal lymph nodes. There is a high risk of metastatic disease being present in palpable nodes. In impalpable lymph nodes the risk of micrometastatic disease is upto 25%.

Again minimally invasive options such as dynamic sentinel lymph node biopsy and videoendoscopic inguinal lymphadenectomy are now used to reduce the morbidity associated with inguinal lymphadenectomy which includes wound complications and lower limb lymphoedema.

Systemic Treatment Options The response to systemic treatment remains poor although there is a role for neoadjuvant treatment in more extensive disease prior to surgery.

Immunotherapy is still in the trial phase but represents an alternative option for patients with systemic disease.

Conclusions Penile cancer is a rare malignancy and the prognosis for patients with systemic disease remains poor.

However, those with localised disease to the penis or limited disease in the inguinal nodes have a good prognosis.

About The Urology Foundation The Urology Foundation is the UK's only charity representing all urological diseases including prostate, bladder, kidney and male reproductive cancers and non-malignant conditions including incontinence, urinary tract infections (UTIs), erectile dysfunction and kidney stones.

We are committed to improving outcomes, quality of life and saving lives through investment in ground-breaking research, training in technical skills and innovative technologies and practices, education and awareness.

Working with researchers, urologists, nurses and allied healthcare professionals, influencers and decision makers, patients and their families and those with an interest in urological diseases, we are improving the nation’s urology care. www.theurologyfoundation.org

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Diabetes

54

Unlocking Men's Health: Pharmacists' Vital Role in Managing the Disease of Obesity Written by Dr Harriet Treacy1 and Professor Carel Le Roux1,2 Beyond BMI, Dublin, Ireland

1

Diabetes Complications Research Centre, University College Dublin, Ireland

2

Dr Harriet Treacy

Professor Carel Le Roux

Introduction

The pathophysiology causing T2D

We have seen a significant evolution in the primary treatment goal for type two diabetes (T2D) over the last two decades.

The first big shift came when a primary glucocentric approach, aimed at lowering glucose and HbA1c, evolved to incorporate a complications-centric approach, focused on reducing the downstream macro and microvascular complications such as cardiovascular disease, chronic kidney disease, and retinopathy.

Arguably, the most significant shift, one which takes a more upstream, “root-cause” approach to managing T2D is currently underway. This shift to a “weightcentric” approach acknowledges the underlying pathophysiology of T2D as a disease that is both caused by, and complicated by, dysfunctional and excess fat accumulation, as such, making it an complication of the disease of obesity. For too long, obesity and T2D, have been treated as disparate disease states. Here, we will explore the critical intersection between these two disease states, with a specific focus on men, because men represent half of the population with the disease of obesity, but only 20% of people currently receiving treatment for the disease of obesity. Our aim is to help pharmacists recognize and understand the importance of treating obesity, both as a disease in its own right and as an upstream treatment for T2D, thus empowering pharmacists to play a pivotal role in supporting men living with obesity and T2D.

Obesity causes T2D through recognised pathophysiology, including insulin resistance, chronic inflammation, adipokine dysregulation, ectopic fat deposition, beta-cell dysfunction, hormonal imbalances, and gut microbiota alterations.

Obesity is characterised by chronic low-grade inflammation of adipocytes (fat cells).

Dysfunctional adipocytes secrete proinflammatory cytokines, such as TNF-alpha and interleukin-6 (IL-6), contributing to insulin resistance and directly impairing the function of pancreatic beta cells responsible for producing insulin. Adipocytes, being a metabolically active endocrine organ, also secrete hormones such as leptin (a regulator of adipocyte mass). Despite this, people living with obesity and T2D have pathognomonic symptoms of increased hunger and a lack of satiety.

An Upstream Approach to T2D Taking a weight-centric approach to T2D treatment has a significant impact on disease progression.

Weight loss of at least 15%, has disease modifying effects and often results in remission of T2D which reduces the risk of macro and microvascular complications.

Thus, by treating the disease of obesity, we can not only prevent T2D, but often cause T2D to go into remission.

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The Weight Maintenance Challenge

this stigma and promote effective chronic disease management.

One of the pressing challenges in adopting a weight-centric approach is the difficulty of sustaining weight loss. While diet and exercise play crucial roles in health gain, it's important to acknowledge the complex interplay of genetic, biological and environmental factors that influence an individual's ability to lose weight, and more importantly, maintain that weight loss. Lifestyle treatments are successful in treating the disease of obesity in approximately 20% of patients, but it appears that the motivation of the patient is not a predictor of success but rather success is determined by the biology of the disease of obesity and how the lifestyle treatment alters this pathophysiology. Pharmacological therapies, like GLP-1 or GLP-1/GIP agonists, are becoming a mainstay in the treatment of obesity as they target the subcortical areas of the brain where our appetite is regulated thus targeting the underlying biological drivers of obesity. Overcoming this elusive weight maintenance challenge, requires an evolution in how we approach obesity as a disease. As healthcare professionals, we need to move away from the outdated thinking that obesity is simply a “lifestyle choice” to treating it as a chronic disease best managed under a chronic disease management framework.

Top Tips for Pharmacists to Support Men living with obesity:

A Shared Internalised Stigma People living with type 2 diabetes and obesity often hold the belief that the disease they live with is their fault. It’s not hard to see how this internalised stigma came about given the outdated thinking around obesity as a lifestyle choice. Moreover treatment for the disease was linked in the past with overpromising cosmetic benefits.

Therefore, men might be reluctant to ask health-care professionals for help due to misconceptions that the responsibility for weight loss is entirely their own, that they will be blamed for the disease, and that the benefits are only cosmetic. There are a number of ways pharmacists can support men living with obesity to combat

1. Educate on Obesity as a Disease: Begin by counselling patients on the fact that obesity is not a simple lifestyle choice.

Help them understand that it involves complex physiological factors beyond their control, reducing any potential feelings of self-blame or guilt.

2. Educate About the ObesityT2D Connection: Take the time to explain the causative relationship between obesity and T2D. Use evidence-based information to emphasise that addressing obesity is a crucial aspect of managing their diabetes effectively and visa versa. Move the focus of obesity treatment away from “weight loss” to “health gain”.

3. Multidisciplinary Collaboration: Encourage them to take a holistic approach to the complex disease of obesity.

Collaborate with other healthcare professionals, including dietitians, exercise specialists, and psychologists, to provide comprehensive care.

A multidisciplinary approach can be highly effective in addressing the complex factors contributing to obesity and T2D. 4. Focus on Technical Management: Emphasize the technical aspects of managing obesity and related conditions.

This includes practical guidance on how to use medications effectively, such as insulin pens or anti-obesity medications.

Ensure patients are comfortable with the tools and techniques needed to manage their disease.

5. Promote Independence and Autonomy: Encourage men to take an active role in managing the disease of obesity. Provide opportunities for them to exert independence, autonomy, and ownership over decision-making to improve their engagement and compliance with treatment.

References available on request

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

Call for papers: make your contribution to Hospital Professional News  Articles  Research Papers  Reviews  Programme Descriptions  Reports Case Reports  Letters to Editor  Support fellow hospital professionals as well as aspiring junior professionals and early-year hospital pharmacists  Practice reports share innovations on any area of practice, including delivering clinical services, pharmacy administration, or new approaches to inform and engage with patients  Perspective articles focus on a specific field or discipline and discuss current advances or future directions, and may include original data as well as expert insight and opinions

Contact: Kelly Jo Eastwood at: kelly-jo@ipn.ie or Danielle Norton - danielle@hospitalprofessionalnews.ie

PHARMACYNEWSIRELAND.COM

Mental Health

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Men’s Mental Health 2023: Mindfulness and Mental Health Promotion Written by Professor Brendan Kelly, Brendan Kelly is Professor of Psychiatry at Trinity College Dublin and author of “Resilience: Lessons from Sir William Wilde on Life after Covid” (Eastwood Books, 2023).

Mental illness is common, complex, and costly. The World Health Organization (WHO) points out that one in every eight people in the world live with a mental disorder.1 Anxiety and depressive disorders are recognisably the most common conditions, notwithstanding cultural variations in descriptive terminology across communities, societies, and countries. Overall, mental illness is very common, with almost one billion people affected directly and many others impacted indirectly: family, friends, colleagues, and wider communities.2 Like women, men can be affected by a broad range of mental illnesses including mood disorders, anxiety disorders, schizophrenia, substance misuse, attentiondeficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and various other conditions.3 In 2023, the US National Institute of Mental Health noted that “certain symptoms may be more common in men than women, and the course of illness can be affected by a person’s sex. Researchers are only now beginning to tease apart the various biological and psychosocial factors that may impact mental health. Men are less likely to have received mental health treatment than women in the past year”.4 This article looks at two key themes in this area: mental health promotion for men and the

increasing evidence that supports mindfulness-based interventions for various mental illness and psychological problems, especially depression.

Mental Health Promotion for Men It is often said that “men don’t talk” and this is a reason why men are reluctant to seek help for mental health problems. The situation is, however, significantly more complex than that. Recent research paints a more detailed, useful picture about why men tend not to access care when it is needed, and how this might be addressed.

In 2022, a focus group study in Sydney looked at five groups of men and two groups of stakeholders who had frontline experience working with men (e.g., men’s groups, health clubs, mental health advocates), in order to explore “challenges and opportunities for men’s mental health promotion”.5 Following analysis of the focus groups, these researchers identified a “need to provide better direction for gender-sensitised approaches to community-based mental health promotion for men. Especially evident was the influence of gender roles, relations and identities as well as the importance of framing conversations in ways that resonate with potential end users”.

In other words, mental health promotion strategies for men need to be tailored to men’s emotional

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habits, communication styles, and behaviour patterns. The researchers in Sydney concluded that “strategies are needed that address, or at least consider, men’s restrictive emotionality and emotional awareness, the interiority of mental health, and stigmatisation of mental health promotion and practices.

Highlighted throughout, from both men and stakeholders, was the significance of advancing men’s mental health and wellbeing by anchoring mental health promotion to acceptable locations, contexts and behaviours”.

But how can this be put into practice? Any comments about “men” and “women” are always generalisations, and there will inevitably be many exceptions.

But this kind of research strongly indicates a need to consider common male behaviours when designing mental health interventions. This should be entirely possible owing to increased research into a broad range of treatments for mental illness, many of which can be readily adapted to the needs of specific groups, such as men.

Mindfulness-based approaches are a good example of how this can be achieved.

Mindfulness for Men Despite the fact that “mindfulness” has become a buzzword in psychotherapy and popular culture in many countries, the practice still holds substantial value, especially when it is practiced with trained teachers or in supervised groups. Recent years have seen growing interest in mindfulness and meditation retreats which are focused on men’s mental health and men’s psychological wellbeing, so mindfulness merits particular attention as an increasingly accepted way of maintaining mental health for men.

Mindfulness means paying attention to the present moment, as simply and directly as possible. It involves developing a careful, curious awareness of the sensations, thoughts, and emotions that are present, but trying not to change or judge them. It involves staying focussed

on the present moment as much as possible, and when the mind wanders, gently re-directing it back to direct sensations: the feeling of your feet on the floor, the texture of a book in your hands. Mindfulness is both simple and challenging at the same time.

The idea of mindfulness is rooted in Buddhist and early Hindu psychology and forms a key part of meditative practices in both of these spiritual traditions, among others. Over recent decades, mindfulness has also become part of psychotherapeutic approaches to a range of mental illnesses and psychological symptoms in both women and men. More specifically, there is now convincing evidence that particular courses of mindfulnessbased therapies provided over an eight-week period help to prevent relapse of depression in many people.6 Data to support this approach have accumulated rapidly and steadily in recent years, and merit attention.

In 2021, one “systematic review and network meta-analysis” of “mindfulness-based cognitive therapy [MBCT] for prevention and time to depressive relapse” found 23 relevant publications of which 17 were randomised controlled trials.7 The results clearly supported the effectiveness of MBCT compared to treatment as usual (TAU).

According to the authors, “MBCT is more effective than TAU in the long-term in preventing relapse of depression and has statistically significant advantages over TAU and placebo for time to relapse of depression. No statistically significant differences were observed between MBCT and active treatment strategies for rate of relapse or time to relapse of depression”.

Learning the skills of mindfulness and how to apply them is clearly a powerful way to help prevent relapse of depression for many people, albeit that this practice does not appeal to everyone.

Some people prefer approaches that are based primarily on other forms of psychotherapy or medication, so it is important to

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understand the patient’s views about mindfulness before, during, and after treatment.

problems or mental illness, mindfulness can offer a powerful way to improve general wellbeing.

What Is It About Mindfulness That Helps?

For men, the evidence supporting mindfulness offers a valuable reason to consider this approach to promoting mental wellness and addressing psychological problems.

The benefits can be subtle but profound, provided mindfulness is practiced with diligence, care, and commitment. Mindfulness is not the answer to everything for men, but it often helps.

In 2022, one “systematic review and meta-ethnographic synthesis” of MBCT in major depression sought to “systematically review and synthesize the experiences of participants with depression taking part in MBCT”.8 These researchers identified 21 qualitative studies of fair quality on this theme.

They found that, “across 21 studies of participants with current or previous depression who had participated in MBCT, three overarching themes were developed: ‘Becoming skilled and taking action’, ‘Acceptance’ and ‘Ambivalence and Variability’.”

The researchers also noted that “participants became skilled through engagement in mindfulness practices, reporting increased awareness, perspective and agency over their experiences. Participants developed acceptance towards their experiences, self and others”.

Sources and Further Reading 1. World Health Organization.

Mental Disorders. Geneva: World Health Organization, 2022. (https:// www.who.int/news-room/factsheets/detail/mental-disorders).

2. Kelly BD. Mental Health in Ireland: The Complete Guide for Patients, Families, Health Care Professionals and Everyone Who Wants to Be Well. Dublin: The Liffey Press, 2017.

3. Castle D, Coghill D (editors).

Comprehensive Men’s Mental Health. Cambridge: Cambridge University Press, 2021.

4. National Institute of Mental Health. Men and Mental Health.

Bethesda, MD: National Institute of Mental Health, 2023 (https://www. nimh.nih.gov/health/topics/menand-mental-health).

5. Sharp P, Bottorff JL, Rice S, Oliffe JL, Schulenkorf N, Impellizzeri F, Caperchione CM. ‘People say men don't talk, well that's bullshit’: a focus group study exploring challenges and opportunities for men’s mental health promotion. PLoS One 2022; 17: e0261997 (https://doi. org/10.1371/journal.pone.0261997) (Link to licence: https:// creativecommons.org/licenses/ by/4.0/).

6. Segal Z, Williams M, Teasdale J. Mindfulness-Based Cognitive Therapy for Depression (Second Edition). New York and London: The Guilford Press, 2018.

7. McCartney M, Nevitt S, Lloyd A, Hill R, White R, Duarte R. Mindfulness-based cognitive therapy for prevention and time to depressive relapse: systematic review and network meta-analysis.

Acta Psychiatrica Scandinavica

2021; 143: 6-21 (https://doi. org/10.1111/acps.13242) (Link to licence: https://creativecommons. org/licenses/by/4.0/).

8. Williams K, Hartley S, Langer S, Manandhar-Richardson M, Sinha M, Taylor P. A systematic review and meta-ethnographic synthesis of mindfulness-based cognitive therapy for people with major depression. Clinical Psychology and Psychotherapy 2022; 29: 1494-1514 (https://doi. org/10.1002/cpp.2773) (https:// creativecommons.org/licenses/ by/4.0/).

9. Purser RE. McMindfulness: How Mindfulness Became the New Capitalist Spirituality. London: Repeater Books, 2019.

10. Goldberg SB, Tucker RP, Greene PA, Davidson RJ, Wampold BE, Kearney DJ, Simpson TL. Mindfulness-based interventions for psychiatric disorders: a systematic review and meta-analysis. Clinical Psychology Review 2018; 59: 52-60 (https:// doi.org/10.1016/j.cpr.2017.10.011).

Despite plentiful evidence to support various mindfulness-based interventions in both men and women, mindfulness has become a victim of its own popularity.

Too often, caricatured versions of mindfulness are presented as quick solutions to complex problems, or easy ways to sidestep challenging inter-personal issues that need to be addressed.9 These misrepresentations are disappointing. Mindfulness is a very useful tool but is not the answer to everything. While more research is needed in certain areas, various levels of evidence now support mindfulness-based psychological therapies for some people with mild and moderate depression, anxiety disorders, self-harming behaviour, substance misuse, obsessive-compulsive disorder, and eating disorders.2 These conditions often prove difficult to treat in practice, so any new therapies which are supported by evidence are welcome.

There is also evidence that mindfulness can help to promote holistic health in chronic medical illness, deepen psychological care during cancer treatment, and assist in terminal care settings, with particular evidence of benefit in depression, pain conditions, smoking, and addictive disorders.10 Finally, for some people without psychological

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Androgen Deprivation Therapy Use Mapping European Association of Urology Guideline Practice Across Europe: An Audit of Androgen Deprivation Therapy Use Before Prostate Cancer Surgery in 6598 Cases in 187 Hospitals Across 31 European Countries Written by Steven MacLennana, Nuno Azevedob, Eilidh Duncanc, Jennifer Dunsmorea, Louise Fullwoodd, Nicolaas Lumene, Karin Plassf, Maria J. Ribalf g, Monique J. Roobolh, Daan Nieboerh, Natasha Schoutenf, Ted A. Skolarusi j, Emma Jane Smithf, James N'Dowa, Nicolas Mottetf k, Alberto Brigantil on behalf of the Pan-European National Urological Society IMAGINE Collaborative a

Academic Urology Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK Department of Urology, Entre o Douro e Vouga Medical Center, Santa Maria da Feira, Portugal

b c

Health Services Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK Pinsent Masons, Leeds, UK

d e

Dept. of Urology, Ghent University Hospital, Ghent, Belgium

European Association of Urology Guidelines Office, Arnhem, The Netherlands

f

g

Uro-Oncology Unit, Hospital Clinic University of Barcelona, Barcelona, Spain

Department of Urology, Erasmus University Cancer Institute, Erasmus Medical Centre, Rotterdam, The Netherlands

h i

Department of Urology, Dow Division of Health Services Research, University of Michigan, Ann Arbor, MI, USA

Veterans Affairs Health Services Research & Development, Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA j

Urology Department, University Hospital, University Jean Monnet, Saint-Etienne, France

k l

Department of Urology, University Vita e Salute-San Raffaele, Milan, Italy

Numerous examples highlight that adherence to urology clinical practice guidelines (CPGs) is suboptimal.1, 2, 3, 4, 5, 6, 7, 8, 9 It is known that such evidence-practice gaps hamper high-quality health care provision.10, 11 Fortunately, there is a body of empirical and theoretical work dedicated to understanding behaviours such nonadherence to CPGs and how to facilitate guideline-adherent behaviour.12, 13, 14 To prioritise which implementation problems in the European urological setting should be investigated further, the Impact Assessment of Guidelines Implementation and Education (IMAGINE) group reviewed the European Association of Urology (EAU) guidelines for strong recommendations with level 1a evidence to identify recommendations with little scope for nonadherence, while acknowledging that there may very occasionally be justifiable clinical or patient preference reasons for nonadherence. We then surveyed EAU guideline panels to nominate recommendations for which there was known/ suspected heterogeneity in

practice and for which addressing this heterogeneity would have significant a benefit in terms of patient outcomes and experience or the economic burden. Using this prioritisation method, we chose an oncology recommendation to investigate further: Do not offer neoadjuvant androgen deprivation therapy (ADT) before surgery for patients with prostate cancer (PCa).15 Evidence demonstrates that ADT before radical prostatectomy (RP) for PCa has no benefits in terms of strong clinical endpoints16 but has significant side effects (eg, hormonal changes, cardiovascular disease, diabetes, osteoporosis), as well as hidden and real costs associated with administration and management of these side effects.

Therefore, neoadjuvant ADT meets the Choosing Wisely campaign definition of “low-value care” (care with little or no benefit, and potential harm and cost).17

study showed that guidelinediscordant ADT use ranged from 20% to 60% across the country.4 US studies have also demonstrated that ADT is used in patients who are unlikely to benefit and may experience harm.18, 19 For example, one US study estimated that 20% of prostatectomy patients inappropriately received neoadjuvant ADT20 and another noted that approximately one in eight men received ADT discordant with guidance, with an estimated economic impact of low-value ADT of approximately $42 000 000 per year in the US setting.21 What is clear from these estimates is that ADT overuse has been variable and is problematic for patients and health care systems internationally.

However, a clear contemporary picture of ADT use across Europe is not readily available. To address this, we aimed to survey European urology departments to assess current ADT use patterns.

Both European and American guidelines recommend against neoadjuvant ADT before surgery, yet this practice appears to remain. For instance, an Italian

The objective of the study was to describe adherence to the EAU guidelines on ADT use before surgery for prostate cancer in European countries.

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Patients and methods Design, setting, and participants This was an observational cross-sectional study using a retrospective audit of recent ADT practices in a multicentre international setting across 31 European countries.

We used nonprobability purposive sampling deployed via collaborating centres in the IMAGINE network, which represents national societies in EU member states plus Norway, Russia, Serbia, Switzerland, Turkey, the UK, and Ukraine. We asked collaborating centres to audit 20 or 40 eligible patients (depending on whether the centre had a high or low case volume, as defined below) and eight or 16 sites according to population size in that country (countries with a population >35 million were asked to contribute 16 sites). First, we asked about differences between EAU and national guidelines and for a description of the differences. We also asked how ADT is reimbursed in the country.

The data collection period was from March 1, 2020 to October

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31, 2021. The retrospective audit included patients treated from January 1, 2017 to May 1, 2020.

The recommendation to refrain from administering neoadjuvant ADT is from the EAU guideline on prostate cancer and remained the same during the study period. It has been endorsed by the EAU, the European Society for Radiotherapy and Oncology (ESTRO), and the International Society of Geriatric Oncology (SIOG) since 2016. The European Society of Urogenital Radiology (ESUR) added endorsement in 2017 and the European Association of Nuclear Medicine (EANM) added endorsement in 2019. For brevity and because of widespread use and understanding of the term, we refer to these iterations as the EAU guideline throughout the manuscript.

Sampling We anticipated that practice patterns may differ between high- and low-volume centres, academic and community hospitals, and public and private hospitals, so we sought to purposively sample for a range of hospitals. There is no agreed definition of high and low case volume in the literature22, 23, 24, 25 so our definition was based on consensus agreed by our clinical expert steering group (all co-authors of the paper). We used a pragmatic cutoff of >50 prostatectomy cases per year as a practical proxy for high-volume centres and <50 for low-volume centres. We asked the national society representatives in each country to fulfil the sampling criteria within their country.

A bespoke online data collection platform was created. The local user at each site had a unique user identity and password. Users were able to log and see their own data only and did not have access to data from other sites. No identifiable personal participant or patient information was collected, the hospitals reviewed data for their own patients, and no personal data were transferred to or processed by IMAGINE, so the study fell outside the General Data Protection Regulation requirements. Therefore, this audit was classified as a service evaluation and did not require review of sponsorship and ethics.

The data were encrypted and stored on secure ISO27001compliant servers located in Europe. To retain anonymity, we used numerical codes for each country in the results.

We used the two following inclusion criteria for the audit:

Fig. 1. Distribution of the adherence rate across centres (1) patients with histologically proven adenocarcinoma of the prostate and (2) patients undergoing RP with curative intent.

We excluded RP in patients with metastatic disease (any T any N M1) and salvage RP for recurrent PCa after radiotherapy or another active therapeutic option besides radiotherapy (eg, cryotherapy, high-intensity focused ultrasound).

We used a random date generator inbuilt in the audit software to mitigate against selection biases.

This generated random dates at each site (excluding weekends and national holidays). Participants were asked to select the first eligible patient undergoing RP on the date suggested by the random date generator. If no eligible patients underwent RP on that day, excluding salvage RPs, participants chose the next date on which an eligible patient underwent RP. 2.3. Outcome measures and statistical analysis Our primary outcome was the proportion of patients treated with guideline-adherent or -nonadherent practice.

Specifically, adherence to the guideline recommendation was defined as no ADT prescription.

Adherence rates were described by country, and differences in the adherence rate within countries were compared across three factors (academic vs community hospital; public vs private hospital; low-volume vs high-volume centre) using χ2 tests.

Patients who received ADT because they had originally opted for external beam radiotherapy (EBRT) but subsequently changed their mind and opted for surgery are retained in the analysis and considered to have been treated in nonadherence to the guideline because in practice they received ADT before surgery.

This is addressed further in the discussion section.

A global test was performed to analyse whether there were differences in adherence rate between the different hospital types by fitting a multilevel model with nesting of hospitals in countries using nested random effects. Type of hospital, funding, and case volume were included as covariates.

A priori subgroup analyses focussed on localised PCa (categorised as low, intermediate,

or high risk) and locally advanced cancer. The following definitions were used: low risk, prostatespecific antigen (PSA) <10 ng/ ml and Gleason <7 (International Society of Urological Pathology [ISUP] grade group 1) and stage cT1–2a; intermediate risk, PSA 10– 20 ng/ml or Gleason 7 (ISUP grade group 2/3) or stage cT2b; high risk, PSA >20 ng/ml or Gleason >7 (ISUP grade group 4/5) or stage cT2c; and locally advanced PCa, any PSA, any GS (any ISUP grade group), and stage cT3–4 or cN+.

Results Our audit included 6598 patients from 187 hospitals in 31 countries. Most centres included were public hospitals (166/187, 89%) and most had a high case volume (148/187, 79%; Supplementary Table 1). All participating sites used either the EAU guidelines concerning ADT before surgery or had national guidelines that did not differ from the EAU on this recommendation (Supplementary Table 1).

Approximately two-thirds (21/31) of the participating countries fully reimburse ADT via their public health system either without conditions or on application by the urologist/oncologist and approval by an external physician.

In the remaining countries there is partial reimbursement by

the public health care system (Supplementary Table 1).

Adherence to the guideline was very high, with 98% of patients (6466/6598) treated in accordance with the guideline. In total, 68% of the centres had a guideline adherence rate of 100%. The median adherence rate was 100%, with a 25th percentile of 98% and a minimum of 69% (Fig. 1).

Adherence in different hospital types across all countries The differences in adherence rate across different subgroups among all countries in a multivariable model are shown in Table 1. The odds of adhering to the guideline was 1.42 times higher for public than for private hospitals, although this difference is statistically nonsignificant and the 95% confidence interval (CI) indicates imprecision and uncertainty, ranging from roughly halving the odds to quadrupling them (95% CI 0.48–4.17). Likewise, the odds of adhering to the guideline was higher in the community than in the academic setting, but the estimate is imprecise and not statistically significant (adds ratio [OR] 1.41, 95% CI 0.62–3.20). The odds of adhering to the guideline was lower for low-volume than for highvolume hospitals, but this finding is not statistically significant, and the estimate is imprecise (OR 0.56, 95% CI 0.22–1.43).

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Table 1. Odds ratios for nonadherence to the recommendation to not give androgen deprivation therapy before surgery for prostate cancer by funding, setting, and volume across all countries included in the study

Characteristic

Odds ratio (95% CI)

p value

Funding (public vs private)

1.42 (0.48–4.17)

0.5

Setting (community vs academic)

1.41 (0.62–3.20)

0.4

Case volume (low vs high)

0.56 (0.22–1.43)

0.2

CI = confidence interval.

Adherence in different hospital settings within countries There were no statistically significant differences in adherence between high-volume and low-volume hospitals (Fig. 2A) or between public and private hospitals (Fig. 2B). There was a statistically significant difference in adherence rate between academic and community hospitals in country 60 (81% vs 98%; Fig. 2C).

Low-risk PCa Across the 31 countries, 1057 patients had low-risk PCa, of whom 99.5% (n = 1053) were treated in adherence to the EAU ADT guideline. In total, 98% of the centres had an adherence rate of 100% for the low-risk subgroup; the lowest adherence rate was 50% (Fig. 3, Fig. 4). There were no statistically significant differences in adherence rate across the different categories (volume, funding, and setting) for the lowrisk group.

Fig. 2. Proportion adherent to the guideline for (A) high- and low-volume centres, (B) private and public hospitals, and (C) academic and community centres in each country

Fig. 3. Distribution of the proportion patients treated in adherence to the guideline, stratified by risk group.

PCa = prostate cancer

Types of ADT given and reasons for nonadherence Intermediate-risk PCa There were 3011 patients with intermediate-risk PCa across the 31 countries, of whom 99% (n = 2982) were treated in adherence to the guideline. In total, 88% of the centres had an adherence rate of 100% for the intermediate-risk group; the lowest adherence rate was 60% (Fig. 3, Fig. 4; note that 1 centre with a rate of 0% had no patients with intermediate-risk PCa).

High-risk PCa There were 1706 patients with high-risk PCa across the 31 countries, of whom 97% (1661) were treated in adherence to the guideline. In total, 83% of the centres had an adherence rate of 100% for the high-risk subgroup; the lowest adherence rate was 57%. There were statistically significant differences in country 60 (Fig. 3, Fig. 4).

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Locally advanced PCa In total there were 772 patients with locally advanced PCa, of whom 718 (93%) were treated in adherence to the guideline. In total, 80% of the centres had an adherence rate of 100% for the

subgroup with locally advanced PCa; the lowest adherence was 0% (Fig. 3, Fig. 4).

Among the 132 patients receiving ADT, 53 (40%) had an antiandrogen, 58 (44%) had a luteinising hormone–releasing

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Fig. 4. Proportion of patients treated in adherence to the guideline in each country, stratified by risk group. PCa = prostate cancer hormone (LHRH) agonist, nine (7%) had an LHRH antagonist, ten (8%) had combined LHRH and antiandrogen treatment, and one (0.75%) had surgical castration.

Of the 132 nonadherence instances, no reason was given for 68 (52%), a reason was given for 64 (48%), and more than one reason was given for some cases. The reasons are outlined in Figure 5.

Frequently reported reasons for nonadherence included clinical decisions to try to improve oncological outcomes or parameters such as tumour volume, prostate volume, or the risk of positive margins. There were some instances of a decision change whereby the health care provider had initially planned EBRT but the patient then opted for surgery after neoadjuvant ADT had commenced. In some instances the patient felt that the side effects were intolerable after experiencing or becoming more fully informed about ADT side effects. Other reasons for ADT before surgery

included an attempt to control the cancer because of long waiting lists, and ADT initiation by a previous provider.

Discussion This study mapped adherence to EAU guidelines in 6598 patients from 187 hospitals across 31 countries. A network of national societies willing to contribute to guideline audits in association with the EAU was established.

Nonadherence to ADT guidance was variable across sites. Although differences across risk groups were minimal, adherence appeared

to be more variable in the high-risk group (ranging from 0% to 43%) but no prespecified or post hoc statistical tests were performed to investigate this issue. No statistically significant differences were found across centre types, Fig. 5. Frequency of reasons reported for giving ADT before surgery. BRFS = biochemical recurrence-free survival; CSS = cancer-specific survival; OS = overall survival; ERBT = external beam radiotherapy; RP = radical prostatectomy; ADT = androgen deprivation therapy

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and any results derived from the multivariable models should be interpreted with caution because the CIs are imprecise. However, given the strong rating and level 1a evidence for the recommendation to avoid ADT before PCa surgery, our clinically meaningful threshold for nonadherence should be very low. Our results should prompt discussion on what such a threshold should be in settings involving high certainty and a strong recommendation.

Reasons for providing ADT before surgery, such as attempting to reduce the tumour volume before surgery or the risk of positive margins, are somewhat supported by the evidence base but do not translate into better oncological outcomes, and therefore do not warrant nonadherent practice because this may lead to harmful side effects with associated management costs. However, this reasoning does give insight into the belief of some urologists regarding the consequences of ADT use.

ADT causes metabolic changes associated with higher risk of cardiovascular disease, stroke, diabetes, and bone fractures:26, 27, 28, 29 changes in psychological function impacting sexual function and relationships, as well as emotional lability, impaired cognition, and depression;30 and fatigue, which is also associated with anxiety and depression.31 ADT is also associated with an increase in the risk of Alzheimer’s disease.32 There are additional oncological disadvantages of ADT including false-negative lymph nodes and surgical margins, and postoperative PSA is usually undetectable, so detecting recurrence is impossible for a considerable period.

Additional cost consequences of ADT use, whether appropriate or inappropriate, include medical management;26, 33, 34 dietary changes and exercise programmes35, 36, 37 are also not free of cost. The clinical relevance is that in instances

of inappropriate ADT use, the consequences for the patient are serious and the implications for the health care provider represent an additional workload; for the payer, the additional treatments and other supervised exercise/ dietary interventions have associated costs. Although their results may not be externally valid outside of Canada, the finding by Krahn et al.38 that management of ADT-associated adverse events increases costs by 100–265% is sobering.

Use of ADT as an interim measure to control PCa because of long waiting lists was one reason for inappropriate ADT use and could just about be justified during disruptive events such as pandemics. However, the recruitment period for our project means that we cannot investigate whether this happened during the COVID-19 pandemic.

A possible explanation for the finding that guideline adherence is high in most countries is that we are seeing the “tail end” of ADT deimplementation. That is, ADT overuse, at least before surgery, was a problem in the past but is now waning. This suggestion is bolstered by reports of higher levels of problematic ADT use from some within-country studies dating from 2002 to 2015, with inappropriate use ranging from 20% to 60%.4, 18, 19, 20, 21 A “tail end” characteristic of ADT deimplementation was proposed

by Skolarus and colleagues39 in the US setting, albeit in the context of ADT monotherapy for localised prostate PCa. They found that ADT overuse in that setting has decreased over time, but that some overuse remains; they used qualitative methods to explore patient- and urologist-level barriers and facilitators to stopping such low-value ADT use.40 They structure their investigation using the theoretical domains framework (a synthesis of >30 theories of behaviour and behaviour change organised in 14 domains)41 and the capability, opportunity, and

motivation-behaviour model of the Behaviour Change Wheel.42 They found that urologists sometimes find it difficult to advise against ADT when a patient and their relatives request it (something we also found in our study), coupled with the fear that they may lose patients to other providers if they did not agree. A small number of urologists, but still worrying in its implication, prefer to rely on their own experience rather than guidelines and believe that ADT is a reasonable approach.

Other facilitators were related to opportunities to avoid prescribing ADT, such as collaborative decision-making and comparison of one’s own practice to others in multidisciplinary team meetings (eg, tumour boards). In institutions where such resources are not available, opportunities for appropriate ADT prescription are potentially missed.40

to ensure that consent to nonadherent ADT is fully informed, and a top-down approach via formulary restrictions at the organisation level. The latter two suggestions are being researched further in an implementation randomised controlled trial

by Skolarus and colleagues.39 Results from that study will have important relevance for ADT overuse elsewhere and for deimplementation research more generally. Further research to understand patient and provider barriers and facilitators to ADT overuse in the European setting is required.

One of the reasons for ADT before surgery in our audit was that EBRT was initially planned but the patient then opted for surgery. Although we accept that these instances could have been removed from the data set, we felt that it was important, especially for the patient perspective, to retain these cases because in practice such patients still received ADT before surgery and may experience ADT-related adverse events. More research is required to understand this circumstance, but if patient-provider dialogue and decision-making is sufficient, then patients should fully understand the implications of ADT alongside weighing up the side-effect profiles of surgery and radiotherapy and be less likely to change their minds.

Finally, while it was not the focus of our study, we recognise that many patients with low-risk disease had radical surgery, which is also discordant with current guideline recommendations; this may be considered for further investigation in a future study. The fact some of those patients with low-risk PCa had both surgery and ADT is worrying.

Going forward, ADT deimplementation could be addressed via interventions such as education on guidelines and training on evidence-based medicine. Other more tailored interventions could be directed at fostering high-quality decision-making, such as the development of decisions aids with patients and their families

In brief, any inappropriate ADT use is worrying, is costly for health care systems, and leads to avoidable adverse events for patients.

Strategies towards discontinuing inappropriate ADT use should still be pursued.

Conclusions Adherence to EAU recommendations for ADT before RP appears to be generally followed for patients with low or intermediate risk. The picture for patients with high-risk PCa is more variable. Although some reasons may appear justifiable, the absolute number of men at risk of harm is worryingly high and the economic impact is alarming. A deeper understanding of the circumstances under which urologists are willing to practice against guidelines warrants further research and may inform strategies to facilitate the discontinuation of inappropriate ADT. References available on request

Irish Endocrine Society Conference Please save the date for the 47th Annual Meeting of the Irish Endocrine Society scheduled for 24th/ 25th November in Rosses Point, Sligo.

The lead organiser for the 47th Annual Meeting is Dr Siobhan Bacon with the assistance of the Committee.

Please save the date for the 28th Annual Study Day scheduled for the Royal College of Physicians, 6 Kildare Street, Dublin 2 for Friday 26th January 2024.

Visit www.irishendocrinesociety.com for further details, including registration and the programme.

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IBD 63

New endoscopic tools in Inflammatory Bowel Disease Written by Olga Maria Nardone1,2, Rosanna Cannatelli2,3, Subrata Ghosh4, Marietta Iacucci1,5 1

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

2

Department of Public Health, University Federico II of Naples, Naples, Italy

Gastroenterology Unit, ASST Fatebenefratelli-Sacco, Department of Biomedical and Clinical Sciences, ‘Luigi Sacco’ University Hospital, Milan, Italy 3

4

APC Microbiome Ireland Centre, College of Medicine and Health, University College Cork, Cork

NIHR Birmingham Biomedical Research Centre, University Hospitals NHS Foundation Trust, University of Birmingham, Birmingham 5

In the last decade, short- and long-term treatment targets in inflammatory bowel diseases (IBD) evolved, shifting towards objective measures of disease activity.1, 2 Hence, the role of endoscopy is becoming more and more relevant.

In this context, new advanced endoscopic techniques are now available and can provide a more comprehensive endoscopic and histological assessment. Virtual electronic chromoendoscopy (VCE), endocytoscope, and confocal laser endomicroscopy (CLE) converge towards a deeper ultra-structural characterisation of the mucosa, reducing the gap with histology, which is increasingly considered a measure of remission depth and favourable outcome.2, 3 We provide an overview of the evolution of endoscopic armamentarium to assess the grade of inflammation, healing and detect/characterise dysplasia in IBD with an additional focus on how the implementation of Artificial Intelligence (AI) might revolutionise clinical management of IBD toward personalised medicine no longer considered hype but reality.

Through the Eyes of Virtual Electronic Chromoendoscopy VCE is widely available in most endoscopic units and enhances the mucosal and vascular intestinal architecture. Mainly, this helps differentiate between patchy and mild inflammation versus endoscopic remission, a key therapeutic goal in IBD patients.

Whilst narrow-band imaging (NBI, Olympus Japan) uses optical filters for a narrow band of blue and green light; optical enhancement iSCAN (iSCAN-OE, Pentax, Japan), flexible imaging colour enhancement and LASEREO system (FICE, Fujinon), which

included the linked-colour imaging (LCI), and blue-laser imaging (BLI) use a post-processing digital software algorithm to recreate virtual images.4 Recently, new software was released from Olympus, the EVIS X1, with two new modes to define better Texture and Colour Enhancement Imaging (TXI) which improves the structure and brightness of the endoscopic images and Red Dichromatic Imaging (RDI) with the purpose to enhance the blood vessels and bleeding.5 Currently, the application of VCE in IBD ranges from the assessment of the inflammation to the detection, characterisation and therapeutic management of colonic lesions during surveillance colonoscopies.

Endoscopic assessment of endo-histologic remission Several new scores have been developed by using VCE platforms.

Paddington International Virtual Chromoendoscopy Score (PICaSSO)6, 7 graded mucosal (including elongated crypts, scars, micro erosions, ulcers) and vascular changes (such as sparse vessels, a vessel with dilation or crowded and bleeding) and ranged from 0 to 15 (Figure 1). In a large multicentre international study, endoscopic remission was defined by a value equal to or less than 3, and PICaSSO showed a strong correlation with five histological scores, namely Robarts Histological Index (RHI), Nancy Histological Index (NHI), Villanacci Simple Score, Geboes Score and Extent, Chronicity, Activity and Plus Score (ECAP) with Pearson’s correlation between 0.77 and 0.79.

Furthermore, it has also shown very good interobserver variability with K agreement of 0.88 and PICaSSO <3 predicted good longterm outcomes at 6 and 12 months

with a hazard ratio (HR) of 0.19 and 0.22, respectively.8 It was initially developed and validated on the i-scan platform, then reproduced on the other endoscopic platforms currently available showing an intraclass correlation coefficient of 0.825. Moreover, the correlation between PICaSSO assessed by NBI and BLI/LCI showed a good correlation with RHI (0.83 and 0.63, respectively) and with NHI (0.79 and 0.65, respectively).9 Notably, it has been demonstrated that endoscopic remission measured with VCE PICaSSO reflected composite endoscopic-histologic remission, increasingly explored as an ultimate endpoint in Ulcerative Colitis (UC) for predicting specified clinical outcomes at 12 months.10 Regarding other platforms, NBI combined with magnification distinguished a three-categories score. BV-H (honeycomb-like blood vessels) and BV-BB (blood vessels shaped like bare branches) were associated with endoscopic healing, whilst BV-V (blood vessels shaped like vines) was linked to histological activity.11 Moreover, mucosal vascular pattern (MPV) graded by NBI as obscure expressed more acute cell infiltration and depletion of globet cell compared to clear MPV (26% vs. 0% and 32% vs. 5%, respectively).12 Similarly, LCI was used to develop three categories of scores such as LCI-A (no redness), LCI-B (redness with visible vessels) and LCI-C (redness without visible vessels), which showed a strong correlation with the histopathology Matts score.13 A recent meta-analysis compared the correlations between endoscopy and histologic disease activity scores across several endoscope technologies and

found no significant difference among them. However, VCE was more accurate in predicting histological remission than White Light Endoscopy (WLE).14 As a more recent VCE, the new Dual Red Imaging (DRI) is a new tool that uses the wavelengths 600 and 630 nm and strongly correlates with Mayo Endoscopic Score (MES). DRI maintained remission at 2 years of follow-up.15 To date, PICaSSO is the only validated and reproduced score that all endoscopic platforms can use.

Regarding CD, the current approach for scoring endoscopic activity is the Simple Endoscopic Score (SES-CD),16 despite several limitations. Therefore, recently, a new scoring tool named the modified multiplier of the SES-CD (MM-SES-CD) has been developed, including the evolution of treatment endpoints into the definition of endoscopic remission.17 This can predict the achievement of endoscopic remission while on active therapy by considering each parameter’s prognostic value. Hence, it is more accurate than the original SES-CD scoring approach for predicting endoscopic remission (comparison of area under the curves on the testing cohort for MM-SES-CD vs. original SES-CD p = 0.0052).

These implicate that this score can identify patients with a low baseline probability for endoscopic remission with standard therapies in whom treat-to-target monitoring with biomarkers, therapeutic drug concentrations and repeated endoscopy may be most beneficial.

Surveillance colonoscopy a) for detection of colonic lesions The most recent European Society

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64 IBD Figure 1: Paddington International Virtual Chromoendoscopy Score (PICaSSO) and some examples with iscan

Moreover, the Japan NBI Expert Team (JNET) classification is based on vessels and surface patterns and ranges from types 1, 2A, 2B to 3, showing prediction of dysplasia and submucosal invasion.31 It has been used in IBD patients in a small study on 19 UC patients with UC-associated neoplasms, and the JNET type 2A had a low positive predictive value (PPV, 50.0%) and a high negative predictive value (NPV; 94.7%).

However, the inter-observer and intra-observer agreements among experts were fair (0.401 and 0.387, respectively).32 Furthermore, the Kudo classification assessed by FICE on 205 colonic lesions predicted histology with 91% sensitivity and 76% specificity.33 of Gastrointestinal Endoscopy guidelines18 suggested performing surveillance colonoscopy with Dye Chromoendoscopy (DCE) or VCE after appropriate training.

0.62) and not inferior to DCE (RR 0.72).22 A possible explanation of this can be related to the fact that more lesions can be found once dysplasia is detected in a patient.

A multicentre study on 188 patients showed no differences between VCE (iscan) and HDWLE in detecting dysplasia during surveillance colonoscopies (14.9% vs. 24.2%, respectively, p = 0.14) with a similar withdrawal time.19 Similarly, another prospective randomised study conducted on 129 IBD patients showed no difference between DCE and VCE (iscan), with detection of 17.9% versus 11.3% (p = 0.2). However, in this case, the withdrawal time was significantly higher in the DCE group (p < 0.001) compared to the VCE group.20 A randomised controlled trial (RCT) on 48 patients who underwent both VCE and DCE confirmed these data and included patients’ preferences for VCE.21 More recently, a metaanalysis on 11 RCT (1328 patients) showed no difference between VCE, DCE and HD-WLE in the per-patient analysis; however, in the per-dysplasia analysis, VCE was inferior to HD-WLE (RR

However, there is still an ongoing debate about the best technique for surveillance colonoscopy.

Previous studies showed that DCE did not increase dysplasia detection compared with WLE with targeted and random biopsies.23, 24 In recent times, high definition (HD) endoscopy and VCE have become widely available, and hence DCE, WLE, NBI, and VCE with targeted biopsy sampling are all considered acceptable modalities for surveillance when using HD colonoscope.25 b) Characterisation of the colonic lesion Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendation consensus has introduced the modified Paris classification, taking into account the morphology (polypoid or nonpolypoid), borders and ulcerations to characterise colonic lesions

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associated with IBD.26 However, the surface was not considered.

However, The Kudo pit pattern, assessed by DCE or VCE, strongly correlated with histology in predicting dysplasia (73% vs.

71% respectively).27, 28 The Frankfurt Advanced Chromoendoscopic IBD LEsions (FACILE) classification developed with DCE and VCE, considered as the morphology of nonpolypoid lesion (OR 3.13), irregular vessel architecture (OR 3.49), signs of inflammation within the lesion (OR 2.42) and irregular surface pattern (OR 8.89) as predictors of dysplasia.29 Recently, European Crohn’s and Colitis organization (ECCO) topical review on the endoscopic report introduced the new ‘5S’ features, which include Site, Size (using biopsy forceps as reference standard), Shape (polypoid, non-polypoid, or lateral spreading tumour, distinct or indistinct borders, presence of ulcers), Surface (Kudo pit pattern or FACILE classification) and Surrounding (mucosal activity, colitis area/ non-colitis area, or other lesions in surrounding area).30

VCE is widely available and can be easily used by pushing ‘in realtime’ the button on the handpiece of the scope. The newly VCE validated PICaSSO score can assess inflammation accurately and has made endoscopy closer to histology. In addition, VCE can be adopted as a surveillance colonoscopy technique after adequate training for detection and characterisation of dysplasia associated with IBD, enhancing the morphology, borders, and surface of the lesion and guiding therapy with organ sparing.

Confocal Laser Endomiscroscopy CLE is a highly innovative endoscopic technique as it provides new insight into several gastrointestinal diseases. It was introduced in 2006 to provide ‘in vivo histology’ with very high magnification, and resolution of the images of the mucosal layer based on a cellular and subcellular level after applying a systemic fluorescent agent (i.e., fluorescein sodium) injected intravenously before imaging. This system is based on a probe down the accessory channel of an endoscope.

65

Figure 2: pCLE images of (a) crypts architecture; (b) cell sheddings and plumes of fluorescein; (c) tortuosity of the vessels; (d) leakage of fluorescein. pCLE, probe confocal laser endomicroscopy

Mauna Kea Technologies, Paris, France (Figure 2). In IBD, CLE was used for structural and functional assessment of the intestinal epithelium, characterisation and classification of inflammatory activity and mucosal healing (MH) in active disease, dysplasia detection and molecular imaging for precision medicine.3, 34, 35 The assessment of MH in IBD was a further application of CLE since it could accurately distinguish between patch/mild inflammation and MH. Hundorfean36 developed a MH score by using endomicroscopic scoring system (eMHs). This showed high sensitivity, specificity, and accuracy values (100% with 95% confidence interval [CI] of 15.81%–100%; 93.75% with 95% CI of 69.77%–99.84%, and 94.44%, respectively) and a good correlation with the histological Gupta score (rs = 0.82, P < 0.0001) and the endoscopic Mayo subscore (MES) (rs = 0.81%, P < 0.0001).

The ability of CLE to predict disease relapse and clinical outcome was first assessed by Kiesslich et al.37 They observed local epithelial barrier defects with increased cell shedding with fluorescein leakage in IBD patients with subsequent relapse 12 months, indicating that CLE can relapse or define a stable disease when the barrier function is intact.

Karstensen et al.38 evaluated confocal features in response to various treatment regimens (anti-tumor necrosis factor (TNF), thiopurines, steroids, etc.) in patients with UC using the probe-based CLE system and correlated colonic CLE appearances with histopathology and macroscopic appearance before and after the intensification of the therapy 6–8 weeks later. Fluorescein leakage, microerosions, tortuosity of the crypts, distortion of the crypt openings, inflammatory infiltrates and decreased crypt density were frequently present in active UC as opposed to inactive UC and controls. Interestingly, a decline in histopathology score after medical treatment escalation correlated with diminished crypt tortuosity, distortion of crypt openings, and decreased crypt density.

Buda et al.39 composed an outcome score by probe confocal laser endomicroscopy (pCLE), combining fluorescence and crypt diameter (p < 0.01), able to predict disease flare during a 12-month follow-up period in patients affected by long-standing UC. Pericrypt fluorescence >3100 pixels and a crypt diameter >90 μm increased the probability of disease relapse significantly.

scopes used by well-trained IBD endoscopists are equal to pCLE in assessing the disease. However, future studies are required.

Confocal laser endomicroscopy and molecular imaging The additional application of molecular endoscopy in IBD allows topical application of labelled probes, mainly antibodies, against specific target structures expressed in the tissue to predict response or failure to biological therapies. This leads to individualised and personalised IBD therapy.

The first molecular target of interest in IBD was TNF. A phase II clinical trial investigated the impact of membrane-bound TNF (mTNF) binding by a fluorescent-labelled adalimumab anti-TNF antibody visualised by CLE ‘in vivo’ endoscopy on clinical outcome.

Patients with a higher number of cells mTNF positive have a higher probability of clinical relapse compared to patients with lower cells mTNF positive.42 Similarly, Rath et al. analysed the ex vivo topical administration of fluorescein-labelled antiadhesion molecule antibody fluorescein isothiocyanate (FITC) labelled α4β7 (vedolizumab) in CD patients.43

Regarding CD, Tontini et al. demonstrated that CD endomicroscopy findings were predictors of the need for therapy escalation and progression of disease with transmural damage and complication such as strictures or perianal diseases within 1 year of follow-up.40

Patients with positive α4β7– expressing mucosa cells before vedolizumab induction were considered responders to new vedolizumab therapy as opposed to non-responders’ patients in whom no positive α4β7– expressing cells were observed during prior ex vivo examination.

However, in a recent study,41 pCLE did not add significant advantages in respect of VCE, giving rise to the idea that the new HD-VCE

Preliminary data presented at ECCO 2021 have investigated the predictors of response to biologics in 29 IBD patients using

computerised image analysis of pCLE in vivo and the binding of fluorescent-labelled biologics ex vivo. Vessel tortuosity was the only parameter that was significantly altered (reduced) after treatment (p < 0.05) in all patients.

Additionally, in UC, treatment significantly reduced fluorescein leakage through the colonic mucosa (p < 0.05), whereas, in CD patients, it reduced crypt area, eccentricity, and inter-crypt distance (p < 0.05).

Targeted biopsies were further taken for FITC-labelled infliximab and anti-integrin-α4β7. The endoscopic procedure was repeated at weeks 12–14 to assess therapeutic response. Ex vivo, higher mucosal binding to the biological agent pre-treatment was associated with a higher likelihood of response to the treatment.

Interestingly, the magnitude of this prediction of response was greater in UC (area under the ROC curve (AUROC) 83%, accuracy 77%, PPV 89%, NPV 50%) compared to CD (AUROC 58%, accuracy 64%, PPV 40%, NPV 78%). Noteworthy genes predictive of response were identified. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13 and MAPKAPK2 involved in pathways such as inflammation, chemotaxis, TGFsignalling and extracellular matrix showed good prediction of antiTNF response (AUROC > 0.7).44 However, despite the potential advantages, molecular imaging of CLE is far from having widespread clinical use as it requires expert endoscopists, specialised equipment and needs further validation and increases the cost.

Nevertheless, it provides the basis for a new era of precisely tailored medicine.

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66 IBD

Figure 3: After the application on the mucosa of a mucolytic agent N-acetylcysteine, (a) honeycomblike structure of colonic mucosa with methylene blue 0.2%; endocytoscope images of (b) elongated crypts architecture; (c, d) infilitration of the cells between the crypts; (e) drop out/necrosis of the crypts with infiltration of the cells.

Endosytoscopy Endocytoscopy (ECS; CF- Y-00581 prototype, Olympus Japan) is a recent high-ultra magnification endoscopic technique that provides in vivo microscopic imaging during endoscopy, with ultra-high magnification ranging from 450-fold to 1400-fold.

After the application on the mucosa of absorptive agents, such as methylene blue, toluidine blue or cresyl violet, alongside a mucolytic agent (N-acetylcysteine) which allows better penetration of the contrast agent, EC allows looking at cells

and nuclei of mucosal surfaces by producing an image close to histology3 (Figure 3).

Several studies have shown that ECS is a reliable technique to assess endoscopic and histological remission with a high concordance between EC and histology (100%). Of note, EC could differentiate precisely inflammatory cells, such as neutrophilic, basophilic, eosinophilic granulocytes and lymphocytes getting closer to histology.

The significant advantage is the reduced need for biopsy specimens. Indeed, biopsies can assess only a limited area, whereas ECS is an optical diagnosis tool which can sample a wider area in vivo of the colonic mucosa.

Bessho et al.45 developed the first endocytosocpy score (ECSS), which evaluated the shape and the distance between crypts and the visibility of microvessels.

This score showed a strong correlation with Matts’s histopathological score and a substantial correlation with Geboes histopathological score.

A further score by Ueda46 et al. is correlated with MES for mild and

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moderate UC patients. Deformed pits with distorted crypt lumen with the irregular arrangement or disruptive or disappeared pits were considered active disease features. Therefore, patients with these characteristics had more relapsed in the follow-up period.

Nakazato et al.44 developed an ECS score (ECSS), which strongly correlated with histological severity. Subsequently, the same authors investigated if ECS can distinguish patients in histological remission from patients with histologically active disease among patients in endoscopic remission.45 Notable, the ECSS score had good diagnostic accuracy, with a sensitivity of 77% (95% CI, 59–89), specificity of 97% (95% CI, 83–99), and accuracy of 86% (95% CI, 75–93) to predict histological remission in patients with UC. Recently we assessed the correlation between endocytoscopy and histology in a prospective study including 29 UC patients.47 An endocytoscopy scoring system (ECSS) was developed based on Nakazato et al. score by including endoscopic findings representative of disease activity (infiltration of the cell). Importantly we found

that endocytoscopy features such as crypt architecture, distance between crypts, cellular infiltration, and visibility of microvessels were strongly correlated with RHI (r = 0.89; 95% CI, 0.51–0.98) and NHI (r = 0.86; 95% CI, 0.42–0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27–0.70).

Furthermore, RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways in healing and nonhealing samples and their correlation with endoscopic scores defined by ultra-high magnification with histology scores. We identified genes relevant to TGF-β signalling such as TGFBR2, PDZK1IP1, USP2, and YOD1 and macrophage recruitment into tissues such as RNASET2, neutrophil and plasma cell function RNF4 and PIM2, and tumour suppressor genes human homolog of Drosophila headcase (HECA) and BIN3. These were shared by MES and ECSS-defined healing and histological healing.48 In an innovative study by Maeda et al.49 a computer-aided diagnosis (CAD) based on an endocytoscopy system was used to predict persistent histologic activity and long-term clinical prognoses.

CAD revealed good performance

67 measures in terms of sensitivity, specificity, and accuracy of 74% (95% CI: 65%–81%), 97% (95% CI: 95%–99%), and 91% (95% CI: 83%–95%) respectively.

Despite the encouraging results, EC requires dedicated training to achieve good competence before its implementation in clinical practice. However, high costs represent a limitation for its use in routine clinical practice in the management of IBD patients.

Artificial Intelligence in IBD: Hype or Reality?

The use of AI-assisted endoscopy in IBD is a rapidly evolving area of research with promising results and additional benefits for more precise endoscopic diagnosis.

Given the significant heterogeneity in presentation, disease course, and treatment response in IBD, AI represents a step towards an objective assessment of the disease.

AI’s potential applications in IBD include diagnosis, identifying mucosal disease activity assessment, predicting response to therapy/recurrence/ complications/hospitalisations, and detecting dysplasia.

The studies on AI-IBD patients published so far are primarily focused on the assessment of inflammation versus remission, mainly using machine learning

algorithms based on frames and videos of colonoscopies.

To objectively evaluate healing or disease progression, Bossuyt et al. built an algorithm called red density based on an evaluation of the redness map and vascular pattern recognition which correlated with endoscopic and histological disease activity in a cohort of 29 UC patients and control.50

Gottlieb et al. compare the performance of a recurrent neural network model with a human reader score. Importantly this system produced accurate Mayo and ulcerative colitis endosopic index of severity (UCEIS) scores with agreement/reproducibility of κ = 0.84 and 0.85, respectively.53

Subsequently, Takenaka et al., in a prospective study based on a deep convolutional neural network (CNN) construct on 40,758 images validated in 875 UC patients, developed a system that predicted endoscopic remission with 90% accuracy, κ = 0.80 and histological remission with 93% accuracy, κ = 0.86.52

Furthermore, we have recently developed the first VCE AI system to accurately distinguish in realtime endoscopic activity and remission in UC colonoscopy videos of both WLE and VCE. A total of 1090 endoscopic videos (638,287 frames) from 283 patients came from the PICaSSO multicenter study were used to develop a CNN to distinguish ER/ activity and predict HR/activity.

This AI-based CAD system detected endoscopic remission/ activity (PICaSSO ≤ 3) in VCE videos with a sensibility of 79%, specificity of 95%, and the AUROC 0.94. It is worthy to note that it also predicted histologic activity/ remission and the occurrence of adverse clinical outcomes.54

Due to high interobserver variability in endoscopy, we expect that AI results could be accurately reproduced, leading to standardising the assessment of disease activity. Furthermore, it can significantly contribute to the accuracy, precision, and reproducibility of central reading in clinical trials. In this context,

Finally, a recent study using a set of 614 biopsies from 307 patients with UC enrolled on a prospective multicentre study used a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate the PICaSSO Histologic Remission Index (PHRI) and identify active from quiescent UC. Importantly this AI algorithm

A further study by Stidham et al. demonstrated the ability of deep learning techniques to distinguish disease in remission versus moderate/severe disease using MES with AUROC of 0.97 and agreement to human reviewer scores, κ = 0.86.51

accurately predicted histological remission and differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy.55 Conclusions In recent years several innovative and necessary steps have been taken in the endoscopic assessment of IBD, including prediction of histology, treatment response, and molecular labelling.

Advances in VCE have led to a focus on microscopic details no longer invisible to the human eye, thereby reducing the gap with histology and increasing detection and characterisation of dysplasia associated with IBD. AI systems support clinicians in interpreting and standardising findings such as grading inflammation, detecting adenomatous polyps, predicting histology and thereby clinical outcomes.

However, the road to IBD precision medicine is still challenging.

In the near future bioinformatics tools and integration of multi-omics including faecal metagenomic, serum metabolomic and proteomic profiles will revolutionise IBD management and shed the light on a new fascinating and promising target to achieve: molecular healing and drive precision medicine.

References available on request

News Saint John Of God Hospital and SpunOut Launch YouthMed.Info Saint John of God Hospital, in partnership with SpunOut, has launched a new digital platform to provide accessible information about mental health medicines for younger people.

YouthMed.Info is a one-stopsource for younger people seeking reliable information on mental health medicines, including how they work, the symptoms they help with, and potential side effects.

Caroline Hynes, Senior Pharmacist at Saint John of God Hospital and Project Lead for YouthMed.Info said, “Younger people are underserved by mental

health medicines information resources available today. We know that they seek information from online video platforms such as YouTube and TikTok. YouthMed.Info offers a reliable, supportive and informative space for younger people to learn about the medicines they have been or may be prescribed in a format that’s acceptable to them.

“The website currently hosts eight animated videos covering a variety of mental health medicines. As the project progresses, we will upload more content on other medicines, including those for younger children and their parents, as

well as answering concerns younger people may have on specific side-effects.”

Ian Power, CEO SpunOut says, “More and more, we hear from younger people with a mental health diagnosis as to how overwhelming they find it to understand the current information available on medicines, as it is targeted towards adults and is often a complex explanation of the medicines used to treat different conditions. Partnering with the team of mental health specialists supporting YouthMed.Info, we wanted to create a platform that younger people can access in

a safe environment so that they can fully inform themselves and better understand the treatment prescribed to them.”

YouthMed.Info was developed entirely in-house by a volunteer group of clinical and academic pharmacists, consultant psychiatrists and nurses from the hospital, Saint John of God Community Services Lucena Clinic, RCSI University of Medicine and Health Sciences, University of Edinburgh, and in collaboration with a focus group of young people via SpunOut, Ireland’s youth information and support platform.

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68

Parkinson's Disease

Molecular genetics of Parkinson’s disease: Contributions and global trends Written by Manabu Funayama1,2, Kenya Nishioka2, Yuanzhe Li2 and Nobutaka Hattori1,2,3 Research Institute of Disease of Old Age, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan 1

Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan 2

Neurodegenerative Disorders Collaborative Laboratory, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0106, Japan 3

Parkinson’s disease (PD) is a progressive neurodegenerative disease whose main symptoms are motor dysfunctions, such as tremor, rigidity, bradykinesia, and postural instability. Selective degeneration of dopaminergic neurons in the substantia nigra of the midbrain underlies these symptoms. PD patients often have comorbid non-motor symptoms that include autonomic dysfunctions, such as constipation and orthostatic hypotension, as well as psychiatric symptoms, such as anxiety and depression.

Thus, PD is not a disease of the central nervous system alone, but rather a systemic disease.

Because the prevalence of PD increases with age, it is clear that aging is a risk factor for its development. Environmental factors are also thought to be important, as exposure to pesticides and other chemicals can cause PD symptoms.

Advances in genetic research methods have provided insights into how genetic backgrounds contribute to the development of PD. Accordingly, PD is a complex genetic disease that is caused by a combination of aging, environmental factors, and genetic factors. There are two major ways to identify genetic factors in PD (Fig. 1). One is to investigate rare

Fig 1 caption: Strategies to identify genetic factors in PD and applications of the findings. The search for genes associated with PD relies on the molecular genetic characteristics of PD patients and the classification of samples into familial PD and sporadic PD groups. After PD-associated genes are discovered, cellular and animal PD models are used to reveal pathophysiological functions and for precision medicine applications

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Mendelian forms of PD and identify the causative genes. The other is to identify risk variants from genetic statistical analyses of large groups of subjects. While there are advantages and disadvantages in each approach, both are necessary to provide a more complete picture of this disease. Genetic studies have identified over 200 PDrelated genes.1 However, regional differences, associated with variations in ethno-social factors, have complicated molecular genetic studies of PD. Here, we discuss the current status and challenges of molecular genetics research on PD. Molecular genetics of Mendelian forms of PD It has been a quarter of a century since the alpha-synuclein gene (SNCA) was reported as the causative gene for the autosomal dominant form of PD.2 In the early days of Mendelian PD research, the prevailing approach used to discover disease-related genes

and variants included identifying loci from positional cloning of large families, using artificial chromosome libraries, such as yeast artificial chromosomes (YACs) and bacterial artificial chromosomes (BACs) to detect the genes and identify patientspecific variants by sequence analysis. This approach led to the discovery of SNCA and PRKN.2, 3 With the completion of the Human Genome Project and the advent of next-generation sequencers, the throughput has been dramatically improved, and the resulting gene maps and sequences have become more readily available.4 Together, these molecular genetic Mendelian PD studies have identified 24 genes or loci that have been registered in the Online Mendelian Inheritance in Man (OMIM) database as being involved in the development of PD. PRKN The most frequent causative gene of PD in Japan is the PRKN

A combination of three effective Parkinson’s therapies

in one convenient gel formulation for intestinal infusion1 Carbidopa monohydrate

Levodopa (20 mg/ml)

Increased levodopa bioavailability with LECIGON®

(5 mg/ml)

Entacapone (20 mg/ml)

S t a n d a r d LC I G *

... a reduced levodopa dose can be given

The same effective and stable plasma levodopa levels are achieved

*Levodopa-Carbidopa Intestinal Gel 1. Lecigon Summary of Product Characteristics, 2021.

ABBREVIATED PRESCRIBING INFORMATION. Lecigon 20 mg/ml + 5 mg/ml + 20 mg/ml intestinal gel. 1 ml contains 20 mg levodopa, 5 mg carbidopa monohydrate and 20 mg entacapone. Presentation: Yellow or yellowish-red opaque viscous gel. Indications: Treatment of advanced Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia when available oral combinations of Parkinson medicinal products have not given satisfactory results. Dosage and administration: Adults/Elderly: Administration by a portable infusion pump directly into the duodenum or upper jejunum via a percutaneous endoscopic gastrostomy(PEG) tube or radiological gastrojejunostony tube. Please consult Summary of Product Characteristics (SmPC) for further information. Only pump Crono LECIG (CE 0476) may be used for the administration of Lecigon. The dose should be titrated to achieve the optimal clinical response in the individual patient, which involves maximising the functional ON-time during the day by minimising the number and duration of OFF episodes (bradykinesia) and minimising ON-time with disabling dyskinesia. Total dose/day of Lecigon is composed of three individually adjusted doses: the morning bolus dose, the continuous maintenance dose, and extra bolus doses. Treatment is usually limited to the patient’s awake period. If medically justified, Lecigon can be administered up to 24 hours/day. The maximum recommended daily dose is 100 ml (2000 mg levodopa, 500 mg carbidopa monohydrate and 2000 mg entacapone. Please consult SmPC for further information. Total morning dose is usually 5–10 ml (100–200 mg levodopa) but not exceeding 15 ml (300 mg levodopa). Continuous maintenance dose is usually 0.7–5.0 ml/hour (15–100 mg levodopa/hour). Extra bolus doses are given if the patient becomes hypokinetic and are normally less than 3ml. An increase in the continuous maintenance dose should be considered if the need for extra doses exceeds 5 doses per day. Please consult SmPC for further information. After initial titration, the morning dose and maintenance dose are fine-tuned over the course of a few weeks.

Lecigon is initially given as monotherapy. If needed, other anti-Parkinsonian medicinal products can be taken concurrently. If treatment with other anti-Parkinsonian medicinal products is discontinued or changed, it may be necessary to adjust the doses of Lecigon. Sudden deterioration in response with recurring motor fluctuations may indicate that the tube has dislocated to the stomach. This needs confirmation by X-ray and may require repositioning. Please consult SmPC for further information. The cartridge is for single use only and should not be used for more than 24 hours. Children: There is no relevant indication for use in children and adolescents. Contraindications: Hypersensitivity to the active substances or any of the excipients, narrow-angle glaucoma, severe heart failure, severe cardiac arrhythmia, acute stroke, severe hepatic impairment. Non-selective MAO-inhibitors and selective MAO type A inhibitors are contraindicated and should be discontinued at least two weeks prior to initiating therapy with Lecigon. Conditions in which adrenergics are contraindicated. Previous neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis. Suspected undiagnosed skin lesions or a history of melanoma. Please consult SmPC for further information. Warnings and precautions: Not recommended for the treatment of drug-induced extrapyramidal reactions. Caution in ischaemic heart disease, severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or of convulsions, past or current psychosis, chronic wide-angle glaucoma, concomitant administration of antipsychotics with dopamine receptor blocking properties or with medicines which may cause orthostatic hypotension. In patients with a history of myocardial infarction who have residual atrial nodal or ventricular arrhythmias, cardiac function should be monitored with particular care during the period of initial dosage adjustments.

Monitor all patients for mental changes, depression with suicidal tendencies, and other serious mental changes. Neuroleptic malignant like syndrome with secondary rhabdomyolysis may occur on abrupt dose reduction/discontinuation of Lecigon. Patients should be monitored for the development of impulse control disorders and review of treatment is recommended if such symptoms develop. Patients and caregivers are advised to monitor for melanomas on a regular basis when using Lecigon. Dose may need to be adjusted downwards to avoid levodopa-induced dyskinesia. Periodically evaluate hepatic, haematopoietic, cardiovascular and renal function during extended therapy. Lecigon contains hydrazine, a degradation product of carbidopa that can be genotoxic and possibly carcinogenic. Reported complications for levodopa/carbidopa in clinical studies include bezoar, ileus, implant site erosion/ulcer, intestinal haemorrhage, intestinal ischaemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumoperitoneum and post-operative wound infection. Sudden or gradual worsening of bradykinesia may indicate an obstruction in the tubing system and should be investigated. Weight loss has been associated with the active substances contained in Lecigon, and caregivers should therefore be aware of weight loss. Monitoring of weight is recommended to avoid severe weight loss. Prolonged or persistent diarrhoea that appears during use of entacapone could be a sign of colitis. In case of prolonged or persistent diarrhoea, treatment with the medicinal product should be discontinued and other appropriate medical treatment and investigation considered. Replacement of Lecigon with either levodopa and a DDC inhibitor without entacapone or other dopaminergic therapy may be necessary and should be done slowly. For patients who experience progressive anorexia, asthenia and weight loss within a relatively short period of time, a general medical evaluation including liver function assessment should be considered. Please consult SmPC for further information. Interactions: Antihypertensives, antidepressants, anticholinergics, dopamine receptor antagonists, benzodiazepines, isoniazide, phenytoin, papaverine, sympathicomimetrics , iron, protein-rich diet, amantadine and dopamine agonists (e.g. piribedil) may increase levodopa-related adverse events. Lecigon dose adjustment may be needed when used with these medicines. Lecigon can be taken with MAO type B inhibitors (e.g. selegiline) although serious orthostatic hypotension may occur and the dose of levodopa may need to be reduced. Lecigon may affect metabolism of medicinal products such as S-warfarin and patients should be monitored during initiation with Lecigon therapy when used with this medicine. Please consult SmPC for further information. Pregnancy and lactation: Lecigon is not recommended during pregnancy or in women of childbearing potential not using contraception unless the benefits for the mother outweigh the possible risks to the foetus. It is unknown whether carbidopa and entacapone or their metabolites are excreted in human milk. Breastfeeding should be avoided during treatment with Lecigon. Driving and operation of machinery: Caution; Lecigon can have a major influence on the ability to drive and use machines. Refrain if somnolence and/or sudden sleep episodes occur.

Undesirable effects: Weight loss, anxiety, depression, insomnia, dyskinesia, Parkinson’s disease /exacerbation of parkinsonism (e.g. bradykinesia), orthostatic hypotension, nausea, constipation, diarrhoea, pain in muscles and tissues, musculoskeletal pain, chromaturia, fall. Complications of the device and surgery: Postoperative wound infection, abdominal pain, excessive granulation tissue, complication of device insertion, incision site erythema, post-procedural discharge, procedural pain, procedural site reaction. Refer to SmPC for other undesirable effects. Adverse events should be reported via HPRA Pharmacovigilance, website: www.hpra.ie. Special precautions for storage: Store in a refrigerator 2°C - 8°C. Do not freeze. Store in the original package in order to protect from light. For storage instructions after first opening of the medicinal product, refer to the summary of product characteristics.

Pack size: 7 x 47 ml cartridges. Marketing authorisation holder: LobSor Pharmaceuticals AB, Kålsängsgränd 10 D, SE-753 19 Uppsala, Sweden. Distributed by Clonmel Healthcare Ltd, Clonmel, Co. Tipperary. Marketing authorisation number: PA23144/001/001. Medicinal product subject to medical prescription. A copy of the summary of product characteristics is available upon request or alternatively please go to: www.clonmelhealthcare.ie Last revision date: March 2022. Date of Preparation: October 2022. 2022/ADV/LEC/268H

70

Parkinson's Disease variant in the PRKN gene and the juvenile PD phenotype, and found patient-specific gene expression changes (Fig. 3). Although this downregulated gene has a different chromosomal location from the PRKN gene, it has been reported to be expressed in the nervous system and may be functionally related to PRKN. Thus, for autosomal recessive diseases with monoallelic variants in genes such as PRKN, other loci should be considered. These strategies include (1) seeking deletions, duplications, and often-missed biallelic variants, such as those in transcriptional regulatory regions, (2) seeking biallelic or polygenic variants, (3) investigating patient susceptibility to the disease, and (4) considering other unrelated causes. Therefore, it is necessary to make careful assessments based on family history and clinical considerations in the diagnosis of PD. PTEN-induced kinase 1 (PINK1)

Fig 2 caption: Pseudo-heterozygotes in the PRKN gene. Copy number variations tested by qPCR showed that the PD patient (green) had a heterozygous duplication in exons 6–7. The PD patient inherited a duplication of exons 3–7 from the father (blue) and a deletion of exons 3–5 from the mother (orange), resulting in compound heterozygous variants in the PRKN gene

gene, which is the causative gene of autosomal recessive juvenile PD, as reported by Kitada et al. in 1998.3 We recently published the results of a study of the PRKN gene in over 2000 cases, and identified biallelic variants in PRKN that are observed in 8.1% (98/1204) of familial PD and 5.8% (65/1118) of sporadic PD cases.5 It is important to note that this population included many patients who were clinically diagnosed as likely to have PRKN variants and were actively selected for genetic analysis. Therefore, the sampling bias is likely to have been strong, and the frequency of PRKN variants is estimated to be a little lower than that observed in the study. We also found PD patients with a putative pathogenic monoallelic rare variant in the PRKN gene, with a frequency of 2.5% (57/2322). A comparison of clinical symptoms between the biallelic and monoallelic variants showed that the age at onset was 29.6 ± 9.8 years for the biallelic variants and 45.2 ± 15.9 years for the monoallelic variant, which indicates an earlier age of onset for the biallelic variants.5 Additionally, more cases of Hoehn and Yahr stage IV or V were observed in the biallelic variants in patients who had the disease for at least 15 years.5

The PRKN gene is the causative gene of autosomal recessive juvenile PD, and therefore, a person with a monoallelic variant is presumed to be an unaffected carrier. However, the frequency of the PRKN monoallelic variant is slightly higher in Japanese PD patients than the Leucine richrepeat kinase 2 (LRRK2) variant, a cause of autosomal dominant PD (discussed further below). Thus, the PRKN monoallelic variant may have some influence on the development of PD. Because the PRKN gene is located at a common fragile site, it is prone to site-specific gaps and breaks due to chromosomal fragility.6 Indeed, the PRKN gene is a cluster of deletions and duplications in exons 2 through 7. Quantitative PCR (qPCR) and Multiplex Ligationdependent Probe Amplification (MLPA) are simple and widely used tests for copy number variations such as deletions and duplications. However, these methods only target a part of a gene, and the results therefore need to be interpreted carefully.

For example, we reported a pseudo-heterozygous variant in a PD patient whose father had a duplication in exons 3–7 and whose mother had a deletion in exons 3–5. The patient inherited the mutant allele from both parents

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and developed juvenile PD, but was incorrectly identified as having a heterozygous duplication in exons 6–7 due to the gene dosages of the parental mutant alleles canceling each other out in qPCR testing (Fig. 2).7 Thus, genetic testing of only the patient may miss the biallelic variants, and therefore, it is advisable to test the patient as well as close relatives, including those who have not yet developed the disease. However, some variants, such as variants in the promoter region and small inversions involving only a partial region of the PRKN gene, may be difficult to identify even with trio analysis. When small inversions are present, the abnormality cannot be detected by sequence analysis using the Sanger method or by copy number variation analysis using the qPCR or MLPA methods.

Therefore, even if one genetic test is negative, diligent testing should be continued if there is clinical suspicion of gene mutation.8 The long-read sequencing method is a useful genetic analysis method that should help identify the underlying genetic variants.

For a more complete analysis, it is necessary to consider genes other than PRKN that are involved in the pathogenesis of the disease. We have conducted RNAseq analysis of patients with both a monoallelic

The second most frequent gene after PRKN as a causative gene for autosomal recessive PD is PINK1. PINK1 is a PD gene discovered in 2004 from a genetic analysis of families in Sicily, Italy.9 Subsequent follow-up studies revealed many PD-related variants.

PINK1 is a mitochondrial kinase.

Single nucleotide variants (SNVs) in PINK1 are more common than copy number variants (CNVs) in PRKN. We performed genetic analysis of PINK1 in 1700 PD patients and identified PINK1 variants in 1.8% of young-onset familial PD and 0.009% of youngonset sporadic PD.10 PINK1 and parkin are known to cooperate and are involved in mitochondrial quality control.11 We found a total of four PD patients with digenic PRKN-PINK1 variants.10,12 These digenic variants seem to have younger age of onset than biallelic variants in PINK1 or PRKN.12 However, the small number of cases makes it unclear whether these differences are significant.

Leucine rich-repeat kinase 2 (LRRK2) The most frequent PD causative gene in Europe and the United States is LRRK2, which was first reported in 2004 as the causative gene of the autosomal forms of PD.13, 14 Originally, the LRRK2 gene was mapped to chromosome 12 in a study of Japanese families with an autosomal form of PD.15 The causative locus, PARK8, was mapped to chromosome 12 and linked to LRRK2. Although this gene is historically associated with Japan, the frequency of the LRRK2 gene in PD in Japan is very low compared with Caucasians.16 Conversely, the LRRK2 gene p.G2019S variant

71 analysis technology has evolved, and high-throughput techniques have improved dramatically, new discoveries will likely remain difficult to make. For example, when wholeexome sequencing is performed using small PD families, hundreds of candidate causative variants will be identified; however, with few exceptions, there is only one causal variant per family, regardless of its size. Investigators must therefore implement various techniques to narrow down the number of candidate variants from hundreds to one. In familial PD studies, it is expected that for at least 80% of the families, a single candidate variant and the causative gene will remain unidentified.

PD risk genes and variants Genome-wide association studies (GWAS)

Fig 3 caption: RNAseq analysis of autosomal recessive juvenile parkinsonism (ARJP) patients with PRKN single heterozygous variants. RNAseq analysis of five ARJP patients (right half) and five controls (left half) shows one example of a gene whose expression is prominently and significantly downregulated only in ARJP patients

is highly prevalent in Europe, the United States and Arab countries, including those in North Africa.17 We analyzed approximately 1400 PD patients and estimated that the frequency of LRRK2 variants in Japan is 1.7% in familial PD, 0.3% in sporadic PD, and 1.0% in all PD patients.16 Most PD patients with LRRK2 variants had families in which the mode of inheritance was thought to be autosomal dominant.

However, some PD patients appeared to have sporadic PD with no known cases in the family, indicating incomplete penetrance.

Clinical features such as tremors (78.3%), postural instability (73.9%), gait with small steps (55.6%), constipation (40.0%) and olfactory disturbances (41.7%) were also frequently observed, and there was no significant difference in clinical symptoms among pathogenic variants.16 Other genes in familial PD In 2011, Vacuolar protein sorter-35 (VPS35) was reported as the first causative gene for autosomal dominant PD based on wholeexome analysis using nextgeneration sequencing.18 Since the report of VPS35, one or two genes a year have been reported as causative PD genes by studies using the same methodology. In

a report from Japan, coiled-coilhelix-coiled-coil-helix domain containing 2 (CHCHD2) and prosaposin (PSAP) were reported as novel genes for familial PD, though they have a very low frequency in Mendelian PD.19, 20 CHCHD2 is the first PD-causing gene involved in the mitochondrial respiratory chain complex, and PSAP is also involved in a lysosomal disease, similar to glucocerebrosidase (GBA1).19, 20 Despite their very low frequencies, these genes are important for understanding the pathogenesis of PD and as potential therapeutic targets. In particular, age-dependent decline in motor function and loss of nigrostriatal dopaminergic neurons have been observed in mouse models of PSAP, suggesting that PSAP may be useful as an animal model of PD.20, 21 Other familial PD-causing genes include DJ1, ATP13A2, GIGYF2, HTRA2, PLA2G6, FBXO7, EIF4G1, DNAJC6, SYNJ1, and DNAJC13, all of which are infrequent in Japanese PD. However, the functions of these gene products, including intracellular trafficking, oxidative stress, mitochondria, phospholipid membranes and ubiquitin-proteasome system, are all predicted to be

involved in the pathogenesis of PD.22,23,24,25,26,27,28,29,30,31 Difficulties in discovering new PD-causing genes One of the problems with Mendelian PD research is the lack of research targets. It has been reported that the percentage of Mendelian-inherited diseases for which the cause could be identified by whole-exome analysis is about 20%.32 Because PD is a complex genetic disease with a late onset, the rate of cause-identification is expected to be even lower. One approach to overcome this limitation is to collect as many subjects as possible in the same family with Mendelian PD. In the case of manifest PD, collecting more genetic samples over multiple generations yields a higher probability of identifying the cause of the disease, but in many cases, the parents or grandparents with PD had died by the time the proband developed the disease.

For example, in the PARK8 family mentioned above, the causative gene locus was successfully identified after more than 20 years of intra-family research and DNA sampling, including from those who did not develop the disease.33,34,35 Even though genetic

GWAS have been conducted to identify genetic factors that contribute to the pathogenesis of sporadic PD. To identify these factors, GWAS and meta-analysis on GWAS (Meta-GWAS) have been employed. In GWAS, microarray technology is used to genotype relatively frequent single nucleotide polymorphisms (SNPs). SNPs with large differences in frequency between the patient and control groups can be identified. Genes located near hit-SNPs, which are significantly more or less frequent in the patient group, are presumed to be more likely to influence the development of sporadic PD. As a result of multiple GWAS, several important genes have been identified as being risk factors for PD. Among them, SNCA and LRRK2 were found to be causative genes for the Mendelian forms of PD, but GWAS revealed that they are also involved in the development of sporadic PD.36, 37 Two GWAS studies in Europeans and Japanese populations have shown that LRRK2 is a common risk factor for PD regardless of race. However, Europeans share a unique variant, p.G2019S, while p.R1628P and p.G2385R are variants unique to Asians.38, 39 According to the GWAS catalog, about 200 genes related to PD have been reported so far.1 Furthermore, a recent metaanalysis of GWAS identified 90 independent variants in 78 genomic regions associated with PD; however, how these variants affect pathogenesis remains largely unknown.40 Therefore, it is likely that more genes will be reported to be involved in PD pathogenesis in future MetaGWAS. Clarifying how these many genes may be related to or affect PD onset as well as other clinical manifestations may require new approaches that combine artificial intelligence, deep learning, gene

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72

Parkinson's Disease

expression data, metabolomics, and other technologies. The findings from these combined approaches are expected to contribute to the prediction of PD onset and prognosis as well as to the implementation of targeted medicine strategies and therapeutics.

GBA1 GBA1 is the causative gene for Gaucher disease (GD), a lysosomal disorder.41 GD is a recessively inherited disease caused by variants in the GBA1 gene. Notably, in GD families, many GD-naive GBA1 variant carriers have family members who develop PD.42, 43 This suggests that a monoallelic GBA1 variant may be a risk factor for developing PD, and in fact, GBA1 was found to be a common and frequent risk factor for the development of PD in different populations, including Japan.44, 45 Variants of GBA1 known to be associated with PD development include p.E326K, p.T369M, p.N370S and p.L444P, which decrease the activity of glucocerebrosidase, the enzyme encoded by GBA1, and consequently reduce the ability to degrade alpha-synuclein in lysosomes.46 Variants of GBA1 have different frequencies in different races. For example, p.E326K has a frequency of 1–5% in the general European population, but is very rare in Asia.

Polygenic risk score (PRS) PD is thought to be caused by a complex interaction of multiple genetic risk factors with

environmental factors and aging.

The identification of novel risk genes and variants for PD by GWAS is a promising approach for discovering a small number of common causative genes or risk variants. The PRS is calculated for each individual based on the weighted sum of the risk variants, assuming that the patient has many risk variants. PRS has been shown to correlate with the actual risk of developing the disease, and by examining the distribution of scores within a population, it is possible to identify individuals at particularly high risk for the disease. Foo et al. identified 11 PD-risk SNVs in a meta-GWAS of Asian samples.47 Two of these (SV2C and WBSCR17) were novel PD risk genes. The PRS was calculated using these SNVs, and it was shown that the age of onset decreased with each additional copy of the risk allele.47 Similar PRS calculations using the previously reported 90 risk variants in a European sample showed no significant difference in risk prediction in spite of the 8-fold greater number of SNVs.47 Thus, these findings suggest that the PRS calculation based on GWAS for each race is significant for disease prediction, and that the weights of individual risk SNVs differ by race.

Efforts to address regional and racial differences in PD Genetic regional and racial differences in PD are observed

for many genes. For example, the MAPT gene, encoding the microtubule-associated protein tau, was detected as a risk factor for PD in a GWAS of a Caucasian population, but not in a GWAS of a Japanese population.36, 37 However, several Japanese families have been affected by variants in MAPT.48, 49 Most molecular genetic studies of disease have been conducted primarily in Caucasians for various geopolitical, cultural, linguistic, and economic reasons.50 However, as the examples of GBA1 and MAPT show, the lack of molecular genetic studies in multiracial populations is an important issue that must be resolved in future PD research.

Genetics of PD (LARGE-PD).52,53,54 Each hub collects thousands of patient and control samples to determine racial genetic background, polygenic risk scores, and other metrics. GP2 makes its data and analysis scripts available to the public and runs educational programs on how to use them to perform various analyses in the cloud. Through such open science, GP2 is expanding its reach beyond Caucasians to include both patients who have not previously been included in studies and researchers who have not previously had the opportunity to conduct large-scale genomic analysis studies.

The Global Parkinson’s Genetics Program (GP2) is a worldwide international consortium established under the auspices of Aligning Science Across Parkinson’s (ASAP) to actively promote research in regions where genomic research has not been actively conducted before and where English is not the native language.51 For this reason, the GP2 web page (https://gp2.org) is available in Arabic, Chinese, French, German, Japanese and Spanish, in addition to English.

GP2 has hubs in various locations, such as the East Asian Parkinson Disease Genomics Consortium (EAPDGC) in East Asia, which includes Japan, the Genomics Consortium Africa (IPDGC Africa) in Africa, and the Latin American Research Consortium on the

In this review, we described the current status of molecular genetics research on PD, its challenges, and the efforts to address them. Studying the molecular genetics of PD is a crucial first step in understanding the disease, because it advances our knowledge of the relationship between phenotype and genotype.

Whether by revealing the full etiopathogenesis of the disease, uncovering novel pathogenetic mechanisms, or leading to other exciting findings, future molecular genetic studies are likely to foster major advances in our understanding of this debilitating neurodegenerative disorder in the near future.

Conclusion

References available on request

News HSE marks Breast Cancer Awareness Month This Breast Cancer Awareness Month, the HSE’s BreastCheck programme is encouraging women to choose screening and take up their BreastCheck appointment when they are invited.

BreastCheck is the free national breast screening programme offered to women aged 50 – 69, offering screening and swift access to onward assessment and treatment if it is needed.

Breast screening helps find breast cancer early. Around 3,500 women are diagnosed with breast cancer in Ireland every year and about a third of these people will have cancer detected through screening.

Breast cancer is the second most common cancer in women in Ireland and a 2023 national survey1 for BreastCheck found

that 48% of Irish adults have either been personally affected by or have had someone close to them affected by breast cancer.

BreastCheck Programme Manager Suzanne Lynch said, “We know that women may have questions about breast cancer screening and this Breast Cancer Awareness Month we want to give them all the information they need to help them to choose screening – especially women who are being offered breast screening for the first time.

Women can expect their first appointment between the age of 50 and 53. We are particularly keen for women to take up their first screening appointment because it is an age when we know women are less likely to attend. We also know that when a woman comes for one screening test, she is likely

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

to come back regularly. And recent research2 has found that women who develop breast cancer have a stronger survival rate if they have regularly taken part in screening.”

BreastCheck Clinical Director Professor Fidelma Flanagan said: “Every year we screen about 170,000 women and detect about 1,100 cancer cases. While we know that most people’s screening results are normal and no cancer is found, for some women, a fear of finding something wrong may stop them coming for screening. Our national survey1 earlier this year found that 59% of women identified a “fear of finding something wrong” as one of the reasons they wouldn’t come for screening. However, screening can help to find cancer

early, when it may be easier to treat, giving you a better chance of recovery. But I have to emphasise that screening is not for women with symptoms of cancer. If any woman is worried that something may be wrong, do not wait for your screening appointment - go to your GP immediately.”

Prof Flanagan explains, "Breast screening aims to find changes in your breast, at an early stage, and reduce the number of new cases and deaths associated with breast cancer. It’s important for women also to be aware that no screening programme will detect every cancer. So as well as regularly attending screening, we should all be breast aware and know what is normal for each of us and know the symptoms to watch out for.”

Pharmacy Abstract 73

Antimicrobial Prevalence Survey National antimicrobial point prevalence survey in adult inpatient mental health facilities in Ireland Written by S Fagan, M Donnelly, A Clancy, M Regan, A M Maher, C Ryan, S Armitage, M Shah, P Sheehan, C Mannion, O Gallagher, R Foran, C Devine, B Love. HSE Community Antimicrobial Pharmacist Group Author Contributions: This paper is dedicated in memorandum to Sarah Fagan Background Antimicrobial use in mental health inpatient settings has not been extensively examined in Ireland.

The Healthcare-Associated Infection and Antimicrobial Use in Long-Term Care Facilities (HALT) study 2016 found that Irish long-term care facilities caring for residents with psychiatric conditions had an antimicrobial prevalence rate of 7.7%, higher than the European average of 4.9%. National community antimicrobial prescribing guidelines are available at www. antibioticprescribing.ie. In addition, a preferred antibiotic initiative for community settings advocates prescribers to choose ‘Green’ (preferred) antibiotics over ‘Red’ (reserved) agents.

Reserved agents are considered to have more adverse effects, drug interactions and potential for development of antimicrobial resistance. The patient safety implications of antimicrobial stewardship along with an ageing population, and potential drug– drug interactions between many antimicrobials and psychotropic medications prompted a review

of antimicrobial use practices in mental health services.

Sarah Fagan

Methods A sample of adult inpatient mental health facilities (MHF) operated by the state's Health Service Executive (HSE) were surveyed by community antimicrobial pharmacists (AMPs) between November 2021 and January 2022. AMPs reviewed patients’ medication charts for systemic antimicrobial prescriptions in the previous 30 days in addition to medical notes and laboratory results (where available).

Adherence to HSE National community antimicrobial guidelines and the systems and structures in place to support antimicrobial stewardship were assessed.

Results In total, 1003 patients in 51 MHFs were surveyed. At the time of survey, 6.3% (n=66) patients were on a systemic antimicrobial and 15% (n=153) had received a systemic antimicrobial within the previous 30 days. Prophylaxis accounted for 50% of antibiotic use (3.3% of all patients), with the

most common indication being the prevention of urinary tract infection (UTI) (58%). Prophylaxis duration exceeded six months in 61% of prescriptions. The median duration of treatment courses was seven days. The proportion of ‘Green’ (preferred) antimicrobials versus ‘Red’ (reserved) antimicrobials was 58% versus 38%. Coamoxiclav, a ‘Red’ agent was the most commonly prescribed antibiotic for treatment of infection (31%). Adherence with choice of antimicrobial agent as per national antimicrobial guidelines was 76%; adherence of dosing regimen was 75% and adherence with recommended duration was 46%. The main themes for nonadherence with choice of agent were use of unnecessarily broad spectrum agents, nitrofurantoin prescribed in renal impairment

and inappropriate formulation of nitrofurantoin chosen. Dipstick urinalysis was performed routinely (on admission and/or at designated intervals) for persons asymptomatic of UTI in 53% (n=27) of MHFs. Conclusions This PPS established antimicrobial use practices in HSE MHFs and identified opportunities for improvement relating to the safe and optimal use of antimicrobials.

Key national recommendations from this survey were: • Patients on urinary antibiotic prophylaxis ≥6 months should be reviewed with a view to de-prescribing.

• Routine use of dipstick urinalysis for asymptomatic patients to support diagnosis of UTI should cease.

• All nursing and medical staff should be aware of national antimicrobial prescribing guidelines for community published on www.antibioticprescribing.ie.

• Where an antimicrobial is considered necessary, a ‘Green’ agent (preferred) should be selected instead of a ‘Red’ agent (reserved) where possible.

• Prescribe the shortest effective duration for antimicrobials.

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74 News

Revolutionising High Blood Pressure Treatment Dr Conor Judge, a senior lecturer of applied clinical data analytics with University of Galway’s College of Medicine, Nursing and Health Sciences, and Consultant Nephrologist at Saolta University Health Care Group Credit - Martina Regan

A University of Galway researcher has secured funding from the Health Research Board (HRB) to advance blood pressure treatment using artificial intelligence.

The project led by Dr Conor Judge - An Artificial Intelligence approach to improving blood pressure treatment - is set to revolutionise the management and treatment of hypertension, a critical health issue affecting more than 1.4 billion people around the world.

The funding of ¤700,000 has been awarded under the HRB’s Clinician Scientist Fellowships (CSF) 2023 scheme.

The research project will run for four years and aims to address

the significant care-gap in hypertension management, which currently requires people with the condition to visit their doctor frequently, thus posing a challenge to both the person with hypertension and the healthcare providers, by exploring the potential of artificial intelligence in enhancing treatment decisions.

Initially, the project will analyse two extensive clinical trials on blood pressure treatment to train a computer program to make treatment decisions similar to clinical hypertension experts. Following this, safety features will be integrated into the AI program to ensure reliable recommendations,

especially in unfamiliar medical scenarios. The project will carry out comprehensive surveys with both clinicians and people being treated for high blood pressure to gauge their perceptions of AI-driven treatment. The final step involves a thorough evaluation of the AI program's efficacy in recommending blood pressure treatments in a real world setting.

Dr Conor Judge, a senior lecturer of applied clinical data analytics with University of Galway’s College of Medicine, Nursing and Health Sciences, and Consultant Nephrologist at Saolta University Health Care Group said, “Doctor capacity is a crucial factor that limits how well we can control

high blood pressure, leading to a significant gap in managing this condition worldwide.”

“The overarching goal is to personalise hypertension management, thereby bridging the existing care-gap and significantly reducing the global burden of hypertension-related complications. The project's findings could potentially set a precedent for employing AI in managing other critical health conditions, marking a significant stride towards integrating AI in routine clinical practice.”

The research will be supervised by Professor Martin O'Donnell, Dean of the College of Medicine, Nursing and Health Sciences and Professor of Neurovascular Medicine at University of Galway, and Consultant Geriatrician at Saolta University Health Care Group.

Professor O’Donnell said, “Artificial Intelligence Clinical Decision Support Systems (AICDSS) for Hypertension holds considerable potential to improving hypertension management but require rigorous evaluation before assimilation into routine clinical practice.

“This scheme is designed to fund health and social care practitioners who have completed their PhD and are engaged in clinical care delivery.

The primary aim is to nurture these professionals into independent clinician researchers with a profound ambition to influence policy and practice through their research endeavours.”

Calls for Review into Spinal Surgeries The 35th Irish Hospital Consultants Association (IHCA) conference heard calls for the external review into spinal surgeries to be systemic in nature.

The IHCA, which represents over 95% of hospital Consultants in Ireland, saw its members gather in Dublin for their annual conference.

Sinn Féin leader Mary-Lou McDonald, TD and Labour Leader Ivana Bacik, TD were among those addressing members.

Consultants say that the external review being commissioned is of utmost importance, first and foremost for the patients concerned, but also for any patient, child or adult, who is on a waiting list to have surgery in Ireland.

For too long now, Consultants have been urging the Government to implement measures aimed at cutting wating lists and filling the over 900 vacant consultant posts. Funding of ¤4 billion must be allocated in Budget 2024 to build and open essential additional hospital beds, theatres, diagnostics, and other facilities already announced by the Minister for Health.

In terms of the external review, the IHCA say justifiable concerns have been raised regarding both the terms of reference and who the review is ultimately reporting to and that it is not too late to allay these concerns.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

IHCA President, Prof Rob Landers says the Taoiseach and Minister need to take firm control and make the necessary adjustments to ensure the external review is systemic in nature, with the authority to see any documentation and evidence available. It cannot in effect be allowed to report to itself, Professor Landers said.

“Scoliosis patients and their families who, for decades have had to battle the system find themselves having to do so again.

“The battle many have to go through in healthcare is real. For hospital consultants, it’s a battle for theatre time, facilities and basic equipment. A battle with

antiquated systems. A battle against the impacts of later patient presentations leading to increased complexity and often a battle to be heard.

“It is fundamental that this review is systemic in nature because what it concludes and ultimately recommends will influence how all hospitals approach complex surgeries, innovation, risk evaluation and resourcing into the future.

“The cultural and governing environment in which healthcare professionals’ function is critical to patient outcomes. When we are dealing with serious, highly complex surgery, it matters even more.”

News 75

First National Lead appointed to head New Office for Child and Youth Mental Health The HSE has announced the appointment of Donan Kelly as Ireland’s first National Lead for Child and Youth Mental Health.

Mr Kelly brings with him extensive leadership and mental health experience from his roles as Chief Operating Officer in Pennine Care NHS Foundation Trust and Service Director for the Oxfordshire & BSW Mental Health Directorate. He has previously worked in Child and Adolescent Mental Health Services in both Ireland and Australia.

Speaking about his new role, Donan Kelly said, “Our new office will provide leadership, oversight and support to services and programmes that relate to child and youth mental health. To ensure that services are integrated and support young people through the promotion of good mental health, early intervention and, when the need arises to ensure there are clear pathways to additional supports, including specialist mental health services.

“Our immediate focus will be on bringing together the work of the HSE Child and Youth Mental Health Service Improvement Programme, implementation of related Sharing the Vision policy recommendations and National Clinical programmes. We will work in partnership with key areas such as primary care, disabilities, education, Tusla, our voluntary, community and social partners, and of course young people and families, to develop services.”

He will join Dr Amanda Burke, recently appointed Clinical Lead for Youth Mental Health, in running the HSE’s new Child and Youth Mental Health Office.

The office is responsible for the Child and Youth Mental Health Service Improvement Programme, designed to build capacity in CAMHS and youth mental health through the development of specialist services and clinical programmes. It will also provide leadership, operational oversight, and enhanced governance.

The HSE has made CAMHS and youth mental health service improvement a priority and has made significant improvements, such as five new CAMHS Hubs to support CAMHS Teams in delivering enhanced responses to children, young people and their families/carers in times of acute mental health crisis. Support from these Hubs is designed to be over a short period of time, as they provide targeted and intensive intervention and support with flexibility to respond to different young people’s or parent/carer needs. The appointment of Mr Kelly represents another step forward in this programme of work, which will deliver for children and young people across Ireland.

Speaking about the work of the new office, Dr Amanda Burke, HSE Clinical Lead for Youth Mental Health said, “As a CAMHS consultant psychiatrist working in the west of Ireland, ongoing service improvement has been a key area of focus for me. I am

delighted to work with Donan in the new National Child and Youth Mental Health Office, as I believe his professional experience and personal commitment place him in an ideal position to lead and support our work. I look forward to working together with him and all of our HSE colleagues to bring about positive changes in mental health services for children and young people.”

David Walsh, National Director, Community Operations, HSE welcomed the new appointments, “The new Child and Youth Mental Health Office builds on service improvements already started in CAMHS and will effect important changes in mental health supports and services for children and young people in Ireland. The HSE is fully committed to working in partnership with staff, service users and families, in order to achieve the goal of a modern and fit for purpose youth mental health service that meets the needs of those who require support.”

Master Surgeon Educators Induction Professor Kevin Barry, Director of National Surgical Training Programmes at RCSI, has been admitted as a Member of the American College of Surgeons (ACS) Academy of Master Surgeon Educators.

Professor Barry was among a group of 63 esteemed surgical educators who were inducted at a ceremony on 6 October in Chicago.

He has been a consultant general surgeon at Mayo University Hospital, where he established a symptomatic breast clinic, since 1999. In 2008 he joined the symptomatic breast team at Galway University Hospital, where he continues to work closely with the multidisciplinary team, before joining RCSI in 2021 as Director of National Surgical Training Programmes, playing a pivotal role in maintaining the highest standards of excellence within RCSI’s surgical training work.

A graduate of University College Cork, Professor Barry obtained his FRCSI in 1990 before completing further training in the USA. He was awarded an MD by UCC on

the basis of his research and has authored more than 130 peerreviewed publications.

Professor Kevin Barry, Director of National Surgical Training Programmes, RCSI

This is the sixth cohort of members of the academy, which works to advance the science and practice of education across all surgical specialties. Individuals are selected as members, associate members, or affiliate members following a stringent peer review process.

Distinguished leader Members actively engage in furthering the Academy’s programmes and goals, which include advancing the science and practice of innovative lifelong surgical education, training and scholarship, and positively impacting quality and patient safety through lifelong surgical education and training. Professor Barry joins the Academy ranks with Professor Oscar Traynor, Professor of Postgraduate Surgical Education at RCSI, who was inducted in 2022.

RCSI President, Professor Laura Viani said: “I am delighted to congratulate Professor Barry on the occasion of his induction

into the ACS Academy of Master Surgeon Educators. Professor Barry is a distinguished leader in surgical training and education at both national and international levels, and his dedication and contributions to the field have earned him this most prestigious honour.”

Dr LD Britt, past president of the ACS and co-chair of the Steering Committee of the Academy, commented: “The Academy of Master Surgeons Educators, a vital and ‘living body’ of the American College of Surgeons, continues its legacy of advancing the science and practice of surgical education. The Academy is pleased to induct the 2023

cohort of distinguished and highly accomplished educators.

“This recognition is a true testament to the unwavering commitment of the College to develop and promote ‘best practices’ in surgical education, with the overarching goal to always improve patient care.”

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

76 News

New Hope for Gestational Diabetes Patients Mother of three Zara Sheerin with Professor Fidelma Dunne, University of Galway who managed the EMERGE clinical trial into treatment of women who suffer gestational diabetes and Chloe Ryan, Research Assistant on the trial Credit Martina Regan

Researchers at University of Galway have taken a significant step forward in the management of gestational diabetes mellitus after a clinical trial involving pregnant women provided new hope for expectant mothers suffering the condition.

• Women receiving metformin gained less weight throughout the trial and maintained this weight difference at the 12-week post-delivery visit.

Gestational diabetes is a global health issue affecting almost 3 million pregnant women worldwide every year. It is a condition characterised by elevated blood sugar levels during pregnancy, posing increased health risks for both mothers and their babies.

• Importantly, delivery occurred at the same mean gestational age (39.1 weeks) in both groups. There was no evidence of any increase in preterm birth (defined as birth before 37 weeks) among those who received metformin.

Professor Fidelma Dunne, Professor of Medicine at University of Galway and Consultant Endocrinologist at Saolta University Health Care Group, managed the EMERGE, randomised, placebo-controlled trial, funded by the Health Research Board, involving more than 500 pregnant women.

• Infants born to mothers who received metformin weighed, on average, 113g less at birth, with significantly fewer infants classified as large at birth, or weighing over 4kg (8lbs 8 ounces).

It found: • Women assigned to metformin were 25% less likely to need insulin, and when insulin was necessary, it was started later in the pregnancy. Metformin is used routinely in the treatment of Type 2 Diabetes and has been widely available for over 60 years.

• Fasting and post-meal sugar values in the mother were significantly lower in the

metformin exposed group at weeks 32 and 38.

• While there was a slight reduction in infant length (0.7cm), there were no other significant differences in baby measurements.

• There were slightly more babies who were small at birth but this did not reach statistical significance.

The study also revealed no differences in adverse neonatal outcomes, including the need for intensive care treatment for new-borns, respiratory support, jaundice, congenital anomalies, birth injuries or low sugar levels.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

“The results from the EMERGE study are a significant step forward for women with gestational diabetes. Metformin has emerged as an effective alternative for managing gestational diabetes, offering new hope for expectant mothers and healthcare providers worldwide.”

Additionally there were no variations in rates of labour induction, caesarean delivery, maternal haemorrhage, infection or blood pressure issues during or after birth.

Professor Fidelma Dunne presented the results (on Tuesday October 3, 2023) at the 59th Annual Meeting of the European Association for the Study of Diabetes in Hamburg, Germany.

Professor Dunne said: “While there is convincing evidence that improved sugar control is associated with improved pregnancy outcomes, there was uncertainty about the optimal management approach following a diagnosis of gestational diabetes.

“In our pursuit of a safe and effective treatment option we explored an alternative approach – administering the drug metformin.

A previous trial compared metformin to insulin and found

it to be effective, yet concerns remained, especially regarding preterm birth and infant size.”

To address concerns comprehensively, the team at University of Galway conducted a ground-breaking placebocontrolled-trial, filling a critical gap in the gestational diabetes treatment landscape.

• 535 pregnant women took part, with 268 receiving metformin and 267 a placebo.

• 98% of women remained in the trial until delivery, with 88% completing the 12-week postdelivery follow up assessment.

• Only 4.9% of women discontinued medication due to side effects, highlighting the safety of the interventions.

Professor Dunne said: “Traditionally, gestational diabetes has been managed initially through dietary advice and exercise, with insulin introduced if sugar levels remain sub-optimal.

While effective in reducing poor pregnancy outcomes, insulin use is associated with challenges, including low sugars in both the mother and infant which may require neonatal intensive care, excess weight gain for mothers, and higher caesarean birth rates.

“For mothers with gestational diabetes, they are also at greater risk of high blood pressure and preeclampsia.

“Babies born to mothers with gestational diabetes face their own set of risks, such as excessive weight at birth, birth injuries, respiratory difficulties and low sugar levels after delivery potentially requiring admission to neonatal intensive care. Gestational diabetes also increases the lifetime risk of diabetes for these mothers and their children. In addition mothers have an elevated lifetime risk of cardiovascular disease. Furthermore, low and middle-income countries bear a significant burden of gestational diabetes cases.”

Professor Dunne added: “The results from the EMERGE study are a significant step forward for women with gestational diabetes.

Metformin has emerged as an effective alternative for managing gestational diabetes, offering new hope for expectant mothers and healthcare providers worldwide.”

Switch to Simponi and drive on

Effectiveness of golimumab in rheumatology patients after failure of initial TNFαi therapy - A pooled data analysis.1 Simponi, in combination with methotrexate (MTX), is indicated for:2

• the treatment of moderate to severe, active rheumatoid arthritis in adults when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate.

• the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX

Scan here to download ‘Switch to Simponi and drive on’ leaflet

patients with risk factors for skin cancer. Heart Failure: Golimumab should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and golimumab must be discontinued in patients who develop new or worsening symptoms of heart failure. Some cases had a fatal outcome. Neurological events: Use of anti-TNF therapy, including golimumab, has been associated with cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and peripheral demyelinating disorders. Discontinuation of golimumab should be considered if these disorders develop. Carefully consider the benefits and risks before initiation of therapy in patients with a history of demyelinating disorders. Surgery: Patients requiring surgery whilst on golimumab therapy should be closely monitored for infections. Autoimmune processes: If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with golimumab and is positive for antibodies against double-stranded DNA, treatment should be discontinued. Haematological reactions: There have been post-marketing reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anaemia, and thrombocytopaenia in patients receiving TNF-blockers, including golimumab. Patients should be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias. Discontinuation should be considered in patients with significant haematologic abnormalities. Vaccinations/therapeutic infectious agents: It is recommended that live vaccines or any therapeutic infectious agents should not be given concurrently. Allergic reactions: If an anaphylactic reaction or other serious allergic reaction occurs, administration of golimumab should be discontinued immediately, and suitable treatment initiated. The needle cover of the pre-filled pen contains latex and may cause allergic reactions in those sensitive to latex. Special populations: Older patients (≥ 65 years): Adverse events, serious adverse events and serious infections in patients aged ≥65 were comparable to those observed in younger patients.

However, caution should be exercised when treating the elderly, particular attention should be paid to infections. There were no patients age 45 and over in the nr-Axial SpA study. Paediatric patients (<18 years): Vaccinations: it is recommended that prior to initiating golimumab therapy, paediatric patients be brought up to date with all immunisations in agreement with current immunisation guidelines. Excipients: Simponi contains sorbitol (E420). In patients with rare hereditary problems of fructose intolerance, the additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. INTERACTIONS Combination of golimumab and other biological therapeutics used to treat the same conditions as golimumab, including anakinra and abatacept is not recommended. PREGNANCY AND LACTATION Administration of golimumab is not recommended during pregnancy or breast-feeding. Women of childbearing potential should use adequate contraception and continue its use for at least 6 months after the last golimumab treatment. SIDE EFFECTS Refer to SmPC for complete information on side effects Very Common (≥ 1/10): upper respiratory tract infection; Common (≥1/100): bacterial infections, lower respiratory tract infections, viral infections, bronchitis, sinusitis, superficial fungal infections, abscess, leukopenia (including neutropenia), anaemia, allergic reactions, autoantibody positive, depression, insomnia, dizziness, headache, paraesthesia, hypertension, asthma and related symptoms, dyspepsia, gastrointestinal and abdominal pain, nausea, gastrointestinal inflammatory disorders, stomatitis, alanine aminotransferase increased, aspartate aminotransferase increased, pruritus, rash, alopecia, dermatitis, pyrexia, asthenia, injection site reaction, chest discomfort, bone fractures were reported. Serious, including fatal adverse events have been reported including septic shock, lymphoma, leukaemia, melanoma, Merkel cell carcinoma, hepatosplenic T-cell lymphoma*, leukopenia, thrombocytopaenia, pancytopaenia, aplastic anaemia, agranulocytosis, serious systemic hypersensitivity reactions (including anaphylactic reaction), skin exfoliation, vasculitis (systemic), sarcoidosis, demyelinating disorders, congestive heart failure, arrhythmia, ischaemic coronary artery disease, thrombosis, interstitial lung disease and lupus-like syndrome. * Observed with other TNF-blocking agents. Paediatric population: pJIA: The safety of golimumab has been studied in a phase III study of 173 pJIA patients from 2 to 17 years of age. The average follow-up was approximately two years. In this study, the type and frequency of adverse events reported were generally similar to those seen in adult RA studies. PACKAGE QUANTITIES 1 x 50 mg pre-filled pen containing 50 mg of golimumab in 0.5 ml solution for injection 1 x 50 mg pre-filled syringe containing 50 mg of golimumab in 0.5 ml solution for injection 1 x 100 mg pre-filled pen containing 100 mg of golimumab in 1 ml solution for injection Legal Category: Prescription Only Medicine. Marketing Authorisation Number 50 mg Pre-filled Pen EU/1/09/546/001 50 mg Pre-filled Syringe EU/1/09/546/003 100 mg Pre-filled Pen EU/1/09/546/005 Marketing Authorisation Holder Janssen Biologics B.V., Einsteinweg 101, 2333 CB Leiden, The Netherlands Date of Revision of Text: February 2019 © Merck Sharp & Dohme Ireland (Human Health) Limited 2019. 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. X-083G-Feb2019.

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) References 1. Govoni M, et al. Poster presented at the American College of Rheumatology; Philadelphia, PA, USA; November 10-14, 2022.

Abstract available at Arthritis Rheumatol. 2022; 74 (suppl 9).

2. Simponi Summary of Product Characteristics Feb 2023

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

IE-GOL-00230 Date of Preparation: July 2023

Simponi 50 mg, 100 mg Solution for Injection in pre-filled pen Simponi 50 mg Solution for Injection in pre-filled syringe (golimumab) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing PRESENTATION Simponi 50 mg solution for injection in pre-filled pen Simponi 50 mg solution for injection in pre-filled syringe Simponi 100 mg solution for injection in pre-filled pen INDICATIONS Rheumatoid Arthritis (RA): Simponi, in combination with methotrexate (MTX), is indicated for: the treatment of moderate to severe, active rheumatoid arthritis in adults when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate; the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX. Simponi, in combination with MTX, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function; Psoriatic Arthritis (PsA): Simponi, alone or in combination with MTX, is indicated for the treatment of active and progressive PsA in adults when the response to DMARD therapy has been inadequate. Simponi has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease and to improve physical function. Ankylosing Spondylitis (AS): Simponi is indicated for the treatment of severe, active AS in adults who have responded inadequately to conventional therapy. Non-radiographic axial spondyloarthritis (nr-Axial SpA): Simponi is indicated for the treatment of severe, active nr-Axial SpA who have had an inadequate response to or are intolerant to NSAIDs. Ulcerative colitis (UC): Simponi is indicated for treatment of moderately to severely active UC in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies. Polyarticular juvenile idiopathic arthritis (pJIA): Simponi 50mg in combination with MTX is indicated for the treatment of polyarticular juvenile idiopathic arthritis in children with a body weight of at least 40 kg, who have responded inadequately to previous therapy with MTX. DOSAGE AND ADMINISTRATION Simponi should be injected subcutaneously. Treatment should be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of RA, PsA, AS, nr-Axial SpA, UC or pJIA. After proper training in subcutaneous injection technique, patients may self-inject, if their physician deems it appropriate. RA: Simponi 50 mg given once a month, on the same date each month, concomitantly with MTX. PsA: Simponi 50 mg given once a month, on the same date each month, alone or in combination with MTX. AS and nr-Axial SpA: Simponi 50 mg given once a month, on the same date each month. Clinical response is usually achieved within 12-14 weeks of treatment (3 or 4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period. In patients weighing more than 100 kg who do not achieve an adequate clinical response after 3 or 4 doses, increasing the dose of golimumab to 100 mg once a month may be considered, taking into account the increased risk of certain serious adverse reactions with the 100 mg dose compared with the 50 mg dose. UC: Patients weighing < 80 kg: Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2. Patients who have an adequate response should receive 50 mg at week 6 and every 4 weeks thereafter. Patients who have an inadequate response may benefit from continuing with 100 mg at week 6 and every 4 weeks thereafter. Patients weighing ≥ 80 kg: Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks.

During maintenance treatment, corticosteroids may be tapered, following clinical practice guidelines. Clinical response is usually achieved within 12-14 weeks of treatment (after 4 doses). pJIA: Simponi 50 mg administered once a month, on the same date each month, for children with a body weight of at least 40 kg. Clinical response is usually achieved within 12 to 14 weeks of treatment (after 3-4 doses). Missed dose: If a patient forgets to inject Simponi on the planned date, the forgotten dose should be injected as soon as the patient remembers. The patient should be instructed not to inject a double dose. Older patients (≥ 65 years): no dose adjustment required. Paediatric patients (<18 years): For indications other than pJIA, Simponi is not recommended. Patients with renal and hepatic impairment: Simponi is not recommended. CONTRAINDICATIONS Patients with a hypersensitivity to golimumab or any of the excipients; Patients with active tuberculosis (TB) or other severe infection such as sepsis and opportunistic infections; patients with moderate or severe heart failure (NYHA class III/IV). PRECAUTIONS AND WARNINGS Infections: Patients must be monitored closely for infection before, during and for 5 months after cessation of treatment. Exercise caution when considering golimumab in patients with chronic infection or a history of recurrent infection including use of concomitant immunosuppressive therapy. Golimumab should not be given to patients with clinically important active infection. Patients should be advised of the potential risk factors. Bacterial infections (including sepsis and pneumonia), mycobacterial (including TB), invasive fungal and opportunistic infections, including fatalities, have been reported. The invasive fungal infection should be suspected if they develop a serious systemic illness. There was a greater incidence of serious infections, including opportunistic infections and TB, in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg. Serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease, could predispose them to infection. There have been reports of active TB in patients receiving golimumab, including patients previously treated for latent TB. Patients should be evaluated for active or latent TB before golimumab treatment. All such tests should be recorded on the Patient Reminder Card provided with the product. If active TB is diagnosed, treatment with golimumab should not be initiated. If latent TB is diagnosed, treatment with anti-TB therapy must be initiated before initiation of golimumab. Patients on golimumab should be monitored closely for signs and symptoms of active TB and advised to seek medical advice if signs and/or symptoms of TB appear. Hepatitis B (HBV) reactivation: Reactivation of HBV occurred in patients receiving golimumab who were chronic carriers. Some cases had a fatal outcome. Patients should be tested for HBV infection before initiating treatment with golimumab Malignancies and lymphoproliferative disorders: Caution is advised when considering golimumab treatment in patients with history of malignancy or continuing treatment in patients who develop a malignancy, additional caution should be exercised in patients with increased risk for malignancy due to heavy smoking. A risk for the development of malignancies in children and adolescents cannot be excluded. Rare cases, usually fatal, of hepatosplenic T-cell lymphoma (HSTCL) have been reported, the majority of cases occurred in adolescent and young males nearly all on concomitant treatment with azathioprine (AZA) or 6-mercaptopurine (6–MP). The potential risk with the combination of AZA or 6-MP and golimumab should be carefully considered. A risk for the development for HSTCL in patients treated with TNF-blockers cannot be excluded. Colon dysplasia/carcinoma - Screen for dysplasia in all patients with UC who are at increased risk or had a prior history for dysplasia or colon carcinoma. In newly diagnosed dysplasia patients the risks and benefits of continued golimumab use should be carefully assessed. Melanoma and Merkel cell carcinoma (all TNF-blocking agents including golimumab) have been reported, periodic skin examination is recommended, particularly for

78 News

Key insights in precision diabetes medicine delivered in new report Professor John Nolan, executive committee member of the PMDI and Adjunct Professor in the Department of Clinical Medicine, Trinity College Dublin

Diabetes is a significant global health concern but there is no ‘one-size-fits-all’ approach to treatment. A new report published in Nature Medicine suggests the adoption of precision medicine in diabetes prevention, diagnosis, treatment, and prognosis.

Diabetes is a significant global health concern, impacting hundreds of millions of people worldwide. Its diversity of type and its many forms makes it difficult to treat. The heterogeneous nature of diabetes encompasses its various causes, clinical manifestations, and prognoses.

A new consensus report, published in Nature Medicine highlights how precision medicine aims to make meaningful strides towards improving the lives of people living with diabetes.

The report from an international collaboration of over 200 academics - including Trinity scientists – in 28 countries highlights opportunities for the immediate or near-term adoption of precision diabetes medicine in clinical practice, while also emphasising the critical knowledge gaps that are essential to address.

The collaboration, Precision Medicine in Diabetes Inititative (PMDI), produced the report, and its findings are supported by the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD) and the Novo Nordisk Foundation.

“It has involved a tremendous amount of work by many of the world’s experts in precision diabetes medicine,” says Professor John Nolan, executive committee member of the PMDI and Adjunct Professor in the Department of Clinical Medicine, Trinity College Dublin. “This is a major step forward in diabetes care. Accurate and precise diagnosis of the subtype of diabetes is key. Everything around planning for treatment

and prognosis relies on this.

Misdiagnosis is not uncommon,” he said.

Hopeful prospects Diabetes is categorised into several types: type 1 and type 2 diabetes being most prevalent, along with gestational diabetes, monogenic diabetes, and other rare forms of the disease. Diabetes poses a substantial risk of lifethreatening complications and premature death.

John Nolan defines precision medicine as: “an approach that uses person-level information to help minimise error in medical decisions and health recommendations”. The goal is to improve health outcomes, costeffectiveness, and health equity.

The application of precision medicine in diabetes prevention and care offers hopeful prospects for reducing complications and fatalities.

Key takeaways from the report • Clear progress in implementing precision diabetes medicine, shedding light on opportunities for its immediate or near-term clinical application. For instance, precision medicine plays an essential role in diagnosing and treating monogenic diabetes, thanks to major advancements in genetic testing.

• Precision medicine shows potential in managing gestational diabetes.

Notably, specific maternal characteristics have been identified as predictive factors for the success or failure of treatment; these include age, BMI, and a family history of diabetes. Moreover, evidence supports the notion that maternal variables such as BMI, insulin sensitivity, insulin secretion, and dyslipidaemia can contribute to more precise diagnostic assessments.

• In type 1 diabetes prevention, the report identifies genetic risk classification as one of the most promising areas for immediate clinical implementation. There is potential to provide immune interventions for those at highest risk of disease progression.

• Routine clinical features can help predict how well different types of drugs work when treating type 2 diabetes, and how this common form of diabetes can be sub-classified into more precise sub-types.

• While the consensus report highlights areas where precision medicine can have an impact in clinical practice, it also draws attention to research gaps and the need for improved research methods.

Collaborative Campaign for Diabetes Photographed at the TEST Campaign Launch to raise awareness of Type 1 Diatbetes and spotting the signs and symptoms.

The campaign is a collaboration of the Irish Childhood Diabetes National Register and Diabetes Ireland and is supported by Novo Nordisk Ltd. Pictured L-R: Jay Hickey, Eva and Danny Lee, Norah Casey and Professor Edna Roche (ICDNR)

A new collaborative campaign between Diabetes Ireland and the Irish Childhood Diabetes National Register, supported by Norah Casey, Professor Edna Roche, Consultant Paediatrician and Endocrinologist alongside diabetes advocates Eva Lee and her son Danny and Jay Hickey aims to raise aims to raise awareness among the general public about the symptoms of Type 1 diabetes,

equipping individuals to recognise these signs early, seek help and avoid the development of Diabetic Ketoacidosis (DKA).

A delay in the diagnosis of Type 1 diabetes can quickly lead to a life-threatening complication called Diabetic Ketoacidosis or in short DKA. Early recognition of the symptoms and early treatment can prevent the development of DKA.

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

Type 1 diabetes can affect individuals of all ages. It is estimated that around 0.6% of the Irish population (30,895 people) are diagnosed with Type 1 diabetes with numerous adults receiving Type 1 diabetes diagnosis each month.

A very high proportion of children present with DKA at the time of diagnosis of their diabetes with 43% or more than 4 in 10 children having DKA at the time of Diabetes diagnosis and this number has been increasing since 2016.

Children in Ireland have the 10th highest reported incidence of Type 1 diabetes in the world.

The rate of new-onset type 1 diabetes in Irish children and young people is 37.6 cases/100,000/year which is very high. In the period 2019 to 2021, the rate has increased by 21% (or 10% per annum). On average 7 children and teenagers are diagnosed each week with Type 1 diabetes in Ireland.

Delays in the diagnosis of adults with Type 1 diabetes is also an ongoing problem in Ireland. In a recent Diabetes Ireland survey on “Experiencing, Accessing and Using Diabetes Health Services by people with diabetes” 41% of adults living with Type 1 diabetes reported having DKA at the time of diagnosis. Unfortunately, Type 1 diabetes is sometimes not considered as a primary diagnosis when symptoms first appear in adults.

80 Clinical R&D EUROPEAN COMMISSION APPROVES TALVEY® (TALQUETAMAB), JANSSEN’S NOVEL BISPECIFIC THERAPY FOR THE TREATMENT OF PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA The Janssen Pharmaceutical Companies of Johnson & Johnson, has announced that the European Commission (EC) has granted conditional marketing authorisation (CMA) of TALVEY® (talquetamab), as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.1 Talquetamab is a bispecific T-cell engaging antibody that binds to CD3, on the surface of T-cells, and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel target expressed on the surface of multiple myeloma cells and hard keratinised tissues, with minimal to no expression detected on B-cells and B-cell precursors.1 Talquetamab is approved as a weekly (QW) or biweekly (Q2W) subcutaneous (SC) injection, after an initial step-up phase.1 Dr Patrick Hayden, Consultant Haematologist and clinical lead for the myeloma service, at St. James’s Hospital said: “Patients with relapsed and refractory multiple myeloma typically experience frequent changes of treatment, short remissions and poor outcomes.3 Every patient’s disease is unique and requires a treatment strategy tailored to their specific needs. The approval of talquetamab represents an important advance for patients living with this difficult-to-treat blood cancer, as this novel compound has a new cellular target called GPRC5D. This approach has been shown to deliver deep responses in patients with advanced myeloma, many of whom were heavily pre-treated.”

The CMA was supported by positive results from the Phase 1/2 MonumenTAL-1 study (Phase 1: NCT03399799; Phase 2: NCT04634552), evaluating the safety and efficacy of talquetamab in patients with RRMM.4,5 The latest data from the study were recently presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (2-6 June, Chicago) and the 2023 European Haematology Association (EHA) Congress (8-11 June, Frankfurt).

Dr Thorsten Giesecke, General Manager, Commercial Business,

Janssen Sciences Ireland UC, said: “Talquetamab’s approval reinforces our focus on strengthening our multiple myeloma offering by investing in cutting-edge research that will help us continue to improve patient outcomes and importantly, their quality of life. Once available in Ireland, Talquetamab will expand the range of therapeutic options available to clinicians when treating patients with advanced multiple myeloma, offering them flexibility for optimising treatment protocols. Janssen’s legacy in innovation and the development of treatments for multiple myeloma spans more than two decades and we are committed to delivering therapeutics which have the potential to transform clinical outcomes for Irish patients.”

Patients in the study (0.8 mg/ kg Q2W: n=145; 0.4 mg/kg QW: n=143) had received a median of five (range, 2-17) prior lines of therapy and showed meaningful overall response rates (ORR) across both doses. With a median follow-up of 12.7 months, 71.7 percent (95 percent Confidence Interval [CI], 63.7-78.9) of responseevaluable patients treated at the 0.8 mg/kg Q2W dose achieved a response, 60.8 percent achieved a very good partial response (VGPR) or better and 38.7 percent achieved a complete response (CR) or better.1 With a median follow-up of 18.8 months, 74.1 percent (95 percent CI, 66.1-81.1) of response-evaluable patients treated with the 0.4 mg/kg QW dose achieved a response, 59.5 percent achieved a VGPR or better and 33.6 percent achieved a CR or better.1 Responses were durable with a median duration of response not reached (95 percent CI, 13-Not Estimable [NE]) in the 0.8 mg/kg Q2W dose group and 9.5 months (95 percent CI, 6.7-13.3) in the 0.4 mg/kg QW dose group.1 An estimated 76.3 percent and 51.5 percent of patients maintained a response for at least nine months at the 0.8 mg/kg Q2W and 0.4 mg/kg QW doses, respectively.1 The MonumenTAL-1 study also included 51 patients with prior T-cell redirection therapy.2 Patients had received a median of five (315) prior lines of therapy, including prior exposure to a bispecific antibody (35.3 percent), CAR-T cell therapy (70.6 percent) or both (six percent).2 With a median duration of follow-up of 14.8 months, 64.7 percent of patients achieved a response, 54.9 percent achieved a VGPR or better and 35.3 percent achieved a CR or better.2 Median duration of response was 11.9 months (95 percent CI, 4.8-NE) and the 12-month overall survival rate was 62.9 percent.2

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

The most common adverse events (AEs) observed in the study were cytokine release syndrome (CRS; 77 percent, 1.5 percent Grade 3 or 4), dysgeusia (72 percent, all Grade 1 or 2), hypogammaglobulinaemia (67 percent, all Grade 1 or 2) and nail disorders (56 percent, all Grade 1 or 2).1 In addition, 40 percent of patients experienced weight loss, including 3.2 percent with Grade 3 or 4 weight loss.1 The most common infections were upper respiratory tract infection (29 percent, 2.1 percent Grade 3 or 4) and COVID-19 (19 percent, 2.9 percent Grade 3 or 4).1 Neurologic toxicities were reported in 29 percent of patients, including immune effector cell-associated neurotoxicity syndrome (ICANS; 10 percent, 2.3 percent Grade 3 or 4).1 Adverse reactions leading to treatment discontinuation were mainly due to ICANS (1.1 percent) and weight loss (0.9 percent).1 The EC approval follows the U.S. Food and Drug Administration (FDA) approval of talquetamab for the treatment of adult patients with relapsed or refractory multiple myeloma who received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, in August 2023.

‘GETTING TO KNOW WHAT MATTERS TO ME’ COMMUNICATIONS PASSPORT LAUNCHED IN DONEGAL Letterkenny University Hospital and Community Healthcare Cavan, Donegal, Leitrim, Monaghan, Sligo are pleased to present the new ‘Getting to know what matters to me’ communication passport for people living with dementia.

National and international research confirms that admission to an acute hospital can be distressing and disorientating for a person living with dementia. A patient communication passport is a recommended formal system to collect information pertinent to caring for the person living with dementia and should be routinely used to improve the provision of person-centred care (Irish National Audit on Dementia (INAD-2, 2019).

This document supports a person who is receiving professional care, who cannot easily share information about themselves and who may have specific needs or preferences. A person living with dementia may require enhanced care to support their stay in hospital. The person along with their family or carers are invited to record information in the communication passport, for example; likes and dislikes, their background, the important people or places in the person's life and their normal routines and abilities.

The document helps hospital staff to get to know and better understand the person in their care and how best to respond to their needs. It is kept at the patient’s bedside so it is readily accessible to all staff. It should travel with the person and be available for use when the person is experiencing any episode of care.

The Registered Advanced Nurse Practitioner (RANP) Service for Older Person Care in Letterkenny University Hospital (LUH) decided to introduce the ‘Getting to know what matters to me’ communication document as a quality improvement initiative. This was linked with the introduction locally of the national integrated care dementia pathways and acute hospital delirium pathways.

Interdisciplinary colleagues from LUH and community services reviewed national and international document versions and adapted one document for use, countywide. The nurse practitioner’s also met with a person living with dementia who felt very strongly that ‘it was really needed’ and expressed that we ‘need the voice of the person clearly documented’.

Members of the Alzheimer Society Ireland supporting the launch From left: Dawn Thompson, Dementia Advisor – Donegal; Noreen Furey, Homecare Coordinator – Donegal; Aine McColgan, Daycare at Home Coordinator – Donegal; Carol Molloy, Operations Manager for the Northwest and Northeast

81 Alzheimer Scotland and Connolly Hospital kindly granted permission to adapt their ‘Getting to know me’ document with funding supported by the local Nursing and Midwifery Planning and Development Unit.

The name of the document also supports the HSE quality initiative ‘What Matters to You’ reflecting that the person is central in quality care.

Through the Integrated Care Programme for Older Persons (ICPOP) Donegal Dementia Work Stream, discussions were had on how to build awareness and consistency of the use of this document across all services that support people living with dementia. It was agreed that the use of the ‘Getting to know what matters to me’ communication passport would be promoted and used by the Older Persons Services, Community Health Network, ALONE, Alzheimer’s Society of Ireland and Memory Technology Resource Room services.

Registered Advanced Nurse Practitioner’s Graceann O’Donnell said: “We have seen the positive benefits of using this document in hospital. One example of how the document worked well was when staff reported that one of their patients with dementia was declining to get up in the morning or eat breakfast. When the family completed the ‘Getting to know what matters to me’ document it was evident that the gentleman ‘’never got up before 12’’ and ‘’never liked porridge’’. This information informed staff to leave care till later in the morning and provide an alternative breakfast choice.”

“These are very simple, yet very effective ways to improve the person’s hospital care experience and prevent further distress,” added fellow Registered Advanced Nurse Practitioner Olivia Harte.

Dawn Thompson, The Alzheimer Society of Ireland Dementia Adviser for Donegal North & East said, "It brings me great joy to see the Launch of the "Getting to Know What Matters to Me" communication passport. The ASI ensures that the voice of people living with Dementia is present in their care, and this document will allow people with Dementia the ability to get the care they need in unfamiliar situations."

Sean Murphy, Hospital Manager of LUH praised staff for rolling out the initiative.

“This fantastic new initiative focuses on driving innovation and further education to benefit our patients. It is important that we have greater supports in place to ease the journey through our hospital for our patients. Ensuring

we have processes to assist in meeting the needs of our patients is a priority for the hospital.” he added.

The passport is available for download at: https://www.saolta. ie/documents/luh-getting-knowwhat-matters-me IRISH BUSINESSMAN LEADS IRISH AMERICAN COMPANY INTO THE BATTLEFIELD Irish entrepreneur Richard Meehan has led the Boston based company Velico in securing a £4.9m (¤5.7m) contract with the UK Armed Forces and the NHS to support the commencement of clinical trials using the company’s unique development of spray dried plasma. Velico’s spray dried plasma hydrates within minutes and will play a vital role in reducing the number of preventable deaths from bleeding. The company’s solution has been designed for use in life saving roles.

Businessman Meehan joined Velico in 2021 as CEO and President.

Meehan describes Velico as a restart-up and commenced refocusing the company’s direction at delivering spray dried plasma solutions to critical front line services. The company is partially funded by BARDA (U.S Government Agency) and over $100m has been invested to date to develop this technology. In late 2022, Velico began a Phase I safety study for their Frontline On Demand Plasma (ODP) spray demand plasma product in a multi-centre, dose escalation clinical trial.

Richard went onto say, “Our company is laser focused on providing a spray dried plasma solution and committed to working with front line heroes in A&E hospitals, paramedics, and military personnel. This summers’ announcement allows us to accelerate our clinical trials in the UK with our Frontline ODP system.

Plasma has been used since World War II to reduce preventable deaths, and it has taken until now for a decentralised production system to be developed.”

Commenting on this announcement Richard said, “Plasma plays a key role in the prevention of trauma-induced coagulopathy.

Dried plasma has been a much sought-after goal for over two decades now and this trial marks a significant milestone in our mission to provide a lifesaving product for the medical and emergency response community.”

During this summer, the UK Ministry of Defence confirmed support for Velico trials to rapidly advance its “Blood Far Forward Programme” which aims to deliver

Pictured is CEO Richard Meehan of Velico alongside healthcare professionals in a Velico facility in Boston

plasma within 30 minutes to injured personnel.

Velico’s mission is to develop a suite of lifesaving, blood-based technologies and products to improve instant access to rapid transfusion at a critical stage of care.

Velico is a private, clinical-stage medical technology company headquartered in Beverly, Massachusetts, committed to the mission to dramatically reduce the number of preventable deaths caused by bleeding. Lead by an Irish American management team, Velico have just opened an office in Dublin to house their International division.

SANOFI SUPPORTING VULNERABLE COMMUNITIES AS PART OF COMMITMENT TO SOCIAL IMPACT AND FIGHT AGAINST CLIMATE CHANGE As global leaders gather at the United Nations’ 78th General Assembly, Sanofi is delivering vital support to communities beset by climate turbulence and by unmet medical needs. These critical initiatives come as the global healthcare company confirms its commitment to positively impact society by tackling climate change and its consequences for human health.

Ramping up adaptation efforts and initiatives to address the impact of climate change on the health of vulnerable communities becomes increasingly critical. Through Foundation S, Sanofi’s philanthropic organization, the company is strengthening locally led adaptation and health resilience programs for vulnerable communities impacted by climate change. Foundation S is today pledging nearly EUR 40 million through 2030 to support these efforts.

Paul Hudson, Chief Executive Officer, Sanofi said, “Since 2015 and COP21, where Sanofi was the first and only pharmaceutical

company discussing climate change and its impact on human health, we have been making strides to reduce the emissions of our supply chain and minimize the impact our products have on the environment. As we build our road to carbon neutrality by 2030, we also want to help address the broader impacts of climate change on the health of populations by teaming up with all stakeholders. By working with governments, health professionals, patient groups, regulators we can accelerate the decarbonization of healthcare systems, and by expanding our investments in the development of adaptation solutions for climate vulnerable communities. All our company commitments are rooted in concrete, transparent actions and driven by the greater sense of responsibility of playing our part in the global adaptation and fight against climate change.”

Sanofi starts in its own ‘climate’ backyard In line with its objective to get to carbon neutrality by 2030, Sanofi is advancing a holistic, companywide ambition to minimize the environmental impact of its products and activities, across its value chain, while strengthening resilience to environmental changes. To support its strategy, Sanofi plans to invest over EUR 450 million through 2030. These investments notably support company programs on energy efficiency and decarbonization of energy supplies, as well as resource circularity - reduce, reuse, recycle and recover - and reduction of natural resource extraction for water for instance.

Committed to the United Nation’s Race to Zero initiative, the company is building the road to carbon neutrality across all scopes of emissions by 2030, and net zero greenhouse gas emissions by 2045, five years earlier than

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

82 Clinical R&D previous targets. By the end of 2022, greenhouse gas emission had decreased 29% compared to 2019 in scopes 1 & 2 and by 7% in scope 3. In addition, the company has taken an end-to-end approach to reduce the environmental footprint of its products. For example, by 2027, the use of plastic in blister packs for all vaccines will be eliminated. Today, the company is at 33%. Also, 62% of electricity supplied on corporate sites is renewable with a target of 100% by 2030. Sanofi’s latest state-of-theart facilities, such as its Evolutive Facilities of Neuville-sur-Saône in southern France and in Singapore, both set to open in 2025, are carbon-neutral by design, with zero landfilling and 100% of the waste recycled or recovered.

Several pilot programs have also been conducted to assess how Sanofi’s most innovative products can contribute to reducing emissions along the care pathway.

The programs, evaluating medicines and vaccines for RSV, atopic dermatitis, and flu, show that prevention, reduced hospitalizations, decreased outpatient visits and fewer patient consultations have a positive impact on CO2 emissions while improving patients’ health outcome. Additionally, a pilot program on the benefits of utilizing telemedicine for patients with atopic dermatitis showed reduced CO2 emission attributed to less frequent healthcare professionals’ visits while also improving patient comfort and outcomes. Sanofi will continue to implement pilot programs to advance data and understanding of the co-benefits of best-inclass therapies that can improve health outcomes while reducing greenhouse gas emissions.

vaccines, we double our impact to make our planet healthier.”

NEW CARE PATHWAY PROVIDES VITAL SUPPORTS FOR CARDIAC PATIENTS. Patients availing of the new hospital avoidance pathways for cardiac care in the West of Ireland have praised the enhances in care, as they mark World Heart Day, today September 27th.

The Enhanced Community Care pathway for Cardiology has been up and running since March 2023 in the West of Ireland under the joint governance of the Saolta University Health Care Group and Community Healthcare West.

Work carried out by the Galway City Hub has resulted in 300 patients being removed from the Galway University Hospitals wait list through a range of initiatives including list validation, a chest pain initiative, setting up of appointments at the hub instead of the hospital and the redirection of GUH hospital heart failure wait list to the hub.

“The ECC programme has been absolutely transformational for the care of patients with chronic cardiovascular disease. We have seen 298 new patients in the hub and had 1,300 clinical contacts since we started,” said Dr Susan Connolly, Cardiologist with UHG who also leads the cardiology service in the Galway City Integrated Care Hub. Through the work of the enhanced community care programme patients are being treated for their Dr Susan Connolly with her team and patient Noel Ridge at the Galway City Hub

Josep Catllà, Head of Corporate Affairs, Sanofi added, “Sustainability is at the core of Sanofi’s long-term strategy, and it is ingrained in our mindset and behaviors in everything we do.

Whether it’s about accelerating our environmental commitments, improving access to healthcare for vulnerable populations, or building a diverse, equitable and inclusive workplace, we’re driven by the ambition to make a sustainable positive impact for our people, our communities and society overall. This is why we are taking the initiative to help communities around the world to work towards the decarbonization of healthcare systems, which today account for more carbon emissions than air transport. By working with local governments and healthcare actors to significantly reduce those emissions, and by continuing our essential work in delivering firstand best-in-class medicines and

NOVEMBER 2023 • HPN | HOSPITALPROFESSIONALNEWS.IE

chronic heart disease closer to home. This is proving life changing for those now availing of the community based service.

Noel Ridge, a patient at the Galway Integrated Care Hub, where services are provided in an integrated fashion between GPs, practice nurses, community specialist teams and hospital specialist teams, shares how his experience has positively impacted his life: "I've had three heart attacks and been in the hospital nine times in the last 18 months.

But I've come through it.

“The support I receive at the hub provides great comfort because I'm not waiting for hospital appointments that are months or a year apart. If I don't feel well, I can call the hub right away and explain what's happening. Overall, visiting the hub is much more convenient as it is closer to home and appointments are scheduled at specific times, which reduces a lot of stress."

By all working together we make this journey much more manageable for our patients by ensuring they are only receiving appointments that are necessary.

“It’s not just about providing heart failure care, it’s about providing a holistic service that addresses all their needs in terms of being a cardiovascular patient and helping them live with the chronic disease but empowering them so that they can live with that disease,” added Dr Connolly.

Dr John Lally, GP in Galway city described the Enhanced Community Care programme as a ‘game-changer’ for care.

“We are now able to send our patients to community based services for both their diagnostics and their clinical opinion,” he added.

For more on the Cardiology care services in action please see: https://youtu.be/ryLOd426V-E

Dr Connolly added: “One of the main benefits we hear from patients is that they now feel they have a safety net. With the Chronic Disease Management service we meet these patients in hospital and establish the link with the community service.”

NEW SURGICAL HUB FOR GALWAY

Two in five patients in Ireland present with more than one chronic conditions, which traditionally saw each patient attending a wide range of different hospital services. This care is now streamlined in the hub for patients with multiple conditions.

The hub, on the grounds of Merlin Park University Hospital will provide a significant uplift in surgical capacity for the region. It will reduce waiting times for day case procedures by significantly increasing the capacity for elective day case surgery in a dedicated facility.

“We hold regular multi-disciplinary meetings with colleagues across diabetes and nephrology, [who treat chronic kidney problems].

The Saolta University Health Care Group and Galway University Hospitals welcome the progress in developing a new surgical hub in the city.

The three storey surgical hub will consist of four operating theatres (two of which will be commissioned initially), each with scrub room, prep room, anaesthetic room, dirty utility room.

It will also provide two minor procedure rooms, a preassessment area, pre-op preparation area, a reception and waiting area, a recovery area and discharge lounge.

The hub will allow greater access to a range of specialities including dermatology, ENT, Ophthalmology, Oral and Maxillofacial, plastics, urology, vascular and gynaecology.

The Surgical Hub will provide regional capacity across Saolta, under the governance of University Hospital Galway surgical/ perioperative directorate as the local Model 4 Hospital.

Welcoming the progress, Tony Canavan, CEO of the Saolta Group said getting the green light to progress the build was extremely significant.

83 “This surgical hub is a significant step forward in our plans to develop more capacity for the entire region. We have a vision for our health services which will lead to better health outcomes for our communities,” he added.

In granting planning permission for the hub, Galway City Council has also granted the provision of a new bus stop to be located adjacent to the proposed development along with 108 carparking spaces which will further improve patient experience.

Ann Cosgrove, Chief Operations Office with Saolta added: “This surgical hub represents a vital and priority expansion of surgical facilities at a regional level. This designated standalone day case facility will enable the Saolta Group to significantly reduce its waiting lists. It will ensure that all elective care is scheduled and not impacted by emergency or acute patients from across the Saolta region.”

Construction of the Surgical Hub in Galway is due to commence later this year and is due to be operational in early 2025. A tender process has now commenced.

ABBVIE ESTABLISHES NEW ¤23 MILLION EUROPEAN MANUFACTURING SERVICES HUB IN NORTH DUBLIN

The company’s manufacturing presence in Ireland dates back to 1974 and now includes significant operations at six separate Irish locations in Cork, Sligo, Mayo and Dublin. The expanded Clonshaugh site, which celebrates its 30th anniversary next year, now employs close to 400 people.

AbbVie (NYSE: ABBV), a global research-driven biopharmaceutical company with a significant presence across six Irish locations, today opened a new ¤23 million European services hub in Clonshaugh, North Dublin.

The state-of-the-art facility spans two sites within the IDA Business Park in Clonshaugh and serves as an international base for a range of supply chain, manufacturing and engineering services, supporting AbbVie’s global network.

The creation of the new hub – which will support Irish manufacturing plants and company Operations in other European countries including Germany, Italy and the Netherlands – is the latest confirmation of Ireland’s strategic importance within AbbVie’s footprint.

The development is compatible with the short, medium and long term plans for the Merlin Park site.

It will also help reduce congestion on the UHG site to deal with unscheduled care activity and inpatient scheduled care.

AbbVie, which was formed in 2013 following a separation from Abbott, has consistently and significantly invested in Ireland over the course of the past decade. Activities have included the acquisition of Allergan and its significant Irish operations in 2020. Today’s official opening follows a ¤60 million investment in Cork last year and brings total AbbVie investments in Ireland over the past ten years to more than ¤430 million.

Azita Saleki-Gerhardt, AbbVie EVP, Chief Operations Officer, said, "Ireland plays a critical role in supporting AbbVie's international operations and I was delighted

“The surgical hub is a key enabler for the four core infrastructure needs identified by the Saolta Group for the GUH sites. However, it is only the delivery of all four components that will address the infrastructural challenges of the Model 4 Hospital for the patients of the West / North West Region.

both secondary care for the Galway catchment population and tertiary care for the entire West / North West region.

“The progression of the new permanent ED and Women’s and Children’s block, a Cancer Centre and ward block and replacement laboratory at the UHG site and the progression of an elective hospital in Merlin Park remain key priorities,” added Mr Canavan.

3. Cancer Centre and 200 bed ward block

These key developments are fundamental to address the demands for GUH in providing

2. Laboratory Replacement facilities Development

4. Elective Hospital on the Merlin Park site The significant interdependencies between the above programmes mean the delivery of all components are needed to address the key infrastructural challenges of the Model 4 Hospital.

Simon Coveney TD, Minister for Enterprise, Trade and Employment with Global Chief Operations Officer, Azita Saleki-Gerhardt

to join Minister Coveney, IDA leadership and AbbVie employees to officially open our redeveloped site in Clonshaugh. Today's grand opening represents one of AbbVie's many investments in its Ireland-based operations and a continuation of our longstanding partnership with the Irish government. Our new AbbVie North Dublin (AND) facility will be a key node in AbbVie's global Operations network, serving as a European hub bringing together our Dublin-based supply chain, engineering, quality assurance and manufacturing teams for the first time.

“Built with our employees and the future in mind, AbbVie North Dublin features new, improved collaboration spaces and amenities designed to significantly elevate our employees' experiences and make this facility a great place to work for many years to come."

AbbVie Site Director, Marco Froehlich, and Global Chief Operations Officer, Azita Saleki-Gerhardt, with Simon Coveney TD, Minister for Enterprise, Trade and Employment and Michael Lohan, CEO IDA Ireland, at the launch of AbbVie’s new ¤23 million European manufacturing services hub in North Dublin

1. The Emergency Department with Women’s & Children’s Block

CEO of IDA Ireland, Michael Lohan added, ‘’The opening of this new European Services hub is a wonderful addition to the

six locations across Ireland that AbbVie currently operate in. This is a continued endorsement in Ireland as a strategic location for biopharmaceutical investment and one we are very proud of. This new hub will place Ireland at the centre of the European supply chain.

Since AbbVie arrived in Ireland in 1974, the country has continued to grow as a global hub for life sciences and be at the forefront of innovation. IDA is delighted to be a longstanding partner with AbbVie now and into the future.”

AbbVie has been recognised as one of the Best Large Workplaces in Ireland for the past ten years and was also named one of the Best Workplaces for Women for the fifth year in a row.

The company won the ‘Sustainable Business Team’ accolade at the recent 2023 Sustainable Business Awards and was also awarded the ‘Best Use of CSR’ title at the 2023 Life Science Industry Awards in recognition of its’ Week of Possibilities volunteering initiative.

HOSPITALPROFESSIONALNEWS.IE | HPN • NOVEMBER 2023

This is a promotional advertisement from LEO Pharma for IE healthcare professionals.

For the treatment of moderate to severe atopic dermatitis in adult and adolescent patients 12 years and older who are candidates for systemic therapy1

TIME TO PRESS PLAY Not an actual patient. For illustrative purposes only. Individual results may vary.

Adtralza®

The first licensed biologic that inhibits IL-13 alone,1,2 a key driver of atopic dermatitis signs and symptoms.3 Learn more at www.adtralza.ie Prescribing Information for Adtralza® (tralokinumab) 150 mg solution for injection in pre-filled syringe Please refer to the full Summary of Product Characteristics (SmPC) (www.medicines.ie) before prescribing.

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. Indications: Treatment of moderate-tosevere atopic dermatitis in adult and adolescent patients 12 years and older who are candidates for systemic therapy. Active ingredients: Each pre-filled syringe contains 150 mg of tralokinumab in 1 mL solution (150 mg/mL). Dosage and administration: Posology: The recommended dose of tralokinumab for adult and adolescent patients 12 years and older is an initial dose of 600 mg (four 150 mg injections) followed by 300 mg (two 150 mg injections) administered every other week as subcutaneous injection. Every fourth week dosing may be considered for patients who achieve clear or almost clear skin after 16 weeks of treatment. Consideration should be given to discontinuing treatment in patients who have shown no response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve further with continued treatment every other week beyond 16 weeks. Tralokinumab can be used with or without topical corticosteroids. The use of topical corticosteroids, when appropriate, may provide an additional effect to the overall efficacy of tralokinumab.

Topical calcineurin inhibitors may be used, but should be reserved for problem areas only, such as the face, neck, intertriginous and genital areas. If a dose is missed, the dose should be administered as soon as possible and then dosing should be resumed at the regular scheduled time. No dose adjustment is recommended for elderly patients, patients with renal impairment or patients with hepatic impairment.

For patients with high body weight (>100 kg), who achieve clear or almost clear skin after 16 weeks of treatment, reducing the dosage to every fourth week might not be appropriate. The safety and efficacy of tralokinumab in children below the age of 12 years have not yet been established. Method of administration: Subcutaneous use.

The pre-filled syringe should not be shaken. After removing the pre-filled syringes from the refrigerator, they should be allowed to reach room temperature by waiting for 30 minutes before injecting. Tralokinumab is administered by subcutaneous injection into the thigh or abdomen, except the 5 cm around the navel. If somebody else administers the injection, the upper arm can also be used. For the initial 600 mg dose, four 150 mg tralokinumab injections should be administered consecutively in different injection

sites within the same body area. It is recommended to rotate the injection site with each dose. Tralokinumab should not be injected into skin that is tender, damaged or has bruises or scars. A patient may self-inject tralokinumab or the patient’s caregiver may administer tralokinumab if their healthcare professional determines that this is appropriate. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Precautions and warnings: If a systemic hypersensitivity reaction (immediate or delayed) occurs, administration of tralokinumab should be discontinued and appropriate therapy initiated. Patients treated with tralokinumab who develop conjunctivitis that does not resolve following standard treatment should undergo ophthalmological examination. Patients with pre-existing helminth infections should be treated before initiating treatment with tralokinumab. If patients become infected while receiving tralokinumab and do not respond to antihelminth treatment, treatment with tralokinumab should be discontinued until infection resolves. Live and live attenuated vaccines should not be given concurrently with tralokinumab. Fertility, pregnancy and lactation: There is limited data from the use of tralokinumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of tralokinumab during pregnancy. It is unknown whether tralokinumab is excreted in human milk or absorbed systemically after ingestion. Animal studies did not show any effects on male and female reproductive organs and on sperm count, motility and morphology.

Side effects: Very common (≥1/10): Upper respiratory tract infections. Common (≥1/100 to <1/10): conjunctivitis, conjunctivitis allergic, eosinophilia, injection site reaction. Uncommon (≥1/1,000 to <1/100): keratitis. Precautions for storage: Store in a refrigerator (2°C-8°C). Do not freeze. Store in the original package in order to protect from light. Legal category: POM. Marketing authorisation number and holder: EU/1/21/1554/002. LEO Pharma A/S, Ballerup, Denmark. Last revised: October 2022 Reference number: REF-22407 Reporting of Suspected Adverse Reactions Adverse events should be reported.

Reporting forms and information can be obtained from: HPRA Pharmacovigilance, Website: www.hpra.ie Adverse events should also be reported to Drug Safety at LEO Pharma by calling +353 1 4908924 or e-mail medical-info.ie@leo-pharma.com

IL, interleukin.

References: 1. Adtralza® SPC. 2. Duggan S. Drugs 2021;81(14):1657–1663. 3. Bieber T. Allergy 2020;75:54–62.

Further information can be found in the Summary of Product Characteristics or from: LEO Pharma, Cashel Road, Dublin 12, Ireland.

E-mail: medical-info.ie@leo-pharma.com ® Registered trademark

Date of preparation: December 2022 IE/MAT-62263