HPN March 2024

HOSPITAL PROFESSIONAL NEWS IRELAND

HPN March 2024 Issue 118 HOSPITALPROFESSIONALNEWS.IE

Ireland’s Dedicated Hospital Professional Publication

IN THIS ISSUE:

Empowering people worldwide to live healthier at every stage of life

NEWS: Welcome for Critical Medicines List Page 4 RESEARCH: Potential of Biosimilar Medicines Page 9

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

ENDOCRINOLOGY FOCUS: Primary Liver Cancer Page 20 CPD: Osteoporosis Management Page 37 GASTROENTEROLOGY FOCUS: Obesity Therapy in IBD Patients Page 42

PROFILE: Ask the Expert Prof Carel le Roux Page 47 Viatris Newenham Court, Malahide Road, Dublin 17, Dublin, Ireland. Viatris.ie Job Code: CC-2023-001 Date of Preparation: July 2023 www.viatris.ie

This Publication is for Healthcare Professionals Only

EDUCATIONAL: Moderate to Severe Psoriasis Page 52

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

www.hospitalprofessionalnews.ie

March Issue Issue118

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Contents

Foreword

Professor Hannah McGee awarded Honorary Fellowship P4

Editor The HSE has published the 2024 National Service Plan following approval by the Minister for Health, Stephen Donnelly TD and the Minister for Children, Equality, Disability, Integration and Youth, Roderic O’Gorman TD. The National Plan was published just as Hospital Professional News was going to press.

Guaranteed Irish Pharmaceutical Forum P6 Lessons in Patient Safety: Hospital Pharmacist experience P10

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The National Service Plan (NSP 2024) outlines the health and social care services to be provided to the people of Ireland this year. The Government has allocated a budget of ¤23.5bn for this purpose, which is 4.6% above last year’s budget. Of this ¤23.5bn, ¤2.8bn has been provided by the Department of Children, Equality, Disability, Integration and Youth in respect of specialist disability services with a balance of ¤20.7bn provided by the Department of Health, which will allow for 683 new Whole Time Equivalent (WTE) for disability services and 2,268 WTEs for other health and social care services.

Link discovered between stress and gut virome P12 New medical pathway for home dialysis P14 Patient Safety Network announced P18

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• ¤162.8m investment in new service developments, including enhancing mental health and disability services

Recognising Brain Awareness Week P19

• ¤918.7m once-off funding • ¤834.7m to fund increased costs of providing the existing level of service

REGULARS

• Funding to support the implementation of the six new Health Regions

Endocrinology Focus: Ulcerative Colitis P26

The HSE’s focus for 2024 is to improve access to urgent and emergency care; prioritise waiting lists; continue to enhance mental health and disability services, and build on existing partnerships to develop and improve services.

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CPD: Osteoporosis P37 Endocrinology Focus: Gastric Cancer Screening P44

The April issue will carry further details. In other news this issue, The Guaranteed Irish Pharmaceutical Forum, sponsored by MSD, took place where insights were shared around the theme of "Innovation in the Community – Positioning Ireland to Deliver Best Patient Care."

Feature: Urge Urinary Incontinence P58 14

Clinical R&D: P62 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.

SALES EXECUTIVE Avril Boyd avril@hospitalprofessionalnews.ie SALES & TRAINING MANAGER Sibongile Mude s.mude@hospitalprofessionalnews.ie CONTRIBUTORS

GROUP DIRECTOR Natalie Maginnis n-maginnis@btconnect.com

Pauline Dunne | Márcia Carvalho Miriam Forde | Margaret Mullett Michele O’Brien | Ayisha Lightbourne Kate Parry | Werd Al-Najim Dr Charlene Deane | Dr Orlaith Kelly Tammy Strickland | Dr Cathal O’Connor Professor Colm O’Morain Linda Asaad Ghazal Professor Orla Hardiman Professor Humphrey J. O’Connor Professor Moira O’Brien Professor Molly Byrne Professor Andrew W. Murphy Professor Sharleen O’Reilly

EDITOR Kelly Jo Eastwood

DESIGN DIRECTOR Ian Stoddart Design

EDITORIAL danielle@hospitalprofessionalnews.ie

HOSPITALPROFESSIONALNEWS.IE

PUBLISHER IPN Communications Ireland Ltd Clifton House, Lower Fitzwilliam Street, Dublin 2 (01) 669 0562

ACCOUNTS Fiona Bothwell cs.ipn@btconnect.com

It includes:

@HospitalProNews HospitalProfessionalNews

This annual event featured an industry leading line-up within the pharmaceutical sector. The panel discussion featured industry thought leaders Mairéad McCaul Managing Director of MSD Ireland, Shane Ryan General Manager Takeda Ireland and Vice-President of IPHA, Emily Kelly, Community Pharmacist at McCauley Pharmacy, Deputy Colm Burke, T.D., and Angela Clayton-Lea, Acting CEO of Cancer Trials Ireland. Turn to page 6 to read more about this event. On page 9, we highlight a summary report from the 7th Biosimilar Multistakeholder Event which took place recently in Brussels. The event was opened by Rainer Becker, who welcomed the attendees and highlighted the opportunities biosimilars can bring, but also the remaining challenges for health systems to fully exploit the savings from biosimilar competition. Our Special Focus for this month is on Endocrinology and Gastroenterology and we have a wealth of clinically contributed articles across both these fields including Obesity Therapy in patients with Inflammatory Bowel Disease, Developments in Gastric Cancer Screening and Ulcerative Colitis. I hope you enjoy the issue.

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

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News

Hospital Pharmacists welcome Critical Medicine List The European Commission has published today the first Union list of critical medicines, together with the European Medicines Agency (EMA) and the Member States' Heads of Medicines Agencies (HMA). The publication follows the commitment made in the Commission's Communication on addressing medicine shortages in the EU to accelerate the work on this list, originally announced in the EU's pharmaceutical reform proposal. It is an important part of the EU's efforts under the European Health Union to ensure patients have the medicines they need, by fostering the security of supply of critical medicines and preventing shortages from occurring. It is also part of the EU's efforts to improve its resilience and strategic autonomy in the face of geopolitical and unexpected challenges.

A medicine is listed as critical when it is essential to ensure the provision and the continuity of quality healthcare, and to guarantee a high level of public health protection in Europe. This first Union critical medicines list contains more than 200 active substances used in human medicines, which are considered essential in the EU/EEA. The inclusion on this list is not an indication that a medicine is likely to experience a shortage in the near future. Rather, it signifies the critical importance of averting shortages for these specific medicines, as its unavailability could cause significant harm to patients and pose substantial challenges to health systems. The list was developed alongside with the EMA and all

EU Member States. It follows a strict methodology to assess criticality, initially developed during the Commission's Structured dialogue on security of medicines supply launched under the Pharmaceutical Strategy, which was conducted in 2021 and drew lessons from the COVID-19 pandemic. Key stakeholder groups, including patients and healthcare professional organisations and industry associations, were consulted. The European Association of Hospital Pharmacists has welcomed the first version of the Union List of Critical Medicines. However, since the list is based on the European Commission Structured Dialogue and after consulting only a limited number of EU countries, the identified criteria of criticality can be interpreted

very differently and may produce divergent results depending on the country that applies them. EAHP believes that all relevant stakeholders should be involved and should discuss how this list may be improved and what is the best way to carry out the criticality assessment. EAHP supports a common criticality assessment model involving representatives of healthcare professionals, patients and national competent authorities. EAHP disagrees with the definition of three criticality risk levels, which makes the identification of critical medicines more complex. Therefore, keeping only the distinction between “critical” and “non-critical” medicines should be pursued, avoiding the medium risk category.

Honorary Fellowship for Professor McGee Citation reader Professor Deborah McNamara, RCSI Vice-President; Honorary Fellowship recipient Professor Hannah McGee, RCSI Deputy Vice Chancellor for Academic Affairs; and Professor Laura Viani, RCSI President

Professor Hannah McGee, Deputy Vice Chancellor for Academic Affairs at RCSI and Michael J. Dowling, President and CEO of Northwell Health were awarded Honorary Fellowships of the Royal College of Surgeons in Ireland at the 2024 Charter Day Dinner. Honorary Fellowship of RCSI is the highest distinction the College bestows, recognising outstanding achievement in surgery as well

as outstanding achievements in other areas. Professor Hannah McGee has made an outstanding contribution to RCSI, holding roles as professor of psychology and later head of department. In 2010 she was appointed dean and since 2021 she has held the office of Deputy Vice Chancellor for Academic Affairs (DVCAA). In 2010, she led the team that secured

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independent degree-awarding status for RCSI. This landmark achievement in RCSI’s history led directly to RCSI being granted University status in 2019. Her achievements as dean and DVCAA include major curricular reform and establishment of a School of Population Health. Throughout her stellar research career exploring psychosocial aspects of health-related quality of life, Professor McGee published widely, is highly cited and has influenced national and international policy. Key achievements included her central role in establishment of the SPHeRE programme, a generational investment by the HRB in health services research,

and her authorship of the SAVI report, which gave a voice to some of the most vulnerable individuals in our country and retains an enduring influence on Irish society. She has held all key leadership roles in her discipline, including the presidencies of the Psychological Society of Ireland and the European Health Psychology Society. In recognition of her academic achievements, she was awarded a DSc from the National University of Ireland in 2015 and was elected to Membership of the Royal Irish Academy in 2021. Reading the citation for Professor McGee, Professor Deborah McNamara, Vice-President of RCSI said: “Professor McGee has made an outstanding contribution to RCSI. Her scholarship alone places her among RCSI’s top 20 researchers but the fact that this has been achieved while holding key leadership roles in our university is unparalleled. Perhaps her greatest contribution to health sciences is her commitment to developing future generations, our students and junior faculty. “She has been a most distinguished servant of RCSI and in accepting this Fellowship, she does us the great honour of allowing RCSI to continue this association in perpetuity.”

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Appointments for Institute for Clinical Trials World-leading research academic Professor Fidelma Dunne has been appointed Interim Director of the Institute for Clinical Trials at University of Galway.

Professor Fidelma Dunne and John Kilmartin

Professor Dunne has an extensive background in clinical trial management and is ranked number 1 in Ireland and number 6 in the world for her research into gestational diabetes. The University has also announced John Kilmartin, former VicePresident of Regulatory Affairs at Medtronic and an independent medtech regulatory expert, joins the Institute for Clinical Trials as Adjunct Professor. Mr Kilmartin has more than 30 years’ experience in the medtech industry, with a particular focus on the emerging regulatory and clinical frameworks in Europe. Professor Martin O’Donnell, Dean of the College of Medicine, Nursing and Health Sciences and Consultant Geriatrician at Saolta University Health Care Group, said, “We are honoured to have both Professor Fidelma Dunne and Mr John Kilmartin join the Institute for Clinical Trials. Their combined expertise in clinical trials, medical research and regulatory affairs

will significantly contribute to our mission of advancing impactful clinical research. They will help to advance our clinical research goals and will make meaningful contributions to healthcare outcomes.” Professor Dunne added, “Clinical trials in new medicines and devices are vital to improving the health of people living in Ireland and worldwide. Improving health also has economic and societal

benefits. Engaging in clinical trials allows patients in Ireland to receive new medicines and devices early. We have a track record of designing and delivering impactful clinical trials at University of Galway and I am delighted to lead the Institute for Clinical Trials which will have a pivotal role in further enhancing the clinical research landscape in Ireland.” Mr Kilmartin said, “The medtech industry is of huge importance to

Ireland and Europe for the benefit of our patients, health systems and society. I believe that the Institute for Clinical Trials at University of Galway can play a key role in helping to support innovation in medtech by strategically targeting barriers within the Irish ecosystem. It aims to strengthen and further promote growth in the medtech sector, expand treatment options for patients and ultimately contribute to the advancement of healthcare on a broader scale."

Cuts to Waiting List Funding The Irish Hospital Consultants Association (IHCA) says it is unacceptable that funding to tackle waiting lists is being cut in 2024 by ¤36 million (8%) compared with the allocation in 2023, despite record growth in demand for treatment. The waiting list for hospital treatment has increased for each of the past three months, reflecting the significant impact that increased presentations to Emergency Departments and the resulting cancellation of surgical procedures is having on our acute public hospitals this winter. The outpatient waiting list has also risen for the first time since August 2023, increasing by 6,650 in January alone. Consultants are urging the Government to increase funding and honour its pledge to provide treatment in 2024 to all clinically suitable patients waiting more

than three months on the inpatient and day case waiting list. The appeal comes as the latest National Treatment Purchase Fund (NTPF) figures released today reveal that 877,786 people were on some form of hospital waiting list at the end of January, including 86,288 patients awaiting inpatient or day case treatment. In last year’s Waiting List Action Plan, the NTPF made a commitment that patients waiting over three months for 20 highvolume procedures including cataract surgery and hip and knee replacements would receive an offer of treatment before the end of 2023. However separate new figures confirm that this target was missed. A further pledge was made last year to expand this list of procedures so that all clinically suitable patients waiting more

than three months on the inpatient and day case waiting list would be provided with treatment in the public or private systems in 2024. The IHCA warns that meeting this commitment will be a significant challenge given the reduction in waiting list funding from ¤443m in 2023 to ¤407m this year – a reduction of ¤36m or 8%. At the end of January approaching two-thirds of those on the inpatient/day case waiting list (52,718 or 61%) were waiting longer than three months for treatment, exceeding the Sláintecare maximum wait time targets recommended in the 2017 report. The Action Plan for 2023 set a target to reduce waiting lists for appointments and hospital treatment by 10% (-69,000) compared with the number waiting at the start of 2023. Despite treating significantly more patients

than planned last year, the three main waiting lists only decreased by a modest 3% in 2023 due to a higher-than-expected level of patient demand. Furthermore, this modest reduction would not have been achieved had it not been for the fact that 105,000 people were removed from hospital waiting lists in 2023 without treatment through an NTPF ‘validation’ process. Commenting on the most recent waiting list figures, IHCA President Professor Rob Landers, said, “Regrettably, in the short-term, waiting lists are likely to deteriorate further due to the cancellation of many outpatient appointments, inpatient admissions and day case procedures, including chemotherapy and dialysis, due to the record overcrowding we are currently experiencing at many hospitals.”

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Innovation in the Community Positioning Ireland to Deliver Best Patient Care The Guaranteed Irish Pharmaceutical Forum, sponsored by MSD, took place recently where insights were shared around the theme of "Innovation in the Community – Positioning Ireland to Deliver Best Patient Care". Mairéad McCaul, Managing Director, MSD Ireland, Deputy Colm Burke, T.D, Angela Clayton-Lea, Acting CEO of Cancer Trials Ireland, Shane Ryan, General Manager, Takeda Ireland/Vice President, IPHA and Emily Kelly, Community Pharmacist, McCauley Pharmacy. Pic Orla Murray/Coalesce

This annual event hosted by Guaranteed Irish featured an industry leading line-up within the pharmaceutical sector. The panel discussion featured industry thought leaders Mairéad McCaul Managing Director of MSD Ireland, Shane Ryan General Manager Takeda Ireland and Vice-President of IPHA, Emily Kelly, Community Pharmacist at McCauley Pharmacy, Deputy Colm Burke, T.D., and Angela Clayton-Lea, Acting CEO of Cancer Trials Ireland. Optimism reigned throughout panel discussions, looking to the future with hope and practical actions underway to ensure important improvements in data access and collaboration is prioritised. Mairéad McCaul, MD of MSD, spoke about the continued need for collaboration and trust between all stakeholders, similar to what was done during Covid 19 when processes were implemented with speed. The pharmaceutical industry is a significant employer with up to 40,000 people working in the sector in Ireland – a cornerstone of the Irish economy. While it was noted that Ireland has a good reputation for manufacturing, there is a renewed call to focus on enhancing the Research & Development positioning for Ireland and Europe to prevent a drift towards China and the US.

Data is Key The importance of data being at the centre for digital healthcare improvements was discussed. Progress in digital data technology will allow more innovation and access for patients to make informed choices with healthcare professionals. R&D is needed around technology to progress and transfer data to patients. Looking to the future, more wearable devices will feature to capture and share healthcare information. Shane Ryan commented, “From my perspective if you consider the future trends and the shift of healthcare towards the community and the progression of digital technology we're in really good place for patients. Also looking at current and future medicines many of those will have a digital component which will make them very compatible for community care so it's fantastic here today talking about this topic exchanging views and building a network.’’ Trials and Research Angela Clayton-Lea spoke about a number of important issues which are a focus for Cancer Trials Ireland (CTI) at present. The goal for the National Cancer strategy is to have 6% of cancer patients taking part in trials in the near future. Study types need to include more data from an all-Ireland perspective, using CTI as a central hub. Improved data collection

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processes are needed to reach this target. Angela commented, “Increasing focused collaboration between Pharmaceutical Industry and cancer clinical research for the benefit of patients is our main priority. We hope to make data collection processes a main priority this year.’’ Community Pharmacy Communication between all healthcare divisions is vital to provide interoperable health systems which will improve information sharing and access for patients. Emily Kelly, community pharmacist said, “We welcome the task force and commitment from Minister Donnelly for expanding the scope of practice of pharmacists within Community pharmacy. To make it operational we need access to sustainable funding for quality service across the state. Shared health records and a reduction in administration of government schemes would enable this to be expedited and the

role of the community pharmacy enhanced. At McCauleys we are all about solutions for patient health to live healthier lives. These advances would further what we already do for our patients.” Collaboration Deputy Colm Burke discussed the need for a coordinated way of working together with hospitals, the pharmaceutical industry, and universities. Funding is red taped for companies to invest in services to improve patient care. Deputy Burke stated, “The Pharmaceutical industry is a major contributor to the Irish economy with 9 out of 10 of the top companies with a base in Cork. I am committed to ensuring the much-needed funding can be accessed for R&D between all parties involved including universities, pharmaceutical companies and hospitals as we work together to one patient centric goal.” Finally, Mairéad McCaul, Managing Director of MSD Ireland Human Health, praised Guaranteed Irish, acknowledging the role the organisation plays in promoting Ireland and facilitating networking opportunities for likeminded industry experts and leaders to share ideas and create new key relationships.

Shane Ryan, General Manager, Takeda Ireland/Vice-President, IPHA and Emily Kelly, Community Pharmacist at McCauley Pharmacy. Pic Orla Murray/Coalesce

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HSE Approves Seven Life-enhancing Medicines Osteoporosis, antimicrobialresistant infections and several types of cancer are among the ailments that will be tackled by seven drugs newly approved by the HSE. These seven new life-enhancing drugs will be funded from the ¤20 million funding recently allocated for new medicines in 2024. Dr Colm Henry, Chief Clinical Officer, HSE, said, “These newly approved drugs will have a profound impact on those who need them. With these seven drugs, we hope to be able to continue to support people to live healthier, happier lives in the future. “The approved medicines will be available under the Community Drugs Schemes and other arrangements, ensuring equitable access for those whose treatment requires them. The HSE has a robust assessment in place for approving medicines, with decisions based on several factors, including clinical need, efficacy and effectiveness. Many

of the newly approved drugs are responding to a previously unmet need. They will target conditions that existing approved medications cannot treat, such as infections caused by multidrug-resistant (MDR) bacteria.” “Cefiderocol (Fetcroja®) has been approved for the treatment of adults who have antimicrobialresistant infections. In these cases, no other medication has been effective. Cefiderocol presents a new opportunity to treat extremely vulnerable patients, for whom medication options are limited. “Given the growing issue of antimicrobial resistance, it will be important to limit the use of this drug to cases that are otherwise beyond help,” Dr Henry explained. Postmenopausal women, with severe osteoporosis who have had a major osteoporotic fracture (within the previous year and who are at imminent risk of another fragility fracture) will benefit from the approval of Romosozumab (Evenity®).

There were approximately 32,000 new fragility fractures diagnosed in Ireland in 2019, with annual figures expected to increase to 51,000 by 2034 as Ireland’s population ages. Osteoporotic fractures are associated with substantial pain and disability; they can result in an older person needing long-term care and, can ultimately result in earlier deaths. "This reimbursement agreement will target a very specific, at-risk, subgroup of postmenopausal women," said Dr Henry. "It's a first-in-class medication and could prevent these women from requiring additional care. It's also been shown that severe fractures in older age can result in morbidity within one year. Providing these medications could have a significant benefit for this population in the future." Three medications [Osimertinib (Tagrisso®); Atezolizumab (Tecentriq®); and Atezolizumab (Tecentriq®)] to treat adults with non-small cell lung cancer (NSCLC) have also been approved. "NSCLC is known to have a

high rate of tumour recurrence post-surgery. However, these new medicines can prevent recurrence and potentially prolong a patient's chance of survival post-treatment," Dr Henry noted. Another group of vulnerable people to benefit from this round of approvals is transplant patients. “Transplant patients are immunosuppressed to reduce the risk of organ rejection. This, however, leaves them susceptible to other infections, such as cytomegalovirus (CMV). Maribavir (Livtencity®) treats CMV and will reduce the risk of infection and illness for patients.” Finally, through Ireland’s participation in the Beneluxa Initiative, a collaboration between Belgium, the Netherlands, Luxembourg, Austria, and Ireland, Atidasagene autotemcel (Libmeldy®) was approved to treat metachromatic leukodystrophy (MLD). MLD is a rare genetic disease and Libmeldy is a onetime therapy designed to correct this gene mutation.

New Pharmacy Guidebook Guidance for pharmacists to manage symptoms of iron deficiency anaemia (including supporting self-care) and to prevent the condition has been shared in a new handbook from the International Pharmaceutical Federation (FIP). “With the increasing role of pharmacists in the healthcare system, pharmacists can play a vital role in providing health information on the prevention and management of iron deficiency anaemia. It is, therefore, a pleasure to present this comprehensive handbook for

pharmacists to serve as a guiding resource. “This handbook was developed in response to the recommendations from a FIP roundtable report in 2022, which highlighted the increasing opportunity for pharmacists to contribute to achieving the World Health Organization’s target of reducing anaemia by 50% among women of reproductive age by 2025,” said FIP CEO Catherine Duggan. The handbook describes iron deficiency anaemia roles for pharmacists in community pharmacies, hospitals and research. It also provides the

knowledge needed to offer advice to special populations, such as children, non-pregnant women of reproductive age, pregnant individuals and breastfeeding mothers, elderly people with chronic diseases, and patients with chronic blood loss. Anaemia is a global public health concern, affecting individuals of all ages and demographic groups, with implications for health, morbidity and mortality. It stems from many factors, including diet, chronic illnesses, infections, hereditary blood disorders and other conditions related to blood loss and reduced

haemoglobin levels. While anaemia manifests as decreased haemoglobin or haematocrit levels, iron deficiency anaemia is the most prevalent type. The report adds, “In conclusion, this handbook serves as an invaluable resource for pharmacists in managing IDA, underpinning the importance of pharmacists’ role in screening, managing, treating, patient education and holistic self-care practices. It is recommended to accompany this handbook with further CPD and resources for other types of anaemia.”

PMI Raise over ¤10,000 for LauraLynn The Pharmaceutical Manufacturers Institute have raised an incredible ¤10,340 for LauraLynn. The money was raised at the annual PMI Christmas Lunch and this amount is the highest ever raised at the charity event. Fiona O’Hara, President and Fiona Dunphy, Commercial Manager with the PMI recently went over to LauraLynn and met with their CEO, Kerry McLaverty, for a cheque presentation. LauraLynn's mission is to provide a Community of Care that delivers evidence-based, personalised services to children with palliative care needs, complex care needs and complex disabilities, while also providing family support services and a home to our residents where quality-of-life is paramount.

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Clinical Guidance for Surgical Hubs Professor Deborah McNamara, RCSI Vice President and co-lead National Clinical Programme in Surgery; Stephen Donnelly, Minister for Health; Professor Laura Viani, President, RCSI; Professor Cathal Kelly, Vice-Chancellor and CEO, RCSI

President, RCSI). The work was commissioned by the HSE Chief Clinical Officer Dr Colm Henry. Minister Donnelly said: “I was delighted to launch the new Surgical Hubs Clinical Guidance document here at RCSI this morning. This document, with its guidance recommendations on issues for surgical hubs such as surgical hub infrastructure, clinical governance, and patient pathways, is a significant step forward in the delivery of the surgical hub programme. The guidance aims to support the speedy and sustainable introduction of Surgical Hubs to reduce waiting times for scheduled care. Clinical Guidance for Surgical Hubs has been published by the Elective Surgical Hubs Clinical Design Group. The guidance is aimed at supporting the timely implementation of the six new surgical hubs which are intended to reduce waiting lists for scheduled surgical care. The guidance was welcomed by Minister for Health Stephen Donnelly during an address to the annual Health Service Quality Improvement and Innovations Conference, hosted by the RCSI National Clinical Programmes in Surgery, Trauma and Orthopaedics and Emergency Medicine. Surgical hubs are ring-fenced surgical facilities containing operating theatres, treatment rooms, and other services necessary to deliver ambulatory, minor and day case procedures. They are designed to provide high-volume, low-complexity care. The development of the hubs is a major step forward in the separation of unscheduled and scheduled care which is critical to reduce the adverse impact of winter emergency department surges on surgical activity.

The clinical guidance document covers areas such as patient pathways, sustainability, infrastructure, staffing, patient safety, referrals, escalation plans and clinical governance. According to the Clinical Design Group, it is essential that all existing surgical capacity in existing Model 2 and Model 3 hospitals is protected so that the surgical hubs are able to provide additional capacity to meet the very high levels of demand. Extra capacity The Group is recommending that, in the short term, in order to deliver the extra capacity as speedily as possible, the centralised model used by the National Treatment Purchase Fund is used as a template for managing patient access to the surgical hubs. This is a well-established and qualityassured system and would ensure equity of access and waiting times, irrespective of patient location or hospital of origin. Local governance and ownership of surgical hubs is key to their rapid development, as is integrating with existing services such as radiology, infection control, health and safety, medical records, portering and administration, say the Group.

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While emergency escalation of care should be very rare, it is essential that seriously ill patients and accompanying staff can move efficiently to an ambulance bay if a patient needs to be transferred and resuscitation trolleys should be easily accessible. Further recommendations include: • The establishment of new patient pathways to ensure a sufficient flow of patients into each surgical hub

“Progress is being made, with work underway at Mount Carmel, a contractor appointed to deliver the hub in Swords, planning permission granted for Merlin Park in Galway, and decisions expected shortly on planning permission for Cork, Limerick and Waterford. The surgical hub at the Reeves Centre in Tallaght has been very successful in reducing waiting lists and treatment times and I look forward to the new hubs underway delivering equally positive results.”

Significant step forward

Professor Deborah McNamara said: “We are really pleased to see progress in the development of new surgical hubs. The expansion of elective surgical services, through these new hubs, will help improve access to timely scheduled surgical care for patients requiring straightforward procedures. With the new health regions being established, there is a real opportunity to consider the optimum structures and networks for the delivery of scheduled and unscheduled surgical services across each region, in keeping with local demand, capacity, infrastructure and geography.

The Elective Surgical Hubs Clinical Design Group was chaired by Professor Deborah McNamara, RCSI Vice-President and co-lead of the National Clinical Programme in Surgery and Professor Frank Keane (Past

“We hope that this clinical guidance will support the delivery of the six surgical hubs as early as possible, so that they can begin to provide surgical care and reduce waiting times for patients,” added Professor McNamara.

• Protocols for nurse-led discharge should be in place • Referral letters or booking forms should provide sufficient information to allow for administration to be completed before admission, or nurse led pre-assessment and preadmission as appropriate. • Ensuring all consultation rooms support virtual clinics to reduce unnecessary travel for patients and enable optimal use of the new infrastructure.

Biosimilars

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Demonstrating the Potential of Biosimilar Medicines Summary Report – 7th Biosimilar Multistakeholder Event, Brussels

On the 13th of December, the European Commission organised the seventh multistakeholder event on biosimilar medical products, aiming to raise awareness about biosimilars towards all stakeholders and demonstrate their potential to improve access to and affordability of medicines. The event took place in Brussels, Belgium (hybrid), with over 80 participants joining in person and more than 300 connections online. Together with 19 speakers coming from different stakeholder groups, they discussed the impact of biosimilar competition, upcoming losses of exclusivity in the biologics pipeline, disparities in biosimilar uptake and access, as well as the consequences of product formulation and administration for healthcare professionals, patients and health systems. The event was opened by Rainer Becker (Director DG SANTE D), who welcomed the attendees and highlighted the opportunities biosimilars can bring, but also the remaining challenges for health systems to fully exploit the savings from biosimilar competition. Therewith, he also announced the recent publication of the EU4Health call for tenders specifications to support the uptake of biosimilars in a multistakeholder approach. After this keynote speech, Ljiljana Vukota (NGO “Everything for

Her”) shared both her and other patients’ journey and experiences with the use of biosimilars, stressing the importance to inform patients and ensure trust about the value of biosimilars to patients and healthcare systems. Following that, Per Troein and Max Newton (IQVIA) presented the key findings of the 2023 report on the impact of biosimilar competition in Europe. This year’s main observations included: persisting access disparities between countries; slowed growth of biosimilar savings from list prices, reflecting the profile of losses of exclusivities; recognition of interchangeability as an important policy step among many others; and the lack of biosimilar pipeline for a significant number of biologics losing exclusivity soon, especially in the area of lowersales value and orphan medicines. Building on the latter observation, a panel discussion was dedicated to upcoming losses of exclusivity in the biologics pipeline and addressing the challenges and lack of biosimilar competition. It was moderated by Petra Wilson (Health Connect Partners), with representatives from the payer (Yannis Natsis (ESIP)), industry (Julie Maréchal-Jamil (Medicines for Europe)), healthcare providers (Prof. Dr. Wolf-Dieter Ludwig (CPME)), patients (Dimitrios Athanasiou (World Duchenne

Organization BoD and Rare Diseases Greece)), and regulatory side (Steffen Thirstrup (EMA)). Asking panellists and the audience about challenges to bring a biosimilar to launch, development and clinical trial costs, expected profitability, regulatory pathways, healthcare provider and patient hesitancy, as well as the complexity of newer biologics were frequently mentioned. In response to that, some aspects of the proposed Pharma Reform, assessing the necessity of phase III clinical trials for certain biosimilars, streamlining regulatory pathways and optimising tendering practices were put forward as potential parts of the solution. Following the networking lunch, the event continued with a session on disparities in biosimilar uptake and access: opportunities across countries, regions and sectors, chaired by Johan Pontén (TLV, SE). Sabine Vogler (GÖG, AT) started with an opening presentation on challenges and good practice examples in pricing, reimbursement and demand-side measures to enhance the uptake of biosimilar medicines, pointing out the importance of having a good mix of demand/supply policies and gathering evidence on their impact. Harald Mische (DG SANTE) gave an overview on how the proposed EU pharmaceutical legislation will stimulate market

entry of biosimilar medicines, including through a broadening of the Bolar exemption, procedural facilitation of authorisations, repurposing of offpatent medicines and modulation of incentives. Esa Heinonen (Fimea, FI) discussed what regulators can do to enhance the uptake of biosimilars, provided an update on the HMA Biosimilar Working Group activities and called for improved collaboration between the various stakeholders. Despoina Makridaki (EAHP) shared challenges and opportunities for biosimilar uptake specific to the inpatient sector, based on EAHP’s access to medicines, biosimilar and procurement position papers. She noted that barriers should be faced in a collaborative way and policies should incorporate the expertise and scientific knowledge of specialists, not in the least hospital pharmacists. Finally, Chara Kani (EOPPY, EL) and Agnieszka Beer (Ministry of Health, PL) shared national best practices, challenges and future actions, for instance regarding biosimilars pricing, HTA, switching and communication strategies. The event concluded with a last session on product formulation/administration and its consequences for patients, healthcare professionals and systems, chaired by Carlos Martin Saborido (Ministry of Health, ES). René Anour (EMA BWP) explained how formulation and device differences between the originator and biosimilars are handled in the regulatory EU-context, providing some hands-on examples. Adrian van den Hoven (Medicines for Europe) shared insights on the topic from an industry perspective, demonstrating how biosimilars can drive improvements and innovation in medicines and the delivery of patient care, and highlighting how a multi-stakeholder approach remains highly relevant to achieve access. Bernard Duggan (IE, HSE) presented the Irish bestvalue-biologics programme and explained how through a gainshare arrangement part of the savings were used to fund service delivery and enhancements for the benefit of patients. Lastly, Ana Soldo (HR, Croatian Chamber of Pharmacists) gave a presentation on the role of pharmacists, how they can support the use of biosimilars, and in particular educate patients, healthcare professionals and journalists.

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

10 Pharmacy Lessons

Lessons learned in Patient Safety: My observations and reflections while working within the healthcare system in the UAE Written by Linda Asaad Ghazal, Pharmacist II, Quality and Patient Safety - BCPS, Msc.QSHM, CPHQ,CPPS - Imperial College London Diabetes Centre

Over my professional career, I amassed 20 years of practical experience in healthcare as a pharmacist and a quality healthcare advocate. As a healthcare professional practicing pharmacy in UAE, I have always been enthusiastic about improving the quality of care. My belief that Patient Safety is a paramount concern and a top priority in healthcare started in 2009 when I completed my MSc in Quality and Safety in Healthcare Management from RCSI Dubai, a branch campus of the Royal College of Surgeons in Ireland (RCSI) in the United Arab Emirates. Since then, as a healthcare professional, I have been seeing and reflecting on the development of patient safety awareness and science in healthcare. In this article, I would like to share a few insights and experiences on this fundamental principle in healthcare. The global landscape of health care is changing, with health systems working in increasingly complex environments, patient safety is a big and growing global public health challenge and an international healthcare goal. The United Arab Emirates (UAE) is part of this global community striving for excellence in healthcare and has made significant strides to improve patient safety in its healthcare system. In UAE healthcare system, the Ministry of Health and Prevention (MoHaP) oversees the national

healthcare regulations. The emirates have regional healthcare authorities’ departments, like the Department of Health (DOH) in Abu Dhabi and the Dubai Health Authority (DHA) in Dubai, to regulate each region's medical sectors. The Departments of Health shape the regulatory framework for the health system, inspects against regulations, enforces standards, and encourages the adoption of world–class best practices and performance targets by all healthcare service providers in the Emirate. In this article, I want to highlight three main facts, that in my opinion, have contributed to the advancement of the quality of care while nurturing patient safety approaches in the healthcare system in the UAE. First of all, the ‘vision’ to provide world-class health and social care services must exist before any sort of implementation. The UAE does not only have a ‘vision’ but also stringent regulations governing the clinical practices in all healthcare settings to support it. Healthcare providers should adhere to strict guidelines in all process of clinical pathways, including but not limited to best practice clinical guidelines, correct diagnosis, updated best practice guidelines of medication management, verifying prescriptions, safe medication administration procedures, providing clear instructions

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

to patients, and verifying the authenticity of the medications. The department of health (DoH) implemented standards, policies, and initiatives to promote healthcare quality, implementing a total quality management system to ensure the safe and effective use of medications. JAWDA, which is the Arabic translation of ‘Quality,’ is a program that was launched in 2014. It supplies a framework designed to assess the quality performance of health providers in Abu Dhabi based on a set of quality outcome indicators under main areas like safety, effectiveness of care, timeliness of service delivery, and patient-centric delivery of care. The Department of Health (DoH) has signed an agreement with the Emirates Classification Society (TASNEEF) to Certify Healthcare Providers in the Emirate of Abu Dhabi for JAWDA Data Certification. JAWDA Data Certification (JDC) is a process to improve the quality and accuracy of health data and clinical coding in the Emirate of Abu Dhabi. It is an initiative of the Department of Health (DoH) to enhance the transparency and trust between healthcare providers, payers, patients, and regulators. JDC involves auditing the claims and coding processes of healthcare facilities, as well as validating the data submission of key performance indicators (KPIs) for quality measurement. The objective of JDC is to ensure that the health data reflects the actual services provided and the outcomes achieved, and to support the improvement of patient safety, clinical effectiveness, and patient experience. JDC is based on a set of standards and guidelines that are aligned with international best practices. In 2023, The Department of Health - Abu Dhabi announced its accreditation by the prestigious International Society for Quality in Health Care External Evaluation Association (ISQua EEA). DoH received this accreditation for its commitment to quality and patient safety in health and social care. The accreditation recognizes DoH’s adherence to international

standards in healthcare services, ensuring continuous improvement and excellence in service delivery. Another key strategic initiative is the effective integration of technology to improve patient safety. Malaffi is the first health information exchange platform in Abu Dhabi. Malaffi, which means “my file” in Arabic, aims to improve healthcare delivery quality, safety. It has a mobile app that allows patients to access their health information and manage their appointments, prescriptions, and referrals. By providing instant access to the patient’s medical file, Malaffi empowers healthcare professionals to make better clinical decisions, enhances coordination and avoids unnecessary duplication of tests and procedures. It is one of the most advanced health Information exchange platforms in the world, providing patient’s health information from a routine checkup, consultation or emergency treatment to laboratory tests or radiology images, all are now collated in their personal file, with their medical history safely and securely stored and instantly accessible when needed. Malaffi is integrated with the National Unified Medical Record (NUMR) program Riayati and Nabidh, the Dubai Health Authority platforms for the secure exchange of reliable healthcare information among licensed health facilities in Dubai, a step that further supports the delivery of an integrated health system for citizens across the UAE. This initiative not only reduces healthcare costs, but also primarily contributes to patient engagement, reduces the risk of medical error, improves medications safety, supports patient empowerment to aid self-care, informed decisionmaking, enhanced medical compliance, and improved trust between patients and medical professionals. Adding to this, I believe the different initiatives and collaboration between pharmacovigilance authorities and

11 healthcare providers, plays an important role in the advancement of providing quality care, an example of this is, healthcare facilities having assigned pharmacovigilance focal points who are tasked with specific responsibilities that include: • Following up with healthcare professionals within the facility for reporting Medication Errors and send any clarification to DOH when required. • Identifying and implementing practices to improve the Pharmacovigilance reporting to DOH. • Educating healthcare professionals on the importance and methods of Medication Errors (ME) to the Pharmacovigilance program. • Receiving emails of safety alerts and recall circulars and disseminating them to healthcare professionals within the facility.

• Becoming a member of the Abu Dhabi pharmacovigilance networking (ADPVN) and participates proactively in its activities. The ADPVN members meet in comprehensive workshops and advanced training days activities to enhance medication safety and encourage safe patient care practices. As a pharmacovigilance focal point of my healthcare organization, I have been following and participating in these initiatives and campaigns and observing their positive impact on improving patient safety and quality of care in different settings and contexts. It is also a great learning opportunity from the inspiring stories, best practices of leading experts and peers worldwide committed to making health care safer and better for everyone. Such activities lead to reframing the relationship between healthcare providers and regulators, resulting in effective communications and positive outcomes.

The standard on reporting medication errors, aims to ensuring system thinking and just culture. It ensures that reported errors are studied, reviewed and that procedures are established to prevent them from reoccurring. The standard also requires that healthcare facilities must develop long-term monitoring plans to ensure that changes come into effect after the medication errors occur. The standard adopts the "Culture of Safety", designed to promote the development and implementation of the Continuous Quality Improvement system. Finally, another important contributing reason to the advancement of quality of care, is the role played by Quality and Patient Safety leaders. Health organisation leaders consider patient safety as a strategic goal as they are aware that patient safety is everyone's responsibility; it is not a one-time event, it is not a theme, it is not about accreditation, but it is a culture, a continuous process of improvement and learning. It is how we do things in our organizations daily. As a pharmacovigilance focal point of my organization and a quality and patient safety function lead of my pharmacy department, I was supported by my leadership to walk the safety talk at an organizational level. Adding to my responsibilities as the organizations’ pharmacovigilance focal point, my role is to: 1. Encourage and collect adverse events, errors and near misses reporting data. 2. Review and analyse the collected data of medications errors, clinical interventions and near misses. 3. Study reported data, highlight systems gaps, show examples as lessons learned. 4. Prepare monthly slides for discussion at the medication management committee, 5. Discuss and recommend corrective actions that can prevent recurrence. 6. Follow up corrective actions’ implementation and monitoring. 7. Slides then will be circulated to all clinical departments for sharing the good practices and learning from mistakes and near misses. 8. Spread the quality and safety talks, meet with the department colleagues on weekly huddles, and with organizational staff on regular

virtual events, discussing Principles of patient safety, quality in healthcare, patient education and engagement, system thinking in analysing medication errors or adverse events, just cultures, medications reconciliations, WHO world patients’ safety campaigns. 9. Mentor other quality champions at different department to disseminate the quality and safety talk. 10. Support improvement projects, continuous educations, and patient safety initiatives. Patient safety practices have come a long way, with valuable lessons. The way forward is for healthcare providers to focus on investments in advanced technologies like artificial intelligence, machine learning, proactive risks management and preventative mitigation strategies. On the other hand, in recent years, a notable surge in collaborative initiatives between higher education institutions and healthcare providers has appeared, marking a transformative approach to addressing patient safety challenges. As a dedicated safety pharmacist, I keenly see this trend as I explore the evolving healthcare landscape. The constructive collaboration between academia and healthcare fosters innovative solutions that enhance patient safety protocols and bridge the gap between theory and practical application. This dynamic partnership promises to advance pharmaceutical practices and cultivate a culture of continuous improvement in the quest for the best patient care in the UAE. To conclude, I would like to add that the drive for excellence, be it in any aspect, must come from ‘within’. Personally speaking, my unwavering commitment to pharmacy extends beyond the confines of dispensing medications. As a pharmacist, I am impassioned to pursue quality and patient safety excellence. It is not merely a professional obligation but a personal mission to ensure everyone receives the highest standard of care. Through continuous education, rigorous adherence to protocols, and a relentless dedication to staying informed about advancements in the field, I strive to contribute to a healthcare environment where patient well-being is paramount. In a world where precision and compassion intersect, I find fulfilment knowing that my role extends far beyond the counter — it reaches into the hearts and lives of those entrusting me with their health.

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

12 News

Researchers Discover Link between Stress and the Gut Virome First Author Dr Nathaniel Ritz is pictured with APC Operations Manager Dr Lorraine Draper who contributed to the research and Corresponding Authors Profs John Cryan, Ted Dinan and Colin Hill

research provides strong causal evidence that the viral component of the microbiome can be used to restore the microbiota-gut-brain axis during stress and a potential treatment strategy for stressrelated psychopathologies.

Researchers at APC Microbiome Ireland (APC), a world-leading SFI research centre based in University College Cork (UCC), have made a world-first discovery in the role the human virome plays in stress management. The findings support the development of potential treatments to reduce stress and stress-related disorders through targeting the virome, the vast community of viruses hosted by every human body. With one in eight people living with a mental disorder across the globe according to the WHO, stress-related psychiatric disorders such as depression and anxiety are extremely prevalent and are significant societal burdens.

ecosystem of other viruses known as bacteriophages that infect bacteria including pathogenic bacteria and can play a vital role in maintaining our health and wellbeing. Over the past decade a new burgeoning field of research studying the human microbiome has taught us that the microbes living in our guts play a pivotal role in many important aspects of our physical and mental health. Indeed it has been shown that the composition of bacteria in the gut changes with stress and that targeting these bacteria may dampen down the effects of stress in animals and humans. However, up to now all the focus has been on bacteria and viruses have been neglected.

Although most people think of viruses in their negative context (e.g. COVID-19, influenza or the common cold) there is a rich

To counter this Prof John Cryan and colleagues teamed up with a leading bacteriophage lab of Prof Colin Hill at APC to decode

the relative contribution of these gut viruses to stress. The study published in Nature Microbiology found for the first time that chronic stress led to changes in virome composition that was associated with behavioural, immune and bacteriome alterations. It supports increasing evidence that braingut interactions may play a key role in how stress is regulated. Understanding the biological consequences of chronic stress offers potential to develop alternative, new therapies for stress-related disorders. Next they showed that through a faecal virome transplant (FVT), whereby the harvested viruses from healthy animals prior to stress, and returned then to the stressed gut, was able to exert remarkable outcomes in preventing stress-associated behavioural and physiological outcomes. The

Women in Leadership Date for your Diary The Pharmaceutical Manufacturers’ Institute Women in Leadership event on March 13th sees Professor Orla Feely, President of UCD in conversation with Diarmuid Gavin, Country Manager with Théa Pharma. The Women in Leadership series is proudly supported by Uniphar Commercial. The event takes place on March 13th, 2024 from 11.30-2pm in the Kingswood House Hotel. Visit www.thepmi. com for more information.

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Dr Nathaniel Ritz, first author on the study said, “Although bacteria in the gut has been the subject of growing research, the way the virome interacts with bacteria and how they affect stress-related health and disease status is largely unexplored. Our research focuses on this and highlights a link between stress-related behaviours and the gut bacteriome and virome which opens up the potential to target the virome to treat and reduce the effects of stress.” Professor Cryan says, “This important research is a step advancement in developing targeted virome therapies that reduce the effects of stress with safer therapeutic interventions, and points to the potential of further research on the dynamics of the microbiota-gut-brain axis to promote gut and brain health” He also cautions that “these are mice studies and validation in humans is now required to assess the potential of the FVT approach. However, given that the virome composition varies greatly among individuals, it may open the door for personalised medicine approaches for stress-related disorders in the future. One thing for certain we must acknowledge that not all viruses are bad and they can play a key role in keeping the keep bad bacteria in our gut at bay especially in times of stress.”

Piperacillin / Tazobactam Piperacillin / Tazobactam Aurobindo 4g / 0.5g powder for solution for infusion. Indicated for the treatment of the following infections in adults and adolescents: Severe pneumonia including hospital-acquired and ventilatorassociated pneumonia Complicated urinary tract infections (including pyelonephritis) Complicated intra-abdominal infections Complicated skin and soft tissue infections (including diabetic foot infections)

Treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above. Piperacillin/Tazobactam Aurobindo may be used in the management of neutropenic patients with fever suspected to be due to a bacterial infection.

Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Name and active ingredients: Piperacillin/Tazobactam Aurobindo 4g/0.5g powder for solution for infusion. Each vial contains piperacillin (as sodium salt) equivalent to 4g piperacillin and tazobactam (as sodium salt) equivalent to 0.5g of tazobactam. One vial of powder for solution for infusion contains 9.4 mmol (216mg) of sodium. Indications: Piperacillin/Tazobactam is indicated for the treatment of the following infections in adults and children over 2 years of age (see SmPC sections 4.2 and 5.1): Adults and adolescents: severe pneumonia including hospital-acquired and ventilator-associated pneumonia, complicated urinary tract infections (including pyelonephritis), complicated intra-abdominal infections, complicated skin and soft tissue infections (including diabetic foot infections). Treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above. Piperacillin/Tazobactam Aurobindo may be used in the management of neutropenic patients with fever suspected to be due to a bacterial infection. Children 2 to 12 years of age: complicated intra-abdominal infections. Piperacillin/Tazobactam Aurobindo may be used in the management of neutropenic children with fever suspected to be due to a bacterial infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Posology: Adult and adolescent patients: Infections: The usual dose is 4g piperacillin / 0.5g tazobactam given every 8 hours. For nosocomial pneumonia and bacterial infections in neutropenic patients, the recommended dose is 4g piperacillin / 0.5g tazobactam administered every 6 hours. This regimen may also be applicable to treat patients with other indicated infections when particularly severe. Treatment every 6 hours for: Severe pneumonia, Neutropenic adults with fever suspected to be due to a bacterial infection. Treatment every 8 hours for: Complicated urinary tract infections (including pyelonephritis), Complicated intra-abdominal infections, Skin and soft tissue infections (including diabetic foot infections). Renal impairment: The intravenous dose should be adjusted to the degree of actual renal impairment (see SmPC section 4.2). Elderly patients: No dose adjustment is required for the elderly with normal renal function or creatinine clearance values above 40 ml/min. Paediatric population (2-12 years of age): For infections, the treatment frequency and dose per kg body weight should be adjusted by indication or condition (see SmPC section 4.2). Use in children aged below 2 years: The safety and efficacy of Piperacillin/Tazobactam Aurobindo in children 0-2 years of age has not been established. No data from controlled clinical studies are available. Treatment duration: The usual duration of treatment for most indications is in the range of 5-14 days. However, the duration of treatment should be guided by the severity of the infection, the pathogen(s) and the patient’s clinical and bacteriological progress. Method of administration: Piperacillin/Tazobactam Aurobindo 4g / 0.5g is administered by intravenous infusion (over 30 minutes). For instructions on reconstitution of the medicinal product before administration, see SmPC section 6.6. Contraindications: Hypersensitivity to the active substances, any other penicillin-antibacterial agent or to any of the excipients listed in section 6.1 of the SmPC. History of acute severe allergic reaction to other beta-lactam active substances (e.g., cephalosporin, monobactam or carbapenem). Special warning and precautions for use: The selection of piperacillin / tazobactam to treat an individual patient should take into account the appropriateness of using a broad-spectrum semi-synthetic penicillin, based on factors such as the severity of the infection and the prevalence of resistance to other suitable antibacterial agents. Before initiating therapy with Piperacillin/Tazobactam Aurobindo, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, other beta-lactam agents (e.g., cephalosporin, monobactam or carbapenem) and other allergens. Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid [including shock]) reactions have been reported in patients receiving therapy with penicillins, including piperacillin / tazobactam. These reactions are more likely to occur in persons with a history of sensitivity to multiple allergens. Serious hypersensitivity reactions require the discontinuation of the antibiotic and may require administration of epinephrine and other emergency measures. Piperacillin/Tazobactam may cause severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalised exanthematous pustulosis. If patients develop a skin rash they should be monitored closely and piperacillin / tazobactam discontinued if lesions progress. Antibiotic-induced pseudomembranous colitis may be manifested by severe, persistent diarrhoea which may be life-threatening. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. In these cases, Piperacillin/ Tazobactam Aurobindo, should be discontinued. Therapy with Piperacillin/Tazobactam Aurobindo may result in the emergence of resistant organisms, which might cause super-infections. Bleeding

manifestations have occurred in some patients receiving β-lactam antibiotics. These reactions sometimes have been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure. If bleeding manifestations occur, the antibiotic should be discontinued, and appropriate therapy instituted. Leukopenia and neutropenia may occur, especially during prolonged therapy; therefore, periodic assessment of haematopoietic function should be performed. As with treatment with other penicillins, neurological complications in the form of convulsions may occur when high doses are administered, especially in patients with impaired renal function. Piperacillin/ Tazobactam 4g / 0.5g contains 216mg of sodium per vial, equivalent to 10.8% of the WHO recommended maximum daily intake of 2g sodium for an adult. Hypokalaemia may occur in patients with low potassium reserves or those receiving concomitant medicinal products that may lower potassium levels; periodic electrolyte determinations may be advisable in such patients. Renal Impairment: Due to its potential nephrotoxicity, piperacillin/tazobactam should be used with care in patients with renal impairment or in hemodialysis patients. Intravenous dosages and administration intervals should be adjusted to the degree of renal function impairment. In a secondary analysis using data from a large multicenter, randomized-controlled trial when glomerular filtration rate (GFR) was examined after administration of frequently used antibiotics in critically ill patients, the use of piperacillin/tazobactam was associated with a lower rate of reversible GFR improvement compared with other antibiotics. This secondary analysis concluded that piperacillin/tazobactam was a cause of delayed renal recover in these patients. Combined use of piperacillin/tazobactam and vancomycin may be associated with an increased incidence of acute kidney injury (see SmPC section 4.5). Haemophagocytic lymphohistiocytosis (HLH): Cases of HLH have been reported in patients treated with piperacillin/tazobactam, often following treatment longer than 10 days. For full information, see SmPC section 4.4. Interaction with other medicinal products and forms of interaction: Refer to section 4.5 of the SmPC. Pregnancy: There are no or a limited amount of data from the use of Piperacillin/Tazobactam Aurobindo in pregnant women. Piperacillin and tazobactam cross the placenta. Piperacillin/ tazobactam should only be used during pregnancy if clearly indicated, i.e., only if the expected benefit outweighs the possible risks to the pregnant woman and foetus. Breast-feeding: Piperacillin is excreted in low concentrations in human milk. Tazobactam concentrations in human milk have not been studied. Women who are breast feeding should be treated only if the expected benefit outweighs the possible risks to the woman and child. Fertility: A fertility study in rats showed no effect on fertility and mating after intraperitoneal administration of tazobactam or the combination piperacillin / tazobactam. Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. Adverse reactions: Very common (≥ 1/10): diarrhoea. Common (>1/100 to <1/10): Candida infection, thrombocytopenia, anaemia, insomnia, headache, abdominal pain, vomiting, constipation, nausea, dyspepsia, rash, pruritus, pyrexia, injection site reaction, alanine aminotransferase increased, aspartate aminotransferase increased, protein total decreased, blood albumin decreased, Coombs direct test positive, blood creatinine increased, blood alkaline phosphatase increased, blood urea increased, activated partial thromboplastin time prolonged. Uncommon (>1/1,000 to <1/100): Leukopenia, hypokalaemia, seizure, hypotension, phlebitis, thrombophlebitis, flushing, erythema multiforme, urticaria, rash maculopapular, arthralgia, myalgia, chills, blood glucose decreased, blood bilirubin increased, prothrombin time prolonged. Rare (>1/10,000 to <1/1,000): pseudomembranous colitis, agranulocytosis, epistaxis, stomatitis, toxic epidermal necrolysis. Not known (cannot be estimated from the available data: pancytopenia, neutropenia, haemolytic anaemia, thrombocytosis, eosinophilia, anaphylactoid shock, anaphylactic shock, anaphylactoid reaction, anaphylactic reaction, hypersensitivity, delirium, eosinophilic pneumonia, hepatitis, jaundice, Stevens-Johnson syndrome, dermatitis exfoliative, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), dermatitis bullous, purpura, renal failure, tubulointerstitial nephritis, bleeding time prolonged, gammaglutamyltransferase increased. Presentation: Clear glass vials of 48ml stoppered with grey colour bromo butyl rubber stopper and sealed with red colour PP/Al flip off seal. 10 vials per carton. Legal classification: POM. Marketing Authorisation Number: PA23467/001/002. Distributed by: Uniphar on behalf of Athlone Pharmaceuticals Ltd. For a copy of the SmPC or further medical information, please contact: medical@kent-athlone.com. Date of preparation: January 2024. IE22/003/02 SmPC January 2023.

Adverse reactions should be reported. Reporting forms and information can be found on the HPRA website (www.hpra.ie) or by email medsafety@hpra.ie Adverse events should also be reported to Kent Athlone Pharma Group on (090) 666 1109 or medical@kent-athlone.com. Additional information available on request.

For further information on this product, please contact your Athlone Pharmaceuticals Key Account Manager or our customer service team. Athlone Pharmaceuticals Ltd., Connaught House, 1 Burlington Road, Dublin 4, Ireland. Tel: + 353 (0) 9066 61109 | Fax: +353 (0) 9066 61921 Email: customer.service@kent-athlone.com

Date of preparation: January 2024 Ref: IE2024/001/00

Prescribing information

14 News

Welcome for National Taskforce Report The Royal College of Physicians of Ireland has welcomed the report and recommendations of the National Taskforce on the Non-Consultant Hospital Doctor Workforce. President, Dr Diarmuid O’Shea, said the report provides an implementation plan that we can work in collaboration with all who have a role to play in ensuring that we continually improve the quality of care we provide, meet the needs of the growing population, while at the same time bring clarity and focus to the needs of doctors training in our health care system. “I wish to thank the Minister for Health Stephen Donnelly, Prof Anthony O’Regan and the members of this group who have, through broad consultation,

captured the critical working environment, support and resources required now to meet the health needs of our population.

to begin to progress this dialogue, frame the vision of physician training in the years ahead and to create an implementation plan.”

“Non-Consultant Hospital Doctors (NCHD) are delivering care throughout Ireland to patients in increasing numbers and it is essential that these recommendations are fully implemented to address many issues they face while working in our hospitals,” Dr O’Shea said.

Currently there are almost 1,800 doctors training in core and specialist hospital-based medical training schemes with the Institute of Medicine, Institute of Obstetricians and Gynaecologists, Faculty of Paediatrics, Faculty of Pathology, Faculty of Public Health Medicine, Faculty of Occupational Health Medicine. This represents an 18 per cent increase from 1,500 doctors in training in 2018.

“The Royal College of Physicians of Ireland, which is Ireland’s largest postgraduate medical training college, is fully committed to working with all involved, including the HSE, to implement the recommendations. I have convened a meeting next month

The college has over 13,000 Trainees, Members and Fellows. The Irish Medical Organisation (IMO) has given a guarded welcome to the publication.

However, it warned that while the recommendations in the report are positive it is critical that there is an implementation plan with sufficient funding to allow the recommendations to become a reality. Speaking today, Dr Rachel McNamara, Chair of the NCHD Committee of the IMO, said, “We have been experiencing everincreasing numbers of NCHDs emigrating to systems where they are valued, supported and offered a work/life balance. The recommendations in this Report go some way to addressing the issues faced by NCHDs today but for any of us to have real confidence we need to see major investment and implementation to make those recommendations a reality.”

New Medical Pathway for Home Dialysis From left, Fiona Moloney Staff Nurse Interventional Radiology, MPUH; Nodlaig McDermott, Clinical Nurse Manager 2 Interventional Radiology, MPUH; Dr Mark Denton, Consultant Nephrologist, Beaumont Hospital; Dr Paul O Hara, Consultant General Physician and Nephrologist, Galway University Hospitals/Portiuncula University Hospital; Lorna Durack, Candidate Advanced Nurse Practitioner, Home Dialysis; Fidelma Gubbins, Clinical Nurse Manager 2, Hospital 1, MPUH; Imelda Mathews, Assistant Director of Nursing, MPUH and Mansu Mathew, Staff Nurse Interventional Radiology, MPUH

Merlin Park University Hospital has introduced a new pathway offering some dialysis patients an alternative to surgery for the insertion of catheters. The new option will reduce waiting times and allow more people to avail of treatment at home following the implanting of peritoneal dialysis catheters. Traditionally these catheters required surgery under general anaesthesia, however, selected patients who meet the criteria will now be offered the procedure

as a day case using ultrasound guidance under a local anaesthetic. The new process will improve the patients' overall experience and allow them to carry out their own treatment at home without having to come to hospital on a regular basis. Peritoneal dialysis is a process of removing excess fluid and waste products from the body by running fluids in and out through the peritoneal catheter and is it is one of the treatments used in kidney failure.

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

"This procedure was developed in order to meet the predicted demands for peritoneal dialysis as a home therapy option of choice for our patients,” said Dr Paul O'Hara, Consultant General Physician and Nephrologist and lead Nephrologist delivering this intervention for the Home Therapies Service. “I trained at Beaumont Hospital under the guidance of Dr Mark Denton, Consultant Nephrologist to get the expertise needed to bring this procedure to the Saolta Group for the first time. Surgical insertion

will still be required for patients who are not candidates for medical insertion, but it will increase the number of patients who can access this service locally and give them the option of having the catheter inserted under ultrasound guidance with conscious sedation or local anaesthesia. “Peritoneal dialysis for the management of end stage kidney disease offers improved patient involvement in the management of their care, better patient experience, autonomy and quality of life with treatment schedules that can be adapted to peoples’ lives, reducing the frequency of hospital attendance,” he added. The Home therapy service will incorporate patients from kidney centres in Galway, Mayo, Sligo and Letterkenny, and it is a key pillar of the home service's development.

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Date of Preparation: January 2024 | Job Code: GEN-IE-00056

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16 Report

W' h

For the purpose of this report, the term

“medicine shortage” covers every (temporary) inability for a community pharmacy to supply patients with the medicinal product requested as a result of For the purpose of this report, the term factors beyond their control, requiring the “medicine shortage” covers every dispensing of an alternative agent or even (temporary) inability for a community pharmacy to supply patients with the discontinuation of an ongoing medical therapy. Shortages of drug-device medicinal product requested as a result of factors beyond their control, requiring the combinations were counted towards dispensing of an alternative agent or even shortages of “medicines”. In terms of discontinuation of an ongoing medical therapy. Shortages of drug-device From antibiotics to cardiovascular reporting/notification to respiratory, most types of medicines continue to be in short supply. PGEU of medicine combinations were counted towards shortages of “medicines”. In terms of shortages, that respondents asked to grew worse compared annual medicine shortages report indicates in 2023were the situation to previous years. In reporting/notification of medicine apply their national definition, available. the Netherlands alone 2.292 shortages were registered lastif year affecting about 5 million people. Other countries

Medicines Continue to be in Short Supply PGEU publishes Annual Report

shortages, respondents were asked to

like Sweden, Portugal and Spain saw a significant increase in the number of shortages. apply their national definition, if available. PGEU President Aris Prins said, “Despite pharmacists continued best efforts to find solutions, shortages still leave many patients without their prescribed treatment. This situation causes frustration and inconvenience for patients and erodes their trust in pharmacists and in the healthcare system. They also cause stress for pharmacy staff and impose an additional administrative burden on pharmacies daily work”. In 2023 every pharmacy across the EU spent on average almost 10 hours per week dealing with medicine shortages. This time has tripled over the last 10 years; precious time which could be devoted to other useful tasks such as providing patients advice on the safe and effective use of medicines. Pharmacies struggle even more to provide patients solutions for shortages given the current healthcare workforce shortage. Strong differences exist among countries regarding the options that pharmacists can explore to find alternatives – for example substitution or compounding – in case the prescribed medicine is unavailable. Pharmacists should be granted greater flexibility and enabled to leverage their skills, knowledge, and experience to efficiently assist patients. “The reform of the EU pharmaceutical legislation is a unique opportunity to build a more resilient supply chain and improve shortages prevention, monitoring, and management. However, we need more immediate measures to address this chronic problem and reverse the negative trend that pharmacists have been denouncing for over a decade. We urge for earlier notification of shortages, for a timelier information to pharmacists and a fairer redistribution of medicines across countries” Prins added. Each year PGEU conducts a survey among its members to map the impact of medicine shortages across Europe from the community pharmacists’ perspective. The 2023 Survey was open to all PGEU member organisations and has been conducted between 4 December 2023 and 17 January 2024. A total

Key Findings

Key Findings

In 2023, medicine shortages continued

In 2023, medicine shortages continued to affect all European grew countries, and to 2022 in most worse compared grew worse compared to 2022 in most countries.

Shortages of medical devices available in pharmacy continue to exist across with significant differences all categories in various European countries, across countries. Pharmacists across the EU spend nearl

Shortages of medical devices available all categories in various European c across countries.

shortages as they did a decade ago, am on average.

Pharmacists across the EU spend nearly three times as much time addressing The burden medicine shortages on p shortages as they did a decade ago, amounting to almost 10 hours perofweek has increased when compared to p on average. patients’ trust in the pharmaceutical su

Despite community pharmacists’ co information, tools, and legal solutions them from effectively helpi The burden of medicine shortages on patients and pharmaciespreventing across Europe

has increased when compared to previous years, negatively impacting patients’ trust in the pharmaceutical supply chain.

Despite community pharmacists’ continued efforts, there are gaps in information, tools, and legal solutions available in many European countries, preventing them from effectively helping patients in case of a shortage.

2

of 26 PGEU members responded to the survey, including Ireland.

compliance with EU and national Ensure availability: Governments laws related to the public service and stakeholders must put obligations of supply chain patients’ needs first when Policy Recommendations actors. Policy makers also need developing national laws and W' h DĞĚŝĐŝŶĞ ^ŚŽƌƚĂŐĞƐ ZĞƉŽƌƚ ϮϬϮϯ to consider the impact of pricing business strategies, respectively. Community pharmacists are, policies on medicines availability These should first and foremost in most cases, successful in and on the security of the aim to ensure a timely and minimising the negative impact supply chain. adequate supply of medicines to of shortages on patients’ health patients. These principles should and ensuring continuity of care. Widen professional competence: apply also to the ongoing reform However, to effectively address The scope of pharmacy practice of the European pharmaceutical the growing problem of medicine should be extended when legislation, where patients’ shortages in Europe, PGEU calls medicines are in short supply, so interests should prevail over on policy makers to adopt pharmacists can use their skills, Question 1. In the last 12 months, have you experienced shortages of medicines in community commercial ones. It is also urgent, bold, and ambitious knowledge, and experience to pharmacy in your country? measures, namely: necessary to ensure effective better manage patient care and

Survey Results (% of responding countries) 100%

ensure continuity of treatment. When medicines are not available, pharmacists should be allowed to substitute with the most appropriate alternative, countries as part of 100% of responding a shared decision-making process (26) experienced medicine with prescribers and patients and/ shortages in the with last 12 months. or in accordance national protocols. Shared electronic

100%

50%

Since 2019, all surveyed Question 1. Inhave the lastexperienced 12 months, countries have you experienced shortages of shortages. 0% Yes

0%

medicines in community pharmacy in your country?

No

(% of responding countries)

Question 2. If you have experienced shortages, how would you compare to the situation in the MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE previous 12 months:

Question 3. If you have experienced shortages in the last 12 months in your country, which medicine classes have been in short supply in community pharmacy? (ATC Level 1, multiple answers per country, % of responding countries) Medicines

Responding countries (%)

Anti-infectives for systemic use (antibiotics)

100%

Respiratory system

96%

Cardiovascular system

92%

Alimentary tract and metabolism

77%

Antineoplastic and immunomodulating agents

77%

Nervous system

77%

Musculo-skeletal system

69%

Vaccines

69%

Blood and blood forming organs

65%

Systemic hormonal preparations, (excl. sex hormones/insulins)

65%

Dermatologicals

62%

Genito-urinary system and sex hormones

62%

Sensory organs

62%

Various

58%

Antiparasitic products, insecticides and repellents

46%

communication tools between medicine shortages in community They added that there is an pharmacy in your 100% pharmacists and prescribers ongoing legislative process for Topcountry, 3 of responding countries (26) (e.g., shared electronic health a medicine shortage protocol experienced medicine shortages records) can facilitate this process allows for therapeutic From those, the three classes of medicines most frequently in short that supply were: in the last 12 months. Since effectively and safely. substitution by a pharmacist in 2019, all surveyed countries have limited circumstances where Develop effective governance experienced shortages. a medicine is in short supply. systems: A close collaboration Normally a pharmacist liaises with Compared to the previous 12 between EU Member States the prescriber for an alternative months, in 2023, in 17 of the 26 and the European Medicines medicine to be supplied, still responding countries the situation Agency (EMA) is needed to requiring a new prescription. grew worse (65%) and stayed the improve reporting, monitoring, same in 6 countries (23%). Only 3 and communication on medicine In 12 out of the 26 responding namely Cyprus, Greece shortages. At national level, more countries (46%) there is a (56%) Anti-infectives for systemic use, countries, Nervous system (60%) Cardiovascular system and North Macedonia registered structural, timely and transparent commonly agreed definition of such as antibiotics improvements when compared to collaboration models medicine shortages at national (84%) between the year before. supply chain stakeholders and level, and in 5 countries (19%) the national competent authorities definition of medicine shortages is In 2022, 76% of the responding must be developed to increase enshrined in the national legislation. countries said the situation had the efficiency and effectiveness of gotten worse or stayed the same in In 18 out of the 26 countries joint notification and assessment 24% of the cases. surveyed (69%), there are practices, and to empower reporting systems for shortages According to the Irish Pharmacy pharmacists in reducing the impact in place that can be used by Union shortages have significantly 6 on European patients. community pharmacists. increased in the last year and Improve communication: It is vital pharmacists in Ireland do not Conclusion to ensure greater transparency and receive sufficient advance availability of medicine shortages In the last 12 months, all warnings of shortages. data. Effective communication, countries that responded to 69% of responding countries early detection and central the PGEU survey experienced experienced shortages of medical assessment of potential shortages medicine shortages in community devices in community pharmacy in can be achieved by connecting all pharmacies. Similar to the previous the last 12 months, which shows medicine supply chain actors and year, a majority of these countries NCAs at national level in consistent a slight increase from last year’s (65%) noted a deterioration in situation (66%). reporting systems. This will ensure the situation compared to the that community pharmacists have preceding 12 months. In a few In terms of measuring how far timely information on current and instances, the situation remained medicine shortages have impacted foreseen medicine shortages. It is unchanged (23%), while a smaller on community pharmacies, over also necessary to increase access percentage of countries reported 90% said they had suffered to the information available across positive improvements (12%). financial loss due to time invested the supply chain. in mitigating shortages while Medicine shortages in community over 80% said they had incurred Compensate financial impact: pharmacies have an impact on increased administrative duties. The resource investment by every medicine class across the pharmacists and pharmacies countries surveyed - shortages The Irish Pharmacy Union said to manage shortages must be of anti-infectives for systemic the workload in management of recognised and valued. use (such as antibiotics) were shortages and associated phone experienced in all countries. calls from patients is rising year Survey Results Furthermore, 96% of the after year, leading to increased When asked if, in the last countries registered shortages of stress in pharmacy staff and 12 months, have there been mental health issues. medicines for the respiratory and

17 Question 3. If you have experienced shortages in the last 12 months in your country, which medicine classes have been in short supply in community pharmacy? (ATC Level 1, multiple answers per country, % of responding countries)

cardiovascular systems (92%). The most frequent medicines in shortage were anti-infectives for systemic use, medicines for the cardiovascular system, and medicines for the nervous system. In a significant number of countries that participated in the survey (27%), the list of medicines facing shortages exceeded 600 at the time of survey completion. When compared to data from the previous year, both evidence and feedback from pharmacists indicate a worsening of the situation, with an increasing number of countries reporting a larger number of medicines in short supply over the course of the year. A total of 69% of the countries that contributed to this year’s study reported encountering shortages of medical devices in community pharmacies, reflecting a slight increase from the previous year's figure of 66%. These shortages span across all categories of medical devices. However, in only 2 countries there are systems to monitor shortages of medical devices, making it difficult to have a clear picture of the situation across Europe. All responding countries indicated that they believe medicine shortages cause distress and inconvenience to patients. The most perceived consequences include treatment interruptions (reported by 88% of countries), increased co-payments due to more expensive or nonreimbursed alternatives (73%), and suboptimal treatment with reduced efficacy (73%). Notably, these percentages have shown an increase compared to the previous years. Available solutions to community pharmacists in the event of shortages vary significantly across European countries. Generic substitution (92% of countries), preparing compounding formulations (50%), and adjusting therapy and posology when the same medicine is available in a different strength (50%) are commonly permitted solutions in many European countries. However, it is worth noting that some of these solutions may be subject to restrictions (e.g. requiring a new prescription). Additionally, the implementation of these solutions can be cumbersome and timeconsuming for both the patient and the pharmacist.

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

18 News

Patient Safety Research Network Announced A new Patient Safety Research Network led by Samuel Cromie, Assistant Professor, Psychology, has been announced by the Health Research Board and the Health Service Executive. The HRB and the HSE announced funding for the five-year, ¤1.25M investment which will establish the Evidence-based QUality Improvement and Patient Safety (EQUIPS) research network. EQUIPS will bring together stakeholder groups, researchers and knowledge users to advance Quality and Patient Safety (QPS) research and create a better understanding among patients and the public about the value and impact of QPS research. The multidisciplinary network will be led by Professor Samuel Cromie, Trinity, with Dr Orla Healy, National Clinical Director of Quality and Patient Safety, Health Service Executive (HSE) as the Lead Knowledge User on the award. Dr Mairead O’Driscoll, Chief Executive of the Health Research Board (HRB) announced the award noting: “The EQUIPS project builds on a 10-year collaboration between the HRB and HSE to

advance quality and patient safety research through the Research Collaboration in Quality and Patient Safety (RCQPS).

Systems, Implementation Science, Medical Education, Psychology, Human Factors and Behavioural Science.”

“Establishing the network aligns with many shared objectives that focus on improving outcomes for patients.

Dr Orla Healy, National Clinical Director, Quality and Patient Safety, HSE, added:

“The network will provide a forum to debate and determine research priorities, support the development of a critical mass of research activity, and position Ireland to engage internationally to ensure we are at the forefront of best international practice when it comes to patient safety research and its application into practice.” Samuel Cromie, Assistant Professor, School of Psychology, added: "EQUIPS is a very exciting opportunity to create a national collaboration to draw together expertise in key research clusters and build the capability and capacity for evidence-based improvements in quality and safety. The team includes 22 coapplicants and 28 collaborators with experience in QPS research spanning a range of disciplinary backgrounds including Health

“Translating our practical experience in quality and patient safety into evidence based, timely research outcomes is essential in a dynamic and evolving healthcare organisation. “At a time when we are focused on integrating services and changing how we structure and deliver healthcare, we have a unique opportunity to create a platform that enables us to capture tacit knowledge in essential fields like patient safety, human factors and public health. In doing so, there is significant potential for the EQUIPS project to positively impact service delivery for people using healthcare.” EQUIPS will have three strands. • The Enable strand will put all the pieces in place to build a thriving research community – events, information sources, capacity and capability building.

• The Understanding and Informing strand will draw on this community, set priorities and strategies for QPS research, identify barriers and enablers and evaluate the network itself to apply the quality improvement cycle to it. • The Focussing strand will consist of clusters to start working on priority QPS research topics, set the agenda for them, put consortia together and start pursuing funding. Two initial clusters will focus on System and Process Design and Implementation and Evaluation. The network incorporates researchers and research groups/ centres from seven Universities in disciplines that include Quality Improvement, Patient Safety Science, Implementation Science, Health Psychology, Human Factors, Health Economics, Safety Culture, Systems Science and Public Health. The project will run from now until November 2028 and is funded equally by the HRB and HSE with an investment of ¤625,000 each.

Impact of Lifestyle Changes on COPD UCC researcher Ciara Hanrahan, with MSc Physiotherapy student Mark Attia Image credit: Jim McCarthy Photography

Researchers at University College Cork (UCC) have found that people with Chronic Obstructive Pulmonary Disease (COPD) see health benefits and improved shortterm quality of life from lifestyle behaviour change interventions. COPD is a complex lung disease and the third leading cause of death in the world. It is a preventable and manageable disease in which people can present with cough, breathlessness and recurrent exacerbations. The World Health Organisation state that approximately 65 million people globally currently live with moderate

to severe COPD and it is estimated that over 380,000 people in Ireland suffer from COPD. Behaviour change interventions are activities developed to change specific behaviour patterns, for example goal setting, demonstration of a task, provision of information, prompts and rewards. Supporting positive changes in behaviour for people with COPD could help to promote a more physically active lifestyle. In this review, led by Ciara Hanrahan, Lecturer in Physiotherapy and PhD candidate at UCC, behaviour change

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

interventions were identified across 12 randomised controlled trials, included over 1200 participants, and results were mapped to a theoretical framework which provides a lens through which behavioural determinants can be observed. Across a study of eight medical databases searched from inception to April 2023, outcomes including steps per day, physical activity levels, exercise capacity and quality of life were most measured. Behavioural change interventions most frequently reported across the studies were counselling, stepcount monitoring, social support and goal setting. While the optimal combination of behaviour change interventions,

their dosage and timing of their delivery is not yet clear, this review reports that using behaviour change techniques incorporating counselling, activity monitoring, goal setting and social support interventions, such as group exercise, feedback from trainers, use of physical activity monitors in the form of pedometers, smart watches and apps may help to influence positive physical activity behaviour in the short-term. This review also indicates that greater improvements in physical activity and quality of life outcomes in those with COPD may be achieved when multiple behaviour change interventions are used together, providing scope for future trials to examine the use of variously combined interventions over longer intervention periods. Published in the Journal of Respiratory Medicine and Research, the study found that where participants were exposed to a greater number of behaviour change interventions, greater improvements in physical activity and health-related outcomes were reported.

Neurology 19

Recognising Brain Awareness National Brain Awareness Week is an annual initiative organized in March each year by the Neurological Alliance of Ireland to promote greater awareness and understanding of the impact of living with a neurological condition as well as the need for investment in services, research and prevention. The Neurological Alliance of Ireland is the national umbrella group for neurological charities.

Written by Professor Orla Hardiman, Professor of Neurology/Head of Academic, Trinity College Dublin

In Ireland, almost 800,000 people are affected by a neurological condition, and up to 1 in 8 consultations in primary care and at least 1 in 5 in emergency medical admissions to hospital are because of a neurological problem. Neurological diseases range from those that are invisible but quality of life- threating (e.g epilepsy, migraine etc) to those that are associated with severe and progressive physical and / or cognitive decline (e.g. motor neurone disease , Parkinson’s Disease Alzheimers Disease). Neurological conditions affect all age groups from the young, the economically active and older people. While some neurological conditions are easily recognizable as they are associated with obvious signs (e.g. established Parkinson’s or Alzheimer’s disease) others can be difficult to diagnose as they are based on history (e.g the epilepsies, migraine etc), or because the early signs may be subtle and generate a wide differential diagnosis (e.g. early motor neuron disease). However, the majority are long term conditions necessitating specialist and multidisciplinary health care throughout life. Clinical Neurology is concerned with the prevention, diagnosis, treatment, and care of people with disorders of the brain and spine. While clinical history and physical examination remain the cornerstone of neurological diagnosis, advances in neuroimaging, blood and CSF based biomarkers, and neurophysiology have enabled refinement of the diagnostic process and have supported treatment planning. For example, modern imaging has altered the classification of Multiple Sclerosis, which is now based on patterns of active inflammation on MRI; a diagnosis of Parkinson’s Disease can be confirmed by a DAT scan, and PET imaging is helpful in subclassifying different types of dementia. Similarly, CSF biomarkers can

help to segregate different types of neurodegeneration, and the presence of elevated levels of neurofilaments can help to predict prognosis in both Multiple Sclerosis and Motor Neuron Disease. Advances in neurophysiology, along with detailed neuroimaging can help to localize seizures and guide surgical resection in selected cases. Advances in neural engineering are driving technologies such as deep brain stimulation for Parkinson’s Disease. Modern genomics can provide categorical diagnoses, as exemplified by the identification of the gene for Duchenne Muscular Dystrophy in 1988, and for Huntington’s Disease 1993. The completion of the Human Genome mapping project has led to the discovery of a multitude of additional genes that have provided greater understanding of the pathobiology of a wide range of neurological conditions. These insights have in turn driven interest and investment in drug discovery for diseases for which effective treatments remain elusive. Indeed, the past 10 years have witnessed exciting developments in effective targeted pharmacological treatments for many neurological conditions. Targeted immunomodulatory therapies have revolutionized the

treatment of multiple sclerosis, such that a newly diagnosed patient can be assured of minimal disability and an excellent quality of life. Genome based therapies are firmly on the horizon for many hereditary conditions. Spinal Muscular Atrophy, a motor neuron degeneration of childhood, is now a treatable disease, as is the adult form of motor neuron disease associated with mutations in the SOD1 gene. Pharmacogenomics can help the selection of appropriate treatments for some forms of epilepsy. And while early trials in Huntington’s disease have been disappointing, exciting new trials are in progress. But early access to specialist services remains a problem , and optimal management remains accordingly curtailed for many Irish citizens. In some instances such as Relapsing Remitting Multiple Sclerosis, we have learned that failure to treat in the early phase of the illness can lead to increased disability in later years. The same is true for poor controlled epilepsy. And increased neurological disability of all types has an adverse effect on all aspects of life. While services have improved over the years with an increase in the number of Neurologists and the appointment of advanced

practitioners and specialist nurses, the requirements associated with evolution of new treatments, and greater need for surveillance continue to outpace the expansion of neurological services. We still lack critical mass to provide uniformly high standards of care across the entire country and to facilitate the necessary degree of sub-specialization. And while the value of high quality hospital-based multidisciplinary services with community outreach is recognised, there is much work to be done to develop and expand these services to all neurology centres. There is also a need to commensurately develop community based neurorehabilitation services that link with those within the acute hospitals across the country to ensure that all of those with neurological disability have uniform access to new therapeutics, and high quality multidisciplinary care as close to home as is possible. National Brain Awareness Week takes place from 11th to 17th March 2024. For more information on National Brain Awareness Week visit the Neurological Alliance of Ireland website www.nai.ie or follow the conversation on social media #brainawarenessweek2024

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Gastroenterology & Endocrinology - Liver Cancer

20

Inequities in primary liver cancer in Europe: The state of play Written by Loreta A. Kondili1, Jeffrey V. Lazarus2 3 4, Peter Jepsen5, Frank Murray6, Jörn M. Schattenberg7, Marko Korenjak8, Lucia Craxì9, Maria Buti National Centre for Global Health, Istituto Superiore di Sanità, Rome, Italy, UniCamillus International Medical University, Rome, Italy

1

CUNY Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA

2

Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain

3

Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

4

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark

5

Beaumont Private Clinic, Beaumont, Dublin 9, Ireland

6

Department of Internal Medicine II, Saarland University Medical Center, Homburg and Saarland University, Saarbrücken, Germany

7

European Liver Patients' Association, Brussels, Belgium

8

Department of Biomedicine, Neuroscience, and Advanced Diagnostics, University of Palermo, Palermo, Italy

9

Liver Unit, Hospital Universitario Vall d'Hebrón, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain

10

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain

11

People in Europe live longer and in better health than ever before, yet considerable health inequities persist between groups of people across and within countries.1 Health inequities are unjust and avoidable or remediable differences in health, determined by a broad range of personal, socio-economic, and environmental factors and the wider set of forces and systems shaping the conditions of daily life, known as the social determinants of health (SDoH).2 According to the conceptual framework proposed by the World Health Organization (WHO) in 2010, SDoH are divided into structural and intermediary with a cascade effect on health equity (Fig. 1).3

tobacco use, unhealthy diet, obesity, and physical inactivity) are the main SDoH related to common cancer risk factors and they are inequity drivers accounting for rising mortality rates within and outside the cancer field.5,6 In the public health field, the role that SDoH play as non-clinical factors in determining different

The relationship between SDoH and cancer outcomes is not linear; it operates through multiple intersecting pathways, reflecting differential exposure to cancer risk factors and different access to health services.4 Socio-economic position, education, living conditions (e.g. housing and overcrowding), and behavioural factors (alcohol and

Fig. 1. Cascade effect of social determinants of health on health equity

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

cancer-related incidence and mortality rates globally and in Europe has become increasingly clear.7,8 One of the biggest challenges of the European Health Union is addressing health inequities. Europe’s Beating Cancer Plan specifically recognises the importance of investigating risk factors and access to care related to SDoH

for complex diseases like cancer as “vital to improve health outcomes”.9 Liver cancer care in Europe is primarily focused on providing medical interventions to treat the disease, but it does not systematically address the many upstream factors that contribute to its incidence and outcomes.

21

of the specific aetiological factors should be interpreted with caution; they are helpful to understand trends within single countries in different periods of time but should not be used as a comparison across different countries. The epidemiological profile of viral hepatitis in different countries differently impacts liver cancer incidence, whereas alcohol-related and, in particular, MASH-related rates could suffer from potential classification biases in specific country reports.

Fig. 2. The incremental impact of social determinants of health in liver cancer

Which role could the healthcare sector have in mitigating social risk factors for liver cancer? It is currently difficult to conduct a systematic review to assess inequities in liver cancer by combining socio-economic and clinical data in Europe due to the lack of standardised and comparable socio-economic data collection across and within countries. In this review, we considered the available data and addressed areas that would merit further investigation, in order to gather more robust and reliable evidence to help identify public health interventions aimed at reducing liver cancer inequities in Europe. The choice to focus on EEA countries and the UK, as a previous EU member state, is dictated by the need to identify an area that can pursue uniform policies (in the case of the EU) or that is at least not too different in terms of gross domestic product (GDP). In fact, the presence of large differences in GDP would be a strong confounding factor in the interpretation and comparison of the available data. Therefore, our work deals only in part with what pertains to structural and economic differences (GDP, political conditions) between countries. In addition, for countries in the WHO European region but outside the EEA, no quality evidence regarding the primary liver cancer pathway is available that could allow for critical analysis of potential inequities. In primary liver cancer, the influence of SDoH can add up and consolidate over time in a path that begins long before the occurrence of liver cancer, deeply affecting health outcomes. To frame the

problem more broadly, we widened the scope and considered how SDoH influence modifiable risk factors for chronic liver disease – such as lifestyle and behavioural factors, access to hepatitis B virus (HBV) vaccination, and hepatitis C virus (HCV) treatment – and, ultimately, for liver cancer in some populations.10 Liver cancer almost exclusively develops in people with chronic liver disease, more frequently in those with cirrhosis. Thus, there are manifold challenges in preventing, detecting, and treating liver disease in early stages, before the potential progression to cirrhosis and liver cancer. Moreover, in specific groups at risk of liver cancer, SDoH can affect both objective health outcomes – such as diagnosis, treatment, survivorship, and quality of life – and subjective health outcomes, e.g. patient-reported outcomes (PROs). Fig. 2 illustrates the incremental impact of SDoH on risk factors for chronic liver disease and cirrhosis as well as liver cancer outcomes.11,12 Liver cancer burden in Europe Liver cancer incidence and mortality rates vary greatly across Europe. The estimated liver cancer age-standardised incidence rates (ASIRs) in 2020 ranged from 4.3 new cases per 100,000 inhabitants in Central Eastern Europe, over 5 and 5.4 in Northern and Western Europe, respectively, to 6.7 in Southern Europe.13 The Global Burden of Disease (GBD) study has shown that in countries with the highest liver cancer ASIRs in 2010, such as France, Spain, and Italy, the estimated ASIRs were lower in 2019 (Fig. 3A).14 In Fig. 3A, a relative ASIR increase in

2019 compared with 2010 was estimated for countries in the top part of the figure, from Sweden (18.6%) to Germany (0.2%). A relative ASIR decrease in 2019 compared with 2010 was estimated for countries in the bottom part of the figure, from Switzerland (1.6%) to Hungary (41,9%). The highest overall relative ASIR decrease in 2019 was estimated for Hungary, however, in 2010, the ASIR for Hungary was 4.5, which is lower compared with the incidence rates estimated for Italy, France, and Spain that ranged from 6.15 to 7.45 per 100,000 inhabitants. In Fig. 3B, estimates of the relative changes in ASIR from 2010 to 2019 by liver cancer cause are presented. The main drivers of the increased ASIR in 2019 in countries on the top of the graph were alcohol-related and non-alcoholic steatohepatitis (NASH) (recently renamed metabolic dysfunction-associated steatohepatitis [MASH]). The relative decrease of ASIR in countries on the bottom of the graph can mainly be attributed to a decrease in the incidence of liver cancer due to viral hepatitis. The ASIR of each liver cancer cause in each country, as estimated by the GBD study in 2019, is shown in Table 2. In Italy, the country with the highest HCV prevalence and liver cancer incidence in Europe, a decreased incidence is estimated following the introduction of direct-acting antiviral (DAA) therapies against HCV infection (Table 2).15,16 Countries with historically low levels of liver disease, such as Nordic countries, may experience an increase in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASH in the future, given the rise of obesity across most European countries.17, 18, 19, 20, 21, 22, 23 However, differences in the role

Liver cancer-related mortality increased by 70% in the EU from 1990 to 2019.24 In 2020, incidence and mortality were similar: an estimated 87,000 Europeans were diagnosed with liver cancer and 78,000 died from it. Liver cancer is amenable to prevention, screening, and treatment; thus, incidence can be reduced and deaths averted. If prevention strategies are not successful, liver cancer incidence is expected to increase by 55% over the next 20 years.25 Liver cancer trends largely reflect those of hepatocellular carcinoma (HCC), which accounts for 7585% of all liver cancers, and intrahepatic cholangiocarcinoma (iCCA), the second most frequent primary liver cancer. HCC is mainly related to cirrhosis due to exposure to risk factors, such as chronic viral hepatitis (B, C, and D), harmful alcohol use, steatotic liver disease (SLD), and tobacco smoking. Overweight/obesity, cirrhosis and/or presence of viral hepatitis are also frequently reported in patients with iCCA.26 In less frequent cases, liver cancer may appear in the absence of cirrhosis, as observed in iCCA, in patients chronically infected with HBV and potentially in patients with SLD. Inequities in liver cancer incidence and risk factor distribution A high liver cancer incidence has been reported in people living in economically disadvantaged areas, with lower household incomes, across and within countries in Europe27, 28, 29, 30, 31, 32, 33, 34 (Table 1). However, it is not clear whether only the deprivation area, controlling for each individual-level SDoH, is independently associated with HCC incidence. HCC incidence rates are mainly related to exposure to one or more risk factors such as HBV, HCV, MASLD, or harmful alcohol consumption which have mutual influence in liver cancer development. Evaluating trends in exposure is important to frame the potential inequities related to

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Gastroenterology & Endocrinology - Liver Cancer

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Fig. 3. Age-standardised incidence rates per 100,000 inhabitants as reported by Global Disease Burden Estimates in 2019 vs. 2010, and change by liver cancer aetiology. (A) Age-standardised incidence rate (per 100,000 inhabitants) as reported by Global Disease Burden estimates in 2019 vs. 2010. Countries are ordered by relative decrease in ASIR (per 100,000 inhabitants) in 2019 vs. 2010. (B) Change in age-standardised incidence rate (per 100,000 inhabitants) as reported by Global Disease Burden estimates in 2019 vs. 2010 by liver cancer aetiology. Countries are ordered by relative decrease of ASIR (per 100,000 inhabitants) in 2019 vs. 2010.

contracting these infections.44,45 Many European countries have guidelines on viral hepatitis testing and vaccination, even though they have a limited focus on migrants and a clear disconnect between the recommendations and actual clinical implementation.46, 47, 48

different types of SDoH, which act synergistically by influencing risk factors for chronic liver disease and cirrhosis, which in turn are known as modifiable liver cancer risk factors. Chronic viral hepatitis Viral hepatitis is recognised as a preventable risk factor in Europe’s Beating Cancer Plan. Its elimination remains the key strategy for the primary prevention of liver cancer.9 SDoH act synergistically to increase the risk of exposure to viral hepatitis and impair the ability to manage it.35 HBV vaccination is a cornerstone of public health policies to prevent viral hepatitis-related liver cancer. Three countries, Denmark, Finland, and Iceland, do not have a national policy for universal HBV vaccination, whereas Hungary targets only adolescents with two not three doses of HBV vaccine.35 The HBV vaccination coverage in infants has shown a decreasing

rate from 2019 to 202237 (Table 1). On a global scale, there is a country-level correlation between the prevalence of HBV vaccination and GDP but it is unknown whether such a correlation exists within Europe.38,39 Only 50% of EU/EEA countries have reached the WHO target of 95% hepatitis B vaccination coverage in newborns, while limitations to HBV vaccine access for key populations, such as people who inject drugs (PWID) are present in several countries.35 Since 2015, the arrival of an unprecedented number of refugees and migrants has led to a migration and humanitarian crisis in the EU. Several Western European countries have experienced an increase in HBV and HCV infections in migrants and refugees who move from countries of high-intermediate endemicity for those infections.40,41 In the 2016 ECDC (European Centre for Disease Prevention

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

and Control) report, migrants accounted for 25% of chronic HBV and 14% of chronic HCV cases in the EU/EEA. In some countries (i.e. Ireland, the Netherlands, and Sweden) the contribution of hepatitis B cases among migrants from intermediate and high-endemicity countries to the overall burden in the host country was estimated to be exceptionally high.42 Hepatitis C in migrants, if not drug users, is often contracted later in life, mostly through exposure in healthcare settings with poor infection control practices. Migration to a lowendemic country at a young age could explain the lower HCV prevalence among migrants compared to the prevalence in the country of origin.43 However, some subgroups from specific geographical locations, potentially vulnerable to infectious liver diseases in their home nations or during their journeys, were more likely to have or be at risk of

In patients with chronic HCV infection, a 70% reduction in the risk of liver cancer was reported after a sustained virologic response to DAA therapy.49 The significant reduction but not the elimination of the risk for HCC in HCV cured patients is particularly relevant among aged populations who have cofactors of morbidity known to accelerate HCC progression, such as diabetes, obesity, and excessive alcohol consumption.50 Limited access to HBV and HCV treatment has been reported among vulnerable risk populations in EU/EEA countries.51 People with increased HCV infection risk, such as PWID, remain the most frequent reservoir of new infections in European countries.52 Insufficient health infrastructure, harm reduction programmes, and low awareness about HCV infection hamper HCV screening, diagnosis, and treatment in PWID in almost all European countries. An integrated approach based on the optimisation of care delivery and increased access to harm reduction and treatment for PWID is needed.35,50,51,53,54 In key populations, personal motivation for screening and curing viral hepatitis may be affected by limited health literacy and stigma. Stigma is a consequence of inequities and a driver in perpetuating them.55,56 Appropriate healthcare should include adequate outreach and

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communication strategies for these populations to reduce stigma, increase awareness and engagement, and make screening and treatments available.57 Alcohol-related liver disease Europe is the region with the highest estimated per-capita alcohol consumption in the world, with a North-South gradient for alcohol consumption and higher than recommended consumption limits.58,59 A global strategy addressing the SDoH impacting alcohol harms is necessary. The incidence of alcohol-related complications earlier in life competes with the occurrence of liver cancer in these populations.60 To reduce socio-economic inequities in alcohol-related mortality, it is worth targeting heavy episodic drinking as a public health strategy to address global alcohol-related health harm.61 Patterns of alcohol consumption across different social groups are not straightforward, and specific SDoH have been shown to affect them in certain groups of the population.62 While the frequency and level of alcohol consumption are higher in more educated groups in some European countries, alcohol-related liver disease (ArLD) remains higher in those with the lowest education level, precarious employment, economic insecurity, a migrant background, or refugee status, and in more deprived populations,63, 64, 65, 66 with sex also affecting this relationship.67,68 For example, in the UK, despite alcohol consumption increasing with income, there is a marked social gradient in alcohol-related mortality, which increases with decreasing socio-economic status (SES), leading to the so-called deprivation paradox.69,70 A more pluralistic perspective on causality considers not only the primary causal agent (in this context, alcohol) but also acknowledges the significance of contextual factors.71 ArLD is one of the most important preventable risk factors for liver cancer in many EEA countries and the UK.18,72 An alcohol intake of 30–50 g/day increases the risk of cirrhosis,73 while an alcohol intake of >60–100 g/day increases the risk of HCC.74 However, the effect of alcohol consumption on liver cancer risk is less clear. Excessive alcohol consumption is a cause of liver cancer and at the same time a cause of the competing risk of death in patients without liver cancer. The net effect may be that patients who continue to consume alcohol, in particular those who misuse alcohol, have a

reduced risk of HCC because they are likely to die before they can develop HCC.75 Alcohol accounts for 20% of HCC cases in Southern European countries (e.g. Italy or Spain), but for up to 63% of HCC cases in Eastern European countries where viral hepatitis has a low contribution to HCC (around 30%).19,76 Alcohol-related HCC was nearly sixfold more common than HCV-related HCC (29.37 vs. 5.39/100,000 adults/year, respectively) in a French study.22 They varied widely across different countries, being the lowest in Poland (ASPR 0.89; 95% CI 0.721.09), Hungary (ASPR 1.17; 95% CI 0.83-1.57) and Latvia (ASPR 1.27; 95% CI 0.91-1.68), and the highest in Austria (ASPR 4.79; 95% CI 3.49-6.38), Switzerland (ASPR 4.53; 95% CI 2.96-6.52), Germany (ASPR 4.21; 95% CI 2.98-5.78) and Finland (ASPR 4.11; 95% CI 2.84-5.80). The overall prevalence of HCC in women is lower than in men, however, among individuals who consume more than 80 g/ day of alcohol, the risk of HCC development in women is almost fivefold higher than in men, while progression to cirrhosis is also more rapid.77,78 Various biological and pathophysiological mechanisms have been suggested to underlie the higher sensitivity of women to alcohol, but the precise mechanisms of hepatocarcinogenesis are not clearly understood.78 It is reported that countries with the greatest gender differences in hazardous drinking were those with the most restrictions on women's behaviour and the greatest gender inequities in daily life. Lower levels of female empowerment and higher unemployment rates were associated with higher gender differences in hazardous drinking.79 Female sex interacts with cancer in complex ways and specifically, the gender disparity in sensitivity to alcohol and HCC development should be evaluated, considering behavioural factors, such as different lifestyles, smoking, and nutritional habits that could account for a higher incidence of ArLD in women.80,81 Metabolic dysfunctionassociated steatotic liver disease Although viral hepatitis is associated with a higher risk of HCC than alcohol use and MASLD, the prevalence of the latter conditions is much higher in the population, due to a global rise in obesity and type 2 diabetes.82, 83, 84 By 2030, the

number of SLD cases is forecasted to increase most in the UK (20.2%) and least in Germany (13.5%). By 2030, the highest SLD prevalence was estimated to be in Italy (29.5%) and the lowest in France (23.6%).83 SLD represents an increasingly important underlying aetiology of liver cancer, with an estimated prevalence of 38% in adults and 13% in children and adolescents in Europe.85, 86, 87 The proportion of HCC attributed to MASLD in the UK increased from <10% in 2000 to 34.8% in 2010. In France, it increased from 2.6% in 1995-1999 to 19.5% in 2010-2014.88 However, steatosis is not always associated with liver impairment. Several conditions or entities such as obesity, type 2 diabetes, or food toxicity overlap, leading to mitochondrial stress that promotes disease progression from simple steatosis to more severe MASLD stages.89 All these conditions could be interlinked with SDoH and thus could be the subject of inequities in their distribution in different groups of populations starting from childhood.90 In a study conducted in Hong Kong, liver-related death increases with age in patients with MASLD, especially among women, whereas in Europe, the leading cause of death in patients with SLD remains unclear. The competing risk for death posed by comorbidities should also be considered.91 Taking an overall overview from the GBD estimates, MASLD seems to be the main contributor to the increase in the ASIR of liver cancer in 8 of the 16 countries reporting an increase between 2010-2019 (Fig. 3B).92 However, this trend warrants reassessment because previous NAFLD databases did not systematically evaluate alcohol consumption. As reported in a prospective observational study conducted in Austria, relevant alcohol intake was found in 29% and 25% of patients with previously diagnosed NAFLD and MASLD, respectively.93 Lower SES and food insecurity related to the increased affordability and consumption of high-fat, high-sugar ultraprocessed foods, might be related to the increased prevalence of SLD and advanced liver fibrosis.56,94 An inability to make healthy lifestyle choices related to income and/ or education level, ethnicity, gender inequities, socio-cultural influences, and commercial determinants of health, have a significant impact on the pathogenesis of MASLD.95 An association of metabolic diseases including MASLD with

exposure to toxic chemicals has been highlighted.96,97 A potential link between the group of anthropogenic fluorinated organic chemicals, widely used in household and industrial products, and liver cancer has been reported in the literature.98,99 The specific impact of exposure to contaminants on the increased prevalence/incidence of MASLD and potential liver cancer risk in the European context should be evaluated, considering also the potential role of SDoH.100 Lack of awareness and low health literacy, strictly correlated with SDoH, affect disease management and harm reduction. In a survey of individuals with SLD, mostly based in Europe, a lack of awareness about the liver fibrosis stage was significantly associated with poor adherence to lifestyle and behaviour adjustments, the main form of disease management.101 Addressing SDoH-related behaviour changes requires interventions that consider cost, cultural diversity, language and health literacy. Progression to cirrhosis Improved and equal access to management of chronic liver disease to avoid progression to cirrhosis is a core element in fighting liver cancer. The need to identify and break down social, cultural, and economic barriers make treatment access more complex for specific groups of the population.12 The evidence reported in Table 1 indicates that socially disadvantaged groups, underserved communities, or those who are unemployed are disproportionately harmed by liver diseases, experiencing both higher incidence and mortality. Inequities in cirrhosis-related mortality were observed in relation to individual and socio-economic levels, with the highest death rates occurring among those with the lowest educational attainment and living in socio-economically disadvantaged areas.34,66,102, 103, 104 Late diagnosis is a challenge, leading to more advanced liver disease at presentation and, potentially, to high rates of liver cancer in the long term.105,106 The Lancet Standing Commission on Liver Disease in the UK highlighted that approximately 75% of patients with cirrhosis were unaware of their disease until presenting as an emergency.33,107 In addition to the reduced allocation of resources, a lack of disease awareness, low health literacy, language barriers, stigmatisation, discrimination, a lack of access to therapy in

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Gastroenterology & Endocrinology - Liver Cancer

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community settings, and fear of disclosing sensitive information, lead to further discrimination, stigma, and late diagnosis in most of the cases.3,108,109 Inequities in the liver cancer care pathway ELPA (The European Liver Patients Association) and Digestive Cancers Europe (DiCE) have called for increased equity in best practices for the prevention, diagnosis, and management of liver cancer in Europe.12,110,111 Only by actively addressing barriers to better care and investing appropriately can Europe provide equitable services for those at risk of or living with liver cancer, and ensure that no patient is left behind.112 The majority of studies on liver cancer have focused on biomedical factors that determine inequities in the prognosis and mortality rate among different populations, without paying specific attention to potential SDoH-related prognostic factors.113 Liver disease care worsens in the most socio-economically disadvantaged regions,114 but most research in the field of liver cancer in Europe neglects the underlying causes of inequities in the liver cancer pathway. In addition, there are no studies in liver cancer on how policies or interventions could impact health inequity. In the following section, we address the available evidence that focuses on the equity issues in each step of the liver cancer care pathway in Europe. Screening and early diagnosis EASL (The European Association for the Study of Liver) recommends HCC screening in patients with cirrhosis and in high-risk groups; however, periodic surveillance in Europe is suboptimal and heterogeneous in clinical practice.12,115 In Europe, only 22% of HCCs were diagnosed by surveillance, and, in more than one-third of cases, surveillance was indicated but missed.102 In 35% of cases surveillance was missed due to the doctor's failure to order surveillance or to diagnose the underlying liver disease. Significantly more patients with MASLD or ArLD had missed surveillance because of undiagnosed liver disease compared with other diagnoses, such as cardiovascular disease, tumours etc.102 Liver health receives less attention than many other health areas, and knowledge about liver health and disease is generally poor among the general

population, patients, general practitioners and non-liver health specialists.55,115,116 The reasons for missed surveillance include a lack of awareness about, adherence to, access to and dedicated programmes that take into consideration the potential effect of SDoH in each of the above mentioned issue.12,102,117 In addition to the application of risk-based approaches that consider liver disease severity, personalised surveillance in HCC should consider SDOH as potentially linked with liver cancer risk.12 This could help to better frame specific populations or groups at higher risk, avoiding screening in those patients without risk and preventing potential screening-related harms.118 In Europe, individual barriers (e.g. low socio-economic background and low health literacy skill and awareness) and contextual barriers (e.g. hard-to-reach health facilities) may be exacerbated by the fact that liver cancer surveillance is commonly offered only by specialists, causing frequent delays in diagnosis due to poor linkage to care and/or absorptive capacity at secondary care institutions.12 The effectiveness of policies and organisational measures should focus on the socio-cultural characteristics of the populations to be reached and, in particular, the most vulnerable groups should be targeted. Access to treatment and survivorship The ability to realise the right to health depends on the ability of individuals to identify and express their health needs, to make healthy choices, and to access effective interventions.119 In most European countries, ideally, the availability of resources could permit the best options for HCC care, however, access to curative treatment and survival are frequently not correlated with the incidence of HCC across different countries and different geographical areas within a country.120 Instead, survival is mainly related to the availability of resources in a specific region, with treatment provided when a cure is possible. Country profiles regarding liver cancer care, through surveys, have been reported very recently by DiCE.111 Of 25 countries, 18 have national guidelines for HCC, though often not well recognised by clinicians, most countries have approved treatment, and all offer some level of reimbursement In addition, the number of physicians and medical specialists, access to medical facilities, the

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confidence that physicians have in the benefit of actively treating patients with HCC, and physicians’ expertise in performing invasive treatments are also factors, not strictly related to SDoH, that determine inequities in liver cancer care in Europe.120 Differences in the patient’s SES could determine access to HCC treatment. Access to new therapies and cancer treatments in clinical trials is generally restricted to expert centres in high-income regions, excluding patients from economically deprived regions.121 The risk of major bias due to the retrospective design of the data collection in several studies and/or limited information about potential confounders, related or not with SDoH, could not be excluded and needs to be explored. Considering the vulnerable populations, for instance, migrants and refugees, there is no data in European countries on their access to liver cancer care, due to the absence of health insurance in their country of transit or arrival, their lack of knowledge regarding healthcare coverage, and language barriers. Quality of life and patientreported outcomes Health-related quality of life (HRQoL) has only been addressed in clinical trials. Only two of the 25 countries that have available data from the DiCE survey, the UK and the Netherlands, collect data on QoL outside of clinical trials.111 In addition, PROs, including HRQoL, are important oncological outcome measures that are still underevaluated and under-reported in most clinical settings in Europe.125 Evaluating the potential role of SDoH in targeting, monitoring, and responding to PROs could enhance the provision of personcentred liver cancer care in Europe, thereby improving the clinical efficacy of established and emerging therapies. Future needs Liver health should be part of a general health policy that considers the role of SDoH. Five essential activities for the integration of social needs into liver cancer health policy can be identified: awareness, adjustment, assistance, alignment, and advocacy.126 Awareness, which is the necessary precondition for all other actions, requires screening for SDoH to identify social risk factors and assets for individuals and groups. The role played by SDoH in liver cancer should be assessed in full detail, clarifying the different

levels to which they belong (structural or intermediary), in order to assess the specific role of each factor and the possible interactions of different factors in liver cancer risk factor distribution, incidence, care and mortality. In particular, socio-economic position should be considered, evaluating specifically the different factors that determine it. Moreover, specific attention should be paid to vulnerable populations whose status is coupled with specificities in relation to structural and intermediate SDoH, that should be investigated in detail. Vaccination coverage, screening uptake, and treatment acceptance in vulnerable populations could indeed be conditioned by further psycho-social, behavioural, and cultural factors, including language and cultural barriers and fear of stigma. For migrants, any assessment would be incomplete and misleading if it does not consider, in addition to SDoH, other important information such as the country of origin, migration status, length of stay in the country of arrival, and travel history. After gaining a thorough understanding of the complex system of factors that can influence health outcomes, it is possible to improve preventative hepatology actions and increase liver cancer health equity.127 Adjustment activities are those aimed at tailoring care to overcome social barriers. In this regard, it might be beneficial to organise access to health services that are appropriate for the target group to be reached or to design proper communication tools. Of further help at an individual level would be the activities of assistance, e.g. connecting patients to social care resources outside of the healthcare system. Appropriate action is then complemented by community-level interventions in terms of alignment, e.g. organising social care assets to facilitate synergies, and advocacy, e.g. working with social care organisations to promote new policies. It would be useful to promote preventive measures and raise public awareness about liver cancer risk factors, empowering individuals with knowledge and encouraging healthy behaviours. The implementation of the European Cancer Inequalities Registry,128 which aims to monitor the entire continuum of the cancer pathway, can help to identify trends, disparities, and inequities in liver cancer in Europe. References available on request

Gastroenterology & Endocrinology - Diabetes

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Ground-breaking Insights into Diabetes Diabetes Ireland have launched the results of the first-ever survey highlighting the lived experience of people with diabetes in Ireland. For further information on “Accessing and Using Diabetes Health Services Survey 2023.” 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. Among adults, 37% reported they were already living with diabetesrelated 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 two or more appointments in the same period, with 67% of them having three 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 HSE LongTerm 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%). Overall, the rates of technology usage (CGM) were very high and there were no differences between Dublin and the rest of the country with insulin pump usage also being similar. However, in openended responses, many people referenced very long waiting lists and difficulties in accessing diabetes-related technology, mainly insulin pump therapy, as well as difficulties in accessing specialist multidisciplinary team members (i.e. dietitians, podiatrists, psychologists etc.). Generally, people rated their health and well-being as good, but one-third assessed it as fair, poor or very poor. 75% of respondents reported that they do not discuss mental health & wellbeing as part of their diabetes care with half welcoming an opportunity to do so. Dr Kate Gajewska, Research & Advocacy Manager, Diabetes Ireland who led the research and undertook the survey analysis, said:

Dr Kate Gajewska

“We regularly 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 task force 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. Cormac Devlin TD, Chairperson of the Cross Parliamentary Group on Diabetes said: “The economic burden of diabetes on the Irish healthcare system is now a major 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 task force 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 forwardthinking in our approach to dealing with diabetes long into the future and the immediate setting up of a force 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.”

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Gastroenterology & Endocrinology - Ulcerative Colitis

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Ulcerative Colitis: A Patient Perspective Written by Tammy Strickland

Ulcerative colitis (UC) has been part of my life for 15-16 years, just over half the time I’ve graced the earth. It’s actually a bit difficult to remember what it was like before my first flare. UC is a strange companion sometimes, especially given the relapsing-remitting nature of the disease and the fact that often the best course of treatment involves supressing the immune system. In an era of quickly-spreading infectious diseases, it can be quite alienating to have a chronic illness that no one has heard of or wants to speak about as it involves the lower gastrointestinal tract. It can be extremely challenging and debilitating in many ways and yet I am adamant that it will not defeat me or people in a similar situation. My Road to Diagnosis When I was 14, I experienced a very bad stomach flu that lasted a week or so. This flu kicked off a year-long UC flare-up that left me very sick, skinny and emaciated. I was visiting the toilet 20 plus times a day (all bloody diarrhoea), losing my usual voracious appetite for food and sleeping as soon as I got back from school. My menstrual cycle ceased completely as I lost more and more weight. Some people in my life feared that I’d developed an eating disorder while others saw me looking gaunt and losing some of my hair and thought that I had some sort of cancer. I tried to keep going as usual in school and after school activities, but in the end, something had to give. At age 15, I was hospitalised for a month, very swiftly diagnosed with UC (pan colitis) after a series of

tests and began treatment. No one in my family or friend network had ever heard of inflammatory bowel disease (IBD) and almost everyone thought it was the same as IBS. No one could understand why I had been so severely affected by something they regarded as innocuous. As a result, and I suppose understandably, I didn’t really want to talk about any of it with anyone as I felt it would only lead to an argument or an insult. Many people in my life unfortunately had the idea that IBD was caused by psychological stress and would tell me to ‘just relax’ a lot. This really bothered me (and still does). Everyone has a certain amount of psychological stress in their lives – it’s part of being alive and being able to adapt and cope with challenges. Naturally, an overdose of it presents problems in us all and can exacerbate many different types of illnesses, including IBD. It’s not causative though. Pointing the finger at an IBD patients’ stress levels as the reason they are unwell at all is extremely inaccurate, unhelpful and unfair. I always knew that stress wasn’t causative and read research papers to prove my point. IBD is of course part genetic, part environmental. I read all about it in immunology textbooks and yet my arguments fell on deaf ears. I was the stressed girl who got sick at important life moments. It took many years to fully accept that people were going to think things about me that I couldn’t change and that I could still ‘own’ my situation and know who I was. Managing IBD Over the Years After diagnosis and a long period on and off steroids, I was prescribed immunosuppressants for about 5 years. I also stayed on a maintenance dose of antiinflammatory medications. I never really experienced as bad a flare as my initial one, although I did

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

unfortunately catch swine flu when I was in transition year in school and that wiped me out completely. I also had the odd extraintestinal symptom including skin, eye and joint inflammation but again these tended to come and go. I was lucky in many ways that I had so many good years responding well to my medications and in remission. It meant that I could travel and live my life without complication. It was only after my most recent flare-up that I switched to biological therapy. This wasn’t without its own challenges. I have frequently picked up nasty infections, including shingles, urinary tract and respiratory tract infections which can make life a little more uncomfortable or severely interrupt it. Having IBD in Adolescence Versus Adulthood Being diagnosed with IBD as a teen was both a relief (to know what was going on) and a scary revelation. The symptoms of UC can be quite frightening (particularly the bloody stools and chronic abdominal pain). Being told I would be on medication for life from a young age was also quite daunting. It’s not something you envision for yourself as a teen – when you really just want to be normal. I always hated taking my many tablets in front of people and covered up my arms that were bruised from venepuncture. I didn’t want anyone asking questions. I think there definitely was a sense of shame in it all. When I was undiagnosed, I was extremely worried that I had bowel cancer and didn’t know what to do. It can be quite difficult to talk about bowel-related topics, especially as a young person, when self-image is everything. I really didn’t want people noticing how often I went to the toilet or for how long I was there, so I tried not to go.

In all honesty, when I saw bloody stools, felt the extreme abdominal pain and had no energy for life anymore, I really thought I was going to die. I was sure of it and almost became resigned to it. When I was brought to see a specialist, I was so relieved to be told that I had IBD and that it was treatable and manageable. I couldn’t believe that I could feel normal again – which is what happened when I started taking steroids for the first time. It was like magic. I was going to live. Mental Health Challenges As previously mentioned, at first I was unwilling to talk about what IBD was and how it impacted my life. Since I was diagnosed as a teenager, I was afraid of how people would view me if I spoke about what was going on. I actually ended up missing my Junior Cert because my first flare was so bad. A lot of people in my secondary school noticed my absence during the Junior Cert and assumed I’d had some sort of breakdown due to exam stress. I never wanted to correct them in a way, because I wasn’t yet comfortable to talk about my UC. This seriously affected my confidence for many years. No one really looked at me the same way after this first flare and I felt that I was required to somehow prove my worthiness or abilities when I was in school or outside of it, so people didn’t regard me in such limiting ways. I couldn’t wait to move away from secondary school – to college and work- where no one would know anything about me ever having medical problems. Of course, IBD never leaves and pretending it doesn’t affect me is never the answer. Dealing with other challenges in life, I learned that there was nothing to be ashamed of in having UC or any other chronic illness and that speaking openly about my symptoms was actually

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Tammy Strickland pictured attending the British Society of Immunology Conference in December 2023 transparent about the difficulties of having IBD is really important to me now. I also really like to share the many good things that have happened over the years with people as my resilience fills me with a sense of pride. When I was in transition year for example, following my first recovery from a flare, a couple of good things happened in school. I starred in my school play and set up a small online business. I also realised that I wanted to be a scientist. My Life Now

quite liberating. These days all of my close friends and family know about my UC and my partner in particular is so supportive. They all understand that some plans need to be cancelled and sometimes I really need rest, especially during a flare. Even with a supportive network, UC can really take its toll on

mental health. Getting the right support is essential for coping with the anxiety that goes with searching for toilets everywhere you go and the depression of knowing your own limitations. One thing I still struggle with is not being too hard on myself. Society can be rather ablest and unforgiving, but that’s really not anything I can control. Being

I have since completed 2 degrees (BSc and MSc) in biomedical fields and travelled during both (to Sweden and the US) to complete my thesis projects. I worked in science for a few years between degrees and published some articles in paediatric neurology. Eventually I was awarded a joint-funding to complete my neuroscience PhD in the Royal College of Surgeons. At the same time, I got heavily involved in science communication and won a national competition for a video I made about epilepsy and circadian rhythms. Ironically, I study the immune system in a great amount of detail and often attend talks about IBD in the preclinical research context. Hearing speakers discuss the debilitating nature of UC and Crohn’s is oddly liberating too. They are severe diseases after all and ‘just relaxing’ won’t cut it. Hearing about all the

new avenues of research is also exciting and brings with it a sense of home that IBD won’t always be such a burden. My UC has remained part of my life and as mentioned above can sometimes interrupt my studies/work. Being open with my employer and my funders is important to ensure that I can finish my project and achieve my goals. Again, I still struggle with typical UC intestinal symptoms when I flare but also as I’ve gotten older, I have experienced more extraintestinal symptoms that I’m not always prepared for. Kidney stones, chronic pain and severe fatigue often dictate my productivity in my work and can frankly be quite disheartening. The focus of my IBD care often doesn’t really cover my extraintestinal symptoms and it can become exhausting trying to advocate for oneself in order to be heard and treated. Being taken seriously is extremely important in any medical scenario, but especially in IBD where sometimes the mental and physical toll of typical and atypical symptoms is underestimated. Involvement in decision-making for my own health is paramount, especially in a disease that often robs you of control in many ways. Lastly, owning and embracing the chaos of IBD is essential for me. I have learned to accept it and am still learning to be kinder and more forgiving of my body, that after all is only doing its best. For further information visit www.crohnscolitis.ie Helpline: +353 1 531 2983

News New Children’s Hospital Project Budget The government has approved enhanced capital and current budget sanctions for the New Children’s Hospital (NCH) project, bringing the total approved budget to ¤2.24 billion (previously approved budget was ¤1.73 billion). Included in this are the design, build and equipping costs (including the Satellite Centres at Tallaght and Connolly) of ¤1.88 billion, and a separate ¤360 million for the integration and transition of services to the NCH, including commissioning, ICT and the Electronic Health Record. The new hospital will be a state-ofthe-art hospital. It will be Ireland’s first fully digital public hospital,

providing 300 individual, inpatient, ensuite rooms - each with its own place for a parent/guardian to sleep. In addition, it will double the current number of critical care beds to 60, and have 93-day beds and 20 dedicated, ensuite mental health (CAMHS) beds. Theatre capacity will be expanded to 22 theatres and procedure rooms. The building will accommodate 5 MRIs and 110 outpatient rooms. The approved increase in the capital budget will address areas identified in the 2019 report, the New Children’s Hospital Independent Review of Escalation in Costs, carried out by PWC. The Report said that the New

Children's Hospital was unique in scope, scale and complexity in comparison to any other health infrastructure project in Ireland's history and was explicit in stating that the project's complexity should not be understated. However, it identified a series of weaknesses in terms of set-up, planning, budget, execution, and governance that have since been addressed. The report considered the alternative option of re-tendering the works. It concluded that this was an unrealistic fall-back option and would have increased costs

further and would have likely resulted in no hospital being built. The 2019 PwC report also noted that a number of risks had the potential to place further cost pressure on the approved capital budget, including contractor entitlements under the contract, the outturn of provisional sums (items for which there could be no cost certainty until their procurement closer to the end of the project), recovery of construction inflation >4%, the need for additional capacity and capability in the NPHDB executive team, and the contractor’s right to claim for additional true costs in line with public works contract provisions.

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Gastroenterology & Endocrinology

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Recent changes in findings at oesophagogastroduodenoscopy (OGD): clinical implications and management Written by Professor Humphrey J. O’Connor MD FRCPI AGAF Trinity Academic Gastroenterology Group - Trinity Centre for Health Sciences, Tallaght University Hospital, Tallaght, Dublin 24. email: oconnor_hj@hotmail.com

Introduction Fibreoptic endoscopy revolutionised the practice of gastroenterology allowing direct visualisation of the gastrointestinal tract and mucosal biopsy to guide accurate diagnosis and treatment of gastrointestinal (GI) disorders. With so much emphasis over the years on service demands, less attention was paid to how much findings at OGD changed to where the clinical picture at OGD today is in many ways quite different to that of 40-50 years ago. Changed findings at OGD often equate with a change in diagnosis and treatment. The aim of this paper is to describe the clinical implications of recent changes in OGD findings and their management. Peptic Ulcer Disease (PUD) The groundbreaking discovery of H. pylori infection 40 years ago pinpointed a critical factor in the causation of peptic ulcer disease (PUD) and gastric neoplasia. Assessment of H. pylori infection status using gastric biopsies is now an integral part of the conduct of OGD and despite initial scepticism, eradication of H. pylori infection has become the treatment of choice for PUD. What was not appreciated at the time of its discovery was how much the prevalence of H. pylori infection was in decline and had been for several decades largely as a result of improvements in socioeconomic conditions in childhood, coupled with improved hygiene and sanitation. There is close correlation between

the prevalence of H. pylori infection and the incidence of its related diseases and a fall in disease expression accompanied the falling infection rate. Consequently, the most obvious change in OGD findings over the past four decades is the dramatic decline in H. pylori -positive PUD and its replacement by gastro-oesophageal reflux disease (GORD). International studies show the fall in PUD is a worldwide phenomenon where the prevalence of PUD probably peaked in the early 1980’s and declined thereafter. The fall in PUD is more pronounced for duodenal ulcer compared with gastric ulcer, and most marked in younger age groups. Idiopathic peptic ulcer disease (IPUD) is diagnosed when ulcers occur where H. pylori, NSAID use, and more unusual causes of PUD have been excluded, including non- H. pylori Helicobacter infection. As H. pylori-positive PUD decreased, IPUD increased. Risk factors for IPUD may be increasing age and multiple comorbidities. In clinical practice, idiopathic ulcers tend to be multiple and recurrent, seem more susceptible to complications, and may be more refractory to treatment. In the absence of data from randomised controlled trials of treatment of IPUD, current advice is to continue full doses of proton pump inhibitors (PPIs) long-term as maintenance treatment. Despite the striking decrease in uncomplicated H. pylori-

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positive PUD, hospitalisation for complicated PUD has not decreased. The problem of peptic ulcer bleeding continues, particularly in elderly females, where about 25% of ulcers present de novo with a complication without antecedent dyspepsia. Systematic review has shown H. pylori infection and NSAIDs are independent and synergistic risk factors for both uncomplicated and bleeding PUD. Clinical trials in high risk patients have shown H. pylori eradication alone may not be enough to eliminate the risk of bleeding and suggest co-prescription of PPIs should continue long-term. Current management of idiopathic bleeding ulcers is poorly defined leaving long-term high-dose PPI therapy as perhaps the best option. Gastroesophageal Reflux Disease (GORD) Several studies have documented the increase in the prevalence of GORD at OGD. For instance, a study from Rotherham, UK found a dramatic five-fold increase in the prevalence of GORD at OGD from 1977-2001 where it was described as a new phenomenon. Epidemiological studies, and studies in primary care, have also documented the opposing time trends of PUD and GORD, the significant increase in time in the prevalence of GORD symptoms, increased GORD-related hospitalisation over the past four decades, and the rise in GORD as a worldwide phenomenon. Upper Gastrointestinal Cancer The arrival of fibreoptic endoscopy came at a time of significant and opposing changes in the incidence of gastric and oesophageal cancer, similar to what was happening between PUD and GORD. Before 1940, gastric cancer was the leading cause of cancer death in American males but went into sharp decline over the time period of 1930 – 1978. As gastric cancer declined, oesophageal adenocarcinoma (OAC) showed a dramatic increase. Diverging time trends also appeared for gastric cardia cancer. H. pylori -related cardia cancer decreased

whereas reflux-related cardia cancer increased and the curves for reflux-related cardia cancer and OAC closely mirrored each other. An important cross-sectional and longitudinal study using cancer registry data from 51 countries confirmed the presence of a worldwide negative association between the incidence and time trends of gastric cancer and OAC, and suggested H. pylori infection might be the key environmental factor exerting opposite effects on the incidence of the two cancers. Studies in H. pylori-positive and H. pylori-negative volunteers found less gastric acidity and decreased density of parietal and chief cells in the H. pylori-positive group which might in turn result in less noxious gastroesophageal refluxate theoretically protecting against OAC. Barrett’s Oesophagus (BO) Barrett’s oesophagus (BO) is defined as a condition in which metaplastic columnar epithelium that predisposes to cancer development replaces stratified squamous epithelium that normally lines the distal oesophagus. BO is an acquired condition occurring in response to gastroesophageal reflux and as the incidence of GORD has increased, so has the incidence of BO. The rise in BO has also paralleled the obesity epidemic, and abdominal obesity in particular is a strong risk factor for BO. There is also a strong inverse relationship between H. pylori infection and BO, especially Cag A-positive strains, and the apparent protective effect of H. pylori is probably mediated by decreasing GORD in infected patients. The ability to easily visualise and biopsy the lower oesophagus at OGD raised the possibility that aggressive screening, surveillance and management of BO might make an impact on the rising threat of OAC and detect OAC at an early curable stage. Surveillance for BO is now firmly established as an integral part of the OGD workload. Patients with OAC discovered as a result of BO surveillance present with earlier stage disease, are less likely to have lymph node involvement, and have better

29 Table: Response to changes in OGD findings Table: Response to changes in OGD findings

Site

Oesophagus

Observed Change

↑ Barrett’s oesophagus

↑ EoE

Stomach

EoE strictures ↓ Helicobacter pylori

↑ Antibiotic resistance Duodenum short-term life expectancy than patients presenting with symptoms of OAC. Advances in therapeutic endoscopy over the past decade or so have made endoscopic mucosal resection the treatment of choice for high grade dysplasia or intramucosal cancer detected during BO surveillance, obviating the need for oesophagectomy with its attendant risks. Following endoscopic resection, metachronous neoplasia can then be prevented by radiofrequency ablation of residual Barrett’s mucosa. The endoscopist has an important role in optimising the value of BO surveillance (Table). High definition white light endoscopy with longer inspection times is associated with increased detection of high grade dysplasia and adenocarcinoma in BO. The optimal biopsy protocol includes sampling of any visible lesions together with systematic four-quadrant biopsies at every 2cm of visible Barrett’s mucosa, the Seattle protocol. Adherence to this protocol is not universal and, ironically, is considerably less in patients where adherence is needed most, those with long segments of BO. Nonadherence to the Seattle protocol has been shown to result in a lower rate of dysplasia detection, whereas adherence can detect dysplasia in 13 times more patients than a nonsystematic biopsy protocol. Ironically, one of the disappointing aspects of endoscopy surveillance for BO has been its negligible impact on the rising tide of OAC. A number of factors might account for this apparent anomaly. About 40% of patients with OAC report no history of chronic reflux symptoms and hence are not likely to ever undergo OGD screening or surveillance for BO. The annual

↑ Coeliac disease

Response

- one minute per cm - visible lesions - four quadrant - every 2cm • Seattle protocol • ≥ 6 biopsies • ≥ 2 sites • Careful stepwise dilatation - off PPI x 2 weeks • Biopsies: - off antibiotics x 4 weeks - Antrum x 2 - Corpus x 2 • ↑ AST-based therapy • Use NGS methods • Retest after therapy - D2 x 4 • Biopsies: - D1 x 2 • One biopsy per pass • Repeat on gluten-free diet • Inspection • Biopsy:

Abbreviations: AST, antimicrobial sensitivity testing; D1, duodenal cap; D2, descending duodenum; Eosinophilic

Abbreviations: sensitivity testing;PPI, D1, proton duodenal cap;inhibitor. D2, descending duodenum; Eosinophilic oesophagitis;AST, NGS,antimicrobial next-generation sequencing; pump oesophagitis; NGS, next-generation sequencing; PPI, proton pump inhibitor.

Figure: Summary of changes in OGD findings over 40 years with apparent transition from H. pylori-positive “phenotype” to H. pylori-negative “phenotype” cancer conversion rate in BO 1983 is only 0.5%, and the majority of patients with BO die of other causes, particularly cardiovascular disease. Also, fewer than 5% of patients with OAC are known GORDthey to have had BO before presented with symptoms. It also appears that approximately 50% of OAC has a distinct phenotype H pylori without evidence of associated intestinal metaplasia or visible BO segments. This non-BO cancer phenotype appears to be more aggressive and has a worse prognosis than the BO phenotype.

EoE

is also responsive to treatment. 2023 EoE has a patchy distribution EoE is characterised clinically and increasing EoE the number of by symptoms of oesophageal biopsies increases OACdiagnostic dysfunction and histologically ↑ GORD yield. Recent ↑ European guidelines by eosinophil-predominant suggest taking at least six inflammation with an eosinophil ↑ BO oesophageal biopsies from at count > 15 eosinophils/ high least two locations focusing on ↑RRCC power field. Since its initial areas with mucosal abnormality. description in 1993, EoE has Second, symptoms or nonincreased in incidence and ↑ Sporadic FGPs biomarkers cannot be invasive prevalence and become a major relied on to monitor EoE. Hence, cause of upper GI morbidity. whether treatment is with PPIs, The natural history of EoE is that swallowed topical steroids, dietary Adenoma of a chronic, perhaps lifelong, measures, or novel biological inflammatory disorder which if left agents such as dupilumab, undiagnosed and untreated leads repeat OGD and biopsies are to HP oesophageal wall remodelling, polyps CD Eosinophilic Gastrointestinal necessary to accurately monitor and possible stricture formation. Disorders (EGIDs) ↑ CD disease activity and document H. pylori-posi�ve IPUD There is no evidence that EoE is a EG & EGE remission. Third, oesophageal Distal GCA PUD Apart from significant changes NSAID ulcers premalignant condition. stricture is a key complication of in existing diseases, the era of H. pylori infection appears to have EoE and endoscopic dilatation is fibreoptic endoscopy has also a protective effect against EoE. an important part of the treatment Abbreviations: BO, Barrett’s oesophagus; CD, coeliac disease; EG, eosinophilic gastritis; EGE, eosinophilic witnessed the emergence of algorithm to help relieve gastro-enteritis; EoE, eosinophilic FGPs, fundic gland polyps; GCA, gastric cancer; GORD, dysphagia gastroThe endoscopist has an eosinophilic GI disorders (EGIDs), oesophagitis; anddisease; preventNSAID food impaction. oesophageal disease; HP, hyperplastic polyp; idiopathic peptic ulcer ulcers, nonimportant roleIPUD, in both diagnosis apparently newreflux clinical disorders. In contrast to benign peptic and management of EoE. First, EGIDs are anti-inflammatory chronic inflammatory steroidal drug ulcers; OAC, oesophageal adenocarcinoma; PUD, peptic ulcer disease; RRCC, strictures, mucosal tears causing EoE can only be diagnosed by conditions characterised by GI reflux-related cardia cancer postprocedural retrosternal pain endoscopy and oesophageal symptoms and pathological lasting several days are common biopsies. EoE has some eosinophilic infiltration of the GI after dilatation in EoE and patients characteristic endoscopy findings mucosa where secondary causes should be advised about this including mucosal oedema, rings, of tissue eosinophilia have been possibility before the procedure. exudates, furrows, and strictures excluded. Although still rare in Careful stepwise dilatation should and an endoscopic reference routine clinical practice, there be performed by experienced score (EREFS) can be calculated appears to be a genuine increase endoscopists adhering to the “rule based on these findings. The in all types of EGIDs including of 3” and published guidelines. EREFS score helps standardise eosinophilic oesophagitis (EoE), recognition and reporting of eosinophilic gastritis (EG) and Non-oesophageal EGIDs in the the main endoscopic features, eosinophilic gastroenteritis (EGE). upper GI tract include EG and has excellent interobserver and EoE is the most prevalent and EGE and endoscopy findings well-studied EGID. intraobservor agreement, and in EG and EGE are normal in

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

• Repeat on gluten-free diet

Abbreviations: AST, antimicrobial sensitivity testing; D1, duodenal cap; D2, descending duodenum; Eosinophilic oesophagitis; NGS, next-generation sequencing; PPI, proton pump inhibitor.

Gastroenterology & Endocrinology

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Figure: Summary of changes in OGD findings over 40 years with apparent transition from H. pylori-positive “phenotype” to H. pylori-negative “phenotype”

1983

2023 ↑ GORD

EoE ↑ OAC

↑ BO

GORD

↑RRCC H pylori

↑ Sporadic FGPs Adenoma

HP polyps

CD H. pylori-posi�ve PUD

Distal GCA

↑ CD

IPUD NSAID ulcers

EG & EGE

Abbreviations: BO, Barrett’s oesophagus; disease;from EG, gastritis; EGE, eosinophilic Figure: Summary of changes in OGD findings over 40 yearsCD, withcoeliac apparent transition H. eosinophilic pylori-positive “phenotype” to H. pylori-negative “phenotype” - Reproduced with permission from John Wiley & Sons Publishers. gastro-enteritis; EoE, eosinophilic oesophagitis; FGPs, fundic gland polyps; GCA, gastric cancer; GORD, gastrooesophageal reflux disease; HP, hyperplastic polyp; IPUD, idiopathic peptic ulcer disease; NSAID ulcers, nonsteroidal anti-inflammatory drug ulcers; OAC, oesophageal adenocarcinoma; PUD, peptic ulcer disease; RRCC, about two-thirds of cases but in the prevalence of HPs published recommendations. PUD, H. pylori infection is now reflux-related cardia cancer decline coupled with a steep increase in Selecting H. pylori therapy based encountered more often in can include mucosal erythema, ulceration, nodularity, and friability. Hence the importance of taking multiple gastric and duodenal biopsies regardless of endoscopic appearances. In terms of prognosis, decreased tissue eosinophilia is associated with improvement in symptoms, and in endoscopic and histological findings. Hence, repeat OGD and biopsies to assess response to treatment remains an integral part of the care plan for EGID patients. Gastric Polyps A gastric polyp is an abnormal growth of tissue originating in the epithelium or submucosa and protruding into the stomach lumen. Over the last few decades, there have been dramatic changes in the spectrum of gastric polyps, both in terms of polyp type, frequency, and anatomical site. In the early years of OGD, hyperplastic polyps (HPs) and adenomas were the dominant polyp types and the emphasis in clinical practice was on assessment of malignant potential. If H. pylori is found in the surrounding gastric mucosa, HPs often regress after successful eradication therapy. The late 1990s saw a progressive

the prevalence of sporadic fundic gland polyps (FGPs). That trend has continued to the present day. Long-term use of PPIs and the absence of H. pylori have emerged as important factors underlying what appears to be an emerging epidemic of sporadic FGPs. An important study from the Netherlands found 1. long-term PPI use was associated with an increased risk of FGPs while short-term (<1 yr) was not, 2. the PPI effect was a class effect, 3. FGPs could occur without PPI use, 4. none of the patients with FGPs had H. pylori or signs of gastritis, and 5. the risk of dysplasia in PPI-associated FGPs was negligible. The epidemic of sporadic FGPs appears to be a worldwide phenomenon and mirrors the exponential rise in the use of PPIs, both appropriate and inappropriate, evident over the past 30 years. H. pylori In the early years of H. pylori eradication, H. pylori-positive PUD was common, eradication and ulcer cure rates were high, and patient reported outcomes were good. With the fall off in

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patients with either functional dyspepsia and normal endoscopy findings, or in the setting of GORD, situations where it is often unclear if eradication of infection might be of clinical value. Patients with functional dyspepsia who obtain sustained relief of symptoms after eradication therapy are now classed as having H. pylori-associated dyspepsia, and it is acknowledged that H. pylori eradication in GORD does not fundamentally change the chronic relapsing nature of the condition. Over the past 30 years, H. pylori itself has become more difficult to eradicate. Treatment regimens that were successful in the 1990s have been undermined by the steep rise of antimicrobial resistance and the efficacy of standard triple therapy in particular has declined as resistance to clarithromycin has increased. In Europe, gastroenterologists in routine clinical practice often prescribe eradication therapy for only seven to ten days (69%), use low dose PPIs (48%), prescribe standard triple therapy where it is likely to be ineffective (46%), and seem slow to adapt to

on prior antibiotic exposure is good practice, yet in recent US surveys, only 38% of healthcare practitioners asked patients about prior antibiotic exposure, and only 58% checked for confirmation of cure after treatment. Obtaining gastric biopsies specifically for H. pylori culture and sensitivity is rare in routine OGD practice, related to factors such as logistical challenges, lack of laboratory back-up, and cost. H. pylori is also a fastidious bacterium where culture is time-consuming and not always successful. Molecular antibiotic resistance testing using Next Generation Sequencing (NGS) methods offers a simpler, faster alternative to traditional culturebased testing and the presence of mutations detected by molecular tests correlates well with culturebased susceptibility tests. NGS methods simultaneously identify DNA mutations in the H. pylori genome responsible for resistance to all the antibiotics commonly used to treat the infection and could conceivably replace culture methods and at least encourage more susceptibility-based H. pylori treatment in clinical practice.

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Coeliac Disease (CD) Coeliac disease (CD) is an immune-mediated enteropathy triggered in genetically susceptible individuals by ingestion of gluten. The last 50 years or more have seen a true increase in the incidence and prevalence of CD. At the same time, the clinical picture of CD has changed. Presentation with classical features such as diarrhoea and weight loss has decreased, and CD now increasingly presents with nonclassical features such as iron deficiency anaemia or mimicking irritable bowel syndrome. Presentation to specialties other than gastroenterology and screendetected CD has increased. Age at presentation has increased while severity of histopathological damage has decreased. In a study that assessed the relationship between CD and H. pylori status, CD was diagnosed in 4.4.% of H. pylori-positive patients compared with 8.8% in H. pylorinegative patients and this strong inverse relationship remained after adjustment for age, gender, and socioeconomic status. Irrespective of time trends in disease frequency and phenotype, small bowel biopsy using endoscopic forceps biopsy of the descending duodenum is the most reliable method of diagnosing villous atrophy. More recently, a single biopsy technique has been shown to improve the quality of duodenal biopsy specimens and ideally endoscopists should take only one biopsy specimen per pass of the forceps. Villous atrophy can be confined to the duodenal bulb and collection of biopsy specimens from D1 can increase the sensitivity of CD detection by 10%. Published guidelines therefore suggest 4 biopsy specimens should be taken from the descending duodenum and 1 or 2 biopsies from the duodenal bulb. A study from the US showed adherence to the proposed standard of submitting 4 or more specimens occurred in only 35% of OGDs, and it is not unusual for coeliac patients to have had a prior OGD where duodenal biopsies were not taken, and the opportunity missed to diagnose the condition. Duodenal biopsy was also more likely if the duodenal mucosa looked abnormal despite the fact that endoscopic markers of CD are most associated with severe pathological changes and lack

diagnostic sensitivity. OGD also has an important role in monitoring CD. Similar to Inflammatory Bowel Disease, the goal of treatment in CD that ensures the best patient outcome is complete mucosal healing. Coeliac serology has excellent sensitivity and specificity in the diagnosis of CD but falls down when it comes to monitoring patients on gluten free diet. Likewise, symptoms in coeliac patients are poorly predictive of mucosal status on gluten-free diet and villous atrophy can occur in the absence of symptoms. Hence, follow up OGD and duodenal biopsy remains the optimal test to assess mucosal recovery on gluten-free diet. Discussion Substantial changes have occurred in OGD findings over the past 40 years or so and the speed of change suggests environmental rather than genetic factors are responsible. The changes are summarised in the Figure and suggest a transition has occurred from features suggesting a H. pylori-positive “phenotype” (DU and GU, distal gastric cancer, hyperplastic or adenomatous gastric polyps) to a H. pylorinegative “phenotype” (GORD, oesophageal and cardia cancer, IPUD, FGPs, EGIDs, increased CD). By reducing gastric acidity, H. pylori may have been protective against reflux disorders whereas the decline in H. pylori with resultant increased gastric acidity has contributed to the rise in reflux related disorders. The obesity epidemic that engulfed the developed world and now extending to developing countries is another likely causative factor that increased as H. pylori decreased. Obesity, particularly central obesity, is closely linked with increasing rates of reflux oesophagitis, BO, OAC, and cardia cancer. Interestingly, possible links have also been suggested between the absence of H. pylori per se and obesity where the lack of H. pylori, especially during childhood, might enhance the risk of obesity later in life, possibly related to increased levels of the appetite-stimulant hormone ghrelin in the H. pylori-negative stomach. The changed findings at OGD have clinical implications and pose some potential dilemmas for everyday clinical practice. PPIs are among the commonest prescribed medications worldwide

and prescription of PPIs has increased about 350% in the past 30 years. The rise in PPI prescribing is sustained by the parallel epidemic of obesity and GORD and the fact that GORD itself is a chronic relapsing disorder where adequate relief of symptoms is often PPI-dependant. However, long-term PPI treatment drives the growth and proliferation of FGPs, now the commonest gastric polyp encountered at OGD. Although currently looked on as non-neoplastic and not warranting ongoing surveillance, we have to admit the long-term prognosis for FGPs is unknown. H. pylori infection is now less common, often diagnosed in settings where the clinical impact of eradication is uncertain, and increasing antibiotic resistance has made successful eradication more difficult to achieve. Current management of H. pylori has to address these new realities. Ideally, eradication therapy should be based on the results of antimicrobial sensitivity testing, not empirical, and new molecular testing might ultimately make that approach more attainable during a busy endoscopy list. Apart from the discovery of H. pylori, one of the unexpected developments of the era of fibreoptic endoscopy has been the emergence of EGIDs, particularly EoE, as new disorders. The inflammatory process in EGIDs has many of the hallmarks of atopic or allergic disorders which have increased worldwide over the last few decades. CD is a lifelong autoimmune enteropathy which has also increased in incidence. EoE and CD both show an inverse relationship with H. pylori infection as if H. pylori in some way protects against these conditions. The debate goes on as to whether the apparent permissive effect on autoimmune and allergic diseases results from the absence of H. pylori per se or is part of the impact of the broader Hygiene Hypothesis. Hygiene Hypothesis suggests early life exposure to a diverse immune stimulating microbiome is fundamental to establishing a competent tolerant immune system whereas depletion of these stimuli in childhood fosters immune deviation and predisposes to the development of autoimmune or allergic diseases later in life in genetically susceptible individuals. Recent changes in OGD findings also have implications for the

conduct of OGD where accurate diagnosis now seems to depend less on appearances and more on obtaining comprehensive and adequate mucosal biopsies. In the oesophagus, non-adherence to validated biopsy protocols significantly reduces the chance of detecting dysplasia in BO and diagnosing EoE. In the stomach, optimal diagnosis of H. pylori infection requires mucosal biopsies from the gastric antrum and body and OGD performed at least two weeks and four weeks off PPI and antibiotic therapy, respectively. In the duodenum, CD is best diagnosed using good quality single biopsy specimens from the first and second parts of the duodenum. Similar biopsy considerations apply to monitoring response to treatment, particularly in EoE and CD, where symptoms and blood tests give inadequate guidance and documenting mucosal healing is increasingly important for long-term prognosis. Conclusions Findings at OGD have undergone a series of important changes over the past 40-50 years driven by environmental factors such as the falling prevalence of H. pylori infection, the obesity epidemic, and the huge rise in prescribing of PPI’s and antibiotics. There appears to be a transition from a H. pyloripositive “phenotype” 40 years ago to a H. pylori-negative “phenotype” today. This transition has important implications for the diagnosis of GI disorders, prescribing, and the conduct of OGD. Sincere thanks to Dr. Gerard Giblin, Mater University Hospital Dublin, for technical help with the Figure and to Mrs. Debbie Burke for expertly typing the manuscript. REFERENCES 1. O’Connor Humphrey J. Review: Forty years of Helicobacter pylori infection and changes in findings at esophagogastroduodenoscopy. Helicobacter 2023; 00: e13026. https://doi.org/10.1111/hel.13026 2. Malfertheiner P, et al. Management of Helicobacter pylori infection: the Maastricht 6th/Florence consensus report. Gut.2022 Aug 8: gutjnl- 2022- 327745 3. Wuesten BLAM, et al. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2023; 55:1124-1146

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Gastroenterology & Endocrinology - Gestational Diabetes

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Delivering Gestational Diabetes Care -

Maternity dietitians’ perspectives on delivering gestational diabetes care, and postpartum follow-up in Ireland: A qualitative study Written by: Pauline Dunne (Ph.D. candidate UCD), Márcia Carvalho (Ph.D. candidate University of Galway), Prof. Molly Byrne (Professor of Health Psychology, University of Galway), Prof. Andrew W. Murphy (Foundation Professor of General Practice, University of Galway), Prof. Sharleen O’Reilly (Associate Professor in Human Nutrition UCD).

Pauline Dunne M.Sc., RD This research is funded under a Health Research Board Collaborative Doctoral Award, 2019 (CDA-2019-001).

Background The prevalence of gestational diabetes mellitus (GDM) in Europe is approximately 5.4%,1 with varying rates influenced by population characteristics, diagnostic criteria, and screening strategies. In the Republic of Ireland, GDM prevalence is reported at 12.4%,2 posing health risks for both mother and child, leading to increased healthcare costs. Women with GDM face upwards of seven-fold risk of developing type 2 diabetes (T2D), with potential implications for health services.3–6 GDM management involves blood glucose monitoring, medical nutrition therapy (MNT), physical activity, and weight management.7,8 While most women manage GDM with these strategies, 15-30% may require metformin or insulin.9 Despite the central role of MNT,10 there are no universally adopted nutrition guidelines for GDM management, leading to inconsistencies in dietary recommendations. Internationally, dietitians have high levels of training and consistency

in GDM management, yet challenges in knowledge translation and resource disparities persist.11–13 In Ireland, limited research exists on dietitian involvement in GDM management,14,15 with no national prevention programme or guideline. This study sought to explore the perspectives of dietitians working in Ireland on GDM management, addressing gaps in understanding and providing insights for potential improvements in care and guidelines. Methods The study employed a qualitative approach, using focus group discussions and individual semi-structured interviews that were conducted from February to March 2021. Participants were required to: (i) be a registered dietitian in the Republic of Ireland, (ii) have a caseload which included women with GDM during pregnancy and/or postpartum, and (iii) be willing to discuss their knowledge, experiences, and perspectives on GDM. A purposive sampling approach aided recruitment,16 with a call out through the Irish Nutrition

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

& Dietetic Institute, Maternity Dietitians of Ireland specialist interest group, and direct call and/ or email to nutrition & dietetic departments at maternity hospitals in Ireland. The study did not predetermine sample size but considered information power and data richness to determine adequacy of sampling.17 The interviews and focus groups were conducted online due to COVID-19 restrictions, and the topic guide focused on GDM diagnosis, treatment, and postpartum care including T2D prevention. Each session was transcribed using Otter.ai, and NVivo v.12 software facilitated coding and analysis. The research team, comprising experienced dietitians and a health psychologist, performed reflexive thematic analysis with an inductive orientation to the data.18-20 The study aimed to identify experiential insights, employing a realist theoretical framework. Data analysis involved six phases, including familiarization, initial code generation, theme development, theme review, definition and naming, and report production.18,21 Theme conceptualisation, identification of boundaries, and coherence were addressed in developing the themes. Regular discussions took place to hone and confirm themes as true reflections of participant contributions. Once themes were developed, they were named, defined, and described with relevant excerpts from the transcripts and refined through regular discussions until the final versions were agreed on. Results Sixteen dietitians from 13 of 19 Irish maternity settings participated. The participants were all female and worked with individuals with GDM with varying levels of frequency. There was significant regional disparity and variation reported in the allocation of dietetic services for GDM.

The three themes generated were: A Complex Layered Role: Dietitians saw their primary role as providing nutritional guidance in a multidisciplinary context. All participants reported varied caseloads. Dietitians reported using a standardised resource, "The National Diet Sheet", ensuring consistency in information delivery. There was a need for empathy in addressing complex needs of patients, particularly when supporting those newly diagnosed with GDM, and challenges in addressing sensitive topics such as gestational weight gain. Challenges to Providing Optimum Care: For many nutrition & dietetic services, the COVID-19 pandemic necessitated a shift to online delivery, impacting group dynamics and peer support. Participants reported improved attendance rates with online education sessions but acknowledged disadvantages such as the lack of peer support. Issues of unequal care distribution, and limited time for health promotion, T2D prevention, and breastfeeding advice were highlighted. Inconsistencies in postpartum care and a lack of defined GDM care pathways were also reported, leading to frustration among participants. Framing Future Health Needs: Participants perceived the sixweek postpartum check (routinely offered to new mothers) as a missed opportunity for T2D prevention. Participating dietitians felt low T2D risk awareness among women (with GDM) and healthcare professionals, as a contributing factor to gaps in follow-up care. The need for a readily accessible T2D prevention programme, improved communication between hospital and community-based services, and a standardised national approach for follow-up (after GDM) were emphasised.

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Discussion The study reveals that dietitians consider themselves central to delivering MNT in GDM care. Despite a perceived national disparity in dietetic resource allocation, participants' experiences and views were generally consistent. The dietitian's role extends beyond traditional nutrition advice, involving nuanced, empathetic management within limited resources. Study findings broadly align with studies from other healthcare settings,11,12,22 however are unique in emphasising the complexity of the dietitian role in GDM management and potential role of the dietitian in postpartum T2D prevention. Participants acknowledged the stigma associated with GDM and recognised the need to sensitively support patients' emotional needs. Notably, there is no minimum standard for dietetic resource allocation in GDM management in Ireland. Many dietitians reported a single contact with an individual during their GDM pregnancy, similar to other studies,12,23 leading to reported disparities in care and insufficient resources to meet growing service demand. The COVID-19 pandemic prompted a shift to online MNT delivery, providing efficiency but raising concerns about reduced patient-centeredness due to diminished peer support. System-level barriers were identified for postpartum dietetic follow-up, with primary care deemed optimal for follow-up services and T2D prevention. Inconsistencies and lack of clarity in postpartum care processes were noted, emphasising the need for a defined follow-up approach. While T2D prevention programmes were deemed crucial, they are

lacking in Ireland. Research demonstrates dietitians as suitable leads for diabetes prevention programmes,24,25 and emphasises the need for tailored programmes for women with GDM.26 Breastfeeding has a key part to play in T2D prevention as it is associated with reduced fasting glucose levels postpartum and lower future T2D risk.27–29 Limited resources impacted dietetic promotion of breastfeeding, although with proper training, dietitians could effectively contribute to breastfeeding support.30,31 Conclusion The development of a robust national MNT framework for GDM management, which defines roles and responsibilities would offer an

evidence-based approach to both service development and clinical decision making. Additionally, provision of training and resources would support dietitians to effectively offer chronic disease prevention programmes, providing health promotion counselling to postpartum women with prior GDM, and addressing long term health risks such as future T2D and cardiovascular disease. Ensuring consistency in MNT delivery through the adoption of evidence-based standards of care is vital to optimise outcomes of MNT for women with GDM. Dunne P, Carvalho M, Byrne M, Murphy AW, O'Reilly S. Maternity dietitians' perspectives on delivering gestational diabetes care, and postpartum follow-up in

Ireland: A qualitative study. J Acad Nutr Diet. 2023 Dec 27:S22122672(23)01766-5. doi:10.1016/j. jand.2023.12.012. Epub ahead of print. PMID: 38158178. Full text of the publication can be accessed here https://authors.elsevier.com/ a/1iX5L7t0kP%7EUZ1. Access is free of charge until March 22nd, 2024.

References available on request

News e-Referral Form for Health Professionals The Asthma Society of Ireland has launched a new, free e-referral platform for healthcare professionals. The platform, available at www.asthma.ie/patient-e-referral, allows healthcare professionals all over Ireland to refer patients or carers with questions/concerns about asthma or COPD to the charity’s Adviceline service. Operating for over 25 years, the Adviceline is a free service which allows users to speak to a respiratory specialist nurse or physiotherapist about various aspects of their asthma or COPD. The service is also available to parents/carers of young people with asthma or COPD. Through the Adviceline, respiratory nurse specialists and physiotherapists provide information and support, promote self-management, and signpost to appropriate healthcare interventions. Healthcare professionals can now, with the permission of the patient, complete a simple form on the asthma society website to refer patients or their carers to the service. The form gathers some basic contact information which will allow a member of the Asthma Society’s Patient Services team to get in touch with the patient directly and arrange an appointment with a nurse specialist or physiotherapist. The form can be accessed by visiting www.asthma.ie HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Gastroenterology & Endocrinology - Haemochromatosis

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Raising awareness of Haemochromatosis Written by Miriam Forde, Executive Director and Margaret Mullett, Honorary President, Irish Haemochromatosis Association

Miriam Forde

Margaret Mullett

Haemochromatosis is more common in Ireland than anywhere in the world, affecting one in 83 people, write Miriam Forde and Margaret Mullett, Irish Haemochromatosis Association

problems, including vague aches and pains, exercise-induced joint pain, osteoporosis, early onset osteoarthritis, chondrocalcinosis (wrists, knees, hips and symphysis pubis, acutely as pseudogout). Arthropathy is a common symptom usually affecting the second and third MCP joints.

Haemochromatosis is a condition where too much iron is absorbed and stored in the body. It can cause liver cirrhosis, liver cancer, arthritis, diabetes and general fatigue. It is hereditary and is more common in Ireland than anywhere in the world, where one in 5 people are carriers and one in 83 people are pre-disposed to be at risk. Haemochromatosis is often underdiagnosed, partly because of low public awareness of the condition, but also because symptoms, including fatigue, joint pain and depression, can be similar to a number of other disorders. If undetected and untreated, it can result in premature death, so early diagnosis is essential to avoid organ damage. Haemochromatosis can easily be managed through venesections or phlebotomies, which remove iron from the body. Diagnosis of haemochromatosis should be no barrier to a patient leading a normal life. Symptoms It is important to screen for hereditary haemochromatosis (HH) and perform serum ferritin and transferrin saturation tests on patients who present with symptoms or who have a family history of haemochromatosis. General presentations include fatigue, lethargy, sleep disturbance and weakness. Haemochromatosis patients can present with musculoskeletal

Other presentations include: • Hepatic: abnormal liver function tests, hepatomegaly, cirrhosis; • Cardiac arrhythmia: congestive cardiac failure, cardiomyopathy; • Endocrine presentations: amenorrhoea, diabetes, decrease in libido, infertility; • Skin: pigmentation, porphyria cutanea tarda; adominal pain and thyroid and parathyroid abnormalities. Diagnosis A simple blood test to check iron status can confirm or rule out iron overload. If both the SF and the TS levels are raised, then a genetic test is carried out to confirm diagnosis. An SF of > 200ug/L in premenopausal women, and > 300ug/L in men and postmenopausal women suggests that the patient may be ironoverloaded. This should prompt a test for fasting TS. Fasting TS of > 45% is strongly suggestive of haemochromatosis and should prompt a test for the HFE gene. Treatment When diagnosed early, haemochromatosis responds well to therapeutic phlebotomy or venesection ie. the removal of a unit of blood. Each 500ml of

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

blood withdrawn contains 250mg iron. The aim is to bring the SF level down to 50-100µg/L. The frequency of venesection depends on initial SF. Treatment initially can be intensive ie weekly or bi-weekly phlebotomy to rapidly reduce ferritin levels. After a normal level has been achieved, the patient is in the maintenance phase and thereafter may require three or four sessions per year. GP practices now provide therapeutic phlebotomy for patients, however many patients continue to attend venesection units and clinics in hospital settings. Blood Donation Since 2019, the Irish Blood Transfusion Service (IBTS) accepts the blood of HH patients who are in maintenance and who are eligible to donate blood. Patients can attend by appointment up to four times a year (minimum of 90 days between phlebotomies). The patient’s hereditary haemochromatosis will continue to be managed by their GP or Consultant, including monitoring of ferritin levels. Patients must have had at least one venesection prior to donation. The cut-off age for eligibility is 69 for first-time HH blood donors. (visit www. giveblood.ie) Nutrition & Lifestyle • Patients should be encouraged to eat a well-balanced diet and drink plenty of water. • Patients should be advised to avoid iron and Vit C supplements and iron-fortified

food. There is no need for a patient undergoing phlebotomy to be prescribed a low-iron diet as the amount of iron removed by phlebotomy is far greater than that present in even a highiron diet. • Alcohol consumption should be kept to a minimum as moderate to heavy alcohol consumption increases the risk of cirrhosis. Abstinence is recommended in those with liver cirrhosis. • Patients with elevated body iron should avoid raw shellfish because of the risk of Vibrio vulnificus (bacterial food poisoning) We regret that a nationally funded screening programme for HH has not yet been established and propose that the National Screening Advisory Committee review a submission to screen for the disorder in Ireland. Miriam Forde is Executive Director and Margaret Mullett is Honorary President of the Irish Haemochromatosis Association. Information and resources on haemochromatosis are available on request from Tel: 01 873 5911 Email: info@haemochromatosis. ie. World Haemochromatosis Awareness Week takes place every year from the 1st to the 7th June. If your hospital would like to display information materials during that time, please contact the Association. For more information, visit www.haemochromatosis.ie

Who is at risk? More men than women can develop symptoms of haemochromatosis because women lose iron through regular blood loss from menstruation and pregnancy. In Ireland, 1 in 5 people carry the gene and 1 in 83 are at risk of developing haemochromatosis. Ireland has the highest incidence of the condition in the world.

How do I get tested? If you are worried about any of the symptoms of iron overload or if someone in your immediate family has haemochromatosis, contact your GP to arrange a simple blood test. If these levels are higher than normal, a gene test (which is a simple blood test) will confirm if you have haemochromatosis. If diagnosed and treated early, patients can go onto live a normal life.

How do I get treated? David Beggy, GAA All Star & Ambassador for the Irish Haemochromatosis Association (IHA), with Margaret Mullett, Honorary President (IHA), Georgina Mullett and Andrea Beggy

HAEMOCHROMATOSIS: IRELAND’S MOST COMMON GENETIC DISORDER

What is haemochromatosis or ‘iron overload’? ‘Iron overload’ or haemochromatosis is a genetic condition where a large amount of iron is absorbed from our diet and deposited in major organs in the body, such as the liver but also the pancreas, heart and joints.

What are the symptoms? Iron builds up slowly in the body, so symptoms might not appear until ages 30-40 years. Symptoms can include: Chronic fatigue Arthritis Diabetes

Liver disorders Reduced sex drive Heart disease

Treatment for haemochromatosis is very simple – blood is removed from the body to reduce iron stores (similar to donating blood), which is known as venesection.

For more information Visit www.haemochromatosis-ir.com or email info@haemochromatosis-ir.com or please call our helpline on (01) 8735911. We are also on social media: Twitter: @IrishHaemAssoc: Facebook: IrishHaemochromatosisAssociation Instagram: @haemochromatosis.ireland

Gastroenterology & Endocrinology - News

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Personalising Treatment for Ulcerative Colitis Left to right Dr Sudipto Das, Principal Investigator at RCSI School of Pharmacy and Biomolecular Sciences, Dr Hannah Fitzgerald, Postdoctoral Researcher, RCSI School of Pharmacy and Biomolecular Sciences, David Clancy, Serosep CTO, Emma Morgan, Serosep CFO and Gráinne Kirwan, Research Assistant, RCSI School of Pharmacy and Biomolecular Sciences A new partnership between RCSI University of Medicine and Health Sciences and Irish diagnostics company Serosep Ltd is set to personalise treatment for ulcerative colitis and ultimately improve quality of life for patients with the condition. Under the new alliance, RCSI researchers will work with Serosep to accelerate the development of new tests to help predict disease progression in ulcerative colitis, a form of inflammatory bowel disease that damages the lining of the gut over time. The condition causes inflammation and ulcers in the large intestine (colon) and rectum. The project will develop technology to identify ulcerative colitis patients who are likely to progress in their disease, ensuring that people get the most effective care for their disease, and sparing people treatments where they are not likely to be of benefit to them. The partnership between Serosep and RCSI is co-funded by Serosep and the Enterprise Ireland Innovation Partnership Programme. At present, medications known as 5-Aminosalicylates (5-ASA) are the most common first line of treatment for mild-tomoderate ulcerative colitis, and as the disease progresses it is typically managed with steroids, immunosuppressants and biological drugs. Treatment regimes There is a pressing need to develop accurate biomarkerbased methods to identify the best treatment regimes for patients soon after diagnosis. “Currently there are no biomarkers which allow prediction of disease progression in patients with ulcerative colitis,” explained Dr Sudipto Das, Lecturer and

Principal Investigator at RCSI School of Pharmacy and Biomolecular Sciences. “Having such biomarkers could augment decision-making for clinicians about whether the patient could benefit from an escalation of treatment at an early stage of the disease.” Dr Das’s team will work with Serosep to validate specific ulcerative colitis biomarkers that the RCSI group has identified in the lab. The plan is to create a new in-vitro diagnostic solution that can support clinicians as they make decisions about the most suitable treatment for the patient based on a panel of biomarkers that can be measured and tracked in samples of their tissue and potentially in the blood as well. “Through recent work in our lab we have identified specific genes that can potentially predict disease progression in adult ulcerative colitis patients,” said Dr Das. “This partnership will allow us to further validate these genes in a larger cohort of patient samples and enable development of a test that can be applied in the clinic to identify patients who are likely to progress at an early stage of disease. This in turn would

allow early treatment for those patients, and sparing patients who are less likely to progress from unnecessary treatment. The ultimate impact of this test would be to improve quality of life in patients with ulcerative colitis.” Collaborative research Serosep Ltd, founded in 1997, is headquartered in Limerick with subsidiaries in London and Johannesburg, and is focused on the clinical in-vitro diagnostic market specifically in infectious disease, which has seen the company build an infrastructure to support its products from conception to commercialisation. Serosep was awarded Irish Medtech Company of the Year in 2022.

for Serosep that will enable us to build expertise in new technologies to further develop our product portfolio and access new markets.” Professor Fergal O’Brien, RCSI Deputy Vice Chancellor for Research and Innovation welcomes the partnership, noting how the goal of personalising treatment will benefit patients. “This partnership will help to move scientific discovery into improved clinical practice, with a tool to help clinicians assess whether it is appropriate to escalate treatment in ulcerative colitis patients,” said Professor O’Brien.

The company is excited to partner with RCSI on the project, according to Serosep CEO Dermot Scanlon. “It will allow us to create knowledge within the company through collaborative research, the outputs of which would present us with the opportunity for strategic diversification in our product offering to support our continued growth.”

“As a health sciences university, we are solely focused on research to drive improvements in human health. Harnessing the expertise of both RCSI and Serosep, this collaboration will ultimately see patients get the treatment that will benefit them while other patients will be spared from side-effects of treatment options that would have been less effective, thus promoting personalised medicine in patients with ulcerative colitis.”

Serosep CTO David Clancy outlined: “The collaboration with RCSI presents an opportunity

The partnership between Serosep and RCSI is supported by the RCSI Innovation team.

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Lead your patients to stronger bones with Prolia®

1-4

10 YEAR DATA 5S

Osteoporosis is a serious ongoing condition and ongoing treatment is required.6,7,8,9*

* Prolia® should not be stopped without considering alternative treatment in order to prevent rapid bone mineral density loss and a potential rebound in vertebral fracture risk.6 PROLIA® (denosumab) Brief Prescribing Information

Please refer to the Summary of Product Characteristics (SmPC) before prescribing Prolia. Pharmaceutical Form: Pre-filled syringe with automatic needle guard containing 60 mg of denosumab in 1 ml solution for injection for single use only. Contains sorbitol (E420). Indication: Treatment of osteoporosis in postmenopausal women at increased risk of fractures. Dosage and Administration: 60 mg Prolia administered as a subcutaneous injection once every 6 months. Patients must be supplemented with calcium and vitamin D. No dosage adjustment required in patients with renal impairment. Prolia should not be used in children aged < 18 years because of safety concerns of serious hypercalcaemia. Give Prolia patients the package leaflet and patient reminder card. Re-evaluate the need for continued treatment periodically based on the benefits and potential risks of denosumab on an individual patient basis, particularly after 5 or more years of use. Contraindications: Hypocalcaemia or hypersensitivity to the active substance or to any of the product excipients. Special Warnings and Precautions: Traceability: Clearly record the name and batch number of administered product to improve traceability of biological products. Hypocalcaemia: Identify patients at risk for hypocalcaemia. Hypocalcaemia must be corrected by adequate intake of calcium and vitamin D before initiation of therapy. Clinical monitoring of calcium levels is recommended before each dose and, in patients predisposed to hypocalcaemia, within 2 weeks after the initial dose. Measure calcium levels if suspected symptoms of hypocalcaemia occur. Renal Impairment: Patients with severe renal impairment (creatinine clearance < 30 ml/min) or receiving dialysis are at greater risk of developing hypocalcaemia. Skin infections: Patients receiving Prolia may develop skin infections (predominantly cellulitis) requiring hospitalisation and if symptoms develop then they should contact a health care professional immediately. Osteonecrosis of the jaw (ONJ): ONJ has been reported rarely with Prolia 60 mg every 6 months. Delay treatment in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventative dentistry and an individual benefit:risk assessment is recommended prior to treatment with Prolia in patients with concomitant risk factors. Refer to the SmPC for risk factors for ONJ. Patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups and immediately report oral symptoms during treatment with Prolia. While on treatment, invasive dental procedures should be performed only after careful consideration and avoided in close proximity to Prolia administration. The management plan of patients who develop ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ. Osteonecrosis of the external auditory canal: Osteonecrosis of the external auditory canal has been reported with Prolia. Refer to the SmPC for risk factors. Atypical femoral fracture (AFF): AFF has been reported in patients receiving Prolia. Discontinuation of Prolia therapy in patients suspected to have AFF should be considered pending evaluation of the patient based on an individual benefit risk assessment. Long-term antiresorptive treatment: Long-term antiresorptive treatment may contribute to an increased risk for adverse outcomes such as ONJ and AFF due to significant suppression of bone remodelling. Concomitant medication: Patients being treated with Prolia should not be treated concomitantly with other denosumab containing medicinal products. Warnings for Excipients: Patients with rare hereditary problems of fructose intolerance should not use Prolia. Interactions: Prolia did not affect the pharmacokinetics of midazolam, which is metabolized by cytochrome P450 3A4 (CYP3A4). There are no clinical data on the co-administration of denosumab

Amgen Ireland 21 Northwood Court, Santry, Dublin 9, Ireland.

and hormone replacement therapy (HRT), however the potential for pharmacodynamic interactions would be considered low. Pharmacokinetics and pharmacodynamics of Prolia were not altered by previous alendronate therapy. Fertility, pregnancy and lactation: There are no adequate data on the use of Prolia in pregnant women and it is not recommended for use in these patients. It is unknown whether denosumab is excreted in human milk. A risk/ benefit decision should be made in patients who are breast feeding. Animal studies have indicated that the absence of RANKL during pregnancy may interfere with maturation of the mammary gland leading to impaired lactation post-partum. No data are available on the effect of Prolia on human fertility. Undesirable Effects: The following adverse reactions have been reported: Very common (≥ 1/10) pain in extremity, musculoskeletal pain (including severe cases). Common (≥ 1/100 to < 1/10) urinary tract infection, upper respiratory tract infection, sciatica, constipation, abdominal discomfort, rash, alopecia and eczema. Uncommon (≥ 1/1000 to < 1/100): Cellulitis, ear infection and lichenoid drug eruptions. Rare (≥ 1/10,000 to < 1/1,000): Osteonecrosis of the jaw, hypocalcaemia (including severe symptomatic hypocalcaemia and fatal cases), atypical femoral fractures, and hypersensitivity (including rash, urticaria, facial swelling, erythema and anaphylactic reactions). Very rare (< 1/10,000): Hypersensitivity vasculitis. Please consult the Summary of Product Characteristics for a full description of undesirable effects. Pharmaceutical Precautions: Prolia must not be mixed with other medicinal products. Store at 2°C to 8°C (in a refrigerator). Prolia may be exposed to room temperature (up to 25°C) for a maximum single period of up to 30 days in its original container. Once removed from the refrigerator Prolia must be used within this 30 day period. Do not freeze. Keep in outer carton to protect from light. Legal Category: POM. Presentation and Marketing Authorisation Number: Prolia 60 mg: Pack of 1 pre-filled syringe with automatic needle guard; EU/1/10/618/003. Price in Republic of Ireland is available on request. Marketing Authorisation Holder: Amgen Europe B.V., Minervum 7061, NL-4817 ZK Breda, The Netherlands. Further information is available from Amgen Ireland Limited, 21 Northwood Court, Santry, Dublin D09 TX31. Prolia is a registered trademark of Amgen Inc. Date of PI preparation: May 2022 (Ref: IE-PRO-0322-00006) Adverse reactions/events should be reported to the Health Products Regulatory Authority (HPRA) using the available methods via www.hpra.ie. Adverse reactions/events should also be reported to Amgen Limited on +44 (0)1223 436441 or Freephone 1800 535 160. References: 1. Prolia® [denosumab], Summary of Product Characteristics. 2. Cummings SR et al, N. Eng. J Med 2009;361:756-765. 3. Holzer G et al, J Bone Miner Res 2009;24(3):468-74. 4. Poole K et al; J Bone Miner Res 012; 27 (suppl1):S44 abstract 1122. 5. Bone HG, et al; Lancet Diabetes Endocrinol. 2017;5:513-23;3-23. 6. Tsourdi E, et al. Bone. 2017;105:11–7. 7. Hernlund E, et al. Arch Osteoporos. 2013;8:136; 8. Kanis JA, et al. Osteoporos Int. 2019;30:3–44; 9. Brown JBMR 2013 Vol28 pp746-752.

© 2022 Amgen Inc. All rights reserved. IE-PRO-0522-00002. Date of preparation: June 2022

CPD 105: OSTEOPOROSIS Continuing Professional Development

CPD

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AUTHORS: Fellow Emeritus, Professor Moira O’Brien, FRCPI, FFSEM, FFSEM(UK), FECSS, FTCD. Consultant in osteoporosis and Sports Medicine since the 70s and osteoporosis since 1990 when she set up the first osteoporosis clinic in the anatomy department of TCD. Founder and President of the Irish Osteoporosis Society. She is currently the only Osteoporosis consultant in Ireland and works in Affidea Dundrum. Michele O’Brien, CEO of the Irish Osteoporosis Society. Michele set up the first Falls Prevention service for senior citizens in Ireland in 2000 and has worked for the IOS Charity for 23 years.

60 Second Summary Osteoporosis is the most common bone disease worldwide. The Irish Osteoporosis Society (IOS) have been saying for decades that it affects all age groups and both sexes. Bone loss is treatable in the majority of cases, yet more men die from the complications of osteoporotic fractures than cancer of the prostate, and men have a higher risk of morbidity and mortality than women. Osteoporosis is a silent disease, there are no signs and symptoms, no one feels bone loss. The commonest cause is low levels of sex hormones, oestrogen in women and testosterone in men. Osteoporosis and osteopenia are both diseases and should be thoroughly investigated, Osteopenia should not be considered “A touch of bone loss”. The effect of medication on the prevention of fractures must be monitored closely to ensure the treatment plan is working and improve compliance. Lifestyle, exercise, stress, diet, sleep are important factors to assess. Effective and safe medications are available to treat osteopenia/Osteporosis. Most medications can cause possible side effects, but the benefits to bone health by preventing future fractures usually far outweighs the possible risks. It is rarely too late to investigate and treat a patient with bone loss, even those in their 90’s with Dowagers humps.

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. Amgen has no editorial oversight of the CPD programmes included in these modules.

Osteoporosis, what you need to know Introduction Osteoporosis is the most common bone disease worldwide, it is a silent disease, as there are no signs and symptoms. There is a significant amount of misinformation and myths about osteoporosis, both in the public and Healthcare domain. For example, the Irish Osteoporosis Society (IOS) have been saying for decades that it affects all age groups and both sexes, yet most believe it only affects old women. Findings from a recent survey by Athena Pharmaceuticals found that one in five adults have fractured a bone since they turned 40, over a third of these people reported to have had a fragility fracture and the rate of these low impact fractures was high amongst 40 to 54 year olds. Prevention ideally should start in childhood, which is why physical activity should be mandatory in all schools and integrated into the school curriculum, as not only does it help to prevent Osteoporosis but obesity and a list of other diseases.

More men die from the complications of osteoporotic fractures than cancer of the prostate and men have a higher risk of morbidity and mortality than women. More women are affected, and more women die from the complications of osteoporotic fractures, than the combined deaths from cancers of the breast, ovaries, and cervix. Now that you have picked your jaw up from the floor, these are some of the many reasons why all health care professionals need to review their knowledge on Osteoporosis, so the prevention, diagnosis and treatment rates can be improved, and why fragility fractures in those under 65 should have bone loss ruled out, as the cost of treating fractures will double by 2030. Osteoporosis is characterised by low bone density, abnormal changes in the microarchitecture of bone tissue, particularly cancellous bone, making it more fragile, with an increased risk of low trauma fractures. It is essential to find the cause/s of bone loss and modify

Continued Professional Development supported by

as many risk factors as possible going forward. The commonest bones to fracture are the cancellous part of the distal radius, the body of the vertebrae or the hip (neck of femur) and vertebrae but any bone can be affected. A low trauma fracture (trip and fall from a standing height or less) is usually the first sign of this silent disease, along with loss of height, postural changes such as their head protruding forward, rounded shoulders and/or a Dowagers hump developing. It is estimated that up to 500,000 people in Ireland may have osteoporosis and that over 50,000 osteoporotic fractures occur each year in Ireland. 1 in 2 women and 1 in 4 men over 65, will develop an osteoporotic fracture in their lifetime, if it is not prevented. Younger people will develop osteopenia and/or osteoporosis if they have risk factors for bone loss, which is why in an ideal world any patient being put on a new medication or diagnosed with a new condition should be red flagged if either place them at risk for bone loss, so a plan can be

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CPD 105: OSTEOPOROSIS The effects of undiagnosed bone loss

The increased osteophytes give a false higher reading on a DXA scan of the lumbar spine, which is why the coloured images on a DXA scan should be viewed and reported as well as individual vertebrae, not just the average of the four vertebrae. Fractures or multiple myeloma or secondaries from cancer in the body of the vertebrae may also cause increased false higher readings, making the bone appear healthier than it is. Cause of back pain must be investigated and addressed, and vertebral fractures ruled out. NOTE: Low bone density increases the incidence of musculoskeletal problems.

implemented to decrease their risk of fracturing. Some of the many examples; Oral steroids, early menopause, eating disorders, RA. 20% of Irish people aged 60+who fracture their hip will die within 6 to 12 months from a blood clot, infection or pneumonia which are the secondary effects of a fracture. Osteoporosis is rarely on a discharge letter or on death certificate, even though reading the notes, the patients were admitted and treated because they had low trauma fractures. In 2022, the cost of acute hip fracture care was estimated at ¤48,569,325 nationally. Many patients in Ireland and worldwide have untreated low trauma osteoporotic fractures, despite the fact that there are effective and safe medications available. Osteoporotic fractures impose a huge social and financial burden in Europe and Ireland, blocking

acute beds, 50% of older people who suffer an osteoporotic hip fracture, lose their independence, have poor quality-of-life, which significantly increases costs to the Health Service. Increasing age is a factor and Ireland has one of the highest rates of fragility fractures in Europe, along with one of the greatest increases in the number of its population over the age of 80. Women and men over the age of 65 are the highest risk group but prevention in earlier life will save millions of euros long term. NOTE: Calcium and vitamin D supplements are not treatments. Intake of Calcium and Vitamin D is essential not only for bone health; however they should preferably be taken through food. How much the patient takes from food should be assessed prior to prescribing a calcium and vitamin D supplement, as many appear to just need vitamin D supplements. 70% of the population will develop back pain in their lifetime,

this may be due to a variety of causes, either local or referred. Back pain associated with loss of height and changes in posture are red flags for osteoporotic vertebral fractures. 50% of women with vertebral fractures go undiagnosed. 75% of people with vertebral fractures may only have intermittent back pain, but 25% will have extreme pain which in many cases the pain can only be relieved by daily injections of teriparatide, which it is believed to occur secondary to the increase in rebuilding of bone. It is very important to differentiate undiagnosed osteoporosis with osteoarthritis and degenerative disc disease, which may affect the L4, L5 nerve roots, causing pain in the distribution of the gluteal and sciatic nerves. This pain is usually aggravated by sitting too long or standing too long. Many patients may have a combination of both osteoporosis and osteoarthritis in the vertebrae.

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There are over 200 causes of bone loss, either the disease itself or the treatment for the disease or lifestyle choices/addictions. Osteoporosis and its associated risk of increased fractures is rarely considered as a complication of these diseases or their treatment. You must find the causes using a multidisciplinary approach to prevent fractures, as many patients have more than one risk factor. Example A 20 year female on Depo Provera who is on an antidepressant that causes bone loss, with low calcium and vitamin D intake and is obese. The most common cause of low bone density in females is oestrogen deficiency and testosterone deficiency in males. Family history of osteoporosis will increase the risk of osteopenia and/or osteoporosis by 70%. Genetic disorders such as cystic fibrosis, osteogenesis imperfecta, diabetes, haemochromatosis, homocystinuria and other metabolic disorders are risk factors. Chromosomal abnormalities such as Turner’s

39

syndrome (XO) and Klinefelter’s (XXY ) in males will result in low sex hormone levels, which is why any men lucky enough to be diagnosed must have their testosterone levels checked. Menstrual problems: Late menarche, first period after the age of 15, irregular periods, PMT, loss of periods for more than 4 months not due to pregnancy, eating disorders or Reduced Energy Deficiency Syndrome RED-S in athletes, early menopause before the age of 45, endometriosis, PCOS and Depo-Provera particularly in the teenage years during the growth spurt. Men who have had a testis removed, cancer of the testes or trauma causing torsion of the testes, viral or bacterial infections, need to be put on a bone loss prevention plan for osteoporosis and may require testosterone replacement therapy. Stress either mental or physical, particularly if they have sleep issues, will increase cortisol levels which will reduce sex hormone levels. Other hormones such as high levels of cortisol, prolactin, thyroxine and parathyroid, growth hormone will affect bone metabolism. Low levels of vitamin D (normal level for bone health should be

70 nmol per litre to 125) affects the absorption of calcium and may cause an increase in the secretion of parathyroid hormone, which takes calcium from bone, to maintain the narrow range of calcium in the blood. Hyperparathyroidism may also be due to an adenoma of the parathyroids. Low levels of vitamin D may be due to lack of exposure to sun, inadequate intake of vitamin D in the diet or as a result of malabsorption including untreated coeliac disease or gluten and wheat intolerance, Ulcerative colitis or Crohn’s disease to name a few. Many drugs can cause bone loss, corticosteroids, chemotherapy, radiation, aromatase inhibitors for breast cancer, androgen suppression for prostate cancer. proton pump inhibitors, warfarin, anticonvulsants and prolactin raising medication. Poor lifestyle advice may also be a cause of developing low bone density. Running or walking they should alter the speed and the course, as bones respond to differences in strain. Cycling and swimming are non-weight bearing exercises. Patients with and without osteoporosis should

not do yoga as it contains forward flexion bending exercises, as this will compress the anterior aspect of the lumbar vertebrae, increasing the risk of fractures, excess stress on the discs and sciatic nerve. Adequate sleep and reducing stress is very important. Nutrition plays an important role, bones require adequate calories, first-class proteins, supplemented milk’s with calcium, vitamin D, vitamin C, iron and folate help absorption. Fluid intake is also essential they should drink at least 12 / to 2 L a day. Diagnosis of osteoporosis 1. A detailed questionnaire (available by email from IOS) which helps find risk factors for bone loss. 95% of those who contact the IOS their causes of bone loss appear to have been assumed. If any cause of bone loss is not found and could be addressed, such as gluten sensitivity, a patient will continue to lose bone and not get the full benefit from their treatment. 2. A DXA scan - DXA is the gold standard for diagnosing osteopenia and osteoporosis, currently it is the best predictor of fractures. DXA helps to monitor response to treatment

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and improve compliance. The DXA definition of osteoporosis is a T score of -2.5. The T score above 1 is normal. Osteopenia is a T score between -1 and -2.49, most fractures occur in the osteopenia range of -1.5 to -2.49. A T score of -2.5 and low trauma fracture or T score of -3 or higher is considered severe osteoporosis. For every one standard deviation of bone mineral density, the relative risk fracture is significantly increased. A DXA scan should measure the posterior anterior view of the lumbar spine, L1 to L4. Ideally the value of each vertebra should be reported not just the total values, as the density may vary, due to osteoarthritic changes, particularly in individuals with scoliosis or a dowagers hump. Increased calcium in the hyaline cartilage of the vertebrae will give a higher T score and a false high result. Increased density may also be due to vertebral fractures, multiple myeloma or secondaries. NOTE: If a person’s DXA scan results decline, the cause/s of the decline should be investigated and addressed, changing their treatment is not the solution, as they could continue to lose bone.

40

CPD 105: OSTEOPOROSIS

3. Blood Investigations for causes of bone loss - List available by email from IOS. This process should also include bone turnover markers in the blood, CTX1 measures bone loss, while PINP measures bone formation. If a patient has stopped taking Denosumab (an antiresorptive) without taking another antiresorptive, or the injection has been delayed for more than approximately 4 weeks, an increase in the blood level of CTX1 may occur, indicating a high risk of spontaneous vertebral fractures. 4. Treatment plan to prevent fractures or further fractures put in place. Monitoring bone health: Effective and safe medications are available to treat osteopenia and osteoporosis. Most medications have possible side effects, but the benefits to bone health by preventing future fractures usually far outweighs the risk. Treatments include Hormone replacement therapy - HRT should not be used in post-menopausal women just to prevent bone loss, unless they have menopausal symptoms. Antiresorptive medication - Bisphosphonates are nonhormonal and have to be incorporated into bone and are appropriate for some patients but not all and they can only be prescribed for 5 years in total. They may cause irritation of the oesophagus and proton pump inhibitors should not be prescribed for patients to tolerate them, as this will cause further bone loss. Monoclonal antibody denosumab (Prolia) The anabolic agent teriparatide for severe Osteoporosis Evenity (Romosozumab) has been approved by the EMA several years ago but is still not available for patients in the ROI. Patients must understand the importance of taking the medication correctly and the consequences of stopping it without consulting their doctor,

especially Prolia for dental work or as many tell the IOS, they read up on the internet they can treat their bone loss without a prescribed medication, all they need to do is buy certain supplements! Compliance is a major problem which can be improved by DXA and 6 monthly bone turnover markers particularly CTX1 if available, as many tell the IOS they fill their bisphosphate prescription but do not take it. If you have noncompliant patients you could refer them to the IOS. The effect of medication on the prevention of bone loss must be monitored ideally by annual or Biannual DXA’s to improve compliance and to ensure the patient is responding to the treatment, as repeat DXA scanning is much cheaper than bone markers. Since bone loss is silent, the IOS does not recommend repeat DXA scanning every 5 years, as significant bone loss can have occurred. A DXA scan contains 10% radiation of a regular chest X-ray, and a person has been exposed to more radiation traveling from Dublin to New York, than having a DXA scan. NOTE: Are those who have heart attacks only monitored once every 5 years? At least these patients, if this was the case would usually have signs or symptoms, with bone loss there are none, except fractures that could have been prevented by monitoring the patient. You must find and treat the causes of osteopenia or osteoporosis. Treatment also depend on whether they are pre or postmenopausal, their age, the results of the questionnaire and blood tests, the DXA result and if they have fractured. Some patients may have difficulty in swallowing or absorbing medication, while others are needle phobic which cognitive therapy can help. It is rarely ever too late to investigate and treat a patient to improve their quality of life and prevent further fractures, the IOS know of 90-year-olds who have significantly improved their bone health and regained their independence.

Exercise 80% of the skeleton is composed of cortical bone and 20% is cancellous. Cortical responds more to weight bearing and differences in strain. Cancellous bone is more sensitive to hormonal changes and is more fragile and is lost first. Osteoclasts are multinucleated giant cells that remove old bone, and this process takes 3 weeks, while the osteoblasts build up new bone and this process takes several months. Weight-bearing activity stimulates the osteoblasts, and they maintain the balance of bone formation and removal. When this balance is disrupted, more bone is removed than replaced causing osteopenia and/or osteoporosis. Weight-bearing exercise plays an essential role in treatment. Patients should be advised by a physiotherapist who specialises in bone health and can understand a DXA scan report. There is no exercise programme that suits all those with bone loss and patients should be individually assessed. It is much safer to initiate exercises with elderly patients without weights, as many have never lifted weights in their life, for elderly patients there are very basic exercises on the IOS website. By slowly increasing the weights this will reduce the risk of the patient being very sore and non-compliant and also reduces the risk of fracturing. It makes no sense to rush into maximum weights, as many calls to the IOS helpline are from those who are in agony or fractured while exercising, especially those who have been instructed to do forward flexion. A patient should be thoroughly investigated and on an Osteoporosis treatment prior to an exercise program being initiated Lifestyle advice on nutrition particularly the importance of adequate calories, fluids as well as vitamin D as it plays an important role in calcium absorption and bone metabolism. Adequate sleep and reducing stress are important factors as they increase bone loss by increasing cortisol levels. Reduce high caffeine intake, excessive alcohol and excessive fibre in their diet no more than 30g a day and cease smoking. References upon request

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CPD Questions Q1 Which of the following is the first step that should be taken when a person has a fragility fracture? a. Calcium and Vitamin D supplements b. Investigation for risk factors for bone loss c. Weight bearing exercise plan d. Initiate HRT Q2 Why should Prolia (Denosumab) not be delayed more than 4 weeks? a. It is fine to put patients on a Prolia drug holiday for more than 4 weeks b. Spontaneous vertebral fractures can occur c. You can for dental implants to be done d. You can for tooth extractions Q3 What below does not affect bone metabolism? a. Cortisol b. Prolactin, Thyroxine and parathyroid c. Vitamin D d. Iron Q4 What one movement should those with bone loss avoid, except for dressing and washing themselves? a. Extension of their back b. Forward flexion of their back c. Walking d. Stair climbing Q5 Which below does not cause false higher readings on a DXA scan report? a. Fractured Vertebrae b. Secondaries c. Osteoarthritis changes d. High intake of Vitamin D

Gastroenterology & Endocrinology

41

Endometriosis: An Overview Endometriosis is a chronic, progressive, inflammatory disease where tissue similar to the lining of the womb is found elsewhere in the body. The disease is estimated to affect 10% (190 million) girls, women and individuals assigned female at birth worldwide. In Ireland it is estimated that 155,000 of women are affected by endometriosis. The condition creates an inflammatory reaction, which can result in the development of scar tissue and lesions throughout the body. There are numerous types of lesions that exist and vary in severity depending on the stage of the disease. What are the symptoms? Endometriosis symptoms may develop before the first menstrual cycle and on past menopause, which can significantly impact quality of life. This disease can be associated with a range of different symptoms including painful periods, menstruation pain, pelvic pain, discomfort during and after sex, unexplained fatigue, bloating, nausea, infertility and more. Pain can be cyclical or daily

and mild to severe. This is not a complete list of symptoms, as endometriosis affects everyone differently and causes a variety of ailments, not all of which are physical, it can also be completely asymptomatic, making it difficult to diagnose and treat.

Written by Ayisha Lightbourne, Co-ordinator, Endometriosis Association of Ireland

Diagnosing Endometriosis A definitive diagnosis is only possible with a laparoscopy. Tissue suspected of containing endometriosis is extracted during the laparoscopy and sent to the pathologist to be examined under a microscope to confirm the diagnosis. The American Society of Reproductive Medicine (ASRM) developed a staging system for the disease and is classified according to prevalence: Stages 1 and 2: minimal to mild disease – superficial endometriosis which is found primarily in the pelvis Stages 3 and 4: moderate to severe disease – deep penetrating endometriosis can be found on the bladder, bowel and on other organs outside of the pelvis. However, prevalence does not correspond with discomfort; someone in stage 1 can have

chronic daily pain, whilst someone in stage 4 may not have any pain at all. This complicates diagnosis because it is frequently overlooked or confused with other illnesses such as IBS and ovarian cysts. Treating Endometriosis There is currently no cure for endometriosis. The different treatment options available for endometriosis aim to decrease the severity of symptoms and improve the quality of life for individuals living with the condition and are also dependent on a person’s individual situation. Hormonal medication, usually in the form of contraceptives, is one of the first types of treatments prescribed to those affected by the disease to help reduce the severity of symptoms. Hormone therapy may include: the pill, IUDs, implants, injections, patches or vaginal rings. Analgesics like paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) can help reduce pain felt by sufferers. NSAIDs are a preferred type of pain relief due to inflammation caused by endometriosis. In some cases, standard pain killers may not be proficient in helping to relieve symptoms and co-codamol/ co-dydramol or opioids may be prescribed. In many cases, surgery is required for the treatment of endometriosis.

Surgical interventions look to remove endometriosis lesions, divide adhesions, and restore nerve pathways. Excision and ablation surgery are the techniques used to treat endometriosis. Excision is the physical removal of the lesions and surrounding tissue while ablation vaporises and destroys the tissue. The recurrence rate with ablation is much higher therefore excision surgery is considered the gold standard. It is a common misunderstanding that a hysterectomy will "cure" endometriosis. This is not true because the lesions do not originate from the uterus. If endometriosis is not treated and removed during a hysterectomy, symptoms may persist after the surgery. Those on HRT (even those without a womb or using an IUD) can benefit by including body identical progesterone into their regimen. A holistic approach is required for managing symptoms and should include complementary and alternative therapies to assist with pain management. Endometriosis can be a debilitating condition. Much more rigorous research is needed to understand the disease better and to learn how to treat the condition more effectively. To find out more visit https://www.endometriosis. ie/ or email info@endometriosis. ie and you can also sign up to become a member of the EAI for free via our website.

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Gastroenterology & Endocrinology - IBD

42

Obesity Therapy in Patients with Inflammatory Bowel Disease Written by Kate Parry1,2 and Werd Al-Najim1,3,4 BeyondBMI, Ireland 2Kings College Hospital, London, United Kingdom 3Conway Institute, University College Dublin, Ireland ProHealth365 Physiotherapy & Nutrition, Ireland

1 4

Kate Parry, Specialist Weight Management and Bariatric Dietitian

Werd Al-Najim, Registered Dietitian

Obesity

disease is active or in remission. The rate of IBD in Ireland is among the highest in the world. According to data from the Irish Society for Colitis and Crohn's Disease (ISCC), it is estimated that around 40,000 people in Ireland have IBD, with approximately 1 in every 160 individuals affected. UC usually affects the rectum but it can extend into the sigmoid and beyond including the entire colon. CD can affect any part of the gastrointestinal tract but most often affecting the ileum and colon. Both the diseases are classified by location and extent; mild, moderate or severe.

A person with a body mass index (BMI) over 30 is classified as having obesity, which can be defined as abnormal or excessive fat accumulation presenting a risk to health. With increasing research in this field, we are aware more than ever that obesity is a complex multifactorial disease with genetic, behavioural, socioeconomic, and environmental origins. According to the World Obesity Federation 2023 the prevalence of obesity is anticipated to rise from 14% to 24% of the population affecting nearly 2 billion adults, children and adolescents by 2035. The rising prevalence of obesity is expected to be steepest among children and adolescents, rising from 10% to 20% of the world’s boys during the period 2020 to 2035, and rising from 8% to 18% of the world’s girls demonstrating a need to provide greater preventative measures. IBD Inflammatory bowel disease (IBD) is a lifelong condition that can cause inflammation and ulcers in the gut. The two most common types of IBD are Crohns disease (CD) and Ulcerative Colitis (UC). People with the disease can go through periods of time where the

IBD and Obesity The incidence of IBD appears to be on the rise, particularly in developing nations where it was previously uncommon. The major common trend which can be noted among these areas is a rise in westernised diets. Modern westernised diets can be characterised by increased consumption of simple sugars and carbohydrates, higher quantities of animal sources compared with plant based sources, heavier reliance on processed foods and overall increase in caloric consumption. In the ESPEN guideline on Clinical Nutrition in inflammatory bowel

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

disease, they acknowledged that in the past obesity has not been associated with the disease, however they note that obesity does not stop in the IBD population and in fact obesity may worsen outcomes. Furthermore, it is increasingly recognised that obesity itself represents a low-grade inflammatory state and has been implicated as a risk factor for adverse outcomes in a number of other chronic inflammatory conditions, including psoriasis and rheumatoid arthritis, however, limited studies have been conducted to look at the relationship between IBD and obesity.

1. Diet and lifestyle

It is important to note that a significant percentage of the IBD population develop loss of lean body mass. With the increased risk of obesity this brings about a new concern over sarcopenic obesity which may occur due to chronically poor nutritional quality, increased rates of protein turnover and gut losses during phases of active flare.

2. Pharmacotherapy

What is obesity therapy? Obesity therapy is a way in which we can support weight loss in individuals living with obesity to improve health. There are multiple types of obesity therapy which are often offered in a step approach.

In Ireland, several services have been established to offer support to individuals through dietary and lifestyle modifications. These services are often provided as part of a multidisciplinary team, comprising professionals such as medical experts, dietitians, psychologists, and exercise specialists. Their aim is to assist individuals dealing with obesity by imparting knowledge on sustainable changes to enhance diet quality, decrease energy intake, boost physical activity, and cultivate new cognitive patterns conducive to altering eating habits.

Developments in pharmacotherapy over the past few years means there are more options available to support individuals living with obesity. Orlistat, a fat binding medication that when taken with food partially inhibits hydrolysis of triglycerides, thus reducing the subsequent absorption, was the only available option for many years. However, Liraglutide and Semaglutide have recently been approved by NICE for managing obesity and can be seen to support weight loss by reduced appetite and hunger with increased fullness and satiety. These medications are encouraged in addition to dietary, lifestyle and behavioural changes.

Bariatric surgery

Sleeve Gastrectomy (SG)

Roux-en-Y Gastric Bypass (RYGB)

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3. Bariatric surgery Bariatric surgery is a surgical procedure used in the management of obesity offering interventions to achieve substantial and sustained weight loss. The two most commonly used surgical procedures are the Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG). RYGB involves creating a small stomach pouch, restricting food intake. The small intestine is then rerouted to this pouch, bypassing a portion of the stomach and upper small intestine. The restrictive and malabsorptive components of RYGB contribute to weight loss. The reduced stomach size limits food intake, while bypassing part of the small intestine alters nutrient absorption. RYGB is associated with significant weight loss. Beyond weight reduction, it often leads to improvements in obesity-related comorbidities such as type 2 diabetes. SG involves removing ~70% of the stomach, leaving a narrow tube or "sleeve." This results in reduced stomach capacity and reduced production of hunger hormones. The procedure primarily relies on restrictive mechanisms, limiting the amount of food the stomach can hold. Additionally, hormonal changes contribute to appetite reduction and weight loss. SG is often chosen for its relative simplicity and lower risk of complications, with positive impacts on obesityrelated conditions. Can weight loss improve IBD outcomes? Patients within this population are

at a high prevalence of sarcopenia and micronutrient deficiencies indicating that on a restrictive diet they may be at risk of further deficiencies and muscle mass loss, especially in catabolic states such as those associated with IBD flares. With limited studies into this field, more research is still required to understand this better. Whilst one study looking at the association of obesity in UC found that as BMI increased by 1 kg/m2, the risk of hospitalisation and surgery rose by 3.4% and 5%, respectively1, another study concluded that patients with obesity had a lower risk of complications.2 Data is similarly limited in CD, with some suggesting that obesity may actually have a protective effect3, a more recent publication found that obesity is associated with decreased rates of disease remission and increased risk of complicated disease course in CD over a six-year follow-up period.4 The impact of obesity therapy on IBD outcomes? Diet and lifestyle interventions as previously discussed, are known as the first line approach for weight loss and should also be considered in the IBD population. It would be advised that specialist dietetic input is provided to ensure the specific needs of this population are being met, depending on type and severity of disease burden as it may not be possible for patients to tolerate the level of ‘healthy’ foods such as fruits and vegetables often encouraged. In addition to diet led interventions, increasing exercise may be linked to reduced risk of active disease

state in UC and CD and has been shown to increase psychological impact in this patient group, as well as weight.5 Pharmacological approaches, such as GLP-1 therapies listed above offer a promising avenue for promoting weight loss. However, use in IBD patients remains limited. One study does report reduced risk of adverse clinical events in individuals with IBD which includes the need for oral corticosteroids, TNF alpha inhibitors, hospitalisation and IBD related surgeries, suggesting these medications may have a positive effect on disease activity.6 However more research is still needed, including looking at CD and UC as distinct entities. Bariatric surgery has been demonstrated as a safe and effective weight loss therapy for those with pre-existing IBD7, however it is important to note that the type of surgery may be an important consideration. This is supported by research that shows that in patients with CD, RYGB is associated with increased IBD medication, whereas SG may result in less weight loss but has a lower rate of severe complications.8 No controlled intervention study has addressed the treatment of obesity in patients with IBD, therefore current ESPEN guidelines recommend against low-calorie diets in patients with active disease and instead recommends endurance training as the first step in any effort to lose weight. Conclusion Understanding the relationship between obesity and IBD is

crucial, given their substantial health impacts. The projected global prevalence of obesity, affecting nearly 2 billion by 2035, demonstrated urgent preventive measures. Simultaneously, the rising incidence of IBD across the world, which includes CD and UC, aligns with an increased shift towards modern Western diets. Although past perceptions did not link obesity to IBD, emerging research does demonstrate potential exacerbations of outcomes in the IBD population. Obesity, recognised as a lowgrade inflammatory state, raises concerns of sarcopenic obesity in IBD patients. Obesity therapy adopts a multicentered approach, including diet and lifestyle modifications, pharmacotherapy, and bariatric surgery. While studies explore the impact on IBD outcomes, limited evidence suggests varied outcomes. Exercise and pharmacological interventions show promise, yet comprehensive research, especially distinguishing between CD and UC, remains imperative. Bariatric surgery remains as an additional option, but considerations regarding surgery type, potential complications, and the absence of controlled intervention studies in IBD emphasise the need for cautious implementation. Addressing the complexities of obesity and IBD requires more evidence-based strategies, with ongoing research to support increasing numbers of individuals navigating this complex area. References available on request

News 100% Compliance for Mental Health Commission For the third year running, the Mental Health Commission has recorded a 100% compliance rate in its inspections of the HSE/South East Community Healthcare’s Grangemore residential support facility in Waterford. Located on the grounds of St. Otteran’s Hospital, Grangemore is an approved Mental Health Commission (MHC) centre providing Continuing Mental Health Care and Rehabilitation to 14 residents. The Mental Health Commission (MHC) plays a key role in inspecting

and measuring compliance to its regulations at inpatient and residential care centres. The MHC holds providers to account for achieving and maintaining a range of standards, identifying areas for improvement in mental health services and helping to ensure that the best possible service is provided to all service users. Welcoming the recent publication of the MHC’s 2023 inspection report on Grangemore, the Head of Service/Mental Health for HSE/South East Community Healthcare (SECH) Anne Donaghey said, “It is heartening when a

respected entity such as the Mental Health Commission has good things to say about mental health services provided in such facilities as Grangemore (which serves the Waterford and South Kilkenny area). Including through the challenging times of pandemic, there is an enormous contribution being made every day by my dedicated colleagues in our mental health services. In congratulating Consultant Psychiatrist in Rehabilitation and Recovery Dr. Darina Sloan, Clinical Nurse Managers (CNMs) 2 Grace King and William Browne, CNM 1

Helen Murphy and all of the team attached to Grangemore on this achievement, I know they’re also keen to include patients and their families for their support in this ongoing success story.” “Patient care remains a priority focus for the HSE, throughout all components of our service delivery. We strive at all times to adhere to the rules and regulations relating to provision of mental health services. We continue to work closely with the Mental Health Commission to ensure that all of our facilities comply with applicable guidelines.”

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

Gastroenterology & Endocrinology - Gastric Cancer

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Developments in Gastric Cancer Screening in Europe Written by Dr Charlene Deane, Dr Orlaith Kelly and Professor Colm O’Morain

intervention can effectively stop progression through this pathway thereby reducing unnecessary cancer deaths.

Dr Charlene Deane

Dr Orlaith Kelly

Professor Colm O’Morain

The current state of play: Gastric Cancer in Europe

screening program, which has resulted in a 5-year survival rate of up to 58%.

Professor Colm O’Morain, Clinical Lead in Gastroenterology & Hepatology and co-researchers Dr Orlaith Kelly, Consultant Gastroenterologist, Connolly Hospital and Dr Charlene Deane, Specialist Registrar in Gastroenterology. Having paired with Centric Healthcare, the Irish Defence Forces, the Construction Workers Health Trust and the Beacon HealthCheck, they will offer invitations to 30-34 year olds to be screened for Helicobacter pylori as part of pilot 1, a primary preventative strategy to gastric cancer.

In 2020, gastric cancer stood as the 6th most commonly diagnosed cancer, with 136,000 new cases diagnosed in Europe alone. Overall, Europe hosts the second-highest incidence of gastric cancer worldwide. While classically associated with Asian countries, European countries such as Portugal, Estonia, and Latvia report age-standardized rates comparable to China. Although the overall incidence of gastric cancer has declined in the past decade, the absolute number of new cases is anticipated to rise as the ageing population grows. In Ireland, the National Cancer Registry has captured approximately 600 new cases of gastric cancer per year (data from 2014.-2021), placing Irish males in the ‘intermediate risk’ category for gastric cancer. Unfortunately, gastric cancer still carries an extremely poor prognosis in Europe as it is frequently diagnosed at an advanced stage. Approximately two-thirds of Irish patients have stage 3 or 4 cancer at diagnosis, with an average 5-year survival rate of only 24%. In contrast, Japan, which has one of the highest incidences of gastric cancer worldwide, has implemented a successful

Gastric Cancer Screening and Europe’s Beating Cancer Plan In 2022, the European Commission published ‘Europe’s Beating Cancer Plan’. This report identified three cancers to target for the development of new national screening programmes: gastric, lung and prostate cancer. However, as it stands, the most cost-effective and feasible method of gastric cancer screening in a European population is largely unknown. Therefore, in response to the recommendations from the European Commission on gastric cancer screening, a research group known as TOGAS (Towards Gastric Cancer Screening Implementation in the European Union) was established. This group involves 20 partners across 14 different EU countries. This group will conduct three pilot projects funded by the European Union to provide initial data on the feasibility and cost-effectiveness of different screening methods in order to address this unknown. Ireland is one of the countries involved in the study and represents countries in Europe with a low-intermediate risk of gastric cancer. The Irish TOGAS team is being led by

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Screening mechanisms and existing Screening Programmes Pathogenesis of Gastric Cancer The Correa cascade defines the pathogenic progression from normal mucosa to atrophic gastritis, gastric intestinal metaplasia, low-grade dysplasia, high-grade dysplasia, and, ultimately, carcinoma. Screening is focused on the disruption this cascade through early detection and treatment of Helicobacter pylori, a known promoter of preneoplastic and neoplastic lesion development, known as primary prevention. Secondary prevention involves the early detection of precancerous and early cancerous lesions. Both approaches aim to intervene at a point where pharmacological or endoscopic

While no gastric cancer screening programme currently exists in Europe, the concept is not new. The Maastricht VI/ Florence consensus guidelines, the Science Advice for Policy by European Academics (SAPEA), and the International Agency for Research on Cancer (IARC) all recommend a ‘screen and treat’ approach in countries in Europe with intermediate and high risk of gastric cancer. Meanwhile, screening programmes have already been effectively implemented in several Asian countries for decades. The earliest gastric cancer screening programme was established in Japan in the 1950s. Since then, numerous randomised controlled trials have been conducted to evaluate the impact of primary and secondary prevention screening strategies on mortality rates. Evidence Supporting Primary Prevention Several randomised control trials have demonstrated the advantage of population screening and treatment of H.pylori in reducing gastric cancer risk. Ford et al. conducted a meta-analysis encompassing seven randomised control trials involving healthy adults with H.pylori infection who received either treatment or a placebo. The pooled analysis revealed an impressive relative risk reduction in gastric cancer mortality for those receiving treatment (RR 0.54; 95% CI 0.400.72), with little heterogeneity among the studies. According to this meta-analysis, the calculated number needed to treat to prevent one case of gastric cancer was 72, and the number needed to treat to prevent one cancerrelated death was 135. Numerous longitudinal observational studies also support the positive impact of population screening. The Matsu Island study, a notable prospective investigation, involved testing and treating adults over 30 for H.pylori. The study reported a 53% reduction in gastric cancer incidence, a 25% reduction in mortality, and no increase in the antibiotic resistance rate of

(pembrolizumab) Infusion 25mg/ml

KEYTRUDA: multiple treatment options for more patients with mNSCLC1

PD-L1 <1% or unknown

PD-L1 1-49%

PD-L1 >50%

NONSQUAMOUS

√

√

√

1st line Combination** Therapy3

SQUAMOUS

√

√

√

1st line*** Monotherapy4

NON-SQUAMOUS AND SQUAMOUS

X

X

√

Line

Histology

1st line Combination* Therapy2

adverse reactions Immune-mediated adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. Most immune mediated adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Immune mediated adverse reactions have also occurred after the last dose of pembrolizumab. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Immune-mediated adverse reactions are immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated nephritis, immune-mediated endocrinopathies (including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism), immune-mediated skin adverse reactions (also including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). Refer to SmPC for more information and management of immune-mediated adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with classical Hodgkin lymphoma undergoing allogeneic HSCT after previous exposure to pembrolizumab. Infusion-related reactions: Grades 1, 2, 3 or 4 infusion reactions including hypersensitivity and anaphylaxis, could be seen with pembrolizumab treatment. Refer to SmPC for more information and management of infusion-related reactions. Patients with Biliary tract carcinoma (especially those with biliary stents) should be closely monitored for development of cholangitis or biliary tract infections before initiation of treatment and, regularly, thereafter. Overdose: There is no information on overdose with pembrolizumab. In case of overdose, monitor closely for signs or symptoms of adverse reactions and treat appropriately. INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. No metabolic drug drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. Corticosteroids can be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. FERTILITY, PREGNANCY AND LACTATION Women of childbearing potential Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Pregnancy No data on use in pregnant women. Do not use during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Breast-feeding It is unknown whether pembrolizumab is secreted in human milk. A risk to newborns/ infants cannot be excluded. Fertility No clinical data available. SIDE EFFECTS Refer to SmPC for complete information on side effects. Pembrolizumab is most commonly associated with immune-mediated adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-mediated and infusion-related adverse reactions. When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment. For additional lenvatinib safety information related to advanced RCC see the SmPC for Kisplyx and for advanced EC see the SmPC for Lenvima. Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, pruritus, rash, fatigue. Common: pneumonia, thrombocytopenia, neutropenia, lymphopenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, dizziness, dysgeusia, pneumonitis, colitis, dry mouth, hepatitis, severe skin reactions, vitiligo, dry skin, eczema, alopecia, dermatitis acneiform, erythema, dermatitis, myositis, pain in extremity, arthritis, influenza like illness, chills, AST and ALT increases, increase in blood alkaline phosphatase, hypercalcaemia, blood bilirubin increased, blood creatinine increased, infusion related reaction. In combination with chemotherapy: Very Common: Anaemia, neutropenia, thrombocytopenia, hypothyroidism, hypokalaemia, decreased appetite, insomnia, neuropathy peripheral, headache, dyspnoea, cough, diarrhoea, vomiting, nausea, abdominal pain, constipation, alopecia, pruritus, rash, musculoskeletal pain, arthralgia, pyrexia, fatigue, asthenia, ALT increase, AST increased. Common: pneumonia, febrile neutropenia, leukopenia, lymphopenia, infusion related reaction, adrenal insufficiency, thyroiditis, hyperthyroidism, hyponatraemia, hypocalcaemia, lethargy, dizziness, dysgeusia, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, pneumonitis, colitis, gastritis, dry mouth, hepatitis, severe skin reactions, erythema, dermatitis, dry skin, dermatitis acneiform, eczema, myositis, pain in extremity, arthritis, acute kidney injury, oedema, influenza-like illness, chills, blood bilirubin increased, blood alkaline phosphatase increased, blood creatinine increased, hypercalcaemia. In combination with axitinib or lenvatinib: Very Common: urinary tract infection, anaemia, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, diarrhoea, abdominal pain, nausea, vomiting, constipation, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pain in extremity, fatigue, asthenia, oedema, pyrexia, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, infusion-related reaction, adrenal insufficiency, hyperthyroidism, thyroiditis, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, dizziness, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, pancreatitis, gastritis, dry mouth, hepatitis, severe skin reactions, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, arthritis, nephritis, influenza like illness, chills, amylase increased, blood bilirubin increased, blood alkaline phosphatase increased, hypercalcaemia. PACKAGE QUANTITIES KEYTRUDA 25 mg/mL: 4 mL of concentrate in a 10 mL Type I clear glass vial. Legal Category: POM. Marketing Authorisation numbers: EU/1/15/1024/002. Marketing Authorisation holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: December 2023. © 2023 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin, D18 X5K7 or from www.medicines.ie. II135_II138 Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to MSD (Tel: 01-2998700) References 1. KEYTRUDA Summary of Product Characteristics, August 2023, available at www.medicines.ie. 2. Gandhi L, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378:2078-2092. 3. Paz-Ares L, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379:2040–2051. 4. Reck, M et al. Pembrolizumab versus chemotherapy for PDL1 positive-non-small cell lung cancer, N Eng J Med 2016, 375(19)1823-1833. ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; mNSCLC=metastatic non–small cell lung carcinoma; PDL1=programmed death ligand 1. Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7, Ireland.

IE-KEY-00845

KEYTRUDA® (pembrolizumab) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION KEYTRUDA 25 mg/mL: One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. INDICATIONS • KEYTRUDA as monotherapy is indicated for the treatment of adults and adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma. • KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults and adolescents aged 12 years and older with Stage IIB, IIC or III melanoma and who have undergone complete resection. • KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with non-small cell lung carcinoma who are at high risk of recurrence following complete resection and platinum-based chemotherapy. • KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. • KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. • KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults. • KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 with a ≥1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. • KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. • KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy. • KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD L1 with a combined positive score (CPS) ≥ 10. • KEYTRUDA as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 1. • KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic HNSCC in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy. • KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma (RCC) in adults. • KEYTRUDA, in combination with lenvatinib, is indicated for the first line treatment of advanced renal cell carcinoma in adults. • KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers. Colorectal cancer (CRC). • KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings: - first line treatment of metastatic colorectal cancer. - treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine based combination therapy. Non-colorectal cancers. • KEYTRUDA as monotherapy is indicated for the treatment of the following MSI H or dMMR tumours in adults with (a) advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation, (b) unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy. • KEYTRUDA, in combination with platinum and fluoropyrimidine based chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus in adults whose tumours express PD-L1 with a CPS ≥ 10. • KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early stage triple negative breast cancer at high risk of recurrence. • KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple negative breast cancer in adults whose tumours express PD L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease. • KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation. • KEYTRUDA, in combination with chemotherapy with or without bevacizumab, is indicated for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD L1 with a CPS ≥ 1. • KEYTRUDA, in combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 1. • KEYTRUDA, in combination with fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumours express PD L1 with a CPS ≥ 1. • KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the first-line treatment of locally advanced unresectable or metastatic biliary tract carcinoma in adults. DOSAGE AND ADMINISTRATION See SmPC for full details. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes. The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL or patients aged 12 years and older with melanoma is 2 mg/kg bodyweight (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. KEYTRUDA must not be administered as an intravenous push or bolus injection. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Treat patients until disease progression or unacceptable toxicity (and up to maximum duration of therapy if specified for an indication). For the adjuvant treatment of melanoma, NSCLC, or RCC, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year. Refer to the SmPC for dosing in neoadjuvant and adjuvant treatment of locally advanced, or early stage triple-negative breast cancer at high risk of recurrence. KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued (a) For Grade 4 toxicity except for: endocrinopathies that are controlled with replacement hormones; or haematological toxicity, only in patients with cHL in which KEYTRUDA should be withheld until adverse reactions recover to Grade 0-1; (b) If corticosteroid dosing cannot be reduced to ≤10 mg prednisone or equivalent per day within 12 weeks; (c) If a treatment-related toxicity does not resolve to Grade 0 1 within 12 weeks after last dose of KEYTRUDA; (d) If any event occurs a second time at Grade ≥ 3 severity. Patients must be given the Patient Card and be informed about the risks of KEYTRUDA. Special populations Elderly: No dose adjustment necessary. Renal impairment: No dose adjustment needed for mild or moderate renal impairment. No studies in severe renal impairment. Hepatic impairment: No dose adjustment needed for mild or moderate hepatic impairment. No studies in severe hepatic impairment. Paediatric population: Safety and efficacy in children below 18 years of age not established except in paediatric patients with melanoma or cHL. CONTRAINDICATIONS Hypersensitivity to the active substance or to any excipients. PRECAUTIONS AND WARNINGS Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations. Immune-mediated

Date of Preparation: February 2024

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

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H. pylori. In a specific examination of a European population, Doorakkers et al. utilised the Swedish National database to assess the impact of H.pylori treatment on gastric cancer incidence, once again confirming the benefits of eradication in reducing mortality. Lastly several randomised control trials with long-term follow-up are underway, with planned analyses in the near future. One of these longitudinal studies being conducted in the UK is the ‘The Helicobacter pylori screening study’ currently due for completion in 2024. Evidence Supporting Secondary Prevention Secondary preventive measures as part of national screening programme have included endoscopy, photofluorography and/or serum pepsinogen levels to identify early neoplastic lesions. The evidence to date is predominantly based in Asian countries and strongly supports good quality endoscopy as the superior screening method out of these three. A recent metaanalysis by Hibino et al. reported a 48% relative risk reduction in gastric cancer mortality among individuals who underwent endoscopic screening. A more targeted screening approach in Europe using secondary screening modalities has also been proposed in several smaller-scale studies. Three particular studies in a European population include those performed by Planade, Segrad and Tepes et al. in France, Germany and Slovenia, respectively. In

these studies, they reported findings on gastroscopy of those undergoing a colonoscopy as part of their national screening service. These studies were performed to determine if concurrent gastroscopy with colonoscopy would benefit this ‘high-risk’ age group. These studies had a positive diagnostic yield of precancerous lesions ranging from 6.4–30% and H.pylori infection ranging from 17-75%. Future Direction and ongoing research European-funded research into screening strategies is ongoing

both as part of the Eurohelican study, which looks at the feasibility of a national screening programme for H. pylori in Slovenia and the TOGAS study. We can expect the results to be published in 2026, and the outcomes will help determine future policy-making decisions on a gastric cancer screening approach. Other areas of research which may positively impact screening strategies in the future include the ongoing research into the potential of engineered probiotics which target H.pylori, vaccination against H.pylori which currently remains at a preclinical stage and the

drive to improve quality in upper gastrointestinal endoscopy through the use of artificial intelligence.

“Funded by the European Union. Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union. The European Union cannot be held responsible for them.”

News Diabetes Ireland Launch New App Diabetes Ireland is delighted to announce the arrival of the multi-award-winning DigiBete Self-Management App and Video Platform in Ireland. Following a successful pilot project in Limerick University Hospital, Diabetes Ireland and DigiBete have spent the past few months training other paediatric diabetes teams on how to use the App to educate their families on managing Type 1 diabetes. The primary aim of the App is; • to improve care for children and young people with diabetes

by helping them manage their condition more effectively. • provide an easy cost-free communication stream for hospital paediatric diabetes teams to engage with families to provide clinical advice and information. The App supports children and adolescents with Type 1 diabetes and their families by giving them a place to organise their diabetes appointments, and ongoing care, and receive access to relevant educational resources. Families will be able to access age-

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

appropriate diabetes information such as quizzes, videos, and food & exercise support.

diabetes management advice such as sick day rules and good care reminders in a matter of minutes.

Families will also be able to develop a record of personalised information about their diabetes care, set reminders of their clinic appointments and receive invites to various family events, education workshops and much more.

Diabetes Ireland CEO Kieran O’Leary said “We are delighted to make DigiBete available to the families of the 3,000 children and adolescents living with Type 1 diabetes in Ireland. We feel this is a fantastic investment that supports children and young people with diabetes and their families and paediatric diabetes teams nationwide. It will also allow us to reach families more directly to offer our services and extend invites to our events.”

A huge benefit for paediatric diabetes teams is that they will be able to share accurate and timely clinical advice and information directly with their families, send appointment reminders and share

Gastroenterology & Endocrinology - Ask the Expert

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Transforming the Obesity Landscape A leading clinical scientist and expert on how the gut and brain communicate, Professor Carel Le Roux was named at the Irish Research Council Researcher of the Year for 2023. He was awarded the prestigious prize for his work on developing safer and more effective treatments of obesity. Director of the Metabolic Medicine Group affiliated with the UCD Diabetes Complications Re-search Centre (DCRC) in the UCD Conway Institute, his research has focused on the impact of diet, exercise, medication and surgery, including bariatric surgery, on enhancing gut-brain signalling for the management and treatment of the disease of obesity. Professor Le Roux was the recipient of a ¤600,000 IRC Laureate funding award in 2018, which he credits with enabling him to lead the development of the ¤16 million European project SOPHIA (Stratification of Obesity Phenotypes to Optimise Future Obesity Therapy) which is addressing obesity and its complications such as type 2 diabetes and chronic kidney disease. We recently spoke to Professor Le Roux to find out more about this important work. Professor Le Roux studied medicine at the University of Pretoria in South Africa and completed his PhD at Imperial College London before becoming Faculty, which is where he started the first obesity clinic. He explains, “The clinic was really a combination of looking at obesity, type 2 diabetes and hypertension. But it brought the field from which I was able to drive my understanding.” When he moved to University College Dublin, Professor Le Roux established a research unit at St Vincent’s, at which many clinical trials have taken place. He says, “It was really in this period from 2012 until now that we have witnessed an incredible increase in powerful treatments that offer the opportunity to change the disease of obesity.” You recently won Researcher of the Year Award: Tell us more about this research “I was very fortunate to win this accolade, which was really based

Professor Carel le Roux

“Our biggest challenge is people that are living with obesity don’t think they have a disease. If people don’t think they have a disease, they do not treat it like a disease….. Furthermore, as an equivalent, many doctors don’t think it is a disease. There still exists an approach and belief that patients need to try harder and get ready for change instead of treating them like we would treat anyone with other conditions”

on our translational research. We were able to show in the basic laboratory, animal house and with clinical research that we can treat the disease of obesity by using signals in the gut and we can enhance the signal through nutritional therapies, through pharmacological therapies and surgical therapies. “If we treat this disease, it becomes under control and can therefore remain under control in the long-term, provided the treatments are sustained. However, if we are able to control

the disease of obesity, that disrupts other diseases such as diabetes or disrupts cardiovascular disease or disrupts chronic kidney disease. So, our work went on to show that you can also reverse the complications of obesity. You can put type 2 diabetes into remission, you can put early chronic kidney disease into remission, and we can now see that we can prevent cardiovascular events as well. “My research started from studying the pathophysiology of the disease, understanding the treatments, and now using the

treatments, not for weight loss but for health gains. “This research takes us back to where we started, now we have so much more insight into the disease, we are understanding the pathophysiology of the disease, and we are now understanding how to approach it. “So the next steps for us lie in understanding that it is not one disease but a cluster of diseases. Now we are deconstructing obesity and if we can define it then we can be more effective at targeting patients who are at the

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

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Professor Carel le Roux grandchildren, or go out with their friends, or put their socks and their shoes on. The activities of daily living without problems. These are the real benefits of these interventions. Ultimately it is about reducing symptoms and reducing complications.” How do you view the role of the Pharmacist in treating patients with obesity?

highest risk, while also targetting those patients who will benefit the most from different interventions.” Tackling Challenges In looking ahead and what the biggest challenges are in this field for 2024, Professor Le Roux told us, “Our biggest challenge is people that are living with obesity don’t think they have a disease. If people don’t think they have a disease, they do not treat it like a disease. They believe that this is their responsibility, and they need to do something about it. But if you have, for example, hypertension, you would go to your doctor and ask for help. “Furthermore, as an equivalent, many doctors don’t think it is a disease. There still exists an approach and belief that patients need to try harder and get ready for change instead of treating them like we would treat anyone with other conditions. We give people lifestyle treatment; we know that is important, but we treat them with biological treatments so that we can get the disease of hypertension under control, and I hope that we get the disease of obesity under control.” So what advice would he give to doctors who accept that obesity is a disease and want to prescribe treatment? “My advice would be that you need to listen to the patient; the proof is in the patient. When we have the effective treatments, we need to get beyond weight loss and think about the health benefits. The first thing that improves is the change in symptoms, they should start feeling less hungry and more full. “The second thing is to shift the patients’ expectations away from weight loss to health gain, especially functional gains. So, it will be someone who is able to play with their children, or

He adds, “My heart goes out to all Pharmacists this year because there has been a tremendous shortage of supply of treatments. Pharmacists were wrongly asked to prioritise the treatment of some diseases over others. Pharmacists are also a part of the public and can have the same preconceptions of the public. “Pharmacists of course, will never knowingly hurt patients, but so many unfortunately have been asked to tell people in public, in the pharmacy that they are not eligible for treatment because the department of health have said that these treatments should be prioritised to patients with type 2 diabetes. “From a hospital pharmacy point of view, it may not be as acute as in the general pharmacy and a public pharmacy but there is still a massive problem. Pharmacists have probably put the disease of obesity back by 5 years, not intentionally of course, but because the system created an environment and consequences where they were not adequately trained and supported.” How do you pharmacists should move forward and move past that? “I think we need to understand what caused the problem, and the cause is that the companies are not able to manufacture these treatments fast enough. Ultimately, if the manufacturing can be improved, the problem will go away. “The patients who are asking for treatment, are correct to ask for help. The doctors who prescribe the treatment, are correct to prescribe biological treatments for a disease. The pharmacists that provide the treatment are correct to provide good pharmacotherapy. But now the manufacturers have to provide more products. Instead of it becoming a circular firing squad where the patients are angry with the pharmacists, and the pharmacists are angry with the doctors what we need to do, is

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

get the manufacturers to provide more medications. “That is what happened with the Covid-19 vaccine. As many will remember, there just wasn’t enough vaccines available and people were really upset with each other and then suddenly there was enough, and the problem went away. I think we really need to focus on where we can make a difference rather than making problems. Until that point, we need to be honest and say there are not enough treatment options right now and we need to do that on a reasonable and rational basis. “For the patients we are not able to provide treatments for, we need to treat them with empathy, like we would have done for those who were very anxious to get Covid-19 vaccines because they were at a very high-risk of dying. We didn’t say you are bad people for asking for it, we said this is a difficult situation and we are working as fast as we can while treating patients with empathy.” How does Irelands obesity treatments compare to Europe and America? Professor Le Roux recognises that due to Irelands healthcare system, public patients are under tremendous pressure, simply because there is not enough clinics to provide these treatments. “Therefore, a lot of our public patients are not getting the treatments provided, because either they don’t have access to a doctor that can prescribe it, because there are not enough doctors that are trained and not enough clinics that can provide this to the public. We do have reimbursement of these treatments within our system, which is a positive. “Those reimbursement processes are robust, but they are used as a budget impact tool rather than a facilitate access to the patients who would benefit most. I think the processes are there, but it is just a mind shift that we must do. We have to think about doing the right thing appose to blocking the wrong thing. We are almost there but not quite yet. “I think from a private point of view, many patients in Ireland have a tradition, where people have bought medications and accessed care privately. This is unfortunate as people are genuinely spending vast amounts of money, very often money they don’t have and the problem with that is that patients are not able to sustain the

treatment because the treatments are expensive, accessing private health care is expensive. My concern is that we need to make sure if a patient is successful, that they are able to sustain the treatments in the long term. What are the three things we need: 1. More public access 2. Reimbursement process which are fair and reasonable, but it needs to be implemented to help people as appose to block people and 3. Thirdly, the private system is able to help but we need to make sure we are not overselling treatments., We should not say to people to have those treatments because they are going to look different or they are going to feel different, we need to say you need this treatment so you can be healthier, so that patients use it for health gains and not for other purposes.” In concluding, Professor Le Roux states, “We should recognise at all levels: the patient, provider, and government’s perspective. We should understand that obesity is a biological disease that we need to treat biologically with nutritional therapies, pharmacological therapies and with surgical therapies. “I think what we need improve equity. Right now, in Ireland, obesity treatment is not equitable and we need to say, ‘which are the patients who will benefit most from this treatment?’ This is not necessarily the patients who are the heaviest, it is the people who will benefit most from a health gain point of view where the evidence is pretty clear. “We need to focus on achieving equity. If treatments for obesity are not equitable, it is going to develop a bad reputation and people are going to resent each other and create uncomfortable position for patients and providers. We have made most of the mistakes we could possibly make and at the moment obesity treatment is not equitable. “The way to do that is to understand the science and if we understand obesity is a disease and how the treatment works and understand what the side effects are and how to minimise the side effects and how to optimize prescriptions then we will achieve most benefit. I think the science is going to be the underlying driver of a better society for us.”

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Promise in Advanced HER2-Negative Breast Cancer Lead author Professor Roisin Connolly, Director of Cancer Research, University College Cork Treatment in a recent study combined a histone deacetylase (HDAC) inhibitor - a drug that causes a chemical change to stop tumor cells from dividing - with two types of immunotherapy known as checkpoint inhibitors, which unharness the power of the immune response against cancer. The study was led by Professor Roisin Connolly of Cancer Research @UCC while based at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, with the results published today in Nature Cancer. The multicenter study included 24 women with HER2-negative metastatic breast cancer in a dose escalation and dose expansion early phase trial. The results of the dose escalation portion of the trial are previously published in Clinical Cancer Research. The study team who aimed to improve response to immune checkpoint inhibitors by sensitizing the tumor microenvironment, found that the combination therapy resulted in a 25% overall response rate in women with advanced HER2 (human epidermal growth factor receptor 2)-negative breast cancer. This means that 25% of women who took the therapy saw their cancer destroyed or significantly reduced.

Patients with triple-negative breast cancer, who have fewer treatment options than patients with other breast cancers, had an overall response rate of 40%. These tumor responses are significant if confirmed as advanced breast cancer, in particular the triplenegative subtype (15% of breast cancers), remains an area of unmet clinical need due to paucity of effective therapies.

“This clinical trial highlights the importance of interdisciplinary collaboration to bring an exciting hypothesis from the laboratory to the clinic, and sets the scene for future trials investigating novel treatment approaches for this patient population” says Dr Roisin Connolly lead principal investigator for the trial.

The average progression-free survival (PFS) was 50% at six months, meaning that half of the participants went six months without their disease worsening.

Correlative science for this clinical trial was led by Dr Evanthia Roussos Torres, Assistant Professor of Oncology at University of Southern California.

“To our knowledge, this is the first published study that investigates treatment with an HDAC inhibitor in combination with dual immune checkpoint inhibitor therapy in patients with advanced breast cancer,” says co-author Elizabeth M. Jaffee, M.D., Deputy Director of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. “Heavily pretreated advanced breast cancer remains an area of unmet need and a combination strategy that results in the ORR and PFS described is of interest.”

Review of National Rare Diseases The Health Information and Quality Authority (HIQA) has published a review of national rare disease strategies in selected countries. This review was requested by the Department of Health to support the development of a new national rare disease strategy for Ireland. A rare disease is defined by the European Commission as a condition that affects fewer than 5 in 10,000 people. There are more than 6,000 known rare diseases, which in total are estimated to affect approximately 6% of Europeans, or approximately 300,000 Irish people. HIQA reviewed the national rare disease strategies of 12 countries: Austria, Australia, Denmark, England, Finland,

France, Germany, the Netherlands, Northern Ireland, Portugal, Scotland and Wales. The review described key aspects of the strategies, including their aims, themes and priorities, and compared them to Ireland’s previous national rare disease strategy, the National Rare Disease Plan for Ireland 2014 – 2018. Improving treatment and coordination of care was an overall aim for most countries. All 12 countries outlined themes of screening and diagnosis, access to healthcare and coordination of services, rare disease research, and patient representation and empowerment. Ireland’s previous strategy included similar aims and themes. Themes not addressed

in that strategy were health workforce education and training, and access to mental health and psychology services. The review also described the actions planned and how countries aimed to support strategy implementation. Many countries, including Ireland, implemented their strategy using a combination of new and existing structures in their health services, with oversight from the department or ministry for health. Most countries outlined funding sources for some or all aspects of their strategies. For countries that did not describe funding sources, or, like Ireland, did not outline a dedicated budget for the strategy, lack of funding was identified

as a challenge to strategy implementation. Michelle O’Neill, HIQA’s Deputy Director of Health Technology Assessment, said: “Rare diseases pose unique challenges, particularly in relation to timely and accurate diagnosis, and access to specialised treatment. A country’s national rare disease strategy aims to reduce the burden of rare diseases, and improve the quality of care for people with rare diseases. This review provides insights into what other countries identified as issues of importance in their national rare disease strategies, the actions undertaken, and how they supported strategy implementation.”

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

50 News

National Service Plan met with Criticism HSE Chairman Mr Ciaran Devane

towards the goal of universal healthcare in line with the ambitions of the Government and the HSE’s Corporate Plan. In doing so, it builds on the growth in funding and in staff we have seen over the past number of years, growth which has enabled Ireland to continue to improve the health and life expectancy of the public. The HSE has published the 2024 National Service Plan following approval by the Minister for Health, Stephen Donnelly TD and the Minister for Children, Equality, Disability, Integration and Youth, Roderic O’Gorman TD. The National Service Plan (NSP 2024) outlines the health and social care services to be provided to the people of Ireland this year. The Government has allocated a budget of ¤23.5bn for this purpose, which is 4.6% above last year’s budget. Of this ¤23.5bn, ¤2.8bn has been provided by the Department of Children, Equality, Disability, Integration and Youth in respect of specialist disability services with a balance of ¤20.7bn provided by the Department of Health, which will allow for 683 new Whole Time Equivalent (WTE) for disability services and 2,268 WTEs for other health and social care services. It includes: • ¤162.8m investment in new service developments, including enhancing mental health and disability services • ¤918.7m once-off funding • ¤834.7m to fund increased costs of providing the existing level of service • Funding to support the implementation of the six new Health Regions The HSE’s focus for 2024 is to improve access to urgent and emergency care; prioritise waiting lists; continue to enhance mental health and disability services, and build on existing partnerships to develop and improve services. Speaking about the HSE’s priorities for 2024, Mr Ciarán Devane, HSE Chairman, said, “The National Service Plan 2024 continues to move the HSE

“The NSP for 2024 is a continuation of the work of the preceding year and represents another year of growth. Together, the two years will see staff increase in the region of +9,000 WTE and funding by ¤3bn. During 2024, we will consolidate the developments of recent years, particularly around access, and ensure we deliver the increased capacity this investment is intended to provide. We want to allow the increased number of clinical staff to care for an increasing number of patients and users of our services.” The Irish Hospital Consultants Association has said that a lack of commitment to open required additional acute hospital beds is ‘wholly inadequate.’ The Association has criticised the lack of commitment in the HSE National Service Plan 2024 to open a specified number of additional general acute hospital beds this year. The Minister for Health, Stephen Donnelly has previously announced plans to open 147 additional acute beds in 2024, however, this is not reflected in the HSE’s National Service Plan. The figure is also significantly below what is required to start addressing the severe overcrowding in our public hospitals and tackle the persistently high waiting times for treatment. The Economic and Social Research Institute (ESRI) has estimated public acute hospitals need 1,000 additional inpatient beds immediately and an extra 330 beds a year just to keep up with demand from increasing population pressures. While any increase in health funding is welcome, the fact that an almost ¤1 billion supplementary budget was required for 2023 outside of the original budget allocation illustrates that the health service continues to

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

be inadequately funded. A similar deficit is now likely in 2024, resulting in a substantial supplementary budget again being required next December to bridge that funding gap. A spokesperson for the IHCA said, “It is deeply disappointing that the Service Plan for 2024 has failed to commit to opening a specified number of additional general public hospital beds this year. “Even if all of the 147 additional beds promised by the Minister for 2024 are opened on time, this would mean a net increase of just 45 hospital beds over and above where we should have been at more than a year ago. “This level of bed expansion, if delivered, is far less than provided for in the National Development Plan, which averages 260 beds per annum, a level the Minister for Health is on record as stating “lowballed” the hospital capacity needs in the first place. “It is also regrettable that the HSE and Government continues to renege on its pledge to commit

the ¤1 billion in funding required to open 1,500 additional rapid build hospital beds across 15 acute public hospital sites this year. “At the same time, the delivery of the promised six surgical hubs and long awaited four elective hospitals must be accelerated in order to provide the capacity that is required to meet all of the Government’s waiting list reduction targets. “It is also particularly concerning that the National Service Plan only delivers a modest increase in the Mental Health Budget to ¤1.308bn in 2024. This is an increase of just ¤34m (2.7%) on the revised 2023 Budget of ¤1.274bn. “Despite a slight overall increase in spending, just ¤3.1m is allocated for new measures in mental health. This is the second year in a row when the level of funding for new measures has actually decreased compared with the previous year: from ¤24m in 2022 to ¤14m in 2023 and to just ¤3.1m in 2024 – a reduction of almost ¤21m or 87% in two years.”

Hospital Professional

ONOURS 2024 The Hospital Professional Honours will take place on Saturday, 14th September 2024 in the Radisson Blu Hotel, Dublin. Entries are now open across a number of categories including:

Haematology Project of the Year Young Hospital Pharmacist of the Year Galapagos Multidisciplinary Team of the Year Fresenius Kabi Innovation in Aseptic Compounding Medisource Hospital Pharmacy Technician of the Year Grünenthal Advancing the Standard of Care in Pain Management Athlone Pharmaceuticals Hospital Pharmacy Team of the Year Excellence in Respiratory Viatris Excellence in Cardiovascular Initiative Pharmasource Hospital Pharmacist of the Year MSD Excellence in Oncology Initiative MSL Distribution Innovation and Service Development Excellence in Patient Safety To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

52 Educational Learning

A Comprehensive Guide to Treating Moderate to Severe Psoriasis Learning Objectives Psoriasis is a chronic multisystem autoimmune disease with prominent skin manifestations and multiple potential co-morbidities such as arthritis, inflammatory bowel disease, cardiovascular disease, and depression. Moderate-severe psoriasis is usually defined by the extent of skin involvement, although special sites or significant impact on quality of life are also considered. Topical measures should still be utilised to manage more severe psoriasis, but advanced systemic and biologic therapies have revolutionised the management of psoriasis. Phototherapy involves use of ultraviolet B or A (in combination with the photosensitiser psoralen). Systemic agents for moderate-severe psoriasis include methotrexate, ciclosporin, apremilast, acitretin, and fumaric acidic esters. Biologic targets include tumour necrosis factor alpha, interleukin-12/23, interleukin-17, and interleukin-23 inhibitors. Oral steroids should never be used to treat psoriasis due to the significant risk of potentially serious rebound flares once they are stopped and given that extremely effective targeted agents are now available. Written by Dr Cathal O’Connor, RCPI dermatology specialist registrar in dermatology dual training in general paediatrics, ICAT paediatric dermatology fellow

Introduction Psoriasis is a chronic multisystem autoimmune disease with cutaneous involvement. It is characterised by the rapid growth of skin cells, leading to the formation of thick, red, and scaly plaques, although other presentations can occur. Approximately 73,000 people have psoriasis in Ireland. Individuals with moderate to severe psoriasis often experience significant physical and psychological co-morbidities. Most patients with psoriasis can be treated in primary care or in the outpatient setting. However, life-threatening presentations such as erythrodermic psoriasis or pustular psoriasis can require intensive inpatient management. While severe psoriasis should be managed by consultant dermatologists with access to advanced therapeutics, this article explores the various treatment options available for moderate to severe psoriasis, highlighting the importance of personalised and multimodal approaches. Understanding Moderate-Severe Psoriasis Psoriasis is driven by immune dysfunction that mistakenly targets healthy skin cells, triggering rapid cell turnover. This abnormal cell proliferation leads to the formation of plaques, commonly found on the elbows, knees, scalp, and lower back. Other patterns of psoriasis include guttate, flexural, pustular, and erythrodermic.

than 10% of the body surface affected, or a psoriasis area and severity index (PASI) over 10. Special sites that may warrant intensive treatment for localised disease include the face, palms and soles, and genitals. Additionally, individuals with severe psoriasis may be more likely suffer from arthritis, uveitis, inflammatory bowel disease, and cardiometabolic complications, highlighting the importance of a systemic approach to treatment. Systemic or biologic therapy should be considered for extensive disease, but topical treatments are often required for localised resistant areas, in tandem with these advanced therapies. Referral to Dermatology Referral to a dermatologist should be considered in the following settings: • The diagnosis is unclear • The response to topical treatment is inadequate • There is significant impact on quality of life • The patient has widespread severe disease (over 10% body surface area) • The patient has persistent involvement of ‘special sites’ – face, palms/soles, genitals • In cases of co-morbidities, psoriatic arthritis, referral and/ or collaboration with other specialties (eg rheumatology in the case of arthritis) Treatment Modalities Treatment for psoriasis can be prescribed in a step-wise ladder, with topical treatments for mild

Moderate to severe psoriasis is usually defined by the extent of skin involvement, with more MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Figure 1

disease and phototherapy, systemic agents, or biologic agents for more severe disease (Figure 1). There are theoretically more potential side effects with immunomodulatory systemic or biologic medications given that they are administered systemically, although they are usually well tolerated when prescribed under the conscientious care of a dermatologist. Topical Treatments Emollients Hydration and emollients are valuable and inexpensive adjuncts to psoriasis treatment. Keeping psoriatic skin soft and moist minimizes the symptoms of itching and tenderness. Additionally, maintaining proper skin hydration can help prevent irritation and thus the potential for subsequent Koebnerisation (development of new psoriatic lesions at sites of trauma). There is no secret emollient of choice for

psoriasis, and patients should be led by which emollient they find most helpful. Corticosteroids Topical corticosteroids exert antiinflammatory, antiproliferative, and immunosuppressive actions. However topical corticosteroids have more limited ability to modify disease when used as monotherapy, so they are often combined with other topical preparations such as vitamin D analogues eg betamethasone/ calcipotriol foam. Less potent topical steroids such as hydrocortisone 1% or Eumovate should be used for facial and genital psoriasis due to greater propensity for skin thinning. There is no benefit to application more frequently than once daily, and adherence to greater than once daily topical corticosteroid therapy is very low. Topical corticosteroids generally can be continued as

Meropenem Meropenem Aurobindo 1g Powder for solution for injection or infusion. Indicated for the treatment of the following infections in adults and children aged 3 months and older: Severe pneumonia, including hospital and ventilatorassociated pneumonia

Complicated intra-abdominal infections

Broncho-pulmonary infections in cystic fibrosis

Complicated skin and soft tissue infections

Complicated urinary tract infections

Acute bacterial meningitis

Intra- and post-partum infections

Treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above. Meropenem Aurobindo may be used in the management of neutropenic patients with fever that is suspected to be due to a bacterial infection.

Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Name and active ingredient: Meropenem Aurobindo 1g Powder for solution for injection or infusion: Each 1g vial of powder for solution for injection or infusion contains 1141.56mg meropenem trihydrate equivalent to 1g anhydrous meropenem. Excipients with known effect: Each 1g vial contains 208mg sodium carbonate approximately 4.0 mmol of sodium (approximately 90mg). Each ml of reconstituted solution contains 50mg Meropenem. Indications: Meropenem Aurobindo 1g powder for solution for injection or infusion is for the treatment of the following infections in adults and children aged 3 months and older (see SmPC section 4.4 and 5.1): Severe pneumonia, including hospital and ventilator-associated pneumonia, Broncho-pulmonary infections in cystic fibrosis, Complicated urinary tract infections, Complicated intra-abdominal infections, Intra- and post-partum infections, Complicated skin and soft tissue infections, Acute bacterial meningitis. Treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above. Meropenem Aurobindo may be used in the management of neutropenic patients with fever that is suspected to be due to a bacterial infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Posology and method of administration: The dose of meropenem administered and the duration of treatment should take into account the type of infection to be treated, including its severity, and the clinical response. A dose of up to 2g three times daily in adults and adolescents and a dose of up to 40mg/kg three times daily in children may be particularly appropriate when treating some types of infections, such as infections due to less susceptible bacterial species (e.g., Enterobacteriaceae Pseudomonas aeruginosa or Acinetobacter spp.) or very severe infections. Adults and adolescents: Severe pneumonia including hospital and ventilator-associated pneumonia, Complicated urinary tract infections, Complicated intraabdominal infections, Intra- and post-partum infections, Complicated skin and soft tissue infections: 500mg to 1g every 8 hours. Management of febrile neutropenic patients: 1g every 8 hours. Broncho-pulmonary infections in cystic fibrosis, Acute bacterial meningitis: 2g every 8 hours. Meropenem is usually given by intravenous infusion over approximately 15 to 30 minutes (see SmPC section 6.2, 6.3 and 6.6). Alternatively, doses up to 1g can be given as an intravenous bolus injection over approximately 5 minutes. There are limited safety data available to support the administration of a 2g dose in adults as an intravenous bolus injection. Renal impairment: The dose for adults and adolescents should be adjusted when creatinine clearance is less than 51ml/min (See SmPC section 4.2). Hepatic impairment: No dose adjustment is necessary in patients with hepatic impairment (see section 4.2 of the SmPC). Dose in elderly patients: No dose adjustment is required for the elderly with normal renal function or creatinine clearance values above 50 ml/min. Paediatric population: Children under 3 months of age. The safety and efficacy of meropenem in children under 3 months of age have not been established and the optimal dose regimen has not been identified. However, limited pharmacokinetic data suggest that 20mg/kg every 8 hours may be an appropriate regimen (see section 5.2 of the SmPC). Children from 3 months to 11 years of age and up to 50#kg body weight: Severe pneumonia including hospital and ventilator-associated pneumonia, Complicated urinary tract infections, Complicated intra-abdominal infections, Complicated skin and soft tissue infections: 10 or 20mg/kg every 8 hours. Broncho-pulmonary infections in cystic fibrosis, Acute bacterial meningitis: 40mg/kg every 8 hours. Management of febrile neutropenic patients: 20 mg/kg every 8 hours. Children over 50kg body weight: The adult dose should be administered. There is no experience in children with renal impairment. Method of administration: Meropenem is usually given by intravenous infusion over approximately 15 to 30 minutes (see SmPC sections 6.2, 6.3, and 6.6). Alternatively, meropenem doses of up to 20mg/kg may be given as an intravenous bolus over approximately 5 minutes. There are limited safety data available to support the administration of a 40mg/kg dose in children as an intravenous bolus injection. Meropenem Aurobindo is a white to pale yellow crystalline powder for solution for injection or infusion in vial. Product after reconstitution is clear colourless to yellow solution. Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in SmPC section 6.1. Hypersensitivity to any other carbapenem antibacterial agent. Severe hypersensitivity (e.g., anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g., penicillins or cephalosporins). Special warnings and precautions for use: The selection of meropenem to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial agent based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial agents and the risk of selecting for carbapenem-resistant bacteria. Enterobacteriaceae,

Pseudomonas aeruginosa and Acinetobacter spp resistance: Resistance to penems of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp. varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in these bacteria to penems. Hypersensitivity reactions: As with all beta-lactam antibiotics, serious and occasionally fatal hypersensitivity reactions have been reported (see SmPC sections 4.3 and 4.8). Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may also be hypersensitive to meropenem. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics. If a severe allergic reaction occurs, the medicinal product should be discontinued, and appropriate measures taken (see SmPC section 4.4). Antibiotic-associated colitis: Antibioticassociated colitis and pseudomembranous colitis have been reported with nearly all anti-bacterial agents, including meropenem, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of meropenem. Discontinuation of therapy with meropenem and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given. Seizures: Seizures have infrequently been reported during treatment with carbapenems, including meropenem. Hepatic function monitoring: Hepatic function should be closely monitored during treatment with meropenem due to the risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytolysis). Use in patients with liver disease: patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem. There is no dose adjustment necessary (see SmPC section 4.2). Direct antiglobulin test (Coombs test) seroconversion: A positive direct or indirect Coombs test may develop during treatment with meropenem. Concomitant use with valproic acid/ sodium valproate/valpromide: The concomitant use of meropenem and valproic acid/sodium valproate/valpromide is not recommended (see SmPC section 4.5). This medicinal product contains 90 mg sodium per dose, equivalent to 4.5% of the WHO recommended maximum daily intake for sodium.The maximum daily dose of this product is equivalent to ≥20% of the WHO recommended maximum daily intake for sodium. Meropenem Aurobindo is considered high in sodium. This should be particularly taken into account for those on a low salt diet. Interactions: No specific medicinal product interaction studies other than probenecid were conducted. Caution is required if probenecid is co-administered with meropenem. The potential effect of meropenem on the protein binding of other medicinal products or metabolism has not been studied. However, the protein binding is so low that no interactions with other compounds would be expected on the basis of this mechanism. For full details, refer to SmPC section 4.5. Fertility, pregnancy and lactation: There are no or limited amount of data from the use of meropenem in pregnant women. As a precautionary measure, it is preferable to avoid the use of meropenem during pregnancy. Small amounts of meropenem have been reported to be excreted in human milk. Meropenem should not be used in breast-feeding women unless the potential benefit for the mother justifies the potential risk to the baby. Effects on ability to drive and use machines: No studies on the effect on the ability to drive and use machines have been performed. However, when driving or operating machines, it should be taken into account that headache, paraesthesia, and convulsions have been reported for meropenem. Adverse events: Common (≥1/100 to <1/10): Thrombocythaemia, headache, diarrhoea, vomiting, nausea, abdominal pain, transaminases increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, rash, pruritis, inflammation, pain. Uncommon (≥ 1/1,000 to <1/100): Oral and vaginal candidiasis, eosinophilia, thrombocytopenia, leucopenia, neutropenia, agranulocytosis, haemolytic anaemia, angioedema, anaphylaxis, paraesthesiae, antibiotic-associated colitis, blood bilirubin increased, toxic epidermal necrolysis, Stevens Johnson syndrome, erythema multiforme, urticaria, blood creatinine increased, blood urea increased, thrombophlebitis, pain at the injection site. Rare (≥ 1/10,000 to <1/1,000): Delirium, convulsions. Not Known (cannot be estimated from the available data): Drug Reaction with Eosinophilia and Systemic Symptoms acute generalised exanthematous pustulosis. Presentation: 1349.56mg of powder in a 40ml Type-I, tubular, clear glass vial with stopper (bromobutyl rubber with aluminium seals having white colour polypropylene discs). Pack Size: Sold in a carton of 10 vials. Legal classification: POM. Marketing Authorisation Number: PA23467/002/002. Distributed by: Uniphar on behalf of Athlone Pharmaceuticals Ltd. For a copy of the SmPC or further medical information, please contact: medical@kent-athlone.com. Date of Preparation: January 2024 Ref: IE21/004/02 SmPC April 2023.

Adverse reactions should be reported. Reporting forms and information can be found on the HPRA website (www.hpra.ie) or by email medsafety@hpra.ie Adverse events should also be reported to Kent Athlone Pharma Group on (090) 666 1109 or medical@kent-athlone.com. Additional information available on request.

For further information on this product, please contact your Athlone Pharmaceuticals Key Account Manager or our customer service team. Athlone Pharmaceuticals Ltd., Connaught House, 1 Burlington Road, Dublin 4, Ireland. Tel: + 353 (0) 9066 61109 | Fax: +353 (0) 9066 61921 Email: customer.service@kent-athlone.com

Date of preparation: January 2024 Ref: IE2024/002/00

Prescribing information

54 Educational Learning long as the patient has thick active lesions. Skin atrophy from topical corticosteroids is rarely a problem unless the medication is continuously applied after the skin has returned to normal thickness or if areas without psoriasis are exposed. Once clinical improvement occurs, the frequency of application should be reduced. For patients in whom lesions recur quickly, topical corticosteroids can be applied intermittently (e.g. on weekends only) to maintain improvement. The addition of noncorticosteroid topical treatments to the treatment regimen can also facilitate reduced dependence on long-term daily topical corticosteroids. The risks of cutaneous and systemic side effects associated with chronic topical corticosteroid use are greater with high-potency formulations compared with lowerpotency formulations. Oral steroids should never be used to treat psoriasis due to the significant risk of potentially serious rebound flares once they are stopped. Vitamin D analogues Calcipotriene and calcipotriol are synthetic forms of vitamin D that regulate skin cell growth and are used alone or used in combination with corticosteroids for enhanced efficacy. Tar Tar is a time-honoured modality for treating psoriasis, although newer (and less messy) treatment options

have reduced its popularity. The precise mechanism of action of tar is not known but may involve aryl hydrocarbon receptors, producing anti-inflammatory and antiproliferative effects. Tar can be helpful as an adjunct to topical corticosteroids, or be combined in the form of LPC e.g. with betamethasone. Patients should be warned that tar products have the potential to stain hair, skin, and clothing. It may help to use them at night and wear inexpensive night clothes (e.g. old pyjamas) as tar products tend to be messy. Patients may also find the odour of tar products unpleasant. Calcineurin inhibitors Topical tacrolimus 0.1% is effective in the treatment of psoriasis in sensitive areas such as the face and intertriginous areas, although likely less effective than topical steroids. However, they are very safe and well-tolerated, so can be used as a prophylactic agent to reduce the frequency of topical steroid use. Topical tacrolimus 0.1% is licensed from 16 years of age, while the 0.03% formulation is licensed from 2 years. However, due to the superior efficacy and lack of increased risk with the stronger version, the 0.1% option should be preferentially prescribed for children. Topical retinoids and salicylic acid Salicylic acid has keratolyic activity and is combined with topical

steroids eg betamethasone/ salicylic acid. Derived from vitamin A, topical retinoids eg tazarotene help normalise skin cell growth and are especially useful in areas with thick scales, such as the palms and soles. However they are used less commonly in Ireland. Phototherapy Ultraviolet (UV) irradiation has long been recognized as beneficial for the control of psoriatic skin lesions. UV radiation may act via antiproliferative effects (slowing keratinisation) and anti-inflammatory effects (inducing apoptosis of pathogenic T cells in psoriatic plaques). Therapeutic doses of UV light can be administered as narrowband ultraviolet B (UVB) phototherapy, or oral or bath psoralen plus ultraviolet A (PUVA) photochemotherapy. Narrowband UVB involves the delivery of 311 nm of UVB radiation. In particular, this is extremely effective for treating guttate psoriasis. Photochemotherapy (PUVA) involves treatment with a photosensitizer (either oral or bath psoralen) followed by ultraviolet A (UVA) radiation (320 to 400 nm). There are concerns about increased risk of skin cancer with very longterm use of PUVA. While individual treatment sessions are very short, a course of phototherapy can last several months, with multiple visits per week. Selection among modalities of phototherapy is based upon consideration of

efficacy, safety, availability, and ease of therapy. Narrowband UVB is generally preferred over PUVA photochemotherapy based upon greater ease of administration (administration of psoralens not required) and a less severe side effect profile. Commercial tanning beds should not be used to treat psoriasis as there is significant variability in the UV output of tanning beds and they are associated with dramatically increased risks of skin cancer. Systemic Medications There are multiple international guidelines on treatment decisions for systemic and biologic medications. Systemic or biologic medications usually have immunomodulatory effects but some such as acitretin reduce keratinocyte proliferation (Figure 2). Patients require a workup to ensure there are no underlying conditions or infections that may become problematic during treatment. Typically patients should have testing before starting treatment for full blood count, renal function, liver function, hepatitis B and C serology, HIV serology, varicella immunity, and tuberculosis infection (usually with interferon-gamma release assays). Methotrexate Methotrexate is a folic acid antagonist which has antiinflammatory effects and has been used for psoriasis for over 50 years. It is also effective for

Figure 2

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

55

Figure 3

the treatment of psoriatic arthritis and psoriatic nail disease. Methotrexate has multiple contraindications including pregnancy, alcoholic liver disease or other chronic liver disease, immunodeficiency syndromes, bone marrow hypoplasia, cytopaenias, or hypersensitivity to methotrexate. Relative contraindications include liver and renal function abnormalities and active infection. In addition, concomitant treatment with certain drugs (eg, nonsteroidal anti-inflammatory drugs, certain antibiotics) can increase risk for methotrexate toxicity. Regular monitoring is essential due to potential liver and bone marrow side effects. Methotrexate is usually administered in an intermittent low-dose regimen such as once weekly, orally or subcutaneously. The usual dose range is between 5 and 25 mg per week. Subcutaneous methotrexate can be used and may be helpful when doses higher than 15 mg/week are needed, as hepatic metabolism

may limit the bioavailability of higher methotrexate doses. Unlike ciclosporin, which is generally used for only a limited duration of treatment because of cumulative renal toxicity, methotrexate can be used for long-term therapy. Folic acid is co-prescribed to protect against some of the common side effects seen with low-dose methotrexate such as stomatitis. Concurrent use of other medications that interfere with folic acid metabolism, such as sulfa antibiotics, can increase the toxicity of methotrexate. Ciclosporin Ciclosporin suppresses T cell activity, reducing inflammation. Usual doses are 3-5mg/ kg/day divided twice daily. Contraindications to ciclosporin therapy include abnormal renal function, uncontrolled hypertension, malignancy, and hypersensitivity to cyclosporine. Caution is indicated in the setting of major infections or poorly controlled diabetes. Cyclosporine also has multiple drug interactions. Ciclosporin is reserved for shortterm use due to potential kidney damage with prolonged use.

Acitretin Acitretin is a retinoid (vitamin D derivative) taken orally, which regulates skin cell growth. Acitretin is particularly useful for patients with pustular psoriasis or in patients with a history of immunodeficiency or neoplasia. Acitretin can be combined with UVB or PUVA. The usual dose range is 10-25mg daily and the onset of action is relatively slow. Monitoring for hypertriglyceridemia and hepatotoxicity are required with retinoid therapy. Common side effects include cheilitis and alopecia. Acitretin is teratogenic; it is only indicated in men and in women of nonreproductive potential. Pregnancy is contraindicated for three years after discontinuing the drug. Apremilast Apremilast, a phosphodiesterase 4 inhibitor, is another oral agent for the treatment of plaque psoriasis. PDE4 inhibition reduces production of multiple cytokines involved in the pathogenesis of psoriasis. Apremilast is costly, priced closer to biologics than to methotrexate. The drug can also be effective for psoriatic arthritis.

Apremilast is associated with a short-term risk of diarrhoea, especially when treatment is started, occurring in roughly 15 to 20 percent of patients. Tolerability of apremilast is improved by slowly ramping up the dose when treatment is initiated. In adult patients with severe renal impairment, the recommended final dose is 30 mg once daily. At the start of therapy, only the morning dose of the above titration schedule is given. Examples of other reported side effects of apremilast include nausea, upper respiratory infection, headache, drug interactions, and weight loss. Periodic monitoring of weight is recommended. Advising patients, their caregivers, and families to be alert for worsening depression, suicidal thoughts, or other mood changes during treatment also is suggested based upon the possibility of a slight increase in risk for depression. Fumaric acid esters Fumaric acid esters (fumarates) are frequently used to treat psoriasis in Germany. Lymphopenia is an occasional side effect of treatment with

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

56 Educational Learning fumaric acid esters. In 2013, two cases of progressive multifocal leukoencephalopathy (PML) were reported in patients who continued to receive long-term fumaric acid ester therapy despite the development of severe lymphopenia. These patients did not have other known causes of immunodeficiency. PML in the setting of fumaric acid therapy for psoriasis has also been reported in patients without severe lymphocytopenia. Biologics Biologics are different from conventional systemic drugs that impact the immune system more globally. Biologics target highly specific parts of the immune system. The biologics used to treat psoriatic disease block the action of specific types of proteins in the immune system, such as tumor necrosis factor-alpha (TNF-alpha), interleukin 17-A, or interleukins 12 and 23 (Figure 3). These cells and proteins all play a major role in developing psoriasis and psoriatic arthritis. TNF-alpha Inhibitors Tumour necrosis factor alpha (TNF-alpha) inhibitors, such as etanercept and adalimumab, target specific immune system proteins involved in psoriasis. Other examples include certolizumab which is pegylated (and therefore does not cross the placenta) and infliximab (which is administered intravenously). Biosimilars are now available for etanercept, adalimumab, and infliximab, which have dramatically reduced their cost. TNF inhibitors are effective for both skin lesions and joint symptoms in psoriatic arthritis, and can be used to treat inflammatory bowel disease in patients who have comorbid disease. IL-12/23 inhibitor Ustekinumab is a human monoclonal antibody that targets IL-12 and IL-23. Ustekinumab is indicated for the treatment of adults and children with moderate to severe psoriasis who are candidates for phototherapy or systemic therapy. Dosing of ustekinumab is weight based. Standard dosing for ustekinumab for adults ≤100 kg is 45 mg given at weeks 0, 4, and every 12 weeks thereafter. A 90 mg dose given in the same regimen is recommended for adults who weigh more than 100 kg. Ustekinumab can also improve psoriatic arthritis. IL-17 Inhibitors Drugs like secukinumab and ixekizumab target interleukin-17, a protein implicated in psoriasis.

These agents are effective for individuals who do not respond well to other treatments, and are typically used as secondline agents after TNF inhibitors or ustekinumab. IL-17 inhibitors can rarely be associated with candidiasis and new-onset inflammatory bowel disease. IL-23 Inhibitors Guselkumab risankizumab, and tildrakizumab are examples of medications that target interleukin-23 by binding to the p19 subunit. Novel/Emerging agents Newer agents for psoriasis include other biologic targets and janus kinase inhibitors Personalized Treatment Plans The management of moderate to severe psoriasis requires a personalized approach, taking into account the patient's overall health, lifestyle, and preferences.

resources can provide valuable information and a sense of community for those navigating the challenges of moderate to severe psoriasis. Managing Emotional Well-being The visible nature of psoriasis lesions can significantly impact an individual's self-esteem and mental health. Mental health support, counseling, and resources can help patients cope with the emotional aspects of the condition. Adherence to Treatment Ensuring patient adherence to prescribed treatments is vital for achieving optimal outcomes. Understanding the importance of consistent treatment and addressing any concerns or barriers to adherence is essential.

Conclusion The treatment landscape for moderate to severe psoriasis has evolved significantly, offering a range of options tailored to individual needs. From traditional therapies like topical treatments and phototherapy to advanced biologics targeting specific immune pathways, dermatologists have a diverse toolkit to address this challenging condition. A holistic approach that considers the patient's overall health, lifestyle, and emotional well-being is essential for comprehensive psoriasis management. With ongoing research and advancements in treatment modalities, the outlook for individuals with moderate to severe psoriasis continues to improve, providing hope for better control of symptoms and an improved quality of life.

Test your Learning

Lifestyle Modifications

1. Which of the following conditions is psoriasis not associated with increased risk of?

Encouraging patients to adopt a healthy lifestyle can complement medical treatments. Smoking cessation, weight management, and stress reduction are important aspects of managing psoriasis.

A Inflammatory bowel disease B Inflammatory arthritis C Intellectual disability D Depression E Cardiovascular disease

Regular Monitoring Patients undergoing systemic treatments require regular monitoring of liver function, blood cell counts, and other relevant parameters. Close communication between healthcare providers and patients is essential to address any emerging concerns promptly. Assessing Comorbidities Psoriasis is associated with an increased risk of cardiovascular diseases, diabetes, and other systemic conditions. Dermatologists often collaborate with rheumatologists when joint involvement is present, ensuring a comprehensive strategy for addressing both skin and joint symptoms. Combination Therapies Dermatologists may opt for combination therapies, such as using a biologic alongside a topical treatment for enhanced efficacy. This approach aims to achieve better control of psoriasis while minimizing potential side effects. Patient Education and Support Educating individuals with psoriasis about their condition is crucial for empowering them to actively participate in their treatment. Patient support groups, online forums, and educational

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

2. Which of the following is an indication for referral to dermatology for specialist care of psoriasis? A Strong family history of autoimmune disease B Greater than 10% body surface area involvement C Presence of extensor limb involvement D Failure to respond to emollient therapy E Joint swelling without evidence of skin changes 3. Which of the following is not a contraindication to methotrexate therapy? A Cytopaenia B Renal failure C Fatty liver disease D History of major cardiovascular event E Alcoholic liver disease 4. Which of the following is not a tumour necrosis factor alpha inhibitor? A Infliximab B Secukinumab C Etanercept D Adalimumab E Certolizumab 5. Which of the following tests should be performed before starting a patient on a biologic agent for psoriasis? A Thyroid function tests B Varicella IgG levels C Fasting lipid levels D HIV viral load E Hepatitis E serology

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Date of Preparation: January 2024 Job Code: GEN-IE-00058

58 Urinary Incontinence

Non-Pharmacological Management of Urge Urinary Incontinence in Women between 40 and 65 Years Old: A Systematic Review Written by Sara Trapani1,2, Giulia Villa3,*, Andrea Poliani3, Silvia Gnecchi4, Debora Rosa3 and Duilio F. Manara3 Department of Obstetrics and Gynecology, IRCCS San Raffaele Hospital, 20132 Milan, Italy

1

Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy

2

Center for Nursing Research and Innovation, Vita-Salute San Raffaele University, 20132 Milan, Italy

3

Department of Onco-Hematology, IRCCS San Raffaele Hospital, 20132 Milan, Italy

4

Bladder issues and conditions affecting the urinary system, referred to as Lower Urinary Tract Symptoms, are widespread worldwide.1 One of these problems is urinary incontinence, defined as “the complaint of any involuntary leakage of urine”.2,3 UI can be classified into three main subtypes. Stress urinary incontinence (SUI) is the urine loss provoked by exertion, physical effort, sneezing or coughing; urge urinary incontinence (UUI) refers to urine leakage accompanied by a sense of urgency that is defined as a sudden and compelling desire to void urine;3,4 and mixed urinary incontinence consists of the combination of SUI and UUI.2 Urinary incontinence has been identified as a World Health Organization health priority,5 also because the number of individuals with UI is projected to increase with time.6 Even though UI is widely discussed in the literature, it remains an undervalued problem.7 In particular, UUI affects quality of life more than other kinds of urinary incontinence,8 but it is not always treated efficiently;9 indeed, urgency often is a problem not easily amenable to modification.10 For this reason, there is a need to plan and evaluate the effectiveness of conservative treatment practices to counteract UUI. A worldwide prevalence study conducted in the last decade reported that the number of patients affected by UUI in 2008 was 49 million.6 Nevertheless, estimates of UUI prevalence differ between studies, so that in the European population, the reported prevalence range is between 1.8 and 30.5%, with greater prevalence among women over 40 years of age.11 For instance, a study conducted in an Italian urban area,12 investigating UI prevalence by age subgroups in a sample of 2900 women, showed that more than one in four women suffered from incontinence episodes from 40 years of age

onwards. In line with statistics, this systematic review focuses on the female population in the range of 40–65 years old, which represents the initiation of the significant occurrence of UI in women.13,14,15,16 In fact, age represents the first predisposing element to the development of UUI, combined with other risk factors: pre-existing clinical conditions, cognitive disorders and a decline in physical function, e.g., hormonal modifications in menopausal women.17 UUI can make people prone to the manifestation of skin infections, sexual dysfunction and depression, with a consequent impact on women’s quality of life, psychosocial health10 and economic burden from both a societal and patient perspective.11,13,17 In particular, a study conducted in the United States18 estimated that in 2007, average annual per capita costs of UUI were USD 1925:USD 1433 in direct medical (physician visits, anticholinergic medications, physical therapy or surgical procedures), USD 66 in direct non-medical (disposable pads or other hygienic products), and USD 426 in indirect costs (earned salary income). According to the European Association of Urology,19 in 2023, the total economic burden of urinary incontinence in Europe was estimated at nearly EUR 40 billion and a total accumulated economic burden of EUR 320 billion is expected in Europe in 2030 if no action is taken.19 The costs of assisting people with UI are also significant in terms of time: patients managed in a long-term acute care facility need about 109 min/day for care, corresponding to EUR 31.30 per patient per day.20,21 Cost of illness studies are useful because they can suggest some potential benefits associated with effective treatments, which is a reason why a resolutive action plan needs to be developed.

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

The treatments that currently exist for UUI can be classified into three categories: surgery, pharmacological therapies and conservative interventions. Drug therapies, such as anticholinergic agents (e.g., oxybutynin or tolterodine) targeting the muscarinic receptors in the bladder, represent the mainstay of pharmacotherapy for the treatment of urgency and were described in a study conducted by Tiwari and Naruganahalli in 2006.22 The choice of pharmacologic therapy, intravesical Botox injections or alternative therapies such as acupuncture depends on the severity of the problem, on the compliance of the patient and on the side effects of the therapy.10 Regarding the surgical procedures, the progress in incontinence surgery over the last 25 years has been enormous and it is reassuring for patients that there is a possibility of being cured with these methods. For example, the tension-free midurethral sling offers long-term cure rates of 70–90%, but patients with urge incontinence do not benefit at all from surgery and, in any case, when symptoms of urgency are predominant, the first line of treatment should be behavioral modifications or conservative measures such as pelvic floor training.10 The use of non-pharmacological treatment could represent a significant new strategy to reduce UUI symptoms alone or in combination with drugs therapy. It could allow a reduction in medication intake, representing a valid and effective intervention that actively involves the patient.1 Given the importance of these non-pharmacological methods, exploring the scientific literature is important to understand the types of interventions available and their effectiveness, in order to make informed treatment decisions, based on up-to-date data, and guarantee interventions with a lower impact on side

effects and costs compared to pharmacological drugs.1 Objectives This systematic review aims to establish the non-pharmacological practices that are effective in managing UUI in women between 40 and 65 years old. The specific review questions are: (I) What types of nonpharmacological practices have been employed to reduce or prevent UUI in women between 40 and 65 years old? (II) What is the effectiveness of these interventions? MATERIALS AND METHODS Study Protocol This systematic review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for systematic reviews of effectiveness evidence.23 The review question, outcomes, inclusion criteria and methods of analysis were predefined, and the protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO), with registration n° CRD42023384195. Physical Interventions In the literature, various kinds of physical interventions are reported as useful strategies to treat urinary incontinence in women. Tailored exercises such as pelvic floor muscle training and bladder rehabilitation could help women to improve UUI symptoms. PSYCHOLOGICAL INTERVENTIONS Hypnotherapy Two RCTs50,51 investigated the efficacy of hypnotherapy in the treatment of UUI. In both studies, hypnotherapy was considered to be a practice focused on emotions identified by participants associated with UUI. In both

59

studies, eight-weekly, onehour, one-on-one hypnotherapy sessions were delivered by a certified hypnotherapist for the non-pharmacological group. Meanwhile, the pharmacotherapy group received a drug treatment with oxybutynin 10 mg/day or tolterodine 4 mg/day. In addition, in the study conducted by Komesu et al. (2020),51 the drug treatment was completed with counseling. The studies did not prove the non-inferiority of hypnotherapy compared to medications; in fact, a reduction in UUI episodes was reported in both treatment groups. Ketai et al. (2021)50 obtained a change in the UUI episodes’ median of −5 (Q1 −2, Q3 −10) in the hypnotherapy group and of −4.5 (Q1 −3, Q3 −7) in the medication group, with a p-value of difference p = 0.60, 8 or 12 weeks after the treatment started. Komesu et al. (2020)51 evaluated the UUI episodes as having a median after 2 months of 1 (Q1 0, Q3 5) in the hypnotherapy group and 1 (Q1 0, Q3 3) for the pharmacotherapy group, after 6 months, the median was 1 (Q1 0, Q3 3) in the hypnotherapy group and 1 (Q1 0, Q3 4) for the pharmacotherapy group, and 12 months after the treatment started, the median was 1 (Q1 0, Q3 3) in the hypnotherapy

group and 1 (Q1 0, Q3 5,5) for the pharmacotherapy group. In conclusion, hypnotherapy seemed to be an alternative treatment for women with UUI because it demonstrated the same values as the drug therapy in terms of the median change between groups. Healthcare Professionals Involved and Setting Healthcare professionals involved in dispensing non-pharmacological interventions were classified into different specialized categories. The main cited figure is represented by physiotherapists with a frequency of 4/14,47,48,49,53,54 even if their interventions are restricted to the rehabilitation field. The second main professional involved is the nurse (3/14).46,47,49,54 Non-pharmacological interventions were also dispensed by hypnotherapists with a frequency of 2/14.50,51 Two different groups of healthcare specialists were represented by the same frequency (1/14): occupational therapists and gynecologists.44,52 In one article, healthcare professionals were identified in general as being responsible for the non-pharmacological intervention. No specific reference was addressed to single healthcare

providers.52 Some articles reported teamwork as a strategic choice to provide the intervention.44,47,49,54 A total of four articles did not specify the involvement of any healthcare provider;40,42,43,45 two of these were dispensed in a telematic way.40,45 Overall, the studies investigating nocturia found a generally positive effect of the proposed interventions on the number of void episodes during the night, but the superiority of any intervention over others cannot be affirmed. Quality of life was investigated as an outcome. Burgio et al. (2008)47 in their RCT compared combination therapy with behavioral training and tolterodine 4 mg/day versus pharmacological treatment alone.47 Quality of life was measured using the OABq health-related quality-of-life scale and the Short-Form Health Survey (SF-12). This outcome was discovered to improve in both groups (at ten weeks and eight months postinterventions); however, the differences between groups were small, even if statistical data were not reported by the authors. Kafri et al. (2007)42 used the Incontinence Quality of Life Instrument (I-QoL). Due to some baseline differences between study groups (rehabilitation group with behavioral training

Figure 1

and medication group through oxybutynin 5 mg/day), a repeatedmeasures analysis was performed. In the within-group comparison, both groups improved significantly over time with respect to urinary symptoms and QoL score (F2,70 = 20.89, p < 0.01). A significant negative association was found between the urinary symptoms and the I-QoL at the end of the three-month follow-up period (rp = −0.35 to −0.62, p < 0.05). Another study investigated this outcome using the Overactive Bladder Questionnaire (OAB-q) qualityof-life measure. No differences were found between groups in the OAB-q at 12 months (87.9 SD 11.6 bladder retraining, 81.6 SD 19.3 drug therapy and 88.9 SD 9.9 combination).48 Finally, Wadensten et al. (2021)40 assessed quality of life in participants randomized to receive access to a treatment app or an information app, using the ICIQ-Lower Urinary Tract Symptoms Quality of Life Module (ICIQ-LUTSqol). The estimated between-group difference was −6.3 (95% CI −10.5 to −2.1) at the 15-week follow-up.40

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

60 Urinary Incontinence Overall, quality of life improved in every intervention group of the described studies, and when this outcome was measured with different tools. Due to the heterogeneity of the articles, the superiority of any intervention over others cannot be affirmed. One study compared bladder training, pelvic floor muscle exercises and a control group without intervention to evaluate the effectiveness for increasing voided volume. It emerged that the bladder training group significantly improved this outcome (p < 0.01) compared with the other groups in which no changes were observed.46 Patient satisfaction and distress were assessed by Burgio et al. (2008)47 in an RCT comparing combination therapy with behavioral training and tolterodine 4 mg/day versus pharmacological treatment alone. The combination group showed a complete state of satisfaction compared to the pharmacological group (53% vs. 40%; difference, 13 percentage points [CI, 1 to 25 percentage points]) ten weeks after the start of the intervention. Moreover, at eight months, the combination group showed improved outcomes (33% vs. 20%; difference, 13 percentage points [CI, 2 to 24 percentage points]). Distress symptoms were improved in both groups, with better scores in the combination therapy group versus the pharmacological group (p < 0.001). In the first ten weeks of the intervention, distress decreased, while in the following period until eight months, the distress scores slightly increased in both groups.47 Brain activation related to a bladder-filling task was explored in an RCT by Ketai et al. (2021) comparing hypnotherapy intervention with drug intervention (oxybutynin 10 mg/day or tolterodine 4 mg/day). It emerged that there was a reduction in left temporoparietal junction activation (p < 0.01) in both groups.50 Adverse Events In four articles, adverse events were reported in both pharmacological and non-pharmacological interventions.42,47,48,51 Three of these articles presented the worst adverse events as occurring in the pharmacological intervention group.42,48,51 Just one article about behavioral training declared the presence of adverse events in a non-pharmacological group.40 Discussion The recognition of UI as a significant clinical issue56

underlines the necessity of identifying effective interventions. The increasing prevalence of UUI has critical implications not only for women’s physical and psychological health10 but also for their social and economic life.11 This systematic review aimed to identify the available interventions to contrast UUI, excluding surgery and drug therapy.22 In this regard, the purpose of this study was relevant for framing up-to-date knowledge in relation to the efficacy of UUI non-pharmacological treatments, closing a current gap in incontinence care, because patients with urge incontinence do not benefit at all from surgery and are often subject to the side effects of drug therapy.10 The literature reports on different strategies to deal with the problem of urinary incontinence, some purely physical (e.g., physiotherapy or bladder training), others physical and psycho-educational (e.g., behavioral training and lifestyle modifications) and others exclusively psychological, such as hypnotherapy. The interventions that emerged in this systematic review could support pharmacological therapy or could be used alone to reduce incontinence episodes because their benefits were demonstrated and these results are in line with an overview of reviews published in 2022: pelvic floor muscle training, biofeedback, electrical stimulation and bladder training were found to be more beneficial than a control for curing or improving UI.1 However, according to our study, the effectiveness of the non-pharmacological interventions cannot be generalized because of the impossibility of conducting meta-analytical analyses due to insufficient statistical data. For the same reason, none of the conservative interventions can be considered more effective than the others. Since the evidence does not allow the superiority of an intervention to be supported over others, the involvement of a health professional is necessary to choose the right treatment according to professional experience, resources and patients’ preferences.57 In order to improve women’s adherence to the therapies, health professionals’ support is essential. The main involved figure is represented by physiotherapists:47,48,49,53,54 nevertheless, their interventions are restricted to the rehabilitation field. The second main involved leaders are nurses,46,47,49,54 whose

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

preventive, curative, palliative and rehabilitative assistance is of a technical, relational and educational nature58 and therefore of a broader spectrum. Nevertheless, in order to guarantee constant, continuous and complete care to women with UUI, it is advisable to ensure teamwork and multiprofessional care.44,47,49,54 Every healthcare professional included in the review, such as hypnotherapists,50,51 occupational therapists and gynecologists,44,52 are able to work on some of the different factors contributing to UUI, and therefore, the collaboration of everyone is necessary.44,47,49,54 Although midwives are competent in counseling women with urogynecological disorders,59 none of the included studies involved this professional in the interventions used to reduce UUI disorders. In fact, midwives have confidence in pelvi-perineal muscles management and are also attentive to the psychological nature of the disease. In addition, they are trained to conduct psychoeducational meetings, mind–body encounters and body awareness to guarantee women’s wellbeing and to prevent UUI complications.60 Health professionals such as physiotherapists and urological nurses with their interventions, act not only on the symptoms of UUI but also on other outcomes, such as increasing satisfaction, reducing distress and improving quality of life.40,42,47,48 In fact, women who are provided with pharmacological therapies generally receive much less attention than patients treated with conservative treatments who receive additional personal attention.42 Nonetheless, this study does not allow the identification of the best intervention with respect to these outcomes, and this is also because personal subjectivity is involved.61 The correlation between objective and subjective outcome measures regarding urinary incontinence is still an open point, and further studies on this topic have been recommended by some authors.46 Regarding adverse events, this study found major side effects in the case of interventions where a drug therapy was employed,42,47,48,51 demonstrating that nonpharmacological treatments are better in terms of safety. Nevertheless, it is important that non-pharmacological treatments are delivered correctly with the help of a health professional to avoid some adverse events that may still occur, such as inguinal hernia40 and back pain.51

Scientific evidence reports that physical interventions can be dated, in their origin, to earlier times: for example, bladder training and pelvic floor muscle training date back to the second half of the 1990s.46 On the other hand, the interest in strategies of a more psychological nature has been discovered in the last years, as demonstrated by the most recent publications on this topic.50,51 Since the second decade of the 21st century, a change in theories has been taking place. In particular, beyond the use of the most accepted therapies such as pharmacotherapy and physiotherapy, mind–body therapy has emerged as an innovative intervention against UUI. The pioneering part consists of the application of a psychological approach to treat a physical problem. As reported by Komesu et al. (2020),51 urinary incontinence provokes emotional distress. In fact, it seems that hypnotherapy, promoting brain activation, improves the consciousness and perception of urinary stimuli, reducing the number of incontinence episodes. The effectiveness of treatments is dependent on the period of time dedicated to the interventions, which varies in the included studies. This fact could affect the effectiveness both in the short and long term. With the passing of time, there is an increasing percentage of incontinence in women after five years of physical intervention such as bladder training. The reduction in the treatment’s effect in the long term seems to be associated with poor compliance and with physiological decline due to aging.43 Conclusions This systematic review showed a range of non-pharmacological strategies that can be helpful to reduce or resolve UUI symptoms. Health professionals should include these interventions in the patient pathway assuring the absence of medication-related adverse events. The choice of treatment should be influenced by the patient’s preferences. The effectiveness of nonpharmacological treatments in patients with UUI is certain but difficult to generalize. They could be safely applied to women with ages ranging from 40 to 65 years, improving their quality of life and reducing symptoms. References available on request

Clinical R&D 61 BOOTS IRELAND PARTNER WITH HYGIENE HUB For the month of February, Boots, in partnership with Hygiene Hub, will match donations made in participating stores to help those living in poverty across Ireland*. Hygiene poverty is being unable to afford everyday items that many people take for granted. Hygiene Hub provides essential personal care items to those in need. Recent research** from Hygiene Hub has shown that people with a disability, those working parttime, students and those having responsibility for children were most likely to experience hygiene poverty. Of those surveyed, 65% of people had experienced difficulties affording hygiene items in the previous year. In the financial year 2023, through donations made by customers, via in store drop off points, and through direct donations by Boots, 1,100KG of items were donated to the Hygiene Hub. Boots has added drop off points to five additional stores around the country, taking the total number of stores accepting donations to fifteen. Drop off points are now located in six locations in Dublin: • Dundrum • Carrickmines • Swords • Malahide • Liffey Valley • Blanchardstown Across Ireland, there are drop off points in Letterkenny, Wicklow Town, Bray and Clonmel. There

Martha Ryan, Head of Human Resources and ESG Lead for Boots with Ciára Dalton, Head of Partnerships at Hygiene Hub

are also three locations in Cork – Douglas, Blackpool, and Half Moon Street as well two locations in Galway - Shop Street and Wellpark. If customers would like to donate items, they can easily purchase them in store or take any new, unused, personal care and household cleaning essentials – including dental products, deodorant, shower gel, shampoo, nappies, toilet roll, razors, period products and hairbrushes to the donation drop off points in participating Boots stores. Products are then distributed by Hygiene Hub’s Community Volunteers to Community Partners – a mix of organisations, charities, and schools. Commenting on the partnership, Martha Ryan, Head of Human Resources and ESG Lead for Boots said, “We very much value our partnership with Hygiene Hub which has been in place since 2022. Matching donations that customers make in store throughout February is a further step in our continued commitment towards the partnership. We hope our customers take advantage of the great value offering available in Boots stores including the Boots Everyday Range to pick up additional items to donate to this very deserving charity.” ‘THE RIGHT CARE IN THE RIGHT PLACE AT THE RIGHT TIME’ The HSE is rolling out new ways of working across community and hospital settings that are allowing patients to access high quality care closer to home and reducing overall waiting times for many healthcare services. These new modernised care pathways will provide service users with access to care by specialist community teams where appropriate, freeing consultant capacity to see patients most in need in a timelier manner. Beneficial impacts include: • Patients able to access routine care services locally via their GP and community teams;

with supported continuous professional development training, ensuring the highest quality of care is delivered to all patients/service users. Meeting the teams delivering ophthalmology, urology, orthopaedics, nephrology and diabetes care to patients in this new and innovative way at St Vincent’s University Hospital today, Minister Donnelly, said: “I am delighted to visit St Vincent’s University Hospital to see first-hand how patients are accessing integrated care in a high quality setting. “This is creating new access points for patients to healthcare that often have the longest waiting lists. We are now ensuring that patients can be seen faster and progress through our health service in a more integrated way. Ensuring they have fewer overall visits to a hospital. “These new care pathways have also reduced overall waiting times for many health care services across our hospitals as patients, who need scheduledcare move from our hospitals to community based care closer to their own homes.” Deirdre McNamara, Director, HSE Strategic Programmes Office (SPO), explained: “By streamlining referral processes, embracing new tools in e-healthcare and allowing for more care to be delivered in the community by advanced nurse practitioners and health and social care professionals, modernised care pathways will help reduce waiting lists and improve the quality of patient care.” FOCUS ON ROSACEA-PRONE SKIN WITH THE ROSATRINE RANGE FROM CITRINE HEALTHCARE Winter skincare is challenging and here in Ireland redness, dry skin, pimples and small dilated blood vessels are as much a sign of winter weather, as the frost and bare trees. Predominantly on the cheeks, forehead and chin, over 3% of the

population suffer from rosacea symptoms. These include redness and irritation, as low temperatures and low humidity attack the skin’s barrier function. UV is one of the biggest triggers of rosacea, so even welcome winter sunshine is a threat for sufferers. A new range for rosacea-prone skin is now available in pharmacies from an Irish Dermatology company, Citrine Healthcare, which provides support for chronic skin conditions. This simple 2 step routine begins with our daily moisturiser for Rosacea-prone skin, Rosatrine Light cream. Rosatrine Light cream with SPF 30 helps to manage the symptoms of redness and keep them at bay. Formulated with Hyaluronic acid to hydrate and soothe, it also contains Vitamin C to help protect the skin barrier, and Niacinamide to reduce the redness in the skin. The Rosatrine Intensive Cream helps to reduce the appearance of redness and calm irritated skin during flare ups. Dermatologically tested on people with sensitive skin, the hydrating cream is formulated with SPF 30 and Azelaic Acid, a powerful antioxidant that is clinically proven to reduce symptoms of intense redness. It also contains Tea Tree oil to reduce bacteria and a green pigment to help even the skin tone. Using both products together, will ensure daily protection from symptoms and help manage and reduce flare ups of redness. Rosacea is a common but underdiagnosed skin condition, women, and those aged over 30 with fair skin, are most likely to suffer. The exact cause is unknown, but rosacea is hereditary and factors like spicy foods, alcohol, sunlight and stress can worsen symptoms according to Sarah O`Leary of the Irish skincare specialists, Citrine Healthcare. “Internal and external factors can damage our skin, not least the weather. When the skin barrier is

• Patients are seen in a more timely manner in line with best practice; • Improved patient experience, with easier access to appointments and a reduction in the number of appointments which the patient needs to attend; • Telehealth options and digital innovations made more available for use when appropriate; • Healthcare professionals being empowered to work to the top of their current grade

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

62 Clinical R&D compromised, skin will feel tight, dry and easily irritated. “It becomes more prone to inflammation and may not tolerate regular moisturising products. Building up the skin barrier with nourishing ingredients will help it to both look better and be more resilient too”. The Rosatrine range was created by Irish-owned Citrine Healthcare in 2022. The range was formulated to provide accessible and clinically effective solutions for those who are dealing with Rosacea-prone skin. Rosatrine Intensive Cream, (¤17.95 for 30ml) and Rosatrine Light (19.50 for 50ml), are available in pharmacies nationwide and online at Citrine Healthcare. https:// citrinehealthcare.com/shop/ As well as pharmacy ranges for Psoriasis-prone skin, Rosaceaprone skin and Dermatitis-prone skin, the Irish skincare company, which was launched in 2021 in west Dublin, also produces a targeted range to help manage the symptoms of acne- prone skin. FLEMING MEDICAL SUPPORTS IRISH RED CROSS Fleming Medical have made a substantial donation of medical and diagnostic equipment to the Irish Red Cross. The Limerick-based medical supplier has organised this donation to help meet the IRC’s requirements for high quality training equipment and to continue their support of the charity’s ongoing humanitarian work. The donation includes a vast selection of diagnostic and simulation equipment including defibrillators, first aid training

manikins, ECG machines, blood pressure monitors, BP arm trainers, nebulisers and patient monitors.

- Emerging evidence indicates that phospholipids contribute to a variety of cognitive processes3.

Supporting the Irish Red Cross

Speaking about the benefits of Krill Oil for brain health, Nils Hoem, Chief Scientist at Aker BioMarine in Norway, the largest supplier of krill oil globally, commented, “Cognitive health is all about making the brain perform at its best even as you age. Krill Oil is a natural source of Choline and Omega-3 DHA, which has been proven to contribute to brain function as well as supporting our other organs too. By taking Cleanmarine Krill Oil you are providing your brain with the key nutrients it requires to maintain your brain health naturally.”

Fleming Medical acknowledges the role that Irish Red Cross plays nationally and internationally. In the event of an emergency, IRC volunteers call on their extensive training to offer life-saving care to those in need. Fleming Medical hopes that the donation of medical and diagnostic equipment will enhance the training and development of the Irish Red Cross’ large network of volunteers. As a leading supplier of medical devices and supplies in Ireland, Fleming Medical want to ensure that the Irish Red Cross has access to essential equipment and supplies that assures their preparedness and readiness in the event of a national and global emergency. Fleming Medical encourages companies with the available resources to show their support to their local IRC branch. A donation of medical supplies and equipment will have a direct impact and enhance the development and capabilities of IRC branches nationwide. Founded over 35 years ago, Fleming Medical is an Irish familyowned business and leading innovator of diagnostic, sports therapy, first aid, and wound care products. The Limerickbased medical supplier designs, produces, and delivers these products under their Medicare and Physiologix brands. Fleming Medical operate successfully in more than 20 countries worldwide and are a trusted partner for Irish and international pharmacy, community health, and hospital healthcare professionals. SUPPORTING BRAIN HEALTH WITH CLEANMARINE KRILL OIL

Fleming Medical have donated medical and diagnostic equipment to support the training and development of Irish Red Cross volunteers nationwide

As August approaches and the summer holidays come to an end, many will be eager to give their body and mind some muchneeded extra nourishment ahead

MARCH 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Dr Nils Home, Aker Biomarine

of the Autumn and Winter months. Cleanmarine Krill Oil is here to help with its concentrated formula which provides all the essential fatty acids required for the normal function of the brain as well as your heart and vision*. With over 97% of the western population deficient in Omega 3 fatty acids1, which is one of the key nutrients required for a healthy brain, it is very important to ensure we are getting our body’s requirement in other ways. Unlike other Omega-3 sources, krill oil is not only a great natural source of Omega-3, but the nutrients are in addition bound to phospholipids, which ensures effective absorption into the cell membranes and into our bodies.† Much research has been carried out in relation to the benefits of krill oil with some very interesting findings emerging on the topic of brain health; - People with higher levels of Omega-3 DHA in their blood are 49% less likely to develop dementia than those with lower levels2. - As much as 60% of our brain weight consists of phospholipids rich in fatty acid Omega-3’s and Choline, and they play a vital role in our cellular function, nerve signalling and cognitive function. Krill oil is naturally rich in vital and brain-supporting nutrients like phospholipids (PC, LPC), Omega-3 EPA & DHA and Choline, therefore nourishing the brain with key nutrients in the exact same form naturally found in the brain, which is a great way to support brain health and function.

Each capsule of Cleanmarine Krill Oil, the highly absorbable form of Omega 3†, contains 590mg of concentrated, high strength Omega 3 with Phospholipids now with even higher levels of EPA, DHA, with naturally occurring Choline and Astaxanthin, plus 10μg of vitamin D3, 200% of your RDI. Cleanmarine Krill Oil (¤24.99RRP for 60 capsules) is available in leading pharmacies and health stores nationwide. For more information on brain health and Cleanmarine Krill Oil log onto www.cleanmarine.ie ASTHMA SOCIETY LAUNCHES NEW E-REFERRAL PLATFORM FOR HEALTHCARE PROFESSIONALS The Asthma Society of Ireland has this month launched a new, free e-referral platform for healthcare professionals. The platform, available on the Asthma Society website at https://www.asthma. ie/patient-e-referral, allows healthcare professionals all over Ireland to refer patients or carers with questions/concerns about asthma or COPD to the charity’s Adviceline service. Operating for over 25 years, the Adviceline is a free service which allows users to speak to a respiratory specialist nurse or physiotherapist about various aspects of their asthma or COPD. The service is also available to parents/carers of young people with asthma or COPD. Through the Adviceline, respiratory nurse specialists and physiotherapists provide information and support, promote self-management, and signpost to appropriate healthcare interventions. Healthcare professionals can now, with the permission of the patient, complete a simple form on the asthma society website to refer patients or their carers to the service.

63 The form gathers some basic contact information which will allow a member of the Asthma Society’s Patient Services team to get in touch with the patient directly and arrange an appointment with a nurse specialist or physiotherapist. The form can be accessed at www.asthma.ie/patient-e-referral Patients or their carers can access the Adviceline or the Asthma Society’s WhatsApp messaging service directly via these numbers: • Asthma Adviceline: 1800 44 54 64 • COPD Adviceline: 1800 83 21 46 • WhatsApp: 086 059 0132 NEW RESEARCH HIGHLIGHTS IMPLICATIONS OF ANTIBIOTIC USE IN HUMAN AND VETERINARY MEDICINE A series of five research publications on Antimicrobial Resistance (AMR) by APC Microbiome Ireland, a worldleading SFI Research Centre based in University College Cork and Teagasc Moorepark, yields new data regarding the implications of antibiotic use in early life and the effects of antibiotics in standard dry cow therapy. Lead author of these publications, Dr Dhrati Patangia, was recruited under

Dr Dhrati Patangia, APC SFI AMR Fellow

the APC AMR PhD Fellowship programme funded by SFI in 2018.A paper published in the international scientific journal Microbiome provides evidence that early life exposure of infants to specific antibiotics could lead to multi-drug resistance. A second publication, in the journal Antibiotics, suggests that antibiotic use does not benefit standard dry cow therapy. Dr Patangia is also lead author on two reviews in highly cited publications; one in the prestigious review journal Trends in Microbiology entitled ‘Vertical transfer of antibiotics and antibiotic resistant strains across the mother/baby axis’ which reviews the mechanisms of mother to infant transmission of antibiotics and antibiotic resistant strains. The second paper published in the journal Microbiology Open Reviews is entitled ‘Impact of antibiotics on the human microbiome and consequences for host health’ discusses the adverse effects of antibiotics on the gut microbiota and thus host health and suggests alternative approaches to antibiotic use. Dr Patangia is a recent PhD graduate from the APC and School of Microbiology, University College Cork. While undertaking her PhD, she was based in Teagasc in Moorepark, Co Cork, building on the close collaborative relationship between UCC

and Teagasc. Dr Patangia was supervised by Professor Catherine Stanton, APC co-Principal Investigator, and Professor Paul Ross, Director of APC, and has won several awards including best poster prize at the 2022 Dublin University Microbiological Society focused meeting.

and persistent effect on the gut microbiome, highlighting the need for new alternatives/strategies to be developed and used where needed to restore the microbial ecosystem and maintain a healthy microenvironment, and reduce the use of prophylactic antibiotics during the crucial infancy stage.”

Dr Patangia says “My interest in the microbiome started in India when I chose the topic for a research module as part of my Masters programme. I was delighted to discover the APC Antimicrobial Resistance PhD Fellowship programme which enabled me to target my PhD on my interest areas: the human microbiome, antibiotic resistance, and early life. While antibiotics provide lifesaving benefits, they come at the cost of the potential development of antimicrobial resistance which could result in a lack of effective medication in certain situations.”

DERBAC M IS BACK TO FIGHT SCABIES AND LICE

APC Director Professor Paul Ross says “The goal of the APC Antimicrobial Resistance PhD Fellowship programme was to train a group of PhD students with specific research skills to create an expert cohort of AMR researchers. AMR is a huge global crises with an anticipated twofold surge in resistance to last-resort antibiotics by 2035, compared to 2005 levels according to the Organization for Economic Cooperation (source WHO).” Professor Philip Nolan, Director General, Science Foundation Ireland, said: “SFI is committed to supporting research excellence to address the future challenges. Antimicrobial resistance is a growing global public health challenge, we congratulate APC and Dr Patangia in their recent scientific discoveries towards a better understanding of and solutions addressing antimicrobial resistance.” Vice President for Research and Innovation at UCC Professor John F. Cryan says “UCC has a research focus on the challenges and opportunities that are shaping the future of our nation and the wider world. UCC scientists at APC are pioneering critical research to combat the global AMR crises through microbiome research.” Teagasc Senior Principal Research Officer and APC PI Catherine Stanton says “There is no doubt that antibiotics are vital for the treatment of certain infections in infants. However, this study has shown that antibiotic exposure in early life has an immediate

Derbac M, Ireland’s only Malathion treatment, used to treat scabies, head lice and pubic lice is back! Available in pharmacies and on prescription, it provides an effective, alternative treatment option at a time where there is limited availability of other treatments available. Scabies is highly contagious through skin-to-skin contact, causing skin sores and can lead to more serious complications such as septicaemia (a bloodstream infection), heart disease and kidney problems. The World Health Organisation (WHO) reports that it is believed at any one time an estimated 200 million people are infected globally1. It’s important that Scabies is treated quickly to prevent its spread. In 2023, an increase of reported scabies outbreaks in Ireland was observed, with 67% of those cases occurring in long-term care facilities2. In August 2023, Malathion was placed on the Health Products Regulatory Authority’s medicine shortage list as being unavailable, highlighting the limited supply until the estimated restock date of 31st January 20243. During this time, persistent use of it’s alternative, Permethrin, may even have led some of the population to develop a resistance to the treatment4. Permethrin, more commonly known as Lyclear, has now also been placed on the HPRA shortages list. This limitation in treatment options has led to increased concern from doctors across Ireland about a potential major public health issue due to the increased number of Scabies cases5. Brand Manager for Derbac M in Ireland, Lucy Manning commented, “At a time where there are limited treatment options available and demand is expected to increase, we are pleased to be able to bring Derbac M back to the market, providing an alternative treatment option to help those suffering from scabies, headlice and pubic lice.”

HOSPITALPROFESSIONALNEWS.IE | HPN • MARCH 2024

(pembrolizumab) Infusion 25mg/ml

KEYTRUDA: multiple treatment options for more patients with mNSCLC1

PD-L1 <1% or unknown

PD-L1 1-49%

PD-L1 >50%

NONSQUAMOUS

√

√

√

1st line Combination** Therapy3

SQUAMOUS

√

√

√

1st line*** Monotherapy4

NON-SQUAMOUS AND SQUAMOUS

X

X

√

Line

Histology

1st line Combination* Therapy2

adverse reactions Immune-mediated adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. Most immune mediated adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Immune mediated adverse reactions have also occurred after the last dose of pembrolizumab. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Immune-mediated adverse reactions are immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated nephritis, immune-mediated endocrinopathies (including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism), immune-mediated skin adverse reactions (also including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). Refer to SmPC for more information and management of immune-mediated adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with classical Hodgkin lymphoma undergoing allogeneic HSCT after previous exposure to pembrolizumab. Infusion-related reactions: Grades 1, 2, 3 or 4 infusion reactions including hypersensitivity and anaphylaxis, could be seen with pembrolizumab treatment. Refer to SmPC for more information and management of infusion-related reactions. Patients with Biliary tract carcinoma (especially those with biliary stents) should be closely monitored for development of cholangitis or biliary tract infections before initiation of treatment and, regularly, thereafter. Overdose: There is no information on overdose with pembrolizumab. In case of overdose, monitor closely for signs or symptoms of adverse reactions and treat appropriately. INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. No metabolic drug drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. Corticosteroids can be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. FERTILITY, PREGNANCY AND LACTATION Women of childbearing potential Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Pregnancy No data on use in pregnant women. Do not use during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Breast-feeding It is unknown whether pembrolizumab is secreted in human milk. A risk to newborns/ infants cannot be excluded. Fertility No clinical data available. SIDE EFFECTS Refer to SmPC for complete information on side effects. Pembrolizumab is most commonly associated with immune-mediated adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-mediated and infusion-related adverse reactions. When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment. For additional lenvatinib safety information related to advanced RCC see the SmPC for Kisplyx and for advanced EC see the SmPC for Lenvima. Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, pruritus, rash, fatigue. Common: pneumonia, thrombocytopenia, neutropenia, lymphopenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, dizziness, dysgeusia, pneumonitis, colitis, dry mouth, hepatitis, severe skin reactions, vitiligo, dry skin, eczema, alopecia, dermatitis acneiform, erythema, dermatitis, myositis, pain in extremity, arthritis, influenza like illness, chills, AST and ALT increases, increase in blood alkaline phosphatase, hypercalcaemia, blood bilirubin increased, blood creatinine increased, infusion related reaction. In combination with chemotherapy: Very Common: Anaemia, neutropenia, thrombocytopenia, hypothyroidism, hypokalaemia, decreased appetite, insomnia, neuropathy peripheral, headache, dyspnoea, cough, diarrhoea, vomiting, nausea, abdominal pain, constipation, alopecia, pruritus, rash, musculoskeletal pain, arthralgia, pyrexia, fatigue, asthenia, ALT increase, AST increased. Common: pneumonia, febrile neutropenia, leukopenia, lymphopenia, infusion related reaction, adrenal insufficiency, thyroiditis, hyperthyroidism, hyponatraemia, hypocalcaemia, lethargy, dizziness, dysgeusia, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, pneumonitis, colitis, gastritis, dry mouth, hepatitis, severe skin reactions, erythema, dermatitis, dry skin, dermatitis acneiform, eczema, myositis, pain in extremity, arthritis, acute kidney injury, oedema, influenza-like illness, chills, blood bilirubin increased, blood alkaline phosphatase increased, blood creatinine increased, hypercalcaemia. In combination with axitinib or lenvatinib: Very Common: urinary tract infection, anaemia, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, diarrhoea, abdominal pain, nausea, vomiting, constipation, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pain in extremity, fatigue, asthenia, oedema, pyrexia, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, infusion-related reaction, adrenal insufficiency, hyperthyroidism, thyroiditis, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, dizziness, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, pancreatitis, gastritis, dry mouth, hepatitis, severe skin reactions, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, arthritis, nephritis, influenza like illness, chills, amylase increased, blood bilirubin increased, blood alkaline phosphatase increased, hypercalcaemia. PACKAGE QUANTITIES KEYTRUDA 25 mg/mL: 4 mL of concentrate in a 10 mL Type I clear glass vial. Legal Category: POM. Marketing Authorisation numbers: EU/1/15/1024/002. Marketing Authorisation holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: December 2023. © 2023 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin, D18 X5K7 or from www.medicines.ie. II135_II138 Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to MSD (Tel: 01-2998700) References 1. KEYTRUDA Summary of Product Characteristics, August 2023, available at www.medicines.ie. 2. Gandhi L, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378:2078-2092. 3. Paz-Ares L, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379:2040–2051. 4. Reck, M et al. Pembrolizumab versus chemotherapy for PDL1 positive-non-small cell lung cancer, N Eng J Med 2016, 375(19)1823-1833. ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; mNSCLC=metastatic non–small cell lung carcinoma; PDL1=programmed death ligand 1. Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7, Ireland.

IE-KEY-00845

KEYTRUDA® (pembrolizumab) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION KEYTRUDA 25 mg/mL: One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. INDICATIONS • KEYTRUDA as monotherapy is indicated for the treatment of adults and adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma. • KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults and adolescents aged 12 years and older with Stage IIB, IIC or III melanoma and who have undergone complete resection. • KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with non-small cell lung carcinoma who are at high risk of recurrence following complete resection and platinum-based chemotherapy. • KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. • KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. • KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults. • KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 with a ≥1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. • KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. • KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy. • KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD L1 with a combined positive score (CPS) ≥ 10. • KEYTRUDA as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 1. • KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic HNSCC in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy. • KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma (RCC) in adults. • KEYTRUDA, in combination with lenvatinib, is indicated for the first line treatment of advanced renal cell carcinoma in adults. • KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers. Colorectal cancer (CRC). • KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings: - first line treatment of metastatic colorectal cancer. - treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine based combination therapy. Non-colorectal cancers. • KEYTRUDA as monotherapy is indicated for the treatment of the following MSI H or dMMR tumours in adults with (a) advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation, (b) unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy. • KEYTRUDA, in combination with platinum and fluoropyrimidine based chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus in adults whose tumours express PD-L1 with a CPS ≥ 10. • KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early stage triple negative breast cancer at high risk of recurrence. • KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple negative breast cancer in adults whose tumours express PD L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease. • KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation. • KEYTRUDA, in combination with chemotherapy with or without bevacizumab, is indicated for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD L1 with a CPS ≥ 1. • KEYTRUDA, in combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 1. • KEYTRUDA, in combination with fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumours express PD L1 with a CPS ≥ 1. • KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the first-line treatment of locally advanced unresectable or metastatic biliary tract carcinoma in adults. DOSAGE AND ADMINISTRATION See SmPC for full details. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes. The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL or patients aged 12 years and older with melanoma is 2 mg/kg bodyweight (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. KEYTRUDA must not be administered as an intravenous push or bolus injection. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Treat patients until disease progression or unacceptable toxicity (and up to maximum duration of therapy if specified for an indication). For the adjuvant treatment of melanoma, NSCLC, or RCC, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year. Refer to the SmPC for dosing in neoadjuvant and adjuvant treatment of locally advanced, or early stage triple-negative breast cancer at high risk of recurrence. KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued (a) For Grade 4 toxicity except for: endocrinopathies that are controlled with replacement hormones; or haematological toxicity, only in patients with cHL in which KEYTRUDA should be withheld until adverse reactions recover to Grade 0-1; (b) If corticosteroid dosing cannot be reduced to ≤10 mg prednisone or equivalent per day within 12 weeks; (c) If a treatment-related toxicity does not resolve to Grade 0 1 within 12 weeks after last dose of KEYTRUDA; (d) If any event occurs a second time at Grade ≥ 3 severity. Patients must be given the Patient Card and be informed about the risks of KEYTRUDA. Special populations Elderly: No dose adjustment necessary. Renal impairment: No dose adjustment needed for mild or moderate renal impairment. No studies in severe renal impairment. Hepatic impairment: No dose adjustment needed for mild or moderate hepatic impairment. No studies in severe hepatic impairment. Paediatric population: Safety and efficacy in children below 18 years of age not established except in paediatric patients with melanoma or cHL. CONTRAINDICATIONS Hypersensitivity to the active substance or to any excipients. PRECAUTIONS AND WARNINGS Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations. Immune-mediated

Date of Preparation: February 2024

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