Fingolimod Teva is indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis for the following groups of adult patients and paediatric patients aged 10 years and older:
Patients with highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy (for exceptions and information about washout periods see the SmPC) or
Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.
of therapy. Patients should report symptoms of infection up to 2 months after discontinuation of fingolimod. Serious, life-threatening, and sometimes fatal cases of encephalitis, meningitis or meningoencephalitis caused by herpes simplex and varicella zoster viruses have occurred with Fingolimod Teva. Treatment should be stopped if these develop, and appropriate treatment initiated. Patients need to be assessed for their immunity to varicella (chickenpox) prior to treatment. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment. Cases of cryptococcal meningitis, sometimes fatal, have been reported after approximately 2-3 years of treatment. If cryptococcal meningitis is diagnosed, fingolimod should be suspended and appropriate treatment should be initiated. Progressive multifocal leukoencephalopathy (PML) has been reported under fingolimod treatment. Before initiating treatment with fingolimod, a baseline MRI should be available (usually within 3 months) as a reference. MRI findings may be apparent before clinical signs or symptoms. If PML is suspected, MRI should be performed immediately for diagnostic purposes and treatment with fingolimod should be suspended until PML has been excluded. Due to the immunosuppressive properties of fingolimod, vaccination against Human papilloma virus (HPV) should be considered prior to treatment initiation. Macular oedema has been reported in patients treated with fingolimod 0.5mg. Perform an ophthalmological evaluation 3–4 months after fingolimod initiation. Evaluate the fundus, including the macula, in patients reporting visual disturbances. Fingolimod Teva should be discontinued if a patient develops macular oedema. Increased hepatic enzymes have been reported in MS patients treated with fingolimod. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, have occurred as early as ten days after the first dose and have also been reported after prolonged use. Do not use fingolimod in patients with severe pre-existing hepatic injury (Child-Pugh class C). Due to the immunosuppressive properties of fingolimod, initiation of treatment should be delayed in patients with active viral hepatitis until resolution. Recent (i.e. within last 6 months) transaminase and bilirubin levels should be available before initiation of treatment. If liver transaminases are at least 5 times the upper limit of normal (ULN) or at least 3 times the ULN associated with any increase in serum bilirubin, Fingolimod Teva should be discontinued. Blood pressure should be regularly monitored during treatment as Fingolimod Teva can cause hypertension. Fingolimod Teva should be used with caution in patients with severe respiratory disease, pulmonary fibrosis and chronic obstructive pulmonary disease. Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported during treatment. If PRES is suspected, Fingolimod Teva should be discontinued. When switching patients from another disease modifying therapy to Fingolimod Teva, a CBC is recommended prior to initiating treatment to ensure that immune effects of the previous therapy have resolved. Vigilance for skin lesions is warranted and a medical evaluation of the skin is recommended at initiation, and then every 6 to 12 months taking into consideration clinical judgement. Patients should be referred to a dermatologist in case suspicious lesions are detected. Patients treated with fingolimod should be cautioned against exposure to sunlight without protection. If lymphoma is suspected during treatment, Fingolimod Teva should be discontinued. Rare cases of tumefactive lesions associated with MS relapse have been reported. Severe exacerbation of disease has been observed rarely in some patients stopping fingolimod. Caution is therefore indicated when stopping fingolimod therapy. If a decision is made to stop treatment with fingolimod a 6-week interval without therapy is needed, based on half-life, to clear fingolimod from the circulation. Caution is indicated with the use of immunosuppressants soon after the discontinuation due to possible additive immune system effects. The safety profile in paediatric patients is similar to that in adults. Cases of seizures, anxiety, depressed mood and depression have been reported with a higher incidence in paediatric patients treated with fingolimod compared to patients treated with interferon beta-1a. It is recommended that paediatric patients complete all immunisations in accordance with current immunisation guidelines before starting Fingolimod Teva. Interactions: Anti-neoplastic, immunomodulatory or immunosuppressive therapies should not be co-administered due to the risk of additive immune system effects. During and for up to two months after treatment vaccination may be less effective. The use of live attenuated vaccines may carry a risk of infections and should be avoided. Treatment with Fingolimod Teva should not be initiated in patients receiving beta-blockers, or other substances which may decrease HR, such as class Ia and III antiarrhythmics, calcium channel blockers (such as verapamil or diltiazem), ivabradine, digoxin, anticholinesteratic agents or pilocarpine. Co-administration of fingolimod with ketoconazole resulted in a 1.7-fold increase in fingolimod and fingolimod phosphate exposure (AUC) by inhibition of CYP4F2. Caution should be exercised with substances that may inhibit CYP3A4 (protease inhibitors, azole antifungals and some macrolides such as clarithromycin or telithromycin). Co-administration of strong CYP3A4 inducers (rifampicin, phenobarbital, phenytoin, efavirenz) should be used with caution as they may reduce the AUC or fingolimod and its metabolite. Concomitant administration with St. John’s Wort is not recommended. Co-administration of fingolimod with oral contraceptives (ethinylestradiol and levonorgestrel) did not elicit any change in oral contraceptive exposure. Pregnancy and lactation: Fingolimod is contraindicated in women of childbearing potential not using effective contraception. Post-marketing data suggest that use of fingolimod is associated with a 2-fold increased risk of major congenital malformations when administered during pregnancy compared with the rate observed in the general population. Women of childbearing potential should provide a negative pregnancy test result before treatment initiation and must receive counselling regarding the serious risk to the foetus. Effective contraception must be used during treatment and for 2 months after discontinuation of Fingolimod Teva. Fingolimod should be stopped 2 months before planning a pregnancy. If a woman becomes pregnant during treatment, fingolimod must be discontinued. When stopping fingolimod therapy for planning a pregnancy the possible return of disease activity should be considered. Women receiving Fingolimod Teva should not breastfeed. Effects on ability to drive and use machines: Has no or negligible influence on the ability to drive and use machines, however, dizziness or drowsiness may occasionally occur when initiating treatment. Adverse reactions: Pneumonia, progressive multifocal leukoencephalopathy (PML), cryptococcal infections, basal cell carcinoma, malignant melanoma, lymphoma, squamous cell carcinoma, Kaposi’s sarcoma, leucopenia, thrombocytopenia, autoimmune haemolytic anaemia, hypersensitivity reactions, seizure, posterior reversible encephalopathy syndrome (PRES), macular oedema, bradycardia, ECG T-wave inversion and acute hepatic failure. Very Common: Influenza, sinusitis, headache, cough, diarrhoea, back pain and increased hepatic enzyme levels. Common: Herpes viral infections, bronchitis, tinea versicolor, lymphopenia, depression, dizziness, migraine, blurred vision, AV block, hypertension, dyspnoea, eczema, alopecia, pruritus, myalgia, arthralgia, asthenia, decreased weight and increased blood triglyceride levels. Consult the Summary of Product Characteristics in relation to other side effects. Overdose: If an overdose constitutes first exposure to fingolimod, it is important to monitor patients with a continuous (real time) ECG and hourly measurement of HR
Teva Pharmaceuticals Ireland, Digital Office Centre Swords, Suite 101 - 103, Balheary Demesne, Balheary Road, Swords, Co Dublin, K67E5AO, Ireland.
Generic Product Launch Fingolimod Teva
0.5 mg hard capsules fingolimod
High Tech Prescription Medicine
Indications
Fingolimod Teva 0.5 mg hard capsules
Fingolimod Teva is indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis for the following groups of adult patients and paediatric patients aged 10 years and older:
Patients with highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy (for exceptions and information about washout periods see the SmPC) or
Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.
Fingolimod Teva Hard Capsules Abbreviated Prescribing Information
Presentation: Each hard capsule contains 0.5mg fingolimod as hydrochloride.
Indications: Fingolimod Teva is indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis (MS) for adult patients and paediatric patients (10 years and older) with: Highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy; Or with rapidly evolving severe relapsing remitting MS defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI. Dosage and administration: For oral administration. Treatment should be initiated and supervised by a physician experienced in MS. Adults: The recommended dose is one 0.5mg capsule taken orally once daily. Children (10 years of age and above): The recommended dose is dependent on body weight. Paediatric patients with body weight ≤40kg: one 0.25mg capsule taken orally once daily. Paediatric patients with body weight >40kg: one 0.5mg capsule taken orally once daily. Paediatric patients who start on 0.25mg capsules and subsequently reach a stable body weight above 40kg should be switched to 0.5mg capsules. The safety and efficacy of fingolimod in children aged below 10 years has not been established. Elderly: Fingolimod Teva should be used with caution in patients aged 65 years and over due to insufficient data on safety and efficacy. Renal impairment: No dose adjustments are needed in patients with mild to severe renal impairment. Hepatic impairment: No dose adjustment needed in patients with mild or moderate hepatic impairment, but caution should be exercised when initiating treatment in these patients. Fingolimod Teva must not be used in patients with severe hepatic impairment (Child-Pugh class C). Contraindications: Immunodeficiency syndrome. Patients with increased risk for opportunistic infections, including immunocompromised patients (including those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies). Severe active infections and active chronic infections (hepatitis, tuberculosis). Active malignancies. Severe liver impairment (Child-Pugh class C). Patients who in the previous 6 months had myocardial infarction (MI), unstable angina pectoris, stroke/transient ischaemic attack (TIA), decompensated heart failure (requiring inpatient treatment), or New York Heart Association (NYHA) class III/IV heart failure. Patients with severe cardiac arrhythmias requiring anti-arrhythmic treatment with class Ia or class III anti-arrhythmic medicinal products. Patients with second-degree Mobitz type II atrioventricular (AV) block or third-degree AV block, or sick-sinus syndrome, if they do not wear a pacemaker. Patients with a baseline QTc interval ≥ 500 msec. During pregnancy and in women of childbearing potential not using effective contraception. Hypersensitivity to the active substance or to any of the excipients. Precautions and warnings: Initiation of treatment results in a transient decrease in heart rate (HR) and may also be associated with AV conduction delays, including the occurrence of isolated reports of transient, spontaneously resolving complete AV block. All patients should have an electrocardiogram (ECG) and blood pressure measurement performed prior to and 6 hours after the first dose of Fingolimod Teva. All patients should be monitored for a period of 6 hours for signs and symptoms of bradycardia with hourly HR and blood pressure measurement. Continuous ECG monitoring during this 6 hour period is recommended. The same precautions as for the first dose are recommended when patients are switched from the 0.25mg to the 0.5mg daily dose. In the event of post-dose bradyarrhythmia-related symptoms, initiate clinical management and monitor the patient until the symptoms have resolved. Very rare cases of T-wave inversion have been reported in adult patients treated with fingolimod. In case of T-wave inversion, the prescriber should ensure that there are no associated myocardial ischaemia signs or symptoms. If myocardial ischaemia is suspected, seek advice from a cardiologist. Fingolimod Teva should not be used in patients with sino-atrial heart block, a history of symptomatic bradycardia, recurrent syncope or cardiac arrest, or in patients with significant QT prolongation, uncontrolled hypertension or severe sleep apnoea. Fingolimod has an immunosuppressive effect that predisposes patients to an infection risk, including opportunistic infections that can be fatal, and increases the risk of developing lymphomas and other malignancies, particularly those of the skin. Before initiating treatment with Fingolimod Teva, a recent complete blood count (CBC) (i.e.
Teva Pharmaceuticals Ireland, Digital Office Centre Swords, Suite 101 - 103, Balheary Demesne, Balheary Road, Swords, Co Dublin, K67E5AO, Ireland.
Freephone: 1800 - 201 700 | Email: info@teva.ie
Prescription Only Medicine.
within 6 months or after discontinuation of prior therapy) should be available.
Assessments of CBC are also recommended periodically during treatment, at month 3 and at least yearly thereafter, and in case of signs of infection. Absolute lymphocyte count <0.2x109/l, if confirmed, should lead to treatment interruption until recovery. Initiation of treatment with Fingolimod Teva should be delayed in patients with severe active infection until resolution. Suspension of Fingolimod Teva should be considered if a patient develops a serious infection and consideration of benefit-risk should be undertaken prior to re-initiation of therapy. Patients should report symptoms of infection up to 2 months after discontinuation of fingolimod. Serious, life-threatening, and sometimes fatal cases of encephalitis, meningitis or meningoencephalitis caused by herpes simplex and varicella zoster viruses have occurred with Fingolimod Teva. Treatment should be stopped if these develop, and appropriate treatment initiated. Patients need to be assessed for their immunity to varicella (chickenpox) prior to treatment. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment. Cases of cryptococcal meningitis, sometimes fatal, have been reported after approximately 2-3 years of treatment. If cryptococcal meningitis is diagnosed, fingolimod should be suspended and appropriate treatment should be initiated. Progressive multifocal leukoencephalopathy (PML) has been reported under fingolimod treatment. Before initiating treatment with fingolimod, a baseline MRI should be available (usually within 3 months) as a reference. MRI findings may be apparent before clinical signs or symptoms. If PML is suspected, MRI should be performed immediately for diagnostic purposes and treatment with fingolimod should be suspended until PML has been excluded. Due to the immunosuppressive properties of fingolimod, vaccination against Human papilloma virus (HPV) should be considered prior to treatment initiation. Macular oedema has been reported in patients treated with fingolimod 0.5mg. Perform an ophthalmological evaluation 3–4 months after fingolimod initiation. Evaluate the fundus, including the macula, in patients reporting visual disturbances. Fingolimod Teva should be discontinued if a patient develops macular oedema. Increased hepatic enzymes have been reported in MS patients treated with fingolimod. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, have occurred as early as ten days after the first dose and have also been reported after prolonged use. Do not use fingolimod in patients with severe pre-existing hepatic injury (Child-Pugh class C). Due to the immunosuppressive properties of fingolimod, initiation of treatment should be delayed in patients with active viral hepatitis until resolution. Recent (i.e. within last 6 months) transaminase and bilirubin levels should be available before initiation of treatment. If liver transaminases are at least 5 times the upper limit of normal (ULN) or at least 3 times the ULN associated with any increase in serum bilirubin, Fingolimod Teva should be discontinued. Blood pressure should be regularly monitored during treatment as Fingolimod Teva can cause hypertension. Fingolimod Teva should be used with caution in patients with severe respiratory disease, pulmonary fibrosis and chronic obstructive pulmonary disease. Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported during treatment. If PRES is suspected, Fingolimod Teva should be discontinued. When switching patients from another disease modifying therapy to Fingolimod Teva, a CBC is recommended prior to initiating treatment to ensure that immune effects of the previous therapy have resolved. Vigilance for skin lesions is warranted and a medical evaluation of the skin is recommended at initiation, and then every 6 to 12 months taking into consideration clinical judgement. Patients should be referred to a dermatologist in case suspicious lesions are detected. Patients treated with fingolimod should be cautioned against exposure to sunlight without protection. If lymphoma is suspected during treatment, Fingolimod Teva should be discontinued. Rare cases of tumefactive lesions associated with MS relapse have been reported. Severe exacerbation of disease has been observed rarely in some patients stopping fingolimod. Caution is therefore indicated when stopping fingolimod therapy. If a decision is made to stop treatment with fingolimod a 6-week interval without therapy is needed, based on half-life, to clear fingolimod from the circulation. Caution is indicated with the use of immunosuppressants soon after the discontinuation due to possible additive immune system effects. The safety profile in paediatric patients is
similar to that in adults. Cases of seizures, anxiety, depressed mood and depression have been reported with a higher incidence in paediatric patients treated with fingolimod compared to patients treated with interferon beta-1a. It is recommended that paediatric patients complete all immunisations in accordance with current immunisation guidelines before starting Fingolimod Teva. Interactions: Anti-neoplastic, immunomodulatory or immunosuppressive therapies should not be co-administered due to the risk of additive immune system effects. During and for up to two months after treatment vaccination may be less effective. The use of live attenuated vaccines may carry a risk of infections and should be avoided. Treatment with Fingolimod Teva should not be initiated in patients receiving beta-blockers, or other substances which may decrease HR, such as class Ia and III antiarrhythmics, calcium channel blockers (such as verapamil or diltiazem), ivabradine, digoxin, anticholinesteratic agents or pilocarpine. Co-administration of fingolimod with ketoconazole resulted in a 1.7-fold increase in fingolimod and fingolimod phosphate exposure (AUC) by inhibition of CYP4F2. Caution should be exercised with substances that may inhibit CYP3A4 (protease inhibitors, azole antifungals and some macrolides such as clarithromycin or telithromycin). Co-administration of strong CYP3A4 inducers (rifampicin, phenobarbital, phenytoin, efavirenz) should be used with caution as they may reduce the AUC or fingolimod and its metabolite. Concomitant administration with St. John’s Wort is not recommended. Co-administration of fingolimod with oral contraceptives (ethinylestradiol and levonorgestrel) did not elicit any change in oral contraceptive exposure. Pregnancy and lactation: Fingolimod is contraindicated in women of childbearing potential not using effective contraception. Post-marketing data suggest that use of fingolimod is associated with a 2-fold increased risk of major congenital malformations when administered during pregnancy compared with the rate observed in the general population. Women of childbearing potential should provide a negative pregnancy test result before treatment initiation and must receive counselling regarding the serious risk to the foetus. Effective contraception must be used during treatment and for 2 months after discontinuation of Fingolimod Teva. Fingolimod should be stopped 2 months before planning a pregnancy. If a woman becomes pregnant during treatment, fingolimod must be discontinued. When stopping fingolimod therapy for planning a pregnancy the possible return of disease activity should be considered. Women receiving Fingolimod Teva should not breastfeed. Effects on ability to drive and use machines: Has no or negligible influence on the ability to drive and use machines, however, dizziness or drowsiness may occasionally occur when initiating treatment. Adverse reactions: Pneumonia, progressive multifocal leukoencephalopathy (PML), cryptococcal infections, basal cell carcinoma, malignant melanoma, lymphoma, squamous cell carcinoma, Kaposi’s sarcoma, leucopenia, thrombocytopenia, autoimmune haemolytic anaemia, hypersensitivity reactions, seizure, posterior reversible encephalopathy syndrome (PRES), macular oedema, bradycardia, ECG T-wave inversion and acute hepatic failure. Very Common: Influenza, sinusitis, headache, cough, diarrhoea, back pain and increased hepatic enzyme levels. Common: Herpes viral infections, bronchitis, tinea versicolor, lymphopenia, depression, dizziness, migraine, blurred vision, AV block, hypertension, dyspnoea, eczema, alopecia, pruritus, myalgia, arthralgia, asthenia, decreased weight and increased blood triglyceride levels. Consult the Summary of Product Characteristics in relation to other side effects. Overdose: If an overdose constitutes first exposure to fingolimod, it is important to monitor patients with a continuous (real time) ECG and hourly measurement of HR and blood pressure, at least during the first 6 hours. If after 6 hours the HR is <45bpm in adults, <55bpm in paediatric patients aged 12 years and above, or <60bpm in paediatric patients aged 10 years to below 12 years, or if the ECG at 6 hours after the first dose shows second degree or higher AV block, or if it shows a QTc interval ≥500msec, monitoring should be extended at least for overnight and until the findings have resolved. The occurrence at any time of third degree AV block should also lead to extended monitoring including overnight monitoring. Neither dialysis nor plasma exchange results in removal of fingolimod from the body. Legal category: POM Marketing Authorisation Number: PA0436/047/001. Marketing Authorisation Holder: Norton Waterford, T/A IVAX Pharmaceuticals Ireland, Unit 301, IDA Industrial Park, Cork Road, Waterford, Ireland Job Code: MED-IE-00050.
Further information is available on request or in the SmPC. Product Information also available on the HPRA website. Date of Preparation: September 2024 | Job Code: FIN-IE-00002 Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to Teva UK Limited on +44 (0) 207 540 7117 or medinfo@tevauk.com
Contents Foreword
First for Cutting-Edge Global AFib Technology in Ireland P4
Medicines for Ireland Announces Expansion P6
Examining the Overprescribing of Benzodiazepines, Z Drugs and Gabapentinoids in Ireland P8
Are scientific standards in science under pressure? P18
Could you help a future pharmacist? P21
Health Impact Award for Professor Murphy P39
Editor
The Irish Hospital Consultants Association (IHCA) is calling for the forthcoming Programme for Government to include the implementation of the recommendations of the Department of Health expert group regarding reform of clinical negligence claims.
St James’s Hospital Pharmacy Team of the Year P56
REGULARS
CPD: Respiratory Syncytial Virus P29
Gastroenterology Special Focus: Gastric Cancer Screening P20
Gastroenterology Special Focus: Liver Disease P26
Endocrinology Focus: Type 1 vs Type 2 Diabetes P37
Clinical R&D: P60
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.
A Department of Health expert group, chaired by Professor Rhona Mahony, recently recommended various new approaches and mechanisms, including the introduction of pre-action protocols, with sanctions for any party who fails to adhere to them.
The Irish Hospital Consultants Association has said implementing these reforms will be crucial to accelerating the resolution times of claims, reducing the cost of litigation, and sparing patients and families from prolonged and stressful legal processes.
You can read more about this on page 5.
In other news on page 7, Pharmacists in both community and hospital settings are well positioned to swiftly detect substandard and falsified (SF) medical products in supply chains, report them to the authorities, and educate and advise affected patients, FIP told the World Health Organisation (WHO) Executive Board in Geneva, Switzerland.
Substandard and falsified (SF) medical products as defined by the World Health Organization, are major threats to public health. Through increasing globalisation, the problem has expanded in both developed and developing countries.
A multiagency working group has recently published a report “Examining the Overprescribing of Benzodiazepines, Z Drugs and Gabapentinoids in Ireland”.
The report was written and produced by a Working Group established by the Medical Council with representatives from across the health sector.
It outlines the key issues identified and recommendations of the Working Group, which was established to review and address overprescribing by doctors of benzodiazepines, z-drugs, and gabapentinoids in Ireland. The recommendations within the report aim to reduce the initiation and inappropriate prescribing of these medicines in the interests of patient and doctor safety, and to support prescribers.
The full details are on page 8.
I hope you enjoy the issue.
First for Cutting-Edge Global AFib Technology in Ireland
Mater Private Network is proud to announce the successful integration of the cutting-edge FARAVIEW™ Software, utilised in the treatment of Atrial fibrillation (AFib), to its Dublin centre of excellence. As one of just seven centres granted early access to this revolutionary technology under limited market release, Mater Private Network is driving the future of cardiac care in Ireland, benefiting hundreds of patients nationwide.
This milestone follows Mater Private Network’s selection as one of only three centres globally to take part in the FARAVIEW technology study into the treatment of AFib, highlighting the Network’s leadership in cardiac electrophysiology. Leading this initiative in Ireland are Prof. Gábor Széplaki, Head of Cardiac Electrophysiology, and Dr. Noel Fitzpatrick, Consultant Cardiologist at Mater Private Network in Dublin.
Atrial fibrillation (AFib) is the most common irregular heart rhythm, with an estimated 8 million patients living with this condition in Europe, suffering from symptoms such as fatigue, palpitations and breathlessness, depending on the severity of the condition. Minimally invasive, innovative technologies such as the FARAPULSE Pulsed Field Ablation System may change the course of treatment for many in the future.
Hospital Staffing Levels Must Increase
The Chair of the Consultants’ Committee of the Irish Medical Organisation (IMO) has said that consultants are not the obstacle to extending routine health services over the weekend but serious investment in staffing and infrastructure, as well as a fundamental change in how hospital care is delivered, are required to support such a move.
Professor Matthew Sadlier was responding to comments made by Minister for Health Jennifer Carroll MacNeill, who said that more consultants were needed in hospitals on the weekends to quicken up the patient discharge process.
Professor Sadlier said, “The reality is that almost all consultants are
currently on rosters which involve covering unscheduled care (i.e. emergencies) on weekends. As most consultants have signed up to the new contract it is evident that there is an appetite amongst consultants to provide enhanced care over weekends.
“However, for this to be effective and produce meaningful results there would need to be an uplift not only in consultant numbers but also amongst all other staff groups within the hospital. Just rostering consultants at weekends in the current situation would just result in significant gaps in the service from Monday to Friday.”
Prof Sadlier said that consultants wanted to see a reduction in trolley numbers in hospitals and
should not be blamed for the slow discharge of patients over weekends. “For patients to be discharged safely over weekends, we would also need available community services. For example, these include stepdown units, community pharmacies, primary care facilities, meals on wheels and more being in a position to provide support on a seven-day basis. Often patients are identified for discharge, but the limiting factor is outside of the hospital.”
Professor Sadlier added that it would be wrong to primarily focus on discharge times in hospitals. “The last thing we want to do is discharge patients too early, which can lead to
Mater Private Network team, led by Prof. Gábor Széplaki & the team from Boston Scientific celebrate the integration of the FARAVIEW technology in the MPN Cath Lab, Dublin
Prof. Gábor Széplaki explains, “At Mater Private Network, we participate in trials of innovative new technology such as this, with the goal of setting new standards in Irish cardiac care and we are delighted with this result. The integration of FARAVIEW mapping with the FARAPULSE PFA System allows us to offer safer, faster, and more precise treatments for those suffering from AFib. As one of the few institutions with access to this cutting-edge development, this technology marks a new era in AFib care in Ireland. We are proud to be a part of that journey, ensuring our patients receive world-class, minimally invasive solutions that significantly improve their quality of life.”
Since adopting the FARAPULSE™ PFA System in 2022, the Electrophysiology team at Mater Private Network has treated over 1,400 patients, targeting cardiac tissue while preserving surrounding structures. The introduction of FARAVIEW™ integrated mapping enhances existing technologies, allowing for precise visualisation of the FARAWAVE NAV catheter on the OPAL HDx Mapping system. This system also reduces the need for X-ray exposure and improves procedural workflow, accuracy, and outcomes for patients.
early readmission and in some cases adverse outcomes and readmissions. Currently our hospitals are judged too much on ‘hotel statistics’ (i.e. admissions, discharges and waiting times) and not sufficient attention is paid to quality of care outcomes which is the purpose of the healthcare system. Of course we want to discharge patients as soon as possible, but this cannot come at the expense of good medicine and maximising clinical outcomes for patients.
“We look forward to working with the Minister to delivering a health service that is capable of meeting the needs of the population.”
Fuel Switch in Air Delivery of Medicines
Sylvia
Kiely, Vice President, Global Supply Chain and Product Strategy Lead, Alexion, AstraZeneca Rare Disease with Brian Murray, Commercial & Same Day Director, DHL Express Ireland
Alexion, AstraZeneca Rare Disease, and DHL Express today announced a landmark partnership in a bid to reduce greenhouse gas emissions (GHG) from the air freight of highly specialised medicines manufactured in Ireland. Alexion is the first company in Ireland to sign up to a 100% switch from traditional aviation fuel to sustainable aviation fuel (SAF). This alternative fuel will reduce GHG emissions by over 80% on average compared to traditional aviation fuel1. The greener fuel will be switched on all European air freight shipments across 19 European countries.
Provided through the DHL GoGreen Plus service, SAF is used as a substitute to conventional fuel and can readily be used as a drop-in replacement in aircraft without the need for modifications to aircraft engines. Produced from waste and residue-based feedstock, such as used cooking oil, SAF has improved sustainability compared to traditional fossil jet fuel which is primarily derived from crude oil.
Reducing the GHG emissions associated with the transport of medicinal products is an important part of AstraZeneca’s wider sustainability strategy. This
includes a focus on partnerships across the healthcare sector including supply chain decarbonisation. From 2030, the aim is to halve the entire value chain footprint (absolute Scope 3 GHG emissions), from a 2019 base year, on the way to becoming science-based net zero by 2045.
Sylvia Kiely, Vice President, Global Supply Chain and Product Strategy Lead, Alexion, AstraZeneca Rare Disease said “Moving our air freight to Sustainable Aviation Fuel is an important milestone in reaching
our Scope 3 targets, with the ambition of being science-based net zero by 2045. Through our partnership with DHL Express we’ve signed up immediately to a 100% change in fuel, rather than scaling up over time, which demonstrates how seriously we take environmental stewardship.”
Brian Murray, Commercial & Same Day Director, DHL Express Ireland said “We are thrilled to partner with Alexion. Our GoGreen Plus service using emissionreduced Sustainable Aviation Fuel demonstrates the tangible impact of collaborative efforts to
IHCA Calls for new Recommendations
The Irish Hospital Consultants Association (IHCA) is calling for the forthcoming Programme for Government to include the implementation of the recommendations of the Department of Health expert group regarding reform of clinical negligence claims.
A Department of Health expert group, chaired by Professor Rhona Mahony, recently recommended various new approaches and mechanisms, including the introduction of pre-action protocols, with sanctions for any party who fails to adhere to them.
As outlined in the report, the primary driver of the rising cost of claims is the cost of care in a relatively small number of very
serious injury claims. Over 50% of healthcare litigation costs come from just 2% of claims, mainly involving severe cases like perinatal brain injury and cerebral palsy.
Pre-action protocols have resulted in reduced legal costs in other jurisdictions, and it is anticipated that their introduction in Ireland would have a similar effect and lead to swifter resolution of claims.
Implementing these reforms will be crucial to accelerating the resolution times of claims, reducing the cost of litigation, and sparing patients and families from prolonged and stressful legal processes.
Consultants have welcomed the government’s commitment, on
the report’s launch, to establish a working group to ensure that its recommendations were “implemented without delay”. The IHCA looks forward to supporting the next Minister for Health in delivering on this commitment.
Commenting on the need for reform, IHCA President Prof Gabrielle Colleran said, “One of the first priorities of the next government should be the swift introduction of pre-action protocols to curtail the surging costs of litigation and to provide speedier resolution of claims for patients.
“The present litigation system in Ireland is excessively adversarial, with clinical negligence claims often taking several years to resolve. This is just adding to the distress
decarbonise the logistics industry and support our customers in achieving their sustainability goals. This initiative aligns perfectly with DHL's sustainability strategy and our goal to achieve net-zero emissions by 2050.”
Countries receiving the medicines under the GoGreen Plus service include Austria, Belgium, Denmark, Estonia, Finland, France, Georgia, Germany, Guernsey, Iceland, Ireland, Italy, Luxemburg, Netherlands, Norway, Portugal, Spain, Sweden and United Kingdom.
faced by patients, their families and healthcare professionals.
“The current protracted claims processes are not fit for purpose and are resulting in increased legal costs that are among the highest in the world.
“Importantly, such costs represent a significant drain on public funds and draw resources away from the provision of healthcare. By working together to implement these reforms, we can not only control rising costs but also ensure better outcomes for patients, healthcare professionals, and the public. The IHCA is eager to engage with the next government to make this vision a reality."
Medicines for Ireland Announces Expansion
Medicines for Ireland (MFI) has announced the addition of two new members, Kora Healthcare and Athlone Pharmaceuticals. This expansion reinforces MFI’s commitment to strengthening the industry voice and delivering on its mission to champion sustainable healthcare solutions and advocate for policies prioritising patient access and affordability.
This is a significant year for the industry as it prepares for the review of the agreement setting out the pricing and supply arrangements for generic, biosimilar, and value-added medicines. MFI is finalising preparations to enter negotiations with the State on the new Framework Agreement where it will advocate for policies that support early market access, invest in
the sustainability of low-cost medicines, encourage switching to biosimilars, and recognise the financial and human benefits of value-added medicines
Commenting on the expansion, Chair of Medicines for Ireland, Paul Neill said: “We are delighted to welcome Kora Healthcare and Athlone Pharmaceuticals as members of Medicines for Ireland. Both companies have a wealth of expertise that will assist the association as we prepare to enter negotiations on a new Framework Agreement with the State. Our goal is to strengthen the agreement to minimise medicine shortages impacting Irish patients while delivering millions in savings for the State.”
Welcoming MFI’s membership approval, Commercial Director
ROI & ROW at Kora Healthcare, Shane Fitzgerald said: “We are proud to join Medicines for Ireland and stand alongside our peers in advancing the availability of affordable medicines in Ireland through new policies that will safeguard supply. Through collaboration with the State, we can continue to drive advancements that ensure patients have access to the medicines they need when they need them.”
Head of Athlone Pharmaceuticals Limited, Barry Doyle said: “Joining Medicines for Ireland is a significant milestone for Athlone Pharmaceuticals. We look forward to contributing to the association’s efforts to make affordable medicines accessible to patients in Ireland. As an MFI member, we will advocate for policies that bolster
Women in Surgery Fellowship
Ms Lauren V. O’Connell has been announced by RCSI as the recipient of the 2025 PROGRESS Women in Surgery Fellowship.
This prestigious bursary, established to promote female participation in surgical training at Fellowship level is awarded by RCSI.
Ms Lauren V. O’Connell will undertake a Fellowship in advanced colorectal cancer at the Peter MacCallum Cancer Centre in Melbourne, Australia allowing
her to gain international exposure in colorectal cancer surgery and further develop her expertise for the benefit of patients.
Currently a Specialist Registrar in General and Colorectal Surgery at the Mater Misericordiae University Hospital, Ms O’Connell graduated with honours from University College Dublin in 2014. She achieved Fellowship of the Royal College of Surgeons in Ireland (FRCSI) in 2024, receiving the Professor W.A.L. McGowan Medal as the top-performing candidate
in Section 2 FRCS across all RCSI surgical subspecialties.
Committed to surgical education, she has also been awarded the Colm Galvey Educator Award (2019) for excellence in undergraduate teaching and has contributed to RCSI’s MRCS Preparation Course and surgical skills workshops for trainees.
Ms O’Connell has over 35 peer-reviewed publications in leading journals, has authored book chapters and has presented at major international conferences. Her research focuses on early-onset colorectal cancer, functional outcomes postresection, surgical education and minimally invasive techniques.
On receipt of the award, Ms O’Connell commented, “I am delighted to be the 2025 PROGRESS Women in Surgery Fellowship recipient and would like
manufacturing in Europe and call for regulations to be viewed through the lens of securing supply for patients.”
Vice Chair of MFI, Deirdre Kelly said, “The expertise both companies bring will be invaluable as we continue to champion policies that prioritise patient access, affordability, and sustainability across the pharmaceutical sector and wider healthcare system.”
Medicines for Ireland members unanimously approved the applications from KORA Healthcare and Athlone Pharmaceuticals at its February meeting. Their expertise will be crucial as the association enters pivotal negotiations to shape the future of medicine pricing and supply in Ireland.
to thank RCSI for their support. This initiative will allow me to engage fully with the considerable opportunities the fellowship has to offer, developing my skills in pelvic, robotic and cytoreductive surgery for advanced colorectal cancers.”
The PROGRESS Fellowship was introduced to help address the barriers to female progression in surgery and to inspire exceptional female surgical trainees, fostering a more inclusive future in the field.
Now in its sixth year, the fellowship nurtures and develops the expertise and skill base of Irish female surgeons, giving them access to international experience in their chosen fields, acquire additional surgical skills, access new technologies and contribute to the advancement of surgical science and practice on the island of Ireland.
Previous PROGRESS Fellowships recipients are Ms Ailín Rogers (2020), Ms Helen Mohan (2021), Ms Christina Fleming (2022), Ms Evelyn Murphy (2023) and Ms Ola Ahmed (2024).
Find more information about the PROGRESS Women in Surgery Fellowship at https:// www.rcsi.com/surgery/training/ fellowship-opportunities/progresswomen-in-surgery-fellowship
Lauren O'Connell
Role of Pharmacy in Falsified Medicines
Pharmacists in both community and hospital settings are wellpositioned to swiftly detect substandard and falsified (SF) medical products in supply chains, report them to the authorities, and educate and advise affected patients, FIP told the World Health Organisation (WHO) Executive Board in Geneva, Switzerland.
Speaking on behalf of FIP during the agenda item on SF, Tjaša Škerl Rifelj, from the International Pharmaceutical Students' Federation, welcomed the WHO Member State mechanism’s efforts to address SF medical
products and facilitate collaboration among stakeholders. In the statement, FIP highlighted its collaboration with WHO as proof of the critical role pharmacists play in detecting and reporting SF products, underscoring the importance of their involvement in tackling this issue, as well as the positive outcomes resulting from this partnership.
Substandard and falsified (SF) medical products as defined by the World Health Organization, are major threats to public health. Through increasing
globalisation, the problem has expanded in both developed and developing countries.
Pharmacists are key to combatting SF medical products because they are healthcare professionals with direct access to patients. Pharmacists are the gatekeeper for appropriate medication management. Pharmacists are not only necessary to ensure supply of medicines in a proper and just manner, but they also check for unauthorised sales of medicines or medical products that are not of certified quality. As the final
member of the pharmaceutical distribution chain as well as often being supply chain managers, pharmacists are crucial in preventing introduction of SF medical products into the supply chain and in promoting adherence to good distribution practices.
During the Executive Board, FIP is also taking part in joint statements on the health and care workforce, climate change, and health emergencies with the World Health Professions Alliance (WHPA) and members of the Health Stakeholder Network (HSN).
Excellent Rating for St Vincent’s University Hospital
St. Vincent’s University Hospital (SVUH) has been awarded an Excellent rating in the prestigious ERN-LUNG Member Activity Performance Tool (LUNG-MAP) survey, solidifying its position as a leader in rare and complex lung disease care across Europe.
As an expert centre for rare lung disease, SVUH has been recognised as one of the leading and highest-performing centres in Europe, rated Excellent by the European Reference Network. SVUH was proud to share this recognition on Rare Disease Day, a global initiative dedicated to raising awareness and improving outcomes for people living with rare conditions. This announcement underscores the hospital’s dedication to delivering world-class care for patients with rare lung diseases, ensuring they benefit from cutting-edge treatment and international collaboration.
The European Reference Network for Rare Respiratory Diseases (ERN-LUNG), made up of 88 centres across Europe, assessed healthcare providers across seven key categories, including Network Activities, Academy, CPMS (Clinical Patient Management System), Registry, Publications, Clinical Trial Network (CTN), and Patient-Related Outcomes (PRO). In health centres all over Europe, SVUH emerged as the topperforming hospital, excelling in all seven categories—a testament to its commitment to clinical excellence, research, and patientcentred care.
Professor Michael Keane, Interim CEO of St. Vincent’s
Cormac McCarthy, Associate Professor and Consultant Respiratory Physician at SVUH and members of his team proudly unveil the plaque marking their designation as a ERN-LUNGEuropean Reference Network for Rare Respiratory Diseases Centre of Expertise for Rare and Complex Diseases
University Hospital, welcomed the recognition, said, “This achievement highlights the dedication of our multidisciplinary teams who work tirelessly to improve the diagnosis, treatment, and care of patients with rare and complex lung diseases. As an integral part of ERN-LUNG, SVUH is ensuring that Irish patients benefit from the highest standard of specialised care, supported by cutting-edge research and international collaboration.”
The European Reference Networks (ERNs) are a flagship initiative of the European Union, designed to connect the best medical expertise across Europe and ensure that knowledge travels to the patient, rather than the other way around. With over 6,000 rare diseases affecting up to 36 million people in the EU, ERNs play a critical role in improving access to high-quality care, accelerating diagnosis, and enabling cross-border consultations between medical experts.
Professor Cormac McCarthy, Associate Professor and
Consultant Respiratory Physician at SVUH, highlighted the significance of this achievement: “SVUH’s recognition as the highest-performing centre in ERNLUNG underscores our dedication to rare lung disease research and care. This distinction means that Irish patients are receiving some of the best rare disease treatment in Europe, right here at home. Our participation in ERN-LUNG enables us to engage in pioneering research, access international expertise, and shape the future of rare lung disease treatment, ultimately improving outcomes for our patients.”
SVUH’s participation in ERN-LUNG allows the hospital to access a secure IT platform where complex patient cases can be discussed by expert panels across Europe. This facilitates faster, more accurate diagnoses and ensures patients
receive the most advanced treatments available, without the need to travel abroad.
The hospital’s commitment to rare disease care aligns with the broader national and European strategy to integrate ERNs into healthcare systems, ultimately improving outcomes for patients with rare and complex conditions. SVUH collaborates closely with Mater and Beaumont hospitals in Dublin, further strengthening Ireland’s position in rare disease expertise and care.
As Rare Disease Day 2025 shines a light on the millions of people living with rare diseases, SVUH’s recognition as a centre of excellence serves as a powerful reminder of the importance of collaboration, innovation, and patient-centred care in transforming lives.
New Report on Overprescribing
A multiagency working group has recently published a report “Examining the Overprescribing of Benzodiazepines, Z Drugs and Gabapentinoids in Ireland”.
The report was written and produced by a Working Group established by the Medical Council with representatives from across the health sector. It outlines the key issues identified and recommendations of the Working Group, which was established to review and address overprescribing by doctors of benzodiazepines, z-drugs, and gabapentinoids in Ireland.
The recommendations within the report aim to reduce the initiation and inappropriate prescribing of these medicines in the interests of patient and doctor safety, and to support prescribers.
Key Recommendations of the Working Group:
1. Improved Service Delivery: Increase resources for Primary Care counselling supports and addiction services to reduce the number of people requiring prescriptions for benzodiazepines, z-drugs and gabapentinoids. Additionally, provision of appropriate resourcing of all prescribers to support patients to reduce their consumption of these drugs.
2. Education: Further educational initiatives should be developed for doctors, pharmacists, and the public to increase awareness of the risks associated with benzodiazepine, z-drug and gabapentinoid use. Training and awareness around overprescribing matters should be a focus of pre-registration education and training of all prescribers.
3. Advancing Transparency in Prescribing Practices: The Working Group proposes that a central repository for data, which would be accessible to prescribers, should be established. The purpose of this is to enhance visibility of private prescribing of controlled drugs, to achieve greater accountability and improve prescribing practices, while ensuring data protection obligations are adhered to.
4. Consideration given to including Pregabalin and Gabapentin in the Controlled Drugs List: The Working Group supports the idea of consideration being given to including pregabalin and gabapentin on the controlled drugs list, as has been done in other countries, such as the UK. However, it acknowledges that this alone may not be enough. Additional improved service delivery (Recommendation 1) is also crucial to ensuring this reclassification has the desired impact on prescription rates and adverse impacts of these drugs.
5. Implementation of Recommendations of the Working Group: The successful implementation of these recommendations will require considerable stakeholder involvement across the Irish healthcare system to be effective. The Working Group recommends the establishment of an implementation group to assess progress on the implementation of the recommendations within this Report.
Commenting on the report, Dr Margaret O’Riordan, Chair of the Working Group and member of the Medical Council said, “The publication of this report and its recommendations is a result of
Dr Margaret O’Riordan, Chair of the Working Group and member of the Medical Council with Professor Eamon Keenan, National Clinical Lead, Addiction Services, HSE and Dr Ritz Purcell
over four years’ work involving multiple healthcare stakeholders in Ireland. It is an excellent example of utilising insights gained from a regulatory process, and working with partners to enhance public protection and patient safety.
“While benzodiazepines may have a role in the treatment of a patient on a time-limited basis, caution and strict monitoring are required when they are prescribed, the overprescribing of benzodiazepines, z-drugs, and gabapentinoids is an issue that affects patient safety and has significant implications for public health. Our report highlights the importance of tailored approaches, the significance of services like pain clinics, mental health, and addiction services, as well as the necessity of medicines reconciliation and review in primary and secondary care settings and during care transitions.
“By exploring various practice settings such as hospitals, primary care, and residential care, as well as dissecting patient cohorts (including older individuals, those with drug dependencies, and new patients with anxiety or pain) targeted solutions can be identified.
“It is important to acknowledge that addressing these issues demands a significant time commitment, especially in General Practice. Limited access to counselling and addiction services further strains both patients and health professionals' efforts to address these needs.
“Doctors have a very clear ethical responsibility regarding the safe prescribing of these drugs, as set out in the Medical Council’s Guide to Professional Conduct and Ethics for Registered Medical Practitioners. If any prescriber is
facing challenges in prescribing these medications, we would strongly encourage them to engage with the HSE Addiction Services for support and guidance.
“This working group was established following an increase in serious complaints relating to the overprescribing of benzodiazepines and the publication of this report and its recommendations is an excellent example of utilising insights gained from a regulatory process to work with partners to enhance public protection and patient safety,” concluded Dr O’Riordan.
Professor Eamon Keenan, National Clinical Lead, Addiction Services, HSE said, “The HSE and HSE Addiction Services welcome the publication of this report.
“We see first-hand the impact the inappropriate use of these medicines can have on public health. From a treatment perspective, benzodiazepines were the fourth most common drug causing presentations to Addiction services in 2023, accounting for 1,477 cases.
“These drugs are also implicated in drug related deaths as recorded on our National Drug Related Deaths Index (NDRDI). Over the years 2012 to 2021, there has been a 45% increase in the number of deaths where benzodiazepines have been implicated and deaths where pregabalin has been implicated have risen from 14 in 2013 to 83 in 2021.
“The recommendation in relation to resourcing services is timely and HSE Addiction Services looks forward to working with stakeholders to implement all recommendations set out in the report,” concluded Professor Keenan.
The Working Group included representatives from the Medical Council, Health Services Executive (HSE) (Addiction Services, Primary Care, Primary Care Reimbursement Service (PCRS), Medicine Management Programme (MMP), Nurse and Midwife Medicinal Product Prescribing), Department of Health (DoH) (Medicines, Controlled Drugs & Pharmacy Legislation Unit, National Patient Safety Office & Mental Health Unit), the Pharmaceutical Society of Ireland (PSI), Irish College of General Practitioners (ICGP), Nursing and Midwifery Board of Ireland (NMBI), Health Products Regulatory Authority (HPRA), and College of Psychiatrists of Ireland (CPI).
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Fast and Fairer Access to Medicines
Just last month, the Irish Pharmaceutical Healthcare Association (IPHA) published a position paper on the 2025 Programme for Government Commitments which makes the case for Faster and Fairer Access to Medicines. This paper, which for the first-time measures access to medicines timelines against the Health Act 2013, finds that patients in Ireland continue to wait almost two years to access new life-enhancing medicines. In welcoming commitments by the new Government, IPHA offers a way forward to reform the system and provide patients with the care they deserve.
The Programme for Government states the Government is committed to ensuring that patients have access to new medicines ‘as quickly as possible.’ Faster and fairer access is essential because patients in Ireland are currently not getting the same treatment that is available in
Oliver O’Connor IPHA Chief Executive
other countries or indeed available to private patients here in Ireland. Clinicians often find themselves in the difficult position of not yet being able to prescribe a new medicine which they know could improve the healthcare outcomes for their patients.
According to the IPHA findings, of the 88 IPHA medicines reimbursed from 2022-2024:
• 617 days was the average reimbursement time from medicine application in the Irish system to patient access.
• For the 45 IPHA cancer medicines reimbursed during these three years, the average time before a patient could access the treatment was 694 days.
• Over this period, there were 17 IPHA orphan medicines reimbursed which took 655 days to patient access.
• On average it took 916 days for 44 IPHA medicines needing a full Health Technology Assessment (HTA) to be available to patients in Ireland, for which state processes accounted for approximately 65% of the time or 593 days.
• Of the 88 IPHA medicines reimbursed, it took on average five months from the final price offer being proposed by a company to the State before the medicine reached the patient.
• 86% of medicines reimbursed during the three-year period were in excess of the 180-day timeline outlined in the Health Act 2013.
Based on these figures, it is clear that the reimbursement system needs to be resourced, governed and designed to operate within the legal 180-days timeline set by the Oireachtas in 2013. Operating within this timeframe will speed up access for patients by a year or more. IPHA are not calling for a change to the law but rather reform of the system to ensure all parties involved adhere to the legislation. This can be achieved by incorporating and adopting Five Key Principles of mutual commitments in the Framework Agreement, due for negotiation in 2025.
Collectively, pharmaceutical companies and the HSE, along with Government support, can create a system that delivers fairer and faster access to new medicines, within the Health Act 2013, and provide patients in Ireland with timely access, ‘as quickly as possible’, to the treatment they need.
Speaking ahead of their Annual Conference in Dublin, Oliver O’Connor IPHA Chief Executive said, “A year can make a big
Welcomes Reduction of Medical Negligence Claims
difference in a patient’s life. In the normal course of events, if the Irish system adhered to the legislation, patients in Ireland could access new medicines within a year rather than, on average, nearly two years after an application for reimbursement, and longer for many cancer and rare disease medicines.
“We now have an opportunity, together, to effectively reform the system and meet the goal of faster and fairer access to new medicines for patients in Ireland.
“We welcome positive steps introduced in recent years by the Minister for Health such as the use of ‘indicative timelines’ by the HSE. The Programme for Government commitments to review the medicines reimbursement process and to implement the Mazars Review recommendations further builds upon this recognition that patients in Ireland deserve better.
“A new Framework Agreement on the pricing and supply of medicines between IPHA and the State is due to be negotiated in 2025. IPHA is proposing Five Key Principles of mutual commitments to be included in the Framework Agreement. If adopted, these Principles will improve patient care, allow for more productive partnerships, improve health system functioning and will fulfil the commitments in the Programme for Government for quicker access to new innovative medicines.”
The Irish Hospital Consultants Association has welcome a reduction in the cost and number of Medical Negligence Claims in 2024.
In a statement they said, “The Irish Hospital Consultants Association (IHCA) welcomes the latest data from the State Claims Agency on medical negligence payouts, which underline the ongoing patient safety and financial challenges facing Ireland’s healthcare system.
“The figures reveal that the sum of medical negligence claims paid in 2024 fell by ¤65.4 million compared with the cost of damages paid in 2023, to ¤210.5 million – a reduction of almost 24%.
“While this decrease is welcome, the current estimated outstanding liability of around ¤5 billion could rise by multiples over the next two decades if unchecked. It is also worth noting that a claim may involve payments for damages across a number of years.
“There is scope for further reform of medical negligence in Ireland, and the IHCA is calling for the implementation of the recommendations of the expert group chaired by Prof Rhona Mahony. Its report, published last year, set out a number of recommendations, such as the adoption of pre-action protocols which, if implemented, should see a continuation in the fall in pay outs.
“Reform of the sector would not only reduce the financial and stress burden placed on the individuals involved, but free up significant resources which could be reinvested in long term investment in the Irish health service. The current protracted claims processes are not fit for purpose and are resulting in increased legal costs that are among the highest in the world.
“This year, the IHCA is advocating for a health system that is ‘Built to be Better’, aiming to reduce the incidence of avoidable medical negligence claims, thereby freeing up funds for greater investment in frontline services, and using savings to modernise public hospital infrastructure.
“Medical negligence reform will be a key pillar of the IHCA’s focus this year, and the Association will continue to engage constructively with policymakers and stakeholders to ensure patient safety remains a top priority. The key goal is to reduce the emotional and financial burden placed on both patients and practitioners throughout the public health system.”
GO BEYOND LOWERING LDL-C
ADD ON TO REDUCE CV RISK
When statins* and ezetimibe are not enough, add on once daily oral bempedoic acid earlier, to help your patients go even further.1,2Δ
* Concomitant use with simvastatin >40 mg daily is contraindicated; please refer to the relevant SmPC for more information.1,2
Δ NILEMDO® and NUSTENDI® are indicated in adults with established, or at high risk for, ASCVD to reduce CV risk by lowering LDL-C levels, as an adjunct to correction of other risk factors, who are on maximally-tolerated statins, or statin-intolerant, or statin-contraindicated with or without ezetimibe or not adequately controlled with ezetimibe treatment.1,2
Abbreviated Prescribing Information Refer to Summary of Product Characteristics (SmPC) prior to prescribing.
Presentation: Each Nilemdo film-coated tablet contains 180 mg bempedoic acid. Each Nustendi film-coated tablet contains 180 mg of bempedoic acid and 10 mg of ezetimibe. Indications: Hypercholesterolaemia and mixed dyslipidaemia: Nilemdo/Nustendi are indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to diet: In combination with a statin (Nilemdo: or statin with other lipid-lowering therapies) in patients unable to reach low-density lipoprotein cholesterol (LDL-C) goals with the maximum tolerated dose of a statin; alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant; or for whom a statin is contraindicated (Nustendi: and are unable to reach LDL-C goals with ezetimibe alone). Cardiovascular disease: In adults with established or at high risk for atherosclerotic cardiovascular disease to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors: in patients on a maximum tolerated dose of a statin with or without ezetimibe or; alone in patients who are either statin-intolerant, or for whom a statin is contraindicated (Nustendi: or in patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets with or without statin.) Posology and method of administration: The recommended dose is one tablet of 180 mg Nilemdo or 180 mg/10 mg Nustendi taken once daily, with or without food. Tablet should be swallowed whole. Concomitant simvastatin therapy: When Nilemdo/Nustendi are co-administered with simvastatin, simvastatin dose should be limited to 20 mg daily (or 40 mg daily for patients with severe hypercholesterolaemia and high risk for cardiovascular complications, who have not achieved their treatment goals on lower doses and when the benefits are expected to outweigh the potential risks). Coadministration with bile acid sequestrants: Dosing of Nustendi should occur either at least 2 hours before or at least 4 hours after administration of a bile acid sequestrant.
Paediatric Population: The safety and efficacy of Nilemdo/Nustendi in children aged less than 18 years have not yet been established. Contraindications: Hypersensitivity to the active substance or any of the excipients (see SmPC); pregnancy; breast-feeding; concomitant use with simvastatin > 40 mg daily. When Nustendi is co-administered with statin in patients with active liver disease or unexplained persistent elevations in serum transaminases; when Nustendi is co-administered with a statin, consult the SmPC for that particular statin therapy. Warnings and precautions: Potential risk of myopathy with concomitant statins: Bempedoic acid increases plasma concentrations of statins. Patients receiving Nilemdo and a statin should be monitored for adverse reactions that are associated with high doses of statins. Statins occasionally cause myopathy. In rare cases, myopathy may take the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria and can lead to fatality. In post marketing experience with ezetimibe, very rare cases of myopathy and rhabdomyolysis were reported. Most patients who developed rhabdomyolysis were taking a statin with ezetimibe. Patients receiving Nilemdo/Nustendi and a statin should be advised of the potential increased risk of myopathy and told to report promptly any unexplained muscle pain, tenderness, or weakness. If such symptoms occur, a lower maximum dose of the same statin or an alternative statin, or discontinuation of Nilemdo/Nustendi and initiation of an alternative lipid-lowering therapy should be considered under close monitoring of lipid levels and adverse reactions. If myopathy is confirmed by creatine phosphokinase (CPK) > 10× upper limit of normal (ULN), immediately discontinue Nilemdo/ Nustendi and any statin. Increased serum uric acid: Bempedoic acid may raise serum uric acid due to inhibition of renal tubular OAT2 and may cause or exacerbate hyperuricaemia and precipitate gout in patients with history of gout or predisposed to gout. Discontinue Nilemdo/Nustendi if hyperuricaemia accompanied with symptoms of gout appear. Elevated liver enzymes: Liver function tests should be performed at initiation of therapy. Discontinue Nilemdo/Nustendi if increase in transaminases > 3× ULN
persists. Renal impairment: Additional monitoring for adverse reactions may be warranted in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2) or patients with ESRD on dialysis. Hepatic impairment: Periodic liver function tests should be considered for patients with severe hepatic impairment (Child-Pugh C) taking Nilemdo. Nustendi is not recommended in moderate to severe hepatic impairment (Child-Pugh B and C) due to unknown effects of increased exposure to ezetimibe. Fibrates: If cholelithiasis is suspected in a patient receiving Nustendi and fenofibrate, gallbladder investigations are indicated, and therapy should be discontinued. Ciclosporin: Caution when initiating Nustendi in the setting of ciclosporin. Ciclosporin concentrations should be monitored. Anticoagulants: Appropriately monitor INR if Nustendi is added to warfarin, other coumarin anticoagulants, or fluindione. Contraception measures in women of child-bearing potential: Before initiating treatment in women of child-bearing potential appropriate advice on effective methods of contraception should be provided, and effective contraception initiated. Patients taking oestrogen-based oral contraceptives should be advised to stop Nilemdo/Nustendi before stopping contraceptive measures if planning to become pregnant. Excipients: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take Nilemdo/Nustendi as it contains lactose. Patients at high risk of cardiovascular disease: Evidence for the use of the fixed combination medicinal product of bempedoic acid with ezetimibe in patients at high risk of cardiovascular disease is only available for the lipid-lowering effect in absence of any cardiovascular risk reduction estimation for ezetimibe in primary prevention patients. Driving and use of machines: Nustendi has minor influence on ability to drive and use machines. Dizziness has been reported. Interaction with other medicinal products: Refer to SmPC for full information on interactions. Adverse reactions: Nilemdo: Common (≥ 1/100 to < 1/10): Glomerular filtration rate decreased, anaemia, gout, hyperuricaemia (includes blood uric acid increased), AST increased, pain in extremity. Uncommon (≥ 1/1,000 to < 1/100): weight decreased, haemoglobin decreased, ALT increased, liver function test increased, blood creatinine increased, blood urea increased, Consult Nilemdo SmPC in relation to other adverse reactions. Nustendi: Common (≥ 1/100 to < 1/10): Glomerular filtration rate decreased, anaemia, decreased haemoglobin, hyperuricaemia (includes uric acid increased), decreased appetite, dizziness, headache, hypertension, cough, constipation diarrhoea, abdominal pain, nausea, dry mouth, flatulence, gastritis, liver function test increased (includes liver function test abnormal), back pain, muscle spasms, myalgia, pain in extremity, arthralgia, blood creatinine increased, fatigue, asthenia, gout, AST increased (for bempedoic acid), blood CPK increased. Uncommon (≥ 1/1,000 to < 1/100): weight decreased, ALT increased, blood urea increased, hot flush, dyspepsia, gastrooesophageal reflux disease, AST increased (for ezetimibe), GGT increased, pruritus (with statin), neck pain, muscular weakness (with statin), chest pain, pain, oedema peripheral (with statin). Frequency not known: Thrombocytopaenia, hypersensitivity (including rash, urticaria, anaphylaxis, angio-oedema), depression, paraesthesia (with statin), dyspnoea, pancreatitis, hepatitis, cholelithiasis, cholecystitis, erythema multiform, myopathy / rhabdomyolysis. Consult Nustendi SmPC in relation to other adverse reactions. Legal Classification: POM. Package quantity, marketing authorisation (MA) number: Nilemdo 28 tablets: EU/1/20/1425/002. Nustendi 28 tablets: EU/1/20/1424/002. MA Holder: Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, 81379 Munich, Germany. Further information available on request from Daiichi Sankyo Ireland Ltd. D09 YF97. Telephone: (01) 489 3000. Fax: (01) 489 3033. Email: medinfo@daiichi-sankyo.ie Date of Preparation: December 2024. JOB ID: IE/BEM/12/24/0005.
Healthcare professionals are asked to report any suspected adverse reactions via the HPRA Pharmacovigilance, Website: www.hpra.ie. Adverse events or a product complaint about a Daiichi Sankyo medicine can also be directly reported to Daiichi Sankyo Ireland Ltd. D09 YF97 by telephone: +353 (1) 4893000.
References: 1. NILEMDO®. Summary of Product Characteristics. Available from: https://www.medicines.ie/medicines/nilemdo-180mg-film-coated-tablets-36336/spc [Accessed December 2024]. 2. NUSTENDI®. Summary of Product Characteristics. Available from: https://www.medicines.ie/medicines/nustendi-180mg-10mg-film-coated-tablets-36337/spc [Accessed Date: December 2024] IE/BEM/12/24/0002 | Date of preparation: January 2025
PHOENIX: Nanomedicine for Organ Transplantation Tolerance
Written by Danielle Nicholson, Pintail Limited
The Future of Organ Transplantation: Science, Innovation, and Hope
Every day, thousands of patients across the globe await the lifesaving gift of an organ transplant. For many, it is a race against the clock, as the demand for healthy organs far outstrips the supply.
However, thanks to remarkable advancements in medical research, organ transplantation is undergoing a revolutionary transformation—one that promises to increase availability, enhance success rates, and change lives.
A History of Life-Saving Breakthroughs
Organ transplantation has come a long way since the first successful kidney transplant in 1954. Since then, surgeons have mastered procedures for transplanting kidneys, hearts, lungs, and livers. Today, with improved surgical techniques and sophisticated immunosuppressive medications, the survival rates of people with transplanted organs have never been higher.
Despite these successes, challenges remain, and researchers work tirelessly to overcome them
Transplantation success rates have seen significant improvements in recent years; however, the necessity for lifelong immunosuppression poses challenges. This ongoing treatment
broadly dampens the immune system of organ recipients, which can lead to increased vulnerability to infections and cancer, as well as heightened risks for cardiovascular and metabolic diseases. For instance, in people with kidney transplants, the likelihood of developing cancer rises from 4-5% after five years to 10% after ten years and exceeds 25% after two decades. This situation places physicians in a difficult position, as they must navigate the delicate balance between reducing immunosuppression to lower the risk of these complications while managing the potential for organ rejection and graft failure. There is a pressing need for new therapies that can promote graft tolerance, potentially reducing or even eliminating the need for lifelong immunosuppression. This is fundamentally the aim of the PHOENIX Project.
The PHOENIX Project
The PHOENIX Project aims to develop a novel nano-immunotherapy consisting of nanoparticles coated with a peptide complex coat designed to reprogram the anti-graft immune cells of the patient, converting them through various processes into regulatory cells that promote graft tolerance. This process aims to create a localised tolerant environment around the transplanted organ, or graft while preserving the overall systemic immunity of the
person with the transplant. The research framework of PHOENIX is grounded in peer-reviewed studies1 that have demonstrated the reprogramming of immune cells to alleviate autoimmune diseases.2 The project partners are adapting this technology to reprogram graft-reactive T cells, which are known to attack transplanted organs, and validating these nano-medicines in pre-clinical models of kidney and liver transplantation, thereby establishing a robust foundation for future clinical trials.
PHOENIX is an EU-funded research project coordinated by Professor Giuseppe Remuzzi, MD, director of the Mario Negri Pharmacological Research Institute in Bergamo, Italy. Five partner institutions across four countries are building on a promising foundation to deliver a novel therapy that will have a transformative, positive effect on people with organ transplants and healthcare generally.
Partners in four countries
Italy: Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Spain: Institut D’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
France: Central Hospitalier Universitaire de (CHU) Rennes and INRAE
Ireland: Pintail Limited
Main objectives
PHOENIX presents an innovative approach to nano-immunotherapy, utilising nanoparticles that are coated with specific peptides. These nano-therapies aim to reprogram the recipient's antigraft immune cells into regulatory cells that foster a tolerant environment for the transplanted organ while avoiding the systemic consequences associated with lifelong immunosuppression. Currently, these nano-therapies are in the preclinical validation stage, being tested in kidney and liver transplants to establish strong evidence for forthcoming clinical trials. The primary objective of the PHOENIX Project is to illustrate that these nano-therapies can initiate the formation of immunoregulatory cell networks
within the graft environment and promote transplant tolerance, all without compromising the host's immune responses to cancers, vaccines or infections.
“This next-generation immunotherapy has the potential to transform the lives of millions of people worldwide by minimizing the risks associated with organ transplantation,” comments Professor Giuseppe Remuzzi, MD, Director of the Mario Negri Institute.
Benefits
PHOENIX paves the way for successful organ transplants without the need for lifelong immunosuppression, offering significant advantages to millions of individuals, healthcare systems, and society in general. The innovative nano-therapies will alleviate the challenges faced by organ transplant recipients, minimising the necessity for additional transplants and shortening the waiting periods for new patients. This approach allows patients to steer clear of the negative consequences associated with long-term immunosuppression, leading to longer, higher-quality lives. Additionally, the impact of PHOENIX’s nano-therapies will be profound, easing the financial strain on healthcare systems.
To learn more about the PHOENIX Project, visit our website (www. phoenix.eu) and join us on X, @phoenix_nano, LinkedIn https:// www.linkedin.com/company/ phoenix-horizon-europe/ and Facebook.
Funded by the European Union. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HaDEA). Neither the European Union nor the granting authority can be held responsible for them.
LIXIANA® was developed with the ageing NVAF patient in mind.1,4 By offering a unique combination of clinical1,4,5 and practical2,6 benefits, LIXIANA® may help reduce the complexity in managing stroke prevention in your ageing NVAF patients.2
LIXIANA® is a once-daily DOAC indicated for:
• Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA).2
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.2
References: 1. Giugliano et al. N Engl J Med. 2013;369:2093-2104. 2. LIXIANA® Summary of Product Characteristics. Available at: https://www.medicines.ie. Accessed June 2024. 3. Kirchhof P et al. Int J Cardiol. 2023. 4. Kato ET et al. J Am Heart Assoc 2016;5(5). pii: e003432. 5. Ruff CT et al. Lancet 2015;385(9984):2288-95. 6. Steffel J et al. Eur Heart J 2018;39:1330-1393.
Indications: Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA). Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. Posology and method of administration: NVAF: Recommended dose is 60 mg edoxaban once daily with or without food. Continue therapy long term. VTE: Recommended dose is 60 mg edoxaban once daily with or without food following initial use of parenteral anticoagulant for at least 5 days. These two treatments should not be administered simultaneously, as per SmPC. Short duration of therapy (at least 3 months) should be based on risk profile of the patient. For NVAF and VTE the recommended dose is 30 mg edoxaban once daily in patients with one or more of the following: moderate or severe renal impairment (creatinine clearance (CrCL) 15-50 mL/min); low body weight ≤ 60 kg; concomitant use of the P-glycoprotein (P-gp) inhibitors, ciclosporin, dronedarone, erythromycin, or ketoconazole. The 15 mg dose of edoxaban is not indicated as monotherapy and should only be used during a switch from edoxaban to VKA in certain patients (see SmPC for full details). Edoxaban can be initiated or continued in patients who may require cardioversion. For transoesophageal echocardiogram guided cardioversion in patients not previously treated with anticoagulants, edoxaban should be started at least 2 hours before cardioversion to ensure adequate anticoagulation. Cardioversion should be performed no later than 12 hours after the dose of edoxaban on the day of the procedure. Confirm prior to cardioversion that the patient has taken edoxaban as prescribed. Paediatric population: Edoxaban is not recommended for use in children and adolescents from birth to 18 years of age with confirmed VTE (PE and/or DVT) event as the efficacy has not been established. If a dose of edoxaban is missed, the dose should be taken immediately and then continued once daily on the following day. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Clinically significant active bleeding. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Lesion or condition, if considered to be a significant risk for major bleeding including current or recent gastrointestinal (GI) ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities. Uncontrolled severe hypertension. Concomitant treatment with any other anticoagulants e.g. UFH, low molecular weight heparins, heparin derivatives (fondaparinux, etc.), VKA or DOACs except under specific circumstances of switching oral anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter. Pregnancy and breast-feeding. Special warnings and precautions for use: Haemorrhagic risk: Caution in patients with increased risk of bleeding such as elderly on ASA. Discontinue if severe haemorrhage occurs. The anticoagulant effect of edoxaban cannot be reliably monitored with standard laboratory testing. A specific anticoagulant reversal agent for edoxaban is not available. Haemodialysis does not significantly clear edoxaban. Renal impairment: CrCl should be monitored at the initiation of edoxaban and afterwards when clinically indicated. Not recommended in patients with end stage renal disease or on dialysis. Renal function and NVAF: A trend towards decreasing efficacy with increasing CrCl was observed for edoxaban
IE/EDX/02/24/0006
Date of preparation: August 2024
compared to well-managed warfarin. Edoxaban should only be used in patients with NVAF and high CrCl after a careful benefit risk evaluation. Hepatic impairment: Not recommended in severe hepatic impairment. Caution in mild or moderate hepatic impairment. Caution in patients with elevated liver enzymes (ALT/ AST > 2 x ULN) or total bilirubin ≥ 1.5 x ULN. Perform liver function testing prior to initiation and then periodically monitor for treatment beyond 1 year. Surgery or other interventions: discontinue edoxaban as soon as possible and preferably at least 24 hours before the procedure. If procedure cannot be delayed, the increased risk of bleeding should be weighed against urgency of the procedure. Restart edoxaban as soon as haemostasis achieved. Prosthetic heart valves and moderate to severe mitral stenosis: Not recommended. Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Not recommended. Patients with active cancer: Not recommended in treatment and/or prevention of VTE. Patients with a history of thrombosis diagnosed with antiphospholipid syndrome: DOACs including Edoxaban are not recommended. Drug interactions: Concomitant use of the P-gp inhibitors ciclosporin, dronedarone, erythromycin, or ketoconazole requires edoxaban dose reduction to 30mg. Edoxaban should be used with caution with concomitant P-gp inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, St John’s Wort). Concomitant high dose ASA (325 mg) or chronic NSAIDs is not recommended. Concomitant ASA at doses > 100 mg and < 325 mg should be under medical supervision only. Very limited experience with dual antiplatelet therapy or fibrinolytics. Possibility of increased bleeding risk with concomitant SSRIs or SNRIs. Adverse reactions: Common: anaemia, dizziness, headache, epistaxis, abdominal pain, lower GI haemorrhage, upper GI haemorrhage, oral/pharyngeal haemorrhage, nausea, blood bilirubin increased, gamma GT increased, cutaneous soft tissue haemorrhage, rash, pruritus, macroscopic haematuria/urethral haemorrhage, vaginal haemorrhage, puncture site haemorrhage, liver function test abnormal. Serious uncommon: thrombocytopenia, hypersensitivity, intracranial haemorrhage (ICH), intraocular haemorrhage, other haemorrhage, haemoptysis, surgical site haemorrhage, Conjunctival/scleral haemorrhage, Blood alkaline phosphatase increased, Transaminases increased, Urticaria. Serious rare: anaphylactic reaction, allergic oedema, subarachnoid haemorrhage, pericardial haemorrhage, retroperitoneal haemorrhage, intramuscular haemorrhage (no compartment syndrome), intra-articular haemorrhage, subdural haemorrhage, procedural haemorrhage. Serious unknown: anticoagulant-related nephropathy. Prescribers should refer to the SmPC in relation to full side effect information. Legal category: POM Package quantities: 60mg / 30mg – 28 tablets. 15mg – 10 tablets. Marketing Authorisation (MA) number: EU/1/15/993/018, EU/1/15/993/005, EU/1/15/993/001 MA holder: Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, 81379 Munich, Germany. Additional Information: Available on request from Daiichi Sankyo Ireland Ltd. Telephone: (01) 489 3000. Fax: (01) 489 3033. Email: medinfo@daiichi-sankyo.ie. Date of preparation: February 2024 IE/EDX/02/24/0002. Adverse events and product complaints should be reported. To report an adverse event or a product complaint about a Daiichi Sankyo medicine, please call Daiichi Sankyo Ireland Ltd. on (01) 4893000. Healthcare professionals can also report any suspected adverse reactions to Daiichi Sankyo medicines to the HPRA (www.hpra.ie).
Calls for Establishment of Regulator to Oversee AI in Healthcare
A Citizens’ Jury on the Use of Artificial Intelligence (AI) in Healthcare has published its verdict, setting out a series of 25 recommendations for health policy-makers on the safe, ethical and inclusive use of AI in Ireland’s healthcare system. The jury has also written an Open Letter to the Minister for Health and to the Minister for Enterprise, Tourism and Employment, setting out the need for an independent regulator and commissioner to oversee AI, alongside a national strategy to chart the course of AI in healthcare over the next five years.
Organised by IPPOSI—the Irish Platform for Patient Organisations, Science and Industry—the jury of 24 individuals, representative of the population of Ireland, convened from September to December 2024 to offer the public’s perspective on this complex topic.
Need for Statutory Regulator & Independent Commissioner
Jurors endorsed the early, lowrisk deployment of high-quality, human-monitored AI tools in helping alleviate pressures on the healthcare system, in pioneering advances in treatment and care, and in empowering individuals to take a more active role in their own health.
However, in so doing, the jury emphasised the need for strong regulation, transparent oversight and robust data security. In this regard, one of the key recommendations agreed by the jury to build public trust in AI is for the establishment of a statutory regulator to oversee the use of AI in healthcare. This body would be responsible for developing and enforcing standards for those using AI, including its licensing, data governance, and monitoring, as well as imposing penalties for breaches. It would also publish compliance reports to advance the development of AI technologies in healthcare that are secure, transparent and accountable.
To complement the work of the regulator, the jury also called for the creation of a separate independent Commissioner for AI in Healthcare to serve as a public interest watchdog and protect patient rights. Their role would be to increase public awareness about how AI is being used in healthcare, make recommendations on the use of individuals’ health data by AI, and independently identify opportunities to strengthen compliance with regulatory standards. The Commissioner would also operate a complaints process for members of the public.
Right to Opt-out
With AI potentially involved in everything from managing waiting lists, to analysing x-rays, to undertaking robotic surgery, the jury emphasised the importance of transparency, patient autonomy and informed consent. While supporting the automatic enrolment of individual health data for training AI, jurors agreed that people must be clearly informed and given the option to opt out. The jury also recommended that patients have the right to be informed when AI is involved in their healthcare and, where feasible, be given the choice to receive diagnosis or treatment without AI involvement.
Among some of the other recommendations were:
• Humans in the Loop—the jury emphasised the importance of human oversight and control over AI-enabled care. While AI can augment and support clinicians, it cannot replace them
• Public education campaign the jury called for a national initiative to communicate to the public about the use of AI across the health system—what it is, what role it plays in care, and how it may involve their personal health data
• National Strategy—the jury suggested that a national strategy detailing the role of AI in healthcare be published by quarter one of 2026, building on the National Artificial Intelligence Strategy published in 2021. This would provide renewed focus on specific ethical and regulatory considerations within the health sector, as well as on stakeholder rights and responsibilities, timelines for implementation, etc.
Professor Richard Greene of University College Cork, a member of the independent Jury Oversight Panel, is an obstetrician and gynaecologist by profession, as well as the HSE’s Chief Clinical Information Officer. With expertise spanning both clinical practice and healthcare technology, he
provides a unique perspective on the role of AI in healthcare: “As a healthcare professional, I welcome the jury’s strong emphasis on keeping humans at the heart of patient care. AI can support us in enhancing decision-making and in delivering better outcomes, but it is an aid to healthcare professionals, not a replacement. To avoid unintended consequences, its use requires continuous oversight, rigorous evaluation, and clear accountability, with humans firmly in the loop.”
For Kim Lennard, a juror from Co. Meath, it is important not only to have regulation and accountability in AI in healthcare but to protect patient rights too.
“As AI becomes a bigger part of healthcare, we need a strong, independent regulator that listens to a wide range of voices and then acts in our interests,” she said. “This body should make sure that AI is used responsibly, ethically, and in a way that truly benefits patients—while holding those who misuse it accountable. But regulation is just one piece of the puzzle. We’re also calling for clear policies and laws to protect patient rights and ensure AI in healthcare meets the needs, values, and expectations of the public.”
Professor Richard Greene, member of the Independent Jury Oversight Panel
The full report of the IPPOSI Citizens’ Jury, including the jury’s Open Letter to the Minister for Health and to the Minister for Enterprise, Tourism and Employment, are available at www.ipposi.ie
Kim Lennard, member of the Citizens' Jury
RAPIDE: Regular and Unplanned Care Adaptive Dashboard for Cross-Border Emergencies
Written by Professor Máire Connolly, University of Galway and Danielle Nicholson, Pintail Limited
Cross-border health emergencies or pandemics can overwhelm health and care services with large numbers of people requiring unplanned care. This results in delays and backlogs to regular (non-pandemic) care leading to unmet clinical needs and poor health outcomes. To mitigate these impacts, healthcare systems must become more resilient and flexible and adapt the delivery of care, including hybrid care for future health emergencies.
RAPIDE is an EU-funded multidisciplinary research project with thirteen partners including the University of Galway coordinated by the Radboud University Medical Center in the Netherlands.
Partners include:
Ireland: University of Galway, Pintail Limited
Netherlands: Radboud University Medical Center, Radboud University, University of Twente, European Forum for Primary Care, National Institute for Public Health and the Environment, HAN University of Applied Sciences
Norway: Norwegian University of Science and Technology
Slovenia: Community Health Centre Ljubljana
Estonia: Proud Engineers
Italy: Accademia Italiana Cure Primarie
Malta: University of Malta
Main aims
The RAPIDE project aims to develop, validate and demonstrate a portfolio of tools to enhance the resilience of healthcare systems during cross border emergencies. RAPIDE’s objectives are to predict regular care needs along the patient pathway and develop hybrid care models for effective patient care.
RAPIDE’s research programme explained
RAPIDE is reviewing and analysing the experience of the COVID-19 pandemic to determine how regular care was impacted, and to identify the interventions and approaches worked best to maintain regular care.
In-depth interviews with healthcare systems managers, clinicians and
GPs in selected EU countries, combined with a rigorous systematic review of the literature, will improve understanding of the impact of health emergencies on regular care. This work will provide valuable input for healthcare policy at national and European levels.
RAPIDE examines how regular (non-pandemic) healthcare was managed during the COVID-19 pandemic across a variety of healthcare settings, including primary care, secondary care, tertiary care, and home-based care in the European context. Modifications to service delivery, workforce strategies, and governance frameworks that supported the continuity of non-pandemic care during the COVID-19 pandemic are examined, as well as the reported impacts and challenges of these modifications on healthcare delivery. It includes findings on adaptations implemented across various health specialities, as well as a detailed exploration of modifications specific to RAPIDE’s three tracer conditions – type 2 diabetes, heart failure, and elective orthopaedic surgeries.
RAPIDE’s participatory research will identify barriers to care among patients including underserved groups and determine how best to maintain regular care during a health emergency. Factors examined including fear of infection in hospitals and primary care facilities, but also a reluctance to place a burden on over-loaded healthcare systems.
Scenario analysis will be performed for operational, tactical and strategic planning. RAPIDE will combine powerful scenarioexploration forecasting models with patient-flow forecasting and resource optimisation tools to curate an effective, adaptive Decision Support System for health system planners and policymakers to use for pandemic preparedness. RAPIDE is also evaluating patient care pathways to explore each constituent component, in terms of cost, location and required competencies. Factors such as urgency, locationspecificity, amenability to relocation, requirements for specific resources, and patient value will be explored, allowing the examination of a variety of optimisation care configurations
and assessing related requirements to inform the development of the RAPIDE logic model.
Using a patient-centred approach, RAPIDE will select the best digital healthcare tools from the published literature and commercial market, which can help us implement our new healthcare logic model. Tools will be co-selected with patients and clinicians for their ability to support virtual, hybrid or community-based delivery of appropriate care, or to enable effective home-based care.
As the RAPIDE approach aims to redefine patient pathways, the input of patients, their carers, hospital clinicians, GPs and community care providers will be essential. Practical, flexible approaches to maintaining usual care during major health crises will be tested in practice, in “living labs”. In the Netherlands, Italy, Slovenia and Malta, scenarios and care models will be developed with healthcare providers and patients and tested in adult patients with chronic conditions or who are undergoing planned elective surgical procedures. The project will also examine how the basic principles of flexible care models can then be translated into the healthcare systems of other European countries.
Using literature findings, lessons from the COVID-19 pandemic, and results from the care optimisation tool, RAPIDE will support the reconfiguration of healthcare services, enabling a blended hospital + community + home care model. To identify and verify effective, acceptable ways to
make our new care configuration a reality, a full-scale demonstration and simulation of the open-access RAPIDE management and hybrid care delivery tools in multiple EU countries will be conducted with key stakeholders.
Prof Máire Connolly, Professor of Global Health and PI of the RAPIDE project at the University of Galway confirmed that “RAPIDE’s long-term goal is for healthcare systems across Europe to utilise novel digital health technologies, models, and approaches to enhance regular non-pandemic care during health emergencies.. RAPIDE's software tools, logical models, care delivery mechanisms and methods, remote care capabilities, patient-empowering technologies, and training resources—co-created with patients and other stakeholders— will facilitate the transition to new models of care. The hybrid care models being developed could also potentially support health care delivery in rural and remote regions in normal situations.”
To learn more about RAPIDE, visit our website (www.rapideproject. eu) and join us on X, https://x.com/ RapideProjectEU and LinkedIn https://www.linkedin.com/ company/rapide-project-eu.
Funded by the European Union. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HaDEA). Neither the European Union nor the granting authority can be held responsible for them.
Vitamin D
Vitamin D Deficiency and Impact on Bone Health
Written by Dr Kevin McCarroll (Consultant Physician & Geriatrician, Bone Health Unit, St James’s Hospital, Dublin and Dr Donal Fitzpatrick (Consultant Physician & Geriatrician, Mater Misericordiae University Hospital, Dublin)
Vitamin D has a crucial role in maintaining normal bone and muscle health, though a significant proportion of the population are deficient. Indeed, in Ireland, 13.1% of the population older than 50 are vitamin D deficient (<30 nmol/l) based on findings from The Irish Longitudinal Study of Ageing (TILDA). In the winter, deficiency affected nearly one in four (24%) with the greatest prevalence (37%) in those aged over 80. Furthermore, about 15% of children and younger Irish adults have been found to be deficient.
Vitamin D is not a nutrient in the traditional sense, but a prohormone that is largely derived from cutaneous synthesis after UVB exposure. However, little or no vitamin D synthesis occurs in Ireland between the months of November and March giving rise to the so-called “vitamin D winter”. Dietary sources are limited and contributing only a small proportion to overall levels, but include fortified foods (milks, breakfast cereals), oily fish and eggs. For this reason, low vitamin D status is particularly common in those with limited sun exposure. A significant prevalence of vitamin D deficiency is observed in individuals with darker skin, who require prolonged sun exposure for adequate synthesis due to the presence of melanin. Notably, a study conducted in Ireland found that 67% of Southeast Asians were deficient in vitamin D.
Vitamin D is required for the adequate absorption of calcium and phosphate from the gut. In deficiency, as little as 10% of calcium is absorbed rising to 40% in those who are vitamin D replete.
This can result in secondary hyperparathyroidism (SHPT), which is associated with bone loss at cortical sites such as the hip, distal radius and humerus. SHPT also blunts the bone density increases in patients with osteoporosis who are on bisphosphonate or denosumab therapy.
A 25-hydroxyvitamin D level of less than 30 nmol/l is generally considered to represent deficiency, can result in SHPT and when severe causes rickets in children and osteomalacia in adults. There is a risk of vitamin D inadequacy when levels are between 30 and 50 nmol/l, which may be deleterious to bone health, though other factors like calcium and phosphate intake interact with vitamin D and play a role. Indeed, higher calcium intake can partially compensate for lower vitamin D status in reducing SHPT. A recent large study of older Irish adults (n=4139) identified that one third with vitamin D deficiency had SHPT, as did nearly 15% with 25(OH)D levels between 30 and 50 nmol/l. This SHPT was associated with lower bone density at the hip consistent with other studies. Based on the same study, it was estimated that 8.5% of Irish adults (aged ≥50 years) may have SHPT in the Winter. In frailer and older adults, this prevalence is likely to be significantly higher. In one study (n=165), nearly one third (30.1%) of Irish patients admitted to hospital with a hip fracture had high parathyroid (PTH) levels due to low vitamin D status.
For patients with low bone density or a diagnosis of osteoporosis, serum 25(OH)D level should be at least ≥50 nmol/l. In about 5-10% with SHPT and 25(OH)D levels
between 50 and 75 nmol/l aiming for a level ≥75 nmol/l is also advised. Indeed, a target level of ≥75 nmol/l is recommended for older adults by some bodies including the American Geriatric Society, particularly for those who are frail and at risk of falls and fractures. Maintaining a 25(OH)D level ≥50 nmol/l is also essential for patients with osteoporosis who are on potent anti-resorptive treatments (e.g. denosumab or zoledronic acid) in order to prevent hypocalcaemia.
In most cases, oral supplementation with 800 to 1,000 IU of cholecalciferol (vitamin D3) daily is sufficient to maintain levels ≥50 nmol/l. However, higher doses may be required if there is poor gut absorption, obesity or liver disease. A variety of vitamin D3 tablets are licensed to treat or prevent deficiency and include daily (800 IU or 1,000 IU), onceweekly (7,000 IU) or once-monthly (25,000 IU). Therapy with 50,000 IU of vitamin D3 once weekly for about 6-8 weeks can be used for more rapid correction of deficiency. More recently, there is the option of supplementing with calcifediol (25 hydroxyvitamin D) which has better gut absorption and results in a faster rise in serum 25(OH)D. This is available as a once monthly (255 mcg) tablet and should be especially considered in those with malabsorption syndromes or significant liver disease.
While the above recommendation applies to adults with low bone density, widespread supplementation of the population is not supported by vitamin D “mega-trials”. However, these included few patients with vitamin D deficiency in whom they were underpowered to examine for differences in fracture rates. However, given the high prevalence of deficiency in the Irish population, a targeted approach has been adopted by the Food Safety Authority of Ireland (FSAI). For fair skinned individuals (aged 12 to 65), daily supplemental vitamin D of 600 IU is recommended during the winter months (end of October to March). For older adults (≥65 years) and individuals with darker skin, supplementation (600 IU daily) is recommended all year round. It is also important to maintain adequate calcium intake for
optimal bone health. In those with low bone density, a calcium intake of up to 1000 mg daily is generally advised (include dietary and supplements). European guidelines also recommend 950 mg daily for adults (≥25 years). Most dietary calcium is derived from dairy products (a portion typically contains 200-250 mg), with three portions recommended per day. However, dairy intake in Irish adults is low at just under two portions daily. Furthermore, the vast majority (97%) of older Irish adults (aged ≥60) in a large study (n=4444) were found to consume less than three dairy portions daily. For those aged ≥65 who consume less than one dairy portion per day, a 500 mg calcium supplement daily is recommended by the FSAI. Combined vitamin D and calcium supplements may have a modest affect in reducing the incidence of hip or any fractures. However, meta-analyses that examined for fracture outcomes also included patients who had adequate calcium intake and vitamin D status. In particular, the benefit of combined supplements appears greatest in those with poorest vitamin D status and lowest dietary calcium intake. In one large study (n=3270) of ambulatory older adults in nursing homes, supplementing with vitamin D and calcium reversed SHPT and fractures rates at the hip by 43% and at non-vertebral sites by 32%. However, not all patients need supplemental calcium, and an individualised approach should be taken. For those with inadequate dietary calcium, supplements can be used to achieve target intake of about 1000 mg daily.
In conclusion, there is a high prevalence of vitamin D deficiency in Ireland which contributes to secondary hyperparathyroidism, bone loss, and fracture risk, especially among older adults and those with limited sun exposure. Achieving a serum 25(OH)D level of at least 50 nmol/L (and ensuring adequate dietary calcium) can mitigate these risks. Addressing vitamin D deficiency is a significant priority at both the public health and individual health levels, requiring targeted interventions to improve awareness and supplementation.
Dr Kevin McCarroll
Dr Donal Fitzpatrick
Dnord (calcifediol) 255 microgram soft capsules
Please refer to the Summary of Product Characteristics (SmPC) for full prescribing information. Further information is available on request.
Presentation: Soft capsule containing 5 mg of ethanol; 22 mg sorbitol (E420) and 1 mg sunset yellow (E110). Orange, oval, soft gelatin capsule, containing a clear, low viscosity and free from particles liquid. Indications: Treatment of vitamin D deficiency (i.e., 25(OH)D levels < 25 nmol/L) in adults. Prevention of vitamin D deficiency in adults with identified risks such as in patients with malabsorption syndrome, chronic kidney disease, mineral and bone disorder (CKD-MBD) or other identified risks. As adjuvant for the specific treatment of osteoporosis in patients with vitamin D deficiency or at risk of vitamin D deficiency. Dosage and administration: Oral administration. Treatment of vitamin D deficiency and prevention of vitamin D deficiency in patients with identified risks: one capsule once a month. As adjuvant for the specific treatment of osteoporosis: one capsule once a month. Higher doses may be necessary in some patients after analytical verification of the extent of the deficiency. In those cases, the maximum dose administered should not exceed one capsule per week. Once plasma levels of 25(OH)D are stabilised within the desired range, treatment should be discontinued, or the frequency of administration lowered. Dnord should not be administered with a daily frequency. The dose, frequency and duration of the treatment will be determined by the prescriber taking into account the plasma levels of 25(OH)D, type and condition of the patient and other comorbidities such as obesity, malabsorption syndrome, treatment with corticosteroids. Dnord is recommended when administration spaced in time is preferred. Serum concentrations of 25(OH)D should be monitored after initiation of the treatment, usually after 3-4 months. The potency of this medicinal product is sometimes expressed in international units. These units are not interchangeable with the units used to express the potency of cholecalciferol (Vitamin D) preparations. Renal impairment, elderly or paediatric patients: Please refer to SmPC. Contraindications: Hypersensitivity to calcifediol or to any of the excipients. Hypercalcemia (serum calcium >2.6 mmol/L), hypercalciuria, calcium lithiasis, hypervitaminosis D. Special warnings and precautions: Hypercalcaemia and hyperphosphataemia: To obtain an adequate clinical response to oral administration of calcifediol, an appropriate dietary calcium intake is also required. Therefore, to control the therapeutic effects, the following parameters should be monitored, in addition to 25(OH)D: serum calcium, phosphorus and alkaline phosphatase as well as urinary calcium and phosphorus in 24 hours. A decrease in serum levels of alkaline phosphatase normally precedes the onset of hypercalcemia. Once parameters are stabilized and the patient is under maintenance treatment, the above-mentioned determinations should be performed regularly, especially for serum levels of 25(OH)D and calcium. Renal impairment: To be administered with caution. Use of this drug in patients with chronic kidney disease should be accompanied by periodic monitoring of serum calcium and phosphorus, and hypercalcemia prevention. Transformation to calcitriol takes place in the kidney; thus, in case of severe renal impairment (creatinine clearance of less than 30 mL/min) a very significant reduction in the pharmacological effects may occur. Heart failure: Special caution is required. The patient’s serum calcium should be monitored constantly, especially in patients on digitalis, because hypercalcaemia may occur and arrhythmias appear. Twice-aweek determinations are recommended at the beginning of treatment. Hypoparathyroidism: 1-alpha-hydroxylase is activated by parathyroid hormone. As a result, in case of parathyroid insufficiency the activity of calcifediol may decrease. Kidney stones: Calcaemia should be monitored since vitamin D increases absorption of calcium and may aggravate the situation. In these patients, supplements of vitamin D should be administered only if the benefits outweigh the risks. Prolonged immobilization: In patients with prolonged immobilization, it may be necessary to reduce the dose in order to avoid hypercalcaemia. Sarcoidosis, tuberculosis, or other granulomatous diseases: To be administered with caution since these conditions lead to a greater sensitivity to the effect of vitamin D as well as to an increase of the risk of adverse effects at doses lower than the recommended dose. It is necessary to monitor serum and urinary calcium concentrations in these patients. Laboratory Tests: Calcifediol may interfere with determination of cholesterol (Zlatkis-Zak method), leading to false increases in serum cholesterol levels. International Units (IU) should not be used for determination of the dose of calcifediol as this could lead to overdosing. Instead, refer to the SmPC for full details on dosing. Interactions: Consult SmPC for detailed information on interactions. Fertility, pregnancy and lactation: Calcifediol is not to be used during pregnancy or breastfeeding. Consult the SmPC for further details. Undesirable effects: Unknown frequency: Hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnoea, rash, localised oedema / local swelling, and erythema), hypercalcaemia and hypercalciuria. The adverse effects related to vitamin D are associated with increased levels of calcium when an excessive intake of vitamin D may occur i.e. associated with overdose or prolonged treatment. The doses of vitamin D analogues required for hypervitaminosis vary considerably from one subject to another. The adverse reactions due to increased levels of calcium can occur initially or at a later stage. Refer to the SmPC for details on symptoms and treatment of overdose. Legal classification: POM. MA numbers: PA23343/001/001. Further information available from: Nordic Pharma Ltd, 4045 Kingswood Road, Citywest Business Park, Co Dublin. Date of Prescribing Information: November 2022. Item code: IE/22/DNO/001-00.
Adverse events should be reported. Reporting forms and information can be found at www.HRPA.ie. Adverse events should also be reported to Nordic Pharma Ireland; info@nordicpharma.ie or +353(0)1 4004141
Date of Preparation: August 2024. Item code: IE-DNO-2400012
Are scientific standards in science under pressure? We present some thoughts about factors that may contribute to bad science in medicine and perhaps elsewhere. These are opinion-based rather than evidence based, but may perhaps generate some discussion. A bibliography is attached. It is appreciated that, to develop this as a paper, specific, referenced examples will be needed.
1. Inadequate training in scientific methods, basic statistics and the principles of logic and evidence based medicine. This is the substrate for all that follows and may be particularly manifest in the plethora of possible treatments during an epidemic and in the pressure to introduce untested treatments in high risk, emotive conditions such as some malignancies. The main question when confronted with these is ‘is there sufficient evidence to warrant a randomised control trial?’.
2. Pressure to publish- if one’s grants and tenure (and
research staff) depend upon publications in high citation journals, the incentives to be flexible in the interpretation of data or even frank fraud must be great. This model is anathema to the concept of an academic institution as a seat of independent learning and scholarship; universities have become big businesses. OK, OK, naive.
3. Maintenance-of-importance-bias. Is it possible that senior persons may occasionally feel pressure to compromise standards, perhaps because of (2), or to sustain their exalted reputation?
4. Financial incentives- look at who funded the project- and who did the analysis.
5. Journal standards. Some previously reputable journals seem to have become prepared to accept suspect papers on fashionable topics, possibly to boost circulation. One example is ‘meta-analyses’ or 'systematic reviews' of fashionable fields such as
Written by Ian M
Graham, Professor of Cardiovascular Medicine, Trinity College Dublin - Co-Chair, ESC Cardiovascular Risk Collaboration
nutrition which are subject to considerable heterogeneity and unpredictable interaction effects. In contrast, drug trials are in general more amenable to this technique.
6. Pressure to review. Journals now require very fast turnaround times and one’s impression is that the standard of reviews has steadily declined. In one’s own field one is sometime staggered at what gets published (examples available from several international journals).
7. Predatory journals (See William Reville’s Irish Time article). Many of us receive many unsolicited invitations per day, often from journals unrelated to our area, and even find ourselves, unasked, on editorial boards. The same applies to endless invitations to conferences that just seem to want a registration fee. (We recently sent a list of conditions of attendance to get rid of endless reminders from a conference on food technology and it was immediately accepted as an oral presentation- ‘please send the registration fee of $899 by return’. It was almost worth going).
8. Artificial intelligence and language processing tools such as Chat GPT: Two recent request for papers on quite complex subjects produced plausible results in about 30 seconds. One needed to be in the field to spot subtle inadequacies. Clearly one should ask for references.
A-I presents opportunities, challenges and substantial threats. It can save much time and avoid errors of omission if used critically. On the other hand, it is likely that journals will be flooded with Chat GPT generated papers that will not in any way reflect the actual knowledge and scholarship of the 'authors'. Efforts to ensure acknowledgement of use of Chat GPT and to analyse and police its use seem to be in their infancy.
Bibliography
Straight and crooked thinking. Robert H Thouless, Pan books, various editions 19301962. Psychologist Thouless
categorises the tricks of debate that we all use at times, be we scientists or politicians.
Teach yourself to think. Edward de Bono, Penguin 1996.
The art of thinking clearly. Rolf Dobelli, Sceptre 2013. Examines cognitive biases.
Bad science. Ben Goldacre, Fourth Estate 2009. Many doctors hate it, but he’s right much more often than he’s wrong. Brilliant on ‘Professor’ Patrick Holford.
Trick or treatment? Simon Singh and Edzard Ernst, Corgi 2009. Dismantles much alternative medicine. But much applies to conventional medicine too.
The tiger that isn’t. Seeing through a world of numbers. Michael Blastland and Andrew Dilnot, Profile books 2008.
Thinking fast and slow. Daniel Kahneman, Penguin 2011. Nobel prize winner on human rationality and irrationality.
Pocket world in figures. Annually from the Economist.
Factfulness. Hans Rosling, Ola Rosling and Anna Rosling Ronnlund, Hodder and Stoughton 2018. Explores our ignorance and misconceptions about basic facts and statistics, and why.
Evidence-based medicine. David L Sackett, W Scott Richardson. William Rosenberg and R Brian Hayes, Churchill Livingstone 1997
The evaluation of trials of therapy. A didactic Guide to nonsense detection. Ian Graham, David Moore, Elaine Kay, Marie-Therese Cooney, Alexandra Dudina, Trinity College Dublin. Irish J Med science 1982, updated frequently in power point format. How and why uncontrolled experience can mislead us. (The original title and that of the current teaching powerpoints, 'a didactic guide to shit detection' was rejected by the editor...)
Humphreys J. Irish Times 21.8.19. “A spotter’s guide to lies, bulls*it and knowledge resistance”. Describes the rise in epistemology based on lies of Trump and Johnson
Reville W. Irish Times 20.9.18. "the dodgy science of wiping your backside; the unverified work in 'predatory' science journals is harming the credibility of the field as a whole".
Presentation: Each spray actuation delivers 27.5mcg of fluticasone furoate. One actuation delivers 8.25mcg of benzalkonium chloride. Indications: Indicated in adults, adolescents and children (6 years and older) for the treatment of the symptoms of allergic rhinitis. Dosage and administration: Intranasal route only. Adults, Adolescents (12 years and over): The recommended starting dose is two spray actuations (27.5mcg of fluticasone furoate per spray actuation) in each nostril once daily (total daily dose, 110mcg). Children (6 to 11 years): The recommended starting dose is one spray actuation (27.5mcg of fluticasone furoate per spray actuation) in each nostril once daily (total daily dose, 55mcg). Children (under 6 years of age): Not recommended for use. Elderly: No dose adjustment required. Renal and Hepatic Impairment: No dose adjustment required. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Precautions and warnings: Systemic effects of nasal corticosteroid may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery. As with all intranasal corticosteroids, the total systemic burden of corticosteroids should be considered whenever other forms of corticosteroid treatment are prescribed concurrently. If there is any reason to believe that adrenal function is impaired, care must be taken when transferring patients from systemic steroid treatment to fluticasone furoate. Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include
Teva Pharmaceuticals Ireland, Digital Office Centre Swords, Suite 101 - 103, Balheary Demesne, Balheary Road, Swords, Co Dublin, K67E5AO, Ireland.
Freephone: 1800 - 201 700 | Email: info@teva.ie
Prescription Only Medicine.
cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. A reduction in growth velocity has been observed in children treated with fluticasone furoate 110mcg/day for one year. Therefore, children should be maintained on the lowest possible efficacious dose which delivers adequate symptom control. It is recommended that the growth of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. Concomitant administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate. Interactions: Fluticasone furoate is rapidly cleared by extensive first pass metabolism mediated by the cytochrome P450 3A4. Based on data with another glucocorticoid (fluticasone propionate), that is metabolised by CYP3A4, co-administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate. Caution is recommended when co-administering fluticasone furoate with potent CYP3A inhibitors including cobicistat-containing products as an increase in the risk of systemic side effects is expected. Co-administration should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side effects, in which case patients should be monitored for systemic corticosteroid side effects. Pregnancy and lactation: Fluticasone furoate should be used in pregnancy only if the benefits to the mother outweigh the potential risks to the foetus or child. Administration of fluticasone furoate to patients who are breast-feeding should only be considered if the expected benefit to the patient is greater than any possible risk to the child. Effects on ability to drive and use machines: no or negligible influence on the ability to drive and use machines. Adverse reactions: Hypersensitivity reactions including anaphylaxis, angioedema. Very Common: Epistaxis. Common: Headache, nasal ulceration, dyspnoea. Consult the Summary of Product Characteristics in relation to other side effects. Overdose: In a bioavailability study, intranasal doses of up to 2640mcg/day were administered over three days with no adverse systemic reactions observed. Acute overdose is unlikely to require any therapy other than observation. Legal category: POM. Marketing Authorisation Number: PA1986/126/001. Marketing Authorisation Holder: Teva B.V., Swensweg 5, 2031GA Haarlem, Netherlands. Job Code: MED-IE-00087. Date of Preparation: October 2024.
Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie.
Adverse events should also be reported to Teva UK Limited on +44 (0) 207 540 7117 or medinfo@tevauk.com
Date of Preparation: January 2025 | Job Code: GEN-IE-00109
Further information is available on request or in the SmPC. Product Information also available on the HPRA website.
Gastroenterology Special Focus: Microbiome
The Forgotten Garden: The Role of Plant-Based Foods in Health and the Microbiome
Written by Dr Lucia Braz, Registered Dietitian, BeyondBMI and Dr Werd Al-Najim, Registered Dietitian, University College Dublin, Prohealth365 Physiotherapy & Nutrition, and BeyondBMI
by ultra-processed foods—items high in refined sugars, unhealthy fats, and additives, yet devoid of essential nutrients and fibre. Their convenience and hyper-palatable nature drive consumption, but the long-term health consequences are severe. The Western diet’s low intake of whole, plantbased foods and its emphasis on processed options are contributing to a host of chronic diseases, including obesity, diabetes, and cardiovascular conditions. However, the less obvious—yet equally critical— impact lies in the disruption of gut microbiome health.
The Microbiome: A Forgotten Ally
In recent decades, Western dietary habits have undergone a seismic shift. Traditional, nutrient-rich plant-based foods have been steadily replaced by ultraprocessed, convenience-driven options. This shift extends far beyond calorie counts, profoundly influencing microbiome health and fuelling the rise of chronic diseases.
For healthcare professionals, understanding the pivotal role of plant-based foods and advocating for their inclusion is not just a dietary recommendation; it is a public health imperative.
The Benefits of Plant-Based Foods
Plant-based foods, including fruits, vegetables, legumes, whole grains, nuts, and seeds, are nutritional powerhouses. Packed with vitamins, minerals, fibre, and phytochemicals, they form the cornerstone of a balanced and healthy diet, promoting longevity and reducing the risk of chronic diseases. These foods confer a multitude of health benefits:
• Nutrient Dense: Plantbased foods provide a broad spectrum of macronutrients, micronutrients, and antioxidants that are not readily available from other food groups. They supply essential vitamins, minerals, fibre, and bioactive
compounds that support cellular function, metabolic health, and disease prevention. Key phytochemicals—such as polyphenols, flavonoids, and carotenoids—play a crucial role in reducing oxidative stress and inflammation, further enhancing overall well-being.
• High Fibre Content: Dietary fibre, unique to plant foods, promotes gut motility, regulates blood sugar levels, and supports weight management.
• Cardiovascular Health: Diets rich in fruits, vegetables, and whole grains are linked to lower cholesterol levels, reduced blood pressure, and decreased risk of heart disease.
• Anti-inflammatory Properties: Phytochemicals, such as flavonoids and carotenoids, have anti-inflammatory effects that protect against chronic diseases.
The Western Diet and Its Downfall
Despite the well-documented benefits of plant-based foods, their consumption is declining in the Western world. Data from national dietary surveys reveal that many individuals fail to meet the recommended five to seven servings of fruits and vegetables per day. Instead, the modern diet is increasingly dominated
The human gut microbiome, a vast ecosystem of trillions of microorganisms, plays a fundamental role in digestion, immune function, and even mood regulation. This microbial community is directly shaped by diet, influencing overall health and disease risk.
Plant-based foods are vital for a healthy microbiome because they:
• Provide Prebiotics: Fibres and resistant starches found in fruits, vegetables, and legumes serve as prebiotics, feeding beneficial gut bacteria.
• Promote Microbial Diversity: Diets rich in plant-based foods foster a diverse microbiome, which is associated with resilience against infections and chronic diseases.
• Supports Short-Chain Fatty Acids (SCFAs) production: When gut bacteria ferment dietary fibre, they produce SCFAs like butyrate, acetate, and propionate. These compounds have antiinflammatory effects, strengthen the gut lining, and regulate immune responses.
Chronic Diseases and the Microbiome Pathway
The decline in plant-based food consumption has far-reaching effects on the microbiome, creating pathways to chronic disease:
• Inflammation: A low-fibre diet starves beneficial gut bacteria, leading to the proliferation of pro-inflammatory microbes. Chronic, low-grade inflammation is a hallmark of conditions like type 2 diabetes and cardiovascular disease.
• Gut Dysbiosis: The imbalance of gut bacteria caused by a processed diet can impair the gut lining’s integrity, leading to increased intestinal permeability or “leaky gut” syndrome. This allows toxins and pathogens to enter the bloodstream, triggering systemic inflammation.
• Metabolic Dysregulation: Dysbiosis can alter how the body processes energy, contributing to insulin resistance and obesity.
Practical ways to cultivate a healthy microbiome through diet include:
Increase Fiber Intake – Aim for at least 30g of fibre daily by incorporating whole grains (e.g., quinoa, oats), legumes (e.g., lentils, chickpeas), and a variety of colourful vegetables, see table 1.
Eat Fermented Foods Daily –Include probiotic-rich foods like yogurt, kefir, sauerkraut, kimchi, or miso to introduce beneficial bacteria and enhance microbial diversity.
Diversify Plant-Based Foods – Rotate different types of fruits, vegetables, nuts, and seeds to encourage a rich and resilient microbiome. Studies show that eating at least 30 different plantbased foods per week leads to greater microbial diversity.
Reduce Ultra-Processed Foods and Artificial Sweeteners – Swap packaged snacks and sugary drinks for whole-food alternatives like homemade hummus with veggie sticks or unsweetened herbal teas.
Ingest Healthy Fats – Incorporate omega-3-rich foods like salmon, walnuts, and flaxseeds, which help reduce inflammation and support gut health.
Limit Red and Processed Meat – Opt for plant-based proteins
Dr Werd Al-Najim
Dr Lucia Braz
Fibre Content of Common Foods
like tofu, tempeh, or beans, which support beneficial gut bacteria without promoting inflammation.
Consume Polyphenol-Rich Foods – Add antioxidant-packed foods like dark chocolate (85%+ cacao), green tea, berries, and extra virgin olive oil to nourish gut microbes.
By making small, sustainable dietary changes, you can actively support a healthier gut microbiome, improving digestion, enhancing immunity, reducing inflammation, and even better mood regulation through the gutbrain axis. Instead of viewing diet as just a source of calories, think of it as a daily tool to cultivate a thriving microbiome that supports long-term health.
microbiome, improving digestion, enhancing immunity, reducing inflammation, and better mood regulation through the gut-brain axis. Instead of viewing diet as just a source calories, think of it as a daily tool to cultivate a thriving microbiome that supports long health.
Fibre Content of Common Foods
(medium, with skin)
Recruiting for 5th-Year Placements NOW!
APPEL (Affiliation for Pharmacy Practice Experiential Learning) is now seeking expressions of interest from pharmacists in community and hospital pharmacy settings who would like to facilitate an experiential learning placement for a final-year pharmacy student in 2026.
If you would like to offer a placement, please email ops@appel.ie now!
In the 5th-year of their M.Pharm programme, students solidify their learning by completing an eightmonth placement in a patientfacing setting before becoming eligible to sit the Professional Registration Examination (PRE) and enter the PSI register. The advantages of facilitating an APPEL placement include:
• Development of your talent pipeline – many students will look to start their career in the organisations where they undertook their placements.
• Continuing Professional Development – Facilitating an APPEL placement provides numerous opportunities for professional development.
• Engagement – participating in the APPEL programme provides you with the opportunity to increase awareness of your pharmacy/organisation among present and future pharmacists.
The next 5th-year placements will run from the 5th of January to the 28th of August 2026. You can confirm your interest in offering a placement by emailing APPEL at ops@appel.ie.
Barrett’s Oesophagus: Diagnosis and Management
Introduction
Oesophageal cancer is the seventh leading cause of cancer mortality worldwide.1 Two major pathological subtypes exist: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Oesophageal adenocarcinoma is the predominant subtype in Europe, North America and Oceania with epidemiological studies in the last decade showing a gradual increase in incidence.2 The focus of this article is Barrett’s oesophagus, an established risk factor for the development of oesophageal adenocarcinoma.
Background
Barrett’s oesophagus (BE), first identified by N. R. Bennett in 1950, is defined as the replacement of squamous epithelium of the distal oesophagus by metaplastic (intestinal-type) epithelium.3 A recent systematic review of risk factors for BE found a prevalence of 0.8% in those without GORD symptoms.4 Prevalence was higher in individuals with known risk factors for BE including family history, male sex, increasing age, GORD and obesity. A positive linear relationship was shown between BE prevalence and the number of risk factors identified, with an increased in prevalence of 1.2 % for each additional risk factor.4
Diagnosis and Surveillance
The diagnosis of Barrett’s oesophagus involves recognition during endoscopy, appropriately targeted biopsies, and histologic confirmation. The Prague criteria are a well-validated and widely accepted system used to diagnose and classify Barrett’s oesophagus at endoscopy. The gold-standard for tissue sampling is the Seattle Protocol, first described in 1993, which consists of four-quadrant biopsies at intervals of every 1–2 cm and separate samples of areas identified by mucosal irregularity along the entire involved segment.
The stepwise progression of Barrett’s metaplasia to highgrade dysplasia and invasive cancer provides an excellent opportunity for screening and surveillance. Screening for BE or oesophageal adenocarcinoma in an unselected population is not currently recommended, however, because of the relatively low risk in the general population.5 The estimated prevalence of BE in a general population is 1-2%, is with an annual risk of progression to high grade dysplasia (HGD) or oesophageal adenocarcinoma of 0.3–0.8%.6, 7 The European Society of Gastrointestinal Endoscopy (ESGE) suggests that, if screening is considered, it should be limited to a select, higher risk population. Similarly, the American College of Gastroenterology (ACG) advocate
Written by E Gibbons, Consultant Gastroenterologist, Letterkenny University Hospital
a single screening endoscopy for individuals with GORD symptoms and three or more risk factors for BE.8
ESGE does advocate for the use of the non-endoscopic cell collection device, Cytosponge by Medtronic, as an alternative to endoscopy for case finding. A recent UK randomised control trial, the Barrett Esophagus Screening Trial 3 (BEST3) showed that the offer of a Cytosponge test was associated with a 10-fold higher rate of diagnosis of BE compared with usual care among a screening population reporting symptoms of reflux disease and taking a PPI.9
Surveillance intervals
Current surveillance intervals for those with confirmed BE are stratified by BE length and dysplasia, as these are both accepted risk factors for disease progression.
For those without dysplasia, ESGE currently recommends a 5 year surveillance gastroscopy for BE with a maximum extent of >1cm and <3cm and a 3 year gastroscopy for BE with a maximum extent of >3cm and <10cm. For patients with an irregular Z-line of < 1 cm, no routine biopsies or endoscopic surveillance are advised.5 Surveillance in those with dysplasia depends on the degree of dysplasia and response to / need for endoscopic eradication therapy. ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient’s life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered.5
Treatment
Chemoprevention
In patients with BE, PPIs are primarily indicated for control of reflux symptoms. There is
however increasing evidence that PPIs may have a chemopreventive effect. In one large meta-analysis which included 12 observational studies with over 150,000 patients, PPI use was associated with a two-fold risk reduction of BE progression to HGD or oesophageal adenocarcinoma.10
Of note, long-term PPI usage has recently garnered interest with regards to potential side effects, including interference in absorption of B12, magnesium and calcium, and enteric infections. These associations have recently been studied in a randomized trial of almost 20,000 patients who received either PPI or placebo and were followed for three years. This trial demonstrated no adverse events associated with three year PPI use, except for a possible increase in risk of enteric infection.11 Based on the available evidence, no recommendation can be made on the optimal PPI dose. ESGE currently recommends double-dose PPI (equivalent to Omeprazole 40 mg twice daily) when undergoing endoscopic treatment, with dose adjustment after this as tolerated.5
Endoscopic therapy
Endoscopic therapy is not currently recommended for those with BE without dysplastic changes.5
For patients with low grade dysplasia (LGD), the risk of progression to high grade dysplasia (HGD) or oesophageal adenocarcinoma is between 9.2 % and 13.4 % per patient per year. A repeat gastroscopy is currently recommended six months after initial confirmation of LGD. If no dysplasia at this six month gastroscopy, the interval can be broadened to one year. ESGE recommends offering endoscopic eradication therapy (EET) to those who have LGD on at least two separate endoscopies. ESGE also recommends EET for BE with confirmed HGD without visible lesions, to prevent progression to invasive cancer. Radiofrequency ablation (RFA) is the ablation method most extensively studied. RFA has proven to be safe and effective in several large prospective randomized and nonrandomized studies.12
ESGE recommends the use of endoscopic mucosal resection (EMR) for visible lesions <20mm with low probability of submucosal invasion (Paris type 0-IIa, 0-IIb) and for larger or multifocal benign (dysplastic) lesions. ESGE suggests the use of endoscopic submucosal dissection (ESD) for lesions suspicious for submucosal invasion (Paris type 0-Is, 0-IIc), for malignant lesions of >20mm, and for lesions in scarred/fibrotic areas. ESGE recommends endoscopic resection as curative treatment for T1a Barrett’s cancer with well/ moderate differentiation and no signs of lymphovascular invasion. It has been shown that the rate of recurrence or metachronous HGD and/ or oesophageal cancer is up to 20–35 % after successful endoscopic resection of focal lesions. As a result of this, most centres follow the two-step strategy of endoscopic resection of all visible lesions, followed by ablation of the remaining BE.
Artificial Intelligence
The ultimate goal of gastroscopy for BE is the detection of early neoplastic changes that are suitable for endoscopic intervention. Guidelines recommend surveillance with high-definition white light endoscopy, virtual and dyeassisted chromoendoscopy and a labour intensive biopsy protocol. Despite well established guidance, a recent meta-analysis of missed oesophageal adenocarcinoma after a diagnosis of BE showed that still about 20% of HGD and oesophageal adenocarcinoma
2. Lin Y, Wang HL, Fang K, Zheng Y, Wu J. International trends in esophageal cancer incidence rates by histological subtype (1990-2012) and prediction of the rates to 2030. Esophagus. 2022;19(4):560-8.
progression to high-grade dysplasia and esophageal adenocarcinoma? An updated meta-analysis. J Cancer Res Clin Oncol. 2021;147(9): 2681-91.
in those with known BE were detected within 1 year from initial diagnosis.13 The use of artificial intelligence as an auxiliary tool has shown potential in detecting oesophageal precancerous lesions and several computer-assisted diagnostic (CADe) systems have been developed to date.14-16 In one pilot study, a convoluted neural network algorithm analysed 458 images and correctly detected early neoplasia with a sensitivity of 96.4%, specificity of 94.2% and accuracy of 94.2% (16). Areas where AI will likely play a role in the diagnosis and management of BE include improving the quality of upper GI endoscopy performed, identifying individuals at risk/ appropriate for screening and as an adjunctive tool for pathologists where great intra-observer variability exists.17
Conclusion
BE remains an important clinical diagnosis as the only recognised precursor for the development of oesophageal adenocarcinoma. In the coming years, a focus on nonendoscopic diagnostic tools and AI systems will likely have a significant impact on BE diagnosis and management.
References
1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63.
3. Barrett NR. Chronic peptic ulcer of the oesophagus and 'oesophagitis'. Br J Surg. 1950;38(150):175-82.
4. Qumseya BJ, Bukannan A, Gendy S, Ahemd Y, Sultan S, Bain P, et al. Systematic review and meta-analysis of prevalence and risk factors for Barrett's esophagus. Gastrointest Endosc. 2019;90(5):707-17.e1.
5. Weusten B, Bisschops R, Dinis-Ribeiro M, di Pietro M, Pech O, Spaander MCW, et al. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2023;55(12): 1124-46.
6. Klaver E, Bureo Gonzalez A, Mostafavi N, MallantHent R, Duits LC, Baak B, et al. Barrett's esophagus surveillance in a prospective Dutch multicenter community-based cohort of 985 patients demonstrates low risk of neoplastic progression. United European Gastroenterol J. 2021;9(8):929-37.
7. Desai TK, Krishnan K, Samala N, Singh J, Cluley J, Perla S, et al. The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett's oesophagus: a meta-analysis. Gut. 2012;61(7):970-6.
8. Shaheen NJ, Falk GW, Iyer PG, Souza RF, Yadlapati RH, Sauer BG, et al. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol. 2022;117(4):559-87.
9. Fitzgerald RC, di Pietro M, O'Donovan M, Maroni R, Muldrew B, Debiram-Beecham I, et al. Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. Lancet. 2020;396(10247): 333-44.
10. Chen Y, Sun C, Wu Y, Chen X, Kailas S, Karadsheh Z, et al. Do proton pump inhibitors prevent Barrett's esophagus
11. Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al. Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Gastroenterology. 2019;157(3):682-91.e2.
12. Wolfson P, Ho KMA, Wilson A, McBain H, Hogan A, Lipman G, et al. Endoscopic eradication therapy for Barrett's esophagus-related neoplasia: a final 10-year report from the UK National HALO Radiofrequency Ablation Registry. Gastrointest Endosc. 2022;96(2):223-33.
13. Visrodia K, Singh S, Krishnamoorthi R, Ahlquist DA, Wang KK, Iyer PG, et al. Magnitude of Missed Esophageal Adenocarcinoma After Barrett's Esophagus Diagnosis: A Systematic Review and Metaanalysis. Gastroenterology. 2016;150(3):599-607.e7; quiz e14-5.
14. Ebigbo A, Mendel R, Probst A, Manzeneder J, Prinz F, de Souza LA, Jr., et al. Real-time use of artificial intelligence in the evaluation of cancer in Barrett's oesophagus. Gut. 69. England2020. p. 615-6.
15. Arribas J, Antonelli G, Frazzoni L, Fuccio L, Ebigbo A, van der Sommen F, et al. Standalone performance of artificial intelligence for upper GI neoplasia: a meta-analysis. Gut. 2020.
16. Hashimoto R, Requa J, Dao T, Ninh A, Tran E, Mai D, et al. Artificial intelligence using convolutional neural networks for real-time detection of early esophageal neoplasia in Barrett's esophagus (with video). Gastrointest Endosc. 2020;91(6):1264-71.e1.
17. Nieuwenhuis EA, van Munster SN, Curvers WL, Weusten B, Alvarez Herrero L, Bogte A, et al. Impact of expert center endoscopic assessment of confirmed low grade dysplasia in Barrett's esophagus diagnosed in community hospitals. Endoscopy. 2022;54(10):936-44.
Liver Disease in Ireland – An Update
Written by Dr Clare Foley, Irish Liver Foundation Research Fellow, Gastroenterology SPR, Mater Misericordiae University Hospital
Chronic liver disease has steadily become one of the leading causes of death worldwide, resulting in an estimated 2 million deaths annually.1 Cirrhosis is the 10th leading cause of death in the United States.2 This piece aims to discuss the main causes of chronic liver disease in Ireland, discuss recent advances in the management of liver disease and highlight some areas of interest for patients and healthcare providers. Although there are many causes of liver disease, the most common aetiological conditions driving chronic liver disease development include alcohol related liver disease, viral hepatitis and increasingly metabolic dysfunction associated steatotic liver disease (MASLD).3 These conditions of course can occur simultaneously and can have a deleterious synergistic effect resulting in increased liver inflammation and development of liver scarring. Internationally the incidence and prevalence of chronic liver disease is increasing significantly, bringing with it significant implications for healthcare systems.4 The natural history of the disease is no different in Ireland and is becoming a significant public health issue that needs urgent action!
Liver inflammation, regardless of cause, results in the development of liver scarring also known as fibrosis. Ongoing inflammation/ liver injury can result in the progression of fibrosis from little to no scarring (stage 1) through to advanced fibrosis/cirrhosis (Stage 4). The complications of advanced cirrhosis include; variceal bleeding, ascites,
encephalopathy and liver cancer/hepatocellular carcinoma (HCC) pose a significant impact on patient morbidity and mortality. These complications result in frequent hospitalisations and significantly impair quality of life and for select patients the only curative option is liver transplantation.
In Ireland the aetiology of chronic liver disease is similar to that of modern western populations. In the late 20th Century alcohol related liver disease and viral hepatitis were the main contributors to cirrhosis development. However, in recent times the prevalence of MASLD, formally known as non-alcoholic fatty liver disease, has increased significantly. A new category of liver disease has been described termed Metabolic/Alcohol related liver disease (Met/ALD) which defines those with MASLD who consume greater amounts of alcohol per week.5
Unfortunately, similar to our neighbours in the United Kingdom, alcohol related liver disease (ARLD) remains the biggest driver of chronic liver disease in this country. In the UK, ARLD resulted in almost 14,000 premature deaths between 2017 and 2019 alone.6 A similar study evaluating ARLD and inpatient hospital admissions in Ireland between 2006 and 2016 demonstrated that deaths from ARLD rose by 29% over the 10-year period.7 ARLD hospital admissions have remained consistently elevated in more recent years, representing just over 50% of inpatient liver disease admissions. ARLD admissions are associated with longer lengths of stay, increased 30-day readmission rates and higher mortality.
The COVID-19 pandemic saw an increase in ARLD admissions and deaths internationally, this was echoed here in Ireland especially between 2020 and 2021.6 Drinking practices changed with an increase seen in at-home alcohol consumption which is felt to have precipitated some
of these ARLD admissions and deaths. This highlights the use of alcohol as a common maladaptive coping strategy worldwide. There are however successful treatment strategies which require multidisciplinary input from liver specialists, general medical physicians, psychiatry and public health. An avenue of development in recent years in Ireland in ARLD includes the implementation of Alcohol care teams in hospital and in the community which are an invaluable resource for patients with alcohol use disorder regardless of their liver disease status.
Ireland is not immune to the global obesity epidemic which has been shown to contribute to many chronic illness such as cardiovascular disease, diabetes mellitus and of course metabolically associated steatotic liver disease.8
MASLD which encompasses metabolic dysfunction associated steatohepatitis (MASH), the silent inflammatory process which drives fibrosis development and cirrhosis progression, is rapidly becoming one of the leading causes of chronic liver disease worldwide. Currently an estimated 30-40% of the world’s population is affected.8, 9 Not only does MASLD related liver cirrhosis pose a risk to patients in the form of decompensation and liver failure there is also a significant association with liver cancer development.8
In an international meta-analysis Thomas et al10 showed that the hepatocellular cancer (HCC) incidence rate was 1.25 per 1000 person-years. The HCC incidence rate was remarkably higher in patients with MASLD with advanced fibrosis or cirrhosis (14.5 per 1000 person-years) than in their counterparts without advanced fibrosis/cirrhosis. Demonstrating that although MASLD without fibrosis has a lower risk of HCC development a risk still remains. Further highlighting the need to act early to manage obesity and reverse MASLD, which is possible.
Successful treatment strategies for MASLD rely predominantly on weight loss. Adoption of the Mediterranean style diet and exercise programmes were the main stay of MASLD management previously but most recently bariatric surgery and certain drugs such as the glucagon-like-peptide 1 (GLP-1) agonists have begun to revolutionise the treatment of MASLD. However accessing these treatments and dietetic support can be increasingly difficult in the public health system in Ireland. This highlights the need for systemic change in order to prevent the potential avalanche of not only advanced liver disease but other health conditions secondary to obesity which could place a significant burden on our healthcare system in the near future.
New treatments in viral hepatitis in the last decade have improved so significantly that a single course of a direct acting antiviral therapy can result in the complete cure of hepatitis C and complete reduction in the risk of developing cirrhosis. These treatments have significantly reduced the need for liver transplantation for decompensated cirrhosis secondary to hepatitis C. Hepatocellular carcinoma (HCC), is a primary liver cancer that occurs as a complication of advanced cirrhosis. Previous treatments for HCC were suboptimal and ultimately a diagnosis of HCC was terminal if the patient was not a candidate for liver transplantation. New interventional radiological procedures, advances in surgical resection techniques, systemic chemotherapies and especially immunotherapies have revolutionised the management of HCC even in patients with decompensated liver disease.
Given the significant constraints that remain on the healthcare system in Ireland, there are limitations that exist in relation to accessing speciality care. With the implementation of the HSE Slainte care model in 2021 more focus has shifted towards disease prevention, identification and community based care. An
example of this model in action includes community based viral hepatitis clinical nurse specialists (CNS) who work closely with general practitioners identifying and treating viral hepatitis C in the community.
Significant advancement in the field of liver disease has occurred in the 21st century. The use of non-invasive markers of fibrosis has radically changed the community management of liver disease and provided referral guidance to general practitioners.
Transient elastography, Fibroscan, is a non-invasive method now widely used to evaluate liver fibrosis and quantify the volume of fatty infiltration. Similarly blood test based scoring systems such as the FIB-4 score are useful in determining whether there is a
significant risk of advanced liver fibrosis which would require further evaluation and specialist input.11 These methods have helped to identify and determine which patients can be managed at a GP/ community level versus those that require hepatology review.
However it must be mentioned that it is not all bad news in relation to liver disease and it’s management in this country. The establishment of the Irish Liver Foundation charity in 2022 has been an excellent source of information and support for patients with chronic liver disease, their families and their healthcare providers. This charity has developed an easily accessible website (www.liverfoundation.ie) and easy to understand patient information leaflets which aim to give patients some autonomy over
their chronic health condition.
The Irish liver foundation also supports liver related research in order to drive improvements in liver related healthcare management in this country.
Similarly, the newly developed Liver Ireland Support Network (LISN) is a not for profit organisation which aims to provide support to patients and their families on the liver transplant journey (www.lisn.ie). This organisation is offering free counselling services for liver transplant patients, providing some holistic care to patients during a very stressful period.
The HSE alcohol programme is also actively engaging and developing strategies which target alcohol related harm. These strategies are crucial in order
to prevent the development of the chronic irreversible alcohol related liver cirrhosis and it’s complications. Online information in relation to alcohol is available through their website and can be a valuable resource for patients and their loved ones. (https://www2. hse.ie/living-well/alcohol/)
Although liver disease in Ireland, especially alcohol related and MASLD, remains a huge burden with significant morbidity and mortality, this author is hopeful that through research and collaboration improvement is possible. We need to work together as a healthcare community to tackle alcohol use disorder and the obesity epidemic nationally.
References available on request
New Therapeutic Solutions for Inflammatory Disorders News
Professor Rosemary O’Connor, Professor of Cell Biology in the School of Biochemistry & Cell Biology, has received ¤1,275,723 for her project entitled 'Exploiting the spatial actions of metabolic and survival factors for therapeutic benefit.'
This research project addresses the Insulin/Insulin-like growth factor (IGF) system, which is essential for normal development, metabolism, and tissue maintenance, but is disrupted in diabetes, cancer, and inflammatory disorders. From a therapeutic perspective, insulin is widely used to treat diabetes, while drugs that block insulin or IGF activity are disappointingly ineffective in cancer. However, some of these drugs originally developed for cancer have been successfully re-purposed to treat Thyroid Eye Disease (TED) by suppressing inflammation associated with this debilitating condition. The project will investigate the basis for this success in TED and test the rationale for this therapy in other inflammatory disorders.
The project will also aim to resolve the previously unanswerable question of how the insulin and IGF-1 receptors that evolved from a common protein and retain many similarities can mediate quite distinct biological outcomes in cells and tissues. The approach to this is made possible by
Professor Aonghus Lavalle and Professor Rosemary O'Connor, recipients of a Research Ireland Frontiers for the Future Programme award
newly available resources and techniques in cellular imaging, incell proteomics and computational protein modelling.
Professor O’Connor said, "This project is at the leading edge of cell signalling research. We aim to define what distinguishes the unique actions of insulin and IGFs in health and disease. It will provide direction for new therapies for inflammatory diseases affecting millions of people."
Opening new avenues for treating Inflammatory Bowel Disease
Professor Aonghus Lavelle, Professor in Clinical Anatomy and Gastroenterologist in the Department of Anatomy & Neuroscience and APC Microbiome Ireland, has received ¤613,556 for his project entitled 'Characterising uncultured bacteria associated with bile acid dysmetabolism and disease severity in IBD.'
Inflammatory bowel disease (IBD), whose main subtypes are ulcerative colitis and Crohn's disease, are important chronic inflammatory condition of the gastrointestinal tract, affecting an estimated 40,000+ people in Ireland. This research project aims to study the role that certain bacteria play in metabolising bile acids in our guts, particularly in people with IBD. Bile acids are special molecules produced by the liver to help with digestion and absorption of dietary fats. Our bodies reabsorb most of these bile acids after the fats have been digested, but some make it into our colon, where bacteria alter them. These altered bile acids (termed 'secondary bile acids') can have a range of important functions related to health and disease. Previous research at UCC
with Professor Harry Sokol’s group in Paris has shown that people with severe IBD have a loss of these secondary bile acids and we have identified a corresponding loss of particular bacteria using gene sequencing techniques that appear to explain these findings. This study is going to recruit people with and without IBD and attempt to culture (or grow) these bacteria from their guts.
Professor Lavalle said, "This project will allow us to determine if these bacteria and the secondary bile acids they produce are important in the disease course of patients with IBD. The goal will then be to establish that re-introducing these bacteria is a viable therapeutic strategy, thus opening up a new avenue for treating IBD."
Gastroenterology Special Focus: Liver Disease
Liver Disease – Public Health Challenge
Written by Dr Omar Elsherif, Consultant Hepatologist, St Vincent’s University Hospital
Mortality from end stage liver disease is high, and a fundamental change in approach at an individual patient level is required to improve outcomes.
Liver disease is a major public health challenge. Anyone involved in acute medicine will fully appreciate the emerging epidemic of liver disease. In contrast to the progress made in improving outcomes in heart disease and stroke, mortality from liver disease has risen dramatically over the past 20 years. Alcohol-related liver disease continues to account for the vast majority of liver related hospital admissions– between 2001 and 2022 alcohol-related liver disease hospital discharges increased by 42%. Patients with alcohol-related liver disease stay in hospital on average three times longer than patients hospitalised for non-alcohol related problems. Alcohol related liver disease accounted for over 45000 hospital bed days in 2022 in Ireland. Epidemiological data on the economic impact of alcohol related liver disease in Ireland is limited. In Northern Ireland, Alcohol related liver disease is now the second
highest contributor to years of working life lost. The mean age of death from alcohol related liver disease is just 57 years.
Addressing the burden of alcoholrelated liver disease requires a multifaceted approach. Firstly, policy change is required to reduce alcohol related harm at a societal level. The implementation of the public health alcohol bill is a positive first step. This has the potential to address the principle modifiable drivers of alcohol related harm – price and availability. The benefits of such an approach have been seen in Scotland where minimum unit pricing (MUP) was introduced in 2018. Although it is too early to appreciate to the full effects of MUP, alcohol-specific death rates have risen more slowly in Scotland compared the rest of the UK since MUP was introduced.
Secondly, there is a pressing need to collect better epidemiological
and geographic data on liver disease related hospital admissions, mortality and access to specialist care. This data is needed for healthcare planning to identify gaps in care to improve outcomes for patients with liver disease. Networks and referral pathways to specialist care can be developed to align with newly established regional hospital groups. For example, Comprehensive multidisciplinary specialist cirrhosis care clinics have been shown to have a big impact on survival in patients with cirrhosis (53% relative risk reduction in 1 year mortality). There is also an opportunity to provide better integrated care to bridge the gap between primary and secondary care for patients with liver disease as part of the slaintecare strategy. We have good examples of where such a data driven approach has worked. The reconfiguration of stroke care and the resultant stepwise improvement in patient outcomes following stroke was catalysed by data from the first national stroke audit (2005-2008). Quality improvement initiatives for patients with liver disease can learn from this model of data driven quality improvement.
Mortality from end stage liver disease is high, and a fundamental change in approach at an individual patient level is also required to improve outcomes. This requires embracing simple methods for early identification of liver fibrosis coupled with disease prevention strategies. Liver disease is just one of the clinical manifestations of harmful alcohol use. Patients with harmful levels of alcohol use have frequent contact with healthcare professionals before liver disease becomes clinically apparent. Obtaining a screening alcohol history in every acute medical admission provides an opportunity to deliver brief alcohol interventions. The AUDIT (alcohol use disorder inventory tool) questionnaire remains the gold standard as a screening instrument. However, it is impractical to use it in all patients admitted through the emergency department. One proposed “pre-screening” technique is to use question 3 of the AUDIT questionnaire (“how often do you
have 5 or more drinks on one occasion?”) followed by the full questionnaire if this is positive. Pharmacotherapy is underutilised in the management of patients with alcohol use disorder, and many patients would potentially benefit from its more widespread use. Drugs such as acamprosate, naltrexone and baclofen are effective as an adjunct to psychosocial therapy to maintain alcohol abstinence. Low dose baclofen can also be used to patients with cirrhosis and hepatic impairment.
Liver transplant remains a lifesaving option in a selected group patients with advanced liver disease who can a transplant survival benefit. Patients with complications of decompensated cirrhosis (i.e. recurrent ascites, hepatic encephalopathy, or variceal bleeding) have high mortality in the absence of an aetiological treatment for the underlying liver disease. Median survival in this group is less than 2 years in the absence of liver transplant. Early discussion with a liver transplant unit is advised before patient’s physical function deteriorates as their liver disease progresses. Organ donation rates have declined across the world following the COVID pandemic and Ireland is not immune to this trend. There is a pressing need to increase organ donation awareness as well as expanding the donor organ pool by using more extended criteria donors and donors after circulatory death. Noval technology such normothermic machine perfusion for donor organs to assess organ viability has revolutionised transplantation. Finally, as a society we need to address the stigma around alcohol related disease. One small step is to avoid stigmatising terms such as “alcoholic”. Stigma results in discrimination, a reduction in health seeking behaviour and reduced alcohol of resources. A consensus statement from the four largest global liver societies have strongly advocated for a change in medical terminology replacing the term “alcoholic” with “alcoholrelated” or “alcohol associated” (i.e. alcohol related hepatitis or alcohol related cirrhosis).
27 Gastroenterology Special Focus: Obesity
The New Lancet Commission Definition of Obesity
Written
by Dr. Faisal I. Almohaileb1, 2 and Professor Carel le Roux2
1Diabetes
Complications Research Centre, Conway Institute, University College Dublin
2College of Medicine, Family and Community Medicine Department, Qassim University
Introduction
Obesity has historically been diagnosed using the Body Mass Index (BMI), a simplified tool for a complex disease that does not consider individual metabolic, cardiovascular, functional, or mental health variations. The Lancet Commission's new obesity classification, was informed by 60 world experts including three Irish experts, Professor Edward Gregg, Professor Carel le Roux, and Vicky Mooney. The Irish Society for Clinical Nutrition and Metabolism (IrSPEN) also endorsed the findings which redefines obesity into Pre-Clinical Obesity and Clinical Obesity. This distinction aims to improve precision in diagnosis and management by shifting the focus from individual weight on the scale to overall health status.
Defining
Clinical and Preclinical Obesity
The core differentiation between the two types of obesity lies in the presence or absence of organ dysfunction rather than absolute weight or BMI.
1. Clinical Obesity is defined when excess adiposity actively impairs organ function, leading to metabolic, cardiovascular, or mechanical complications. These include 18 specifically defined obesity related complications such as hypertension, obstructive sleep apnea, metabolic-associated fatty liver disease (MAFLD), and osteoarthritis.
2. Preclinical Obesity describes individuals with excess adipose tissue who do not yet have organ dysfunction but are at increased risk of progressing to clinical obesity. These individuals may exhibit early warning signs such as insulin resistance, visceral fat accumulation, endothelial dysfunction, or chronic inflammation, the precursors to future disease progression.
While widely used, BMI fails to distinguish between fat and lean mass, assess adipose tissue distribution, or predict metabolic dysfunction. As a result, individuals with a high BMI with no organ dysfunction may be misclassified, whereas those with significant visceral fat at a lower BMI but with organ dysfunction may be overlooked.
The new framework is a multifaceted diagnostic approach:
• Adiposity is not only measured by BMI but also requires thresholds to be met using waist circumference, wait-to hip ratio, waist-to-height ratio, or imagingbased fat quantification.
• Organ function analysis includes liver function tests, inflammatory markers, and cardiovascular risk stratification.
The Look AHEAD and DiRECT trials demonstrated that structured lifestyle interventions can effectively treat patients with clinical obesity who have type 2 diabetes, emphasizing the importance of timely intervention in those with established organ dysfunction. Pharmacologic advances such as semaglutide and tirzepatide, have demonstrated substantial weight loss alongside improvements in organ function, as evidenced by the STEP and SURMOUNT trials. Medications are currently licenced to treat both patients with clinical obesity and preclinical obesity because the evidence supports the idea of preventing patients with preclinical obesity progressing to clinical obesity as well as patients with clinical obesity reverting to preclinical obesity.
In both clinical obesity and preclinical obesity, treatment is often enhanced by multidisciplinary and combining interventions. These approaches can include lifestyle changes, pharmacotherapy, and bariatric surgery. In preclinical obesity, the urgency of the intervention may be
Dr. Faisal I. Almohaileb
less because the goal is to halt the progression of organ dysfunction by addressing modifiable risk factors early.
On a broader scale, public health strategies require better evidence to prove pre clinical obesity and clinical obesity can be prevented. Current strategies, including taxation on processed foods, enhanced urban infrastructure to promote active lifestyles, and targeted educational initiatives to raise awareness about obesity have thus far not impacted the incidence of obesity, but more evidence of the effectiveness of these strategies are awaited.
The reclassification of obesity provides a roadmap to stratify the disease of obesity. It allows healthcare providers to focus on obesity related complications and not only BMI. The reclassification also underscores the necessity of shifting research focus and clinical focus from weight loss to health gain as optimal markers of success.
This refined classification should be integrated into clinical guidelines worldwide, bridging the gap between obesity diagnosis and precision medicine. The future of obesity care lies in early identification, phenotyping, and
Professor Carel Le Roux
personalised interventions, ensuring that treatment is tailored to the patient’s specific needs rather than a one-size-fits-all approach.
In conclusion, the Lancet Commission’s reclassification of obesity marks a shift in obesity medicine, transitioning from weightbased metrics to an organ function approach. By differentiating between clinical and preclinical obesity, this framework enables earlier interventions, supports personalised treatment strategies, and enhances patient outcomes. As its adoption grows within the medical community, it has the potential to redefine global obesity management and inform more effective public health policies.
References
• Gregg EW, et al. (2012). Look AHEAD trial. N Engl J Med. 366:1209-1217.
• Lean ME, et al. (2018). DiRECT trial. Lancet. 391(10120): 541-551.
• Wilding JP, et al. (2021). STEP trials. N Engl J Med. 384:989-1002.
• Jastreboff AM, et al. (2022). SURMOUNT-1 trial. N Engl J Med. 387(3):205-216.
Endocrinology Focus: Type 2 Diabetes
The Evolution of Weight Loss Drugs: Implications for Type 2 Diabetes
Written by Morgan Reid and Dr Christopher Shannon - Diabetes Complications Research Centre, UCD
Type 2 diabetes (T2D) is a progressive metabolic disorder characterized by insulin resistance, beta-cell dysfunction, and chronic hyperglycaemia with significant risk of renal and / or cardiovascular complications. Given the close relationship between T2D and obesity, weight reduction has long been recognized as a key goal for patients with T2D. Although weight loss of 10-15% is associated with improved insulin sensitivity and glycaemic control, traditional approaches to weight management (i.e. diet and exercise) typically do not achieve durable weight reduction. Indeed, only 1 in 5 individuals with overweight or obesity are successful in sustaining >10% weight loss long-term with lifestyle interventions alone. Importantly, weight regain is paralleled by declines in glycaemic control and T2D progression.
In the past two decades, the development of the glucagonlike peptide-1 (GLP-1) receptor agonists has reshaped the therapeutic landscape of chronic weight management and cardiometabolic diseases, including T2D. These drugs elicit greater weight loss than is achieved by lifestyle intervention alone and lead to wide-ranging cardiometabolic benefits. In this article, we discuss what the rapid evolution of these drugs means for patients with T2D.
Clinical development and efficacy of GLP-1 receptor agonists
GLP-1 receptor agonists (GLP-1 RA) mimic endogenous GLP-1, an incretin hormone that enhances glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying, and promotes satiety via central appetite regulation. Although now widely recognised for their efficacy as weight loss drugs, the first GLP-1RA (Exenatide from Eli Lilly) was initially approved in 2005 as a twice daily injectable for T2D. It wasn’t for another ten years that
the daily injectable Liraglutide (Novo Nordisk) was approved for the treatment of obesity. The continued development of this drug class has led to the approval of numerous once-weekly injectable, and one daily oral, GLP-1RAs for patients with T2D. Further innovation in GLP-1 based therapies led to the approval of Tirzepatide (Eli Lilly), a dual glucose-dependent insulinotropic (GIP)/GLP-1 receptor co-agonist, for both T2D and obesity.
Data from multiple large phase three clinical trial series have demonstrated that GLP-1RA reduce HbA1c by 0.9-1.8% in patients with T2D, depending on the agent and dose used. Interestingly, body weight reduction with GLP-1RA treatment is typically lower in patients with obesity and T2D (5-10% weight loss), versus individuals without T2D (~15% weight loss). Notably, dual targeting of GLP-1R and GIPR receptors with Tirzepatide appears even more effective for glycaemic control and weight reduction versus single peptide treatments. Beyond glycaemic control and weight loss, GLP-1RAs have also been shown to reduce the risk of cardiovascular death, stroke, myocardial infarction, and kidney disease in patients with T2D and/or obesity. Clinical trials investigating the efficacy of GLP1RA against metabolic-dysfunction associated steatohepatitis (MASH), peripheral arterial disease, Alzheimer’s and Parkinsons are also ongoing.
Drawbacks of incretin-based therapies
Despite their significant benefits, incretin-based therapies are not without limitations. The most common adverse events include gastrointestinal issues such as nausea and vomiting, which can negatively impact adherence. A related concern is the requirement for sustained therapy, since, as with most weight loss modalities, treatment withdrawal leads to weight regain and rebound risk of
disease progression. Moreover, 25-40% of the weight lost with GLP-1RA treatments is lean mass rather than fat mass. Whilst the functional implications of this are currently unclear, reductions in lean mass are closely associated with decreased energy expenditure and thus likely contribute to the drive for weight regain if treatment is stopped. A major component of lean mass is skeletal muscle, which is especially important for glucose metabolism, mobility and overall metabolic health. The longterm consequences of lean tissue reduction with GLP-1RA therapy in patients with T2D therefore require further investigation, particularly in populations vulnerable to sarcopenia, such as older adults or individuals with pre-existing muscle loss.
Finally, the availability and affordability of newer drugs remain significant barriers, with many healthcare systems and insurance providers offering limited coverage for obesity pharmacotherapy. This raises questions about the feasibility and equitability of the lifelong treatment paradigm needed for continued metabolic benefits. Addressing these challenges will be critical in optimizing the widespread clinical adoption of incretin-based therapies.
Unanswered questions and future directions
Despite the success of incretinbased therapies, there are still important gaps in our understanding. One pressing question is whether preserving lean mass during GLP-1RA treatment could improve outcomes in T2D. Since skeletal muscle is essential for glucose uptake and overall metabolic health, strategies that protect muscle mass during weight loss may further enhance long-term benefits, particularly in high-risk populations (e.g. sarcopenia). Several musclepreserving compounds are currently under investigation with GLP-1RA as potential combination
therapies, including agents targeting the activin and apelin signalling pathways.
The introduction of Semaglutide and Tirzepatide has already prompted shifts in treatment paradigms, with the American Diabetes Association guidelines now prioritizing these agents for weight loss and glycaemic goals in patients with T2D. Looking ahead, several new therapies are in development, potentially pushing the boundaries of metabolic treatment even further. For example, Retatrutide (Eli Lilly) is a triple agonist that targets the GLP-1, GIP, and glucagon receptors, and has shown early promise for even greater weight loss and metabolic improvements than Tirzepatide. Meanwhile, Amgen’s investigational oncemonthly injectable drug MariTide has shown significant promise in Phase two trials, resulting in 17% weight loss and a 2.2% drop in HbA1c in patients in T2D. Paradoxically, this drug combines a GLP-1RA with a GIP antagonist, highlighting that our understanding of incretin biology is still evolving.
As newer therapies continue to emerge, and our understanding of patient responses expands, it may become possible to refine treatment strategies based on individual metabolic phenotypes or genotypes. Future research should focus on personalized medicine approaches, optimizing drug selection for different patient subgroups to maximize efficacy while minimizing side effects. As the field continues to evolve, the next generation of metabolic therapies may not only improve glycaemic control but also address broader aspects of body composition and long-term metabolic health. For healthcare professionals, staying informed about these developments is crucial for optimizing treatment decisions and ensuring that patients with T2D receive the most effective and individualized care possible.
60 Second Summary
Respiratory syncytial virus (RSV) remains a leading cause worldwide of acute lower respiratory tract illness (LRTI) among children under 5 years of age with the highest burden occurring within the first 6 months of life.
With the availability of RSVpreF vaccines, quantification of health benefits is essential to inform vaccination strategies. In this study, we developed an individualbased simulation model of RSV transmission dynamics with vaccination to estimate the number of RSV-related hospitalizations and deaths averted among infants and adults aged 60 years or older in 13 high-income countries from different regions across the world, including the United States, Canada, United Kingdom, Germany, France, Italy, the Netherlands, Sweden, Spain, Ireland, Israel, Japan and Australia.
In alignment with previous studies, our analysis demonstrates the potential for substantial health benefits from RSVpreF vaccines, assuming high vaccination uptake rates. However, uptake rates will depend on various factors such as vaccine acceptability, out-ofpocket costs for receiving RSV vaccines, the inclusion of eligible population groups in publicly funded programs and specific recommendations for program implementation in different countries, which are influenced by cost-effectiveness evaluations of these vaccines.
Given the recent introduction of RSV vaccines in 2023, there is limited real-world experience with vaccine program implementation. Although we used country-specific influenza vaccination coverage in our baseline analysis, recent estimates indicate a substantially lower uptake of RSVpreF vaccines during the 2023–2024 season. Addressing vaccine hesitancy, awareness and accessibility should improve uptake rates, thereby enhancing the impact of RSV vaccination campaigns.
AUTHORS: Zhanwei Du, Abhishek Pandey, Seyed M. Moghadas, Yuan Bai, Lin Wang, Laura Matrajt, Burton H. Singer & Alison P. Galvani
1. REFLECT - Before reading this module, consider the following: Will this clinical area be relevant to my practice?
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.
3. PLAN - If I have identified a
knowledge gap - will this article satisfy those needs - or will more reading be required?
4. EVALUATE - Did this article meet my learning needs - and how has my practise changed as a result? Have I identified further learning needs?
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.
Impact of RSVpreF vaccination on reducing the burden of respiratory syncytial virus in infants and older adults
Respiratory syncytial virus (RSV) remains a leading cause worldwide of acute lower respiratory tract illness (LRTI) among children under 5 years of age1,2, with the highest burden occurring within the first 6 months of life.3 Up to 2% of young children in high-income countries are hospitalised for the management of RSV-associated illnesses, including bronchiolitis, pneumonia, apnea and difficulty in feeding.4,5 RSV can also cause serious illness in older adults, especially among those with comorbidities and risk factors,6 often leading to severe outcomes and hospitalisation. A metaanalysis of high-income countries reported a case-fatality rate of 7% in older adults admitted with RSVassociated LRTI7. The burden of RSV has been comparable to that of seasonal influenza among older adults,8 resulting in substantial short- and long-term healthcare costs and productivity losses.9,10,11,12
Despite continuous efforts to develop RSV vaccines since the 1960s, no vaccine was sufficiently promising to enter phase 3 clinical trials until recently. Historically,
RSV prevention among infants has relied on palivizumab, an expensive, short-term monoclonal antibody administered in five monthly doses to high-risk infants each RSV season.13 Leveraging advances in structure-based vaccinology, the most immunogenic epitopes and conformations were identified to inform the design of vaccines and long-acting monoclonal antibodies.14 Notably, a protein-based vaccine (Abrysvo) is now available to immunise pregnant women between 32 and 36 weeks of gestational age to protect infants through the first 90 days of life after birth.15 In addition, Prefusion F protein-based (RSVpreF) vaccines (Abrysvo and Arexvy) have become available for the prevention of RSV disease in older adults.16,17 Alongside these vaccines, a long-acting monoclonal antibody (nirsevimab) is approved for infant immunisation against RSV-related LRTI in several countries.18,19 Although nirsevimab provides direct, nonactive protection for infants, the lower costs of RSVpreF vaccination20 may provide a more affordable strategy for reducing
disease burden in older adults, pregnant women and infants.
With the availability of RSVpreF vaccines, quantification of health benefits is essential to inform vaccination strategies.12,21 In this study, we developed an individual-based simulation model of RSV transmission dynamics with vaccination to estimate the number of RSV-related hospitalisations and deaths averted among infants and adults aged 60 years or older in 13 highincome countries from different regions across the world, including the United States, Canada, United Kingdom, Germany, France, Italy, the Netherlands, Sweden, Spain, Ireland, Israel, Japan and Australia. We considered vaccine efficacy against severe outcomes (that is, preventing hospitalisation), but assumed no vaccine-induced protection against infection or transmission. Incorporating country-specific demographics, age-dependent contact patterns and estimates of disease burden, we simulated the model with influenza-like vaccination uptake rates to provide a multinational
Reduction in RSV-related hospitalisation (%)
Fig 1: a,b, Estimated reduction in older adults (a) and infants (b). Error bars represent median values and 95% UR of 500 stochastic simulations with vaccination of older adults (a) and pregnant women (b)
perspective on the impact of RSVpreF vaccination programs in these countries. Using model estimates for each country, we further calculated the direct costs of RSV-related hospitalisations and the years of life lost (YLL) averted by vaccination.
Results
We estimated the effective reproduction number, Re (that is, the average number of secondary infections generated by an RSV case), using weekly positivity rates reported for the 2018–2019 RSV seasons across the countries studied here. Australia showed the lowest mean Re value at 1.29, while Germany exhibited the highest at 1.99. Calibrating the transmission dynamic model to country-specific Re values (Extended Data Fig. 1), we ran stochastic simulations to project the total number of hospitalisations and deaths in the absence of vaccination as the baseline scenario.
Without vaccination, the annual burden of RSV varied substantially
across the 13 countries studied, with hospitalisations ranging from a median of 27.9 (95% uncertainty range (UR): 27.0–28.7) per 100,000 older adults in Israel to 214.0 (95% UR: 204.7–222.1) in the United States. Similarly, RSV-related mortality per 100,000 population of older adults varied from a median of 1.8 (95% UR: 1.7–1.8) in Israel to 20.8 (95% UR: 19.9–21.7) in Canada.
Among the infant population, Ireland had the lowest estimated hospitalisation rate, with a median of 520.7 (95% UR: 0–813.5) per 100,000 infants, while the Netherlands exhibited the highest at 3,373.0 (95% UR: 3,104.4–3,611.8). RSV-related mortality also varied substantially, ranging from a median of 0.14 (95% UR: 0.12–0.16) per 100,000 infants in Australia to 3.6 (95% UR: 3.3–3.9) in Israel. Across the countries studied, estimated YLL exceeded 280.2 (95% UR: 268.8–290.6) per 100,000 older adults and 311.5 (95% UR: 271.8–377.9) per 100,000 infants.
Reduction in RSV-related hospitalisation (%)
Health outcomes with vaccination
We applied the calibrated model specific to each country and implemented vaccination programs targeting older adults and pregnant women, mirroring the reported vaccine coverage of these population groups for seasonal influenza preceding the COVID-19 pandemic. Among older adults, averted hospitalisations attributed to RSV vaccination ranged from a median of 15.0 (95% UR: 13.9–16.1) per 100,000 population in Israel to 135.0 (95% UR: 128.9– 142.4) in Canada. The corresponding vaccination uptake rates were reported at 59.8% in Israel and 70.0% in Canada. The estimated numbers of RSV-related deaths averted by RSV vaccination varied, with the lowest at 1.0 (95% UR: 0.9–1.0) and the highest at 11.2 (95% UR: 10.5–11.8) per 100,000 population of older adults, in Israel and Canada, respectively. The reduction in deaths attributed to RSV vaccination varied from 35.2% in Germany to 64.5% in the United Kingdom (Table 1).
Based on averted deaths among older adults in each country, we estimated YLL prevented by RSV vaccination, which ranged from 21.5 (95% UR: 19.7–23.2) per 100,000 population in Israel to 168.7 (95% UR: 158.6–177.9) in the United States.
Among pregnant women, the highest vaccination uptake rates were observed in Australia (61%) and Ireland (61.7%). Compared with the no-vaccine scenario, vaccination of pregnant women would avert a median of 1,060.9 (95% UR: 599.0–1,335.3) RSVrelated hospitalisations per 100,000 infants in Australia, representing the most substantial reduction per capita among all countries studied here. With a 47.4% vaccination coverage of pregnant women, Japan had the largest number of RSV-related mortalities averted, with a median of 1.3 (95% UR: 0.6–1.8) per 100,000 infants. The reduction in deaths attributed to RSV vaccination varied from 4.8% in France to 49.7% in Ireland.
Fig 2: Assuming uptake rates similar to seasonal influenza vaccination in each country, the vaccination scenario is compared with the baseline scenario (without vaccination), with countryspecific reproduction numbers estimated for the 2018–2019 RSV season. Colored bars represent median values of estimates for vaccination of older adults (red, per 100,000 older adults) and pregnant women (cyan, per 100,000 infants), with error bars indicating 95% UR from 500 stochastic simulations
Hospitalisation costs averted (xUS$1,000)
Simulating vaccination scenarios, we calculated the relative reduction in hospitalisations for each country (Fig. 1). The reduction in hospitalisation achieved by vaccination of older adults ranged from 35.2% (95% UR: 33.5–37.1%) in Germany to 64.5% (95% UR: 62.4–66.5%) in the United Kingdom (Fig. 1a). In the case of vaccination of pregnant women, France showed the lowest reduction in RSV-related hospitalisations among infants, with a reduction of 4.8% (95% UR: 1.0–7.4%), while Ireland exhibited the highest reduction, of 49.7% (95% UR: 28.9–70.5%) (Fig. 1b), reflecting vaccination coverage of pregnant women.
Hospitalisation costs averted by vaccination
Using country-specific costs of RSV-related hospitalisation, we calculated the direct costs averted by RSV vaccination. Costs averted by vaccination of older
adults ranged from US$45,202 (95% UR: US$42,100–48,803) in Israel to US$2,540,408 (95% UR: US$2,375,525–2,679,474) in the United States per 100,000 population of adults aged 60 years or older (Fig. 2, red bars). Hospitalisation costs averted per 100,000 infants attributed to the vaccination of pregnant women were lowest in France, at US$498,163 (95% UR: US$117,922–940,689) and highest in Australia, at US$17,855,740 (95% UR: US$9,868,897–22,865,179) (Fig. 2, cyan bars).
Secondary analyses
To investigate the effect of vaccination coverage on the reduction of RSV burden and associated hospitalisation costs, we conducted additional scenario analyses by varying uptake rates in each country. Setting the vaccination coverage to 73% for older adults and 62% for pregnant women in
all countries, the reduction in hospitalisations (compared with baseline) was similar across the countries studied, with overlapping uncertainty ranges of 62–73% for older adults and 18–72% for infants. For the lowest coverages of 38% for older adults and 7% for pregnant women, the reduction in hospitalisations was substantially lower but still consistent across countries, with overlapping uncertainty ranges of 28–41% for older adults and 0–19% for infants.
We further considered countryspecific vaccination coverage of seasonal influenza reported during and after the COVID-19 pandemic. Simulating the model with the vaccination of older adults, we found trends in the reduction of hospitalisations similar to those derived in the baseline scenario with country-specific vaccination coverage before the COVID-19 pandemic. The median reduction in hospitalisations ranged from 39% in Germany to
70% in the United Kingdom. In regard to vaccination of pregnant women, median reduction in hospitalisations among infants varied from 10% in Germany to 44% in Spain.
Discussion
The availability of RSVpreF vaccines provides an important public health measure to mitigate the burden of RSV disease among infants and older adults. Our analysis indicates that vaccination can substantially reduce RSVrelated hospitalisations and deaths, averting inpatient costs. However, this impact varies across countries and is influenced by both uptake rates and local epidemiological characteristics of RSV seasons. For example, Germany has one of the highest burdens of RSV among European countries, with an annual average of 127 hospitalisations per 100,000 adults aged 65 years or older,22 incurring substantial direct
32 CPD 116: RSV
and indirect healthcare costs.23
Given the low influenza vaccination coverage of 38.8% among older adults in Germany, the estimated reduction in RSV-related hospitalisations remains under 40% in this population. Similarly, in countries such as France, Germany and Italy, where maternal immunisation uptake rates are low, the estimated reductions in infant hospitalisations remain under 20% (Fig. 1).
Our secondary analyses show that the outcomes of RSV vaccination may vary across populations, even under the assumption of similar uptake rates and transmissibility; for example, the United States, Canada, Ireland and Japan have similar reproduction numbers, between 1.4 and 1.5. When the vaccination coverage was set to 73% for older adults and 62% for pregnant women across these countries, the projected hospitalisations averted per 100,000 population of older adults varied from 72.5 (95% UR: 1.7–93.0) in Ireland to 140.8 (95% UR: 133.7–148.7) in Canada, indicating the impact of demographic characteristics on vaccination outcomes. However, the relative reductions in outcomes were similar, despite the varying burden of RSV among these countries.
Our model, calibrated to countryspecific reproduction numbers, produces hospitalisation rates consistent with those published in the literature. For instance, one systematic analysis of global, regional and national disease burden reported an overall annual rate of 17.8 (95% UR: 11.9–26.6) hospitalisations per 1,000 infants in high-income countries (using studies with quality scores >0.6).2 In the absence of vaccination, hospitalisation rates estimated in our model per 1,000 infants range from 5.2 (95% UR: 0–8.1) in Ireland to 33.7 (95% UR: 31.0–36.1) in the Netherlands. Similarly, the model generates hospitalisation rates per 100,000 older adults ranging from 97.7 (95% UR: 94.5–100.6) in Sweden to 214.0 (95% UR: 204.7–222.1) in the United States, largely consistent with the unadjusted annual hospitalisation rate of 157 (95% CI: 98–252) in industrialised countries.7
In alignment with previous studies,24,25,26,27 our analysis demonstrates the potential for substantial health benefits from RSVpreF vaccines, assuming high vaccination uptake rates. However, uptake rates will depend on various factors such as vaccine acceptability, out-ofpocket costs for receiving RSV vaccines, the inclusion of eligible population groups in publicly funded programs and specific recommendations for program implementation in different countries, which are influenced by cost-effectiveness evaluations of these vaccines.12,21,28,29,30
Recommendations are likely to consider other RSV interventions, such as nirsevimab, which offers an alternative to maternal vaccination by providing passive immunity to infants. For instance, a recent cost-effectiveness analysis of RSV preventive measures in Canada found that a combined strategy of vaccinating pregnant women with RSVpreF vaccines and immunising high-risk infants with nirsevimab during the RSV season was cost effective, while being comparable to an all-infant, nirsevimab-only program in reducing infant hospitalisations and mortality.21 However, despite regulatory approvals for the use of nirsevimab in several countries studied here, program implementation for infant immunisation remains challenging due to limited supply and high costs, even in high-income countries.31,32,33,34,35,36
Recommendations may also vary across countries, influencing the uptake and prioritisation of RSVpreF vaccines and nirsevimab. For example, in the United States, infants whose mothers have been immunised with RSVpreF vaccines may not receive nirsevimab (depending on risk factors and gestational age),37 making nirsevimab uptake uncertain and dependent on RSVpreF vaccine uptake in pregnant women. Given these uncertainties and varying recommendations, and considering additional factors including costs, our analysis did not include nirsevimab for infant immunisation.
Our study has several limitations. First, we implemented uptake rates at the beginning of model simulations, corresponding to the start of the RSV season in each country. However, vaccination probably occurs throughout the season, and effective uptake rates at the onset of the RSV season may differ from those used in our analysis. In addition, we also used reported vaccine efficacy estimates from clinical trials. However, the real-world effectiveness of these vaccines remains unknown and would be influenced by the characteristics of eligible population, comorbidities and other RSV-associated risk factors. Second, we focused only on the direct benefits of vaccination against severe disease outcomes (hospitalisation and death), and on the reduction of costs associated with RSVrelated hospitalisations. Additional benefits of vaccination, such as reduced rates of medically attended symptomatic RSV for outpatient care, were not considered in this study.12,21,28,38,39 Furthermore, while current evidence is limited, vaccination may reduce transmission and circulation of the virus due to potential herd immunity effects. Without accounting for these factors, our results regarding the health benefits of vaccination are probably conservative. However, in the absence of data on the indirect effects of vaccination against infection or transmission, our model assumptions relied on existing evidence that RSV infection does not confer durable immunity and that reinfection is common.40 Third, we evaluated RSVpreF vaccination over a 1-year time horizon consisting of a single RSV season. However, these vaccines have shown protective efficacy against severe RSV LRTI over two seasons,41,42,43 which could affect uptake rates. Fourth, our estimates of reproduction numbers rely on reported RSV positivity rates in the countries studied. However, various factors can influence such rates, including risks and care-seeking behaviour, testing practices and seasonal forcing. Fifth, our analysis uses hospitalisation costs from published estimates, which may be influenced by the population study
as well as the utilisation of critical care resources by inpatients. Sixth, we did not account for the costs of vaccination programs in our analysis, and thus net direct healthcare cost savings would differ from those estimated here. Costs of vaccination programs would include vaccine transportation, storage, administration, promotion and outreach, wastage and the price per dose of vaccines, which varies by country due to manufacturers’ negotiations. Finally, the cost effectiveness of RSVpreF vaccines and the impact of nirsevimab alongside vaccination were not evaluated in our analysis. Such evaluations would require an extension of the model structure to include country-specific inputs, such as the outpatient burden of RSV and associated costs, recommendations for use of these interventions (for example, risk factors and gestational age of infants) and estimates of productivity losses due to RSVrelated illness.12,21,26,28,44
Given the recent introduction of RSV vaccines in 2023, there is limited real-world experience with vaccine program implementation. Although we used country-specific influenza vaccination coverage in our baseline analysis, recent estimates indicate a substantially lower uptake of RSVpreF vaccines during the 2023–2024 season.45,46,47,48 Addressing vaccine hesitancy, awareness and accessibility should improve uptake rates, thereby enhancing the impact of RSV vaccination campaigns.
Within a few years, the landscape for the prevention of RSVassociated illness has significantly changed, and practical strategies to protect infants and older adults have become available. Our analysis underscores the importance of these advancements, demonstrating that the use of RSVpreF vaccines could substantially reduce the burden of RSV disease. As new data and evidence on the real-world effectiveness of these vaccines accumulate, additional studies can inform optimal vaccination scenarios in different populations. References available on request
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Indications
Pomalidomide Teva 1 mg, 2 mg, 3 mg and 4 mg hard capsules
Pomalidomide Teva in combination with bortezomib and dexamethasone is indicated in the treatment of adult patients with multiple myeloma who have received at least one prior treatment regimen including lenalidomide.
Pomalidomide Teva in combination with dexamethasone is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy.
Pomalidomide Teva Abbreviated Prescribing Information
Presentation: Each hard capsule contains 1mg, 2mg, 3mg and 4mg pomalidomide respectively. Indications: In combination with bortezomib and dexamethasone, Pomalidomide Teva is indicated in the treatment of adult patients with multiple myeloma who have received at least one prior treatment regimen including lenalidomide. Also, in combination with dexamethasone, is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy. Dosage and administration: For oral use. Treatment must be initiated and monitored under the supervision of physicians experienced in the management of multiple myeloma. Dosing is continued or modified based upon clinical and laboratory findings. Adults: Please see SmPC for recommended dosing scheme for pomalidomide in combination with bortezomib and dexamethasone, as well as dose modification instructions for pomalidomide, bortezomib and dexamethasone. Pomalidomide in combination with bortezomib and dexamethasone: Recommended starting dose of 4mg once daily (Day 1 to 14) of repeated 21-day cycles. Pomalidomide in combination with dexamethasone: Recommended starting dose of pomalidomide is 4mg once daily (Days 1 to 21 of each 28-day cycle). Children: Not recommended for use in patients aged 0-17 years. Elderly: No dose adjustment required. Renal impairment: No dose adjustment of pomalidomide is required for patients with renal impairment. On haemodialysis days, patients should take their pomalidomide dose following haemodialysis. Hepatic impairment: Patients with serum total bilirubin > 1.5 x ULN (upper limit of normal range) were excluded from clinical studies. Hepatic impairment has a modest effect on the pharmacokinetics of pomalidomide. No adjustment of the starting dose of pomalidomide is required for patients with hepatic impairment as defined by the Child-Pugh criteria. However, patients with hepatic impairment should be carefully monitored for adverse reactions and dose reduction or interruption of pomalidomide should be used as needed. Contraindications: Pregnancy; Patients of childbearing potential, unless all the conditions of the pregnancy prevention programme are met; Male patients unable to follow or comply with the required contraceptive measures; Hypersensitivity to the active substance or to any of the excipients. Precautions and warnings: Pomalidomide must not be taken during pregnancy, since a teratogenic effect is expected. Please consult SmPC for criteria for patients of non-childbearing potential and counselling for patients of child-bearing potential and respective male partners). Patients of childbearing potential must use at least one effective method of contraception for at least 4 weeks before therapy, during therapy, and until at least 4 weeks after pomalidomide therapy and even in case of dose interruption unless the patient commits to absolute and continuous abstinence confirmed on a monthly basis. If not established on effective contraception, the patient must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated. According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25mIU/ mL must be performed for patients of childbearing potential. This requirement includes patients of childbearing potential who practice absolute and continuous abstinence. A medically supervised pregnancy test should be performed prior to starting treatment, when pomalidomide is prescribed, or in the 3 days prior to the visit to the prescriber once the patient had been using effective contraception for at least 4 weeks. The test should ensure the patient is not pregnant when she starts treatment with pomalidomide. A medically supervised pregnancy test should be repeated at least every 4 weeks, including at least 4 weeks after the end of treatment, except in the case of confirmed tubal sterilisation. These pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber. Patients should not donate blood, semen or sperm during treatment (including during dose interruptions) and for at least 7 days following discontinuation of pomalidomide. Healthcare professionals and caregivers should wear disposable gloves when handling the blister or capsule. Individuals who are pregnant or suspect they may be pregnant should not handle the blister or capsule. Neutropenia was the
Teva Pharmaceuticals Ireland, Digital Office Centre Swords, Suite 101 - 103, Balheary Demesne, Balheary Road, Swords, Co Dublin, K67E5AO, Ireland.
most frequently reported Grade 3 or 4 haematological adverse reaction in patients with relapsed/refractory multiple myeloma, followed by anaemia and thrombocytopenia. Patients should be monitored for haematological adverse reactions, especially neutropenia. Patients should be advised to report febrile episodes promptly. Complete blood counts should be monitored at baseline, weekly for the first 8 weeks and monthly thereafter. Patients may require use of blood product support and /or growth factors. Patients receiving pomalidomide either in combination with bortezomib and dexamethasone or in combination with dexamethasone have developed venous thromboembolic events (predominantly deep vein thrombosis and pulmonary embolism) and arterial thrombotic events (myocardial infarction and cerebrovascular accident). Patients with known risk factors for thromboembolism – including prior thrombosis – should be closely monitored. Action should be taken to try to minimise all modifiable risk factors. Cases of hypothyroidism have been reported. Optimal control of co-morbid conditions influencing thyroid function is recommended before start of treatment. Baseline and ongoing monitoring of thyroid function is recommended. Cardiac events, including congestive cardiac failure, pulmonary oedema and atrial fibrillation, have been reported, mainly in patients with pre-existing cardiac disease or cardiac risk factors. Patients at greatest risk of tumour lysis syndrome are those with high tumour burden prior to treatment. Second primary malignancies, such as non-melanoma skin cancer, have been reported in patients receiving pomalidomide. Physicians should carefully evaluate patients before and during treatment using standard cancer screening for occurrence of second primary malignancies and institute treatment as indicated. Pomalidomide must be discontinued for exfoliative or bullous rash, or if StevensJohnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is suspected, and should not be resumed following discontinuation for these reactions. Dizziness and confusional state have been reported with pomalidomide. Patients must avoid situations where dizziness or confusion may be a problem and not to take other medicinal products that may cause dizziness or confusion without first seeking medical advice. Interstitial lung disease and related events, including cases of pneumonitis, have been observed with pomalidomide. Careful assessment of patients with an acute onset or unexplained worsening of pulmonary symptoms should be performed to exclude ILD. Pomalidomide should be interrupted pending investigation of these symptoms and if ILD is confirmed, appropriate treatment should be initiated. There have been cases of hepatitis that resulted in discontinuation of pomalidomide. Regular monitoring of liver function is recommended for the first 6 months of treatment with pomalidomide and as clinically indicated thereafter. Reactivation of hepatitis B has been reported rarely in patients receiving pomalidomide in combination with dexamethasone who have previously been infected with the hepatitis B virus. Some of these cases have progressed to acute hepatic failure, resulting in discontinuation of pomalidomide. Hepatitis B virus status should be established before initiating treatment with pomalidomide. Cases of progressive multifocal leukoencephalopathy, including fatal cases, have been reported with pomalidomide. PML was reported several months to several years after starting the treatment with pomalidomide. If PML is suspected, further dosing must be suspended until PML has been excluded. If PML is confirmed, pomalidomide must be permanently discontinued. Interactions: Pomalidomide is not anticipated to cause clinically relevant pharmacokinetic interactions due to P450 isoenzyme inhibition or induction or transporter inhibition when co-administered with substrates of these enzymes or transporters. The potential for such interactions, including the potential impact of pomalidomide on the pharmacokinetics of combined oral contraceptives, has not been evaluated clinically. Pomalidomide is partly metabolised by CYP1A2 and CYP3A4/5. It is also a substrate for P-glycoprotein. Co-administration of pomalidomide with the strong CYP3A4/5 and P-gp inhibitor ketoconazole, or the strong CYP3A4/5 inducer carbamazepine, had no clinically relevant effect on exposure to pomalidomide. Co-administration of the strong CYP1A2 inhibitor fluvoxamine with pomalidomide in the presence of ketoconazole, increased mean exposure to pomalidomide. Co-administration of multiple doses of up to 4mg
pomalidomide with 20mg to 40mg dexamethasone (a weak to moderate inducer of several CYP enzymes including CYP3A) to patients with multiple myeloma had no effect on the pharmacokinetics of pomalidomide compared with pomalidomide administered alone. Pregnancy and lactation: Patients of childbearing potential should use effective method of contraception. If pregnancy occurs in a patient treated with pomalidomide, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for evaluation and advice. If pregnancy occurs in a partner of a male patient taking pomalidomide, it is recommended to refer the female partner to a physician specialised or experienced in teratology for evaluation and advice. Pomalidomide is present in human semen. As a precaution, all male patients taking pomalidomide should use condoms throughout treatment duration, during dose interruption and for 7 days after cessation of treatment if their partner is pregnant or of childbearing potential and has no contraception. A teratogenic effect of pomalidomide in humans is expected. Pomalidomide is contraindicated during pregnancy and in patients of childbearing potential, except when all the conditions for pregnancy prevention have been met. It is unknown whether pomalidomide is excreted in human milk. Because of the potential for adverse reactions in breastfed infants from pomalidomide, a decision must be made whether to discontinue breast-feeding or to discontinue the medicinal product, taking into account the benefit of breast-feeding for the child and the benefit of the therapy for the patient. Effects on ability to drive and use machines: Pomalidomide has minor or moderate influence on the ability to drive and use machines. Fatigue, depressed level of consciousness, confusion, and dizziness have been reported with the use of pomalidomide. If affected, patients should be instructed not to drive cars, use machines or perform hazardous tasks while being treated with pomalidomide. Adverse reactions: Pneumonia, bronchitis, upper respiratory tract infection (including viral), sepsis, septic shock, neutropenic sepsis, C. difficile colitis, bronchiolitis, urinary tract infection, herpes zoster, hepatitis B reactivation, basal cell carcinoma, squamous cell carcinoma of the skin, neutropenia, thrombocytopenia, leucopenia, febrile neutropenia, pancytopenia, angioedema, anaphylactic reaction, solid organ transplant rejection, hypothyroidism, hypokalaemia, tumour lysis syndrome, syncope, depressed level of consciousness, intracranial haemorrhage, cerebrovascular accident, cataract, atrial fibrillation, cardiac failure, myocardial infarction, deep vein thrombosis, gastrointestinal haemorrhage, hyperbilirubinaemia, hepatitis, DRESS, TEN, SJS, acute kidney injury, renal failure. Very Common: Influenza, anaemia, hyperglycaemia, decreased appetite, insomnia, peripheral sensory neuropathy, dizziness, tremor, dyspnoea, cough, diarrhoea, vomiting, nauseas, constipation, abdominal pain, rash, muscular weakness, back pain, muscle spasms, fatigue, pyrexia, peripheral oedema. Common: Bronchopneumonia, respiratory tract infection, lower respiratory tract infection, lung infection, nasopharyngitis, lymphopenia, urticaria, hypomagnesaemia, hypocalcaemia, hypophosphataemia, hyperkalaemia, hypercalcaemia, hyponatraemia, hyperuricaemia, depression, confusional state, peripheral sensorimotor neuropathy, paraesthesia, dysgeusia, vertigo, hypotension, hypertension, pulmonary embolism, epistaxis, interstitial lung disease, upper abdominal pain, stomatitis, dry mouth, abdominal distention, pruritus, bone pain, chronic kidney injury, urinary retention, non-cardiac chest pain, oedema, fall, alanine aminotransferase increased, weight decreased, neutrophil count decreased, white blood cell count decreased, platelet count decreased, blood uric acid increased. Consult the Summary of Product Characteristics in relation to other side effects. Overdose: Pomalidomide doses as high as 50mg as a single dose in healthy volunteers have been studied without reporting serious adverse reactions related to overdose. Doses as high as 10mg once-daily multiple doses in multiple myeloma patients have been studied without reported serious adverse reactions related to overdose. The dose-limiting toxicity was myelosuppression. In studies, pomalidomide was found to be removed by haemodialysis. In the event of overdose, supportive care is advised. Legal category: POM. Marketing Authorisation Number: EU/1/24/1868/001048. Marketing Authorisation Holder: TEVA GmbH, Graf-Arco-Str. 3, 89079 Ulm, Germany. Job Code: MED-IE-00090. Date of Preparation: January 2025.
Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie.
Adverse events should also be reported to Teva UK Limited on +44 (0) 207 540 7117 or medinfo@tevauk.com
Further information is available on request or in the SmPC. Product Information also available on the HPRA website. Date of Preparation: January 2025 | Job Code: GEN-IE-00124
Liver
The End of “Fatty Liver”
It won’t be news to you that the disease that we used to refer to as NAFLD is now MASLD: the term Metabolic dysfunction-associated steatotic liver disease now replaces the older term: non-alcoholic fatty liver disease (NAFLD). The change in terminology is more than just words: it reflects our changing understanding of this common and multifactorial steatotic liver disease.
Defining Metabolic-Dysfunction
Associated Liver Disease
Metabolic-Dysfunction
Associated Steatotic Liver Disease (MASLD): These are patients who have steatotic liver disease (at least 5%) and one metabolic associated risk factors [figure 1], no other causes for liver disease, and no or low-risk alcohol consumption. While not part of diagnostic criteria, there is an association between MASLD and other conditions, including Obstructive Sleep Apnoea, Polycystic Ovarian Syndrome, Chronic Kidney Disease, and Cardiovascular Disease.
Metabolic-Dysfunction and Alcohol Associated Liver Disease (MetALD): Patients with steatotic liver disease, one metabolic associated risk factor [figure 1], no other causes for liver disease, and moderate alcohol consumption. Moderate alcohol consumption is defined as 140350g alcohol per week for female patients and 210-420g per week for male patients.
MASH (Metabolic-Dysfunction
Associated Steatohepatitis) was previously known as NASH. Patients have histological features
of hepatocellular injury and inflammation. Fibrosis may or may not be present on biopsy.
MASH cirrhosis: Patients with cirrhosis with a history or evidence of MASH or MASLD.
What should every doctor who looks after patients with metabolic risk factors know about MASLD?
Patients are usually asymptomatic, so a degree of clinical suspicion is needed. It is also common, estimated to be present in up to
Written by Dr Kate McCann, Lifestyle Medicine, Beacon Consultants Clinic
of MASLD. Thrombocytopaenia and neutropaenia are typically associated with cirrhosis.
Laboratory results can also be used to calculate the FIB-4 score. FIB-4 scores have the advantage of being readily accessible in a variety of settings. The score can be calculated using Age in years, AST, ALT, and Platelet count.
[Figure 2] However, studies have found it less reliable in patients <35 or >65 years of age, and in patients with hypertension, type 2 diabetes, and obesity.
30% of the global population has MASLD. MASLD is also found in patients without obesity.
Signs of liver disease are often not present on examination. While there may be a degree of hepatomegaly in some patients with MASLD, this is often not clinically appreciable and evident only on imaging.
While some patients with MASLD may have elevated ALT, AST, and Alkaline Phosphatase, others may have enzymes within normal limits. The presence of persistently elevated liver enzymes, without any other identifiable cause, particularly in patients with diabetes or obesity, should raise clinical suspicions
MASLD may be seen incidentally on abdominal imaging done for other reasons. When imaging specifically for evaluation of MASLD is needed, there is now increasing availability of VibrationControlled Transient Elastography. Also known as Fibroscan, it is painless and non-invasive. As the shear wave is passed through the liver, the speed at which it returns is converted into a liver stiffness score, which correlates to liver scarring and fibrosis.
Treatment
For many patients with MASLD, the cornerstone of treatment is lifestyle interventions.
Alcohol Abstinence: There is no safe amount of alcohol that can be recommended to patients with chronic steatotic liver disease.
Tobacco: Patients with MASLD who smoke should be encouraged
Metabolic Risk Factors for MASLD
• BMI above a healthy weight or increased waist circumference, adjusted for ethnicity
• Increased fasting blood glucose (>5.6mmol/L), HbA1c above 39, or diagnosis of T2DM
• Hypertension, either controlled or uncontrolled
• Elevated Triglycerides
• Decreased HDL
For diagnosis of MASLD, patients should have at least one of these criteria. Note that there is a separate set of criteria for paediatric patients.
• Advantages: This test is less invasive than biopsy, easily accessible, and low cost. There are number of online calculators available.
• What to know? This test should be repeated, as liver disease can progress over time.
• Limitations: It may be less accurate in certain age groups, in patients with some co-morbidities, or patients with heavy alcohol use.
• Understanding the results:
• 0-2 correlates with mild fibrosis
• 3-4 correlates with moderate fibrosis
• 5-6 correlates with severe fibrosis/cirrhosis
and supported to quit smoking as smoking is associated with increased risk of fibrosis.
Nutrition: Gradually making changes to adopt a Mediterranean diet (or a Mediterranean-informed diet) has been associated with improved outcomes. Patients should be encouraged to reduce consumption of ultra-processed foods. Patients may benefit from referral to registered dietitian to help improve diet. Moderate coffee should be encouraged in patients who tolerate or enjoy coffee: In some studies, patients who consumed 3 cups of coffee per day had improvement in MASLD. To minimise sleep disturbance, this should be consumed in the earlier part of the day, at least 8 hours before bedtime.
There is no evidence for the use of supplements or nutraceuticals in MASLD.
Exercise: is an essential part of treatment for patients MASLD. Muscle mass has a reciprocal relationship with MASLD. Patients should be prescribed individualised exercise programmes, ideally including a mixture of strength and cardio, for a minimum of 150 minutes per week. It is important to counsel patient that studies have found that the reduction of intrahepatic lipids in response to exercise is independent of any weight loss. Due to lived experience, many patients may get discouraged with therapeutic exercise programmes if they can’t see results on the scale.
Weight loss of between 5 -10% should be targeted for patients with MASLD who are above
a healthy weight when BMI is adjusted for ethnicity.
We know from studies that patients struggle to implement prescribed lifestyle interventions, and to sustain lifestyle changes. More awareness of these challenges as well as expert, longterm multi-disciplinary support to make long-term therapeutic lifestyle changes is needed.
Patients may also need assessment to exclude any other associated metabolic conditions, including obstructive sleep apnoea and chronic kidney disease. Optimising control of comorbidities such as hypertension, dyslipidaemia, and diabetes, if present, is important. In patients with suspected significant liver disease, where the diagnosis is uncertain, or those with advanced fibrosis, referral to expert hepatology services may be indicated for further assessment.
Prognosis for patients with MASLD is variable. While around half of patients with MASLD will have stable disease, up to 1/3 of patients will have progressive fibrosis. Complications from progressive MASLD include cirrhosis, hepatocellular cancer, and increased all-cause mortality; mortality risk increases with MASLD severity.
Looking to the Future: Pharmaceutical interventions
Resmetirom is an oral thyroid hormone receptor-β (THR-β) agonist. In March 2024, it was approved for use by the FDA in the US under accelerated approval for the treatment of adults with MASH with moderate to advanced liver
fibrosis, no cirrhosis. In studies, this new drug reduced hepatic fat content, improved liver enzymes and non-invasive markers of liver fibrogenesis, and improved liver stiffness scores. Studies also found a reduction in serum lipids, including LDL cholesterol. Resmetirom is under regulatory review in the EU.
Semaglutide – Emerging evidence suggests that treatment with the now-familiar GLP-1a medication may be associated with improvement in intrahepatic lipid deposits and fibrosis in patient with MASLD. The ESSENCE trial (Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis) is an ongoing 5-year, phase 3, randomised, multicentre trial in 2 parts evaluating the effect of semaglutide in patients with MASH and stage 2 or stage 3 fibrosis on biopsy.
Why Awareness of MASLD is important for your Patients
I’m not a hepatologist. Patients are referred for ongoing support managing chronic health conditions. Despite the prevalence of MASLD among my patients: they never present with complaints about their livers. If you are also not-a-hepatologist, that’s probably true for your practice as well. That is because MASLD is, in most cases, a silent disease. And this has special significance for patients with obesity: MASLD is present in between 65-85% of patients with obesity (the incidence increasing with increasing stage/ class of obesity). This becomes especially relevant in the context of
the updated obesity definitions put forward in the Lancet in January 2025. The new evidence-based definitions:
CLINICAL OBESITY: A CHRONIC, SYSTEMIC DISEASE STATE DIRECTLY CAUSED BY EXCESS ADIPOSITY
PRECLINICAL OBESITY: A CONDITION OF EXCESS ADIPOSITY WITHOUT CURRENT ORGAN DYSFUNCTION OR LIMITATIONS IN DAILY ACTIVITIES BUT WITH INCREASED FUTURE HEALTH RISK.
The paper states that the purpose of this new diagnostic framework is to reduce healthcare costs, and should be used to prioritise access to care.
Did you know? In studies of patients living with Type 2 diabetes mellitus and unknown MASLD status, 14% were found to have fibrosis and 3 – 6% were found to have cirrhosis.
I have seen at least 3 young patients with MASH cirrhosis in the previous year. I mean that not just in our professional use of the word “young” (the “young” patient being any patient younger than the doctor) but in that generally lower risk age groups of 3rd and 4th decade. The important thing to note was that the patients had no complaints or symptoms.
Access to care for patients with obesity, with or without complications, is already problematic, not just in Ireland but globally. The concern here is that MASLD is among those complications of obesity that can be clinically subtle - subfertility, pre-diabetes/T2DM, dyslipidaemia, hypertension, and OSA. Without a clinician’s reasonable clinical suspicion, the complications can remain unrecognised in early stages, and the patient classified as “pre-clinical.”
Figure 2
An Even Better Future: Prevention
The risk factors for MASLD include diets high in processed foods and a sedentary lifestyle. In Ireland, ~91% of deaths are due to non-communicable disease. While this article has focused on adult patients, it is estimated that MASLD is present in 5 – 10% of the paediatric population, making it the most common liver disease in children; it is almost always detected incidentally. MASLD and MASH are multifactorial diseases: the aetiology an interplay of genetic, environmental, and lifestyle factors. Addressing the modifiable risk factors is essential. Effective preventative health strategies at to reduce tobacco and alcohol use, reduce consumption of ultra-processed foods, improve nutrition, and increase physical activity should be prioritised, both for best patient outcomes and least healthcare costs.
Fatty Liver
When to Consider that the Patient may have
MASLD?
• Elevated AST or ALT with no explanation
• Presence of 2 metabolic risk factors [figure 1]
• Steatosis seen on imaging
• First degree relative with MASLD cirrhosis
Acknowledging World Obesity Day News
Tuesday 4th March was World Obesity Day and specialists in the Obesity Service, Galway University Hospitals (GUH) raised awareness of this year’s theme; ‘Changing systems for healthier lives’. This campaign calls upon everyone to be a part of positive change needed to deal with obesity.
Dr Sarah Summerville, a Specialist Clinical Psychologist at GUH, says “Until recently, the complex nature of obesity was not fully understood. It is now recognised as a biological, clinical disorder rather than as a reflection of an individual’s intelligence or personality and is affecting about one in four adults in Ireland. We all have a responsibility to compassionately understand and
manage our own beliefs about weight, which are often shaped over generations and driven by media and industry.
“Within the Bariatric Psychology Service in GUH our aim is to provide an accessible, effective and person-centred psychological service aimed at maximising the health, well-being and quality of life of all adults living with obesity. Psychological care is focused on evidenced-based principles of chronic disease management based on lived experiences and moves beyond simplistic approaches of ‘eat less, exercise more’.”
Obesity is a complex, progressive and relapsing chronic disease
Eoin Connolly, Clinical Specialist Physiotherapist; Alby Baby, Candidate Clinical Nurse Specialist; Grace O’Sea, Senior Clinical Psychologist; Paul Cromwell, Bariatric Surgeon; Robert Moloney, Administrator; Dr Enda Murphy, Research Associate; Sinead Molloy, Administrator; Professor Francis Finucane, Consultant Endocrinologist; Síle Ní Mháille, Clinical Specialist Occupational Therapist; Caitriona Lynch, Clinical Nurse Specialist; and Dr Wei Keong Kon
that impairs both physical and mental health.
The specialist obesity service at GUH was established in 2011 but has recently expanded significantly under the direction of the HSE’s National Clinical Programme for Obesity. The service now has a full multidisciplinary team, with psychological, medical, surgical, anaesthetic, nursing, occupational therapy, physiotherapy, social work and dietetic expertise.
This has been a major development for patients with severe and complicated obesity not just regionally, but nationally with patients coming from all over Ireland.
The ethos in the clinical team is one of non-judgmental, timely, compassionate, evidence-based clinical care. There is a very strong focus on clinical research, delivered in close collaboration with the University of Galway.
“This keeps us up to date with the very best drug treatments, the most effective structured lifestyle programmes and the latest obesity surgery techniques,” says Francis Finucane, Consultant Endocrinologist on the team.
“Access to these really effective treatments continues to be a challenge, but we are working to address this all of the time, and things are improving.”
Chris Kane, Hospital Manager, GUH added; “It is important to acknowledge the incredible work being carried out by our Obesity team who are seeing approximately 2,000 new patients every year from all over the country.”
“We’ve learned that to shame and judge only further compounds weight stigma, limiting the opportunity for growth and engagement. On World Obesity Day 2025 we ask that everyone takes an interest in the role that systems play in driving obesity, and how these can be changed to support better health for everyone,” she added.
Figure 3
37 Endocrinology Focus: Diabetes
Understanding Diabetes: Type 1 vs Type 2 Diagnosis and Treatment
Written by Professor Derek O’Keeffe, Consultant Physician/ Professor of Medical Device Technology, University Hospital Galway, Ireland/Digital Health Principal Investigator, CURAM Research Ireland Centre for Medical Devices, Ireland, National Clinical Lead Diabetes, HSE.
Dr Lyle McVicker, University Hospital Galway, Endocrinology SPR, Research Physician, University Hospital Galway
- As endocrinologists, we frequently encounter diagnostic challenges when differentiating between diabetes types. While both Type 1 and Type 2 diabetes share hyperglycaemia as their hallmark, their underlying pathophysiology, management approaches, and progression significantly differ. This article aims to provide hospital practitioners with practical knowledge on diagnosing diabetes, distinguishing between its main types and effectively managing them.
Diagnosing Diabetes
The American Diabetes Association (ADA) and World Health Organization (WHO) have established clear diagnostic criteria for diabetes. A definitive diagnosis requires meeting one of these threshold values:
• Haemoglobin A1C ≥48 mmol/ mol
• Fasting plasma glucose ≥7.0 mmol/L (following at least 8 hours without caloric intake)
• 2-hour plasma glucose ≥11.1 mmol/L during an oral glucose tolerance test (OGTT)
• Random plasma glucose ≥11.1 mmol/L in patients exhibiting classic hyperglycaemic symptoms
Clinicians should consider testing for diabetes when patients present with classic symptoms including polyuria (frequent urination), polydipsia (increased thirst), unexplained weight loss, recurrent infections, delayed wound healing, blurred vision, or fatigue.
For asymptomatic patients, diagnosis should never rely on a single abnormal test result. Confirmation requires a second test, either of the same type or a different one, showing values within the diabetic range. When discordant results occur between tests, repeating the abnormal test is recommended, with careful consideration of factors that might affect glucose or A1C measurements.
Diabetes. But, what type?
The distinction between diabetes types is crucial for implementing appropriate treatment strategies. Type 1 diabetes generally requires insulin replacement
Feature
Type 1 Diabetes
Age of Onset Usually <35 years but can
from diagnosis, while type 2 may initially respond to non-insulin therapies. Figure 1 shows a simple breakdown of the classic clinical features of each type.
Type 2 Diabetes
Typically >40 years but occur at any age increasingly common in younger individuals
Body Mass Index Often normal or underweight
Overweight or obese (BMI) (BMI ≥25 kg/m2)
Symptoms Acute onset, polyuria, polydipsia, Insidious onset, often weight loss, ketosis asymptomatic, may present with complications
Family History Less common, associated with Strong family history autoimmune diseases of diabetes
Not initially required, but may be needed over time
As is true of the old adage, ‘’patients don’t always read the textbooks’’ and as such we are often left scratching our head as to the type of diabetes a patient may have. When clinical features don't clearly point to a specific diabetes type, biomarker testing provides valuable insights:
Islet autoantibody testing is most informative when conducted within three years of diagnosis. Clinicians should test for multiple antibodies including GAD, IA2, and ZnT8, as the presence of multiple positive antibodies strongly supports a type 1 diagnosis. It's important to note that higher false positive rates occur in older adults, which often necessitates confirmation with C-peptide testing for accurate classification.
C-peptide testing becomes particularly useful when evaluating patients with long-duration diabetes. Very low C-peptide levels (<0.24 ng/mL) strongly indicate type 1 diabetes, while intermediate values (0.6–1.8 ng/mL) require
Dr Lyle McVicker
Professor Derek O’Keeffe
Figure 1. Characteristic features of Type 1 and Type 2 Diabetes
could represent type 1 diabetes, MODY, or insulin-treated type 2 diabetes. Measurements should be paired with a serum glucose level to aid interpretation.
When interpreting biomarker results, clinicians should consider the complete clinical picture. A patient with negative autoantibodies but persistently low C-peptide levels might still have type 1 diabetes, particularly if the testing was performed many years after diagnosis when autoantibodies may have disappeared. Conversely, a patient with weakly positive single autoantibody but robust C-peptide production likely has type 2 diabetes with a false positive antibody result. This integrated approach to biomarker interpretation helps resolve diagnostic dilemmas in clinically ambiguous presentations.
Generally speaking, if in doubt regarding the underlying cause of diabetes it is safest to err on the side of caution and treat in a way that most reduces potential harm i.e. diabetic ketoacidosis (DKA). In practice this means oftentimes starting insulin on a patient newly diagnosed with diabetes where uncertainty exists between a diagnosis of type 1 of type 2. This is sometimes done while awaiting antibody results and continued until a short interval clinic appointment following hospital discharge. If after several weeks, antibodies have returned negative and the clinical picture more resembles one of type 2 diabetes the insulin can be carefully tapered off or stopped outright and oral medications instituted.
Challenging Clinical Presentations of Diabetes
Type 1 diabetes in older adults presents unique diagnostic challenges. Despite classic presentations with DKA, type 2 diabetes remains significantly more common in older age groups. Negative autoantibody testing in older adults makes type 1 diabetes much less likely, and routine autoantibody screening isn't necessary if typical type 1 features are absent. For cases with uncertain classification, C-peptide measurement provides valuable confirmation, helping to distinguish late-onset type 1 from insulin-requiring type 2 diabetes, thus guiding appropriate therapeutic approaches.
Indeed, early insulin requirement serves as an important predictive factor for misdiagnosed type 1 diabetes. Patients initially classified as having type 2 diabetes who
Endocrinology Focus: Diabetes
require insulin therapy within three years of diagnosis likely have slowly progressive type 1 diabetes. These patients should undergo comprehensive biomarker testing, including autoantibody and C-peptide assessment, to confirm the correct diagnosis. Early recognition of misclassified type 1 diabetes helps prevent dangerous gaps in insulin therapy and inappropriate treatment with agents that may have limited efficacy.
Pancreatic cancer should be considered in the differential diagnosis of new-onset diabetes, particularly in specific high-risk scenarios. Clinicians should maintain heightened vigilance when diabetes presents in patients over 50 years old without typical metabolic syndrome features, especially when accompanied by unexplained weight loss, abdominal pain, or jaundice. The relationship works both ways - new-onset diabetes can sometimes be the first detectable sign of pancreatic cancer, presenting months before the cancer becomes clinically apparent through other symptoms. Early imaging studies should be considered for patients with suspicious presentations, particularly when multiple risk factors are present.
Maturity-Onset Diabetes of the Young (MODY) represents several monogenic forms of diabetes that should be considered when patients present with atypical features. These typically include relatively mild hyperglycaemia (A1C <58 mmol/mol at diagnosis), strong multigenerational family history of diabetes, absence of typical autoimmune or insulin resistance markers, and onset at a young age (typically before 25-30 years). Patients with MODY may also display distinctive clinical features suggesting specific genetic variants, such as renal cysts, lipodystrophy, or characteristic patterns of glycemic control such as persistently elevated fasting glucose with normal post-prandial values. Genetic testing provides definitive diagnosis and guides targeted treatment approaches for these patients. Awareness is critical as a MODY diagnosis can dramatically change treatment regimens and reduce burden on patients.
Latent Autoimmune Diabetes in Adults (LADA) presents a particular diagnostic challenge as it initially resembles type 2 diabetes but has an autoimmune pathophysiology similar to type 1. These patients typically appear to have type 2 diabetes but experience a more rapid progression to insulin
dependence. GAD autoantibody testing aids identification, and early recognition allows for appropriate treatment planning that accounts for the progressive β -cell failure these patients will experience. Recognizing LADA helps clinicians anticipate the eventual need for insulin therapy rather than persisting with combination oral agents that may prove insufficient.
Modern Diabetes Management: A Practical Guide for Hospital Clinicians
Effective diabetes management requires personalization based on the patient's age, comorbidities, preferences, and social circumstances. While HbA1c targets of ≤53 mmol/mol suit most adults, consider lower targets for selected patients who can achieve them safely, and more relaxed goals (58-69 mmol/mol) for frail elderly patients.
Type 2 Diabetes Management
Most recent international joint consensus guidelines from the ADA and European Association for the Study of Diabetes (EASD) now emphasise the consideration of cardiorenal protection and weight management alongside glycemic control when devising a medication regimen in type 2 Diabetes.
• Metformin: Remains the first-line pharmacological therapy for most patients with type 2 Diabetes due to its proven efficacy, safety profile, low cost, and extensive clinical experience. Metformin has demonstrated modest cardiovascular benefits, is weight neutral or may promote slight weight loss, and has a low risk of hypoglycaemia. Contraindications include severe renal impairment (eGFR <30 mL/min/1.73m2), and dose adjustment is recommended for moderate renal impairment.
• SGLT2 inhibitors: Consider for patients with established cardiovascular disease (CVD), heart failure, or chronic kidney disease regardless of HbA1c. These reduce heart failure hospitalizations and slow CKD progression, particularly in patients with albuminuria.
• GLP-1 receptor agonists: Offer significant cardiovascular benefits for patients with atherosclerotic disease while providing excellent glycemic control and weight reduction. Tirzepatide (dual GIP/GLP-1 agonist) shows superior efficacy for both glucose management and weight loss compared to earlier GLP-1 RAs. It is now
available in Ireland though it's not yet covered by the long-term illness scheme.
• DPP-4 inhibitors: Provide modest glycemic improvements with minimal hypoglycaemia risk and weight neutrality, making them suitable for elderly patients.
• Traditional agents: Sulfonylureas and insulin remain effective for glucose control but carry increased hypoglycaemia risk and weight gain concerns.
Weight management is crucial—5-10% weight loss improves multiple metabolic parameters, while ≥15% loss can induce diabetes remission in some patients. The availability of GLP-1 RAs have revolutionized pharmacological weight management though recent supply shortages have truncated some patients' courses and stopped others from accessing the most potent agents. For patients with BMI ≥35 kg/m2 and suboptimal control despite medication, metabolic surgery should be considered though access to this via both the public and private system in Ireland remains difficult and waiting lists are long.
Despite pharmaceutical advances, lifestyle modifications remain fundamental. Recommend individualized nutrition therapy (Mediterranean, plant-based, or moderate low-carbohydrate approaches) and physical activity (≥150 minutes weekly of moderateintensity activity, resistance training, and reduced sedentary time).
Type 1 Diabetes Management
Person-centred care is essential for type 1 diabetes. Diabetes self-management education and support (DSMES) remains the cornerstone intervention at diagnosis and throughout the patient's life. The DAFNE (Dose Adjustment For Normal Eating) programme, ideally implemented within 6-12 months of diagnosis, equips patients with carbohydrate counting skills and insulin adjustment strategies.
Continuous glucose monitors (CGMs) represent the preferred monitoring approach, focusing on Time in Range (TIR). Recommend patients aim for >70% of time within 3.9–10.0 mmol/L, while minimizing time below 3.9 mmol/L (<4%, ideally <1% below 3.0 mmol/L).
Insulin therapy options include:
• Multiple daily injections (MDI) with basal-bolus regimens (standard approach)
• Hybrid closed-loop systems (insulin pumps linked to CGM with a software algorithm controlling insulin delivery), which improve outcomes and reduce hypoglycaemia
• Connected insulin pens as intermediate technology, providing dose tracking and decision support
Comprehensive Care Considerations for All Diabetes Types
Beyond glycemic control, address cardiovascular and kidney risk:
• Lipid management: statin therapy for patients >40 years or with additional CVD risk factors. Risk level can be assessed
through use of the American College of Cardiology ASCVD risk calculator (Risk Estimator Plus).
• Annual kidney function screening: albuminuria and eGFR
• Regular retinal screening: The National Diabetic Retinal Screening Programme in Ireland facilitates free screening and onward referral to ophthalmology if required.
• Comprehensive foot care: Annual foot examinations to assess skin integrity, vascular status, and neuropathy using monofilament testing and vibration sensation.
The psychological burden of diabetes requires regular screening for diabetes distress, depression, anxiety, and eating disorders. Pay particular attention during care transitions to prevent treatment gaps. Optimal diabetes management requires a multidisciplinary team including
endocrinologists, diabetes specialist nurses, dietitians, and psychologists to address the complex biological, technological, and psychosocial aspects of diabetes care.
Key Takeaways for HospitalBased Clinicians
1. Individualise treatment plans considering the whole person, not just their HbA1c
2. For type 2 diabetes, select medications based on cardiorenal benefits and weight impacts
3. For type 1 diabetes, prioritise education, CGM, and appropriate insulin delivery methods
4. Address cardiovascular and kidney risk factors in all patients
5. Screen regularly for psychological complications
6. Collaborate with a multidisciplinary team for comprehensive care
1. Department of Health (2024), V2. NCEC National Clinical Guideline No. 17 Adult type 1 diabetes mellitus. Available at: http://health.gov.ie/nationalpatient-safety-office/ncec/
2. Management of Hyperglycaemia in type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 1 November 2022; 45 (11): 2753–2786. https://doi. org/10.2337/dci22-0034
3. The Management of type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 1 November 2021; 44 (11): 2589–2625. https://doi.org/10.2337/ dci21-0043
Health Impact Award for Professor Murphy News
Andrew Murphy, a Professor of General Practice at University Galway, has been awarded the Health Research Board Impact Award for 2025.
Professor Murphy, who specialises in primary care research and is a practising GP in Turloughmore, Co Galway, received the award for his exceptional influence on policy and practice in the Irish healthcare system.
Professor Murphy said, “GP-led primary care has led to significant improvement in effectiveness of treatment, patient convenience and cost. HRB funded research across many disciplines has been really important in providing the evidence to support these proposed innovation. The driver of all my research is that general practice has the potential to deliver high-quality care, both chronic and acute, which significantly improves patients’ lives and is highly cost effective.
“When I qualified as a GP in 1992, the care was reactive. But thanks in part to research funding from the HRB over the years, outcomes for patients have improved hugely because of the development of GP-led primary care. Research
funding helps provide the data and evidence needed for service development and opens the door to multi-disciplinary collaborations which are crucial to creating robust recommendations.”
University of Galway’s Professor Molly Byrne, who nominated Professor Murphy for this year’s award, said, “I believe this award is extremely well-deserved as it acknowledges Andrew’s substantial impact in building a collegial and supportive research community. Over the last 25 years, Andrew has enabled, supported and empowered many researchers to conduct research which really impacts on delivery of health services in practice and addresses the most pressing needs of patients in primary care.”
Professor Murphy has led a programme of research seeking to improve prevention of secondary heart disease in primary care since 2000 and he has been influential in significant innovations in GP practice that have been implemented nationwide.
A HRB research award in 2002 supported Professor Murphy’s seminal all-island research on cardiac disease prevention in
Andrew Murphy, a Professor of General Practice at University Galway
general practice. The then largest general practice trial, it is the first general practice paper ever to receive the prestigious Royal Academy of Medicine in Ireland Award.
Its key finding was that intensive, structured GP care, over eighteen months to patients with existing heart disease, reduced hospital admissions from 34% to 26%.
This work informed a review which found secondary cardiac prevention in general practice can extend the lives of patients by six years.
Professor Murphy also contributed significantly to the founding of Heartwatch in 2003, Ireland’s first universally accessible chronic disease management programme for heart disease. An element of his work in this area led to the provision of free Nicotine Replacement Therapy for Medical Card holders.
Professor Murphy continued, “Over my professional lifetime, there has been a sea change, largely for the good, in Irish general
practice. It is now at the epicentre of Irish healthcare. I repeatedly see the importance of this to patients where I practice in Turloughmore.”
Among other achievements he has been a champion of active involvement of public and patients in health research.
Professor Murphy emphasised the importance of collaboration, paying tribute to long-time collaborators Molly Byrne (health psychology), Susan Smith (general practice), Eamon O’Shea (health economics), John Newell (biostatistics), Paddy Gillespie (health economics) and Margaret Cupples (general practice).
Gastroenterology Special Focus: IBD
Beyond the Scope: Advancing IBD Diagnosis and Management with Bedside Ultrasound
Written
by Dr Ella Patchett and Dr Karl Hazel - Department of Gastroenterology, Connolly Hospital Blanchardstown
Introduction
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel conditions characterised by periods of relapsing and remitting disease and progressive bowel damage. The complexity of IBD management and diagnosis lies in its heterogeneous presentation, unpredictable disease course, and the need for lifelong monitoring to prevent complications such as strictures, fistulas, and colorectal cancer.
The aims in management of inflammatory bowel disease include amelioration of patients’ symptoms, to promote endoscopic and histological remission in order to support long-term clinical remission and avoidance of IBD complications.1 Traditionally, this was achieved through regular surveillance endoscopy; the gold standard for assessing mucosal inflammation and guiding therapeutic decisions. Colonoscopy allows for direct visualisation of the intestinal mucosa, enabling biopsies for histopathological evaluation, which remains essential for confirming disease activity and dysplasia surveillance.2 However, it is not without its drawbacks. Endoscopy is an invasive, time-consuming, and costly procedure and creates a burden
on ever-growing Irish waiting lists. It may also be associated with lower patient tolerability, anxiety and discomfort.3 In addition to colonoscopy, crosssectional imaging modalities such as magnetic resonance enterography (MRE) and computed tomography (CT) are frequently employed to assess disease extent, complications, and extramural involvement. While these imaging techniques provide crucial insights, they can also be expensive, time-consuming, and, in the case of CT, expose patients to ionizing radiation.4
In recent years, intestinal or bowel ultrasound (IUS) has emerged as a valuable, non-invasive tool for evaluating IBD. Intestinal ultrasound utilises high-frequency sound waves to generate realtime images of the bowel wall and surrounding structures.5 IUS visualises all bowel wall layers (mucosa, submucosa, muscularis propria, serosa), enabling assessment of transmural inflammation, a hallmark of CD. Unlike endoscopic procedures, IUS is non-invasive, requires no bowel preparation or sedation, and can be performed at the bedside. Key parameters assessed during IUS include:6
- Bowel Wall Thickness (BWT): Increased thickness (>3 mm
in the small bowel and right colon, >4 mm in the left colon) often correlates with active inflammation
- Bowel Wall Hyperaemia using doppler ultrasound: marker of active inflammation
- Wall Stratification: Loss of the normal five-layer bowel wall structure suggests severe inflammation or fibrosis
- Surrounding lymphadenopathy and free fluid: can indicate more severe disease
- Complications associated with IBD: strictures, abscesses and fistula
Unlike colonoscopy, which primarily evaluates mucosal disease, IUS provides additional information on transmural inflammation and extramural complications, making it a complementary modality rather than a replacement.5 The integration of IUS into routine clinical practice has the potential to enhance patient care by providing immediate insights during consultations, thereby supporting a treat-to-target approach in IBD management.
Global Use
Numerous studies internationally, particularly those performed in the US and central Europe, have shown promising results for the introduction of IUS as a standard of care for IBD. The TRUST study was a large multicentre project conducted in over 45 German hospitals which found that IUS can be used to effectively monitor treatment response in patients with active CD.8
Whilst information can be extrapolated from these studies, it is potentially more useful to look at similar studies performed in the UK – slightly closer to home with similar patient cohorts and demographics to an Irish population. Literature of note includes the 2018 METRIC trial.17 In a cohort of 284 patients, the authors conclude both MRE and ultrasound have high sensitivity for detecting the presence of
small bowel disease and both are valid first-line investigations in the assessment of IBD. In a further UK study in 2022, 260 patients were investigated via colonoscopy or MRE to assess lower gastrointestinal symptoms, IBD severity or clinical response to treatment.7 Patients were classified into either IUS-suitable or nonsuitable based on clinical factors e.g. IBD patients without dysplasia surveillance or stricture dilatation. This study determined that 28% of endoscopy patients and 55% of MRE patients were deemed IUS suitable. The primary objective of this work was to assess the cost analysis of introducing IUS as a replacement for endoscopy/MRE for those deemed suitable. They concluded that a projected annual saving of £500,000 could be achieved with the implementation of a IUS integrated programme. IUS in Ireland
Transabdominal ultrasound has been used as a modality for assessing IBD in central Europe; namely Germany and Italy for the preceding decades but has recently been utilised more in other European countries, Canada and the US via a centralised training programmed through the International Bowel Ultrasound Group (IBUS).8 The use of IUS in Ireland has gained acceptance and is now utilised across a small number of sites and will likely have a significant and positive impact on the future management of IBD and other lower GI conditions.9
Firstly, it can provide an accessible point of care investigation which can be performed by an IBD specialist in the outpatient setting. This has the potential to provide immediate treatment altering decisions in the case of an acute IBD flare, aid in endoscopic triage based on severity of findings and reduce the number of invasive tests in cases with a low pretest probability.7 Of note this may be particularly useful in ruling out non-inflammatory conditions such as irritable bowel syndrome and reducing endoscopy demand. Reassuring or normal ultrasound parameters could also be used to justify de-escalation of some
Dr Ella Patchett
Dr Karl Hazel
immunosuppressants and therefore reduce medication exposure for patients. It also serves to escalate therapy in patients on biologics who have not fully responded to treatment and while not listed as a formal target in the updated STRIDE-II treat-to-target guidelines for IBD, IUS is recommended as an adjunct to endoscopy, cross-sectional imaging and biomarkers.a
By providing real time information at the patient’s bedside, IUS can have a positive effect on patient understanding of their own condition. Patients with IBD have been shown in the literature to potentially have a poor level of knowledge surrounding their condition and this is particularly prevalent in the pregnant population.11, 12 Misconceptions and false information can lead to detrimental actions such as stopping biologic medications, increasing the risk of a flare during pregnancy. Patients who have undergone point of care IUS have been shown to have a significant self-reported active disease reported better understanding of all aspects of their disease and disease symptoms and were
more confident in their ability to make informed decisions about managing their disease.10 There are pregnancy-specific IBD clinics in Ireland and by introducing IUS, particularly in these clinics, we can help improve patient knowledge, provide reassurance and also prevents unnecessary radiation to pregnant individuals if further investigations are required. While there are limited studies investigating the use of IUS in pregnancy, the studies thus far have shown that IUS is a useful tool in pregnancy and can detect subclinical inflammation and stratify active inflammation in symptomatic patients.13
Lastly, despite improvements in biological therapy, surgical intervention is required in a significant proportion of patients with IBD.14 Long term inflammation increases the risk of developing strictures, abscesses and fistulae and may ultimately result in emergency surgery.15 While CT and MRI remain the gold standard for postoperative assessment, IUS offers a rapid, bedside, and radiation- and bowel preparation-free alternative for early detection of postoperative
recurrence. Furthermore, this use of IUS, in combination with faecal calprotectin, has been proven to be a valid and reliable tool for monitoring postoperative patients with CD, predicting the risk of postoperative recurrence, allowing for earlier escalation or reinstatement of biologics.16
Limitations
With every imaging modality, there are limitations. CT can provide high resolution images of bowel and extraintestinal complications whilst also being readily available particularly in emergency situations such as suspected perforation.14 As mentioned, CT is associated with radiation exposure which is a concern for the predominantly young demographic of patients who require frequent scanning. MRE can provide a radiation free alternative to CT and can provide high diagnostic accuracy for detecting the presence and activity of CD with reasonable interobserver agreement.4 This is in direct comparison to IUS which has the potential to be limited by operator skill and inter-operator variability. Patient preference and experience is also a crucial role in determining a choice of modality.
the overall burden of MRE was relatively low, it was still notably higher than that of IUS and patient willingness to undergo repeat testing was less when compared to IUS.9
In conclusion, the field of inflammatory bowel disease continues to evolve and the role of IUS is becoming increasingly significant due to its non-invasive nature, real-time assessment and radiation-free advantages. While traditional imaging modalities such as MRI, CT, and endoscopy remain important in IBD diagnosis and management, IUS offers a costeffective, accessible, and patientfriendly alternative, particularly for disease monitoring and treatment response evaluation. Increased training, investment, awareness of IUS’s diagnostic accuracy and patient benefits will see it become a key component in Ireland’s IBD care strategy. Moving forward, a multimodal approach combining endoscopy, cross-sectional imaging, and IUS will likely optimise disease management, ensuring patients receive timely and effective care.
References available on request
Gastroenterology Special Focus: Crohn’s Disease
Latest Research on Crohn’s Disease
Impact of Upadacitinib Induction and Maintenance Therapy on Health-related Quality of Life, Fatigue, and Work Productivity in Patients with Moderately-to-severely Active Crohn’s Disease
Written by Subrata Ghosh1, Brian G Feagan2, Rogério Serafim Parra3, Susana Lopes4, Adam Steinlauf5, Yoichi Kakuta6, Namita Joshi7, Wan-Ju Lee7, Ana P Lacerda7, Qian Zhou7, Si Xuan7, Kristina Kligys7, Nidhi Shukla7, Edouard Louis8
1College of Medicine and Health and APC Microbiome Ireland, University College Cork, Cork
2Robarts Research Institute, Western University, London, ON, Canada
3Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
4Centro Hospitalar e Universitário São João, Porto, Portugal
5IBD Clinical Center, Mount Sinai Hospital, New York
6Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
7Health Economics & Outcomes Research, AbbVie Inc., North Chicago
8Department of Gastroenterology, Centre Hospitalier Universitaire de Liège, Liège, Belgium
Crohn’s disease [CD] is a chronic, progressive, and relapsing inflammatory bowel disease [IBD] affecting the gastrointestinal tract.1 Current treatment approaches focus on symptom control via early clinical response and clinical remission, inflammation control as measured by biomarkers, and endoscopic response with the ultimate goal of achieving mucosal healing.2 Available treatment options include immunomodulators, corticosteroids, and biologic agents; however, these do not always elicit or maintain clinical response and may induce adverse effects, indicating the need for additional therapeutic options.3–7
Health-related quality of life [HRQoL] is a multidimensional construct focusing on patients’ perceptions of their physical, psychological, and social functions.8 Patients with IBD report poor HRQoL and disability, fatigue, and work impairment.9 CD-related symptoms can severely affect patients’ HRQoL, including: physical function, such as fatigue, sleep quality, and pain; social function, such as loss of social satisfaction; psychological function, including depression and anxiety; and aspects of work productivity.10–15 Approximately half of patients with moderatelyto-severely active CD have some degree of work impairment, with annual indirect costs from work impairment estimated at $29,524 per patient.16
Fatigue, a common, burdensome,17 yet largely unexplored2 symptom, is experienced by patients with
CD9 irrespective of disease activity.18 It affects more than 80% of patients with active disease19 and is associated with poor HRQoL, more active disease, reduced work productivity, and higher rates of unemployment.15,20,21
Patient perspectives on fatigue, work productivity, and HRQoL are important, given the considerable burden fatigue poses on patients’ HRQoL,22,23 the potential lack of awareness among health care professionals of the importance of this symptom,17 and the relevance of HRQoL and patient-reported outcomes to patients’ acceptance and adherence to therapy.24 The Selecting Therapeutic Targets in Inflammatory Bowel Disease [STRIDE-II] initiative identified restoration of HRQoL as a crucial long-term treatment goal, independent of achieving clinical remission, normalisation of biomarkers of inflammation, and endoscopic/histological mucosal healing.2
The phase 3 induction and maintenance trials [U-EXCEL, U-EXCEED, and U-ENDURE] demonstrated the efficacy and safety of upadacitinib in patients with moderately-to-severely active CD with regard to achievement of clinical remission and endoscopic response.25 In this analysis, we report the effects of upadacitinib on disease-specific and generic HRQoL measures, fatigue, and work productivity/daily activity in patients participating in the U-EXCEL, U-EXCEED, and U-ENDURE trials.
Materials and Methods Study design
U-EXCEL [NCT03345849] and U-EXCEED [NCT03345836] were phase 3, multicentre, randomised, double-blind, placebo-controlled, induction trials of the efficacy and safety of upadacitinib in patients with moderately-to-severely active CD who had an inadequate response or intolerance to one or more conventional and/or biologic therapies, as previously described.25 Both U-EXCEL and U-EXCEED trials consisted of a 12-week induction period and a 12-week extended treatment period for patients who did not achieve clinical response at the end of the induction period. U-EXCEED also included an open-label, upadacitinib induction arm, to achieve sufficient clinical responders for the subsequent maintenance trial.
U-ENDURE [NCT03345823] was a 52-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, maintenance trial investigating the efficacy and safety of upadacitinib for patients with CD who achieved clinical response in U-EXCEL and U-EXCEED.
The trials were conducted at 277 sites in 43 countries globally.
Study cohort
As previously described,25 in the U-EXCEL and U-EXCEED induction trials, patients 18–75 years old were randomised 2:1 to receive oral upadacitinib 45 mg once daily [QD] or placebo QD.25
Moderately-to-severely active
CD was defined as average daily stool frequency [SF] ≥ 4 and/or abdominal pain score [APS] ≥ 2, along with a Simple Endoscopic Score for CD [SES-CD; excluding the narrowing component subscore] ≥ 6 [≥ 4 for patients with isolated ileal disease], confirmed by a central reader. Patients had a diagnosis of CD for at least 3 months. A protocol-specific taper was initiated at Week 4 for patients receiving corticosteroids at baseline of induction treatment; the taper was continued at the beginning of the maintenance trial for patients who did not complete it during induction. A clinical response was defined as ≥ 30% decrease in average, daily, very soft or liquid SF and/or average daily APS, with neither value greater than at baseline. Patients with a clinical response following 12 weeks of upadacitinib 45 mg were enrolled in U-ENDURE and re-randomised 1:1:1 to receive upadacitinib 15 mg QD, upadacitinib 30 mg QD, or placebo QD for 52 weeks of maintenance treatment.
Patient-reported outcomes
To capture the potential benefits of upadacitinib treatment on HRQoL, fatigue, and work productivity, we assessed clinically meaningful improvements for several patientreported outcome measures. The measures assessed included the Inflammatory Bowel Disease Questionnaire [IBDQ], Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue], Short-Form Health Survey-36 version 2 [SF-36v2] Physical Component Summary [PCS] and
Mental Component Summary [MCS], EuroQol 5 Dimension [EQ-5D], and Work Productivity and Activity Impairment in Crohn’s Disease [WPAI-CD]. Outcome measures were collected at induction Weeks 4 and 12 and maintenance Week 52 of the upadacitinib trials.
The IBDQ is a disease-specific instrument comprising 32 Likerttype questions measuring HRQoL.26 It covers four subdomains: bowel symptoms [eg, abdominal pain, loose stools], systemic symptoms [eg, sleep patterns, fatigue], emotional function [eg, irritability, anger, depression], and social function [eg, work attendance]. An increase of ≥ 16 points in IBDQ total score from baseline27 and a total score ≥ 170 points are considered IBDQ response and remission, respectively.28
The FACIT-Fatigue is a Likerttype questionnaire with 13 items measuring fatigue,29,30 and increases of ≥ 9-points from baseline to Weeks 4 or 12 of induction or Week 52 of maintenance were considered as meaningful within-person change [MWPC].31
productivity and performance of daily activities.39 It comprises four domains, namely presenteeism [impairment while working], absenteeism [work time missed], overall work impairment, and activity impairment.39 A decrease of ≥ 6.1% in presenteeism, ≥ 6.5% in absenteeism, ≥ 7.3% in overall work impairment, and ≥ 8.5% in activity impairment were considered an MWPC.40
Statistical analyses
Analyses for U-EXCEL and U-EXCEED were conducted using the intention-to-treat population [ie, all randomised patients who received one or more doses of upadacitinib]. For U-ENDURE, analyses were performed on data from patients who achieved a clinical response to upadacitinib during induction.
The SF-36v2 is a generic HRQoL instrument with eight subscales measuring functioning [physical functioning, perception of general health, role limitations due to physical health challenges, bodily pain, vitality, role limitations due to emotional challenges, social role functioning, and mental health] and yielding PCS and MCS scores. Higher scores indicate better HRQoL.32–34 An increase of ≥ 4.1-points for PCS and ≥ 3.9-points for MCS between baseline and Weeks 4 or 12 of induction, respectively, or Week 52 of maintenance were considered to have met the MWPC criteria.35
Figure 1 Percentage of patients reporting clinically meaningful improvements in IBDQ response, IBDQ remission, ...
EQ-5D is an instrument used for the evaluation of generic health status and HRQoL. Patients classify their health according to five dimensions [mobility, self-care, usual activities, pain/ discomfort, anxiety/depression] at three different levels [no problems, some problems, unable/extreme problems] and rate their current health status on each dimension using a visual analogue scale [VAS] from 0 [worst imaginable health state] to 100 [best imaginable health state].36,37 An increase of ≥ 9.2 points in EQ-5D VAS from baseline to Weeks 4 or 12 of induction or Week 52 of maintenance was considered to constitute MWPC.35,38
The WPAI-CD is a diseasespecific instrument assessing the impact of CD on work
Patient demographic and baseline characteristics were summarised with descriptive statistics. The proportions of patients who achieved clinically meaningful improvements [via MWPC] in IBDQ response, IBDQ remission, FACIT-Fatigue, SF-36v2 PCS, and SF-36v2 MCS from baseline to Weeks 4 and 12 of induction and Week 52 of maintenance were reported. Comparisons were made between the upadacitinib 45mg and placebo groups in the U-EXCEL and U-EXCEED induction trials, and between the upadacitinib 15 mg or upadacitinib 30mg and placebo groups in the U-ENDURE maintenance trial. Adjusted risk differences of upadacitinib compared with placebo, 95% confidence intervals, and p-values were calculated using the Cochran–Mantel–Haenszel test. Risk differences were adjusted for randomisation strata in the U-EXCEL and U-EXCEED induction trials (baseline corticosteroid use [yes or no], endoscopic disease severity [SES-CD < 15 or ≥ 15], and number of prior biologics with inadequate response or intolerance [0, 1, or > 1 for U-EXCEL; > 1 or ≤ 1 for U-EXCEED]), as well as in the U-ENDURE maintenance trial (prior induction population [failure or non-failure to biologics], APS/ SF clinical remission status [yes or no], and endoscopic response [yes or no] at the end of induction). Calculations were based on nonresponder imputation; multiple imputation was incorporated to handle missing data due to the COVID-19 pandemic.
The content of this slide may be subject to copyright: please see the slide notes for details.
Figure 1 Percentage of patients reporting clinically meaningful improvements in IBDQ response, IBDQ remission, FACIT-Fatigue, SF-36 PCS, SF-36v2 MCS, and EQ-5D at [A, B] Week 4 and [C, D] Week 12 of the U-EXCEL and U-EXCEED induction trials; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001 for upadacitinib versus placebo. An increase of ≥ 16 points in IBDQ total score from baseline and a total score ≥ 170 points were considered IBDQ response and remission, respectively. An increase of ≥ 9-points in FACIT-Fatigue, ≥ 4.1-points in SF-36v2 PCS, ≥ 3.9-points, SF-36v2-MCS, and ≥ 9.2-points in EQ-5D VAS from baseline was considered an MWPC. CI, confidence interval; EQ-5D VAS, EuroQol 5 Dimension Visual Analogue Scale; FACIT-Fatigue, Functional Assessment of Chronic Illness–Fatigue; IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary; MWPC, meaningful within-person change; PBO, placebo; PCS, Physical Component Summary; SF-36v2, Short-Form Health Survey-36 version 2; UPA, upadacitinib.
To examine the relationship between clinical remission, endoscopic response, or corticosteroid-free remission and individual HRQoL measures, we compared HRQoL outcomes in
upadacitinib-treated patients who achieved clinical remission, endoscopic response, or corticosteroid-free remission with those who did not achieve these pre-specified outcomes at induction Week 12, using the chi square test. Clinical remission was defined as Crohn’s Disease Activity
Index [CDAI] < 150 at Weeks 4 and 12. Endoscopic response was defined as a decrease in SESCD > 50% from baseline [or for patients with baseline SES-CD of 4, at least a 2-point reduction from baseline]. In patients taking corticosteroids at baseline, those who discontinued corticosteroid
Percentage
use for CD and achieved CDAI clinical remission at Week 12 were considered to have achieved corticosteroid-free remission. A similar analysis was conducted to evaluate the relationship between the proportion of patients who achieved clinically meaningful improvements in FACIT-Fatigue and general HRQoL measures of SF-36v2 PCS and MCS. All missing values were considered non-response.
Results
Patient baseline characteristics
A total of 1021 patients in U-EXCEL and U-EXCEED and 502 upadacitinib clinical responders in U-ENDURE were included in this analysis. Baseline characteristics and demographics were similar across treatment groups and have been previously reported.25
CD had a substantial negative impact on the patients enrolled in the upadacitinib trials, as demonstrated by baseline outcome scores. Mean IBDQ scores at baseline were below 130 [range: 117–122 across groups], which is indicative of severely active disease.41 Both SF-36v2 PCS and MCS baseline scores ranged from 38 to 40, which is lower than the average in healthy individuals [50 and 46, respectively].42,43 For FACITFatigue, baseline scores ranged from 23 to 25, which is substantially below the general population average of 44.44 Mean EQ-5D VAS scores ranged from 49 to 53, which is lower than the average score [80] in the general population.45
BDQ response and remission
Gastroenterology Special Focus: Crohn’s Disease
and mental function as assessed by SF-36v2 PCS and MCS, as well as general HRQoL measured by EQ-5D were observed in patients treated with upadacitinib 45 mg compared with placebo [proportions of patients with improvements ranging from 52.0–57.9% vs 37.2–45.8% for SF-36v2 PCS and MCS and EQ-5D, p < 0.05; Figure 1A, B]. Differences between upadacitinib and placebo for SF-36v2 PCS and MCS and EQ-5D VAS were even greater at Week 12 [Figure 1C, D]. At maintenance Week 52, approximately a third [29.9–36.9%] of patients treated with upadacitinib 15 mg and slightly less than half [41.9–49.3%] treated with 30 mg achieved clinically meaningful improvements in SF-36v2 PCS/MCS and EQ-5D compared with approximately onefourth [18.7–21.3%] of patients in the placebo group [Figure 2B].
WPAI-CD domains
In the U-EXCEL induction trial, a greater percentage of upadacitinib-treated patients compared with placebo had an IBDQ response [71.0% vs 50.2%; p ≤ 0.001] and achieved IBDQ remission [44.2% vs 23.7%; p ≤ 0.001] as early as Week 4 [Figure 1A]. The differences in IBDQ response and IBDQ remission between upadacitinib and placebo were sustained at induction Week 12 [Figure 1C]. Similar results were observed in the U-EXCEED induction trial [Figure 1B, D]. At maintenance Week 52 of U-ENDURE, a greater percentage of patients receiving upadacitinib 15 mg and 30 mg as maintenance treatment achieved an IBDQ response and IBDQ remission compared with placebo [IBDQ response: 39.1%, 53.5% vs 20.4%; IBDQ remission: 36.1%, 45.2% vs 13.5%, all p ≤ 0.001; Figure 2A].
Figure 2 Percentage of patients reporting clinically meaningful improvements in [A] IBDQ response, IBDQ remission, FACIT-Fatigue, and [B] SF 36v2 PCS, SF-36v2 MCS, and EQ-5D at Week 52 of the U-ENDURE maintenance trial; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001 for upadacitinib versus placebo. An increase of ≥ 16 points in IBDQ total score from baseline and a total score ≥ 170 points were considered IBDQ response and remission, respectively. An increase of ≥ 9-points in FACIT-Fatigue, ≥ 4.1-points in SF-36v2 PCS, ≥ 3.9-points SF-36v2-MCS, and ≥ 9.2-points in EQ-5D VAS from baseline was considered an MWPC. CI, confidence interval; EQ-5D VAS, EuroQol 5 Dimension Visual Analogue Scale; FACIT-Fatigue, Functional Assessment of Chronic Illness–Fatigue; IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary; MWPC, meaningful within-person change; PBO, placebo; PCS, Physical Component Summary; SF-36v2, Short-Form Health Survey-36 version 2; UPA, upadacitinib.
The proportions of patients with clinically meaningful improvements in all four WPAI-CD domains were observed in patients treated with upadacitinib compared with placebo in the induction and maintenance trials [Figures 3 and 4]. Overall, the greatest improvements were observed in overall work impairment and activity impairment. At Week 4 of the induction trials, 55.0–59.6% of patients treated with upadacitinib 45 mg experienced clinically meaningful improvement in overall work impairment, compared with 46% in the placebo group [Figure 3A, B]. Similar improvements were noted at Week 12 [Figure 3C, D]. At Week 52, improvement in overall work impairment was greater in patients treated with upadacitinib 15 mg and 30 mg compared with placebo [33.7% and 42.0% vs 19.7%; p ≤ 0.05; Figure 4B].
Volume 18, Issue 11, November 2024, Pages 1804–1818, https://doi.org/10.1093/ecco-jcc/jjae083 may be subject to copyright: please see the slide notes for details.
Discussion
FACIT-Fatigue
Improvements in FACIT-Fatigue were observed as early as Week 4 of both induction trials with a greater percentage of upadacitinibtreated patients experiencing less fatigue than placebo [Figure 1A, B]. Between-group differences prevailed at Week 12 [Figure 1C, D]. At Week 52 of maintenance, a greater proportion of patients
receiving upadacitinib 15 mg and 30 mg experienced improvement in FACIT-Fatigue compared with placebo [U-ENDURE: 28.4% and 43.3% vs 16.9%; p ≤ 0.01; Figure 2A].
SF-36v2 PCS and MCS and EQ-5D VAS
At Week 4 of the induction trials, greater improvements in physical
For patients with moderately-toseverely active CD with one or more conventional and/or biologic therapy failure, upadacitinib 45 mg induction treatment improved fatigue and disease-specific and generic HRQoL measures compared with placebo. A greater proportion of patients treated with upadacitinib versus placebo achieved an IBDQ response, IBDQ remission, and clinically meaningful improvements in FACIT-Fatigue, SF-36v2 PCS and MCS, and EQ-5D as early as Week 4, which were generally sustained through Week 12. A higher percentage of patients receiving upadacitinib induction treatment achieved improvement in WPAICD presenteeism, absenteeism, and overall work impairment
see the slide notes for details.
Figure 3 Percentage of patients reporting clinically meaningful improvements in WPAI-CD presenteeism, absenteeism, overall work impairment, and activity impairment at [A, B] Week 4 and [C, D] Week 12 of the U-EXCEL and U-EXCEED induction trials; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001 for upadacitinib versus placebo. Presenteeism, absenteeism, and overall work impairment are reported only for patients who were employed at baseline. MWPC for presenteeism was defined as a ≥ 6.1% decrease from baseline. MWPC in absenteeism was defined as a ≥ 6.5% decrease from baseline. MWPC for activity impairment was defined as a ≥ 8.5% decrease from baseline. MWPC for overall work impairment response was defined as a ≥ 7.3% decrease from baseline. CI, confidence interval; MWPC, meaningful within-person change; PBO, placebo; UPA, upadacitinib; WPAI-CD, Work Productivity and Activity Impairment in Crohn’s Disease.
versus placebo in U-EXCEED, which included patients with a history of inadequate response or intolerance to one or more biologic therapies for CD. These findings suggest that upadacitinib may be a treatment option for patients who have previously failed
other therapies. Furthermore, among patients who had a clinical response at Week 12 of induction, improvements in fatigue, HRQoL, and work productivity were sustained or enhanced through 52 weeks of maintenance treatment with upadacitinib 15 mg and
upadacitinib 30 mg compared with placebo. Dose-dependent improvements in IBDQ response and remission, FACIT-Fatigue, SF-36v2 PCS and MCS, EQ-5D, and the WPAI-CD domains were observed.
Differences between upadacitinib and placebo groups in clinical remission were observed as early as Week 4 in both induction trials25; we can hypothesise that early clinical improvements along with tapering of corticosteroid use would parallel disease-specific [IBDQ response and remission] and generic [FACIT-Fatigue, SF36v2 PCS, and SF-36v2 MCS] HRQoL improvements that are sustained with long-term treatment [U-ENDURE]. For example, when we analysed the relationship between achievement of clinical remission, endoscopic response, or corticosteroid-free remission and HRQoL measures at Week 12 of the induction studies, we found that a greater proportion of patients who achieved these outcomes [vs those that did not] had concurrent improvements in IBDQ response, IBDQ remission, FACIT-Fatigue, and SF-36v2 PCS and MCS. Furthermore, patients who reported clinically meaningful improvements in FACIT-Fatigue [relative to those who did not] at Week 12 also reported improvements in physical and mental function [via SF-36v2 PCS/MCS]. The early HRQoL improvements may be explained by the rapid action of Janus kinase inhibitors46 and their impact on disease symptoms.47
Improvements in IBDQ response, IBDQ remission, FACIT-Fatigue, SF-36v2 PCS, SF-36v2 MCS, and EQ-5D were consistent between the mixed study population in U-EXCEL [ie, patients with prior conventional or biologic therapy failure] and patients with prior biologic failures in U-EXCEED, indicating that upadacitinib treatment can lead to early HRQoL improvements irrespective of prior treatment failures. Consistent with the STRIDE-II recommendations, which highlight normalisation of quality of life as a core treatment goal,2 the onset of treatment response for HRQoL and fatigue, apparent as early as Week 4 of treatment, suggests that upadacitinib may enable patients with CD to establish and maintain a sense of normality shortly after initiating therapy.
Fatigue is the most common and burdensome systemic symptom reported by patients with CD.23 The overwhelming lack of energy or continuing tiredness that is not relieved48 has a negative
often remains unaddressed during treatment due to prioritisation of clinical remission. The findings of this study indicate that patients receiving upadacitinib may experience early fatigue improvement at Week 4 of treatment. The sustained improvements in fatigue through Weeks 12 and 52 compared with placebo indicate that the effect observed in patients treated with upadacitinib is not subjective to a placebo effect. Additionally, limited understanding of the multifaceted nature of fatigue prevents health care professionals from addressing, assessing, or asking patients about fatigue, and in turn, prevents patients from reporting it and challenging fatigue as an inevitable symptom.49 Early improvements in fatigue may facilitate early doctor–patient discussions about common perceptions of fatigue, and enable monitoring or allaying patients’ relevant health concerns that affect their quality of life.50
Patients with CD experience significant physical [eg, poor sleep quality],51 emotional, and mental health challenges [eg, depressive symptoms, stress, anxiety],52,53 and are willing to trade a considerable part of their life expectancy for full recovery from the disease.54 These challenges are associated with worse quality of life and are partly explained by adverse illness perceptions resulting from patients’ thoughts of the chronic nature of the disease and having to live with uncontrollable symptoms.52,55 The early and sustained improvements in HRQoL and work productivity observed with upadacitinib may contribute to the modification of illness perceptions and more effective disease management, particularly when combined with referrals to psychological and/ or social support.52,56 Considering the need to take a holistic view of patients’ health and HRQoL, including physical, emotional, and social aspects as well as their ability to work during clinical interventions,2,57 these findings are encouraging for patients receiving upadacitinib treatment.
The strengths of the U-EXCEL, U-EXCEED, and U-ENDURE trials include the employment of a wide array of patientreported outcomes, such as IBDQ, FACIT-Fatigue, SF-36v2 PCS and MCS, EQ-5D, and WPAI-CD, which captured different aspects of diseasespecific and generic HRQoL and work productivity in patients with CD receiving upadacitinib treatment. Additionally, patient
patients reporting clinically meaningful
Gastroenterology Special Focus: Crohn’s Disease
Figure 4 Percentage of patients reporting clinically meaningful improvements in WPAI-CD [A] presenteeism, absenteeism, and [B] overall work impairment, and activity impairment at Week 52 of the U-ENDURE maintenance trial; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001 for upadacitinib versus placebo. Presenteeism, absenteeism, and overall work impairment data are reported only for patients who were employed at baseline. MWPC for presenteeism was defined as a ≥ 6.1% decrease from baseline. MWPC in absenteeism was defined as a ≥ 6.5% decrease from baseline. MWPC for activity impairment was defined as a ≥ 8.5% decrease from baseline. MWPC for overall work impairment was defined as a ≥ 7.3% decrease from baseline. CI, confidence interval; MWPC, meaningful withinperson change; PBO, placebo; UPA, upadacitinib; WPAI-CD, Work Productivity and Activity Impairment in Crohn’s Disease.
data were collected and assessed longitudinally, including early time points, which enabled observing the onset and sustainability of HRQoL improvements. The randomised, double-blind, placebo-controlled design and the overall large sample size of the trials attest to the internal validity of the findings. The trials also had certain limitations, as the findings cannot be generalised to real-world settings and patients with milder CD who were not represented in the sample. Future trials investigating long-term HRQoL improvements beyond Week 52 of treatment with upadacitinib are warranted.
Conclusion
In addition to the achievement of clinical remission and endoscopic improvements, the study findings indicate that upadacitinib improves disease-specific and generic HRQoL, fatigue, and work productivity in patients with CD with prior conventional or biologic treatment failure. HRQoL improvements in patients receiving upadacitinib were observed as early as Week 4 and sustained through 52 weeks of maintenance treatment. Future observational studies using real-world data are warranted to provide insight into long-term HRQoL-related benefits for patients with CD receiving upadacitinib treatment.
References available on request
New Research for Inflammatory Bowel Disease
see the slide notes for details.
Researchers from RCSI University of Medicine and Health Sciences have uncovered a novel mechanism linking inflammatory bowel disease (IBD) with an increased risk of a serious blood clotting disorder, venous thromboembolism.
The study, published in Nature Communications, identifies a specific subset of immune cells that may contribute to excessive blood clotting in IBD patients, revealing potential therapeutic targets for reducing this risk. IBD, which includes Crohn’s disease and ulcerative colitis, affects millions worldwide and is associated with systemic inflammation. Patients with IBD face a significantly higher risk
of developing blood clotting complications, including deep vein thrombosis and pulmonary embolism, but the underlying causes have remained unclear.
The research team, led by Professor Roger Preston, Associate Professor, RCSI School of Pharmacy and Biomolecular Sciences, discovered that activated immune cells called CD4+ T cells, which are critical in IBD-associated inflammation, express tissue factor, a key initiator of blood clotting. These tissue factor-expressing cells were found in both the intestine and bloodstream of IBD patients, suggesting they may contribute to an increased risk of clot formation.
“Understanding the mechanisms behind the heightened clotting risk in IBD patients is crucial for developing safer, more targeted treatments,” said Professor Preston. “Our findings show that this subset of T cells not only drive gut inflammation but also have the potential to contribute to blood clotting, which may help us understand why IBD patients face a greater risk of serious clotting disorders.”
The study also pointed to a possible solution. The team found that activated protein C (APC), an anti-inflammatory and anticoagulant protein in the blood, can help counteract the clotting activity of these T cells. When attached to the T cells, APC
reduces their ability to trigger clot formation, offering a potential new treatment approach.
“These findings are particularly exciting because they suggest that targeting this pathway in T cells could help manage clotting risk in IBD patients” added Dr Preston. With IBD incidence rising globally, this research has important implications for improving patient outcomes. Current anticoagulant therapies carry bleeding risks, making targeted anti-inflammatory approaches such as an APC-based strategy particularly promising.
The study was supported by funding from Research Ireland, Children’s Health Ireland and the Health Research Board.
Gastroenterology Special Focus: Crohn’s Disease
Management and Treatment of Crohn’s Disease
Written by Dr Orlaith Kelly, Consultant Gastroenterologist & Ronald Chia, Blackrock Health
Introduction
Crohn’s disease is a type of inflammatory bowel disease and is defined by transmural inflammation that can exist anywhere between from the mouth to anus. It is associated with diarrhoea and bleeding but also more systemic features such as mouth ulcers, abdominal pain, nausea and vomiting, loss of appetite, weight loss, malnutrition, loss of energy and anaemia. Compared to ulcerative colitis, Crohn’s disease can appear more subtly. Disease can be complicated by fistulae (connecting tracts between the bowel and other organs or skin surface), strictures (narrowing), or abscesses/ collections.1 Disease mainly affects the ileal, ileocolonic, or colonic regions.1 Treatment approaches in recent years have focused on a treat to target approach in order to avoid complications and digestive damage in the long run.2
Complications include
Intestinal obstruction
Malignancy
Immunomodulator-associated sepsis1
Extraintestinal manifestations include
Liver disease
Metabolic bone disease
Kidney stones
Pathophysiology
Crohn’s disease is thought to develop due to an interaction of genetic, environmental and immune factors and is complex in its aetiology similar to other chronic illnesses such as diabetes or multiple sclerosis with multiple susceptible genotypes (> 200 genetic SNP mutations associated) and a myriad of possible triggers.3
Intestinal macrophages, neutrophils, and helper T-cells (TH-1, TH-17) are the primary mediators of the inflammatory cascade in the gastrointestinal tract.4, 5 Ileocaecal damage has been identified in particular, which has resulted in anemia in the form
of fecal bleeding and reduced capacity to absorb vitamin B12. Crohn’s also starts from the superficial mucosal layer and creates ulcers from the inflammation and spreads into deeper layers. If detected early, endoscopic findings can identify hyperemia and edema in the inflamed mucosal layers. Skip lesions form from these deep ulcers as well.6
Epidemiology
In Ireland, approximately 40,000 people were diagnosed with inflammatory bowel disease according to a study published in January 2024. Severity was noted to vary to an unknown extent.7 It has equal gender distribution and a peak incidence in early adulthood/adolescence and again in middle age demographics.
Throughout the world, the rates of Crohn’s disease vary, likely related to genetic predisposition and industrialization. In the United States, Crohn’s disease mainly affects people in rural or urban areas, and northern Europeans and people of Jewish descent also contribute to high incidence rates.8 Meanwhile, prevalence in Asians, Africans, and South Americans living in North America is low.8 However, there is emerging data that reveals rising incidence rates in industrialized areas throughout Asia, Africa, and Australasia.9
Current Treatments/ Management
Medical management
Treatment algorithms for Crohn’s disease are vast because of varied disease location. Severity and complications at outset. Therefore, more refined and individualised approaches need to be taken for each patient so that they are cared for appropriately.
Mild to moderate disease would sometimes warrant the use of corticosteroids to stabilize the disease. However, chronic use is not advised because of potential side effects emerging such as osteoporosis, osteonecrosis, and adrenal insufficiency.1
For more severe staging of Crohn’s, TNF-alpha inhibitors like infliximab and adalimumab are commonly used to lower the inflammatory response. These are known to be more effective than immunomodulators such as azathioprine. However, combination therapies using infliximab and azathioprine still prove to be more effective than administering each approach individually.1
Methotrexate continues to be used as another medication for Crohn’s disease especially in the paediatric population, but it is also commonly known to lead to hepatotoxicity, especially if taken at doses higher than what is prescribed.10
Other classes of biologic agent are also effective and used widely for treatment of Crohn’s disease. These include IL-12 or IL-23 inhibitors (such as ustekinumab or risankizumab), JAK inhibitors (such as tofacitibnib or upaticitinib), anti-integrin antibodies (such as vedolizumab) and sphingolipid (such as ozanimod or etrasimod).
Surgical Treatment
Complications involving strictures, bowel obstructions, or malignancies are some primary justifications for why ileorectal strictureplasty and surgical resection would be necessary. The emergence or potential of fistulating disease and risk of bleeding and perforation would also contribute to justification for either option.11 Perianal disease
often requires management of septic complications or drainage procedures and occasionally diversion ileostomy and with severe Crohn’s colitis refractory to medical treatment colectomy can be required.
Long-term Monitoring
After remission, according to STRIDE2 consensus guidelines, patients are advised to check their biomarkers (CRP and fecal calprotectin) with their providers every 6 to 12 months to measure the level of effectiveness in therapeutic response. However, upon newly developed Crohn’s disease or recurrence, then the American Gastroenterology Association recommends that patients check their biomarkers every 2 to 4 months. Patients should also have routine endoscopies or imaging to check on the status of their remission.12
Dietary Management
Patients who are anaemic with ileal disease often benefit greatly by adding vitamin B12 supplements to their diet to account for their fecal blood loss.10 Weight maintenance and diet trigger avoidance during flares are also important aspects of dietary management. In paediatrics in particular and also in difficult to manage penetrating disease, exclusive or partial enteral nutrition can be used to treat the disease as an elemental diet.
Ronald Chia
Dr Orlaith Kelly
Gastroenterology Special Focus: Crohn’s Disease
Psychological Support
As with any chronic disease, Crohn’s disease can be difficult for patients to navigate and cope with. It greatly affects quality of life parameters and can be challenging on an everyday basis. Ultimately, IBD patients have higher levels of anxiety and depression. Psychological support from IBD nurses and clinical psychologists is an important part of the overall multidisciplinary treatment provided to Crohn’s patients.
Current Research/Novel Therapies
Endoscopic procedures are improving in their capacity to identify the recurrence of Crohn’s disease. A POCER postoperative index was used in the context of ulcer size and anastomosis, meaning that this was used to measure the severity of Crohn’s with regards to the level of anastomotic recurrence.13 This is a newly defined index, which warrants further investigation before its use can be generalised.13
Another important therapy that is emerging in clinical importance is the use of the Lemann index. Like the POCER postoperative index, the Lemann index is also focused on the progression of Crohn’s disease and the assessment of damage to any impacted areas of the bowel. More specifically, the latter index also has a grading system ranging between 0 to 3 (least to most severe), and it measures the inflammatory damage to all parts of the bowel.14 Studies have been conducted to relate the use of the Lemann
index to a patient’s quality of life. The general outcome is that the Lemann index and quality of life have significant negative correlation.14, 15 Therefore, the viability of using this index is validated as an additional tool for Crohn’s disease assessment in clinical trials. However, with additional studies, there should be great prospects to incorporate the Lemann index into clinical practice and personalise the treatments that are given to IBD patients to ensure more effective and efficient recovery.
Combination therapies are still being explored with deeper research into infliximab and methotrexate uses targeted towards geriatric and pediatric populations alike. New monoclonal antibodies are being considered to broaden the options for Crohn’s disease.16 The dashboard approach of looking at potential genetic predisposition, immune activation factors and environmental triggers are also continuing to be researched in an effort to provide better overall therapeutic strategies for this challenging condition.
References
1. Ranasinghe IR, Tian C, Hsu R. Crohn Disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Feb 7]. Available from: http://www.ncbi.nlm.nih. gov/books/NBK436021/
2. Srinivasan AR. Treat to target in Crohn’s disease: A practical guide for clinicians. World J Gastroenterol. 2024 Jan
7;30(1):50–69.
3. Matthews SM, Eshelman MA, Berg AS, Koltun WA, Yochum GS. The Crohn’s disease associated SNP rs6651252 impacts MYC gene expression in human colonic epithelial cells. PLoS ONE. 2019 Feb 22;14(2):e0212850.
4. Gálvez J. Role of Th17 Cells in the Pathogenesis of Human IBD. ISRN Inflamm. 2014 Mar 25;2014:928461.
5. Targan SR. Biology of inflammation in Crohn’s disease: mechanisms of action of anti-TNF-a therapy. Can J Gastroenterol J Can Gastroenterol. 2000 Sep;14 Suppl C:13C-16C.
6. Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. The Lancet. 2007 May 12;369(9573):1641–57.
7. Crohn’s & Colitis Ireland [Internet]. [cited 2025 Feb 7]. IBD Explained. Available from: https://crohnscolitis. ie/support/diagnosis/ explanation/
8. Ghersin I, Khteeb N, Katz LH, Daher S, Shamir R, Assa A. Trends in the epidemiology of inflammatory bowel disease among Jewish Israeli adolescents: a population-based study. Aliment Pharmacol Ther. 2019 Mar;49(5):556–63.
9. Coward S, Clement F, Benchimol EI, Bernstein CN,
Avina-Zubieta JA, Bitton A, et al. Past and Future Burden of Inflammatory Bowel Diseases Based on Modeling of Population-Based Data. Gastroenterology. 2019 Apr 1;156(5):1345-1353.e4.
10. Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. J Crohns Colitis. 2020 Jan 1;14(1):4–22.
11. Campbell L, Ambe R, Weaver J, Marcus SM, Cagir B. Comparison of conventional and nonconventional strictureplasties in Crohn’s disease: a systematic review and meta-analysis. Dis Colon Rectum. 2012 Jun;55(6):714–26.
12. Ranasinghe IR, Tian C, Hsu R. Crohn Disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Feb 7]. Available from: http://www.ncbi.nlm.nih. gov/books/NBK436021/
13. De Cruz P, Hamilton AL, Burrell KJ, Gorelik A, Liew D, Kamm MA. Endoscopic Prediction of Crohn’s Disease Postoperative Recurrence. Inflamm Bowel Dis. 2022 May 4;28(5):680–8.
14. Pariente B, Torres J, Burisch J, Arebi N, Barberio B, Duricova D, et al. Validation and Update of the Lémann Index to Measure Cumulative Structural Bowel Damage in Crohn’s Disease. Gastroenterology. 2021 Sep 1;161(3):853-864. e13.
15. Straksyte V, Kiudelis G, Gineikiene I, Janciauskas D, Basevicius A, Lukosevicius S, et al. Lemann Index for Assessment of Crohn’s Disease: Correlation with the Quality of Life, Endoscopic Disease Activity, Magnetic Resonance Index of Activity and C- Reactive Protein. Open Med. 2019 Nov 7;14:785–91.
16. Optimal Doses of Methotrexate Combined with Anti-TNF Therapy to Maintain Clinical Remission in Inflammatory Bowel Disease | Journal of Crohn’s and Colitis | Oxford Academic [Internet]. [cited 2025 Feb 7]. Available from: https:// academic.oup.com/ecco-jcc/ article/9/4/312/488446.
Break the habit with Varenicline Teva
Varenicline (alone or in combination with nicotine replacement therapy (NRT)) is recommended by the HSE as first-line treatment for smoking cessation.1
Available on private prescription only.
Varenilcine 0.5mg and 1mg Film-Coated Tablets Abbreviated Prescribing Information Presentation: Each film-coated tablet contains varenicline citrate equivalent to 0.5mg and 1mg varenicline. Indications: Varenicline is indicated for smoking cessation in adults. Dosage and administration: Oral use. Adults: The recommended dose is 1mg Varenicline twice daily following a 1-week titration (see SmPC for details). Children: Not recommended for use. Elderly: No dosage adjustment is necessary. Elderly patients are more likely to have decreased renal function, prescribers should consider the renal status of an elderly patient. Renal impairment: No dosage adjustment is necessary for patients with mild (estimated creatinine clearance >50ml/min and ≤80ml/min) to moderate (estimated creatinine clearance ≥30ml/min and ≤50ml/min) renal impairment. For patients with severe renal impairment (estimated creatinine clearance <30ml/min), the recommended dose of Varenicline is 1mg once daily. Hepatic impairment: No dosage adjustment is necessary. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Precautions and warnings: Physiological changes resulting from smoking cessation, with or without treatment with Varenicline, may alter the pharmacokinetics or pharmacodynamics of some medicinal products, for which dosage adjustment may be necessary (examples include theophylline, warfarin and insulin). As smoking induces CYP1A2, smoking cessation may result in an increase of plasma levels of CYP1A2 substrates. Changes in behaviour or thinking, anxiety, psychosis, mood swings, aggressive behaviour, depression, suicidal ideation and behaviour and suicide attempts have been reported in patients attempting to quit smoking with Varenicline. Depressed mood, rarely including suicidal ideation and suicide attempt, may be a symptom of nicotine withdrawal. Clinicians should be aware of the possible emergence of serious neuropsychiatric symptoms in patients attempting to quit smoking with or without treatment. If serious neuropsychiatric symptoms occur whilst
Teva Pharmaceuticals Ireland, Digital Office Centre Swords, Suite 101 - 103, Balheary Demesne, Balheary Road, Swords, Co Dublin, K67E5AO, Ireland.
Freephone: 1800 - 201 700 | Email: info@teva.ie
Prescription Only Medicine. Further information is available on
on Varenicline treatment, patients should discontinue Varenicline immediately and contact a healthcare professional for re-evaluation of treatment. Smoking cessation, with or without pharmacotherapy, has been associated with exacerbation of underlying psychiatric illness (e.g. depression). In clinical trials and post-marketing experience there have been reports of seizures in patients with or without a history of seizures, treated with Varenicline. Varenicline should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold. At the end of treatment, discontinuation of Varenicline was associated with an increase in irritability, urge to smoke, depression, and/or insomnia in up to 3% of patients. In such instances, tapering should be considered. Patients taking Varenicline should seek immediate medical attention if they experience signs and symptoms of myocardial infarction or stroke. Interactions: Varenicline has no clinically meaningful drug interactions (see SmPC for further details). No dosage adjustment of Varenicline or co-administered medicinal products listed below is recommended. In vitro studies indicate that Varenicline is unlikely to alter the pharmacokinetics of compounds that are primarily metabolised by cytochrome P450 enzymes. Furthermore, since metabolism of Varenicline represents less than 10% of its clearance, active substances known to affect the cytochrome P450 system are unlikely to alter the pharmacokinetics of Varenicline, therefore a dose adjustment of Varenicline would not be required. Varenilcine is not known to affect the pharmacokinetics of metformin, digoxin, bupropion and warfarin. Coadministration of cimetidine, with Varenicline increased the systemic exposure of varenicline by due to a reduction in varenicline renal clearance. In patients with severe renal impairment, the concomitant use of cimetidine and Varenicline should be avoided. Pregnancy and lactation: As a precautionary measure, it is preferable to avoid the use of varenicline during pregnancy. A decision on whether to continue/discontinue breast-
feeding or to continue/discontinue therapy with varenicline should be made taking into account the benefit of breast-feeding to the child and the benefit of varenicline therapy to the woman. Effects on ability to drive and use machines: Varenicline may have minor or moderate influence on the ability to drive and use machines. Varenicline may cause dizziness, somnolence and transient loss of consciousness, and therefore may influence the ability to drive and use machines. Adverse reactions: Diabetes mellitus, suicidal ideation, depression, hallucinations, psychosis, seizure, cerebrovascular accident, transient loss of consciousness, myocardial infarction, angina pectoris, tachycardia, atrial fibrillation, electrocardiogram ST segment depression, gastritis, haematemesis, severe cutaneous reactions including Stevens Johnson Syndrome and Erythema Multiforme, angioedema. Very Common: Nasopharyngitis, abnormal dreams, insomnia, headache, nausea. Common: Bronchitis, sinusitis, weight increased, decreased appetite, increased appetite, somnolence, dizziness, dysgeusia, dyspnoea, cough, gastrooesophageal reflux disease, vomiting, constipation, diarrhoea, abdominal distension, abdominal pain, toothache, dyspepsia, flatulence, dry mouth, rash, pruritus, arthralgia, myalgia, back pain, chest pain, fatigue, liver function test abnormal. Consult the Summary of Product Characteristics in relation to other side effects. Overdose: In case of overdose, standard supportive measures should be instituted as required. Legal category: POM. Marketing Authorisation Number: 0.5mg PA1986/129/001, 1mg PA1986/129/002. Marketing Authorisation Holder: Teva B.V., Swensweg 5, 2031GA Haarlem, Netherlands. Job Code: MED-IE-00084. Date of Preparation: July 2024.
References: 1. Stop Smoking. National Clinical Guideline No. 28, 2022.
events should be reported. Reporting forms and information can be found at www.hpra.ie.
50 HPH Winner Profile
ONOURS Hospital Professional 2024
GSK ViiV Infectious Diseases Project of the Year
Innovators in Infectious Disease Management
Dr Peter Barrett and the Health Protection Team at the Department of Public Health, Cork & Kerry, have been awarded the GSK ViiV Infectious Diseases Project of the Year 2024. Recognised for their pioneering Acute Health Protection Duty Room initiative, the team has transformed the management of infectious diseases in the region, ensuring a rapid, structured, and sustainable response to emerging health threats.
Revolutionising Health Protection with the Duty Room Model
Launched in October 2022, the Acute Health Protection Duty Room was developed in response to the growing complexity and volume of infectious disease notifications in Cork and Kerry, particularly following the COVID-19 pandemic. This new model centralised and streamlined the
management of cases, allowing the team to shift from a reactive to a proactive approach in handling public health threats.
By enhancing both internal and external communication mechanisms, the Duty Room has ensured faster and more accurate information dissemination to healthcare providers, nursing homes, and community settings. It has also facilitated a complete
Dr Peter Barrett and the Health Protection Team, Department of Public Health, Cork & Kerry, winners of the GSK ViiV Infectious Diseases Project of the Year presented by Youssef Youssef, Business Unit Head, HIV, GSK ViiV Ireland
transition from paper-based to electronic disease surveillance systems, significantly improving the accuracy and timeliness of public health responses.
Dr Peter Barrett, the Project Lead, commented on the Honour:
"Receiving this Honour means a great deal to our team. It’s an acknowledgment of the highquality service that our staff in the Department of Public Health South West continue to provide for the population of Cork and Kerry."
Key Achievements and Impact
• Efficient Management of Cases: Since its launch, the Duty Room has handled thousands of cases of notifiable diseases and hundreds of outbreaks efficiently.
• Enhanced Communication: 95% of staff reported that communication processes work well, and 93% expressed overall satisfaction with the Duty Room model.
• Robust Surveillance: Shifted to 100% electronic surveillance for infectious diseases, reducing administrative delays and enhancing the quality of data available for decision-making.
• Staff Satisfaction and Support: 95% of staff felt adequately supported, and 91% reported effective learning opportunities within the Duty Room.
These achievements highlight the Duty Room's success in creating a resilient and responsive public health infrastructure capable of managing both routine and emerging infectious disease threats.
Innovations in Infectious Disease Management
The success of the Duty Room initiative lies in its innovative approaches, which include:
• Daily Huddles: Facilitated real-time information exchange and case management, with 91% of staff agreeing that these were effective.
• Standard Operating Procedures (SOPs): Established clear roles and responsibilities for all team members, ensuring consistent and high-quality responses to public health threats.
• Electronic Surveillance and Reporting: Automated reporting processes have reduced delays in case detection and escalation, improving the overall efficiency of the public health response.
These innovations have set a new benchmark for infectious disease management not just in Cork and Kerry but across Ireland, with several other regional Departments of Public Health now exploring the Duty Room model for adoption.
A Collaborative Multidisciplinary Approach
Dr Barrett’s leadership has been instrumental in fostering a strong multidisciplinary approach, with contributions from:
• Epidemiologists: Leading disease surveillance and data analysis.
• Public Health Nurses: Managing case investigations and follow-up care.
• Administrative and Logistical Staff: Ensuring smooth operations and resource allocation.
• Specialist Registrars and Senior Medical Officers: Providing clinical oversight and expertise.
This collaborative model has not only improved the speed and accuracy of the public health response but has also created a collegial environment for staff training and development
Youssef Youssef, Business Unit Head, HIV at GSK ViiV Ireland, praised the team’s efforts:
"Infectious diseases present ongoing challenges globally. This Honour is a celebration of the exceptional achievements of our
Youssef Youssef, Business Unit Head, HIV, GSK ViiV Ireland with Dr Peter Barrett and the Health Protection Team, Department of Public Health, Cork & Kerry
healthcare professionals in Ireland, who continue to make a direct impact on patient care."
National Recognition and Future Directions
The success of the Duty Room has attracted national attention, with Dr Barrett invited to present the model at the National Public Health Engagement Day and to chair a National Working Group on Multidisciplinary Team Working in Health Protection. The model’s scalability and effectiveness have prompted other Public Health departments in Ireland to consider adopting similar approaches.
Plans for the future include:
• Expanding Automation: Increasing the use of electronic surveillance and reporting tools to further enhance efficiency.
• Standardising Training: Developing a national training framework based on the Duty Room model to upskill public health professionals across Ireland.
• Integrating with Primary Care: Strengthening partnerships with GPs and community healthcare providers to ensure seamless management of infectious diseases from notification to resolution.
Dr Barrett said, “Receiving this Honour means a great deal to our team. In public health we have been through a pretty tumultuous time over the last few years. Obviously, in trying to manage a pandemic, our speciality has also
gone through a lot of reform and restructuring and so it has been a busy time and a lot of change for our staff. This is acknowledgement of the high quality service that our staff in the Department of Public Health South West are continuing to provide for the population of Cork and Kerry.”
Youssef Youssef, Business Unit Head with GSK Viiv said, “The GSK × ViiV team are honoured to sponsor the Infectious Diseases Project of the Year for 2024, recognising exceptional achievements from our remarkable hospital professionals here in Ireland.
“Infectious Disease present ongoing challenges globally, putting increased pressure on our healthcare system and its staff. This demands dedication, innovative solutions and research to find new approaches to enhance the field of infectious disease.
“Our commitment to sponsoring this honour stems from our focus of being Ambitious for Patients, Accountable for Impact, and Doing the Right Thing, driven from our purpose of uniting science, talent & technology to get ahead of disease together.
“This is where we believe this award gives our healthcare professionals the recognition they deserve, and an opportunity to celebrate those key contributions that are directly impacting patients and enhancing care in the field.”
Congratulations to Dr Peter Barrett and the Health Protection Team at the Department of Public Health, Cork & Kerry, for their outstanding contribution to infectious disease management and public health protection!
52 HPH Winner Profile ONOURS Hospital Professional 2024
Viatris Excellence in Cardiovascular Initiative
Beaumont Hospital’s Cardiac Rehabilitation Team: Leaders in Cardiovascular Care
The Cardiac Rehabilitation (CR) Team at Beaumont Hospital has been awarded the Viatris Excellence in Cardiovascular Initiative for 2024. Recognised for their comprehensive and patientcentred approach to cardiac rehabilitation, the team’s work has significantly improved medication adherence, clinical outcomes, and quality of life for cardiac patients across Ireland.
Transforming Cardiac Care with an Accredited Programme
Beaumont Hospital’s Cardiology Department is the first and only centre in Ireland and the UK to achieve international accreditation in cardiac rehabilitation and secondary prevention. The team manages the largest annual throughput of cardiac patients in Ireland, providing a model of
care that has been internationally recognised for its excellence.
The CR programme combines medical management, lifestyle interventions, and psychological support in a 10-week supervised exercise circuit, complemented by group education sessions on medication management and lifestyle changes. This holistic approach ensures that patients
Winners of the Viatris Excellence in Cardiovascular Initiative 2024 Beaumont Cardiac Rehabilitation Team with Niamh Brennan, Marketing Lead, Viatris and host Marty Whelan
receive comprehensive care tailored to their individual needs.
Alison Cahill, Sadhbh Ni Cheallaigh, and Lorna Carroll, who accepted the Honour on behalf of the team, commented:
"We are thrilled and delighted to accept this Honour on behalf of our entire team. This recognition motivates us to continue delivering first-class care to our patients."
Key Achievements and Impact
o International Accreditation:
The first CR centre in Ireland and the UK to be accredited, setting a benchmark for excellence in cardiac care.
o Medication Optimisation: Clinical audits identified that 31% of patients required medication adjustments during the programme, significantly improving adherence and outcomes.
o Impressive Outcomes:
• 53% of patients achieved a lowdensity lipoprotein cholesterol (LDL-C) level of <1.8 mmol/l by the end of CR.
• 77% of patients achieved blood pressure targets of <140/90 mmHg.
• 92% of patients knew their cholesterol levels and how to manage them effectively.
Patient Satisfaction: Achieved a mean PACIC score of 3.58, exceeding international benchmarks for CR patient satisfaction.
These achievements underscore the success of Beaumont’s CR programme in not only reducing cardiovascular risk factors but also enhancing patients' understanding and management of their own conditions.
Innovations in Multidisciplinary Care
The success of the CR programme lies in its multidisciplinary team (MDT) approach, which includes:
o Specialist Nurses and Nurse Prescribers: Conduct risk assessments and adjust medications promptly.
o Clinical Pharmacists: Lead weekly group sessions on medication adherence and provide individual consultations.
o Clinical Psychologists: Address mental health and behavioural aspects of cardiac recovery, promoting adherence to treatment regimens.
o Dietitians and Exercise Specialists: Provide tailored advice on nutrition and physical activity.
This MDT approach ensures seamless care coordination and leverages the expertise of each
team member to optimise patient outcomes.
Addressing Medication Adherence: A Key Priority
Medication adherence is crucial for preventing recurrent cardiac events. Beaumont’s CR team introduced several initiatives to improve adherence:
o Weekly Group Pharmacy Sessions: Educate patients on medication purpose, side effects, and practical tips for managing prescriptions.
o Psychological Support: Address beliefs about medication and promote adherence through motivational interviewing and cognitive reframing.
o Digital Health Integration: Use of smart screens and multimedia in the CR waiting area to reinforce key messages on medication adherence.
These initiatives have led to a 21% reduction in medication non-adherence and a significant decrease in patients' concerns about medication side effects
Patient-Centred Success Stories
The CR team’s patient-centred approach is reflected in numerous success stories:
o Personalised Care: Clinical pharmacists conduct pre-session reviews of patient histories to address specific concerns during group education.
Winners of the Viatris Excellence in Cardiovascular Initiative 2024 Beaumont Cardiac Rehabilitation Team with Niamh Brennan, Marketing Lead, Viatris
o Empowering Patients: Sessions emphasise the importance of medication adherence as a form of selfempowerment, helping patients take control of their health.
o Feedback-Driven Improvements: Regular patient feedback is used to refine and expand CR services, ensuring that the programme evolves to meet patient needs effectively.
Patients have consistently expressed high satisfaction with the programme, highlighting the compassionate care and the effectiveness of the multidisciplinary approach.
Future Directions - Scaling Excellence Nationally
The success of Beaumont’s CR programme has set a benchmark for cardiac care in Ireland. Looking ahead, the team aims to:
o Expand the Role of Pharmacists: Increase the frequency of pharmacist-led sessions to further improve medication adherence.
o National Rollout: Advocate for a standardised national model of CR based on Beaumont’s success, with enhanced MDT roles including nurse prescribers and clinical psychologists.
o Advanced Digital Health Tools: Integrate more digital solutions to support remote monitoring and follow-up of CR patients.
Accepting the Honour team members Alison Cahill, Sadhdbh ni Cheallaigh and Lorna Carroll told us, “We are thrilled and delighted, and feel very privileged to accept this Honour here tonight because we are accepting it collectively on behalf of our entire team of staff who deliver first class service to patients.
“Through all our team members skills we are able to offer a well-rounded service and help get patients back on the road to recovery and to full health. For those hospital professionals such as in our team who work constantly on the front-line, we are always striving for a better service that will benefit our patients, engage with our patients and which is all about giving our patients the best opportunity and the easiest access to help them stay well and out of hospital.
“To get recognition for that work is our sign to keep going.”
Enis Otuk, Country Manager Ireland, Viatris said, “Viatris is a global healthcare company uniquely positioned to bridge the traditional divide between generics and brands, combining the best of both, to more holistically address healthcare needs globally. With a mission to empower people worldwide to live healthier at every stage of life, we provide access at scale.
“In Ireland, we have over 1,600 dedicated colleagues across five sites who work to provide access to medicines, develop innovative solutions and improve healthcare for patients.
“As the Country Manager for Ireland, it is my great pleasure to congratulate the finalists of the Viatris Excellence in Cardiovascular Initiative Award 2024.
“It is wonderful to showcase the commitment of cardiovascular healthcare professionals and teams in Ireland. This Honour recognises the pivotal role that these professionals play in driving excellence through innovation in cardiovascular services and care for their patients.
“Thank you all for your ongoing dedication to patients across Ireland.”
54 HPH Winner Profile ONOURS Hospital Professional 2024
MedFind Solutions Innovation and Service Development
Innovation in Maternity Care
The National Maternity Hospital’s Affirmation Project: Innovating Maternity Care in Ireland
The National Maternity Hospital (NMH) has been awarded the MedFind Solutions Innovation and Service Development Honour for 2024. Recognised for their pioneering project, The Impact of Affirmation Cards During Pregnancy, Birth, and Postnatal, the team’s work has significantly improved the mental well-being and birth experiences of women across Ireland.
Empowering Women Through Positive Affirmations
The Affirmation Project was spearheaded by Alice Hoffmeister, Community Midwifery Manager, who identified the powerful impact of spoken affirmations in reducing anxiety and enhancing confidence during labour and the postnatal period. With funding from the NMH Foundation, over
800 sets of affirmation cards were distributed nationally within a six-month period in 2023, demonstrating the scalability and effectiveness of this initiative.
The cards, designed to counteract fear and promote self-belief, cover all stages of maternity care—from pregnancy to the postnatal period. Each set includes positive messages that
Matthew Farrelly, Chief Executive Officer, MedFind Solutions with Alice Hoffmeister, winner of the MedFind Solutions Innovation and Service Development Honour. Alice’s project was – The Impact of Affirmation Cards During Pregnancy, Birth and Postnatal: A Research Stidy, the National Maternity Hospital
empower women to manage pain, reduce anxiety, and focus on a positive birth experience.
Alice Hoffmeister, reflecting on the Honour, stated: "This means so much to me and to the wider team. It truly is a validation of all the hard work that has gone into promoting a positive birth experience for women."
Key Achievements and Impact
Improved Mental Well-being:
100% of surveyed women reported increased selfconfidence and reduced fears due to the affirmation cards.
97.5% said they would recommend the cards to a friend. 96% reported that the cards helped them have a more active birth.
Broad Reach and Accessibility
Over 800 sets of cards were distributed nationally, making a significant impact across Ireland.
Blank cards were later introduced to allow women to personalise their affirmations, further enhancing the sense of empowerment and ownership over their birth experience.
Inclusive and Transferable Model
Plans to translate the cards into multiple languages are already underway, ensuring that women from diverse backgrounds can benefit.
The project’s simplicity and effectiveness make it easily replicable both nationally and internationally.
These outcomes highlight the project’s success in transforming maternity care by focusing on mental well-being and positive reinforcement.
A Patient-Centred and Evidence-Based Approach
The Affirmation Project was built on a solid foundation of evidence-based practice: Research-Driven
A study conducted via an anonymous online questionnaire (n=160) showed that 74% of women felt anxious about pregnancy and childbirth.
After using the affirmation cards, all respondents reported feeling more confident and less fearful.
Compassion-Focused Framework
The project was inspired by antenatal compassion-focused therapies that enhance the
Matthew Farrelly, Chief Executive Officer, MedFind Solutions with Alice Hoffmeister, National Maternity Hospital
oxytocin-soothing system—vital for a positive birth experience.
Positive affirmations were used to mitigate fear and anxiety, thereby promoting the natural release of oxytocin during labour.
This evidence-based approach not only ensured the effectiveness of the project but also provided a strong case for its expansion and adoption by other maternity units across Ireland.
Innovations that Made a Difference
Several innovative aspects set the Affirmation Project apart: Customisable and Inclusive: Blank cards were added to the sets following feedback, allowing women to write their own affirmations, thus enhancing engagement and personalisation.
Plans for multilingual versions aim to ensure accessibility for non-English-speaking women accessing maternity services in Ireland.
Phase Two - Breastfeeding Affirmation Cards
A second phase of the project introduced five additional cards focusing on positive reinforcement for breastfeeding.
These cards aim to support women during the often challenging postnatal period, ensuring a smoother transition to breastfeeding and early parenthood.
Community Engagement: The cards were promoted through Domino Midwives’ social
media platforms, ensuring wide reach and engagement among expecting mothers.
These innovations demonstrate the team’s commitment to continuous improvement and their deep understanding of the needs of maternity service users.
Feedback and Testimonials: A Positive Reception. Feedback from both patients and healthcare professionals has been overwhelmingly positive:
High Satisfaction Rates: 100% of respondents reported that the cards alleviated their fears, with many highlighting the positive impact on their mental well-being during labour.
Encouraging Active Births: Women reported feeling more in control and empowered during labour, leading to a higher incidence of active births and reduced need for medical interventions.
Professional Endorsements
Matthew Farrelly, CEO of MedFind Solutions, praised the initiative for its simplicity and impact, "This project is a shining example of how simple innovations can make a profound difference in patient care."
The positive reception from both patients and professionals underscores the project’s effectiveness and potential for further expansion.
Looking Forward - Expanding the Affirmation Project
The National Maternity Hospital team plans to:
Broaden Distribution: Expand the distribution of affirmation cards to other maternity hospitals in Ireland.
Evaluate and Innovate: Conduct further studies to assess long-term outcomes and refine the affirmation cards based on patient feedback.
Integrate Technology: Develop a mobile app with audio affirmations to support women during labour and the postnatal period. By focusing on mental well-being, empowerment, and inclusivity,
the Affirmation Project is wellpositioned to transform maternity care not just in Ireland, but globally. Congratulations to the National Maternity Hospital’s Community Midwifery Team for their outstanding contribution to innovation in maternity care!
Alice Hoffmeister, The National Maternity Hospital commented, “This means so much to me and to the wider team. It truly is a validation of all the hard work that has gone into promoting a positive birth experience for women.
“These Honours are so important to recognise the work healthcare professionals do and encourage continuous improvement in services.
“It is important to acknowledge that no idea is too small and we should all be making the best use of our supports in the hospital. Together we will be able to strive forward and make the best difference to patient care.”
Sandra Cullen, Hospital Sales Manager, MedFind Solutions also stated, “Established and headquartered in Ireland, MedFind Solutions is a full service, leading pharmaceutical support, and services partner.
“Specialising in the procurement and supply of exempt medicinal products and licensed medicines, MedFind covers all therapeutic areas. From our Aseptic compounding service to the supply of critical care antidotes, we engage with our Hospital Pharmacy colleagues daily, ensuring that every patient receives the right medicine, at the right time, in a fully compliant manner.
“The combination of MedFind’ s EU and UK footprint also means they are strategically placed to offer access across geographies and mitigate against potential supply chain issues from our Dublin and London offices.
“The combination of a high-quality service level, a diverse and strong portfolio and competitive pricing adds significant value to MedFind’ s customer base according to Hospital Sales Manager, Sandra Cullen: “Getting the right medications to the patients who need them most is at the core of everything we do in MedFind,” explains Sandra.
“We’ve built an incredibly experienced team who have a wealth of knowledge behind them, but we have also kept the business agile so that we can adapt swiftly to the ever-changing patient requirements. We believe in closing the gap in patient access for effective medicines and niche therapies.”
56 HPH Winner Profile ONOURS Hospital Professional 2024
Athlone Pharmaceuticals Hospital Pharmacy Team of the Year
St James’s Hospital Pharmacy Team: Excellence in Pharmacy Practice and Teamwork
The Pharmacy Department at St James’s Hospital has been awarded the Athlone Pharmaceuticals Hospital Pharmacy Team of the Year 2024. Recognised for their dynamic, collaborative, and innovative approach to pharmacy practice, the team has set new standards in medication management, patient safety, and clinical efficiency.
A Team Built on Collaboration and Innovation
The pharmacy team at St James’s Hospital is known for its dynamism, energy, and collegiality. Their ability
to seamlessly integrate clinical pharmacy services across different specialties has transformed medication management within the hospital. Daily, pharmacists, technicians, and support staff work together to ensure that medications are prescribed accurately, patients understand their treatments, and clinical staff are kept informed about the latest in medicines management.
Gail Melanophy, Director of Pharmacy, speaking on behalf of the team, stated: "We are deeply honoured to win this category, as teamwork truly reflects the core of
who we are and what we stand for. Every member of our team works tirelessly, day in and day out, with one shared goal: to improve patient care."
Key Achievements and Impact
Medicines Reconciliation Efficiency: The introduction of Clinical Support Technicians (CSTs) has significantly improved the speed and accuracy of medicines reconciliation.
62% of patients now receive a medicines reconciliation within 24 hours of admission.
Winners of the Athlone Pharmaceuticals Hospital Pharmacy Team of the Year – the Pharmacy Department at St James’s Hospital with Barry Doyle, Head of Athlone Pharmaceuticals
Pharmacists saved an average of 17.6 minutes per reconciliation, allowing an additional 12.5 patients to receive clinical pharmacist reviews daily.
Digital Transformation in Oncology
Successfully transitioned 90% of prescriptions from paper to the National Cancer Information System (NCIS).
Introduced a new Closed System Transfer Device in collaboration with procurement teams to enhance safety in chemotherapy administration.
Aseptic Compounding Innovation
Implemented a compounding robot in the Aseptic Compounding Unit, the busiest in Ireland, producing 30,000 products annually.
In its first month, the robot compounded up to 50% of the total day ward requirements, improving efficiency and reducing the risk of repetitive strain injuries among staff.
These initiatives have not only improved patient outcomes but have also demonstrated a commitment to safety, efficiency, and the well-being of staff.
Innovations that Set New Standards
The St James’s Hospital pharmacy team has introduced several pioneering practices:
Clinical Support Technician (CST) Service
CSTs obtain and document comprehensive medication histories, allowing pharmacists to focus more on clinical reviews and direct patient care.
Risk Management and Safety Initiatives
Revised the Controlled Drug Identification Chart and conducted audits on the safety of pen injector devices, enhancing medication safety across the hospital.
Pharmacy-Led Education and Training
Launched in-house training programmes for technicians and clinical pharmacists, ensuring continuous professional development and high-quality service delivery.
These innovations highlight the team’s strategic focus on leveraging technology and upskilling staff to enhance service delivery.
A Commitment to Education and Professional Development
The St James’s Hospital pharmacy team is not only dedicated to patient care but also to advancing the pharmacy profession through education: Training and Mentorship: Hosted placements for pharmacy
students and student technicians, integrating them into clinical services, aseptic compounding, and medicines management.
Research and Presentations: Encouraged students to present their project work at national conferences and to the hospital’s Pharmacy and Therapeutics Committee.
Knowledge Sharing: Pharmacists regularly conduct presentations for nursing staff on the role of pharmacy in clinical practice, enhancing interdisciplinary collaboration.
This focus on education ensures that staff are continually developing their skills and are motivated to deliver the highest standards of care.
Patient-Centred Success Stories
The team’s efforts have had a direct and positive impact on patient care:
Faster Access to Chemotherapy: The robotic compounding system has reduced waiting times for chemotherapy products, allowing patients to begin treatment sooner.
Improved Medication Safety: The CST initiative has led to more accurate medication histories, reducing the risk of adverse drug events and ensuring patients receive the correct medications promptly.
Enhanced Patient Understanding: Pharmacists lead group education sessions to help patients understand their
medications better, promoting adherence and empowering patients in their own care.
Feedback from patients has been overwhelmingly positive, with many highlighting the professionalism, efficiency, and empathy demonstrated by the pharmacy team.
A Vision for the FutureExpanding Innovation
The St James’s Hospital pharmacy team’s future plans include:
Expanding the Role of CSTs: To cover more clinical areas, ensuring faster and more accurate medication reconciliations hospital-wide.
Scaling Robotic Compounding: Increasing the proportion of products compounded robotically to enhance efficiency and safety further.
National Leadership: Sharing best practices and supporting other hospitals in adopting robotic compounding and CST models, setting a benchmark for pharmacy services in Ireland.
Barry Doyle, Head of Athlone Pharmaceuticals, praised the team’s achievements:
"It is never an easy task to shortlist pharmacy teams from such a cohort that demonstrates high standards of professionalism and care daily. St James’s Hospital’s pharmacy team has truly set a benchmark in excellence."
Congratulations to the St James’s Hospital Pharmacy Team for their outstanding contribution to pharmacy practice and patient care!
Barry Doyle, Head of Athlone Pharmaceuticals said, “At Athlone Pharmaceuticals, we are very proud to sponsor the ‘Hospital Pharmacy Team of the Year’ Honour. It is never an easy task to shortlist pharmacy teams from a cohort which demonstrate such high standards of professionalism and caring daily. It is important to support and acknowledge the teams whose exceptional efforts and dedication contribute so much to patient care.
“Congratulations to the 2024 finalists.
“Athlone Pharmaceuticals is one of the fastest growing generic pharmaceutical companies in Ireland and is delighted to begin our association with the 2024 Hospital Professional Honours. Athlone Pharmaceuticals is part of the Kent-Athlone Pharma Group, working alongside our sister company Kent Pharma in the UK.
“I would also like to say to all the finalists here tonight, and all the guests, thank you for the exceptional work that you do, the excellence that you demonstrate. It is obvious here in this room this evening that there was a huge number of exceptionally talented and skilled hospital professionals in the room.”
Winners of the Athlone Pharmaceuticals Hospital Pharmacy Team of the Year – the Pharmacy Department at St James’s Hospital with Barry Doyle, Head of Athlone Pharmaceuticals
58 HPH Winner Profile ONOURS Hospital Professional 2024
Medisource Hospital Pharmacy Technician of the Year 2024
Caroline Scoops Hospital Pharmacy
Technician Honour
Caroline Monahan: A Trailblazer in Pharmacy Practice and Medisource Hospital Pharmacy Technician of the Year 2024
Caroline Monaghan, winner of the Medisource Hospital Pharmacy Technician of the Year with Pat Tehan, Managing Director, Medisource
Caroline Monahan, Senior Pharmaceutical Technician and Medicine Management Technician Supervisor at Tallaght University Hospital (TUH), has been awarded the Medisource Hospital Pharmacy Technician of the Year 2024. Recognised for her outstanding leadership, innovation, and dedication to advancing the role of hospital pharmacy technicians, Caroline has set new standards in medication management and patient care.
Championing Innovation and Expanding the Technician Role
Caroline’s career at TUH spans over 22 years, during which she has been instrumental in developing the Medicine Management Technician (MMT) service— the first of its kind in
Ireland. Starting in 2012 with just four trial wards, Caroline has expanded the service to 12 fully serviced wards, including ICU and PACU, by 2024. Her pioneering work has been crucial in optimising medication management, reducing nursing workload, and enhancing patient safety.
In response to her win, Caroline Monahan stated:
"I am truly honoured to receive this title. It’s incredibly gratifying to see Hospital Pharmacy Technicians being recognised as an integral part of the wider healthcare team."
Key Achievements and Impact
• Efficiency Gains: Caroline’s leadership in the MMT service led to a 20% reduction in drug round times, saving 9 hours of nursing time per week per ward.
• Innovation in Training: As lead tutor for the Medicines Management Accredited Programme (MMAP), Caroline has trained numerous technicians, ensuring a high standard of medication management across the hospital.
• Accuracy Checking Technician (ACT) Service: Established an ACT service in the dispensary, which freed up 23 hours of pharmacist time per week for patient-facing roles.
• Medication History Service: Launched a Medication History Taking Technician service in January 2024, allowing technicians to support pharmacists in identifying pre-admission medication discrepancies. This initiative has been widely praised for enhancing patient safety and medication accuracy.
These achievements underscore Caroline’s commitment to enhancing pharmacy services and optimising resource allocation within the hospital.
Innovations that Set New Standards
Caroline’s forward-thinking approach has led to several innovative practices, including:
• Specialist ICU Technician Service: Introduced a specialist MMT service in the ICU, where technicians manage complex and high-risk medications using electronic prescribing systems.
• Accuracy and Safety Initiatives: Implemented inhouse training and standard operating procedures (SOPs) for Accuracy Checking Technicians (ACT), ensuring precise medication dispensing and reducing the risk of errors.
• Medication Reconciliation Service: Co-authored a winning poster at the National Association of Hospital Pharmacy Technicians (NAHPT) conference titled “The Roadmap to the Implementation of a Medication Reconciliation
Technician Service in an Acute Hospital Setting”.
These initiatives have not only improved workflow efficiency but have also set a benchmark for best practices in hospital pharmacy services across Ireland.
Dedication to Education and Mentorship
Caroline’s contributions to pharmacy practice extend well beyond her immediate responsibilities. She has been a key advocate for professional development, providing training and mentorship to junior technicians:
• Training Lead: As lead tutor for the NICPLD MMAP course, Caroline has trained and mentored technicians, helping them develop expertise in medication management.
• Knowledge Sharing: Regularly delivers workshops and presentations to pharmacy staff, sharing her extensive knowledge and experience.
• Support for Junior Technicians: Known for her approachable leadership style, Caroline has played a pivotal role in shaping a supportive learning environment within the pharmacy department at TUH.
A Legacy of Leadership and Professionalism
Caroline’s leadership and unwavering dedication to enhancing the role of pharmacy technicians were instrumental in the TUH MMT team winning
Caroline Monaghan, winner of the Medisource Hospital Pharmacy Technician of the Year with Pat Tehan, Managing Director, Medisource
the Team of the Year award at the HPN Awards in 2016. Her efforts to optimise skill mix and improve patient care through strategic innovations reflect her deep understanding of pharmacy practice goals.
Pat Tehan, Managing Director of Medisource, praised Caroline’s achievements:
"Caroline’s dedication to advancing the pharmacy technician role and her innovative approach to service delivery are truly inspiring. She embodies the professionalism and forwardthinking mindset that this Honour seeks to recognise."
Looking Forward: A Vision for Sustainable Pharmacy Practice
Caroline’s future vision focuses on expanding the role of pharmacy technicians further into clinical areas. This includes:
• Extending the Medication History Service to additional wards.
• Enhancing the ACT Programme to cover a broader range of high-risk medications.
• Promoting Innovation: Continuing to advocate for the use of technology and digital tools to streamline medication management processes. Her strategic focus on sustainability, efficiency, and patient safety ensures that the pharmacy services at TUH are well-positioned to meet the challenges of an evolving healthcare landscape.
Pat Tehan, Managing Director of Medisource added, “Medisource are delighted to sponsor the HPN Hospital Pharmacy Technician of the Year again this year.
“Established in 2004 and celebrating our 20th anniversary on the weekend of the honours, Medisource continues to be a wholly Irish owned company with 30 experienced staff, with our mission to source and supply exempt medicines to all parts within the Irish healthcare system. We work with a wide range of organisations, including multinationals to niche biotech companies around the world to source and deliver urgent medicines to patients in Ireland.
“Our continued commitment is an emphasis on personal communication to ensure that medicines are sourced and delivered within the required timeframe and that such sourcing is done only through verified and legitimate distribution channels within regulations. We offer a global reach and commit to significant local stockholding so that your patient doesn’t have to suffer a break in treatment.
“We invest heavily in our human resources so that we can provide live information through one to one communications.”
Congratulations to Caroline Monahan for her exceptional achievements and for setting new standards of excellence in hospital pharmacy practice!
Clinical R&D
ASTELLAS’ PADCEVTM (ENFORTUMAB VEDOTIN) PLUS KEYTRUDA® (PEMBROLIZUMAB) SHOWS LONG-TERM EFFICACY IN FIRST-LINE TREATMENT OF LOCALLY ADVANCED OR METASTATIC UROTHELIAL CANCER (LA/MUC)
• Enfortumab vedotin plus pembrolizumab continues to demonstrate superior efficacy versus chemotherapy in a broad population, reinforcing the combination as standard of care in first-line treatment of la/muC
• At nearly 30 months of follow-up in the Phase 3 EV-302 trial, the combination doubled median overall survival and progressionfree survival compared to chemotherapy, with no new safety signals identified.
Astellas Pharma Inc. CEO: Naoki Okamura, recently announced additional follow-up results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) evaluating the efficacy and safety of enfortumab vedotin, a Nectin-4 directed antibody-drug conjugate, plus pembrolizumab, a PD-1 inhibitor, in patients with previously untreated locally advanced or metastatic urothelial cancer (la/ mUC). The results showed a sustained overall survival (OS) and progression-free survival (PFS) benefit consistent with the findings of the primary analysis after an additional 12 months of follow-up (median follow-up of 29.1 months). This data was presented during a rapid oral session (Abstract 664) at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) 2025.
Thomas Powles, M.R.C.P., M.D., Professor of Genitourinary Oncology at Queen Mary University of London; Director, Barts Cancer Center, London; EV-302 Primary Investigator
“These latest findings from the EV-302 trial reaffirm the primary results, which demonstrated survival improvements for patients treated with enfortumab vedotin and pembrolizumab that were previously unprecedented in locally advanced or metastatic urothelial cancer. These data show that the potential survival benefit has become even more robust with extended follow up and further solidify the combination as standard of care.”
Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% confidence interval [CI], 0.430.61). The median OS was 33.8 months for the combination versus
15.9 months for chemotherapy. The OS benefit was observed in all prespecified subgroups, including cisplatin eligible and ineligible subgroups. Enfortumab vedotin plus pembrolizumab also reduced the risk of disease progression or death by 52% versus chemotherapy (HR = 0.48, 95% CI, 0.41-0.57). The median PFS was 12.5 months for the combination versus 6.3 months for chemotherapy. The safety profile was consistent with previous findings and no new safety concerns were identified.
In addition to longer follow-up data, an exploratory analysis evaluating treatment outcomes and safety profile in patients with confirmed complete response (cCR) will also be presented. Among patients evaluable for response, confirmed objective response rate (cORR) was 67.5% for enfortumab vedotin plus pembrolizumab compared to 44.2% for chemotherapy. Median duration of response (DOR) was 23.3 months (95% CI, 17.8-not estimable [NE]) for the combination and 7.0 months (95% CI, 6.2-9.0) for chemotherapy. A cCR was achieved in 30.4% of patients treated with enfortumab vedotin plus pembrolizumab and 14.5% of patients treated with chemotherapy. Median duration of cCR was not reached for the combination and 15.2 months (95% CI, 10.3-NE) for chemotherapy. In patients with cCR, grade ≥3 treatment-related adverse events occurred in 61.7% of patients in the enfortumab vedotin plus pembrolizumab arm compared to 71.9% in the chemotherapy arm. There were no treatment-related deaths in the cCR subgroup.
Roger Dansey, M.D., Chief Oncology Officer, Pfizer
“Patients with bladder cancer can face a poor prognosis, particularly in the advanced stages, and until recently had few available treatment options. The updated EV302 results show sustained longterm efficacy in a broad population that includes both cisplatin eligible and ineligible patients and reinforce this combination’s ability to reshape the urothelial cancer treatment landscape.”
Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas
“The combination of enfortumab vedotin and pembrolizumab was the first approval to offer an alternative to platinum-containing chemotherapy, which had been the standard of care for first-line locally advanced or metastatic urothelial cancer for decades. We are delighted that the additional
follow-up results of the EV-302 trial show a durable benefit. These data represent yet another milestone in our long-standing commitment to helping patients around the world live longer and healthier lives.”
Enfortumab vedotin plus pembrolizumab is approved for the treatment of adult patients with la/mUC in the United States, the European Union, Japan and a number of other countries around the world. Enfortumab vedotin is also approved as a single agent for the treatment of adult patients with la/mUC who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy.
GROUND-BREAKING RESEARCHERS FROM AROUND
IRELAND HONOURED AT IRISH CANCER SOCIETY RESEARCH AWARDS 2025
People involved in groundbreaking research projects around the country were honoured at the Irish Cancer Society Research Awards on Thursday, February 20th, at the Irish Cancer Society Head Office in Ballsbridge, Dublin.
In 2024 alone, the Irish Cancer Society funded over 25 new research projects and over 180 cancer researchers.
The event, hosted by the Irish Cancer Society’s Head of Research, Dr Claire Kilty, celebrates some of the amazing work in cancer research being carried out by nominees around Ireland, funded by the Irish Cancer Society.
Among those to claim top honours were Translational and Clinical Project of the Year Award winner, Dr Karen Slattery, whose research identified new therapeutic targets for the treatment of highgrade serous ovarian cancer. Translational research looks at
Dr Karen Slattery, Translational and Clinical Project of the Year Award winner
Fitzpatrick, PhD Researcher of the Year Award winner
applying laboratory findings to real-world settings, to treat or prevent human disease.
Translational and Clinical Project of the Year Award winner, Dr Karen Slattery, said: “My research is focused on understanding how ovarian cancer impacts the immune system. We observed that ovarian cancer patients have dysfunctional immune cells, including important cancer-fighting immune cells called Natural Killer cells and T cells.
“By studying the makeup of abdominal fluid that has cancer cells from ovarian cancer patients, we were able to identify a specific type of fat molecule, known as a phospholipid, that is a key driver of this immune dysfunction.
“Importantly, blocking the uptake of this phospholipid into Natural Killer cells was able to restore their ability to kill cancer cells. These findings may guide the design of future immunotherapies for patients with advanced ovarian cancer.
“Winning this Irish Cancer Society Research Award is a deeply humbling and significant milestone in my career as a scientist. It is an honour to receive recognition for the years of hard work I’ve put into this research.
Jennifer
“Working on this project has been incredibly rewarding, and I am proud of the contribution we’ve made to the field of ovarian cancer research.”
The prize of PhD Researcher of the Year went to Jennifer Fitzpatrick. Jennifer’s project, called ‘The CHildhood and adolescent cancer survivors’ physical Activity and Movement Programme’ (CHAMPs) is a global first of its kind. The programme was developed, in collaboration with families, to support young people (aged 10 to 19 years) who have had cancer. CHAMPs is a free, personalised, 12-week physical activity programme, based entirely in the young person’s’ home and guided by their ability and interests for activity.
PhD Researcher of the Year Award winner, Jennifer Fitzpatrick, who is based in the Technological University of the Shannon, said: “Receiving a nomination for an Irish Cancer Society Research Award is such an honour. It recognises me dedicating the last four years of my work to improving the lives of young people who have had cancer. Seeing first-hand the impact CHAMPs can have on families is incredibly emotional, but also extremely rewarding.
“I am truly grateful for the platform to develop a global first-of-its-kind programme for young people who have had cancer, but to also be recognised for this achievement is such a privilege.”
Congratulating the winners, Irish Cancer Society Head of Research Dr Claire Kilty said: “Cancer research in Ireland has a huge impact on the lives of people affected by cancer. It is a driving force in improving not only treatments and outcomes, but in quality of life beyond cancer. It was fantastic to get an appreciation of the amazing cancer research projects currently happening right across the country.
“We are proud to be the largest voluntary funder of cancer research in Ireland. However, none of the vital research we fund would be possible without the support of the public, especially on days like Daffodil Day. We would encourage everyone to please get out there and support Daffodil Day in whatever way you can on March 28th.”
ST JOHN OF GOD HOSPITAL BECOMES THE FIRST IRISH HOSPITAL TO INTRODUCE RTMS AS A TREATMENT FOR DEPRESSION
St John of God Hospital has announced the introduction of Repetitive Transactional Magnetic Stimulation therapy, in an expansion of its treatment options
for patients with depression. This non-invasive therapy offers a new option for patients who have not had sufficient success with conventional depression treatments. St John of God Hospital will be the first hospital to deliver this treatment for depression on a consultant-led basis.
rTMS is a modern treatment for depression that prioritises convenience, comfort, and safety while delivering significant benefits for those with treatment-resistant depression. rTMS uses magnetic pulses to stimulate specific brain regions, promoting the brain’s ability to form new connections and regulate mood.
Around 21 million people in Europe, or 4.5% of the population, experience depression, with higher rates in women (8.8%) than men (5.3%). In Ireland, 12% of young people (15-24 years) report chronic depression, the highest rate in Europe.
rTMS is a consultant-led service that offers a unique combination of effectiveness, convenience and safety. The treatment is performed on an outpatient basis and requires no anaesthesia, meaning patients can drive, work, and resume daily activities immediately after their sessions. Its non-invasive nature makes it an attractive option for a wider range of individuals.
Consultant Psychiatrist and Head of
Neuromodulation Services Simon Mitchell, who is one of the experts leading the rollout at St John of God Hospital has commented on the announcement, saying
“The introduction of rTMS at St John of God Hospital represents significant advancement in our mental health services. This non-invasive treatment offers new hope to our patients who haven’t found relief through traditional methods. This expansion of our psychiatric services reflects St John of God Hospital’s ongoing commitment to providing the most advanced, evidence-based treatments to our patients.”
The effectiveness of rTMS treatment for depressive disorders and treatment-resistant depression has been firmly established in recent years. rTMS was approved for depression treatment by the U.S. Food and Drug Administration (FDA) in 2008, and the UK’s National Institute for Health and Care Excellence (NICE) has also appraised the evidence of the treatment. Clinical studies have shown that approximately 50% of patients experience significant symptom relief with rTMS treatment, with about onethird achieving remission from their depression symptoms.
The typical treatment course consists of daily sessions over 4-6 weeks, with each session lasting about 20-40 minutes.
HSE HEALTH APP
The Department of Health and HSE launched the first version of the HSE Health App today. It is one of the first initiatives delivered as part of Digital for Care, Ireland’s health and social care digital framework. From today anyone aged 16 and over can download the app for free from Google Play or the App Store, however first phase functionality will be most useful for expectant mothers.
First phase functionality allows people to:
• carry a digital list of self-declared medications and see a list of medicines received through the Drugs Payment Scheme or Medical Card Scheme
• store your European Health Insurance Card (EHIC), medical card, Long-term Illness card (LTI), Drugs Payment Scheme card (DPS) and GP Visit card
• access flu and COVID-19 vaccination records
• easily find information about HSE services, such as EDs and Injury Units
• view maternity service appointments (for expectant mothers)
Consultant psychiatrists, Dr Simon Mitchell and Dr Attila Szigeti with Deputy Chief Executive Sarah Almasry, Chief Executive of Saint John of God Hospital , Damien O'Dowd, and consultant psychiatrist Dr Giedrius Gerulskis at the launch of the Hospitals new rTMS service in Stillorgan
Clinical R&D
A verified MyGovID is needed to access personal health information
To log in to the HSE Health App and access personal health information, you will need a verified MyGovID account. A verified MyGovID proves who you are and ensures we are giving personal health information to the right person.
If you do not have a verified MyGovID, you will still be able to use the app to find information about health conditions and HSE services.
Minister for Health, Jennifer Carroll MacNeill TD, said, “Today marks an exciting milestone in our journey to digitise patient health records with the public launch of the first version of our new HSE Health App. This App is an exciting milestone where we begin to give patients digital access to their own health information and will make it easier for everyone to navigate the health service.
“We can now ensure that every patient is provided with easily accessible health information that is accurate and trustworthy. The phased introduction of appointment notifications and reminders will make it easier for people to manage their care.
aitriona Heffernan, National Clinical Innovation Lead, HSE Spark Innovation Programme; Dr Gloria Kirwan, Senior Lecturer, RCSI School of Graduate Healthcare Management; Dr Colm Foster, Director of Academic Programmes, RCSI Graduate School of Management; Sara McDonnell, Executive Director, RCSI Graduate School of Management and RCSI Online
“I know the App development team have also consulted with a number of patient organisations so that their needs are incorporated into the design process to ensure the App is patient-centred.”
The HSE is working with colleagues across government to integrate the HSE Health App with the Government Digital Wallet that will be released later this year.”
Bernard Gloster, HSE CEO, said, “There has been much progress made in modernising the data capabilities and digital technologies of our health service in recent years. The launch of the first version of the new HSE Health App represents the next step forward in our digital transformation journey, as we seek to harness the power of data and innovation to help improve access to care for patients and enhance efficiencies across services. Through utilisation and ongoing development of digital tools, such as the new HSE Health App, we see a future where our patients and the people who care for them are empowered and better informed about their care.
I will continue to ensure that we prioritise providing increased access for patients to their data and to interact with our health services to improve their experiences.”
Damien McCallion, HSE Chief Technology and Transformation Officer said, “Anyone who wishes to, can use the first version of the HSE Health App. It gives people secure access to their COVID-19 and flu vaccination records, digital medications lists, medical cards and EHIC cards, all in one place. Expectant mothers can also view upcoming maternity appointments in the app.
“This is just the beginning - the app is an evolving programme of work, with new services and features planned each year, including expanding the appointment functionality for all public hospital appointments. This is a challenging undertaking but a key priority to deliver for everyone under our care.
“The app is one aspect of the digitisation of the health service and a major priority as we face new challenges and ensure we can provide the health service the country needs and deserves.”
TEVA LAUNCHES POMALIDOMIDE TEVA
Teva Pharmaceuticals is pleased to announce the launch of Pomalidomide Teva, available in 1mg, 2mg, 3mg and 4mg hard capsules (21 capsules).
Pomalidomide Teva indications:
• In combination with bortezomib and dexamethasone is indicated in the treatment of adult patients with multiple myeloma who have received at least one prior treatment regimen including lenalidomide.
• Pomalidomide Teva in combination with dexamethasone is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy.
For any queries or further information, please contact your local Teva representative or contact Teva on 1 800 201 700.
Further product information is available upon request or from the SmPC available at HPRA.ie.
Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to Teva UK Limited on +44 (0) 207 540 7117 or medinfo@tevauk.com.
Date of preparation: February 2025
Job code: GEN-IE-NP-00136
TECVAYLI®(TECLISTAMAB) BISPECIFIC ANTIBODY APPROVED FOR REIMBURSEMENT IN IRELAND FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA
Johnson & Johnson Innovative Medicine has announced that TECVAYLI® (teclistamab) as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) has been approved for reimbursement in Ireland. Patients must have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. The announcement follows conditional marketing authorisation (CMA) from the European Commission (EC) granted in 2022 for teclistamab, a bispecific antibody that redirects CD3-positive T-cells to B-cell maturation antigen (BCMA)expressing myeloma cells to induce the killing of tumour cells.
Multiple myeloma remains an incurable blood cancer, with nearly all patients relapsing and requiring subsequent therapy. As the disease progresses, relapses for patients become more aggressive with each new line of therapy, and remissions become progressively shorter.4 Approximately, 380 people are diagnosed with multiple myeloma each year in Ireland.
Prof Siobhan Glavey, Consultant Haematologist said: "Multiple myeloma is a complex disease, and despite important scientific progress, patients who develop relapsed and refractory disease after having been exposed to three major drug classes have limited therapeutic options and generally face poor outcomes. This new treatment option has the potential to provide substantial clinical benefit and new hope to patients, with high rates of deep and durable responses as well as the added convenience of being off-the-shelf. The reimbursement of teclistamab in Ireland marks a major step towards ensuring Irish patients have access to the most innovative treatments available.”
Michaela Hagenhofer, General Manager Commercial Operations, Johnson & Johnson Innovative
Medicine Ireland said: "Our ambition to eliminate multiple myeloma is stronger today than ever before. We aim to reach this goal by investing in cutting-edge innovations that address individual patient needs and offer healthcare professionals options they have not had before. We are proud to have provided early access of teclistamab to Irish patients which not only provided valuable extra time but also allowed clinicians to gain real-world experience with a bispecific. The reimbursement of teclistamab in Ireland marks exciting progress on this journey and we are proud to bring this innovation to Irish myeloma patients.”
The approval was supported by positive results from the multicohort, open-label Phase 1/2 MajesTEC-1 study (NCT03145181 and NCT04557098), evaluating the safety and efficacy of teclistamab in adults with RRMM (n =165). Patients received a weekly subcutaneous injection of teclistamab at a dose of 1.5 mg/ kg, after receiving step-up doses of 0.06 mg/kg and 0.3 mg/kg. In the study, 104 out of 165 patients achieved an overall response rate (ORR) of 63 percent (95 percent Confidence Interval [CI]; range, 55.2–70.4) after a median of five prior lines of therapy.1 Notably, 58.8 percent of patients receiving teclistamab achieved a very good partial response (VGPR) or better and 39.4 percent achieved a complete response (CR) or better. The median time to the first confirmed response was 1.2 months (range, 0.2–5.5 months) and the median duration of response was 18.4 months (95 percent CI; range, 14.9–not estimable).
Results from the MajesTEC-1 study were also published in The New England Journal of Medicine and showed that treatment with teclistamab resulted in deep and durable responses. The median duration of progression-free survival was 11.3 months (95 percent CI; range, 8.8–17.1) and the median duration of overall survival was 18.3 months (95 percent CI; range, 15.1–not estimable).
Adverse events (AEs) were consistent with this patient population. The most common AEs were cytokine release syndrome (72 percent; 0.6 percent Grade 3, no Grade 4), neutropenia (71 percent; 64 percent Grade 3 or 4) and anaemia (55 percent; 37 percent Grade 3 or 4). Infections were frequent with the most common being upper respiratory tract infections (37 percent; 2.4 percent Grade 3 or 4) and pneumonia (28 percent; 19 percent Grade 3 or 4).
Hypogammaglobinaemia occurred
in 123 patients (75 percent) and 39 percent of patients received intravenous or subcutaneous immunoglobulin therapy. Neurotoxic events were low grade (15 percent; 14 percent Grade 1 or 2) and five patients (three percent) had immune effector cell-associated neurotoxicity syndrome.
PORTIUNCULA UNIVERSITY
HOSPITAL TO MARK WORLD KIDNEY DAY
World Kidney Day which took place on 13 March marks a global campaign aimed at raising awareness around kidney disease. This year’s theme, “Are Your Kidneys OK? Detect Early, Protect Kidney Health,” highlights the importance of recognising kidney disease risk factors as well as early detection and intervention in preventing and managing the disease.
Dr Paul O’Hara, Consultant General Physician and Nephrologist at Portiuncula University Hospital said, “World Kidney Day gives us an opportunity to stop and think about kidney disease, raise awareness of it and encourage everyone to actively know what their own kidney health measures are.
“Education is a key part of managing any chronic illness and kidney disease is no different. The risk factors associated with Chronic Kidney Disease (CKD) include diabetes, obesity, high blood pressure, long term use of over the counter medications, heart disease and family history of kidney disease. If you are over 50 or in the high risk category, it is important to get screened for CKD.”
This year to mark World Kidney Day, Portiuncula University Hospital’s kidney clinic will hold
Patient Ray Quinn from Ballinasloe with Dr Paul O’Hara, Consultant General Physician and Nephrologist and Alexandra Rose, Clinical Nurse Specialist at the Kidney Day Ward, Portiuncula University Hospital.
an information awareness stand in the outpatient department on Thursday, 13 March from 9am to 12 noon. Clinical staff will be in attendance to answer any questions you have and to raise awareness of high blood pressure, obesity and diabetes which are the leading cause of kidney disease in Ireland.
Since it opened four years ago, the hospital's kidney clinic under the remit of Dr Paul O’Hara has been providing care to patients with kidney conditions across the hospital's catchment area of East Galway and Roscommon. The kidney clinic treats a wide range of kidney conditions, with referrals from both the hospital and GPs. Between 2023 and 2024 the kidney clinic saw a 15% increase in new referrals, reviewed almost 600 patients and saw a 62% increase in patients with kidney disease receiving infusion-based therapies. Patients receiving haemodialysis and those undergoing kidney transplants are cared for at Merlin Park University Hospital.
Last month the existing kidney day ward was relocated to the new 50-bed ward block to provide additional capacity in a new clinical space, significantly enhancing patient care to the highest standards.
ALK’S ALLERGY TREATMENT ACARIZAX®(12 SQ-HDM SLIT)
NOW APPROVED FOR CHILDREN AGED 5+ IN IRELAND
ALK today announces that ACARIZAXx® has received a paediatric indication extension for the treatment of moderate to severe house dust mite allergic rhinitis disease, making it available for children aged 5 years and older in Ireland. Previously approved for patients aged 12+, this development marks a milestone in allergy treatment, broadening access to an innovative therapy that addresses the underlying cause of house dust mite allergic rhinitis.
Studies suggest that allergic rhinitis is the most common
allergic condition, affecting approximately 26% of Irish people, with house dust mites being the most common allergen. The condition can lead to disturbed sleep, impaired concentration, worsened asthma symptoms, school absenteeism and increased psychosocial burden.
ACARIZAX® is a sublingual immunotherapy (SLIT) tablet designed to treat the root cause of house dust mite allergy rather than just alleviating symptoms. By gradually desensitising the immune system, SLIT helps reduce the severity of allergic reactions over time, leading to long-term symptom relief and reduced reliance on symptomatic medications such as antihistamines and nasal steroids.
Dr Juan E Trujillo Wurttele and Dr Sadhbh Hurley together as the paediatric allergy team in Cork University Hospital and coordinators of the MSc of allergy and clinical immunology in UCC said, “House dust mite allergic rhinitis is often overlooked but can profoundly impact children’s daily lives. Expanding Acarizax’s indication to younger children represents a major step forward in addressing this unmet medical need, providing a long-term treatment option that can improve both symptoms and overall quality of life.”
ACARIZAX® has been approved for reimbursement in the UK through the NHS for the treatment of moderate to severe house dust mite allergic rhinitis disease in people 12 to 65 years that is persistent despite symptom relieving medicine, following a positive recommendation from NICE (National Institute for Health and Care Excellence). This expands access for eligible patients, providing them with a clinically proven, long-term treatment option that can significantly improve quality of life while also relieving a financial burden for patients.
ALK General Manager Emil Stage Olsen added, “This extension brings the benefits of Acarizax to younger children. This approval reflects our ongoing dedication to transforming allergy treatment and providing healthcare professionals with advanced solutions for paediatric allergic rhinitis management. It aligns with ALK’s broader mission to improve allergy management and enhance patient outcomes.”
For more information about ACARIZAX® and ALK’s commitment to allergy care, visit www.alk.net.
