HPN February 2024

HOSPITAL PROFESSIONAL NEWS IRELAND

HPN February 2024 Issue 117 HOSPITALPROFESSIONALNEWS.IE

Ireland’s Dedicated Hospital Professional Publication

IN THIS ISSUE: NEWS: Patient Safety initiative Recognition Page 6 STUDY: New Report on Waiting Lists Page 9 HONOURS: Launch of the 2024 Hospital Professional Honours Page 14 Legal Category: Product subject to prescription which may not be renewed (A).

Marketing Authorisation Number: EU/1/18/1345/001 4 vials; EU/1/18/1345/002 5 vials Marketing Authorisation Holder: AstraZeneca AB, SE-151 85, Södertälje, Sweden.

Further product information available on request from: AstraZeneca Pharmaceuticals (Ireland) DAC, College Business and Technology Park, Blanchardstown Road North, Dublin 15, Ireland.

Freephone 1800 800 899.

ONDEXXYA® is a trademark(s) of the AstraZeneca group of companies.

This medicinal product is subject to additional monitoring.

Veeva ID: IE-5804

Date of Preparation: January 2024

This Publication is for Healthcare Professionals Only

ONCOLOGY FOCUS: ESMO Coverage 2023 Page 29 CPD: Osteoporosis Management Page 37 ONCOLOGY FOCUS: Exercise & Haematological Cancer Page 46 ONCOLOGY FOCUS: High Risk Multiple Myeloma Page 53

150mg film coated tablets

In the PAOLA-1 trial, Lynparza + bevacizumab maintenance therapy showed a median overall survival benefit of >6 years in first-line HRD+ advanced ovarian cancer patients 1,2*

Lynparza is now reimbursed via the ODMS in combination with bevacizumab for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a BRCA1/2 mutation and/or genomic instability.1

Safety: Adverse events profile has been found to be generally consistent with the known safety profiles of Lynparza and bevacizumab individually.1,2 Please refer to the Summary of Product Characteristics for further information before making any prescribing decisions.

Further information is available upon request. *Results of the 5-year final analysis are not statistically significant.

This information is intended for healthcare professionals only.

BRCA, breast cancer gene; FIGO, International Federation of Gynecology and Obstetrics; HRD, homologous recombination deficiency; ODMS, oncology drug management scheme.

References 1. Lynparza (olaparib) Summary of Product Characteristics. Available at www.medicines.ie 2. Ray-Coquard I et al. Ann Oncol. 2023 Aug;34(8):681-692.

ABBREVIATED PRESCRIBING INFORMATION LYNPARZA® (olaparib) 150mg & 100mg FILM-COATED TABLETS Consult Summary of Product Characteristics (SmPC) before prescribing.

Indication: Ovarian Cancer: • As monotherapy for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy. • As monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

• Lynparza in combination with bevacizumab: As maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a BRCA1/2 mutation and/or genomic instability.

Breast Cancer: • As monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy. • As monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2 negative locally advanced or metastatic breast cancer. Patients should have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless patients were not suitable for these treatments.

Patients with hormone receptor (HR)-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy. Adenocarcinoma of the pancreas: As monotherapy for the maintenance treatment of adult patients with germline BRCA1/2-mutations who have metastatic adenocarcinoma of the pancreas and have not progressed after a minimum of 16 weeks of platinum treatment within a first-line chemotherapy regimen. Prostate Cancer: • As monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent. • In combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.

Presentation: 150mg and 100mg olaparib film-coated tablets.

Dosage and Administration: Treatment should be initiated and supervised by a physician experienced in the use of anticancer therapies. Patient selection: First-line maintenance treatment of BRCA-mutated advanced ovarian cancer: Before Lynparza treatment is initiated for first-line maintenance treatment of high-grade epithelial ovarian cancer (EOC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC), patients must have confirmation of deleterious or suspected deleterious germline and/or somatic mutations in the breast cancer susceptibility genes (BRCA) 1 or 2 using a validated test. Maintenance treatment of platinum-sensitive relapsed ovarian cancer: There is no requirement for BRCA1/2 testing prior to using Lynparza for the monotherapy maintenance treatment of relapsed EOC, FTC or PPC who are in a complete or partial response to platinum-based therapy. First-line maintenance treatment of HRD positive advanced ovarian cancer in combination with bevacizumab: Before Lynparza with bevacizumab treatment is initiated for the first-line maintenance treatment of EOC, FTC or PPC, patients must have confirmation of either deleterious or suspected deleterious BRCA1/2 mutation and/or genomic instability determined using a validated test. Adjuvant treatment of germline BRCA-mutated high risk early breast cancer: Before Lynparza treatment is initiated for adjuvant treatment of HER2 negative high risk early breast cancer, patients must have confirmation of deleterious or suspected deleterious gBRCA1/2 mutation using a validated test. Monotherapy treatment of gBRCA1/2-mutated HER2-negative metastatic breast cancer: For germline breast cancer susceptibility genes (gBRCA1/2) mutated human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, patients must have confirmation of deleterious or suspected deleterious gBRCA1/2 mutation before Lynparza treatment is initiated. gBRCA1/2 mutation status should be determined by an experienced laboratory using a validated test method. First-line maintenance treatment of gBRCA-mutated metastatic adenocarcinoma of the pancreas: For first-line maintenance treatment of germline BRCA1/2-mutated metastatic adenocarcinoma of the pancreas, patients must have confirmation of a deleterious or suspected deleterious gBRCA1/2 mutation before Lynparza treatment is initiated. gBRCA1/2 mutation status should be determined by an experienced laboratory using a validated test method. Monotherapy treatment of BRCA1/2-mutated metastatic castration-resistant prostate cancer: For BRCA1/2-mutated metastatic castration-resistant prostate cancer (mCRPC), patients must have confirmation of a deleterious or suspected deleterious BRCA1/2 mutation (using either tumour or blood sample) before Lynparza treatment is initiated. BRCA1/2 mutation status should be determined by an experienced laboratory using a validated test method. Treatment of mCRPC in combination with abiraterone and prednisone or prednisolone: No genomic testing is required prior to using Lynparza in combination with abiraterone and prednisone or prednisolone for the treatment of patients with mCRPC. Genetic counselling for patients tested for mutations in BRCA1/2 genes should be performed.

Posology: Recommended dose in monotherapy or in combination with bevacizumab for ovarian cancer or in combination with abiraterone and prednisone or prednisolone for prostate cancer or endocrine therapy is 300mg (two 150mg tablets) twice daily, equivalent to a total daily dose of 600mg. The 100mg tablet is available for dose reduction. Tablets should be swallowed whole and not chewed, crushed, dissolved or divided and may be taken without regard to meals. Lynparza monotherapy: Patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy should start Lynparza treatment no later than 8 weeks after completion of their final dose of platinum-containing regimen.

Lynparza in combination with bevacizumab: When Lynparza is used in combination with bevacizumab for the first-line maintenance treatment of high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer following completion of first-line platinum-based therapy with bevacizumab, the dose of bevacizumab is 15 mg/kg once every 3 weeks. Lynparza in combination with endocrine therapy: Please refer to the full product information of the endocrine therapy combination partner(s) (aromatase inhibitor/anti-oestrogen agent and/or LHRH) for the recommended posology. Lynparza in combination with abiraterone and prednisone or prednisolone: When Lynparza is used in combination with abiraterone for the treatment of patients with mCRPC, the dose of abiraterone is 1000 mg orally once daily. Abiraterone should be given with prednisone or prednisolone 5 mg orally twice daily. Please refer to the full product information for abiraterone. Duration of treatment: First-line maintenance treatment of BRCA-mutated advanced ovarian cancer: Patients can continue treatment until radiological disease progression, unacceptable toxicity or for up to 2 years if there is no radiological evidence of disease after 2 years of treatment. Patients with evidence of disease at 2 years, who in the opinion of the treating physician can derive further benefit from continuous treatment, can be treated beyond 2 years. Maintenance treatment of platinum-sensitive relapsed ovarian cancer: For patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer, it is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity. First-line maintenance treatment of HRD positive advanced ovarian cancer in combination with bevacizumab: Patients can continue treatment with Lynparza until radiological disease progression, unacceptable toxicity or for up to 2 years if there is no radiological evidence of disease after 2 years of treatment. Patients with evidence of disease at 2 years, who in the opinion of the treating physician can derive further benefit from continuous Lynparza treatment, can be treated beyond 2 years. Adjuvant treatment of germline BRCA-mutated high risk early breast cancer: It is recommended that patients are treated for up to 1 year, or until disease recurrence, or unacceptable toxicity, whichever occurs first. Monotherapy treatment of gBRCA1/2-mutated HER2-negative metastatic breast cancer: It is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity. The efficacy and safety of maintenance retreatment with Lynparza following first or subsequent relapse in ovarian cancer patients has not been established. There are no efficacy or safety data on retreatment of breast cancer patients. First-line maintenance treatment of gBRCA-mutated metastatic adenocarcinoma of the pancreas: It is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity. Monotherapy treatment of BRCA1/2-mutated metastatic castration-resistant prostate cancer: It is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity. Medical castration with luteinising hormone releasing hormone (LHRH) analogue should be continued during treatment in patients not surgically castrated. Treatment of mCRPC in combination with abiraterone and prednisone or prednisolone: It is recommended that treatment

©2024 AstraZeneca. All rights reserved.

IE-5713 | Date of Preparation: January 2024

be continued until progression of the underlying disease or unacceptable toxicity when Lynparza is used in combination with abiraterone and prednisone or prednisolone. Treatment with a gonadotropin-releasing hormone (GnRH) analogue should be continued during treatment in all patients, or patients should have had prior bilateral orchiectomy. Please refer to the product information for abiraterone. There are no efficacy or safety data on retreatment with Lynparza in prostate cancer patients. If a patient misses a dose of Lynparza, they should take their next normal dose at its scheduled time. Dose adjustments: Treatment interruption to manage adverse reactions such as nausea, vomiting, diarrhoea, anaemia and dose reduction can be considered. Recommended dose reduction is to 250mg (one 150mg tablet and one 100mg tablet) twice daily, equivalent to a total daily dose of 500mg.

If further dose reduction is required, then reduction to 200mg (two 100mg tablets) twice daily, equivalent to a total daily dose of 400mg is recommended. Concomitant use of strong or moderate CYP3A inhibitors is not recommended and alternative agents should be considered. If a strong CYP3A inhibitor must be co-administered, recommended dose reduction is to 100mg (one 100mg tablet) twice daily, equivalent to a total daily dose of 200mg. If a moderate CYP3A inhibitor must be co-administered, recommended dose reduction is to 150mg (one 150mg tablet) twice daily, equivalent to a total daily dose of 300mg. Elderly: No adjustment in starting dose is required. Renal impairment: For patients with moderate renal impairment (creatinine clearance 31 to 50 ml/min) the recommended dose is 200mg (two 100mg tablets) twice daily, equivalent to a total daily dose of 400mg. Lynparza can be administered in patients with mild renal impairment (creatinine clearance 51 to 80 ml/min) with no dose adjustment.

No studies have been conducted in patients with severe renal impairment or end-stage renal disease (creatinine clearance ≤ 30 ml/min) and Lynparza is not recommended for use. It may only be used in patients with severe renal impairment if the benefit outweighs the potential risk with careful monitoring of renal function and adverse events. Hepatic impairment: Can be administered in patients with mild or moderate hepatic impairment (Child-Pugh A or B) with no dose adjustment. Not recommended in patients with severe hepatic impairment (Child-Pugh C).

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Breast-feeding during treatment and for 1 month after the last dose.

Warnings and Precautions: Haematological toxicity: Treatment should not be started in patients until they have recovered from haematological toxicity caused by previous anticancer therapy (haemoglobin, platelet and neutrophil levels should be ≤CTCAE grade 1). Baseline testing followed by monthly monitoring of complete blood counts is recommended for first 12 months of treatment and periodically thereafter. Treatment should be interrupted and appropriate haematological testing should be initiated if patient develops severe haematological toxicity or blood transfusion dependence.

Myelodysplastic syndrome/Acute Myeloid Leukaemia (MDS/AML): If MDS/AML is suspected, the patient should be referred to a haematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged haematological toxicity, MDS/AML is confirmed, Lynparza should be discontinued and the patient treated appropriately. Venous Thromboembolic Events: Monitor patients for clinical signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate. Patients with a prior history of VTE may be more at risk of a further occurrence and should be monitored appropriately. Pneumonitis: Interrupt Lynparza treatment and promptly investigate as appropriate. Discontinue Lynparza if pneumonitis is confirmed and treat patient appropriately. Hepatotoxicity: If symptoms of hepatotoxicity develop, perform liver function tests (LFTs) and promptly clinically evaluate patient. In cases of suspected drug induced liver injury (DILI) treatment should be interrupted or discontinued. Embryofoetal toxicity: Lynparza could cause foetal harm when administered to a pregnant woman. Pregnancy/contraception: Lynparza should not be used during pregnancy. Women of childbearing potential must use two forms of reliable contraception, before starting Lynparza, during therapy and 6 months after receiving the last dose.

Two highly effective and complementary forms of contraception are recommended. Male patients and their female partners of childbearing potential should use reliable contraception during therapy and for 3 months after receiving the last dose. Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg or 150 mg tablet, that is to say essentially “sodium-free”.

Drug Interactions: The recommended Lynparza monotherapy dose is not suitable for combination with myelosuppressive anticancer medicinal products. Caution and close monitoring if vaccines or immunosuppressant agents are co-administered. Effect of other drugs on Lynparza: Strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. erythromycin, diltiazem, fluconazole, verapamil) are not recommended. If co-administered, the dose of Lynparza should be reduced. It is also not recommended to consume grapefruit juice. Strong CYP3A inducers (e.g. phenytoin, rifampicin, rifapentine, carbamazepine, nevirapine, phenobarbital, and St John’s Wort) are not recommended with Lynparza as the efficacy of Lynparza could be substantially reduced. The magnitude of the effect of moderate to strong inducers (e.g. efavirenz, rifabutin) on olaparib exposure is not established, therefore the co-administration of Lynparza with these medicinal products is also not recommended. Effect of Lynparza on other drugs: Caution and appropriate clinical monitoring is recommended when sensitive CYP3A substrates or substrates with a narrow therapeutic margin (e.g. simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus and quetiapine) or P-gp substrates (e.g. simvastatin, pravastatin, dabigatran, digoxin and colchicine) are combined with Lynparza. Lynparza may reduce efficacy of hormonal contraceptives. Lynparza may increase the exposure to substrates of BCRP (e.g. methotrexate, rosuvastatin), OATP1B1 (e.g. bosentan, glibenclamide, repaglinide, statins and valsartan), OCT1, MATE1, MATE2K (e.g. metformin), OCT2 (e.g. serum creatinine), OAT3 (e.g. furosemide and methotrexate). Caution if co-administered with any statin.

Pregnancy and Lactation: Women of childbearing potential should not become pregnant while on Lynparza and not be pregnant at the beginning of treatment. A pregnancy test should be performed prior to treatment and considered regularly throughout treatment. The efficacy of some hormonal contraceptives may be reduced if co-administered with Lynparza. Therefore, an additional non-hormonal contraceptive method should be considered during treatment. For women with hormone dependent cancer, two non-hormonal contraceptives should be considered. Lynparza could cause foetal harm when administered to a pregnant woman. Lynparza is contraindicated during breast-feeding and for 1 month after receiving last dose. Male patients must use a condom during therapy and for 3 months after receiving last dose when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients must also use highly effective contraception.

Male patients should not donate sperm during therapy and for 3 months after treatment.

Ability to Drive and Use Machines: Asthenia, fatigue and dizziness have been reported and patients who experience these symptoms should observe caution when driving or using machines.

Undesirable Events: Consult SmPC for full list of side effects. Very common: Anaemia, neutropenia, leukopenia, nausea, vomiting, diarrhoea, dyspepsia, dysgeusia, decreased appetite, fatigue (including asthenia), headache, dizziness, cough, dyspnoea. Common: Lymphopenia, thrombocytopenia, transaminases increased, stomatitis, upper abdominal pain, rash, blood creatinine increased, venous thromboembolism. Uncommon: Myelodysplastic syndrome/Acute myeloid leukaemia, hypersensitivity, dermatitis, mean cell volume increased. Rare: Angioedema, erythema nodosum. Not known: Drug induced liver injury.

Legal Category: Product subject to prescription which may not be renewed (A) Marketing Authorisation Number: EU/1/14/959/002-003 (100mg tablets); EU/1/14/959/004-005 (150mg tablets).

Marketing Authorisation Holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden.

Further product information available on request from: AstraZeneca Pharmaceuticals (Ireland) DAC, College Business and Technology Park, Blanchardstown Road North, Dublin 15.

Tel: +353 1 609 7100.

LYNPARZA is a trade mark of the AstraZeneca group of companies.

Date of API preparation: 08/2023 Veeva ID: IE-5348 Adverse events should be reported directly to: HPRA Pharmacovigilance, Website: www.hpra.ie Adverse events should also be reported to AstraZeneca Patient Safety on Freephone 1800 800 899

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

Call for papers: make your contribution to Hospital Professional News  Articles  Research Papers  Reviews  Programme Descriptions  Reports Case Reports  Letters to Editor  Support fellow hospital professionals as well as aspiring junior professionals and early-year hospital pharmacists  Practice reports share innovations on any area of practice, including delivering clinical services, pharmacy administration, or new approaches to inform and engage with patients  Perspective articles focus on a specific field or discipline and discuss current advances or future directions, and may include original data as well as expert insight and opinions

Contact: Kelly Jo Eastwood at: kelly-jo@ipn.ie or Danielle Norton - danielle@hospitalprofessionalnews.ie

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February Issue Issue117

5

Contents

Foreword

Over 1,500 Consultants sign new contract P7

Editor In one of our lead stories this month we reveal that 1,548 consultants have signed the new contract since it was launched last March.

This means that more than 35% of the total number of consultants working across the health service are now on the new contract.

Hundreds more applicants are also being processed by the Health Service Executive (HSE). There has been a significant increase in the number of consultants who are employed across the health service, with a large increase occurring during the last four years.

Record growth in Ireland’s ‘hidden waiting lists’ P8 Predicting the progression of ulcerative colitis P12

8

Launch of the 2024 Hospital Professional Honours P14

The top three specialities that are seeing the largest uptake of the contract to date are General Medicine, Anaesthetics and Surgery.

Coverage from ESMO Congress P29

You can read more about this on page 7.

Ask the Expert – Professor Sean O’Reilly P42

12

Biomarkers in Cancer Treatment P47

This validation involves hospital administration contacting patients on waiting lists to ensure that they are still available to attend appointments or require their procedure. Many patients will have made alternative arrangements due to the length of time on the waiting list or may no longer be suitable for treatment. The largest number of such outpatient removals under the NTPF co-ordinated validation last year were in the West.

REGULARS

Feature: Dry Eye Disease P11 CPD: Osteoporosis P37

29

Oncology Focus: NSCLC Updates P41

The release of the latest National Treatment Purchase Fund (NTPF) figures confirm that the three main waiting lists reduced by just over 18,800 (3%) last year – a shortfall of more than 50,000 against target.

Oncology Focus: Pancreatic Cancer P50 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.

PUBLISHER IPN Communications Ireland Ltd Clifton House, Lower Fitzwilliam Street, Dublin 2 (01) 669 0562 GROUP DIRECTOR Natalie Maginnis n-maginnis@btconnect.com EDITOR Kelly Jo Eastwood EDITORIAL danielle@hospitalprofessionalnews.ie ACCOUNTS Fiona Bothwell cs.ipn@btconnect.com

In other news, on page 8, data analysed by the Irish Hospital Consultants Association (IHCA) confirms that the modest reduction in waiting lists seen in 2023 would not have been achieved had it not been for the fact that around 105,000 people were removed from hospital waiting lists last year without treatment through a National Treatment Purchase Fund (NTPF) ‘validation’ process.

47

SALES EXECUTIVE Avril Boyd avril@hospitalprofessionalnews.ie SALES & TRAINING MANAGER Sibongile Mude s.mude@hospitalprofessionalnews.ie CONTRIBUTORS Dr Grainne Shiel | Dr Jason McGrath Dr Gordon Daly | Dr Damir Vareslija Professor Moira O’Brien Michele O’Brien Professor Sean O’Reilly Trinity St James’s Patient Representative Group Professor Leonie Young David Hackett Dr Stephen Maher Dr Nikolett Warner Dr Roisin McAvera Professor Ann Hopkins Professor Siobhan Glavey

DESIGN DIRECTOR Ian Stoddart Design HOSPITALPROFESSIONALNEWS.IE

@HospitalProNews HospitalProfessionalNews

The data comes on the back of a report which has detailed that high waiting lists for cancer diagnosis and treatment could be significantly reduced by the use of teledermatology technology. But only six hospitals out of 13 national dermatology departments are currently using the HSE-approved service. The report – carried out by economist Jim Power for AllView Healthcare – also declares, “the barriers preventing a greater use of these technologies in all Irish hospitals needs to be addressed, adding “potentially fatal skin cancers are being missed or treatment delayed due to the slow uptake of private dermatology service.”

This issue also sees the launch of the 2024 Hospital Professional Honours. After a hiatus of over three years, we are delighted that the Honours will once again take place in the Radisson Blu, Dublin on September 14th of this year. The HPN Honours are the most influential and respected networking event, lauding excellence, innovation and service development; judged by key influencers including renowned respected experts. Turn to page 14 to read more about the Honour Categories and how you can enter.

I hope you enjoy the issue.

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

6

News

Recognition for Patient Safety Initiative Dr Peter Lachman, Lead, RCPI’s expert Quality Improvement faculty

managing risk, not simply about responding to incidents. S.A.F.E involves teaching clinical teams in a practical, jargon-free way, supporting them to understand what they do well, what needs to improve, and how they can measure the impact of changes they make.”

A patient safety education programme offered by the Royal College of Physicians of Ireland (RCPI) has received international recognition following its publication in the 2023 edition of the Global State of Patient Safety.

Situation Awareness For Everyone (S.A.F.E), a 6-month collaborative patient safety education

programme, has been featured as a case study in the annual patient safety report published by the Institute of Global Health Innovation at Imperial College London.

In the report, Dr Peter Lachman, who leads RCPI’s expert Quality Improvement faculty, said: “The concept behind the programme is that patient safety should be about

The report which places Ireland 7th in the OECD Patient Safety Country Ranking showcases S.A.F.E and its excellence in safety measurement and improvement from the patient, family and carer perspective.

Now in its 6th cohort at RCPI, S.A.F.E provides multidisciplinary clinical teams with the skills and knowledge to implement an innovative safety improvement bundle. Applications for S.A.F.E. are open with clinical teams invited to join in March 2024.

Based on the findings of the Global State of Patient Safety, the report sets out three recommendations to improve the measurement of patient safety: 1. Assessment: A more balanced and comprehensive set of global patient safety indicators is required to address the data gaps identified in this report, and to ensure comparable data is available for all countries. Consensus is required on the minimum set of indicators that all countries should report on.

2. Adoption: A global repository of safety measurement and improvement interventions should be developed and made freely available to frontline teams of practitioners and researchers across the world.

3. Activation: To ensure the faithful adoption of interventions, patients, families and carers must be given the agency to become active and equal partners in the delivery of safe care.

Hospital Pharmacy Survey EHMA and EAHP are conducting a survey targeting hospital pharmacists and pharmacy managers, focusing on the collection and sharing of data related to medication demand and stocks. The survey aims to identify how hospitals currently gather and share data on medication stock and demand, identify any barriers to collecting information on medicines stocks, and explore the workload implications and digitalisation requirements for hospital pharmacy workflows in relation to data collection.

Following the COVID-19 pandemic, a key strategic

goal for the European Union is a strong European Health Union. Enhancing the role of the European Medicines Agency is a key policy pillar to building a European Health Union. The resulting new mandate for EMA to establish a European Shortages Monitoring Platform (ESMP) will impact hospital pharmacists' and pharmacy managers' workloads as data will need to be shared on medication stocks with national/ regional authorities for the ESMP. During the pandemic, hospitals played a key role in managing and preventing medicine shortages by sharing information on medication demand and stocks with National

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Competent Authorities for better inventory management. This activity is anticipated to be extended for hospital pharmacists under the new EMA legislation.

To raise the visibility of hospitals' capacity to collect and share data on demand and medication inventories to NCAs for the new EMA mandate this research aims to:

information on medicines stocks.

• Explore any workload burden and needs to digitalise hospital pharmacy workflows associated with collecting and sharing medication inventory data with national/regional competent authorities.

• Identify how hospitals collect and share data on medication stock and demand.

The survey will remain open for three months. The results will be collected and published in a briefing paper that will be shared with EU policymakers and the European Medicines Agency.

• Identify the barriers to collecting the relevant and necessary

Visit www.eahp.eu for further details.

News

7

Over 1,500 Consultants sign new Contract The Minister for Health, Stephen Donnelly, has announced that 1,548 consultants have signed the new contract since it was launched last March.

This means that more than 35% of the total number of consultants working across our health service are now on the new contract.

Hundreds more applicants are also being processed by the Health Service Executive (HSE).

There has been a significant increase in the number of consultants who are employed across our health service, with a large increase occurring during the last four years.

There are 4,235 consultants (whole-time equivalents) currently working in the public health service. In comparison, there were 3,250 consultants (wholetime equivalents) in December 2019, which highlights the very substantial 30 per cent growth in the number of consultants working in our public health service over this period.

Minister for Health Stephen Donnelly said, “I am delighted to see the positive response to the Public-Only Consultant Contract.

The introduction of this contract represents a landmark in delivering Universal Healthcare. It is a progressive contract that puts the interests of patients to the fore.

This new contract is facilitating a transition away from the provision of private care in public hospitals and ensuring that state resources are provided in accordance with patient need rather than a patient’s ability to pay. The contract compares very favourably with other health services around the world, and it is clearly proving attractive to potential candidates."

The 1,548 Public-Only Contracts includes 306 new entrant consultants who have joined our health service and 1,242 consultants who have switched from their previous contracts.

The top three specialities that are seeing the largest uptake of the contract to date are General Medicine, Anaesthetics and Surgery.

A key objective of the PublicOnly Consultant Contract is to extend the hours that consultants, who are senior clinical decisionmakers, are on duty across the health services.

Under this contract, consultants can be asked to work 8am to 10pm Monday to Friday and 8am to 6pm Saturday as part of their core 37-hour week. The contract is a public only contract, meaning consultants will only treat public patients in public hospitals.

• a 37-hour week from 8am to 10pm Monday to Friday and 8am to 6pm Saturday

The new Sláintecare contract includes:

• more flexibility for consultants who want to work share, do less than whole-time, work compressed hours or opt for different work patterns

• basic pay of ¤217,325 ¤261,051 on a six-point scale

• additional remuneration for on-call duties and overtime as applicable • supports for medical education training and research

New Health System Research Funding A Medical Council-supported research programme is among eight successful programme awards* to receive funding by the HRB. Professor Deirdre Bennett of University College Cork is leading the programme, ‘Educating Healthcare Professionals for Climate Change Resilient and Sustainable Healthcare Systems.’

The programme has been awarded ¤2,475,908.

With humanity facing a triple planetary crisis of climate change, pollution and loss of biodiversity.

Prof. Bennett’s research aims to prepare healthcare professionals to actively contribute to resolve the global planetary crisis.

According to Prof Bennett, “the outcome will be a healthcare system that is not only more responsive to climate challenges, but a contributor to broader sustainability goals, benefiting patients and the planet alike.”

Dr Bernadette Rock, Head of Research & Regulatory Data Insights at the Medical Council said, “The Medical Council is delighted to bring its expertise and experience to this research by exploring how outputs might influence regulatory policy, and examining the best methods for integrating topics of climate change and sustainability into the professional development of doctors.

“One of the outputs of the planned research will be a competency framework applicable to all healthcare professionals, and the role of the Council will involve exploring how this framework can be integrated into the education and training of doctors from undergraduate through to continuing professional development.

“The scientific evidence is unequivocal that climate change has profound direct and indirect

Dr Bernadette Rock, Head of Research & Regulatory Data Insights at the Medical Council

impacts on health and wellbeing, and the World Health Organisation has identified climate change as the greatest health threat of the 21st century.

“This research is reflective of the Medical Council’s commitment to equipping a new generation of medical practitioners with knowledge and skills in climate change and sustainability. It will be used to empower healthcare professionals to address the challenges posed by climate change, working towards a healthier and more sustainable future.”

The Medical Council regulates medical doctors in Ireland. The

Council's purpose is to protect the public by promoting and better ensuring high standards of professional conduct and professional education, training, and competence among doctors.

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

News

8

Record Growth in ‘Hidden Waiting Lists’ Professor Rob Landers the largest number of removals from the outpatient waiting lists were: Galway University Hospital (11,642), Tallaght University Hospital (10,664), the Mater Hospital (8,565), University Hospital Limerick (7,419), Cork University Hospital (6,063) and CHI at Crumlin (5,128). Together they account for almost half (49,481 or 47%) of all validated removals from the waiting lists without an appointment or treatment.

The release of the latest National Treatment Purchase Fund (NTPF) figures confirm that the three main waiting lists reduced by just over 18,800 (3%) last year – a shortfall of more than 50,000 against target.

New data analysed by the Irish Hospital Consultants Association (IHCA) confirms that the modest reduction in waiting lists seen in 2023 would not have been achieved had it not been for the fact that around 105,000 people were removed from hospital waiting lists last year without treatment through a National Treatment Purchase Fund (NTPF) ‘validation’ process.

on waiting lists to ensure that they are still available to attend appointments or require their procedure. Many patients will have made alternative arrangements due to the length of time on the waiting list or may no longer be suitable for treatment. The largest number of such outpatient removals under the NTPF coordinated validation last year were in the West.

This validation involves hospital administration contacting patients

A further breakdown of the figures reveals the six hospitals with

The waiting list for inpatient and day case procedures increased over the past 12 months by almost 4,200 (5%). While the number awaiting an outpatient appointment fell by around 22,500 (4%), this reduction is offset by record increases in other so-called ‘hidden lists’, such as the 9,500 additional people placed on the Outpatient Suspensions list, which is an increase of 30%.

In total over 869,300 people were on some form of hospital waiting list at the end of December – a reduction of just 766 (0.1%) compared with the start of 2023.

Hospital Group

Number of Outpatient Removals due to NTPF validation to end Nov 2023

Saolta University Health Care Group

25,908

Dublin Midlands Hospital Group

22,073

Ireland East Hospital Group

21,835

South/South West Hospital Group

14,108

Children’s Health Ireland Group

10,351

University of Limerick Hospitals Group

9,448

RCSI Hospital Group

973

TOTAL

104,696

The Government’s Action Plan for 2023 had set a target to reduce waiting lists for appointments and hospital treatment by 10% (-69,000) compared with the number waiting at the start of 2023. Despite treating significantly more patients than planned last year, the main waiting lists only decreased by a modest 3% due to a higher-than-expected level of patient demand. The inability to accurately forecast this additional demand also contributed to the almost ¤1 billion supplementary budget for Health last year.

Commenting on today’s waiting list figures, IHCA President Professor Rob Landers, said, “The Government needs to expedite its new ¤407 million Waiting List Action Plan for 2024 and show more ambition in terms of delivering the additional hospital capacity that is required to meets its reduction targets.

“The inability to accurately predict the expected levels of patient demand last year stymied the previous Action Plan from the outset. This cannot be repeated in 2024. It is therefore vital that the health service management is agile and open to reviewing its figures and actions throughout the year in order to achieve real and sustainable solutions for patients.

“This is without doubt the busiest time of year for our health service, and while we welcome the fact that the number of patients waiting on trolleys in our Emergency Departments is down compared to the first weeks of January last year, we must ensure that as much focus and emphasis is applied to all parts of our public hospital system all the year round.

“The key solution, of course, is the immediate significant expansion in hospital capacity.

In April last year, the Minister for Health’s announcement of a rapid build programme to open 1,500 additional hospital beds across 15 acute public hospital sites in 2023 and 2024 was welcomed.3 The Government needs to implement that plan immediately and commit the promised ¤1 billion capital budget to open these beds as indicated.

“What Consultants want to ascertain on behalf of their patients is when are we going to see these 1,500 additional beds in place, the promised six surgical hubs open and operating, together with the long awaited four elective hospitals.”

A further breakdown of the figures reveals the six hospitals with the largest number of removals from the outpatien lists were: Galway University Hospital (11,642), Tallaght University Hospital (10,664), the Mater Hospital (8,565), Univ

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

News

9

New Study on Waiting Lists High waiting lists for cancer diagnosis and treatment could be significantly reduced by the use of teledermatology technology.

But only six hospitals out of 13 national dermatology departments are currently using the HSEapproved service, a major new report has concluded.

The report – carried out by economist Jim Power for AllView Healthcare – also declares: “the barriers preventing a greater use of these technologies in all Irish hospitals needs to be addressed, adding “potentially fatal skin cancers are being missed or treatment delayed due to the slow uptake of private dermatology service.”

Teledermatology refers to the use of static digital images to triage, diagnose, monitor, or assess skin conditions without the need for the patient to be physically present.

By taking advantage of available technologies, teledermatology can also improve productivity while providing the same level of access to high quality care for the patient, ensuring patients receive timely care in the most appropriate setting.

AllView Healthcare is a leading provider of teledermatology services in Ireland. Its services are HSE approved and national provider to the Vhi for its members.

AllView Healthcare Clinics and use specialist imaging equipment to record a series of high definition microscopic and macroscopic images of the skin complaint.

Mr Power points out that skin cancer is the most common cancer in Ireland with over 13,000 new cases diagnosed every year.

This is expected to double by 2040 according to the National Cancer Registry of Ireland.

His report says the outpatient waiting list for dermatology services increased by 87.6 per cent between December 2015 and December 2023, from 29,955 to 56,203. In December 2023, adults accounted for 84 per cent of this total at 47,240, and children accounted for 16 per cent at 8,963. In December 2023, there was a further 1,109 patients on the inpatient dermatology waiting list.

The time people are waiting for diagnosis and treatment is also growing longer: in 2014 14.9 per cent of outpatients were waiting for more than 12 months. This stood at 19.6 per cent in December

2023. “This deterioration in the length of the waiting list is of deep concern, given that early detection and intervention is essential for a better outcome for the patient and a less expensive treatment process,” the report states.

It points out that the role teledermatology can play in the diagnosis and treatment of skin cancer in the UK health service is fully recognised in a paper produced by the NHS and British Association of Dermatologists and the systems are in place to support it. All Northern Ireland GPs have been issued with a dermatoscope attached to an iPod to take images which is the only way that referrals will be accepted and is how the NHS Northern Ireland trusts are dealing with their four-year waiting lists.

Mr Power’s report states that the National Clinical Programme for Dermatology (NCPD) recommended strategic investment in piloting initiatives such as teledermatology. It concluded that such initiatives, if implemented properly, would “shorten waiting lists and times and improve access and quality of care delivery for Irish dermatology patients.”

According to the study for AllView Healthcare, “The main long-term benefit of using teledermatology is to ensure patients receive timely care in the most appropriate setting, thereby increasing capacity for those patients who need face-to-face appointments.

It is clear that early detection and early intervention is essential for better patient outcomes and also in terms of treatment costs for the health service.”

It said the key conclusion of a research article published in the Journal of Public Health relating to Ireland, was that, “The cost of managing a case of melanoma diagnosed at Stage IV (¤122 985) was more than 25 times more expensive than managing a case diagnosed at Stage IA (¤4,269).”

The report concludes, “Waiting lists for dermatological services are unacceptably high and are proving very persistent. The situation is likely to worsen as demographic and climate-related factors push up the incidence of skin cancer over the coming years. Stakeholders believe the system is in crisis, but that there are proven remedies. The role of teledermatology in reducing

Eoin O'Reilly, AllView Healthcare CEO

waiting lists and achieving better patient outcomes is fully recognised in countries such as the US and UK. The barriers preventing a greater use of these technologies in all Irish hospitals needs to be addressed.”

It adds that, “some stakeholders believe that potentially fatal skin cancers are being missed or treatment delayed due to the slow uptake of a private teledermatology service under contract to the HSE to clear waiting lists. One hospital which signed up said that one in five patients it referred were diagnosed with skin cancer, including some with malignant melanomas.”

Since winning a HSE contract in October 2021, AllView Healthcare has received patients from just six hospitals in Dublin, Drogheda, and Cavan out of the 13 offering various levels of adult dermatology care and the report says this may be partly down to a dispute between consultants.

This at a time when AllView Healthcare has the capacity to take on an extra 19,000 patients that went unused and it is looking like the same capacity for 2024 will go unused unless more hospitals open their doors. Hospitals using AllView Healthcare’s teledermatology service have achieved the largest waiting-list reductions with one dermatology consultant saying that “one in five people of those cases we sent to AllView had a skin cancer. On average their care was brought forward by 14 months”.

The National Clinical Programme for Dermatology (NCPD) recognised a pilot study for the use and benefits of teledermatology in an Irish context stating: “the use of photography as a triage tool offers the potential to shorten waiting lists and improve healthcare access and delivery while identifying and fast-tracking patients with suspicious skin lesions. The process will also allow patients

with evidently benign lesions to be discharged, representing cost efficiencies for dermatology.”

Commenting on the findings in Mr Power’s report, Mr Eoin O’Reilly, CEO of AllView Healthcare, stated: “The report clearly confirms the facts we have already been seeing on the ground and how Ireland is slow to follow the rest of the world in moving towards teledermatology as a tool in the hospitals tool kit to be used to enable patients’ faster access to a consultant’s diagnosis.

“We constantly hear of high-profile cases such as Sarah Ferguson, Duchess of York's, recent melanoma and Chris Evans and Molly-Mae Hague’s skin cancer diagnosis in last year, however there are over 50,000 patients waiting for their first appointment across Ireland, based on our own data and that of global trends it means hundreds of these may have melanoma.

“Recently both Temple Street and Crumlin Hospital have started to use the service for children in certain age categories, yet adult dermatology departments still don’t want to see it put in place in some key hospitals.

“Allview use teledermatology as a key tool in our overall dermatology service. It is now the new model for the privately insured patients across Ireland who can get seen in 10 days or less, yet the exact same service is not made available to patients in some public hospitals who are over four years on a waiting list and that seems to make no sense at all.”

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

10 News

Investment in Neurosurgical Technology The advanced technology solution will be used in cranial surgery to place electrodes for people undergoing Deep Brain Stimulation Treatment

Blackrock Health, combining Hermitage, Blackrock, Galway and Limerick Clinics’, has invested ¤1.5 million in new neurosurgical technology that will facilitate robotic cranial and spinal surgery. The ExcelsiusGPS® Robotic Navigation Platform has been installed in the Hermitage Clinic and is now operational for spinal surgery, with training for cranial surgery due to take place before the end of Q1 2024. Once training has been completed, the

Hermitage Clinic will be the first hospital in Ireland to offer cranial robotic surgery.

In a significant development for people living with Parkinsons Disease and other neurological conditions, the advanced technology solution will be used in cranial surgery to place electrodes for people undergoing Deep Brain Stimulation Treatment (DBS). DBS is a long-term treatment option for patients with selected movement disorders, which involves

implanting neurotransmitters in the brain. All Spinal and Cranial Neurosurgeons will be fully conversant in the use of the ExcelsiusGPS robot navigation platform. The team has already undertaken training and some consultants will participate in observerships in the United States to deliver new surgical techniques at Blackrock Health Hermitage Clinic.

The ExcelsiusGPS® can facilitate more minimally invasive surgeries,

translating to smaller incisions, less tissue damage, reduced postoperative pain, shorter hospital stays, and faster recovery times.

The system is also designed to streamline the surgical workflow and reduce radiation exposure to surgeons and staff. This revolutionary robotic navigation platform is the world’s first technology to combine a rigid robotic arm and full navigation capabilities into one adaptable platform for accurate trajectory alignment in spine surgery.

Gordon Dunne, CEO of the Blackrock Health Hermitage Clinic said: “The ExcelsiusGPS® platform will have a huge impact for patients by improving safety and accuracy within operating theatres. The acquisition of the robotic platform marks an important milestone in neurosurgery not only in the Hermitage Clinic, but for patients across Ireland who will be treated with this technology. At Blackrock Health Hermitage Clinic, we are committed to surgical excellence and delivering new technologies to provide best in class care for our patients.”

DigiBete Diabetes App Launches in Ireland Diabetes Ireland has announced the arrival of the multi-awardwinning DigiBete Self-Management App and Video Platform in Ireland.

Following a successful pilot project in Limerick University Hospital, Diabetes Ireland and DigiBete have spent the past few months training other paediatric diabetes teams on how to use the App to educate their families on managing Type 1 diabetes.

The primary aim of the App is; • to improve care for children and young people with diabetes by helping them manage their condition more effectively.

• provide an easy cost-free communication stream for hospital paediatric diabetes teams to engage with families to provide clinical advice and information.

The App supports children and adolescents with Type 1 diabetes and their families by giving them a place to organise their diabetes appointments, and ongoing care, and receive access to relevant

educational resources. Families will be able to access ageappropriate diabetes information such as quizzes, videos, and food & exercise support.

The App supports children and adolescents with Type 1 diabetes and their families by giving them a place to organise their diabetes appointments, and ongoing care, and receive access to relevant educational resources. Families will be able to access ageappropriate diabetes information such as quizzes, videos, and food and exercise support.

as sick day rules and good care reminders in a matter of minutes.

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

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

To date, 11 of the 18 paediatric diabetes clinic teams have completed their training (available at https://www.diabetes.ie/livingwith-diabetes/child-diabetes/ diabetes-digibete/)

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

To access the App, families need to contact their diabetes team to obtain a code and easy selfregistration instructions and we would encourage all families to speak to their team today or at their next appointment.

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

We hope the remaining paediatric diabetes teams register for DigiBete in the coming months so that it will be available to all families by the end of 2024. Meanwhile, families can access the various education resources on the platform by visiting https://www.digibete.org/ Diabetes Ireland has partnered with West Pharmaceutical Services, a global leader in innovative solutions for injectable drug administration to support the rollout of DigiBete in Ireland. “We are excited to partner with Diabetes Ireland to help bring this important resource to families of children and young people living with diabetes in Ireland, which will enable them to access support and manage their condition more effectively,” said Aileen Kinsella, VP & General Manager, Global Pharma at West. “West has played a significant role in helping to deliver diabetes care globally for over 90+ years and continues to be a leading global supplier of containment solutions for the major injectable drug manufacturers in the diabetes market.”

Dry Eye Disease 11

Dry eye renaissance: Escalating cases meet with innovation Two decades ago, managing dry eye disease was straightforward.

Practitioners were able to offer a few options: artificial tears, prescription cyclosporine ophthalmic emulsion (Restasis; Allergan), and punctal occlusion.

Since then, our options have multiplied. With novel treatments and diagnostics, we’ve entered an era of innovative management for this common condition—a kind of dry eye renaissance.

Progress is essential because dry eye’s incidence is growing. Partly attributable to increased diagnostic skill, the spike is also driven by our population’s advancing age, irritants such as contact lens wear and extended screen time,1 and an awareness among patients that they don’t have to live with scratchiness, burning or blurred vision. Results from a large US study confirmed this escalation, showing an increase in dry eye’s overall prevalence, annual prevalence and incidence between 2003 and 2015.2 Fortunately, we now have the power to respond to this trend thoughtfully and comprehensively.

Today, we can identify and address not only the symptoms of dry eye but its causes. We can reach patients who are uninsured or underinsured with an affordable

generic formulation of Restasis.3 And we can improve the calibre of clinical trials by using precision diagnostics to standardise end point analyses.

For clinicians, the evolution of dry eye management is as much a responsibility as an opportunity.

Only by staying informed about the growing spectrum of products can we do our best to manage this intractable condition.

Treatment timeline Since Restasis was introduced in 2003, anti-inflammatory drops have been at the heart of dry eye management. Over the past 7 years, the category has diversified with FDA approvals of a high-concentration cyclosporine ophthalmic solution (Cequa; Sun Ophthalmics); lifitegrast ophthalmic solution (Xiidra; Novartis), an antagonist that blocks LFA-1; and loteprednol etabonate ophthalmic suspension (Eysuvis; Kala Pharmaceuticals), a topical corticosteroid.

But the latest treatments don’t address inflammation, focusing instead on other drivers of dry eye. The nasal spray varenicline solution (Tyrvaya; Viatris) is a partial nicotinic receptor agonist that stimulates the secretory nerves, causing the release of

Written by David Wirta, MD and George N. Magrath, MD, MBA, MS

aqueous from the lacrimal gland to stimulate the production of tears.

Perfluorohexyloctane ophthalmic solution (Miebo; Bausch + Lomb, Novaliq), approved in May 2023, is a nonaqueous topical that prevents tears from evaporating.

In two large phase three trials, the drug significantly reduced the signs and symptoms of dry eye in patients with a history of the condition and clinical indications of meibomian gland dysfunction.4 Cyclosporine ophthalmic solution (Vevye; Novaliq), formerly CyclASol, was approved in June 2023. Free of water, preservatives, oils, and surfactants, cyclosporine ophthalmic solution is designed to offer early and durable efficacy for patients.

Of course, medications are not the only option for managing meibomian gland dysfunction. FDAapproved devices include OptiLight (Lumenis), which uses intense pulsed light therapy; LipiFlow (Johnson & Johnson Vision), a thermal pulsation system; iLux (Alcon), which applies compression and light-based heat; and the TearCare System (Sight Sciences) for heat and gland expression.

Additional treatments with unique mechanisms are on the horizon.

Topical formulations being investigated in phase three clinical trials include: • BRM421 (BRIM Biotechnology), a synthetic peptide that sparks tissue regeneration and corneal repair, reduces inflammation, and improves tear quality • Reproxalap (Aldeyra Therapeutics), a reactive aldehyde species inhibitor that reduces inflammation • SI-614 (Seikagaku), a modified hyaluronate that stabilises the tear film and promotes corneal wound healing • Tivanisiran (Sylentis), a small interfering RNA that controls pain and inflammation by inhibiting the synthesis of TRPV1 • Visomitin (Mitotech), a cardiolipin peroxidation inhibitor that sustains and restores mitochondrial function to target inflammation, corneal damage, tear deficiency, and gland tissue regeneration Diagnosis precision

Corneal Staining

Without precise diagnostic tools, practitioners would be unable to provide personalised treatment. The old standby is the Schirmer test, which determines whether eyes are underproducing or overproducing tears. But tear film can now be analysed with InflammaDry (Quidel), which detects an inflammationlinked enzyme, MMP-9, to identify patients who may benefit from anti-inflammatory therapy. Also available are the ATD TearScan 300 microassay (Advanced Tear

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

12 Dry Eye Disease Diagnostics), which identifies dry eye by measuring lactoferrin and IgE levels in tears, and the Osmolarity System (TearLab), which measures the aqueous content of the tear film by checking for heightened electrolytes.

Experimental diagnostics are promising. TeaRx technology (DiagnosTear) performs a multiparameter assay on a tiny tear sample to make a differential dry eye diagnosis. This 10-minute assay could become the first available at the point of care.

Other strategies may help standardise clinical trials. BEDx (Boston Eye Diagnostics) is an imaging technology that captures

clear photographs of corneas stained with fluorescein and other images of the ocular surface. In an automated and repeatable manner, the device takes several pictures and volume averages them to create an image that is in focus across multiple depths. The system’s objectivity may level the grading of corneal staining photos.

Standardised grading may also be supported by a modified version of the National Eye Institute’s corneal fluorescein staining scale (Figure).

In a recent study, researchers at Lexitas introduced a modified scale to support more reliable and repeatable assessment methodology for examiners.5

A practice-changing trend The dry eye renaissance has changed not only our armamentarium but the way we provide care. Because managing the condition is often time consuming, many practices are opening dry eye centres6 that accommodate diagnosis and treatment without affecting other clinic scheduling. Their services include cash pay therapies such as LipiFlow, vitamins and artificial tears for patients seeking care beyond what their insurance will cover. Cataract surgeons have also focused on dry eye management,7 because resolving symptoms before a procedure can support the

accuracy of refractive calculations and limit postsurgical discomfort.

There’s no doubt that advances in dry eye management and diagnosis are making a difference for patients, but questions remain.

Can issues such as diet8 and climate exacerbate dry eye?

Should lifestyle recommendations such as better hydration and turning off ceiling fans be part of our treatment plans? Answers are sure to emerge as we pursue further research, building on today’s advances with nextlevel discoveries about this multifactorial condition.

References available on request

News

Predicting Progression of Ulcerative Colitis A new partnership between RCSI University of Medicine and Health Sciences and Irish diagnostics company Serosep Ltd is set to personalise treatment for ulcerative colitis and ultimately improve quality of life for patients with the condition.

Under the new alliance, RCSI researchers will work with Serosep to accelerate the development of new tests to help predict disease progression in ulcerative colitis, a form of inflammatory bowel disease that damages the lining of the gut over time. The condition causes inflammation and ulcers in the large intestine (colon) and rectum.

The project will develop technology to identify ulcerative colitis patients who are likely to progress in their disease, ensuring that people get the most effective care for their disease, and sparing people treatments where they are not likely to be of benefit to them.

The partnership between Serosep and RCSI is co-funded by Serosep and the Enterprise Ireland Innovation Partnership Programme.

At present, medications known as 5-Aminosalicylates (5-ASA) are the most common first line of treatment for mild-tomoderate ulcerative colitis, and as the disease progresses it is typically managed with steroids, immunosuppressants and biological drugs.

There is a pressing need to develop accurate biomarkerbased methods to identify the best treatment regimes for patients soon after diagnosis.

“Currently there are no biomarkers which allow prediction of disease

Dr Hannah Fitzgerald, Postdoctoral Researcher, RCSI School of Pharmacy and Biomolecular Sciences; David Clancy, Serosep CTO; and Dr Sudipto Das, Principal Investigator at RCSI School of Pharmacy and Biomolecular Sciences

progression in patients with ulcerative colitis,” explained Dr Sudipto Das, Lecturer and Principal Investigator at RCSI School of Pharmacy and Biomolecular Sciences.

“Having such biomarkers could augment decision-making for clinicians about whether the patient could benefit from an escalation of treatment at an early stage of the disease.”

Dr Das’s team will work with Serosep to validate specific ulcerative colitis biomarkers that the RCSI group has identified in the lab. The plan is to create a new in-vitro diagnostic solution that can support clinicians as they make decisions about the most suitable treatment for the patient based on a panel of biomarkers that can be measured and tracked in samples of their tissue and potentially in the blood as well.

“Through recent work in our lab we have identified specific genes that can potentially predict disease progression in adult ulcerative colitis patients,” said Dr Das.

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

“This partnership will allow us to further validate these genes in a larger cohort of patient samples and enable development of a test that can be applied in the clinic to identify patients who are likely to progress at an early stage of disease. This in turn would allow early treatment for those patients, and sparing patients who are less likely to progress from unnecessary treatment. The ultimate impact of this test would be to improve quality of life in patients with ulcerative colitis.”

to support its products from conception to commercialisation.

Serosep was awarded Irish Medtech Company of the Year in 2022.

Collaborative research

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

Serosep Ltd, founded in 1997, is headquartered in Limerick with subsidiaries in London and Johannesburg, and is focused on the clinical in-vitro diagnostic market specifically in infectious disease, which has seen the company build an infrastructure

Serosep CTO David Clancy outlined: “The collaboration with RCSI presents an opportunity for Serosep that will enable us to build expertise in new technologies to further develop our product portfolio and access new markets.”

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14 Honours

Hospital Professional

ONOURS 2024 Fresenius Kabi Innovation in Aseptic Compounding

This Honour Category is open to qualified, trained pharmacists and technicians engaged in the preparation of injectable and other sterile products for individual patient use. The judges will be looking for an individual within a pharmacy department or a pharmacy team that can best demonstrate innovation in safety and quality within their department.

This could be through SOPs, cost saving projects, submitted posters, clinical trials medication, interaction with other departments, identification and fulfilment of training needs or other. The project/ process should show measurable results of having improved the service that they provide to the pharmacy department or their patients.

Judges will be looking for: The judges will be looking for an individual within a pharmacy department or a pharmacy team that can best demonstrate innovation in safety and quality within their department while incorporating innovative initiatives.

The project/process should show measurable results of having improved the service that they provide to the pharmacy department or their patients. This award does not differentiate between large and small hospitals. It also does not differentiate between a public and private hospital. The entry needs to demonstrate measurable results attributable to the innovations Who can Enter: Each submission will be judged by an independent

judging panel. There will be no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Honours 15 Hospital Professional

ONOURS 2024 Medisource Hospital Pharmacy Technician of the Year It is evident that hospital pharmacy technicians are playing an increasingly important supporting role as pharmacists are increasingly spending more time with patient consultations and engaging local stakeholders.

The shift in emphasis from dispensing to healthcare provision has meant that the wider pharmacy team has to pull together – hospital pharmacy technicians capture the essence of this in everything that they do.

This Honour will recognise the recipient's important contribution to the hospital pharmacy technician profession. The judges will be looking for those who can demonstrate promotion of the role of the hospital pharmacy technician and those who continue to champion excellence through forward thinking and innovation.

The recipients achievements will be an inspiration to those pursuing innovative practice, to those striving to raise standards and to pharmacists who, through their professionalism, provide models for others within hospital pharmacy.

Judges will be looking for:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health  Evidence of a large variety of skills, attributes and accomplishments  Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy technicians as a profession encompass  Evidence of an understanding of the goals of pharmacy and a significant contribution to achieving these goal Who can enter This category is open to all hospital pharmacy technicians

working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself. Each submission will be judged by an independent judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

16 Honours

Hospital Professional

ONOURS 2024 Haematology Project of the Year

This Honour demonstrates that as the HPN Honours continue to grow they diversify to recognise a wider range of areas of expertise.

This category is open to professionals and teams who work within the haematology field and who have demonstrated excellence within a specific project. The recipient will demonstrate significant contributions to the haematology field.

Judges will be looking for:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of haematology health  Evidence of a large variety of skills, attributes and accomplishments

 Evidence of an individual or team strong in character, cumulative professional accomplishments  Evidence of an understanding of the goals of haematology and significantly contributing to how these goals may be achieved Who can enter: This category is open to all hospital professionals working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Honours 17 Hospital Professional

ONOURS 2024 Young Hospital Pharmacist of the Year

Hospital pharmacists are vital elements of medical and care management within the secondary care setting and those in their infancy years in the profession can hint at leadership excellence that inspires and develops the potential of others.

The Young Hospital Pharmacist of the Year recognises rising talent and potential amongst those at the beginning of their careers – those individuals who are already demonstrating that they can make a difference to their profession and the patients they serve.

This Honour focuses specially on the talent we will all rely on to deliver services for the next two decades and beyond, the young professionals currently delivering and planning services at the sharp end, but whose skills will be vitally important over the coming years.

Judges will be looking for:  Effective communication skills with both staff and patients  A commitment to mentoring or other leadership skills  Operating within their own department and liaising with key staff members and management and developing key communication skills  A dedication and commitment to furthering the profession in the future Who can enter: This category is open to all hospital pharmacists under the age of 30 working in any hospital department in Ireland.

Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent

judging panel. There will be no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

18 Honours

Hospital Professional

ONOURS 2024 Galapagos Multidisciplinary Team of the Year

Treatment of patients is, in most cases, a combined effort of several individuals and it is recognised that the outcome of a procedure is optimal when the professionals do indeed work together as a team.

 Examples of systems that have facilitated the communication of information needed for different professions to bring together their skills to help patients

This Honour will seek to recognise those who can demonstrate added value by their contribution. The judging panel will want to see actual multidisciplinary healthcare working and actual examples of it in practice as well as an outline of what lessons have been learnt from its implementation.

 Examples of crossdisciplinary learning and support

Judges will be looking for:  Entries clearly demonstrating how groups of hospital professionals are working together to enhance care, for example by describing the difficult process of developing an effective team and barriers

 Evidence of impact on patient care and professional development arising from multidisciplinary work Who can enter: This category is open to all hospital professionals working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be no personnel from any of the

sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Honours 19 Hospital Professional

ONOURS 2024 Grünenthal Advancing The Standard of Care in Pain Management This category will help advance the quality of pain management in Ireland by recognising and rewarding initiatives or management approaches that improve the Standard of Care.

Central to this, the Honour will identify those individuals, and/or teams that are innovative with existing or new technologies and/ or procedures, that have real scope to improve the Standard of Care.

The judges across this category will be looking for those who can show they have overcome challenges to provide outstanding care for those with severe chronic pain conditions.

The Honour is open to any individual and/or team which is primarily focused on the treatment and management of severe chronic pain, providing direct patient care.

Judges will be looking for:  Innovation Pain Management that is patient-centred and evidence-based, and can demonstrate a clinically meaningful change in patient Quality of Life  Appropriate access to multidisciplinary care

through the involvement of the wider team, specialists and disciplines to ensure expert care  A commitment to the advancement of pain management across Ireland and further afield. Work which is carried out in the direct hospital setting, or within the academic, clinical research settings Of particular interest will be those initiatives that are easily replicable across other centres and pain types, optimize existing resources, or are supported by a convincing case that would secure additional resources to support their execution.

Who can enter: This category is open to all hospital professionals/ teams working within any pain management hospital departments in Ireland.

Applications can be through

nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

20 Honours

Hospital Professional

ONOURS 2024 Athlone Pharmaceuticals Hospital Pharmacy Team of the Year

There are many key elements to building a productive team including communication and co-operation. Good communication means everyone is aware of their own responsibilities and what the team’s goals are whilst cooperation leads to increased productivity.

A team which excels is the one who work together to improve their efforts. They comprehend the importance of ongoing improvements and how this helps to support the overall objectives of the department.

This Honour is open to any hospital pharmacy team with a minimum of three team members.

Judges will be looking for:  Effective communication skills with both staff and patients

 Demonstration of a commitment to mentoring or other leadership activities  Operation within their own pharmacy liaising with key staff members and management and developing key communication skills  A dedication and commitment to furthering the profession into the future Who can enter: This category is open to all pharmacy teams working within any hospital in Ireland.

Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Honours 21 Hospital Professional

ONOURS 2024 Excellence in Respiratory

This Honour has been established to recognise a respiratory clinician or team who is providing compassionate care, over and above that usually undertaken in a respiratory career.

The project can come from any background but must involve those working predominantly in the respiratory field.

The judges will be looking for a project that demonstrates deliverable outcomes within respiratory care and that has really supported and evidenced the difference made to the patient experience in respiratory care.

 Clearly described respiratory interventions  Clear evidence of innovation and new ways of working  Clarity of leadership and evidence of how these qualities have benefited the team  Quantifiable improvements in patient care, including clinical outcomes Who can enter:

Judges will be looking for:

This category is open to all hospital professionals working within any hospital in Ireland. Applications can be through nominating an individual or yourself.

 Entries that can clearly demonstrate defined objectives for quality improvement within a project

Each submission will be judged by an independent judging panel. There will be no personnel from any of the

Applications can be through nominating an individual or yourself.

sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

22 Honours

Hospital Professional

ONOURS 2024 Excellence in Patient Safety

The Excellence in Patient Safety Honour will seek applicants who have shown commitment and dedication to improving patient safety/ medication safety amongst patients in the secondary care setting. This may be through team working with consultants, nurses or pharmacy colleagues.

The end result will be to improve this area for patients in terms of medication efficacy and adherence, for example.

The Honour will encompass all areas of patient safety within the hospital sector in Ireland and invites applications from those working across any discipline within secondary care.

Judges will be looking for:  Entries clearly demonstrating recent patient safety initiatives to the betterment of a specific therapeutic area

 Evidence of those who have offered patient safety expertise to the profession, perhaps through lecturing  Entries showcasing patient safety initiatives or innovation within a field pertinent to any discipline or therapeutic area that will have a positive impact on both the profession and patients  Examples of crossdisciplinary learning and support  Evidence of impact on patient care and professional development arising from patient safety initiative Who can enter: This category is open to all hospital professionals working across any discipline.

Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Honours 23 Hospital Professional

ONOURS 2024 Viatris Excellence in Cardiovascular Initiative

The Viatris Excellence in Cardiovascular Initiative is a new Category for 2024, which seeks to recognise the pivotal role that cardiovascular healthcare professionals and teams play in improving or displaying innovation in cardiovascular services and care for Ireland’s patient population.

 Evidence of working effectively across organisational and departmental boundaries to deliver excellence in cardiovascular care

This Honour will be looking for those individuals and/or teams that can demonstrate quality improvement, effective leadership, good teamwork and effective use of resources.

 An innovative project/ development/service or new approach in the field or a research project involving cardiovascular care

Judges will be looking for submissions that address prevention, diagnosis or treatment in the field of cardiovascular conditions throughout Ireland.

Judges will be looking for:  Excellence and leadership across the field of cardiovascular and its development

 Evidence to show that innovative practice has markedly enhanced the field and its development

 A multidisciplinary approach to clinically using medicines Who can enter: This category is open to all hospital professionals working in the fields of Cardiology in any Irish hospital. Applications can be through nominating an individual or yourself.

judging panel. There will be no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

Each submission will be judged by an independent

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

24 Honours

Hospital Professional

ONOURS 2024 Pharmasource Hospital Pharmacist of the Year

The Pharmasource Hospital Pharmacist of the Year Honour recognises a hospital pharmacist who demonstrates leadership and exemplifies the evolution of the pharmacy profession towards an expanded role in healthcare.

The recipient will demonstrate significant contributions to the pharmacy industry overall resulting in meaningful improvements in the quality of patient care and improved delivery models as well as the role of pharmacy in the healthcare team.

Judges will be looking for:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health

 Evidence of a large variety of skills, attributes and accomplishments  Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy as a profession encompasses  Evidence of an understanding of the goals of pharmacy and significantly contributing to how these goals may be achieved Who can enter: This category is open to all hospital pharmacists working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be

no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Honours 25 Hospital Professional

ONOURS 2024 Infectious Diseases Project of the Year The Infectious Disease Project of the Year will seek to recognise those hospital professionals who have displayed levels of excellence and dedication within any category of HIV and/or Infectious Disease in Ireland.

Key roles for the Infectious Disease professionals include educating pharmacy, medical and nursing staff, auditing prescribing patterns and trends and projects or initiatives that support patients with Infectious Disease or Patients Living with HIV. Judges will be hoping to see examples of excellence in practice, multidisciplinary team working across departments and those who have excelled in the fields of education and/ or communication about Infectious Disease.

Judges will be looking for:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of this field, professionals within it and public health

 Evidence to show that innovative practice has markedly enhanced the field and its development  An innovative project/ development/service or new approach in the field or a research project within the field of Infectious Disease  Evidence of the initiation or development of interdisciplinary research projects and networks  Evidence of a large variety of skills, attributes and accomplishments Who can enter: This category is open to all hospital professionals working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

26 Honours

Hospital Professional

ONOURS 2024 MSD Excellence in Oncology Initiative

The MSD Excellence in Oncology Initiative seeks to recognise the pivotal role that oncology healthcare professionals and teams play in improving or displaying innovation in oncology services and care for Ireland’s patient population.

This Honour will be looking for those individuals and/or teams that can demonstrate quality improvement, effective leadership, good teamwork and effective use of resources.

Judges will be looking for submissions that address prevention, diagnosis or treatment in the field of oncology throughout Ireland.

Judges will be looking for:  Excellence and leadership across the field of oncology and its development  Evidence of working effectively across

organisational and departmental boundaries to deliver excellence in oncology  Evidence to show that innovative practice has markedly enhanced the field and its development  An innovative project/ development/service or new approach in the field or a research project involving oncology  A multidisciplinary approach to clinically using medicines Who can enter: This category is open to all hospital professionals working in the fields of oncology in any Irish hospital. Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be

no personnel from any of the sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours. If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Honours 27 Hospital Professional

ONOURS 2024 MSL Distribution Innovation and Service Development

This Honour will be presented to a practising hospital consultant, pharmacist, specialist and/or team working within any hospital department, in recognition of a project which could easily be accomplished regardless of hospital size or staff, which need not be sophisticated, and which serves a useful purpose or has recently been published.

The judges will be looking for significant innovation in practice, method or service directly or indirectly resulting in improved patient care and/or advancement of the profession. We know that many hospital professionals have initiated exciting programmes in their hospitals and we would like to recognise them.

Judges will be looking for:  Entries that can clearly demonstrate defined

objectives for quality improvement within a project  Clearly described interventions  Clear evidence of innovation and new ways of working  Clarity of leadership and evidence of how these qualities have benefited the team  Quantifiable improvements in patient care, including clinical outcomes Who can enter: This category is open to all hospital professionals working across any discipline.

Applications can be through nominating an individual or yourself.

Each submission will be judged by an independent judging panel. There will be no personnel from any of the

sponsoring companies or IPN Communications LTD on the judging panel.

Short-listed finalists will be invited to an Honours Ceremony at the Radisson Blu, Dublin on Saturday, September 14th, 2024.

Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the Honours.

If your entry is shortlisted, the organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the Honours including all press materials.

To Enter: For an entry form or for further information please contact Danielle Norton at: danielle@hospitalprofessionalnews.ie Entry Deadline: Friday, April 26th, 2024 Hospital Professional Honours – Saturday 14th September, 2024 – Radisson Blu Dublin

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

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ESMO 2023

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ESMO 2023 – Setting Strong Impulses for a Better Future in Oncology

After five days filled with practicechanging data, intense discussions and educational sessions addressing the needs and issues currently arising for oncology professionals and impacting patients with cancer worldwide, the ESMO Congress 2023 sent home its more than 33,000 participants from 144 countries with plenty of food for thought and ample material to enrich their medical practice.

As the annual culminating point of the Society’s efforts to disseminate science-based evidence that oncologists can translate into better patient care, the highly anticipated 2023 edition of the Congress delivered in several important ways on the ESMO promise to stand by the side of oncologists and make a difference in the lives of people with cancer.

The latest scientific discoveries, which came in abundance this year and spanned the areas of cancer biology, prevention, early detection and treatment, including in disease categories with significant unmet needs, were not only showcased but also contextualised within the wider body of evidence in sessions dedicated to helping clinicians

optimise patient management in their home institutions. Meanwhile, researchers from around the world found in Madrid a stimulating atmosphere in which to exchange new ideas and engage in the kind of cross-fertilisation of disciplines and projects that will breed more innovation in the years ahead.

Various forums provided young oncologists and women in oncology opportunities for professional growth to overcome the different challenges associated with a career in this field. A special session was also dedicated to enhancing the training in this speciality and attracting talented medical students to embody the future of medical oncology, which will depend on a sufficient and qualified workforce to uphold current achievements in cancer diagnosis, treatment and care.

To ensure oncology indeed follows a path of improvement for all patients globally, discussions orchestrated by the ESMO Resilience Task Force or the ESMO Climate Change Task Force turned to novel approaches to making the profession more sustainable—both in its intrinsic ability to continue serving patients while caring for the well-being of the doctors, and in its contribution to protecting the environment, and thus the health systems, in which it operates.

From the point of view of availability, out-of-pocket costs and accessibility of antineoplastic medicines, the presentation of the second ESMO study highlighted the obstacles and opportunities related to the fast-paced development of innovative therapies, focusing on how to mitigate resulting health

ESMO Director of Public Policy, Professor Jean-Yves Blay

disparities, as well as investigating the actions needed to put the most basic treatments within reach of patients in low- and middleincome countries.

As the attendees who brought the Congress 2023 to life go their ways, ESMO will continue to work on this and other issues of relevance to the global action against cancer. It is uniquely positioned to do so, drawing as it can on lasting bonds of solidarity that tie the Society to its worldwide membership.

Studies presented at the ESMO Congress 2023 set new standards of care across a wide range of tumour types Evidence is building up that strong political action has the potential to tackle two of our era’s biggest challenges: climate change and the increasing burden of cancer on society. At the opening press conference of the ESMO Congress 2023 which took place 20-24 October in Madrid, Spain, a slew of studies marking meaningful advances in the treatment of various tumour types were announced together with new insights into potential cancer risks from air pollution, which ESMO has translated into a concrete call to action for

policymakers with a Public Policy Manifesto addressing this and other critical issues for oncology.

In a context where air pollution is increasingly understood to be a driver of both global warming and cancer on a broader scale than previously suspected, mitigation strategies take on a new importance that ESMO has already been actively advocating for in EU policy circles. “With its 33,000 members, ESMO is producing the science and the information that national and EU political decision-makers need to adapt our healthcare systems to evolving priorities in oncology,” said ESMO Director of Public Policy Prof.

Jean-Yves Blay, highlighting the role of cancer prevention in improving the resilience of Europe’s health systems, an imperative widely recognised since the pandemic and reiterated in the ESMO Public Policy Manifesto.

“We need, on the one hand, structural resilience to ensure cancer patients can continue to be treated in periods of crisis, and, on the other, a resilient oncology workforce,” said Blay. “We have seen shortages of human resources in many countries at the same time as we have experienced increasing workloads due to the growing number of

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

ESMO 2023

30

ESMO President, Professor Andrés Cervantes

cancers being diagnosed and treated each year, and which are putting pressure on all healthcare systems indiscriminately.”

The Public Policy Manifesto, which crystallises ESMO’s evidence-based approach to tackling cancer both within the bloc and, when feasible, globally, prepares the ground for effective policymaking in anticipation of the 2024 elections for the European Parliament by highlighting necessary measures to protect the oncology workforce and cancer patients—including in times of crisis—as well as major axes of cancer prevention ranging from air pollution and asbestos exposure to tobacco and alcohol consumption.

As Blay reported, another challenging question on which ESMO wants to work with EU policymakers concerns how best to ensure equitable access to the transformative therapies entering clinical practice today for all patients, including those with rare cancers, in the future.

“This is particularly relevant in the current context of evolving EU regulation on health technology assessment,” he noted. Equity is also what motivates ESMO’s advocacy, including through the new manifesto, for the right of cancer survivors to have their

disease forgotten when they seek financial services upon returning to normal life.

clinical trial results announced in a multitude of tumour types and disease settings.

ESMO is also working to help shape the implementation of EU legislation such as the In Vitro Diagnostic Regulation and the upcoming European Health Data Space, which will have an impact on cancer research and will be critical to bringing Europe’s expertise in health technology to global fruition. “ESMO is unique in its size, its global perspective, and its ability to disseminate practicechanging evidence across a broad range of oncological diseases, as is being demonstrated once again with this year’s Congress,” said Blay. “National and EU policymakers therefore naturally listen to the quality of expertise we provide.”

“This ESMO Congress is full of data that will truly change practice for our patients, but in particular, 2023 will go down as the year of lung cancer abstracts,” emphasised ESMO 2023 Scientific Chair Prof. Silke Gillessen, anticipating the profusion of therapeutic advances that will be the subject of many presentations over the next five days.

A look at the highlights of the ESMO 2023 scientific programme As the Society’s flagship annual meeting, the ESMO Congress is one of the foremost forums in which evidence is discussed and disseminated, within the oncology community and to the wider public. Accordingly, the scientific programme of the ESMO Congress 2023 is the reflection of a field of medicine where progress is rapid and wide-sweeping, with important

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

In the field of gynaecological malignancies, promising new results covering the entire spectrum of cervical cancer and with the potential to change the treatment landscape, will also be presented throughout the ESMO Congress.

ESMO President Prof. Andrés Cervantes commented: “Cervical cancer is still very prevalent, especially in low and middleincome countries, and this Congress brings good news to women suffering from all stages of the disease.”

Meanwhile, new treatment combinations could for the first time in decades lead to changes in the standard of care for advanced urothelial carcinoma, the most common form of bladder cancer. “In particular, a new drug combined with immunotherapy will, if approved, replace the standard chemotherapy that we have been administering for over 20 years as the first line of treatment,” Gillessen continued.

In metastatic prostate cancer, a new type of precision nuclear medicine capable of delivering targeted radiation to cancer cells, and thus preserving surrounding tissue, showed its potential to move up in the therapeutic sequence by delaying disease progression compared to the standard second-line treatment.

Findings which, according to Gillessen, are made all the more promising by the good tolerability of the novel therapy.

Based on further results to be presented during a presidential session on Sunday, two other targeted therapeutic approaches are also pushing back the survival horizon for heavily pretreated patients with metastatic breast and colorectal cancers. “KRAS mutations are present in almost half of all colorectal cancers and have traditionally been associated with poorer prognosis because they limited the treatment options available to patients. Now, a new combination of antibodies and RAS inhibitors has been shown to improve survival compared to the standard of care and, incredibly, turned this mutation into a positive predictor of better outcomes,” said Cervantes, highlighting the significance of this breakthrough for patients.

In a phase III trial described by Gillessen as a research prowess for a rare disease, important new answers were also obtained regarding the optimal course of treatment for people suffering

31

ESMO 2023 Scientific Chair, Professor Silke Gillessen

from RET-mutant medullary thyroid cancer—a rare endocrine tumour—as a selective RET inhibitor demonstrated its superiority to other, broaderspectrum targeted therapies approved in this indication.

living, and showed small or no effects on breast cancer risk,” said Professor Béatrice Fervers, Head of Prevention Cancer Environment Department, Léon Bérard Comprehensive Cancer Centre, France.

“This year is one that will be remembered in oncology, and not just by the record 30,000 attendees we are expecting to join the Congress from 144 countries,” concluded ESMO 2023 Press Officer Dr. Angela Lamarca. “With over 2,500 studies to be presented, including 147 presidential and proffered papers set to change clinical practice, there will be a before and an after to the ESMO Congress 2023.”

In the study, home and workplace exposure to pollution in 2419 women with breast cancer was compared to that in 2984 women without breast cancer over the period 1990-2011. The results showed that breast cancer risk increased by 28% when exposure to fine particle (PM2.5) air pollution increased by 10 µg/ m3 – approximately equivalent to the difference inPM2.5 particle concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particle air pollution (PM10 and nitrogen dioxide). Fervers and colleagues now plan to investigate the effects of pollution exposure during commuting to get a complete picture of effects on breast cancer risk.

Air Pollution and Breast Cancer Risk Women living and working in places with higher levels of fine particle air pollution are more likely to get breast cancer than those living and working in less polluted areas. Results of the first study to take account of the effects of both residential and workplace exposure to air pollution on breast cancer risk are presented at the ESMO Congress 2023 in Madrid, Spain.

“Our data showed a statistically significant association between long term exposure to fine particle air pollution, at home and at work, and risk of breast cancer. This contrasts with previous research which looked only at fine particle exposure where women were

Professor Charles Swanton, the Francis Crick Institute, London, UK, whose research suggesting how PM2.5 particles may trigger lung cancer in non-smokers was presented at ESMO Congress 2022, stressed the importance of the new findings with breast cancer.

from where they are absorbed into breast and other tissues.

There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumour promotion possibly through inflammatory processes, similar to our observations in non-smokers with lung cancer,” he said. “It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression and progression of breast tumours,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particle exposure and cancer, and there are good clinical and economic reasons for reducing pollution in order to prevent cancers,” said Professor Jean-Yves Blay, ESMO Director of Public Policy.

Following on a proposal from the European Commission in

October 2022 to reduce the limit for PM2.5 particles in the air from the current 25 µg/m3 to 10 µg/m3 by 2030, ESMO urged a reduction in the PM2.5 limit still further to 5 µg/m3, in line with the World Health Organisation’s air quality guidance. “Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumour types, including breast cancer,” Blay added. “We have a responsibility to push for this change, not only for people in Europe but worldwide where there are big variations in the pollution landscape.” The lower limit was indeed adopted by the European Parliament’s Environment, Public Health and Food Safety Committee in June 2023.

More recently, in September 2023, the European Parliament adopted in plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for Fine Particulate Matter (PM2.5) at 5 µg/m3. This adoption opens interinstitutional negotiations between the co-legislators – European Parliament, European Commission and EU Council – to agree on the final text of the directive.

“These very small particles can penetrate deep into the lung and get into the bloodstream

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Professor Charles Swanton, the Francis Crick Institute, London, UK

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” the ESMO Public Policy Director concluded.

Advances in Gynaecological Cancer Research Results from highly anticipated phase 3 clinical trials in gynaecological cancers with, among others, new data that cover the entire spectrum of managing patients with cervical cancer, will be presented at the ESMO Congress 2023 in Madrid, Spain. The late-breaking studies will be featured in Presidential and Proffered Paper Sessions, and could change the treatment landscape for women with these cancers. The new therapies tested delayed the time to relapse and, in some cases, lengthened survival.

“These are exciting results that address unmet needs in gynaecological cancers,” said Professor Krishnansu S. Tewari, Director - Gynecologic Oncology Programme, University of California, Irvine, USA. Novel findings will be revealed across the range of gynaecological cancers, including cervical, ovarian, and endometrial cancers.

Cervical cancer usually presents as locally advanced disease in women who have not undergone screening. At this stage, the cancer is too large to remove

surgically, and the standard treatment is chemotherapy with radiation. “Cervical cancer occurs in young women who are typically in the midst of their careers and have small children at home,” said Tewari. “Standard treatment does lead to remission, but within two to three years the cancer can come back. Two trials that will be presented at the ESMO Congress 2023 will reveal new ways of treating locally advanced cervical cancer that significantly delay relapse, giving women who are in the prime of their lives more time free of cancer.”

In one study, 68% of women who received the immunotherapy drug pembrolizumab on top of standard treatment were cancer-free at two years, compared to 57% of women allocated to placebo on top of standard treatment. A second study tested the impact of giving a combination of two different chemotherapy drugs ahead of standard treatment with chemotherapy plus radiation – a strategy called induction chemotherapy. Women with locally advanced cervical cancer who received induction chemotherapy were 35% more likely to be cancer-free at five years and 39% more likely to be alive at five years compared to those who received standard treatment only.

“Induction chemotherapy could be an accessible treatment option because these drugs are available around the world, including in lowresource countries,” noted Tewari.

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Also in cervical cancer, trials will be presented showing improvements in survival and delays in relapse with new treatments for women with cancer that has spread to other parts of the body or has come back after initially being treated with chemotherapy plus radiation.

One trial tested the novel therapy tisotumab vedotin in women who had already received treatment for their metastatic or relapsed cervical cancer. The drug, which combines an antibody and an anti-cancer drug, lengthened survival, delayed relapse, and more often caused tumour shrinkage compared with chemotherapy.

In ovarian cancer, achieving remission is a high unmet need, as approximately 85% of patients experience recurrent disease, with almost no long-term survival after recurrence. At the ESMO Congress 2023, randomised trial data will be discussed showing that a novel targeted therapy, called senaparib, delayed the time to relapse in patients with newly diagnosed advanced disease.

Studies will also be presented in endometrial cancer, the most common gynaecological cancer in the US and Europe. In Europe, more than 121,000 women were diagnosed with endometrial cancer in 2018 while in the US, it is estimated that over 66,000 women will be diagnosed in 2023. While there is no screening test, there is an early symptom -- post-menopausal bleeding -- which means that most endometrial cancers can be cured with a hysterectomy. Tewari said: “Unfortunately, for the 15-20% of patients that have more aggressive disease, treatment options are very limited and that’s why the

“Cervical cancer occurs in young women who are typically in the midst of their careers and have small children at home…..Standard treatment does lead to remission, but within two to three years the cancer can come back. Two trials that will be presented at the ESMO Congress 2023 will reveal new ways of treating locally advanced cervical cancer that significantly delay relapse, giving women who are in the prime of their lives more time free of cancer”

studies that will be presented at the ESMO Congress are remarkable. Two trials showed that adding immunotherapy to standard chemotherapy treatment significantly delayed relapse of the cancer in women with advanced/ recurrent endometrial cancer compared to chemotherapy alone.”

Tewari commented that the results that will be presented at the ESMO Congress 2023 have a very good chance of leading to regulatory approval of new treatments. He said: “These trials have set the stage for women with gynaecological cancers to receive state-of-the-art therapies that delay the time to relapse, allowing women struggling with these cancers to live longer and live better.”

Multiple Myeloma

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Use of the European Organisation for Research and Treatment of Cancer multiple myeloma module (EORTC QLQ-MY20): a review of the literature 25 years after development Written by K. Forde1, K. Cocks1, J. R. Wells2, I. McMillan2, C. Kyriakou3 & EORTC Quality of Life Group 1

Adelphi Values, Patient-Centered Outcomes, Bollington, Cheshire

2

Previously Adelphi Values, Patient-Centered Outcomes, Bollington, Cheshire

3

Department of Haematology, University College London Hospitals NHS Foundation Trust, London

Multiple Myeloma (MM) is a haematological cancer that affects multiple organs and is associated with complex symptoms.1 However, due to treatment option advances, MM survival rates have significantly improved in the past 25 years.2,3,4 Despite the constantly evolving treatment landscape for MM, it remains an incurable and progressive disease, that requires either continuous or intermittent therapies to maintain disease stability and sustain or prolong the survival.5 Disease symptoms, in addition to treatment side effects caused by multiple lines of therapies, can severely impact on patient’s wider health-related quality of life (HRQoL). For example, fatigue and pain are physical symptoms commonly reported by patients with myeloma which significantly impair HRQoL.6, 7 In addition to extended survival, it is important to understand how new and combination treatments may affects patients’ lives, therefore, it is recognised that patient-reported outcome (PRO) measures are vital to assess in clinical trials and in the management of MM.8 The European Organisation for Research and Treatment of Cancer Quality of Life Multiple Myeloma Questionnaire (EORTC QLQ-MY20), developed in 1999, is a MM specific PRO measure consisting of 20 items within four domains (disease symptoms [DS], side effects of treatment [SE], future perspectives [FP] and body image [BI]).9 The original module QLQ-MY24, released in 1996, included 4 additional items under the domain of Social Support (SS) that was subsequently removed due to observed ceiling effects.10 The QLQ-MY20 module is used in conjunction with the EORTC Core Quality of Life Questionnaire (QLQ-C30) designed for use in oncology patients more generally.

The MM module has been

translated into over 70 language versions,11 is a MM-specific measure used most globally and is one of the most extensively validated instrument for use in MM clinical research.10, 12 Since the module’s development, the treatment for MM has changed.13 The original validation of the QLQ-MY20 was largely in newly diagnosed patients and the module was focused on the expected side effects of conventional chemotherapy and steroids when it was originally developed.9 The conventional chemotherapy in 1999 was mainly melphalan, cyclophosphamide, vincristine and doxorubicin.

Although it is recognized that patients with myeloma can be treated with a variety of different chemotherapy drugs and regimens, it was felt that the side effects of conventional chemotherapy and steroids may more adversely affect the HRQoL of the patients for a longer period of time. However, after 1999, no-chemotherapy treatments (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies and other novel agents) have been introduced. The increase in survival rates coupled with the rapid progression in therapeutic options for patients with myeloma have implications for the HRQoL outcomes and side effects for this population. Osborne et al published a review in 2012 identifying issues important to patients and whether existing instruments comprehensively cover the current treatment landscape and patient experience.12 While the QLQ-C30 and QLQ-MY20 were acknowledged as the instruments which had good conceptual coverage and had undergone the most extensive validation in patients with myeloma, no instruments were identified as covering all issues relevant to patients, signifying the need for a MM module update that will represent HRQoL taking into

account current therapy issues and HRQoL concerns to patients today.

The EORTC guidelines provide a four-phase framework for updating existing modules.14 As part of Phase I (generation of QoL issues), a literature review assessing the use of the QLQ-MY20, and any reported methodological issues was performed. The following article details this literature review which aimed to explore: 1. In which types of clinical studies the module has been used 2. To what extent has the module been used in both newly diagnosed and relapsed patients 3. The types of treatments/ therapies the module has been used to assess 4. How and where the modulerelated endpoint is positioned within randomised controlled trials (RCTs) 5. How the module results are reported, and the prominence given to these results 6. The statistical results from QLQMY20 subscales in RCTs 7. PRO limitations identified from interventional studies and validity/reliability issues raised in psychometric validation studies METHODS Literature search, eligibility criteria and screening The primary search was conducted using the Ovid SP platform, accessing the electronic bibliographic databases: Medline, EMBASE and PsycINFO. Searches combined the use Keyword search (i.e., reference is identified if it includes the specified term within its bibliographic reference) and a Subject Heading search. Subject Headings are a controlled set of terms used in bibliographic databases to index articles by

topic. A supplementary search in Google scholar was also performed and references that had not been previously identified were reviewed for inclusion. Only papers published between 1996 and 2020 were sought as this reflects when the MM module (MY24) was first released. The searches sought publications referencing ‘Multiple Myeloma’ in addition to ‘MY20’, ‘MY24’ or ‘EORTC’ or containing reference to the QLQ-MY20 domains.

Abstracts were included if they were reporting a clinical study of any design that generated data using the QLQ-MY20/24 or a study to evaluate the QLQ-MY20/24, including the assessment of the psychometric properties of the module (validation study).

Only abstracts reporting original research were included thus reviews, conference proceedings and book chapters were excluded.

The full-text publications were sought for all references meeting these criteria. When a single study was referenced across multiple references only the most comprehensive or relevant publication (e.g., HRQoL focused) was retained. Clinical studies were categorized as interventional (i.e., RCT’s, clinical trial – singlearm, clinical trial – cross over) or observational (i.e., crosssectional and longitudinal/cohort) study designs.

Data extraction General information (e.g., author, title and year and location of the study) was collected for all studies.

For all clinical studies information about the disease severity (i.e., newly diagnosed/relapsed), and other clinical outcome assessments (COAs, including patient-reported outcomes) used was extracted. For trials (RCT’s, single, and cross-over arm) further information about the study design, reporting and presentation of results were extracted. Further

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a second reviewer. Any cases of disagreement or uncertainty were then discussed, and consensus was established in all instances by the study team based on the inclusion criteria. For the extraction of statistical data, all data extracted was checked by a statistician to ensure accuracy.

RESULTS The search yield 502 unique records (Fig. 1) of which 74 publications were taken forward for review (33 full-text articles and 41 conference abstracts).

Study designs where QLQ-MY20 is used The studies had a wide international spread and in recent years there has been a growth in scientific publication on the use of the QLQ-MY20 in both clinical and instrument validation studies.

There has been an increase in the use of the QLQ-MY20 in RCTs, single-arm clinical trials and cross-sectional observational studies over time.

QLQ-MY20 instrument use in observational and interventional studies When stated, interventional and observational studies included either exclusively relapsed patients (n = 24/43, 55.8%, 14 of which were interventional), newly diagnosed patients (n = 10/43, 23.3%, seven of which were interventional), and a mix of newly diagnosed and relapsed patients (n = 9/43, 20.9%, none of which were interventional).

Over time, both observational and clinical trials increasingly utilized the QLQ-MY20 with samples of relapsed patients and mixed samples of newly diagnosed and relapsed patients.

in-depth extraction of RCTs was performed, including type of statistical analysis on QLQ-MY20 data and comparisons between groups. For validation studies data on the instrument structure and data distribution, reliability, validity and ability to detect change/

interpretation of change scores was extracted.

Interrater agreement Data extraction was initially performed by one reviewer, the indications of the first reviewer were subsequently checked by

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With the exception of two observational studies,15, 16 all 65 studies used the QLQ-MY20 in conjunction with the EORTC QLQ-C30 as required by the EORTC modular measurement approach. The COAs used in conjunction with the EORTC QLQ-C3017 and QLQ-MY2010 module largely assessed peripheral neuropathy (e.g., FACT-GOGNtx),18 HRQoL (e.g., EQ-5D-5L),19 emotional wellbeing, particularly anxiety and depression (e.g., HADS),20 fatigue (e.g., FACIT),21 sleep quality (e.g., PSQI)22 and functional impairment (e.g., KPS).23 QLQ-MY20 instrument use in interventional trials QLQ-MY20 subscales were most commonly defined in

studies as secondary (n = 11/21, 52%) or exploratory (n = 6/21, 29%) endpoints.

Trends over time (for the reporting periods 2006–2010, 2011–2015, and 2016–2020) were assessed across interventional studies and four notable trends were observed.

Over time, the proportion of RCTs, relative to single-trial arm and cross-over trials, increased from n = 0 between 2006 and 2010 to n = 5/7 between 2011 and 2015 to n = 10/13 between 2016-2020. Similarly, the number and proportion of trials utilizing a sample of patients who have experienced their 1st or subsequent relapses, relative to being newly diagnosed, increased over time from n = 1/2 between 2006 and 2010 to n = 4/7 between 2011 and 2015, and n = 9/13 between 2016-2020. The average QoL sample size increased from 144 between 2006 and 2010 to 479 and 465 between 2011 and 2015 and 2016 and 2020 respectively. In recent years, there has also been more questionnaires used in conjunction with the QLQMY20; between 2006 and 2010 only two additional questionnaires were used alongside the QLQMY20, however, five were used between 2016 and 2020. No differences were observed in the types of treatments/therapies the QLQ-MY20 has been used to assess, the endpoint hierarchy that the QLQ-MY20 was selected for, the study phase it was used in or the presentation of QoL results in the form of tables, figures and/or in text.

The review of interventional study papers highlighted the main limitations with the PRO instruments or analysis/results as reported by authors (Table 2). Some issues are those generally affecting PROs rather than specific to the QLQ-MY20 such as differential dropout or poor completion rates potentially biasing the analysis, low baseline levels of symptoms limiting the opportunity to show improvement, single arm studies, short term PRO data collection and lack of standardization in collection and analysis of PROs across trials limiting comparison of results across studies. Issues raised which may be more specific to the QLQ-MY20 were the need for thresholds for meaningful change at the individual patient level, the need for consistency across studies in definitions of meaningful change, discrepancy between patient-reported ‘tingling hands and feet’ and the clinician

35

Figure 1

studies highlighted potential ceiling effects for the BI subscale.

No issues with item reliability (Cronbach’s alpha) were identified for the multi-item scales.10, 17, 25,26,27, 29, 30 Test-retest reliability was assessed in one article25; all four QLQ-MY20 subscales had high test-retest reliability (ICC ≥ = 0.85).

Two articles assessing factor analysis were inconsistent with one showing acceptable fit25 and one suggesting item reduction in the SE subscale.27 External validity convergent/ discriminant validity was reported in two full text articles.

Kontodimopoulos N. et al. (2012) demonstrated correlations between SF-36 domains and QLQ-MY20 domains, Graca Pereira M et al. (2019) found correlations between QLQ-MY20 domains and QlQ-C30 total score, Satisfaction with social support scale (SSSS), and the HADS. Eight articles reported known groups validity across a range of groups (albumin, haemoglobin, beta 2 microglobulin,10, 17, 25,26,27,28, 30, 31 performance status, gender, age and presence of fractures). Three articles demonstrated ability to detect change.10, 25, 26 DISCUSSION reported peripheral neuropathy events, higher incidence of AEs or more severe AEs not translating into an impact on the PRO scores and potential lack of sensitivity of current questions to pick up variations in HRQoL depending on treatment administered. Another paper suggested that elements such as dosing convenience were currently not adequately measured by the available PROs. Role of QLQ-MY20 alongside clinical endpoints in RCTs The statistical significance of any mean difference comparisons between groups and any time to deterioration (TTD) comparisons between groups is reported.

Most trials evaluated the meaning of the PRO results in context with the clinical results. Five of the 15 trials were comparing triplet versus doublet therapy combination therapies. It was common in these studies for no statistically

significant differences between treatment groups to be observed and for authors to interpret this as a positive result, demonstrating the addition of an agent to the combination did not impact on HRQoL. Four studies reported statistically significant differences between groups for the SE subscale (lenalidomide (Revlimid), dexamethasone [Rd] vs melphalan, prednisone, thalidomide [MPT], carfilzomib, dexamethasone [Kd] vs bortezomib, dexamethasone [Vd], melphalan, prednisone, thalidomide followed by thalidomide maintenance [MPT-T] vs melphalan, prednisone, lenalidomide followed by lenalidomide maintenance [MPR-R] and salvage autologous stemcell transplantation [sASCT] vs nontransplantation consolidation [NTC]). One study reported longer time to deterioration for one arm for the DS subscale (once weekly vs twice weekly). One study reported longer time to

deterioration for the SE subscale (Kd vs Vd). Another study reported differences between arms with respect to FP at later timepoints (IRd vs Rd). One small study24 noted clinically relevant differences between cyclophosphamidebortezomib-dexamethasone (VCD) plus placebo and VCD plus clarithromycin for DS and SE, and statistically significant differences with respect to BI. In addition to these formal comparisons between treatment groups the RCTs also reported the proportion of patients with improved/stable/worsened QLQMY20 scores, association of clinical endpoints (response, time to progression and toxicity) with the QLQ-MY20 scales and the effect of age on HRQoL benefit.

QLQ-MY20 validation studies Nine validation studies were identified in the review.10, 17, 25,26,27,28,29,30,31 Four validation

The objective of this literature review was to review the use of the QLQ-MY20, since its first release 25 years ago, as the first validated module for patients with myeloma designed to be used with the EORTC QLQ-C30.

The MM specific PRO measure consists of 20 items across four domains (refined from the original 24-item module [MY24] following early phase research). This literature review focused on the period after its publication in 1996 through to 2020.

There were a few drivers for this review. At the time of the original validation study the majority of clinical trials were in newly diagnosed patients and there was limited data for validation of the QLQ-MY20 in relapsed/ refractory patients. Over the time period since the original publication of the QLQ-MY20, the treatment landscape has changed dramatically and patients with

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myeloma now undergo multiple lines of treatment and relapses.

We wanted to use this review to see if the use of the questionnaire in relapsed patients has increased accordingly. The review aimed to summarise the range of studies the questionnaire has been reported in, how the data from the QLQMY20 was reported and how the results impacted on the evaluation of the treatments in the studies alongside clinical endpoints. We also wanted to collate any further psychometric evaluations of the QLQ-MY20 to see if any issues have emerged as the use of the questionnaire changed.

Seventy-four studies, that used the QLQ-MY20, were reviewed following screening, of which there were 15 RCTs, 6 single arm or cross-over trials, 44 observational and nine instrument validation studies, indicating diverse and extensive use of the QLQ-MY20 in several different clinical settings and investigations. The review of the published literature did not highlight any specific problems with the QLQ-MY20, however, qualitative interviews are ongoing to further explore the patient experience of symptoms and side effects of novel treatments.

A revised version of the QLQMY20 is therefore warranted to ensure all concepts of interest are captured; concepts assessed by the additional COAs reported should be explored further in Phase I and II (generation of QOL issues and construction of the item list) of modular development

and considered for inclusion in the updated version of the QLQ-MY20.

The RCTs highlighted that often no difference between treatments were observed with respect to the QLQ-MY20 subscales but that in conclusion often this was a desirable outcome, especially regarding the SE subscale (e.g., demonstrating that adding a further agent to a combination regimen does not have a detrimental impact on QoL). As new treatment regimens and new combination therapies continue to be developed, this should be a key consideration at the design stage for a RCT. The QoL comparisons should be non-inferiority rather than superiority and ensuring there is sufficient sample size to declare non-inferiority where applicable.

It is also important for robust meaningful change thresholds to be determined in order that noninferiority margins can be defined.

To date there has been one study on deriving meaningful change31 but further development of these may be required. The RCT data also supported the QLQ-MY20 subscales being related to clinical outcomes and supporting and supplementing the conclusions from the clinical endpoints. A number of studies investigated the relationship of the QLQ-MY20 scales with clinical outcomes such as time to progression and response.

Indicative of the expansion of the treatment portfolio and changing prognosis for patients,

the proportion of RCTs using the QLQ-MY20 increased over time from n = 0 in the first 5 years to n = 10/13 in the last 5 years. The proportion of trials in patient post their 1st or subsequent relapses, relative to being newly diagnosed, increased over time from n = 1 in the first 5 years to n = 9/13 in the last 5 years. Over these time periods there were no observed trends for QoL endpoints to move up the hierarchy, however, this could be due to the inevitable time lag between research and publication of findings.

Similarly, there were no trends or improvements in the reporting of QLQ-MY20 results in tables/ figures rather than text alone; generally the reporting of the QLQ-MY20 included tables and/or figures throughout the period.

There were a few instances where limitations of the QLQ-MY20 were highlighted by individual papers.

One issue was the need for work on meaningful change thresholds for the QLQ-MY20. Although this has since been addressed by Sully et al31 more studies in this area would be beneficial in the future.

Some studies used an additional peripheral neuropathy questionnaire alongside the QLQ-MY20 and one noted a discrepancy between the QLQ-MY20 item ‘tingling hands and feet’ and the clinician-reported peripheral neuropathy, which could indicate the need for more detailed items in the QLQ-MY20 on this side effect. Amongst the psychometrics studies, the instrument performed consistently well. One potential

issue found in some studies was a ceiling affect for the BI subscale so this may warrant further investigation and may be the case for certain populations.

Potential limitations of our study include comprehensiveness of the usage of the QLQ-MY20. Our search will have identified any studies reporting results from the QLQ-MY20 but we acknowledge that this will exclude any studies that have used the instrument but not published any results from it. There will also be key multiple myeloma trials not in this review as they used only the QLQ-C30 or a different PRO. Regardless we have shown across a broad range of studies where the QLQ-MY20 has been used some of the trends over time in terms of patient populations and study designs.

In conclusion, the QLQ-MY20 has been shown to perform well psychometrically since its initial validation. The QLQ-MY20 scales have been supportive of clinical endpoints in RCTs and have been used to understand the patients’ QoL alongside improved response and time to progression outcomes.

To maintain content validity in today’s MM treatment landscape (i.e., to ensure the instrument is relevant to MM patients and captures their symptoms and side effects of novel treatments and later lines of therapy) qualitative interviews with patients and health care professionals and an update to the QLQ-MY20 is underway to incorporate findings.

Oncology News Liam McTrial Programme Profile Dr Richard Bambury, Dr Brendan Noonan and Dr Jack Gleeson pictured along with some of the UCC and CUH trials team at the launch of the Liam Mc Trial at Cork University Hospital

meet their health and wellbeing needs on a holistic basis beyond standard treatment.

The Irish Cancer Society Liam Mc Trial (short for Linking In with Advice and supports for Men

with Metastatic Cancer) will see selected participants engage in a 12-week programme that aims to

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The research trial will see men receive specialist nurse and dietician support weekly, as well as twice-weekly physiotherapy sessions to empower them to maintain physical activity so important for quality of life. This will be complemented by access to social work and psychological

supports to ensure their practical and emotional as well as physical needs are met.

The two-year pilot initiative is the result of a ¤300k funding commitment awarded to UCC from the Irish Cancer Society as part of its continued efforts to address crucial survivorship issues for cancer patients, and encourage associated service improvements, as well as supporting Irish cancer research.

Should the approach prove successful in improving quality of life among trial participants, it is hoped to roll the model out to many more categories of male cancer patients nationwide as a new standard of care.

CPD 105: OSTEOPOROSIS Continuing Professional Development

CPD

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AUTHORS: Fellow Emeritus, Professor Moira O’Brien, FRCPI, FFSEM, FFSEM(UK), FECSS, FTCD. Consultant in osteoporosis and Sports Medicine since the 70s and osteoporosis since 1990 when she set up the first osteoporosis clinic in the anatomy department of TCD. Founder and President of the Irish Osteoporosis Society.

She is currently the only Osteoporosis consultant in Ireland and works in Affidea Dundrum.

Michele O’Brien, CEO of the Irish Osteoporosis Society. Michele set up the first Falls Prevention service for senior citizens in Ireland in 2000 and has worked for the IOS Charity for 23 years.

60 Second Summary Osteoporosis is the most common bone disease worldwide. The Irish Osteoporosis Society (IOS) have been saying for decades that it affects all age groups and both sexes. Bone loss is treatable in the majority of cases, yet more men die from the complications of osteoporotic fractures than cancer of the prostate, and men have a higher risk of morbidity and mortality than women.

Osteoporosis is a silent disease, there are no signs and symptoms, no one feels bone loss. The commonest cause is low levels of sex hormones, oestrogen in women and testosterone in men.

Osteoporosis and osteopenia are both diseases and should be thoroughly investigated, Osteopenia should not be considered “A touch of bone loss”.

The effect of medication on the prevention of fractures must be monitored closely to ensure the treatment plan is working and improve compliance.

Lifestyle, exercise, stress, diet, sleep are important factors to assess.

Effective and safe medications are available to treat osteopenia/Osteporosis.

Most medications can cause possible side effects, but the benefits to bone health by preventing future fractures usually far outweighs the possible risks.

It is rarely too late to investigate and treat a patient with bone loss, even those in their 90’s with Dowagers humps.

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

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

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

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

3. PLAN - If I have identified a

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

4 previous steps, log and record your findings.

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

Osteoporosis, what you need to know Introduction Osteoporosis is the most common bone disease worldwide, it is a silent disease, as there are no signs and symptoms.

There is a significant amount of misinformation and myths about osteoporosis, both in the public and Healthcare domain.

For example, the Irish Osteoporosis Society (IOS) have been saying for decades that it affects all age groups and both sexes, yet most believe it only affects old women.

Findings from a recent survey

by Athena Pharmaceuticals found that one in five adults have fractured a bone since they turned 40, over a third of these people reported to have had a fragility fracture and the rate of these low impact fractures was high amongst 40 to 54 year olds.

Prevention ideally should start in childhood, which is why physical activity should be mandatory in all schools and integrated into the school curriculum, as not only does it help to prevent Osteoporosis but obesity and a list of other diseases.

More men die from the complications of osteoporotic fractures than cancer of the prostate and men have a higher risk of morbidity and mortality than women.

More women are affected, and more women die from the complications of osteoporotic fractures, than the combined deaths from cancers of the breast, ovaries, and cervix.

Now that you have picked your jaw up from the floor, these are some of the many reasons why all health care professionals need to review their knowledge on Osteoporosis, so the prevention, diagnosis and treatment rates can be improved, and why fragility fractures in those under 65 should have bone loss ruled out, as the cost of treating fractures will double by 2030.

Osteoporosis is characterised by low bone density, abnormal changes in the microarchitecture of bone tissue, particularly cancellous bone, making it more fragile, with an increased risk of low trauma fractures. It is essential to find the cause/s of bone loss and modify

as many risk factors as possible going forward.

The commonest bones to fracture are the cancellous part of the distal radius, the body of the vertebrae or the hip (neck of femur) and vertebrae but any bone can be affected. A low trauma fracture (trip and fall from a standing height or less) is usually the first sign of this silent disease, along with loss of height, postural changes such as their head protruding forward, rounded shoulders and/or a Dowagers hump developing.

It is estimated that up to 500,000 people in Ireland may have osteoporosis and that over 50,000 osteoporotic fractures occur each year in Ireland. 1 in 2 women and 1 in 4 men over 65, will develop an osteoporotic fracture in their lifetime, if it is not prevented.

Younger people will develop osteopenia and/or osteoporosis if they have risk factors for bone loss, which is why in an ideal world any patient being put on a new medication or diagnosed with a new condition should be red flagged if either place them at risk for bone loss, so a plan can be

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CPD 105: OSTEOPOROSIS The effects of undiagnosed bone loss

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

NOTE: Low bone density increases the incidence of musculoskeletal problems.

implemented to decrease their risk of fracturing. Some of the many examples; Oral steroids, early menopause, eating disorders, RA. 20% of Irish people aged 60+who fracture their hip will die within 6 to 12 months from a blood clot, infection or pneumonia which are the secondary effects of a fracture. Osteoporosis is rarely on a discharge letter or on death certificate, even though reading the notes, the patients were admitted and treated because they had low trauma fractures.

In 2022, the cost of acute hip fracture care was estimated at ¤48,569,325 nationally.

Many patients in Ireland and worldwide have untreated low trauma osteoporotic fractures, despite the fact that there are effective and safe medications available.

Osteoporotic fractures impose a huge social and financial burden in Europe and Ireland, blocking

acute beds, 50% of older people who suffer an osteoporotic hip fracture, lose their independence, have poor quality-of-life, which significantly increases costs to the Health Service. Increasing age is a factor and Ireland has one of the highest rates of fragility fractures in Europe, along with one of the greatest increases in the number of its population over the age of 80. Women and men over the age of 65 are the highest risk group but prevention in earlier life will save millions of euros long term.

NOTE: Calcium and vitamin D supplements are not treatments.

Intake of Calcium and Vitamin D is essential not only for bone health; however they should preferably be taken through food. How much the patient takes from food should be assessed prior to prescribing a calcium and vitamin D supplement, as many appear to just need vitamin D supplements.

70% of the population will develop back pain in their lifetime,

this may be due to a variety of causes, either local or referred.

Back pain associated with loss of height and changes in posture are red flags for osteoporotic vertebral fractures. 50% of women with vertebral fractures go undiagnosed. 75% of people with vertebral fractures may only have intermittent back pain, but 25% will have extreme pain which in many cases the pain can only be relieved by daily injections of teriparatide, which it is believed to occur secondary to the increase in rebuilding of bone.

It is very important to differentiate undiagnosed osteoporosis with osteoarthritis and degenerative disc disease, which may affect the L4, L5 nerve roots, causing pain in the distribution of the gluteal and sciatic nerves. This pain is usually aggravated by sitting too long or standing too long. Many patients may have a combination of both osteoporosis and osteoarthritis in the vertebrae.

There are over 200 causes of bone loss, either the disease itself or the treatment for the disease or lifestyle choices/addictions.

Osteoporosis and its associated risk of increased fractures is rarely considered as a complication of these diseases or their treatment.

You must find the causes using a multidisciplinary approach to prevent fractures, as many patients have more than one risk factor. Example A 20 year female on Depo Provera who is on an antidepressant that causes bone loss, with low calcium and vitamin D intake and is obese.

The most common cause of low bone density in females is oestrogen deficiency and testosterone deficiency in males.

Family history of osteoporosis will increase the risk of osteopenia and/or osteoporosis by 70%.

Genetic disorders such as cystic fibrosis, osteogenesis imperfecta, diabetes, haemochromatosis, homocystinuria and other metabolic disorders are risk factors. Chromosomal abnormalities such as Turner’s

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syndrome (XO) and Klinefelter’s (XXY ) in males will result in low sex hormone levels, which is why any men lucky enough to be diagnosed must have their testosterone levels checked.

Menstrual problems: Late menarche, first period after the age of 15, irregular periods, PMT, loss of periods for more than 4 months not due to pregnancy, eating disorders or Reduced Energy Deficiency Syndrome RED-S in athletes, early menopause before the age of 45, endometriosis, PCOS and Depo-Provera particularly in the teenage years during the growth spurt.

Men who have had a testis removed, cancer of the testes or trauma causing torsion of the testes, viral or bacterial infections, need to be put on a bone loss prevention plan for osteoporosis and may require testosterone replacement therapy.

Stress either mental or physical, particularly if they have sleep issues, will increase cortisol levels which will reduce sex hormone levels. Other hormones such as high levels of cortisol, prolactin, thyroxine and parathyroid, growth hormone will affect bone metabolism.

Low levels of vitamin D (normal level for bone health should be

70 nmol per litre to 125) affects the absorption of calcium and may cause an increase in the secretion of parathyroid hormone, which takes calcium from bone, to maintain the narrow range of calcium in the blood.

Hyperparathyroidism may also be due to an adenoma of the parathyroids.

Low levels of vitamin D may be due to lack of exposure to sun, inadequate intake of vitamin D in the diet or as a result of malabsorption including untreated coeliac disease or gluten and wheat intolerance, Ulcerative colitis or Crohn’s disease to name a few.

Many drugs can cause bone loss, corticosteroids, chemotherapy, radiation, aromatase inhibitors for breast cancer, androgen suppression for prostate cancer. proton pump inhibitors, warfarin, anticonvulsants and prolactin raising medication.

Poor lifestyle advice may also be a cause of developing low bone density. Running or walking they should alter the speed and the course, as bones respond to differences in strain. Cycling and swimming are non-weight bearing exercises. Patients with and without osteoporosis should

not do yoga as it contains forward flexion bending exercises, as this will compress the anterior aspect of the lumbar vertebrae, increasing the risk of fractures, excess stress on the discs and sciatic nerve.

Adequate sleep and reducing stress is very important.

Nutrition plays an important role, bones require adequate calories, first-class proteins, supplemented milk’s with calcium, vitamin D, vitamin C, iron and folate help absorption. Fluid intake is also essential they should drink at least 12 / to 2 L a day.

Diagnosis of osteoporosis 1. A detailed questionnaire (available by email from IOS) which helps find risk factors for bone loss. 95% of those who contact the IOS their causes of bone loss appear to have been assumed. If any cause of bone loss is not found and could be addressed, such as gluten sensitivity, a patient will continue to lose bone and not get the full benefit from their treatment.

2. A DXA scan - DXA is the gold standard for diagnosing osteopenia and osteoporosis, currently it is the best predictor of fractures. DXA helps to monitor response to treatment

and improve compliance. The DXA definition of osteoporosis is a T score of -2.5. The T score above 1 is normal. Osteopenia is a T score between -1 and -2.49, most fractures occur in the osteopenia range of -1.5 to -2.49. A T score of -2.5 and low trauma fracture or T score of -3 or higher is considered severe osteoporosis. For every one standard deviation of bone mineral density, the relative risk fracture is significantly increased. A DXA scan should measure the posterior anterior view of the lumbar spine, L1 to L4. Ideally the value of each vertebra should be reported not just the total values, as the density may vary, due to osteoarthritic changes, particularly in individuals with scoliosis or a dowagers hump.

Increased calcium in the hyaline cartilage of the vertebrae will give a higher T score and a false high result. Increased density may also be due to vertebral fractures, multiple myeloma or secondaries.

NOTE: If a person’s DXA scan results decline, the cause/s of the decline should be investigated and addressed, changing their treatment is not the solution, as they could continue to lose bone.

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CPD 105: OSTEOPOROSIS

3. Blood Investigations for causes of bone loss - List available by email from IOS. This process should also include bone turnover markers in the blood, CTX1 measures bone loss, while PINP measures bone formation. If a patient has stopped taking Denosumab (an antiresorptive) without taking another antiresorptive, or the injection has been delayed for more than approximately 4 weeks, an increase in the blood level of CTX1 may occur, indicating a high risk of spontaneous vertebral fractures.

4. Treatment plan to prevent fractures or further fractures put in place.

Monitoring bone health: Effective and safe medications are available to treat osteopenia and osteoporosis. Most medications have possible side effects, but the benefits to bone health by preventing future fractures usually far outweighs the risk.

Treatments include Hormone replacement therapy - HRT should not be used in post-menopausal women just to prevent bone loss, unless they have menopausal symptoms.

Antiresorptive medication - Bisphosphonates are nonhormonal and have to be incorporated into bone and are appropriate for some patients but not all and they can only be prescribed for 5 years in total.

They may cause irritation of the oesophagus and proton pump inhibitors should not be prescribed for patients to tolerate them, as this will cause further bone loss.

Monoclonal antibody denosumab (Prolia) The anabolic agent teriparatide for severe Osteoporosis Evenity (Romosozumab) has been approved by the EMA several years ago but is still not available for patients in the ROI. Patients must understand the importance of taking the medication correctly and the consequences of stopping it without consulting their doctor,

especially Prolia for dental work or as many tell the IOS, they read up on the internet they can treat their bone loss without a prescribed medication, all they need to do is buy certain supplements!

Compliance is a major problem which can be improved by DXA and 6 monthly bone turnover markers particularly CTX1 if available, as many tell the IOS they fill their bisphosphate prescription but do not take it. If you have noncompliant patients you could refer them to the IOS. The effect of medication on the prevention of bone loss must be monitored ideally by annual or Biannual DXA’s to improve compliance and to ensure the patient is responding to the treatment, as repeat DXA scanning is much cheaper than bone markers. Since bone loss is silent, the IOS does not recommend repeat DXA scanning every 5 years, as significant bone loss can have occurred. A DXA scan contains 10% radiation of a regular chest X-ray, and a person has been exposed to more radiation traveling from Dublin to New York, than having a DXA scan.

NOTE: Are those who have heart attacks only monitored once every 5 years? At least these patients, if this was the case would usually have signs or symptoms, with bone loss there are none, except fractures that could have been prevented by monitoring the patient.

You must find and treat the causes of osteopenia or osteoporosis.

Treatment also depend on whether they are pre or postmenopausal, their age, the results of the questionnaire and blood tests, the DXA result and if they have fractured. Some patients may have difficulty in swallowing or absorbing medication, while others are needle phobic which cognitive therapy can help.

It is rarely ever too late to investigate and treat a patient to improve their quality of life and prevent further fractures, the IOS know of 90-year-olds who have significantly improved their bone health and regained their independence.

Exercise 80% of the skeleton is composed of cortical bone and 20% is cancellous. Cortical responds more to weight bearing and differences in strain. Cancellous bone is more sensitive to hormonal changes and is more fragile and is lost first. Osteoclasts are multinucleated giant cells that remove old bone, and this process takes 3 weeks, while the osteoblasts build up new bone and this process takes several months.

Weight-bearing activity stimulates the osteoblasts, and they maintain the balance of bone formation and removal. When this balance is disrupted, more bone is removed than replaced causing osteopenia and/or osteoporosis.

Weight-bearing exercise plays an essential role in treatment.

Patients should be advised by a physiotherapist who specialises in bone health and can understand a DXA scan report. There is no exercise programme that suits all those with bone loss and patients should be individually assessed. It is much safer to initiate exercises with elderly patients without weights, as many have never lifted weights in their life, for elderly patients there are very basic exercises on the IOS website. By slowly increasing the weights this will reduce the risk of the patient being very sore and non-compliant and also reduces the risk of fracturing. It makes no sense to rush into maximum weights, as many calls to the IOS helpline are from those who are in agony or fractured while exercising, especially those who have been instructed to do forward flexion. A patient should be thoroughly investigated and on an Osteoporosis treatment prior to an exercise program being initiated Lifestyle advice on nutrition particularly the importance of adequate calories, fluids as well as vitamin D as it plays an important role in calcium absorption and bone metabolism. Adequate sleep and reducing stress are important factors as they increase bone loss by increasing cortisol levels.

Reduce high caffeine intake, excessive alcohol and excessive fibre in their diet no more than 30g a day and cease smoking.

References upon request

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

Oncology Focus News

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Improved Outcomes for NSCLC Reported Dr. Nasser Altorki examines a CT scan of a patient's chest. Credit: Weill Cornell Medicine

A new study reported that patients with non-small cell lung cancer (NSCLC) treated with a combination of low-dose radiation and immunotherapy had higher progression-free survival compared to patients who received immunotherapy alone two years after treatment. The findings from researchers at Weill Cornell Medicine, NewYork-Presbyterian and Columbia University Vagelos College of Physicians and Surgeons offer hope to those affected by NSCLC, the most common type of lung cancer in the United States—81 percent of all lung cancer diagnoses.

Chemotherapy is frequently coupled with immunotherapy for treating people with lung cancer, but this study, published in Nature Communications on Dec. 19, suggests another option. “The addition of low-dose radiation with immunotherapy could increase the options available to patients, particularly those who can't tolerate chemotherapy,” said Dr. Nasser Altorki, chief of the Division of Thoracic Surgery at Weill Cornell Medicine and NewYorkPresbyterian/Weill Cornell Medical Center and the paper’s lead author.

Dr. Zachary Walsh, MD/PhD candidate at Columbia University Vagelos College of Physicians and Surgeons, was also co-first author on this study.

Dual Treatment Eradicates Tumor Cells Previously, an investigatorinitiated clinical trial at NewYorkPresbyterian/Weill Cornell Medical Center conducted by Dr. Altorki and colleagues enrolled 60

patients with early-stage NSCLC. The randomized phase 2 trial, sponsored by AstraZeneca, coupled radiation with durvalumab, an immune-boosting “checkpoint inhibitor.” These drugs work by releasing the brakes on the immune system to induce a response against tumor cells, but their effects may be insufficient to fully eliminate the cancer.

“Using a low dose of radiation to enhance the immune response, rather than a high dose to destroy the tumor, was a novel feature of the trial,” said co-senior author Dr. Timothy McGraw, professor of biochemistry at Weill Cornell Medicine. “From that perspective, I believe Dr. Altorki’s trial design remains unique.”

Dr. Benjamin Izar, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and medical oncologist at NewYorkPresybeterian/Columbia University Irving Medical Center, was also co-senior author on the paper.

The initial findings, published in Lancet Oncology in 2021, demonstrated that the combo treatment eradicated significantly more tumors than immunotherapy alone. In fact, the combination

invoked a “major pathological response”—one that kills more than 90% of the cells in the tumors that were surgically removed and analyzed during the course of the study.

But would it also improve patient survival? To find out, the researchers continued to follow the cohort for an additional two years.

associated with freedom from cancer recurrence,” said Dr. Altorki, who is also the David B. Skinner, M.D. Professor of Thoracic Surgery and the leader of the Experimental Therapeutics Program in the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

The results of the extended study indicated that the dual therapy reduced the chances of cancer recurrence and extended progression-free survival. Six of the individuals who received immunotherapy alone died of cancer. However, in the “dualtherapy arm” of the trial, there was only one death from cancer and five deaths unrelated to cancer recurrence.

The researchers discovered that participants who mounted a major pathological response harbored tissue-resident T cells in their blood—even before treatment had begun. “You wouldn’t normally expect to find these cells in circulation,” said Dr. Altorki.

Their presence suggested that, in these individuals, the immune system had already detected the tumor and initiated a response.

Examining participants’ T-cell repertoire could potentially identify individuals who would benefit from combination treatment.

The team also found that cancerfree survival is accompanied by heightened immune activity.

Individuals who received immunotherapy plus radiation and had major pathology responses had more activated T cells in their blood compared to those who did not have a major pathology response. “The appearance of these activated T cells was

The researchers intend to follow up on this observation in an upcoming trial to assess how radiation stacks up against chemotherapy as a means of bolstering immunotherapy. “We’ve shown that radiation works,” said Dr. Altorki. “But does it work as well as—or even better than— chemotherapy? That’s what we want to answer now.”

Cancer-free survival correlates with activated immune response

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

Oncology Focus: Expert Profile

42

Ask the Expert – Professor Seamus O’Reilly Professor Seamus O'Reilly, Clinical Cancer Trials Ireland

over 3,900 patients have been enrolled in cancer clinical trials in our unit. It allows patients access to the latest available treatments, creates an environment of inquiry, of standards in a unit and it also accelerates innovation in a unit as we are bringing in newer treatments, and newer platform agents, years before they would come into place if we waited until they are approved by the regulatory bodies and then reimbursed by the government.

Prof Seamus O’Reilly BSc MD PhD FRCPI is Consultant Medical Oncologist at Cork-Mercy and South Infirmary Victoria University Hospitals, Clinical Lead at Cancer Trials Ireland, and Clinical Professor at University College Cork. A graduate of University College Galway (BSc, MB BCh BAO, MD) he completed basic specialist training at Trinity College Dublin affiliated hospitals and medical oncology training at John Hopkins Hospital, Baltimore, MD where he was subsequently Assistant Professor in Medical Oncology. During fellowship training there he completed a PhD in Clinical Investigation and focused on Cancer Pharmacology in his research. He is a founding trustee of the South Eastern Cancer Foundation and Cork ARC Cancer Support House and was National Specialty Director in Medical Oncology at the Royal College of Physicians in Ireland from 2013-2021 mentoring projects on litigation in breast cancer, climate change, rare tumor management, survivorship, pharmaco-economics, dental oncology, cyber security and the impacts of the COVID-19 pandemic on healthcare staff and patients.

At Cancer Trials Ireland he founded the National Green Cancer Clinical Trials Initiative in 2022, and is a member of the Executive Board of the Breast

International Group (2021-5), The National Research Ethics Committee, Advisory Board of the National Cancer Registry, Irish Health Research Forum Steering Group, the steering committee of the All Ireland Cancer Research Institute, and The European Society of Medical Oncology Climate Change Taskforce, and Oncology Pro Group. He is deputy editor of British Journal of Cancer Reports. His main research focus are clinical trials in breast cancer, sustainability in healthcare, and survivorship.

We recently spoke with him to learn more about the work of this vital organisation, and to hear about his recent talk at the European Society for Medical Oncology (ESMO) Congress at the end of last year.

Cancer Care and Cancer Research Giving us a brief overview of his career path to date, Professor O’Reilly told Hospital Professional News, “ I have been involved in clinical trials since my training days, having established a clinical trials unit in Waterford and a clinical trials unit in Cork. Thus, the length of time I have been completing cancer research is the same as my cancer care work.

“We are very committed to cancer care in Cork; our unit had its 20th anniversary last year and

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“This allows people to access care at an earlier stage. Where clinical trials are embedded into cancer care, the outcomes for patients are better, and that's a hugely important thing.”

Professor O’Reilly notes that currently, oncology is at an ‘exciting stage’ within Ireland, with many new agents in the pipeline.

He continues, “There is a drug class called anti-body drug conjugates and there are 160 of these in development globally at present. It is unclear which one of them is going to be the next transformative treatment. But it offers hope for patients where the standard treatment isn’t as good as it could be, or patients have side effects from treatment or the treatment simply does not exist.

So creating an environment in our hospitals where patients have access to this innovation is of great significance.

“With Cancer Trials Ireland we have four main themes - for the next four years. The first one is streamlining. In order for patients to get access to these newer treatments, we need to be efficient in what we do and how we do things. We are competing with other countries. For instance, in Latin America, there are 22 cities with populations of over a million people. So if a company tries to set up a trial there, they have huge access to a very diverse patient grouping to establish infrastructure. When we are being looked at as an environment to

do trials, we need to be aware of the companies of choice, and the investigators of choice, in regards to where the drugs are.

“Streamlining our trials in terms of getting the regulator aspects and processes quicker is really important.”

The government has recognized and established a National Research Ethics Committee. And Professor O’Reilly sits on one of the committees of that. He explains that this is where clinical trials are reviewed.

“Historically,” he adds, “they were reviewed by various ethics committees around the country.

But now there's one major ethics committee. That allows economies of scale and expertise and also transparency in terms of efficiency. It is an incredibly wellrun organisation but there are also issues such as data protection that are involved in a clinical trial activation and there are insurance issues etc.

“Much like other enterprises, you're only as good as your weakest link and you're only as fast as your slowest part. A major aspect of my role is to look at how we can get these things done more quickly by getting involved, looking at the stakeholders involved, and engaging with all of them.

“The second aspect is getting more studies into Ireland. The 160 drugs that we talked about and getting patients access to those studies is a key thing for many people in our organisation and for other investigators in our organisation. There are international meetings taking place all the time; we go to those meetings and interact with the companies that are making these drugs and with the international co-operative groups that are involved in the trials, to highlight Ireland's infrastructure and development, the intellectual capital that is here, and the patients here that would benefit from it.

“The third thing is succession.

In any organisation we need to nurture the next generation. We have more oncologists now in Cork and we're interviewing for our

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“Where clinical trials are embedded into cancer care, the outcomes for patients are better, and that's a hugely important thing” 11th consultant post. In 2005, we were down to one consultant at one stage so those developments are needed as cancer medicine is increasing. The information that we see is accelerating, so if you take all of the information that was developed since the start of civilization to the thousand, that same amount of information is created every year now.

“Medical knowledge doubles every 75 days and when I started as a Medical Oncologist, my first consultant post was in 1995 and then you could do everything. But now, to stay up to date in one disease area, you need to read 7 papers a day, 365 days a year.

“That just goes to show how things have evolved and so we look at succession planning we look at ways of nurturing the next generations so they can you know be involved in clinical trials.”

Competing Needs Professor O’Reilly acknowledges that there are competing needs as the majority of healthcare workers are women.

“Often, the time when women start a new career is also when they are starting to raise families.

We need to create a structure that allows women to participate in this, in addition to their job and we need to build an environment to make it easy for them to engage.

If you look at the Irish healthcare landscape, and the people doing clinical research, the majority of research staff in clinical trials in Ireland are nurses.

“Building an infrastructure where we can encourage, recruit, and retain nurses and data managers in our system is also hugely important. It is not just about

doctors and who will lead to studies. If you don't have a team, you can't build around it. So building an environmentwhere people will want to come and get involved and stay in clinical trials is hugely important.

“The final theme is sustainability. If we look at the carbon footprint of clinical trials, it is half the carbon footprint of Denmark which is a country of 5 million people.

Healthcare is very climateunfriendly. If you take for instance the carbon footprint of health care in the United States, it is the same as the entire nation of the United Kingdom. The carbon footprint of the NHS, the UK health system, is the same as the nation of Croatia.

“If someone has a robotic hysterectomy today in Cork, the carbon footprint of that is someone driving in a car from Madrid to Moscow. If someone has a tosalectomy in Cork and that generates 15 kilograms of waste, to incinerate that is 5,000 litres of water as the carbon footprint of nine families for a day. That's just one operation.

“Climate change is very bad for cancer it disrupts cancer care.

Fossil fuel pollution contributes to cancer, in France, they calculated that 3% of their breast cancer cases are due to fossil fuel pollution from cars. To put that in context, 7% of breast cancer in Ireland is due to alcohol. It's a problem that's getting worse.

We're all affected by it, 40% of our citizens were affected by global warming last year either through flooding or extreme weather events. We want to build sustainability into clinical trials and also awareness of it.

“Last year in 2022 we set up the national green cancer clinical trials

initiative and we've established a green charter for cancer trials in Ireland. As the clinical lead, the board of charged me to integrate a green charter into what we do. That ranges from if we have a meeting, we look at what type of sandwiches we order. A vegetarian sandwich's carbon footprint is half of a carnivore sandwich. It also extends into things like pensions and financial planning. In a study of hospitals in Boston, where they monitor energy consumption and they also declare how much money they have. What they found was that the carbon footprint of their financial Investments was three times greater than the carbon footprint of the energy used by the hospitals.

“Our group published a paper last year called ‘Climate Toxicity’ which is the impact of climate change on cancer care and the impact of cancer on climate change. It's the first time the term has been used in medical literature. Our ambition is to look at other groups and green clinical trial groups globally and to integrate with them, work, and collaborate with them to be a sustainable clinical trial group.”

Professor O’Reilly states that it is imperative the medical profession speak up.

“The decisions that need to be made about healthcare, about climate change, are political in addition to individual. But if the medical community is silent about this, it's very hard for the politicians to be vocal.

“We need to speak up. Both in terms of the impact of climate change on our patients, in terms of cancer care but also in terms of being more active and more responsible in healthcare. I think that sometimes people feel that healthcare is so important, that the same standard shouldn’t apply to it as everything else.

But I think that's a missed opportunity, especially since it contributes so much.”

Climate Toxicity It was this paper which led to Professor O’Reilly and his team being invited to present at the 2023 European Society of Medical Oncology Congress.

He tells us, “My talk was mainly about the impact of climate change on cancer care and it ended with what we should

do next, which is probably the important part. We looked at the ways in which we can make our healthcare more sustainable. I worked with Catherine Wedik, the co-author of the climate toxicity paper to put the talk together.

“It's a living document that pulls from various sources around in the literature as regards to how we can make an organization more carbon-friendly. The other aspect we talked about was work within clinical trials and we assessed the carbon footprint of a clinical trial. That was carried out in conjunction with the group in the Institute of Cancer Research in the United Kingdom.

“I am also a member of the Executive Board of the Breast International Group and I spoke at their meetings last year. We've developed a survey of breast cancer trials organisations globally. The Breast International Group covers 50 members from five continents and the survey targeted them to see what their experience with climate change was, and what would it take to develop a green clinical trial initiative, so to speak. That survey was completed around Christmas and we are analysing it with the ambition to see what that shows and note the level of interest in this and what the barriers would be to implementing it.

“But the countries that are represented in it, Spain, France, Greece, Canada, and Australia, just to name a few, have all been affected by climate change.

There's been a good level of enthusiasm, support, and interest, particularly by the leadership of the Breast International group about the initiatives. Using the energy of so many groups being involved, to bring about initiatives that would make our clinical trials Arena more climate responsive, is the ambition.

“Whilst we are talking about climate toxicity, there is also a phrase known as climate therapy.

This presents the topic in a more positive way. I think a lot of people are very scared about climate change because they feel that they're very vulnerable to it, particularly younger people.

They also feel that the people of influence and power are higher up than them and are going to be least affected by it.

“Climate change here really started in the 1950s and 1960s and while w are the group that got the most

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

Oncology Focus: Expert Profile

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Professor Seamus O'Reilly, Clinical Cancer Trials Ireland

from fossil fuels, we are also the group that's not going to be affected that's very frustrating for the younger generation.”

Tree of Solutions There was great interest and further discussion on the back of Professor O’Reilly’s talk but he is quick to add that ‘sometimes there's inspiration and perspiration.’

He explains, “The inspiration part is the paper on climate change but the perspiration part starts now in terms of implementing and doing things. Of course, it’s going to be slow to begin with but there is a lot of interest in it.

“I have highlighted that the average medical student gets maybe two hours of information about climate change during their medical training, for something that's going to be hugely important in their lifetime. But I think also if we could also embed the awareness of climate change in terms of disposable objects, disposable items, in terms of

how we practice, and being less wasteful in terms of what we do.

That will be the biggest thing.

“Our aim at the moment is to look at certain disease types and develop a ‘Tree of Solutions’.

The ‘Tree of Solutions’ in oncology will look at guidance to reduce unnecessary testing and guidelines, in terms of how we prescribe chemotherapy, such as how we could maybe use more oral tablets than IV because they have less of a carbon footprint.

There's plastic associated with it. Plastics need petrochemicals to generate, to make plastics you need petrochemicals. Those kinds of practical things that people could think of but that would become embedded in what they do. That is the ambition.

“I probably spoke about climate change maybe five or six times last year and what people are really taken aback by, is the impact of healthcare on climate change and how damaging our practice is to climate change.

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

“Our group published a paper last year called ‘Climate Toxicity’ which is the impact of climate change on cancer care and the impact of cancer on climate change. It's the first time the term has been used in medical literature.

The second aspect is how enthusiastic the younger generation is and how engaged they are. I think that's very reassuring and I think we all need to be involved here. We all have a stake here.

“Clinical trial units were established owing to the Belfast agreement. Professor Paddy Johnson, who is Professor of Cancer Medicine in Belfast, looked at the Belfast agreement and integrated an All-Ireland National Council initiative. It is one of the best three outputs of the Good Friday Agreement.

“The National Cancer Institute got involved with the government and clinical trial units. So the clinical trial units we see around the country today are a direct result of

the Good Friday Agreement. After that, it accelerated things. When we set up units in Waterford, we had to set up an ethics committee, we had to set up clinical trials, and we had to set up fundraising in the community to fund a research nurse.

“But when I moved to Cork, after the Good Friday Agreement was signed, the government got involved in setting up these clinical trials with a grand funding mechanism and the grant was due in 2001. A building was built, nurses were hired, and you didn't have to go out into the community to fundraise to get to each stage. It accelerated us and it was a huge example of where government funding can just come in and transform.”

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Indication: Monotherapy in the treatment of partial onset seizures in adults and adolescents from 16 years of age with newly diagnosed epilepsy. As adjunctive therapy: In the treatment of partial onset seizures in adults, adolescents, children and infants from 1 month of age with epilepsy, in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy and in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.

Dosage and administration: Route of administration: Oral. Adults: monotherapy: Initially 250mg to 500mg twice daily. If 250mg given twice daily initially increase to 500mg twice daily after 2 weeks. Dose can be increased to 1500mg twice daily Dose can be increased by 250mg or 500mg twice daily every two weeks depending upon the clinical response Add-on therapy: 500mg twice daily. Can be increased up to 1500mg twice daily. Paediatric population: monotherapy: The safety and efficacy have not been established. Add-on therapy 6 months to 17 years (weighing less than 50kg): 10mg/kg twice daily, can be increased up to 30mg/kg twice daily. Dose changes should not exceed increases or decreases of 10mg/kg twice daily every two weeks. The lowest effective dose should be used Add on therapy infants aged 1 month to less than 6 months; Initial dose 7mg/kg twice daily. Dose can be increased by 7mg/kg twice daily every two weeks to max dose 21mg/kg twice daily. Elderly: Adjustment of the

dose is recommended in patients with compromised renal function. Renal impairment: daily dose must be individualized See SmPC. Hepatic impairment: 50% reduction of the daily maintenance dose is recommended when the creatinine clearance is <60ml/min/1.73m2.

Contraindications: Hypersensitivity to the active substance or other pyrrolidone derivatives or to any of the excipients.

Precautions and warnings: Renal impairment.

Complete blood cells counts if weakness, pyrexia, infections or coagulation disorders reported. Monitor patients for signs of depression and / or suicidal ideation and behaviours. Monitor for psychotic symptoms, irritability and aggressiveness. Monitor for aggravation of epilepsy. Caution in patients with QTc prolongation, concomitantly treated with drugs affecting QTc interval or in patients with pre-existing cardiac disease or electrolyte disturbance.

Interactions: Methotrexate, macrogol.

SmPC for detailed information.

See

Pregnancy and lactation: can be used during pregnancy, if after careful assessment it is considered clinically needed. Breast-feeding is not recommended.

Driving / using machines: Patients are advised not to drive or use machines until it is established that their ability to perform such activities is not affected.

Undesirable effects: Nasopharyngitis, somnolence, headache, anorexia, depression, hostility/aggression, anxiety, insomnia, nervousness/irritability, convulsion, balance disorder, dizziness, lethargy, tremor, vertigo, cough, abdominal pain, diarrhoea, dyspepsia,

vomiting, nausea, rash, asthenia/fatigue, thrombocytopenia, leukopenia, suicide attempt, suicidal ideation, psychotic disorder hallucination, confusional state, amnesia, vision disturbance, pancreatitis, hepatic failure, acute kidney injury. , infection, pancytopenia, neutropenia, agranulocytosis DRESS, ECG QT prolonged, encephalopathy, Neuroleptic malignant syndrome, hepatic failure, Toxic epidermal necrolysis, Stevens -Johnson Syndrome, erythema multiforme, rhabdomyolysis.

(Please refer to the Summary of Product Characteristics for detailed information) Legal category: POM Marketing Authorisation PA22697/012/001

Price: Number:

Marketing Authorisation Holder: Syri Pharma Limited t/a Thame Laboratories Floor 0, 1 WML, 1 Windmill Lane, Dublin 2, D02 F206, Ireland.

(Distributed by Advanz Pharma Ltd in Ireland) Date of preparation: Sept 2022 Adverse events should be reported.

Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to Syri Pharma Medical Information via telephone on 00 44 330 1359 422 or via e-mail at medinfo@syripharma.com Reference: 1. Data on file Levetiracetam 100mg/ml oral solution January 2024 (v2.0) - savings (p.1) IE/LVI/PM/0006 Date of Preparation - January 2024

Exercise & Cancer

46

Exercise and Haematological Cancer: The Patient Experience physiotherapy had been planned prior to my discharge. But my discharge was hastened due to pressure on beds. The recovery from treatment was difficult not least because of the long time being bedridden in a confined space. In retrospect my recovery from the treatment might have been foreshortened if I had put greater focus on rehabilitation during and after my treatment.

Written by Members of the Trinity St James’s Patient Representative Group and Dr Grainne Sheill

Currently there are over 200,000 people living with and beyond cancer in Ireland and that number is expected to double over the next 25 years.

Approximately 10% of these patients have had haematological cancers such as lymphomas, leukaemia’s or myeloma.1 Cancer and Exercise Treatment options for haematological cancers include watch-and-wait approaches, chemotherapy, radiotherapy, immunotherapy, and stem cell transplantation (SCT). Long term and late effects following treatments include reduced physical functioning, fatigue, pain, physical inactivity and depression, mainly associated with steroid induced myopathy.

Graft versus host disease (GVHD) occurring following SCT can lead to significant morbidity, and it can take years to recover pretransplant physical abilities Although patients may be advised to rest and avoid intensive exercises, there is an established body of evidence demonstrating the potential effects of exercise to improve physical and psychosocial functioning in patients undergoing treatment for cancer. The current evidence in haematological cancer also suggests that exercise interventions are safe and effectively improve quality of life, cancer related fatigue and depression and trials are ongoing examining the effects of exercise on a variety of other treatmentrelated side effects,2 however

pathways to support patients to exercise are underdeveloped.

Exercising During and after Treatment for Haematological Cancer Three patients living with or after haematological cancer talk about their experience of staying active during cancer treatment: Pt 1: When I was diagnosed, I was fit and engaged in regular exercise but I was told to stop all levels of exercise and activities including housework. As I progressed through my induction (treatment) I began to return to exercise in particular cycling and yoga which I continued right through both stem cell transplants even bringing my yoga mat into the hospital. Some staff were encouraging and facilitated my yoga by taking me off my drip for an hour. After each stem cell transplant, I returned to cycling and tennis as soon as my energy levels allowed. As my disease progressed, I dealt with pathological fractures which interrupted and reduced my activity levels. I received targeted physiotherapy following bone fractures. I continued to cycle, walk and do yoga over the past seven years through many lines of treatment and bone damage and sclerotic skin GVHD. All efforts to exercise have been through my own determination.

Pt 2: I had a stem cell transplant in 2013 as treatment for Chronic Mylo Monositic Leukemia.

The treatment was in isolation wards. The treatment and care provided was excellent. I believe

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Pt 3: I am on a daily treatment for CLL; I have been in treatment for 20 years. I exercise with a trainer twice a week. I started with pilates and have moved to personal training sessions with weights and cardio. My bone density has increased; my muscle strength and muscle definition have noticeably improved. I am 73 and I am able to get up off the floor unaided after a workout. After a session I feel amazing - the endorphin release lasts for a long time. Because I am active nearly everyday I do not allow myself to dwell on my diagnosis.

Development of Haematological Exercise Support and Services Despite the known benefits of exercise, only 20-40% haematological cancer survivors participate in regular exercise.

All patients are advised to avoid inactivity and be as active as possible during and after cancer treatment. If possible, the current guidance is for patients to aim for 150 minutes of moderate intensity or 75 minutes of vigorous intensity aerobic exercise per week, plus 2–3 days of resistance training of major muscle groups.

Patients outline what they feel would have encouraged them to include their physical activity levels during and after their cancer treatment: Pt 1: (I think) patients should be assessed and given guidance and encouragement to be active and exercise right from diagnosis through stem cell transplants and beyond. Simply asking and reminding patients about activity levels should be included in the questions asked at each check up…Advice about post treatment exercise programmes – PERCS and Exwell should be offered to every patient.

Pt 2: An assessment of exercise needs prior to, during and post treatment together with personalised advice on

appropriate exercises would be of huge benefit. Provision of this advice by physiotherapists with experience of dealing with cancer patients would be particularly beneficial. This service would improve patient well-being and perhaps reduce the need and cost of medical interventions required following treatment.

Pt 3: Since diagnosis in 2003 to now, I cannot recall being advised to exercise as part of my treatment regime. I was always active and exercise was something I did not do for the first year and a half after diagnosis as I was exhausted from treatment.

Going back to being active was something I did on my own working with a physio on a one to one or in a group setting…

The benefits I have received have been immeasurable. Exercise should be part of the regime for all patients.

As survival from haematological cancer continues to improve, an increasing number of people are living with treatment related side-effects. With increasing awareness of the benefits of increasing physical activity levels and physical fitness in this group, there is a need for dedicated exercise programmes tailored to individual’s needs.

The physiotherapy department in St James’s Hospital are currently developing their exercise rehabilitation pathway for haematological cancer. A directory of current cancer rehabilitation services available nationally in Ireland is available here: Home | Cancer Rehabilitation www.cancerrehabilitation.ie References 1. National Cancer Registry Ireland (2022) Cancer in Ireland 19942020: Annual statistical report of the National Cancer Registry.

NCRI, Cork, Ireland.

2. Knips L, Bergenthal N, Streckmann F, Monsef I, Elter T, Skoetz N. Aerobic physical exercise for adult patients with haematological malignancies.

Cochrane Database of Systematic Reviews 2019, Issue 1. Art. No.: CD009075.

DOI: 10.1002/14651858.

CD009075.pub3

HRD Biomarkers

47

Homologous Recombination Deficiency as a Biomarker in Cancer Treatment Written by Dr Jason McGrath (Postdoctoral Research Fellow), Dr. Gordon Daly (Ph.D. Researcher), Dr. Damir Vareslija (Lecturer and Principal Investigator), and Prof. Leonie Young (Professor, Scientific Director Beaumont RCSI Cancer Centre).

Department of Surgery, Royal College of Surgeons in Ireland & Beaumont Hospital Introduction to Homologous Recombination Deficiency Homologous recombination deficiency (HRD) represents a pivotal concept in oncology, characterized by a functional loss in the homologous recombination repair (HRR) pathway. Essential for repairing DNA double-strand breaks (DSBs), the most severe forms of genetic damage, HRD arises from mutations in genes like BRCA1, BRCA2, and others.1 These mutations, whether inherited (germline) or acquired (somatic), impede the cell's ability to repair DSBs. The concept of "BRCAness" extends this definition, describing tumours with similar molecular characteristics to BRCA mutation-induced HRD, caused by defects in other HRR pathway genes such as ATM, ATR, or RAD51c.

Currently, it's estimated that a notable percentage of cancer patients, particularly those with triple-negative breast cancer (TNBC) and HER2-negative breast cancers, exhibit some form of HRD. However, due to the restricted criteria of current testing methodologies, a substantial number of these patients might be missed. This underdiagnosis means that many individuals who could benefit from targeted therapies like PARP inhibitors are not receiving them. Thus, HRD testing becomes instrumental in

guiding treatment decisions and tailoring personalized cancer therapy strategies.

Therapeutic Implications of HRD in Cancer The presence of HRD in tumours significantly influences their response to certain chemotherapy agents and targeted therapies, particularly PARP inhibitors.2 This sensitivity is due to the limited DNA repair options available to cancer cells with HRD, making them more vulnerable to DNA-damaging agents. HRD status serves as a crucial biomarker for forecasting the efficacy of treatment.

Dr Jason McGrath

Dr. Gordon Daly

Methods of Testing for HRD HRD testing encompasses evaluating mutations in BRCA1 and BRCA2 genes and assessing for "BRCAness" through alterations in other HRR pathway genes. Genomic instability scores, derived from genomic scars like Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-Scale State transitions (LSTs), quantify the impact of HRD on a tumour's genome.

Additionally, RAD51 foci tests provide a direct measure of HRR functionality. Several of these tests have received FDA approval, varying by region and regulatory guidelines.3 Methods of HRD testing are summarised in Figure 1.

Dr. Damir Vareslija and Prof. Leonie Young

Figure 1. An Overview of HRD Testing Modalities. The diagram illustrates the three primary components of HRD testing: Germline and somatic mutations in HRR genes, including BRCA1/2 and genes associated with BRCAness; the Genomic Instability Score, which incorporates factors such as LOH, TAI, and LSTs; and HRR Functional Status, assessed by the Rad51 Foci Test, which is indicative of the cell’s ability to perform homologous recombination repair. Diagram was designed on Biorender.com

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

HRD Biomarkers

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Figure 2. The ctDNA-Based HRD Testing Process. This flowchart depicts the steps involved in using circulating tumour DNA (ctDNA) to assess HRD in patients, starting with the collection of a liquid biopsy, followed by plasma separation and ctDNA extraction. The sample is then analyzed for ctDNA mutations and methylation patterns, which informs clinical applications such as treatment selection, ongoing treatment monitoring, and the detection of treatment resistance. Diagram was designed on Biorender.com.

Challenges and Limitations in HRD Testing

accurately determining HRD with existing assays.

HRD testing has advanced, but it encounters numerous obstacles.4 Tests may overlook the full scope of HRD, particularly in tumours exhibiting BRCAness without BRCA mutations, leading to potential underestimation of HRD. The nuanced interpretation of test results and their application to treatment strategies add complexity. Additionally, challenges such as insufficient quality or quantity of FormalinFixed Paraffin-Embedded (FFPE) samples can compromise test results. Selection of tumour areas for testing demands accurate evaluation due to tumour evolution and heterogeneity, which can affect the homologous recombination pathway and the effectiveness of treatments.

Moreover, Variants of Uncertain Significance (VUS) in HRR genes, especially noted in ovarian cancers, present difficulties due to scarce data. These issues underscore the intricate nature of

Future Directions in HRD Testing The future of HRD testing is marked by potential advancements including sophisticated genomic sequencing and artificial intelligence-driven tools. These could detect subtler signs of HRD and BRCAness, revealing HRD in a larger subset of cancer patients.

Liquid biopsies for analyzing circulating tumour DNA (ctDNA) represent a cutting-edge, noninvasive technique for cancer diagnostics, including the identification of HRD (summarised in Figure 2).5 ctDNA is shed into the bloodstream from tumours and can be sampled through a simple blood draw. This method allows for the detection of cancer-specific genetic mutations or epigenetic alterations, including those associated with HRD, without the need for invasive tissue biopsies.

It also enables the analysis of genomic scarring patterns such as LOH and LSTs. Liquid biopsies

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

can provide a comprehensive snapshot of the tumour's genetic landscape, facilitating real-time disease monitoring and allowing for the dynamic assessment of tumour evolution and response to treatment. This approach is particularly valuable for patients who cannot undergo traditional biopsy procedures or have tumours that are difficult to access.

methods, potentially identifying HRD from subtle genomic changes that current tests may miss.

Machine learning algorithms can also integrate diverse data types, including genomic, transcriptomic, and clinical data, to provide more accurate predictions of treatment response and prognosis.

Beyond ctDNA, other functional assays that could prove beneficial for HRD testing include assays for detecting deficiencies in the ATM, ATR, and CHK1/2 pathways, which are involved in the DNA damage response.6, 7 Techniques such as CRISPR-Cas9 gene editing could also be used to identify potential HRD by disrupting HRR genes and observing the effects on cellular repair mechanisms.

Advancements in HRD testing are revolutionizing the field of personalized cancer therapy. By improving detection accuracy and expanding the scope of identified patients, these developments hold the promise of more effective and tailored cancer treatments. As technologies like ctDNA analysis evolve, they are set to enhance our understanding and management of HRD in cancer, ensuring that more patients benefit from targeted therapies like PARP inhibitors.

The continuous research and development in this area are crucial for realizing the full potential of HRD testing in oncology.

Artificial Intelligence (AI) holds potential in HRD testing by analyzing complex datasets to identify patterns and predict HRD status. AI can process large genomic datasets faster and with more precision than traditional

Conclusion

References available on request

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Pancreatic Cancer

50

Pancreatic cancer: overcoming chemotherapy resistance using synthetic anti-miRs Written by David Hackett (Ph.D. student)1, Dr. Jason McGrath (Postdoctoral Research Fellow)2, Dr. Stephen G. Maher (Associate Professor in Translational Oncology)1 Department of Surgery, Trinity St. James's Cancer Institute, Trinity Translational Medicine Institute, St. James's Hospital, D08 W9RT Dublin, Ireland. 2Department of Surgery, Royal College of Surgeons in Ireland (RCSI).

1

David Hackett

the third leading cause of cancerrelated death in the European Union.2 It has already reached this status in the United States.

Pancreatic Cancer: A Tough Nut to Crack!

Pancreatic cancer presents a significant clinical challenge.

Currently, the 5-year survival rate for patients diagnosed with this cancer is only 12%, the lowest among all solid malignancies.1

Pancreatic ductal adenocarcinoma (PDAC), arising in the exocrine portion of the pancreas, is the most common histological subtype of pancreatic neoplasm. It accounts for over 90% of cases of pancreatic cancer. PDAC is expected to surpass breast cancer, becoming

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

A multitude of factors contribute to the extremely poor prognosis of PDAC. Early-stage or localized disease is often asymptomatic.

Additionally, the majority of patients present with nonspecific symptoms when the cancer is in a locally advanced or metastatic stage.

As a result, only 20% of patients are eligible for curative surgery.3 Consequently, approximately 80% of patients with PDAC undergo treatment with multidrug chemotherapeutic regimens and, in some cases, radiotherapy.

However, due to the aggressive tumour biology and both inherent and acquired drug resistance in PDAC cells, many patients respond poorly to current treatments.

MicroRNA Therapeutics: A Promising Anti-Cancer Treatment Approach?

MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs comprising 20–25 nucleotides.

They play a crucial role in gene expression regulation by imperfectly pairing with the 3′-untranslated region (3′-UTR) of target mRNA. MiRNAs have been identified as key modulators in numerous cellular processes, including those that contribute to chemotherapy resistance in various tumours.4 Therefore, miRNA-based therapy may offer a new, promising path in cancer treatment, either as a standalone option or in combination with existing standard-of-care regimens.

Figure 1 Proposed miR-31-ATOX1 Axis

51

Figure 2. Testing feasibility of delivery of miR-31 anti-miRs. Synthetic miR-31-modulating oligos co-coupled to chemotherapycoupled nanoparticles may allow stable delivery to PDAC organoids.

Organoids will be developed using fresh tumour samples from PDAC patients. This diagram was created using Biorender.com.

Overcoming Pancreatic Cancer Chemotherapy Resistance Using Anti-miRs The multi-drug regimen FOLFIRINOX, comprising folinic acid, 5-FU, irinotecan, and oxaliplatin or cisplatin, is the standard first-line treatment for patients with metastatic PDAC. While FOLFIRINOX often stabilizes the disease, most patients rapidly develop resistance to the therapy.5 Cisplatin, a platinum agent used in treating a variety of solid malignancies, induces DNA damage to promote cell death. However, only 1–4% of the drug reaches the nucleus,6 indicating that drug trafficking and sequestration are crucial in cisplatin resistance.

A small copper (Cu) chaperone known as ATOX1 (Antioxidant 1) plays a role in Cu transport and homeostasis within cells.

ATOX1 binds Cu(I) ions in the cytosol and delivers them to the Cu-transporting ATPases in the trans-Golgi network. This process is essential for the biosynthetic maturation of secreted Cudependent enzymes. Studies

have shown that cancer cells with higher resistance to cisplatin exhibit significantly elevated levels of ATOX1.7 However, the literature presents conflicting results; some studies indicate that deletion of ATOX1 leads to reduced sensitivity to cisplatin in certain contexts.8, 9 Thus, the exact role of ATOX1 in cellular resistance to platinumbased chemotherapeutics is not yet fully understood.

Our research group has demonstrated in PDAC, as well as in malignant pleural mesothelioma,10 that the loss of a specific microRNA, miR-31, promotes cellular sensitivity to platinum-based chemotherapies, such as oxaliplatin, cisplatin, and carboplatin. In silico analysis has identified ATOX1 as a putative target of miR-31.

We have observed that miR31 regulates the expression levels of ATOX1 in PDAC cells.

Suppressing miR-31 in these cells using synthetic anti-miRs leads to increased intracellular levels of ATOX1 and enhanced chemosensitivity (Figure 1A).

Furthermore, direct overexpression of ATOX1, independent of miR31, significantly also increases the sensitivity of PDAC cells to cisplatin.

This finding strongly suggests a link between miR-31 and ATOX1, forming a drug resistance axis that warrants further investigation. We hypothesize that miR-31 binds to the 3′-UTR of ATOX1 mRNA, leading to either repression of protein translation or degradation of the mRNA transcript (Figure 1B). Intriguingly, it has been reported that platinum drugs can bind specifically to the ATOX1Cu heterodimeric complex.6

Collectively, our findings imply that suppressing miR-31 may promote the cytoplasmic-to-nuclear trafficking of cisplatin via ATOX1, thereby potentially explaining the restored chemosensitivity observed in PDAC cells.

A. In PDAC cells, low levels of miR-31 enhance cellular sensitivity to cisplatin (CDDP), while high levels of miR-31 lead to increased resistance to CDDP. MiR-31 modulates the levels of the Cu chaperone ATOX1. Specifically, PDAC cells with overexpressed miR-31 show low levels of ATOX1. In contrast, cells with suppressed miR-31 exhibit high levels of ATOX1. CDDP may act as a 'hitch-hiker,' increasing in the cytoplasmic-to-nuclear transport of CDDP. B. ATOX1 mRNA is a predicted target of miR-31. We propose that miR-31 suppresses ATOX1, either through mRNA degradation or inhibition of protein translation.

This diagram was created using Biorender.com.

The Future for miRNA-Based Therapeutics in Pancreatic Cancer The field of miRNA-directed therapeutics is rapidly emerging within oncology. A handful of miRNA-based drugs are currently under clinical trials for various cancers, with some demonstrating promising outcomes.11 A notable figure in this area is Dr. Glen Reid, Associate Professor at the University of Sydney Medical School. Reid developed TargomiRs, a therapeutic based on a miR-16 mimic, delivered via anti-EGFR antibody-targeted bacterial minicells. The TargomiRs

underwent a phase I trial in patients with recurrent malignant pleural mesothelioma (MesomiR-1 trial), where it showed both safety and preliminary signs of efficacy.12 Despite the potential of miRNA replacement or inhibition in oncology, significant challenges remain. These include susceptibility of miRNAs and anti-miRs to degradation by ribonucleases in biological systems, poor penetration through cell membranes, risks of off-target toxicities, and potential triggering of unwanted immune responses.13 To advance miRNA-based drugs to phase III clinical trials, these issues must be addressed.

Looking forward, our group aims to study the effect of miR-31 on chemosensitivity in PDAC tumour spheroids and organoids using fresh samples from PDAC patients.

We will employ gold nanoparticles, known for their efficiency as inorganic vectors in maintaining the stability of synthetic miRNAs during delivery. This approach will allow us to assess the feasibility of delivering anti-miRs directed against miR-31 to PDAC cells.

These models will enable us to determine if co-coupling synthetic anti-miR-31-modulating oligos with chemotherapy-coupled nanoparticles can enhance the sensitivity of PDAC cells to standard chemotherapeutics (Figure 2). The co-administration of miR-31 anti-miRs with conventional platinum-based chemotherapy could potentially convert non-responders to responders, offering a promising avenue for improving treatment outcomes in patients with PDAC. References on request

ENOS Conference

52

Reflections on the 2023 European Nursing of Oncology Society Conference and upcoming Irish Cancer Society research funding opportunities Written by Dr Nikolett Warner, Cancer Survivorship Research Officer, Irish Cancer Society

In October 2023, the 16th European Nursing of Oncology Society’s Conference (EONS16), ‘Cancer nursing: Building on innovation and building back better in healthcare’ took place in Madrid.

The conference, which took place alongside the European Society for Medical Oncology (ESMO) Annual Congress, hosted a variety of talks spanning the cancer nursing field.

Sessions focused on issues such as cancer screening, palliative/end of life care, health promotion, and supportive, patient-centred care.

Attending EONS16 on behalf of the Irish Cancer Society’s Research Team, it was incredible to witness first-hand the breath of innovative research projects. At the Irish Cancer Society, we are committed to supporting capacity building in the Irish nursing workforce, through funding innovative, high quality cancer research. Over the last ten years, thanks to the generous support of our donors, we have invested over ¤30 million in cancer research.

A number of these Irish Cancer Society-funded researchers presented their work at EON16, including, for example, Yvonne Hanhauser, Advanced Nurse Practitioner in Breast Care, St James’s Hospital. She presented at a Satellite Symposium on “The

Role of Cancer Nurses in the Management of gBRCAm HER2- Breast Cancer”. Ms Hanhauser spoke to her experience developing a decision aid for women identified as having a higher lifetime risk of developing breast cancer due to having a BRCA1/2 alteration. This is a part of her Cancer Nursing Research Award which she received in 2019 (CNRA19HAN) and is co-funded by the Irish Cancer Society and the National Cancer Control Programme.

This symposium highlighted the surgical management of genetic risks, nursing considerations for PARP inhibitors for managing gBRCAm HER2 breast cancer (Santiago González Santiago, MD), and provided insights into the patient experience (Eva Schumacher-Wulf).

Another Irish Cancer Society researcher presenting at EONS16 was Ms Sophie Mulcahy Symmons, who was invited to speak about her research on promoting cancer screening among under-represented populations. Ms Mulcahy Symmons, a social, nursing and allied health doctoral scholar, is currently undertaking her research titled ‘Promoting HPV Cervical Screening: co-designing an educational intervention to overcome barriers and promote screening uptake in underrepresented groups’ (CRS21SYM), supervised by Dr Aoife de Brun and Dr Amanda Drury in University College Dublin. This

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

session, focusing on health promotion, prevention and screening, showcased research being carried across Spain, Ireland, Croatia, and Korea.

More broadly, the conference covered a range of fascinating research projects, including the opening keynote presentation, delivered by Prof Daniel Kelly (Cardiff University) which detailed nurse-led interventions for symptom management, and highlighted the vital role that nurses play in this domain. The second keynote, presented

by Dr Gülcan Bağçivan (Koç University), spoke to the priorities for future research in cancer nursing. Technological advances in improving care for people affected by cancer, and caregivers for people with cancer, were highlighted as the core area of interest, and discussion also focused on Public and Patient Involvement (PPI).

EON16 was a fantastic showcase of the high-quality research being carried out by oncology nurses and allied health professionals internationally. The Irish oncology research community was wellrepresented, with many Irish Cancer Society researchers disseminating their work.

We will continue to support innovative and patient-centred research, and to recognise those researchers, support staff, and PPI contributors who have gone above and beyond to further the Irish cancer research landscape.

In 2023, the Irish Cancer Society funded over 100 researchers and awarded 30 new projects.

In recognition of this ongoing incredible work, our forthcoming Annual Research Awards, which takes place on 24 February at Regent’s House, Trinity College Dublin, will acknowledge and pay tribute to the great work in our research community. The Awards are free to attend and anybody with an interest in cancer research is more than welcome to attend to hear shortlisted PhD and Senior Researchers of the Year present their work. Award winners will be announced on the night.

Looking ahead, the Irish Cancer Society is delighted to have a number of upcoming opportunities to apply for funding in 2024, including: • Our summer studentships, which are currently accepting applications; • Our Scholarships (February); • Our Networking awards and Project Seed Funding (March); • Our Allied Health Professional Research Awards (April); • Our Patient Advocate in Research Champion Awards and our PPI in Research Awards (May).

As always, please do stay up to date with our funding calls through our research newsletter, or alternatively, get in contact with any queries at: research@irishcancer.ie.

Myeloma

53

High-Risk Multiple Myeloma Written by Dr Roisin McAvera (Postdoctoral Researcher RCSI), Miss Niamh McAuley (PhD Student RCSI), Prof Ann Hopkins (Associate Professor RCSI), Prof Siobhan Glavey (Clinician-Scientist Beaumont Hospital/RCSI)

Introduction Multiple myeloma (MM) is a haematological malignancy characterised by the clonal expansion of malignant plasma cells in the bone marrow.

MM manifests clinically as hypercalcaemia, renal failure, anaemia and bone lesions (known as CRAB features), with a median age of diagnosis of 71 in Ireland.1 MM affects around 384 people in Ireland each year1 and despite advancements in treatments remains incurable in 2024, as patients eventually relapse.

At a genomic level MM is extremely heterogeneous, meaning patients present with a wide range of different genetic abnormalities. As a result, patient outcome and response to treatment also varies. Despite this, personalised treatment plans are still in their infancy relative to those in some of the more common solid cancers, with MM patients generally treated in a similar manner. Treatment of MM normally consists of a combination of two, three or even four drugs from different classes. Treatment approaches vary, depending on patient fitness, co-morbidities, disease features and eligibility for an autologous stem cell transplant (ASCT). Initial treatment in Ireland at present consists of one of the following National Cancer Control Programme (NCCP)-approved

regimens; RVD (bortezomib, lenalidomide, dexamethasone), VMP (bortezomib, melphalan, prednisone), CyBorD (cyclophosphamide, bortezomib, dexamethasone), Rd (lenalidomide, dexamethasone) or most recently D-VTD (daratumumab, bortezomib, thalidomide, dexamethasone).

Notwithstanding significant improvements to patient prognosis as a result of these drug combinations, the median survival of MM patients is currently still low, at around 6 years.2 However, in reality patient outcome varies significantly.

‘High-risk’ MM patients tend to

Dr Roisin McAvera

Niamh McAuley

have a median survival of 2-3 years, whilst for ‘standard-risk’ patients this is 7-10 years.2 There are several methods to identify high-risk patients and, as a result, a major clinical challenge is the lack of standardisation.

Ideally, a standardised approach to risk-stratification would aid with streamlined characterisation of patient response in different risk groups, and potentially enable risk-adapted treatment plans in the future. In this article, we will discuss some of the commonly employed methods to identify high-risk MM, with a focus on those related to our own research at the Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin.

Current Risk Classification Most current classification systems used for MM incorporate common cytogenetic abnormalities as detected by fluorescence in situ hybridisation (FISH). In 2005, the International Myeloma Working Group (IMWG) introduced the International Staging System (ISS) to stratify patients into three prognostic groups. ISS criteria are based on the clinical levels of serum β2 microglobulin and serum albumin. In 2015, this was revised (R-ISS) to include the level of lactate dehydrogenase (LDH) and several cytogenetic abnormalities, specifically high-risk cytogenetic abnormalities t(4;14), t(14;16) or del(17p).3 The R-ISS criteria are shown in Table 1.

Table 1. Revised International Staging System (R-ISS) for Risk Classification of MM

Stage I

All of the following: • Serum albumin ≥3.5 gm/dL • Serum beta-2-microglobulin <3.5 mg/L • No high-risk cytogenetics • Normal serum LDH level Stage II Not fitting Stage I or III Stage III Both of the following: • Serum beta-2-microglobulin >5.5 mg/L • High-risk cytogenetics [t(4;14), t(14;16), or del(17p)] or elevated serum lactate dehydrogenase level Table 1. Revised International Staging System (R-ISS) for Risk Classification of MM Additionally, the Mayo Stratification for Myeloma and Risk-adapted Therapy (mSMART) guidelines | HPN • FEBRUARY HOSPITALPROFESSIONALNEWS.IE 2024 use several more genetic factors to guide genetic risk, such as gain(1q), p53 mutation, and gene

Stage III

Both of the following: • Serum beta-2-microglobulin >5.5 mg/L • High-risk cytogenetics [t(4;14), t(14;16), or del(17p)] or elevated serum lactate dehydrogenase level Table 1. Revised International Staging System (R-ISS) for Risk Classification of MM

Myeloma

54

Additionally, the Mayo Stratification for Myeloma and Risk-adapted Therapy (mSMART) guidelines use several more genetic factors to guide genetic risk, such as gain(1q), p53 mutation, and gene signatures (Table 2) (4). Profiling – MMProfiler ™ SKY92 Gene Expression

Gene expressionTrisomies profiling (GEP) has become increasingly popular in MM risk prediction, offering better Table 2. The mSMART Guidelines Standard-Risk t(11;14) standardisation and sensitivity than FISH. Accordingly, several gene signatures that can accurately t(6;14) identify molecular subgroups of MM patients and predict prognosis have been identified. To date, two High-Risk High-risk genetic abnormalities: gene signatures have  been t(4;14)commercialised – the MyPRS® which detects a 70-gene signature known as  t(14;16) GEP-70, and the MMProfiler™ which detects a 92-gene signature known as SKY92 (6, 7). Both are  t(14;20) commonly incorporated into ongoing clinical trials and have proved to successfully identify high-risk  del(17p) mutation patients. However, thep53MMProfiler™ is currently the only GEP test with CE-IVD (in vitro diagnostic)  gain(1q) approval, meaning it meets European standards to be used in a clinical setting. The MMprofiler™ R-ISS Stage III of 92 genes in MM plasma cells from patient bone marrow. Dependent on determines the expression High plasma cell S-phaseexpressed, a score is calculated and anything equal or above 0.827 the way these genes are collectively GEP: High risk signatures is considered high-risk with a predicted survival of less than 2 years (2). Additionally, the MMProfiler™ Double-hit MM: t(14;16), Any two high-risk factors can detect t(4;14), t(11;14), t(14;20) and gain(1q). Several studies have shown that using Triple-hit MM: Any three high-risk factors MMProfiler™ can overcome the need for FISH and in fact provide additional information often missed

by FISH. The MMProfiler™ is already used in private healthcare settings in the UK, and in several NHS Table 2. The mSMART Guidelines clinical trials. We are currently investigating its use in Ireland in newly-diagnosed MM, and our Roughly half of MM patients present with trisomies of odd-numbered chromosomes, and generally preliminary results show a particularly high proportion of Irish patients are classified as high-risk this is associated with better prognosis (5). Translocations t(11;14) t(6;14) are considered to only Additionally, the Mayo Stratification is currently the can predict treatment response, described in more detail later in this andMMProfiler™ (>30%).

Several trials are article. also Additionally, investigating whether response, GEPMMProfiler™ test with CE-IVD (incan vitro with treatment preliminary results showing it for Myeloma andeffect Risk-adapted del(13) found have a neutral on prognosis, observed in 15-20% andis2% of patients respectively. t(4;14) is predict diagnostic) approval, meaning can aid clinical decision making to Therapy (mSMART) guidelines in 50% of patients and predicts observed inmore around 10-15% of patients, whilst areit present in only 2-5% 1% with preliminary results showing it t(14;16) can aidand making to and escalate or deescalate treatment meets European standards escalate or deescalate treatment use several genetic factors poor outcome, however itclinical ist(14;20) also decision be patient used in outcome. a clinical setting.

(PROMMIS trial, NCT02911571). to guide genetic risk, such and as all considered not included in current classification of patients respectively, to have a detrimental effecttoon (PROMMIS trial, with NCT02911571).

ItThis is highlights hoped that will ultimately justify incorporation The data MMprofiler™ determines It is hoped that these data of will the gain(1q), p53 mutation, gene guidelines. the needthese Del(17p) is associatedand loss of p53 and is found in around 10% of newly-diagnosed patients. the expression of 92 genes in ultimately justify incorporation signatures (Table 2). for ongoing improvement of riskMMProfiler™ routine MM diagnostic and/or treatment workflows Gain(1q) is presentinto in around 35-40% of patients, and is often found alongside del(1p), present inin Ireland.

MM plasma cells from patient of the MMProfiler™ into routine stratification systems.

4

Roughly half of MM patients

boneabove marrow.

Dependent on the MM diagnostic and/or treatment around 20%trisomies of casesof(5).

However, Gene del(1p) is currently not included in the classification present with oddExpression Profiling – way these genes are collectively workflows in Ireland.

Interestingly, both1and gene signatures herelater include many located on chromosome 1. In numberedChromosome chromosomes, systems. abnormalities are described in more detail in this article.

MMProfiler ™described SKY92 expressed, a scoreAdditionally, isgenes calculated Interestingly, both gene generally this is associated with and anything equal or above del(13) is found in 50% of patients and predicts poor outcome, however it is also not included in expression profiling (GEP) fact, 30% of5 Translocations genes makingGene up GEP-70 are located on0.827 chromosome 1, with most upregulated genes on signatures described here better prognosis. is considered high-risk has become increasingly popular current classification guidelines. This highlights the need for ongoing improvement of survival risk- of less include many genes located on t(11;14) and t(6;14) are considered with a predicted chromosome 1q, on 1p. Several of the SKY92 genes are also on1. chromosome MM risk prediction, offering chromosome In fact, 30% to have a neutral effect on and mostindownregulated stratification systems. than 2 years.7 Additionally, the better standardisation and

of genes making up GEP-70 prognosis, observed in 15-20% and MMProfiler™ can detect upregulation t(4;14), 1, as respectively.

NUF2 and LBR. From our have t(14;16), identified of NUF2, located sensitivity thanown FISH. analysis, Accordingly, wet(11;14), are located on chromosome 1, on 2%such of patients t(4;14) t(14;20) and several gene signatures that can with most upregulated genes is observed in around 10-15% of gain(1q).

Several studies have 1q, as a potential driver ofaccurately the SKY92 high-risk phenotype. identify molecular disease on chromosome 1q, and most patients, whilst t(14;16) and t(14;20) shown that using MMProfiler™ are present in only 2-5% and 1% of patients respectively, and all considered to have a detrimental effect on patient outcome. Del(17p) is associated with loss of p53 and is found in around 10% of newly-diagnosed patients.

Gain(1q) is present in around 35-40% of patients, and is often found alongside del(1p), present in around 20% of cases.5 However, del(1p) is currently not included in the above classification systems.

Chromosome 1 abnormalities are

Chromosome 1q

subgroups of MM patients and predict prognosis have been identified. To date, two gene signatures have been commercialised – the MyPRS® which detects a 70-gene signature known as GEP-70, and the MMProfiler™ which detects a 92-gene signature known as SKY92.6, 7 Both are commonly incorporated into ongoing clinical trials and have proved to successfully identify high-risk patients. However, the

can overcome the need for FISH and in fact provide additional information often missed by FISH. The MMProfiler™ is already used in private healthcare settings in the UK, and in several NHS clinical trials. We are currently investigating its use in Ireland in newly-diagnosed MM, and our preliminary results show a particularly high proportion of Irish patients are classified as high-risk (>30%). Several trials are also investigating whether MMProfiler™

downregulated on 1p. Several of the SKY92 genes are also on chromosome 1, such as NUF2 and LBR. From our own analysis, we have identified upregulation of NUF2, located on 1q, as a potential driver of the SKY92 highrisk disease phenotype.

Chromosome 1 instabilities are the most common genomic alterations contributing to MM pathogenesis, resulting in the gain/amplification of chromosome arm 1q or the loss of regions on the Chromosome 1q shorter 1p arm. These chromosome 1 cytogenetic abnormalities are indicative of high-risk disease.

Chromosome 1 instabilities are the Various tumour suppressor genes are located on 1p. Downregulation or loss of such genes associate most common genomic alterations contributing1q to MM with worse survival. Moreover, 30% of patients present with gain or amplification at pathogenesis, diagnosis. resulting in the gain/amplification Abnormalities of 1q may induce increased genetic instability in MM, and typically manifest with Table 3: Chromosome 1 inferior prognosis.

Although both copy number variations of chromosome 1q are considered “highabnormalities associated with MM risk”, gain(1q) does not appear to be as detrimental as amp(1q) (Table 3).

Gain(1q) One extra copy of some portion of chromosome 1q (3 total copies) Amp(1q) Two or more extra copies of chromosome 1q (4 or more total copies) Del(1p) Poor prognosis due to downregulation/ loss of tumour suppressors Table 3: Chromosome 1 abnormalities associated with MM. As chromosome 1 is the largest human chromosome, a plethora of possible therapeutic candidate

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

55

of chromosome arm 1q or the loss of regions on the shorter 1p arm. These chromosome 1 cytogenetic abnormalities are indicative of high-risk disease.

Various tumour suppressor genes are located on 1p. Downregulation or loss of such genes associate with worse survival. Moreover, 30% of patients present with gain or amplification 1q at diagnosis.

Abnormalities of 1q may induce increased genetic instability in MM, and typically manifest with inferior prognosis. Although both copy number variations of chromosome 1q are considered “high-risk”, gain(1q) does not appear to be as detrimental as amp(1q) (Table 3).

As chromosome 1 is the largest human chromosome, a plethora of possible therapeutic candidate genes reside in tow. Interestingly, patients with chromosome 1 alterations have not benefitted from novel treatments as well as other genetic subgroups. To address this, our research team is designing and testing novel therapies for the protein products of the gene F11R which is located on 1q23.3. Additionally, we are investigating the function of NUF2, also on 1q23.3. High expression of either of these genes is associated with inferior outcomes in MM. F11R encodes the JAM-A protein whose overexpression has been associated with poor patient prognosis in various cancers (breast, lung, glioma) and most recently in MM. JAM-A is found on diverse cell types, where it plays physiological roles in tight junction formation, angiogenesis and leukocyte extravasation. As the pathophysiological overexpression of JAM-A has been linked with various oncogenic traits; it is intriguing to speculate that attenuation of this protein may impair MM progression. Moreover, we have seen an association between high F11R expression and gain(1q) which further supports its exploration as a novel potential target in high-risk MM patients.

The NUF2 gene is part of the SKY92 gene signature, and is upregulated in high-risk MM. Similar to F11R we see a link between high expression and presence of gain(1q). NUF2 facilitates normal chromosomal segregation and centromere microtubule attachment. Abnormal expression of NUF2 leads to mitotic dysregulation and further chromosomal instability associating with reduced survival.

We aim to find novel therapies that may target high NUF2 expression.

Extramedullary Disease In rare cases, extramedullary disease (EMD) may also occur and is characteristic of high-risk MM. This is a particularly aggressive manifestation of MM whereby the malignant plasma cells have become independent of bone marrow and may infiltrate other organ systems. This occurs in around 7% of MM patients at diagnosis (primary EMD), and up to 20% at the relapsed stage (secondary EMD).8 Prognosis is extremely poor, with survival rates of less than 3 years at diagnosis, and less than 1 year in refractory patients. The incidence of EMD is on the increase, potentially because most novel therapeutics target the bone marrow and thus surviving cells post-treatment have adapted mechanisms to survive outside of this microenvironment.

Regarding the genomic make-up of EMD in MM, definitive studies are currently lacking. However, the few that have been performed generally show an increased rate of high-risk abnormalities in patients presenting with EMD.9 Examples include t(4;14), gain(1q) and del(13). Moreover, t(11;14), which is generally considered standard-risk, is less likely to occur in EMD. Patients classified as GEP-70 high-risk are also five times more likely to experience EMD than standard-risk patients.

Of interest, several studies have shown high chromosome 1 instability in EMD patients, namely deletions of 1p and gains of 1q, reinforcing the role chromosome 1 plays in high-risk disease. We currently have an ongoing study investigating the genetics of EMD in Irish MM patients.

Conclusion High-risk MM represents an aggressive subtype of MM with particularly poor outcome. How high-risk disease is defined can vary, due to the heterogeneity of the disease and varying clinical manifestations. We propose that standardising how it is defined is necessary to understand its underlying disease biology. Currently, there are no personalised therapies that specifically target high-risk MM, and thus research should aim to find novel targets. At RCSI, we are trialling the use of the MMProfiler™ test to aid with risk-classification in Ireland, and are investigating several molecular markers of highrisk disease (JAM-A and NUF2) as

potential new therapeutic targets.

Their location on chromosome 1 makes them even more compelling objects of investigation, since chromosome 1 abnormalities are a common occurrence in high-risk MM. Additionally, presentation of EMD is associated with high-risk disease, and we are currently studying its genetic make-up to better understand its pathogenesis. Ultimately, we hope that identifying and understanding high-risk MM will lead to riskadapted therapy approaches and improve outcome for this poor prognostic group.

Empowering Patients In response to a lack of patientfriendly materials on MM research, the MM research group in RCSI recently launched a patient-driven resource discussing MM research in Ireland with the support of the Health Research Charities Ireland, the Health Research Board and Breakthrough Cancer Research.

Co-developed by patients, clinicians and researchers, this booklet aims to aid patients and their caregivers in understanding their role in MM research. It is essential to equip patients with knowledge to not only navigate their diagnosis, and treatment options but also to develop an understanding of informed consent and how they may contribute to advancing MM research in Ireland. This booklet can be freely downloaded using the following QR code.

References 1. Ireland NCR. Cancer in Ireland 1994-2022. 2022.

2. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management.

Am J Hematol. 2022;97(8):1086107.

3. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al.

Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015;33(26):2863-9.

4. Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013;88(4):360-76.

5. Kumar SK, Rajkumar SV. The multiple myelomas - current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol. 2018;15(7):40921.

6. Shaughnessy JD, Jr., Zhan F, Burington BE, Huang Y, Colla S, Hanamura I, et al. A validated gene expression model of highrisk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109(6):2276-84.

7. Kuiper R, Broyl A, de Knegt Y, van Vliet MH, van Beers EH, van der Holt B, et al. A gene expression signature for high-risk multiple myeloma.

Leukemia. 2012;26(11):2406-13.

8. Bansal R, Rakshit S, Kumar S. Extramedullary disease in multiple myeloma. Blood Cancer J. 2021;11(9):161.

9. McAvera R, Quinn J, Murphy P, Glavey S. Genetic Abnormalities in Extramedullary Multiple Myeloma. International Journal of Molecular Sciences.

2023;24(14).

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

56 News

¤10m to Support Core Mental Health Minister for Mental Health and Older People Mary Butler

Recently, the Sharing the Vision National Mental Health Conference took place at Dublin Castle.

The Conference provided an opportunity for stakeholders to discuss developments in national mental health policy and delivery, and to review how Sharing the Vision is driving the delivery of a modern, patient-centered mental health service which is focused on best practice, innovative service development, and improved service delivery. The Conference

was convened and opened by Minister for Mental Health and Older People Mary Butler with contributions from Taoiseach Leo Varadkar and Minister for Health Stephen Donnelly.

Opening the Conference, Minister Butler said, "Over the lifetime of this government, investment in mental health services has grown to ¤1.3 billion. Today’s announcement of a further ¤10 million to support the clinical programmes and youth mental

health, further highlights the government’s recognition of mental health as a central component to overall health. I look forward to working with colleagues in my department and the HSE to identify service improvements and innovations that can be underpinned and delivered through this funding."

The Conference, organised by the Department of Health with the support of the Health Service Executive (HSE), marks the end of

the first phase of implementation of the national mental health policy, and provides an opportunity to reflect on the successes and challenges over the last three years.

Minister Butler stated, "Ensuring that the voice of patients, and lived experience is embedded in mental health services and policy implementation is so important.

Mental health services should not be developed in a vacuum, and only by ensuring that the voice of those who use services, and those who have experienced mental health difficulties and have experienced recovery, should always be taken into account.

Only by doing so can we ensure that our policies and services are modern, and person-centred. In 2023, 19,000 people accessed Mental Health Recovery Colleges across Ireland. These colleges have been developed with the voice of those at the very heart of its model, those that are receiving support from these services. The success of these colleges further exemplifies how listening to the lived experience, can positively impact on health services."

Investigating Lewy Body Dementia Trinity research team awarded ¤2.49m by the Health Research Board to investigate Lewy Body Dementia (LBD) which accounts for 20% of the nearly 65,000 people with dementia in Ireland, but fewer than 5% of those affected receive a formal diagnosis.

Researchers will undertake the four-year ‘EMERALDLewy program’ following the award. Lewy body dementia (LBD) includes Parkinson's dementia (PDD) and dementia with Lewy body (DLB). LBD can be characterised by cognitive difficulties, vivid hallucinations and sleep problems, but is a ‘chameleon of sorts’ making its definitive diagnosis difficult.

Patients can go through years of misdiagnosis or remain undiagnosed making life incredibly challenging for them and those caring for them.

The EMERALD-Lewy program will improve the diagnosis, management, and lived experience of patients with LBD and their carers, and is the first large scale

program of research for the Lewy body dementias (LBD) in Ireland.

Gaps in diagnosis and care will be addressed in several ways by improving the rate and quality of diagnosis and management of LBD. Researchers led by Professor Iracema Leroi will support ‘living well’ with LBD by better understanding quality of life, daily lived experiences and peer support. Finally, together with people with LBD and their families, the research team will shape policy and practice to improve quality of life and share knowledge about LBD in Ireland.

This funding will significantly improve diagnostic practices and support in LBD, which will have far-reaching positive effects on individuals, families, and society at large by providing appropriate treatment and support, reducing inequity in diagnosis and treatment, and improving mental health and well-being.

Professor Iracema Leroi, Geriatric Psychiatry, Trinity College Dublin,

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

St James’s Hospital, Global Brain Health Institute (GBHI) and Principal Investigator, said, “This funding from the HRB is a fantastic opportunity to finally move the agenda forward for the 10,000 people with Lewy body dementia living in Ireland.

Improving the recognition of and care pathways for LBD is essential to improve quality of life when living with dementia.”

Because dementia care cuts across disciplines, EMERALDLewy will be conducted by an interdisciplinary team of researchers, clinicians (from geriatric psychiatry, neurology, medicine of the elderly), health economists, psychologists and other disciplines from across Ireland. This type of crossdiscipline working is essential to address the gaps in diagnosis and care for the LBD community in Ireland.

A key element of the program will be patient and carer involvement and participation. Ken Greaney , co-founder of Lewy Body

Ireland and co-applicant for the EMERALD-Lewy program and whose Dad, Dave lives with LBD welcomes the prospect of the positive impact that the programme will make to the lives of people with LBD. Ken added, “It took 7 long years for my Dad Dave to get his diagnosis of Lewy Body Dementia. While it is far too late for him, the Emerald Lewy Project can be part of his legacy, so that we know his suffering was not in vain. Thousands of other people because of Emerald Lewy will no longer travel that road. This project has the power the change the entire landscape of how this cruel illness is diagnosed and understood, helping those who need it, when they need it most.”

Trinity’s award is one of eight successful Applied Programme Awards from the Health Research Board (HRB). The award is valued at ¤2,499,965. The awards were specifically designed to ensure that knowledge generated from the research can be quickly put into policy and/or practice.

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MGD: Meibomian Gland Dysfunction TBUT: Tear Break Up Time 1. Tauber J, Berdy GJ, Wirta DL, Krösser S, Vittitow JL; GOBI Study Group. NOV03 for dry eye disease associated with meibomian gland dysfunction: results of the randomized phase 3 GOBI study. Ophthalmology. 2023;130(5):516-524. 2. Sheppard JD, Kurata F, Epitropoulos AT, Krösser S, Vittitow JL; MOJAVE Study Group. NOV03 for signs and symptoms of dry eye disease associated with meibomian gland dysfunction: the randomized phase 3 MOJAVE study. Am J Ophthalmol. 2023;252:265-274.

3. Steven et al.,2015. Journal of Ocular Pharmacology and Therapeutics, 31(8), pp.498-503.

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58 News

Proof of Concept Award Professor Conor Buckley

The European Research Council (ERC) has announced 102 new proof-of-concept (POC) grants for European researchers, bringing the total number of awardees from last year’s competition rounds to 240.

Professor Conor Buckley, principal investigator in AMBER, the SFI Centre for Advanced Materials and BioEngineering Research, and Professor in Biomedical Engineering in Trinity’s School of Engineering, has secured the ¤150,000 funding for iDISC. Professor Buckley is also affiliated with the Trinity Centre for Biomedical Engineering, and

the Trinity Biomedical Sciences Institute, and is an Honorary Associate Professor in RCSI.

treating disc degeneration, offering new hope and insights for patients suffering from back pain.

He will develop injectable biomimetic hydrogel systems for the lower back that aim to halt degeneration and restore natural biomechanical function through minimally invasive spine treatment strategies.

“This research opens new horizons in minimally invasive spine treatment strategies but also has the potential to enhance patient quality of life, reduce healthcare expenses, and minimise lost productivity throughout the European Union.”

This ERC POC builds on previous research funding to Prof Buckley’s lab from the ERC, Science Foundation Ireland and the Irish Research Council, and provides a continuation of the development of next-generation injectable biomaterials for tissue repair.

iDISC will receive the funding over an 18-month period to progress biomechanical testing, pre-clinical evaluation, and marketing and commercialisation evaluation.

Professor Buckley added, “This Proof of Concept award provides the necessary funding to pioneer innovative solutions in treating back pain, which affects over 600 million people worldwide and is the single leading cause of disability in people under 45 years of age.”

As well as the three main priorities identified, the need for improved staffing was emphasised, along with access to specialist acute care and support for mental health.

Stroke survivors and carers also thought that there needed to be more attention paid to improving the speed of access to services for people with more unusual or atypical stroke symptoms.

based service planning a key part of the Sláintecare strategy.

stroke recovery, and support for mental health.

“We hope this study can contribute to the broader discussion on stroke care, informing policy and practice not only in Ireland but other countries with similar healthcare challenges.”

A major challenge identified by stroke survivors and their families was the difficulty of navigating the care system, compounded by inadequate communication and information dissemination.

Significant difficulties

Dr Eithne Sexton, Lecturer, RCSI School of Population Health and research lead, commented: “These findings point to a need for stroke services that are more consistent nationally and better resourced based on an understanding of the diverse needs of stroke survivors and their families. This type of population-

Stroke survivors and carers related many positive experiences of stroke care through interviews, surveys and a stakeholder meeting, but also revealed significant difficulties in accessing needed services and supports.

This included problems accessing rehabilitation, home care hours, equipment to support

'Priorities for developing stroke care in Ireland from the perspectives of stroke survivors, family carers and professionals involved in stroke care: A mixed methods study' was carried out in collaboration with The Irish Heart Foundation and researchers from UCC and Beaumont Hospital.

It was funded by the Health Research Board.

Speaking following the announcement of iDISC’s ERC Proof of Concept Award Professor Buckley said, “The ERC POC award is a fantastic opportunity to accelerate my lab’s research in developing new strategies in

Priorities for Stroke Care A new study from RCSI’s School of Population Health has found that future developments to Irish stroke services, according to those who are most impacted, must prioritise specialist communitybased rehabilitation, ongoing support for life after stroke and better information and support for navigating services.

The study, published in PLOS ONE, is the first in Ireland to feature the opinions of those directly affected by stroke; including survivors, their family carers and healthcare professionals. The researchers made a concerted effort to ensure that survivors with communication and cognitive difficulties were included.

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

News 59

Viatris scores victory for Irish charity!

Viatris employees joined the Irish Wheelchair Association last month in the Sport Ireland Campus, Blanchardstown, Dublin, for a fast-paced and entertaining wheelchair basketball event. The experience raised over EURO 6,000 for the registered charity, which runs corporate team building days with the underlying aims of changing attitudes and facilitating access to sports and support facilities for people with disabilities. The event is part of a pan-European #BuildingHealthierCommunities initiative at Viatris, a global healthcare company, which aims to engage employees and local healthcare communities across Europe to support social and environmental projects. The unique, fun-filled experience was enjoyed by 100 employees from Ireland and across Europe.

Melissa Fisher, Country Manager Commercial for Viatris Ireland explained, “We’re privileged to join the Irish Wheelchair Association in this wonderful Sport Ireland facility today and to experience adapted physical activity through wheelchair basketball.

“Our value is to empower people to live healthier at every stage of life and the team within Viatris decided to take this value one step further. When we think about what a community means, it means all of us collectively; it’s where we live, where we work, where our families are.

“If we localise our global mission, what that translates into is ‘let’s try and make the whole community healthier’ and if we can, it has a natural impact.”

Melissa went on to say, “In Ireland we support approx. 30 Irish charities and organisations each year, nominated and chosen by our employees. We are humbled by these partnership efforts as we see they can make a real difference in the local community. People can truly be empowered to live healthier when their communities are thriving.

However, these collaborations also influence our employees, helping them not only understand the challenges of the communities we serve, but also embrace what makes individuals unique and realise their own potential.

Viatris in Ireland has a large footprint: with over 1600 colleagues across the island and five manufacturing sites, Melissa believes it is important therefore, to understand the key issues at the forefront of communities up and down the country.

Christopher Hoey, Acting Chief Executive Officer, Irish Wheelchair Association commented: “One in four people in Ireland lives with a disability. As a population we are living longer and, consequently, the likelihood of acquiring a physical disability is higher. In times of funding challenges for Irish charities, we welcome the continued support of companies like global healthcare company,

Viatris, which help us to maintain our much-needed services in the community. Our wheelchair basketball activities are open to all to avail of and have fun playing, while building on the fundamental values of being a team and raising vital funds. We’re delighted that the funds donated at the Viatris event today will help us in our efforts to expand our sports programme in the West of Ireland.”

“Ireland is synonymous with the word ‘community’ and it is imperative for Viatris that we can showcase how we support that.

Fundamentally, our core isn’t just about medicine, it’s about what else we can do to bring real value to people’s lives and to their health.

“Our ecosystems must evolve and be more deliberate if we are to be a truly inclusive society. Perhaps we start with doing simple things but we do those simple things consistently – and if we do them consistently well – we can connect a little bit better and a little bit more.”

Viatris’ #BuildingHealthierCommunities initiative supporting social and environmental projects across Europe. Image: Viatris/Roger Kenny

Wheelchair basketball teamwork in action, as Viatris colleagues aim for a basket. Image: Viatris/Roger Kenny

From L to R: Aishling Goulden, Stephen Callanan, Sam Jablansky (IWA), Janet Hand, Róisín Wallace, Melissa Fisher, John Fulham (IWA), Emma Travers, Paul Ryan (IWA) - Image: Viatris/Roger Kenny

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

60 Clinical R&D GROUNDBREAKING EV-302 TRIAL SIGNIFICANTLY EXTENDS OVERALL SURVIVAL AND PROGRESSION-FREE SURVIVAL IN PATIENTS TREATED WITH ENFORTUMAB VEDOTIN AND PEMBROLIZUMAB IN FIRST-LINE ADVANCED BLADDER CANCER Astellas Pharma recently announced results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) for enfortumab vedotin in combination with pembrolizumab versus chemotherapy. The combination improved overall survival (OS) and progression- free survival (PFS) with statistically significant and clinically meaningful results in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2023 as part of the Presidential Session (Abstract #LBA6).

The EV-302 study met its dual primary endpoints of OS and PFS, compared to platinum and gemcitabine chemotherapy.

Patients treated with enfortumab vedotin and pembrolizumab experienced: • Median OS of 31.5 months (95% CI: 25.4-NR) compared to 16.1 months (95% CI: 13.9-18.3) in the chemotherapy arm. o Significantly prolonged OS, reducing the risk of death by 53% compared to treatment with chemotherapy (Hazard Ratio [HR]=0.47; 95% Confidence Interval [CI]: 0.38-0.58; P<0.00001).

• An Independent Data Monitoring Committee determined that OS crossed the pre-specified efficacy boundary at interim analysis.

• Median PFS of 12.5 months (95% CI: 10.4-16.6) compared to 6.3 months (95% CI: 6.2-6.5) in the chemotherapy arm. o 55% reduction in the risk of cancer progression or death compared to treatment with chemotherapy (HR=0.45; 95% CI: (0.380.54); P<0.00001).

• Consistent OS results across all pre-defined subgroups, including cisplatin eligibility and PD-L1 expression level.

The most common (≥3%) Grade 3 or higher adverse events (AEs) related to treatment with enfortumab vedotin and pembrolizumab were rash maculo-papular, hyperglycemia, neutropenia, peripheral sensory

neuropathy, diarrhea, and anemia.

The safety results in EV-302 are consistent with those previously reported with this combination in EV-103 in cisplatin-ineligible patients with la/mUC. No new safety issues were identified.

Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas “The remarkable findings presented today demonstrate that the combination of enfortumab vedotin and pembrolizumab could offer longer survival and more time without disease progression for patients with advanced urothelial cancer. The presentation of this data is an important milestone for this patient population, and we look forward to continued discussions with regulatory authorities as we work to expedite bringing this therapy to those who need it most.”

Among secondary endpoints, results demonstrated a 68% confirmed objective response rate (ORR) (95% CI: 63.1-72.1, P<0.00001) in patients treated with enfortumab vedotin plus pembrolizumab, versus an ORR of 44% (95% CI: 39.749.2) in patients treated with chemotherapy. In the enfortumab vedotin plus pembrolizumab arm, 29.1% of patients experienced a complete response, and 38.7% of patients experienced a partial response, compared with 12.5% and 32.0% in the chemotherapy arm, respectively. The median duration of response (DOR) was not reached in the enfortumab vedotin plus pembrolizumab arm, versus 7 months (95% CI: 6.2-10.2, P<0.00001) in the chemotherapy arm.

The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatinor carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.

The EV-302 trial is intended to serve as the basis for global submissions and as the confirmatory trial for the

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

U.S. accelerated approval of this combination. In April 2023, the U.S. Food and Drug Administration (FDA) granted an accelerated approval to enfortumab vedotin in combination with pembrolizumab for the treatment of adult patients with la/mUC who are not eligible to receive cisplatin-containing chemotherapy based on tumor response rate and durability of response from the EV-103 trial.

The EV-302 trial is part of an extensive program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Topline results of the EV-302 trial were announced in September 2023.

irishoffice@consilienthealth.com.

NEW SMOKING CESSATION MEDICATION CITIDARON® (CYTISINE 1.5 MG TABLETS) LAUNCH IN IRELAND ON JANUARY 1ST, 2024

Access to the new service will be available at centres based in Dublin, Galway, Limerick, Louth and Meath. This will bring the total number of clinics offering female health consultations with a specialist GP to 27 nationwide.

In a significant advancement in the battle against nicotine addiction, Consilient Health Ireland, is delighted to announce the launch of their new prescription-only medication (POM), Citidaron®.

This novel treatment indicated for smoking cessation and reduction of nicotine cravings in smokers who are motivated to quit will be available to patients across Ireland from January 1st, 2024. In Ireland, approximately18% of individuals still smoke, many are struggling to quit, despite being aware of the known side effects.

Citidaron® is a nicotine-free, effective, fast treatment indicated for smoking cessation and reduction of nicotine cravings in smokers who are willing to stop smoking.2 Citidaron®, a plant alkaloid, targets the same receptors in the brain as nicotine, but with a stronger binding affinity and less stimulation.2 This means that it can help reduce nicotine cravings and withdrawal symptoms more effectively than nicotine itself, making it easier for individuals to quit smoking while potentially having fewer side effects due to the weaker overall stimulation of the receptors.

Ireland’s commitment to becoming a smoke-free country by 20251 means that such advancements could not only help individual smokers but also significantly impact public health initiatives.

With Citidaron’s introduction, the path to a smoke-free life is more accessible and supportive than ever before.

For more information on Citidaron visit https://www. consilienthealth.ie/ or contact

IRISH LIFE HEALTH ANNOUNCES CONTINUED EXPANSION Irish Life Health, one of Ireland’s leading health insurance providers, has announced the expansion of the female health specialist GP service, with access to a further 11 in-person Centric Health clinics, set to be available by the end of Q1 2024. Irish Life Health’s female health service offers an initial digital consultation with GPs who are specialist in female health issues, as well as direct access to an in-person consultation if a referral is required*.

Since the launch of this first of its kind female health consultation in August 2023, almost half the consultations are for issues relating to menopause which aligns with research commissioned by Irish Life Health in July 2023**, which found that almost half of 35 – 54 year olds are worried about perimenopause or menopause.

A further 1 in 3 appointments are for women aged 18 – 34 which highlights the need for such services amongst younger women in Ireland. The Irish Life Health research identified that 89% of 18 - 34 year olds want to understand more about female health with 75% curious about their fertility status.

The average consultation time through this service is 20 minutes, giving more time to women to discuss their female health concerns in comparison to a standard GP consultation.

The female health consultation offers Irish Life Health members access to a GP consultation by phone or video, potentially a diagnosis and a recommended course of action with an in-person appointment at one of Centric Health’s specialist female health clinics across Ireland. This benefit is available on all Irish Life Health plans.

To date, almost half of all digital consultations have required an inperson follow-up, with blood tests and scans being the most common services required.

Liz Rowen, Head of Marketing, Irish Life Health said: “Ensuring that our customers have quick and easy access to the care and advice they need is at the heart of what

61 we do. Women across Ireland have indicated that getting fast access to specialist female health expertise is difficult, which is why we developed this service and why we’re continuing to invest in this much needed offering in 2024.

Irish Life Health has committed to investing over ¤30m to build out digital and community-based health services, which includes this female health service and our digital doctor offering.

We are really pleased to see younger people accessing the service as we saw from our research that four in ten 18 – 24 year olds in Ireland are worried about menstruation issues, while four in ten 25 – 34 year olds are worried about fertility issues. I would urge any one of our female members that has such concerns to check out this service.”

Dr Maire Finn, one of Centric Health’s specialist GPs delivering this service for Irish Life Health, comments: “The research carried out by Irish Life Health** indicated that women wanted to know more about the health matters that relate specifically to them and that they were finding it hard to access specialist female health expertise.

We have seen from the response in the first four months that this new Irish Life Health female health consultation is an important and necessary step in providing specialised care and information that women need and want.”

The Irish Life Health survey, which was carried out amongst women aged 18+, revealed insights into perceptions of female healthcare in Ireland. Over half of respondents believe female healthcare is not well serviced in Ireland, while 38% are finding it difficult to get fast access to specialist female health expertise. *Access to the Female Health consultation is available to customers across all Irish Life Health hospital plans for ¤40 per visit (50% discount). Cover for inperson referrals varies by Plan. **Research conducted by Red C in July 2023, featuring a panel of 500+ female representatives aged 18+ NEW PODCAST SERIES LAUNCHED ON GYNAECOLOGICAL CANCERS, WHICH REPRESENT 12% OF ALL FEMALE CANCERS A new podcast series has been launched by The Irish Society of Gynaecological Oncology (ISGO) as a valuable resource for patients undergoing treatment for gynaecological cancers.

whilst most importantly, making a difference for those affected by cancer.”

In the Republic of Ireland, over 1,400 gynaecological cancers are diagnosed annually with 591 diagnosed annually in Northern Ireland, representing over 12% of female cancers. Symptoms of gynaecological cancer may include: abnormal vaginal bleeding or discharge, feeling full too quickly, bloating or difficulty eating, pelvic pain or pressure, abdominal or back pain, a more frequent need to urinate, constipation, itching burning changes of vulva and changes in vulval colour or skin. If you have been experiencing any of these, please visit your healthcare provider.

Dr. John Coulter, Cancer patient Bridget Carr, Dr. Dearbhaile Collins, President ISGO and Eoghan O Sullivan, Breakthrough Cancer Research. Picture by Chani Anderson @capturesbychani

Hosted by G.P., Dr. Doireann O’Leary, and sponsored by Breakthrough Cancer Research, the podcast series shares the stories and first-hand experiences of people who have had a cancer diagnosis. They are joined by healthcare professionals, who provide expert advice, and the podcasts also delve into cuttingedge research and advancements, which aim to improve survival and treatment options.

Episodes include topics focused on specific cancers like ovarian cancer (in particular PARP inhibition) and gestational trophoblastic disease, to topics which bridge all cancer types including experience of palliative care services.

People share their stories of being diagnosed with a genetic cancer syndrome and what this has meant for them and their family as well as patient and public involvement in research. They also explore the psychological and psychosexual consequences of cancer treatment.

Dr. Dearbhaile Collins remarked, “As President of ISGO, I am delighted to present our podcast series in collaboration with Dr. Doireann O’Leary. Our vision is to deliver accurate information to the public from both specialists and patients themselves, to create easily understandable and accessible audios. We are delighted with the engagement from Irish experts in their fields and the frank and insightful personal

experiences from patients. ISGO looks forward to being involved in future podcasts in other areas of gynaecological cancer.”

Tamsin Finlay, one of the contributors on the podcast series remarked “This was a very empowering and therapeutic platform to air my journey of infertility with cancer and my resilience to a state of acceptance and happiness.”

Dr. Doireann O’Leary says: “It’s a privilege to host the ISGO podcast. The patient voice is central to this series. I learned so much from the patient advocates who courageously shared their story and lived experience to help others. I also got to speak to the dedicated consultants who care for them; their lifelong dedication to providing evidence-based care with empathy is inspiring.

This series is a must listen for all women; we discuss gynaecological cancers, ‘red flag’ symptoms never to ignore, how to ‘speak up’ and advocate for yourself in the oftentimes overwhelming healthcare setting. We say the ‘unsaids’. For me, having these conversations was educational, uplifting and inspiring and I know it will be for the listener too!

Jenny Maginn told us “I was diagnosed with advanced ovarian cancer. A year of surgeries and treatments took my independence away and made me very reliant on family and friends. It was important to me after treatment to get back to as normal a life as possible. I wanted to feel valued and to be doing something worthwhile. The opportunity to create a podcast came at the right time. I was ready to be heard so that I could use my experience to help and give me a sense of purpose again. I feel empowered that I have found something I feel passionate about, that I can do and can feel valued for,

ISGO is an all-Ireland venture encompassing all gynaecological cancers whose aim is to advocate for patients through improvements in education training and research.

Breakthrough Cancer Research is Ireland’s leading research charity for poor prognosis cancers. It supports research all over Ireland in gynaecological cancers.

Sponsor Breakthrough Cancer Research is Ireland’s leading research charity for poor prognosis cancers and committed to funding research to improve cancer care and outcomes.

To access the series, please visit Dr. Doireann’s Podcast wherever you get your podcasts.

For further information and support regarding gynaecological cancers please visit: www.thisisgo.ie THÉA PHARMA MAYO SCHOOL ART COMPETITION With the theme “The Eyes are the Window to the Soul!”, Ireland’s No 1 choice for eye care Théa Pharma created and implemented a unique Art competition for Mayo secondary schools. Transition Year students in Co. Mayo were asked to get their creative juices flowing grabbing the opportunity to showcase their talent and charisma.

More than 60 students participated from Balla Secondary School, St. Brendan’s Belmullet, Ballyhaunis Community School, Sacred Heart Secondary School Westport and St. Joseph’s Secondary School, Castlebar. Among them the 10 most creative ideas were selected and presented in a lovely ceremony in Théa’s Headquarters in Castlebar on Tuesday December 12th. All 10 students participated along with their teachers and parents. From the 10, the 3 most charismatic and talented ones were singled out. The Grand

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62 Clinical R&D

Eyes Wide Open: Théa Pharma’s top 10 art competition finalists

Winner received ¤1,000, the second winner ¤500 and the third ¤250.

Théa Pharma’s Country Manager Diarmuid Gavin said: “This is a day that demonstrated all that Ireland stands for, the warmth, the talent, the promise of its younger generation and that our tomorrow is filled with promise because of these young students. This is a great day for Mayo and all its future potential. Everyday 1 out of 2 people suffer from Dry Eyes.

We are proud and honoured to raise awareness on the importance of Eye Care. The Eyes are the Window to the soul. Let’s take good care of them!”.

NEW CHAIR OF NATIONAL RARE DISEASE STEERING GROUP

Kellecher, College Principal at the UCD College of Health and Agricultural Sciences.

“Most important, I believe, is the planned consultative patient forum to facilitate patient input and engagement in all stages of the process.”

A rare disease is defined in Europe as a disease having a prevalence of fewer than 5 cases for every 10,000 persons. There are currently up to 8,000 described rare diseases.

Collectively, these diseases affect around 6% of the population, accounting for an estimated 300,000 individuals in Ireland.

The new Steering Group aims to address Rare Disease service gaps to ensure patients receive timely and accessible care.

It will also consider how best to integrate the European Reference Networks into the national health, as well as identify the core practical requirements of a Rare Disease Registry.

Assessing how best to promote awareness and research around rare diseases will also be a key area for the body.

Professor Cecily Kelleher has been appointed as chair of the newly established National Rare Disease Steering Group, a panel of experts tasked with formulating a plan for the management of rare diseases in Ireland.

The body will develop a new Rare Disease Plan that sets out the vision for the country’s rare disease services, including the actions required to achieve this.

“We will be considering how best to improve access and address gaps in Rare Disease services and to promote awareness among healthcare professionals and the public, employing International best practice and top-quality available research,” said Professor

SANOFI ANNOUNCES END OF PROGRAM EVALUATING TUSAMITAMAB RAVTANSINE AFTER A 2L NSCLC PHASE 3 TRIAL DID NOT MEET A PRIMARY ENDPOINT

An Independent Data Monitoring Committee (IDMC) found that tusamitamab ravtansine as a monotherapy did not meet its dual primary endpoint of progressionfree survival (PFS) compared to docetaxel. Despite an improved overall survival (OS) trend, termination of the program was based on non-improvement in PFS at the final analysis. Tusamitamab ravtansine had a similar safety profile as previously presented with a lower incidence of various important clinical categories of adverse events versus docetaxel.

Trial participants will have the option to stay on their current therapy if they are benefitting, as deemed by their provider, or to transition to an appropriate standard-of-care therapy.

Sanofi will continue exploring the potential of antibody tusamitamabbased ADCs and CEACAM5 research in several types of cancer.

Dietmar Berger, Chief Medical Officer and Head of Development said, “Our team is grateful to the patients, families and healthcare professionals involved in the tusamitamab ravtansine development program. Although the results are not what we hoped for, our research and work to advance potentially transformative therapies in areas of high unmet need for people living with cancer will not stop. We will continue to explore the potential of CEACAM5 as a biomarker in cancer types where it is highly expressed.”

CEACAM5 is a member of the CEACAM family of 12 glycoproteins and may drive cell adhesion and migration, as well as inhibit apoptosis, and may be overexpressed in many different cancer types.

ZITA WEST PRODUCT INFORMATION TZita West is a name synonymous with excellence in the world of fertility and pregnancy. For over 25 years, Zita West has been a trusted name for women and couples who are seeking support and guidance on their journey

to parenthood. From bestselling books on fertility and pregnancy to premium supplements and holistic therapies, the Zita West brand is the gold standard for those who value quality and expertise.

By listing Zita West products, you will be offering your customers access to a brand that has helped thousands of women and couples achieve their dream of starting a family. You can trust that the Zita West range is rigorously researched and developed by a team of experts, using only the highest quality ingredients and materials.

Whether your customers are seeking support with fertility, pregnancy, or postpartum recovery, the Zita West range has something for everyone. From conception support supplements to pregnancy teas and massage oils, every product is designed to support optimal health and wellbeing for both mother and baby.

By listing Zita West, you will be aligning your brand with a trusted and respected name in the world of fertility and pregnancy. Your customers will appreciate the opportunity to access these premium products, and you can feel confident knowing that you are offering them the very best.

Don’t miss out on the opportunity to add the iconic Zita West to your inventory today! https://www.dailymail.co.uk/femail/ commercehealth/article-11644239/ Fertility-expert-Zita-West-helpedcelebs-like-Kate-Winslet-conceivetips.html POOLBEG PHARMA: FURTHER DATA CONFIRMS POLB 001’S POTENTIAL IN CANCER IMMUNOTHERAPYINDUCED CYTOKINE RELEASE SYNDROME (CRS) Poolbeg Pharma, a biopharmaceutical company focused on the development and commercialisation of innovative medicines targeting diseases with a high unmet medical need, has announced promising in vivo results for POLB 001 in addressing cancer immunotherapy - induced CRS.

Sanofi is discontinuing the global clinical development program of tusamitamab ravtansine. The decision is based on the outcome of a prespecified interim analysis of the Phase 3 CARMEN-LC03 trial evaluating tusamitamab ravtansine as monotherapy compared to docetaxel in previously treated patients with metastatic nonsquamous (NSq) non-small cell lung cancer (NSCLC) whose tumors express high levels of carcinoembryonic antigenrelated cell adhesion molecule 5 (CEACAM5).

FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Zita West Product Information Zita West is a name synonymous with excellence in the world of fertility and pregnancy. For over 25 years, Zita West has been a trusted name for women and couples who are seeking support and guidance on their journey to parenthood. From bestselling books on fertility and pregnancy to premium supplements and holistic therapies, the

63 Positive study results POLB 001 demonstrated efficacy in reducing cancer immunotherapyinduced CRS in an in vivo animal model with CRS symptoms significantly improved following administration of POLB 001.

Reductions were seen in all serum proinflammatory cytokines tested.

The results, together with the data from the recent LPS human challenge trial, further support the Company’s strategic expansion of the Phase II ready POLB 001 to treat and prevent cancer immunotherapy induced CRS. The data strengthens and facilitates the expansion of patent applications for POLB 001 in cancer immunotherapy-induced CRS. Market opportunity estimated at over US$1 billion Largely due to the CRS risk (which can be life threatening), administration of cancer immunotherapies, such as bispecific antibodies, is currently restricted to cancer centres which limits uptake of these effective therapies. As an oral therapy to prevent or treat CRS, POLB 001 has the potential to enable broader use of cancer immunotherapies in an outpatient setting. The Company believes that POLB 001 represents a significant market opportunity estimated at > US$1 billion in Multiple Myeloma, High Grade Lymphoma and Acute Lymphoblastic Leukaemia alone.

Cancer immunotherapies are being widely developed across a broader range of haematological malignancies, solid tumours and immune inflammatory diseases, which represents an even greater market opportunity.

In the U.S., the American Cancer Society estimates that there will be 24.6 million cases of cancer by 20301,2. Cancer immunotherapies, such as bispecific antibodies and CAR T cell therapy, are rapidly moving into earlier lines of treatment in many tumour types, with these markets anticipated to grow to US$100bn+ (~35% CAGR) by 20303 .

Independent Advisory Board Supportive of POLB 001’s Potential Poolbeg convened an Independent Advisory Board with international Key Opinion Leaders, healthcare payers and clinical trial experts, which endorsed the attractiveness of POLB 001’s Target Product Profile (TPP) and its potential as an oral therapy to address the significant unmet medical need of cancer immunotherapy induced CRS. POLB 001 has been shown to reduce hyperinflammation without complete ablation of an effective

immune response, which makes it potentially a very attractive therapy for this disease area.

David Allmond, Chief Business Officer of Poolbeg Pharma, commented: “POLB 001 has the potential to revolutionise the impact of cancer immunotherapies by enabling safer and broader use in an outpatient setting, reducing healthcare resource utilisation and making these next generation cancer treatments more widely available to the patients that need them. The pharmaceutical sector is seeking an effective solution for CRS and, as an oral therapy, we believe there is a significant opportunity for POLB 001 to meet this critical unmet medical need and have a positive impact on global health.”

THE AKKERMANSIA COMPANY™ LAUNCHES THEIR TWO PIONEERING PRODUCTS CONTAINING PASTEURIZED AKKERMANSIA MUCINIPHILA MUCT IN IRELAND

with Stress Management, a blend of 30 billion pasteurized Akkermansia muciniphila mucT cells, chamomile extract, and essential B-vitamins. This tablet not only supports gut health but also contributes to psychological well-being. Additionally, The Akkermansia Company™ offers Weight Management with Glucose Control, a food supplement promoting weight management and blood sugar control. Each tablet contains 30 billion pasteurized Akkermansia muciniphila mucT cells, with EGCG Green Tea supporting weight control. Chromium helps maintain optimal glucose levels, and Vitamin B2 strengthens mucous membrane health.

Excitingly, these groundbreaking products have officially launched in Ireland since January 2024. The Akkermansia Company™ invites the Irish community to embrace these advancements, unlocking the potential of Akkermansia mucT for improved health and well-being.

BLACKROCK HEALTH INVESTS ¤1.5 MILLION IN NEUROSURGICAL TECHNOLOGY

An international leader in developing “next generation” probiotic and postbiotic supplements, The Akkermansia Company™ is on a mission to shift the focus of the microbiome health paradigm from symptoms to root cause. Founded in 2016

by Profs. Patrice Cani and Willem M de Vos (inventors on the Cani et al. application), the company discovered, named, patented, and developed Akkermansia mucT, which plays a major role in helping to maintain a healthy gut microbiome.

Blackrock Health, combining Hermitage, Blackrock, Galway and Limerick Clinics’, has invested ¤1.5 million in new neurosurgical technology that will facilitate robotic cranial and spinal surgery. The ExcelsiusGPS® Robotic Navigation Platform has been installed in the Hermitage Clinic and is now operational for spinal surgery, with training for cranial surgery due to take place before the end of Q1 2024. Once training has been complete, the Hermitage Clinic will be the first hospital in Ireland to offer cranial robotic surgery.

In a significant development for people living with Parkinsons Disease and other neurological conditions, the advanced technology solution will be used in

cranial surgery to place electrodes for people undergoing Deep Brain Stimulation Treatment (DBS). DBS is a long-term treatment option for patients with selected movement disorders, which involves implanting neurotransmitters in the brain. All Spinal and Cranial Neurosurgeons will be fully conversant in the use of the ExcelsiusGPS robot navigation platform. The team has already undertaken training and some consultants will participate in observerships in the United States to deliver new surgical techniques at Blackrock Health Hermitage Clinic.

The ExcelsiusGPS® can facilitate more minimally invasive surgeries, translating to smaller incisions, less tissue damage, reduced postoperative pain, shorter hospital stays, and faster recovery times.

The system is also designed to streamline the surgical workflow and reduce radiation exposure to surgeons and staff. This revolutionary robotic navigation platform is the world’s first technology to combine a rigid robotic arm and full navigation capabilities into one adaptable platform for accurate trajectory alignment in spine surgery.

Gordon Dunne, CEO of the Blackrock Health Hermitage Clinic said, “The ExcelsiusGPS® platform will have a huge impact for patients by improving safety and accuracy within operating theatres. The acquisition of the robotic platform marks an important milestone in neurosurgery not only in the Hermitage Clinic, but for patients across Ireland who will be treated with this technology. At Blackrock Health Hermitage Clinic, we are committed to surgical excellence and delivering new technologies to provide best in class care for our patients.”

Outcome from clinical trials demonstrate a significant relationship where Akkermansia mucT plays a crucial role in preventing the entry of harmful toxins and fats into the body.

The key to overcoming lifestyle diseases lies in restoring the natural levels of Akkermansia mucT, promoting a healthier life.

Acknowledging the significance of gut health, The Akkermansia Company™ has introduced a range of products to support overall well-being.

Among their innovative offerings is the Gut Support

HOSPITALPROFESSIONALNEWS.IE | HPN • FEBRUARY 2024

For patients taking apixaban or rivaroxaban with life-threatening or uncontrolled bleed

RELY ON THE ONLY ANTIDOTE TO SHUT OFF FXa INHIBITOR ACTIVITY1-3,* INDICATION For adult patients treated with a direct FXa inhibitor (apixaban or rivaroxaban) when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.1

ONDEXXYA (andexanet alfa) is the Only Approved Antidote to Shut-off FXa inhibitor Activity1-3

Rapid

Reverses FXa inhibition within 2 minutes after bolus1,†

Effective

93% decrease in FXa inhibitor activity in patients receiving apixaban (-93.3%, 95% CI: -94%; -93%)‡ and rivaroxaban (-94.1%, 95% CI: -95%; -93%)1

Consistent

79% of patients had excellent or good haemostatic efficacy at 12 hours (N=296)1,§ 79% of 169 patients taking apixaban and 80% of 127 patients taking rivaroxaban.1

Adverse events in ONDEXXYA-treated patients were non-serious and non-severe.5,II No thromboembolic events or serious or severe adverse events were observed.

The most common side effects were mild to moderate infusion-related reactions .1,¶ *In ANNEXA-A (n=31) and ANNEXA-R (n=39), randomised, double-blind, placebo-controlled studies conducted in healthy older volunteers (aged 50-75 years), ONDEXXYA bolus followed by continuous infusion was associated with a 92% (apixaban-treated subjects) and 97% reduction (rivaroxaban-treated subjects) in anti-FXa activity from baseline to nadir for low- and high-dose, respectively (P<0.0001). In these clinical trials no serious or severe adverse reactions were reported. The most frequently observed adverse reactions were mild or moderate infusion-related reactions. Refer to Summary of Product Characteristics for full safety profile.1,5; †And sustained throughout the 2-hour IV infusion in older, healthy volunteers1; ‡From baseline to nadir1; §Excellent ICH haemostasis: ≤20% increase in volume compared with baseline at both 1 and 12 hours; Good ICH haemostasis: ≤35% increase compared with baseline at 12 hours; Excellent GI haemostasis: Less than 10% decrease in corrected haemoglobin and haematocrit at 12 hours compared with baseline; Good GI haemostasis: ≤20% decrease (correction done by subtracting 1 g/dL from the haemoglobin or 3% from the haematocrit for each unit of packed red blood cells given) and ≤2 units of coagulation intervention required6; IIPooled safety in older, healthy volunteers; ¶PCC is not indicated to treat patients with FXa-inhibitor–related bleeding. Characterised by a range of symptoms, including flushing, feeling hot, dysgeusia, cough, and shortness of breath.1 CI, confidence interval; FXa, factor Xa; GI, gastrointestinal; ICH, intracranial haemorrhage; IV, intravenous; PCC, prothrombin complex concentrate; SmPC, summary of product characteristics.

References 1. Ondexxya. Summary of product characteristics. 2. Kcentra. Summary of product characteristics. 3. Praxbind. Summary of product characteristics.

4. Siegal DM, et al. N Engl J Med. 2015;373(25):2413-2424. 5. Connolly SJ, et al. N Engl J Med. 2016;375(12):1131-1141.

Abridged Prescribing Information 200 mg POWDER FOR SOLUTION FOR INFUSION (andexanet alfa) Consult Summary of Product Characteristics before prescribing.

Indication: ONDEXXYA is indicated for adult patients treated with a direct factor Xa (FXa) inhibitor (apixaban or rivaroxaban) when reversal of anticoagulation is needed due to lifethreatening or uncontrolled bleeding. Presentation: Powder in a 20 mL vial (Type I glass) with a stopper (butyl rubber). Pack size of four vials. Dosage and Administration: Restricted to hospital use only. Andexanet alfa is administered as an intravenous bolus at a target rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion of 4 mg/min (low dose) or 8 mg/min (high dose) for 120 minutes. Reversal of apixaban/rivaroxaban: The recommended dose regimen of Ondexxya is based on the dose of apixaban/rivaroxaban the patient is taking at the time of anticoagulation reversal, as well as on the time since the patient’slast dose of apixaban. Measurement of baseline anti-FXa-level should support the clinical decision of starting treatment (if level is available in an acceptable time frame). Refer to SmPCfor recommended dose of Ondexxya based on the last dose of apixaban/rivaroxaban. Restarting antithrombotic therapy: Following administration of Ondexxya and cessation of a major bleed, re-anticoagulation should be considered to prevent thrombotic events due to the patient’s underlying medical condition.

Antithrombotic therapy can be re-initiated as soon as medically indicated following treatment if the patient is clinically stable and adequate haemostasis has been achieved.

Medical judgement should balance the benefits of anticoagulation with the risks of re-bleeding. Elderly: No dose adjustment is required in elderly patients (aged ≥ 65 years).

Renal impairment: The effect of renal impairment on andexanet alfa exposure levels has not been evaluated. Based on the existing data on clearance, no dose adjustment is recommended. Hepatic impairment: Based on the existing data on clearance of andexanet alfa, no dose adjustment is recommended. The safety and efficacy have not been studied in patients with hepatic impairment. Paediatric population: The safety and efficacy of andexanet alfa in children and adolescents have not been established. No data are available. Refer to SmPC for instructions on reconstitution of the medicinal product before administration. Contraindications: Hypersensitivity to the active substance or to any other ingredients. Known allergic reaction to hamster proteins. Refer to SmPC for a full list of excipients. Warnings and Precautions: Limitations of use: Andexanet alfa is not suitable for pretreatment of urgent surgery. Use for edoxaban- or enoxaparin-reversal is not recommended due to lack of data. Andexanet alfa will not reverse the effects of non-FXa inhibitors. Thrombotic events: Thrombotic events have been reported following treatment with andexanet alfa. Patients being treated with FXa inhibitor therapy have underlying disease states that predispose them to thrombotic events. Reversing FXa inhibitor therapy exposes patients to the thrombotic risk of their underlying disease.

In addition, independent pro-coagulant effect of andexanet alfa, mediated by inhibition of tissue factor pathway inhibitor (TFPI), has been demonstrated, which may pose a risk of developing thrombosis. Duration of this effect in bleeding patients is not known. Laboratory parameters such as anti- FXa activity, endogenous thrombotic potential (ETP), or markers of thrombosis might not be reliable for guidance. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate after completion of treatment. Use of andexanet alfa in conjunction with other supportive measures: Andexanet alfa can be used in conjunction with standard haemostatic supportive measures, which should be considered as medically appropriate. Interaction with heparin: Use of andexanet prior to heparinization e.g. during surgery should be avoided as andexanet causes unresponsiveness to heparin. Use of andexanet as an antidote for heparin or low-molecular weight heparin has not been evaluated and is not recommended. Infusion-related reactions: In case of mild or moderate infusion reactions, careful observation may be sufficient. For moderate symptoms, consideration may be given to a brief interruption or slowing of the infusion with resumption of the infusion after symptoms subside. Diphenhydramine may be administered. Drug Interactions: No interaction studies with andexanet alfa have been performed. Pregnancy and Lactation: There are no data from the use of andexanet alfa in pregnant women. Andexanet alfa is not recommended during pregnancy or in women of childbearing potential not using contraception. It is unknown whether andexanet alfa is excreted in human milk. A risk to newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with andexanet alfa. There are no data on the effects of andexanet alfa on human fertility. Ability to Drive and Use Machines: Andexanet alfa has no or negligible influence on the ability to drive and use machines. Undesirable Events: Consult SmPC for full list of side effects, including those reported in healthy patients. Frequency in patients with major bleeds: Common (> 1/100 to < 1/10): cerebrovascular accident, ischaemic stroke, acute myocardial infarction, myocardial infarction, deep vein thrombosis, pulmonary embolism, pyrexia. Uncommon (≥ 1/1,000 to < 1/100): cerebral infarction, transient ischaemic attack, cardiac arrest, iliac artery occlusion, infusion related reactiona a reported signs/symptoms (rigors, chills, hypertension, oxygen desaturation, agitation and confusion) were transient and mild to moderate in severity. Legal Category: Product subject to prescription which may not be renewed (A). Marketing Authorisation Number: EU/1/18/1345/001 Marketing Authorisation Holder: AstraZeneca AB, SE-151 85, Södertälje, Sweden. Further product information available on request from: AstraZeneca Pharmaceuticals (Ireland) DAC, College Business and Technology Park, Blanchardstown Road North, Dublin 15, Ireland. Freephone 1800 800 899. ONDEXXYA® is a trademark(s) of the AstraZeneca group of companies. Date of API preparation: 02/2023 Veeva ID: IE-4783

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Veeva ID: IE-4874 Date of Preparation: April 2023