HPN 2022 August

HOSPITAL PROFESSIONAL NEWS IRELAND

HPN August 2022 Issue 99 PEER REVIEW HOSPITALPROFESSIONALNEWS.IE

Ireland’s Dedicated Hospital Professional Publication

IN THIS ISSUE: NEWS: Honour for RCSI’s First Female Microbiology Professor Page 8 REPORT: A Hospital Pharmacist working amongst Paramedics Page 14

C I B I N Q O is indic ate d for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

FEATURE: Reconfiguring a Model of Eye Care Page 18 TRAINING: The Use of Case Method in the Learning Process Page 22 PEER REVIEW: Malignant Pleural Effusion Page 36

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions. © 2022 Pfizer Inc. All rights reserved.

July 2022. PP-CIB-IRL-0036

This Publication is for Healthcare Professionals Only

CPD: Management and Treatment of Polymyalgia Rheumatica Page 49 PEER REVIEW: Deactivation of Implantable Cardioverter Defibrillators Page 74

PRESCRIBING INFORMATION (PI).

SKYRIZI®▼ (risankizumab) 75 mg solution for injection in pre-filled syringe; Skyrizi 150 mg solution for injection in pre-filled pen and Skyrizi 150 mg solution for injection in prefilled syringe. Refer to Summary of Product Characteristics (SmPC) for full information before prescribing. PRESENTATION: Skyrizi 150 mg solution for injection in pre-filled pen/ syringe: each prefilled pen/syringe contains 150 mg risankizumab in 1 mL solution. Skyrizi 75 mg solution for injection in pre-filled syringe: each pre-filled syringe contains 75 mg risankizumab in 0.83 ml mL solution. INDICATION: Plaque Psoriasis: For treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. Psoriatic Arthritis: alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs (DMARDs). DOSAGE AND ADMINISTRATION: Intended for use under guidance and supervision of a physician experienced in diagnosis and treatment of psoriasis. Dosage: The recommended dose of Skyrizi is 150 mg by subcutaneous injection at weeks 0, 4, and every 12 weeks thereafter (either as two 75 mg pre-filled syringe injections or one 150 mg pre-filled pen or pre-filled syringe injection).

Two 75mg pre-filled syringes should be injected for the full 150 mg dose. Consider discontinuation of treatment in patients showing no response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. Special Populations: Elderly: No dose adjustment required. Renal or hepatic impairment: No dose adjustment required.

Paediatric Population: No data available. Overweight patients: No dose adjustment required. CONTRAINDICATIONS: Hypersensitivity to any of the active substances or excipients. Clinically important active infections (e.g. active tuberculosis). SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Skyrizi may increase the risk of infections. In patients with a chronic infection or history of recurrent infections, or known risk factors for infection, Skyrizi should be used with caution. Treatment with Skyrizi should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. Patients should be evaluated for tuberculosis infection prior to initiating treatment. Anti-TB therapy should be considered prior to initiating Skyrizi in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Completion of all appropriate immunisations should be considered prior to initiating therapy. If a patient has received live vaccination (viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment with Skyrizi. Patients treated with Skyrizi should not receive live vaccines during treatment and for at least 21 weeks after treatment.

If a serious hypersensivity reaction occurs, administration of Skyrizi should be discontinued immediately and appropriate therapy initiated. Excipients with known effect (75 mg solution for injection only): Skyrizi contains 68.0 mg sorbitol and less than 1 mmol sodium (23 mg) per 150 mg dose. INTERACTIONS: The safety and efficacy of Skyrizi in combination with immunosuppressants, including biologics or phototherapy have not been evaluated. PREGNANCY AND LACTATION: Women of Childbearing potential: An effective method of contraception during treatment and for at least 21 weeks after treatment should be used. Pregnancy: Limited data available.

It is preferable to avoid the use of Skyrizi during pregnancy as a precautionary measure. Lactation: It is not known whether Skyrizi is excreted in breast milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A decision should be made whether to discontinue/abstain from Skyrizi therapy, taking into account the benefit of breast-feeding to the child and the benefit of Skyrizi therapy to the woman. Fertility: The effect of Skyrizi on human fertility has not been evaluated. ADVERSE REACTIONS: See SmPC for full details on adverse reactions. Very common adverse reactions (≥1/10): Upper respiratory infections. Common adverse reactions (≥1/100 to <1/10): Tinea infections, headache, pruritus, fatigue and injection site reactions. ▼ This medicinal product is subject to additional monitoring.

This will allow quick identification of new safety information.

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

LEGAL CLASSIFICATION: POM (S1A). MARKETING AUTHORISATION NUMBERS/PRESENTATIONS: Skyrizi 75 mg solution for injection in pre-filled syringe (Pack of 2 pre-filled syringes): EU/1/19/1361/001; Skyrizi 150 mg solution for injection in prefilled pen: EU/1/19/1361/002; Skyrizi 150 mg solution for injection in pre-filled syringe: EU/1/19/1361/003. Not all presentations may be marketed. Further information is available from: AbbVie Ltd., 14 Riverwalk, Citywest Business Campus, Dublin 24, D24XN32. DATE OF REVISION: November 2021 PI/1361/004 HRQoL, Health-Related Quality of Life; PASI, Psoriasis Area Severity Index.

REFERENCES: 1. Gordon KB, et al. Lancet 2018; 392: 650-661. 2.

Ryan C et al. Poster presented at the 27th European Academy of Dermatology & Venerology (EADV) Congress 2018; September 12– 16; Paris, France.

SKYRIZI® Summary of Product Characteristics, available on www. medicines.ie.

Date of preparation: May 2022 | IE-RISN-220006

When it comes to your patient’s

psoriasis treatment goals

What means everything to the patient?

The potential for nothing left on their skin.1,2

* Nothing on the skin: Defined as 75% achievement of PASI90 at Week 16 and ≥50% achievement of PASI 100 at Week 52 in UltIMMa-1 and UltIMMa-2.1 High skin clearance matters to patients: Patients who achieve and maintain high levels of skin clearance (PASI 90-99 or PASI 100) have significantly better HRQoL than those with lower levels of skin clearance (PASI 75-89).2 Sustaining high skin clearance or complete skin clearance is associated with incremental and durable benefits in HRQoL and mental health of psoriasis patients.2

Launching Launching

Flucloxacillin Flucloxacillin Powder Powder for for solution solution for for injection/infusion injection/infusion 500mg 500mg

1000mg 1000mg

2000mg 2000mg

PRESCRIBING INFORMATION: Consult the Summary of Product Characteristics for further information. Additional information isINFORMATION: available uponConsult request.

500mg,Characteristics 1000mg and 2000mg for solution for PRESCRIBING the Flucloxacillin Summary of Product for furtherpowder information.

Additional injection/infusion.

Activeupon ingredients: flucloxacillin500mg, sodium,1000mg each 10mL contains 500mg information is available request. As Flucloxacillin and vial 2000mg powder for flucloxacillin solution for (25.5mg sodium approximately), 20mL vial contains 1000mg flucloxacillin (51mg sodium approximately), 50mL vial injection/infusion. Active ingredients: As flucloxacillin sodium, each 10mL vial contains 500mg flucloxacillin containssodium 2000mgapproximately), flucloxacillin (102mg sodium approximately).

Indications: the treatment of the 50mL following (25.5mg 20mL vial contains 1000mg flucloxacillin (51mgForsodium approximately), vial infections2000mg due to beta-lactamase producing staphylococci and other sensitiveForGram-positive organisms such as contains flucloxacillin (102mg sodium approximately).

Indications: the treatment of the following streptococci – skin and soft tissue infections abscesses,and cellulitis, impetigo),organisms upper respiratory infections due to beta-lactamase producing (like staphylococci other infected sensitiveburns, Gram-positive such as tract infections pharyngitis, tonsillitis, respiratory (like pneumonia, streptococci – skin(like and soft tissue infections (likesinusitis), abscesses,lower cellulitis, infected tract burns,infections impetigo), upper respiratory bronchopneumonia, pulmonary abscess), bone and joint infections (like osteomyelitis and arthritis), endocarditis. tract infections (like pharyngitis, tonsillitis, sinusitis), lower respiratory tract infections (like pneumonia, Prophylaxis in cardiovascular surgery (valve prostheses, artery prostheses) and orthopedic surgery (arthroplasty, bronchopneumonia, pulmonary abscess), bone and joint infections (like osteomyelitis and arthritis), endocarditis. osteosynthesis and arthrotomy).

Consideration shouldartery be given to official appropriate use of Prophylaxis in cardiovascular surgery (valve prostheses, prostheses) and guidance orthopediconsurgery (arthroplasty, antibacterial agents.

Posology and method of administration: is on indicated if oraluse route osteosynthesis and arthrotomy).

Consideration should be givenParenteral to officialtherapy guidance appropriate of impracticable agents. or unsuitable as inand the case of severe diarrhoea or vomiting andtherapy particularly for urgent treatment antibacterial Posology method of administration: Parenteral is indicated if oral route of severe infection.

Routes of administration: 500mg vial Intramuscular (im), intravenous (iv), intrapleural and impracticable or unsuitable as in the case of severe diarrhoea or vomiting and particularly for urgent treatment intraarticular.

1000mg vial and 2000mg vial – intramuscular and intravenous only. Intravenous injection/ of severe infection.

Routes of administration: 500mg vial - Intramuscular (im),routes intravenous (iv), intrapleural and infusion should1000mg be administered slowly. Dosage depends on age, and renal function as well as theinjection/ severity intraarticular. vial and 2000mg vial – intramuscular and weight intravenous routes only. Intravenous and nature of thebeinfection.

Adultsslowly. and adolescents ≥ 12 years – Total dailyand dosage 1g to 4g,asadministered in three infusion should administered Dosage depends on age, weight renaloffunction well as the severity to four divided doses, by iv or im injection.

Severe infections: to 8gdaily per dosage day administered four infusions (over and nature of the infection.

Adults and adolescents ≥ 12 years up – Total of 1g to 4g,inadministered in three 20 four to 30divided min). No single injection or infusion should exceed dose of 12g in perfour dayinfusions should not be to doses, bybolus iv or im injection.

Severe infections: up to2g.

8g Maximum per day administered (over exceeded.

In surgical prophylaxis: 2g iv (bolus or infusion) upon induction of anesthesia, to be repeated every 20 to 30 min). No single bolus injection or infusion should exceed 2g. Maximum dose of 12g per day should not 6h be for 24h in In vascular orthopedic for 48h in cardiac or coronary surgery.toMethicillin-susceptible exceeded. surgicaland prophylaxis: 2gsurgery, iv (bolusand or infusion) upon induction of anesthesia, be repeated every 6h Staphylococcus aureus.

2g everyand 6h,for increasing to 2g every 4h in patients weighing >85kg. Children for 24h in vascular and Endocarditis: orthopedic surgery, 48h in cardiac or coronary surgery.

Methicillin-susceptible under 12 years of age –Endocarditis: In mild to moderate 25 toto50mg/kg/24 administered threeChildren to four Staphylococcus aureus.

2g everyinfections: 6h, increasing 2g every 4h hours in patients weighingin>85kg. equally12divided doses or ivtoinjection. infections: to 100mg/kg/24 in threeintothree four divided under years of age by – Inimmild moderateSevere infections: 25 to Up 50mg/kg/24 hours hours administered to four doses.

No single bolus injection or infusion should exceed 33mg/kg.

Methicillin-susceptible Staphylococcus equally divided doses by im or iv injection. Severe infections: Up to 100mg/kg/24 hours in three to four divided aureus.

Endocarditis: 200mg/kg/24 hours in three to four divided doses.

Premature infants, neonates, sucklings doses. No single bolus injection or infusion should exceed 33mg/kg. Methicillin-susceptible Staphylococcus and infants – Risk of200mg/kg/24 kernicterus;hours only in usethree in premature infants andPremature neonates infants, after rigorous risk-benefit aureus.

Endocarditis: to four divided doses. neonates, sucklings assessment. is generally only with use 25mgin topremature 50mg/kg/24 hoursand divided into three four equal doses. and infants –Treatment Risk of kernicterus; infants neonates after or rigorous risk-benefit Maximum daily dose 100mg/kg/24 hours. functionhours – Renaldivided excretion withdoses. renal assessment.

Treatment is generally withAbnormal 25mg torenal 50mg/kg/24 intoslowed three in or patients four equal insufficiency. severe renal insufficiency (creatinine clearance considerslowed dose reduction or with extension Maximum dailyIndose 100mg/kg/24 hours. Abnormal renal function<10ml/min) – Renal excretion in patients renal of dose interval.

Maximum recommended dose in adults is 1g every 8 to 12 hours.

In anuric patients maximum insufficiency. In severe renal insufficiency (creatinine clearance <10ml/min) consider dose reduction or extension dosage 1g everyMaximum 12 h. Flucloxacillin not significantly removed dialysis no supplementary dosages need of dose isinterval. recommended dose in adults is 1g by every 8 to hence 12 hours.

In anuric patients maximum be administered during or at end of dialysis period.

Hepatic impairment – Dose reduction not necessary. dosage is 1g everyeither 12 h. Flucloxacillin not significantly removed by dialysis hence no supplementary dosages need Intrapleural and intraarticular dose 250mgperiod. to 500mg onceimpairment daily. Contraindications: Hypersensitivity to be administered either during –orUsual at end of isdialysis Hepatic – Dose reduction not necessary. the active substance or excipients, should be given patients with history of hypersensitivity to beta-lactam Intrapleural and intraarticular – Usual dosenot is 250mg toto 500mg once daily.

Contraindications: Hypersensitivity to antibiotics, patients with previous history of flucloxacillin-associated jaundice/hepatic dysfunction.

Not suitable the active substance or excipients, should not be given to patients with history of hypersensitivity to beta-lactam for ocular or subconjunctival administration or intrathecal injection.

Special warnings and precautions for use: antibiotics, patients with previous history of flucloxacillin-associated jaundice/hepatic dysfunction. Not suitable Before initiating therapy with administration flucloxacillin check patient history concerning for ocular or subconjunctival or intrathecal injection.

Special previous warningshypersensitivity and precautionsreactions for use: to beta-lactams.

Cross sensitivity betweencheck penicillins cephalosporins is well documented.

Serious and Before initiating therapy with flucloxacillin patientand history concerning previous hypersensitivity reactions to beta-lactams. Cross sensitivity between penicillins and cephalosporins is well documented. Serious and

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

occasionally fatal hypersensitivity reactions have been reported in patients receiving beta-lactam antibiotics, occurrence more with parenteral compared to oral therapy.

Reactionsreceiving more likely to occur antibiotics, in patients occasionally fatalfrequent hypersensitivity reactions have been reported in patients beta-lactam with historymore of beta-lactam hypersensitivity.

If allergic reaction occurs discontinue and occurrence frequent with parenteral compared to oral therapy.

Reactions more flucloxacillin likely to occur in institute patients appropriate therapy.

Feverish generalized erythema associated with pustula occurring at treatment initiation may with history of beta-lactam hypersensitivity. If allergic reaction occurs discontinue flucloxacillin and institute be a symptom of acute generalised exanthematous pustulosiswith (AGEP); in occurring case of AGEP diagnosisinitiation discontinue appropriate therapy.

Feverish generalized erythema associated pustula at treatment may flucloxacillin administration is contraindicated.

Use within caution patients with evidence of be a symptomand of subsequent acute generalised exanthematous pustulosis (AGEP); case of inAGEP diagnosis discontinue hepatic dysfunction, patients ≥50 years of ageisand those with serious underlying hepatic events may be flucloxacillin and subsequent administration contraindicated.

Use with cautiondisease; in patients with evidence of severe and in extremely rare circumstances deaths Flucloxacillin solutions reconstituted hepatic dysfunction, patients ≥50 years of age and have thosebeen withreported. serious underlying disease; hepatic events maywith be local anesthetics (lidocaine) should not be deaths given by iv administration.

Adjust dose insolutions renal impairment.

Special severe and in extremely rare circumstances have been reported. Flucloxacillin reconstituted with caution essential (lidocaine) in newborns duenot to be riskgiven of hyperbilirubinaemia potential high serum levels of local anesthetics should by iv administration. and Adjust dose in for renal impairment.

Special flucloxacillin due toinreduced rate of Regular monitoring and of blood count, for hepatic renallevels function caution essential newborns duerenal to excretion. risk of hyperbilirubinaemia potential highand serum of recommendeddue during prolonged treatment.

Pseudomembranous colitisofcan occur; if hepatic this develops discontinue flucloxacillin to reduced rate of renal excretion.

Regular monitoring blood count, and renal function flucloxacillin and initiate appropriate therapy.

Prolonged use may occasionally overgrowth of nonrecommended during prolonged treatment.

Pseudomembranous colitis can occur;result if thisindevelops discontinue susceptible organisms.

Caution when administered concomitantly with paracetamol due to increased risk high flucloxacillin and initiate appropriate therapy. Prolonged use may occasionally result in overgrowth ofof nonanion gap metabolic acidosis (HAGMA).

High risk of HAGMA particularly in patients with severe renal impairment, susceptible organisms. Caution when administered concomitantly with paracetamol due to increased risk of high sepsisgap or malnutrition especially if maximum daily paracetamolinused.

Following co-administration close anion metabolic acidosis (HAGMA).

High risk of doses HAGMAofparticularly patients with severe renal impairment, monitoring recommended to detect the appearance of of HAGMA (including testing for urinary 5-oxoproline). sepsis or malnutrition especially if maximum daily doses paracetamol used.

Following co-administration closeIf flucloxacillinrecommended is continued after paracetamol cessation, is advisable to ensure ParticularIf monitoring to detect the appearance of itHAGMA (including testingnoforHAGMA urinarysignals.

5-oxoproline). caution with isdrug-induced liverparacetamol injury in patients withitHLA-B*5701 these Particular disorders flucloxacillin continued after cessation, is advisablehaplotype; to ensure frequency no HAGMAofsignals. increasing in HIV-infected patients who may be at increased risk of exposure to flucloxacillin.

Hypokalaemia caution with drug-induced liver injury in patients with HLA-B*5701 haplotype; frequency of these disorders (potentiallyinlife threatening) can who occurmayespecially at highrisk doses and mayto be resistant Hypokalaemia to potassium increasing HIV-infected patients be at increased of exposure flucloxacillin. supplementation. measure levels during high doses dose flucloxacillin Attention warranted (potentially life Regularly threatening) can potassium occur especially at high and may therapy. be resistant to potassium when combining flucloxacillin with hypokalaemia inducing diuretics or when other risk factorsAttention for development of supplementation.

Regularly measure potassium levels during high dose flucloxacillin therapy. warranted hypokalaemia present.

Contains considerinducing in patients on a or sodium diet. Undesirable effects: when combining flucloxacillin withsodium, hypokalaemia diuretics when controlled other risk factors for development of Common (>1/100 to <1/10): Minor gastrointestinal disturbances.

Uncommon (>1/1000 to <1/100): Rash, urticaria, hypokalaemia present. Contains sodium, consider in patients on a sodium controlled diet. Undesirable effects: purpura. (>1/100 Very rare (<1/10,000): Neutropenia (including agranulocytosis), thrombocytopenia, eosinophilia, Common to <1/10): Minor gastrointestinal disturbances.

Uncommon (>1/1000 to <1/100): Rash, urticaria, haemolyticVery anaemia, anaphylacticNeutropenia shock, angioneurotic oedema, high anion gap metabolic acidosis, purpura. rare (<1/10,000): (including agranulocytosis), thrombocytopenia, eosinophilia, pseudomembranous neurological disorders with convulsions with high iv injection in haemolytic anaemia,colitis, anaphylactic shock, angioneurotic oedema, possible high anion gap dose metabolic acidosis, patients with renal failure, cholestatic changes inpossible liver function laboratory results, pseudomembranous colitis, hepatitis, neurological disordersjaundice, with convulsions with high dose iv test injection in erythemawith multiforme, Stevens-Johnson syndrome,jaundice, toxic epidermal arthralgia, myalgia,test interstitial patients renal failure, hepatitis, cholestatic changesnecrolysis, in liver function laboratory results, nephritis, fever sometimes develops moresyndrome, than 48 hours start necrolysis, of treatment.

Frequency not known: Acute erythema multiforme, Stevens-Johnson toxic after epidermal arthralgia, myalgia, interstitial generalized exanthematous pustulosis, Legal after Category: POM Marketing Authorisation Numbers: nephritis, fever sometimes develops morephlebitis. than 48 hours start of treatment.

Frequency not known: Acute PA2059/069/001, PA2059/069/002, PA2059/069/003.

Authorisation Holder: Fresenius Kabi Deutschland generalized exanthematous pustulosis, phlebitis. Marketing Legal Category: POM Marketing Authorisation Numbers: GmbH, Else-Kroener Strasse 1, Bad PA2059/069/003.

Homburg v.d.H 61352, Germany Further Information: See the Kabi SmPCDeutschland for further PA2059/069/001, PA2059/069/002, Marketing Authorisation Holder: Fresenius details.Else-Kroener Adverse events should be reported. are asked to report any GmbH, Strasse 1, Bad Homburg Healthcare v.d.H 61352,professionals Germany Further Information: See thesuspected SmPC foradverse further reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublinare 2, Tel: +353 1 6764971, +353 1 adverse 6762517. details.

Adverse events should be reported.

Healthcare professionals asked to report anyFax: suspected Website: www.hpra.ie, E-mail: medsafety@hpra.ie.

Adverse events should also be reported to Fresenius Kabi Limited reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517. via emailwww.hpra.ie, Pharmacovigilance.GB@Fresenius-Kabi.com.

Dateevents of Preparation: 2021 IE-IVF-2100004 Website: E-mail: medsafety@hpra.ie. Adverse should alsoAugust be reported to Fresenius Kabi Limited via email Pharmacovigilance.GB@Fresenius-Kabi.com. Date of Preparation: August 2021 IE-IVF-2100004

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

Date of Prep: August 2021 Date of Prep: August 2021 Ref: IE-IVF-2100007 Ref: IE-IVF-2100007

August Issue Issue 99

5

Contents

Foreword

Enhancing Cancer Research in Ireland P7

Editor More than half of people have a favourable opinion about pharmaceutical companies operating in Ireland, according to new research from Ipsos for the Irish Pharmaceutical Healthcare Association (IPHA), the representative organisation for medicines innovators.

RCSI’s first Microbiology Professor receives Honour P8 New appointments at Pharmacy Regulator P12

7

The industry’s public favourability score, at 53%, is up from 44% since a similar poll was conducted in September 2018. When Ipsos measured sentiment towards the industry in June 2020 and in September 2021, the scores were 50% and 54%, respectively.

Turn to page 8 to read the full story.

Experiences of being a Pharmacist amongst Paramedics P14 Cardiothoracic Ward opens at University Hospital Galway P16 Increasing Specialised Care for Eye Patients P18

12

Why is Healthcare still not Safe? P24 REGULARS

The COWORKER Study, developed to investigate the mental health impact of the pandemic on Dublin general hospital staff and to help inform appropriate responses, involved researchers from Trinity College Dublin, St Patrick’s Mental Health Services and RCSI University of Medicine and Health Services. It was led by Declan McLoughlin, Research Professor of Psychiatry at Trinity and Consultant Psychiatrist at St Patrick’s Mental Health Services.

Peer Review: An Overview of Psoriasis P33 Peer Review: Colon Cancer Surgery Implications P40

14

Peer Review: HER2+ Breast Cancer P44

Alarmingly, the high levels of post-traumatic symptoms found in this study are higher than the current best international estimate for healthcare workers. Page 10 carries further details.

CPD: Polymyalgia Rheumatica P49 Peer Review: Epilepsy in Pregnancy P81 Clinical R&D: P98 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 of transmitted in any form without written permission. IPN Communications Ltd have taken every care in compiling the magazine to ensure that it is correct at the time of going to press, however the publishers assume no responsibility for any effects from omissions or errors.

PUBLISHER IPN Communications Ireland Ltd Clifton House, Lower Fitzwilliam Street, Dublin 2 (01) 669 0562 GROUP DIRECTOR Natalie Maginnis n-maginnis@btconnect.com EDITOR Kelly Jo Eastwood DIGITAL MARKETING & EDITORIAL EXECUTIVE Danielle Norton danielle@hospitalprofessionalnews.ie

In other research news, findings from a study exploring the mental health of Dublin’s general hospital staff during the COVID-19 pandemic revealed significant impacts on doctors, nurses and radiographers, including high levels of symptoms of posttraumatic stress disorder (PTSD), depression and suicidal thinking.

18

EDITORIAL editorial@hospitalprofessionalnews.ie ACCOUNTS Rachel Wilson cs.ipn@btconnect.com SALES EXECUTIVE Aoife Tremere aoife.t@hospitalprofessionalnews.ie CONTRIBUTORS Edel Burton | Tatiana Larmak Dr Dale Whelehan | Dr Emma Dorris Mariosa Kieran | Laura Stevenson Dr Padraic Ridge | Dr David Breen Mr Desmond Toomey | Padraig Denn Dr Grainne Sheill | Kelly Coghlan Dr Clare Brady | Dr Richard Conway Dr Kevin McCarroll | Dr Marie Talty Dr Breda Cushen | Dr Rosie Kelly Nicola Perry | Theresa Lowry Lehnen Sarah Cullen | Benedetta Soldati Ashley Costello | Rosie Culhane Gerard Clarke | Mr Paul Nolan Mr James Forde | Charles O'Connor Patrick Collins | Gregory Nason Professor Nicola Dalbeth Professor Geraldine McCarthy Professor Eddie Moloney Dr Stefanie Croghan

HOSPITALPROFESSIONALNEWS.IE

@HospitalProNews HospitalProfessionalNews

Meanwhile, on page 14 Edel Burton outlines her experience as a pharmacist working amongst paramedics. Edel is a second year Structured Population and Health-services Research Education (SPHeRE) scholar in University College Cork and a scholar on the Health Research Board(HRB) Collaborative Doctoral Programme in Chronic Disease Prevention(CDP). Edel is also a clinical pharmacist and recently carried out a placement in the National Ambulance Service (NAS) Clinical Directorate, in Dooradoyle, Limerick.

“I can say with true confidence that this opportunity has challenged me to further explore the execution of integrated care and research. I truly believe that my work with NAS has not only vastly improved the potential value of my research but also optimised my ability to provide holistic patient care,” she says.

This August issue also carries our annual Peer Review clinical special focus and we have a multitude of excellent, contributed features covering topics such as respiratory, oncology, cardiology, dermatology and pharmacy, amongst many others.

I hope you enjoy the issue.

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

6

News

Spark Innovation Award Bernadette Higgins and Anne Murray, winners of the National Spark Ignite Award

idea, at the annual Spark Innovation Programme conference in Dublin last Thursday afternoon.

Two nurses at the Department of Public Health Mid-West have received a top award in recognition of their innovative idea to collect urine samples in a cleaner way in order to improve diagnosis rates of infections, with the aid of a special app.

Public Health Mid-West’s Assistant Director of Nursing (ADON) Bernadette Higgins, and Clinical Nurse Manager 2 (CNM2) in Health Protection, Anne Murray, won the National Spark Ignite award and ¤3,000 seed funding for their ‘Wee Catch It’ innovation

The Spark Ignite award seeks innovative ideas from the 115,000+ HSE employees aiming to improve patient and healthcare outcomes. Spark Ignite is open to all disciplines and departments within the HSE, enabling staff to develop their ideas through validation of clinical need and to determine the market for their proposed solution, product, or service. Successful applicants will

also receive guidance on how to bring their ideas towards reality.

Collecting a clean, accurate midstream urine in babies, children and adults with incontinence in an efficient and hygienic way is challenging, this can lead to contamination of samples and often results in unnecessary antibiotic prescribing and costly unplanned hospital admissions.

Necessity being the mother of invention, Bernadette came up with a solution to improve the ‘clean catch’ urine samples and targeting antimicrobial stewardship with ‘Wee Catch It’.

Bernadette and Anne had previously won the Regional Spark Ignite award and ¤3,000 seed funding in early June.

‘Wee Catch It’ is currently in prototype development phase, and the Public Health nurses will now work towards developing the unique product and software for national and international use.

Prefilled Medicines Syringes in Hospitals The European Association of Hospital Pharmacists (EAHP) has established a Special Interest Group (SIG) to gain more knowledge about the current and future use of prefilled medicines syringes (PFS) in hospitals. EAHP's SIG focused on the Use of Prefilled Syringes in Intensive Care Units and Operating Theatres (financially supported by BD) has prepared two surveys targeting on the one hand professional associations and on the other hand health professionals and managers.

A PFS is a presentation of one or more active medicines, at the required concentration and volume, in the final syringe and ready for parenteral administration to the patient. PFS are intended to reduce error and minimise the time taken to prepare parenteral medicine by staff in clinical areas.

PFS are manufactured/prepared by the pharmaceutical industry or hospital pharmacies.

Several additional benefits and some disadvantages have been reported for PFS. The SIG is preparing a comprehensive literature review on PFS. Usage of PFS in hospitals in North America has been considerably larger than in Europe for many years. Recently the use of PFS in some European countries has increased.

The surveys have been designed to collect the views and opinions of a range of health professionals, managers, and professional associations on the current and future use of PFS. Participation is completely voluntary. It should take approximately 10 to 15 minutes to complete the survey.

Feedback can be shared until the 31st of August 2022. The survey for professional associations is available in English. The survey for individual health professionals and managers can be completed in eight different languages (English, French, German, Hungarian, Italian, Serbian, Spanish and Turkish).

HSE AMRIC e-learning Programme The HSE antimicrobial and infection control team (AMRIC) has developed a series of accredited e-learning modules to support staff working in health and social care services. The 14 courses on infection prevention & control and antimicrobial stewardship are free and they are accredited for continuous professional education points. Participants need to register on www.hseland. ie registration and access to the online modules is free.

Each course takes between 20 – 40 minutes to complete and includes assessments and extend my learning pieces for staff who want to undertake further learning or who want practical activities to help transfer the learning into their local area of work.

The courses are highly interactive throughout and developed using best practice in learning design.

The course was developed to support healthcare staff in

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

all healthcare services across multiple settings. Each course has been accredited by the NMBI for nursing professional development and the RCPI has accredited the programme with continuous professional development points.

Josephine Galway, AMRIC Director of Nursing says, “Every year we see people who are affected by infections associated with healthcare settings. These infections can lead to significant

mortality, psychological and financial losses for person, their family and the health and social care systems. Healthcare associated infections are the most frequent adverse event in healthcare delivery worldwide and is one of the leading causes of the global disease burden. We want to share this accredited, free, online resource with all healthcare services across Ireland to support improved IPC and AMR knowledge and change.”

News

7

UCC to Appoint Experts to Enhance Cancer Research Professor Roisin Connolly, the Professor Gerald O’Sullivan Chair in Cancer Research at UCC, Mary Hickey, Director of Oncology Services for UPMC in Ireland, Professor Helen Whelton, Head of College of Medicine and Health at UCC, and Michael Fetterolf UPMC Director of International Clinical Operations. (Provision)

University College Cork (UCC) and UPMC have announced a new partnership in cancer research, starting with the appointment of two new Professors of Medical Oncology to UCC - key strategic positions in the pursuit of establishing an internationallyrecognised Cancer Research Institute at the university.

The appointment of the two academic oncologists, funded

by UPMC, is backed by the Health Service Executive (HSE) and the National Cancer Control Programme (NCCP) and will establish the foundation for research collaboration between UCC, the University of Pittsburgh and UPMC Hillman Cancer Centre, Pittsburgh.

This international collaboration will be integral to the progression of cancer research across the south of the country and to establish a collaborative research environment, provide greater access to clinical trials for patients,

and embed cutting-edge research in clinical care.

The partnership will appoint a steering committee comprised of representatives from UCC, Cork University Hospital (CUH), UPMC, and the University of Pittsburgh to develop a mutual research vision and to progress collaborative cancer research projects.

This collaboration with UPMC is result of the ambitious UCC Futures initiative that strives to bring the best and brightest Research Leaders to UCC and develop excellence in collaborative research. These Professorships will be fundamental to obtaining future large scale collaborative funding,

receiving regional accreditation from the Organisation of European Cancer Institutes, and will ultimately lead to innovative scientific breakthroughs in the treatment of cancer.

Welcoming the partnership, Professor Roisin Connolly, the Professor Gerald O’Sullivan Chair in Cancer Research at UCC, said, “Our goal is to improve outcomes for patients through translation of innovative scientific findings to clinical trials and practice, bridging UCC and indeed international science with health care for those at risk of or living with cancer.

Recruitment of the best and brightest in cancer research and clinical care to our region will play

a pivotal role in the expansion of UCC’s academic efforts in the cancer space.

"UPMC Hillman Cancer Centre is recognised internationally for its leadership in translational cancer research, and collaboration between our institutions will be significant in the advancement of cancer research programmes in our region and progressing the College of Medicine and Health’s vision for an Academic Cancer Health System. By working together with local, national and international collaborators, we will bring more and better treatment options to the table for cancer patients in Ireland and further afield.”

New Ipsos survey for IPHA Two in five people believe the Covid-19 pandemic will never be fully over, according to new research carried out by Ipsos for the Irish Pharmaceutical Healthcare Association (IPHA).

The research, measuring public attitudes to Covid-19 vaccination and to vaccination in general, shows that half of people believe the Covid-19 pandemic will end eventually while 39% believe it will never fully be over. Just 10% believe the pandemic has already ended.

Over four in five people, or 82%, believe vaccines, in general, are effective while 76% of people trust the medical evidence about vaccines. Over half of people could spontaneously name four vaccine-preventable diseases,

with Covid-19, measles, mumps and rubella cited most often.

Just under half of people, or 48%, have not received adult vaccinations for diseases other than Covid-19. These diseases could include flu, mumps, rubella, Hepatitis B, whooping cough and pneumococcal disease.

The survey finds that 91% of people have been vaccinated for Covid-19, with three in four people having received at least one booster vaccine dose for the disease. One in four people, or 25%, say they are more likely to get vaccinated for other diseases as a result of getting protected against Covid-19.

Bernard Mallee, IPHA’s Director of Communications and Advocacy, said, “Covid-19 vaccination

has substantially altered the course of the pandemic, saving tens of millions of lives globally.

But people are far from putting the pandemic behind them.

Epidemiologists say the pattern of recurring waves is likely to persist.

Ensuring that we have answers for variants of concern is the work of scientists in our industry.

That work is enabled by stable intellectual property rights.

up among adults of vaccines for diseases other than Covid-19 where research shows there is a significant gap in coverage.

“That we have very strong levels of vaccination, including take-up of booster doses, shows that people have confidence in science as the best defence against infection.

Vaccination is effective in stopping serious illness and death.

According to a study, published in The Lancet in June 2022, vaccinations prevented almost 15 million deaths from Covid-19 in 185 countries and territories between December 2020 and December 2021. With the exception of clean, safe drinking water, vaccination is among the most successful and cost-effective public health interventions ever.

“Encouragingly, a significant majority of people believe that vaccines, in general, are effective.

But we would urge greater take-

“Vaccination helps us to stay safe throughout life. It means we don’t have to worry so much about diseases like smallpox, rubella, measles, pneumonia, tuberculosis and polio that used to torment communities across the country.”

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

8

News

Favourable Opinion of Pharma Industry More than half of people have a favourable opinion about pharmaceutical companies operating in Ireland, according to new research from Ipsos for the Irish Pharmaceutical Healthcare Association (IPHA), the representative organisation for medicines innovators.

The industry’s public favourability score, at 53%, is up from 44% since a similar poll was conducted in September 2018. When Ipsos measured sentiment towards the industry in June 2020 and in September 2021, the scores were 50% and 54%, respectively.

Three in five people, or 60%, trust the industry in Ireland, almost

twice the global average measured by an Ipsos survey of people across 29 countries.

More than four in five people, or 83%, believe that the industry makes an important societal and economic contribution. That figure is up slightly from 81% in 2018.

Over half of people, or 55%, believe the industry focuses on what patients need.

Almost nine in 10 people, or 89%, believe in the value of science in tackling unmet medical needs.

More than four in five people, or 83%, believe the past five years has brought significant progress in the development

of new medicines. About the same number recognise the link between medicines and better health outcomes.

Bernard Mallee, IPHA’s Director of Communications and Advocacy, said the survey shows the industry has high levels of public trust.

“The public values science and the industry’s societal and economic impact. That innovator companies are spread across the regions, creating jobs and economic activity, is likely to strengthen that perspective. It is clear, too, that there is an appreciation of the positive health and quality of life impact of medicines. That the industry’s favourability rating

has improved since before the pandemic may reflect heightened public awareness of science in tackling disease. With medicines innovation moving at pace, Ireland should be ready to take advantage of the jobs and health outcomes bonus that comes with the industry. That takes planning between industry, the State and wider stakeholders. We look forward to continuing that trend,” said Mr Mallee.

The next phase of Innovate For Life, the industry’s documentary campaign that tells the story of innovation in medicines, will be released in the coming weeks.

Honour for RCSI's First Female Microbiology Professor Professor Ellen Moorhouse's son and daughter pictured at the event: Dr David Moorhouse, RCSI graduate and Consultant Neurologist at Bon Secours Hospital, and Kathryn Moorhouse, RCSI Library

female Clinical Sciences Professor at RCSI with her appointment as Chair of Microbiology. She continued working at RCSI and Beaumont Hospital until her retirement in 1995.

Today, Professor Moorhouse's portrait is displayed in RCSI's St Stephen's Green campus, and the Ellen Moorhouse Prize in Clinical Microbiology is awarded annually to an undergraduate medical student.

The Department of Clinical Microbiology at RCSI University of Medicine and Health Sciences has renamed its laboratory in honour of the late Professor Ellen Moorhouse.

In a ceremony today at the RCSI Education and Research Centre at Beaumont Hospital, RCSI President Professor Laura Viani unveiled a plaque to mark

the official naming of the 'Ellen Moorhouse Laboratory'.

Professor Ellen C. Moorhouse was born in Dublin in 1928 and studied at RCSI before working in hospitals in Ireland and England.

The RCSI Department of Clinical Microbiology was opened in 1965, and in 1967 Professor Moorhouse became the first

EAHP Congress 2023

RCSI President, Professor Laura Viani, commented: "It is my great honour to unveil the plaque officially naming the Ellen Moorhouse Laboratory at the RCSI Department of Clinical Microbiology at Beaumont Hospital. In the almost 30 years that Professor Moorhouse worked at RCSI, she taught and inspired countless generations of healthcare professionals. This is a fitting tribute to the lasting impact

and influence our first female Clinical Sciences Professor has had at RCSI." For 57 years, the RCSI Department of Clinical Microbiology has been committed to educating the next generation of doctors about sepsis, healthcare-associated infection and antimicrobial resistance and improving patient care through research into the prevention and control of healthcare-associated infections and antibiotic resistance /superbugs for better health outcomes.

Now led by Professor Fidelma Fitzpatrick, the team includes clinicians, other healthcare professionals and scientists, all of whom are actively involved in teaching, research, public engagement and advocacy, in addition to national health policy and health services leadership roles. Informed by its research and clinical activities, the RCSI Department of Clinical Microbiology contributes significantly to healthcare policy, national guidelines and national clinical programmes through membership of national and international committees.

The 27th Annual European Association of Hospital Pharmacists Congress will take place from 22-24 March 2023.

The event will be held next year in Lisbon Congress Centre and will be entitled, ‘From Drug Design to Treatment Success – What Really Matters to Patients?’

Building on the success of previous meetings, EAHP decided to embrace new locations and a more diverse format for its in-person events, enabling the Association to host the annual congress in a new city: Lisbon.

The scientific programme will encompass this wide horizon and provide an insight into these different and distinct, but also overlapping, subspecialities. I am sure that the Congress programme will effectively enable us all to grasp this rather complex landscape and to take home with us some valid answers.

Find out more by visiting www.eahp.eu

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Launching Noradrenaline 1mg/ml concentrate for solution for infusion.

Your patients, your profession, our passion.

ABBREVIATED PRESCRIBING INFORMATION: Consult the Summary of Product Characteristics for further information. Additional information is available upon request. Noradrenaline (Norepinephrine) Kabi 1mg/ml concentrate for solution for infusion. Active ingredient: 1ml concentrate for solution for infusion contains 1mg noradrenaline (norepinephrine) base equivalent to 2mg noradrenaline (norepinephrine) tartrate. Contains 3.4mg sodium per ml. Indications: In adults for use as an emergency measure in the restoration of blood pressure in cases of acute hypotension. Posology and method of administration: When diluted as recommended, each litre contains 40mg noradrenaline base equivalent to 80mg noradrenaline tartrate. If dilutions other than 40mg per litre are used, check infusion rate calculation carefully before starting treatment. Initial rate of infusion – 10-20ml/hour (0.16-0.32ml/min); equivalent to 0.4-0.8mg/hour noradrenaline base. Lower initial infusion rate of 5ml/hour (0.08ml/min); equivalent to 0.2mg/hour noradrenaline base may be preferred. Titration of dose – Once infusion has been established, titrate dose in steps of 0.05-0.1mcg/kg/min of noradrenaline base according to pressor effect observed (see SmPC for details). Continue infusion until adequate blood pressure and tissue perfusion maintained without therapy. Carefully monitor patient. Should only be administered by healthcare professionals familiar with use of noradrenaline and with appropriate monitoring facilities.

Avoid abrupt infusion withdrawal; reduce infusion gradually. No experience in treatment of hepatic or renal impairment. Dose selection for an elderly patient should be cautious, starting at the low end of the dosing range. Safety and efficacy in patients less than 18 years old has not been established. Method of administration – Intravenous use only after dilution. Infuse at a controlled rate using either syringe pump, infusion pump or drip counter. Administer via a central venous catheter. If not using a central venous catheter administer into a large vein whenever possible, particularly an antecubital vein to minimize risk of ischemic necrosis.

Avoid catheter tie-in technique if possible. Contraindications: Hypersensitivity to the active substance or to any of the excipients, hypotension due to blood volume deficit. Do not use with cyclopropane and halothane anaesthetics as this may cause serious cardiac arrhythmias including ventricular fibrillation. Special warnings and precautions for use: Do not use undiluted. Contraindicated in patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed. Should only be used in conjunction with appropriate blood volume replacement. If whole blood or blood plasma is indicated to increase blood volume, administer separately (e.g. use Y-tubing, individual containers). Prolonged administration may result in plasma volume depletion which should be continuously corrected by appropriate fluid and electrolyte replacement therapy.

Frequently check blood pressure and rate of flow to avoid hypertension. Particular caution in patients with coronary, mesenteric or peripheral vascular thrombosis, hypotension following myocardial infarction, angina (particularly Prinzmetal’s variant angina), diabetes, hypertension or hyperthyroidism, major left ventricular dysfunction associated with acute hypotension (supportive therapy should be initiated simultaneously with diagnostic evaluation; reserve noradrenaline for patients with cardiogenic shock and refractory hypotension, in particular those without elevated systemic vascular resistance), liver failure, severe renal dysfunction,

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

ischemic heart diseases and elevated intracranial pressure. Reduce dose if heart rhythm disorders occur during treatment. Cardiac arrhythmias may arise when used in conjunction with cardiac sensitizing agents and may be more likely in patients with hypoxia or hypercarbia. Elderly patients may be especially sensitive to the effects of noradrenaline. Not recommended in children. Where indicated, appropriate replacement therapy of blood or fluid together with adoption of the supine position with elevation of the legs, must be instituted and maintained prior to and/or during therapy with noradrenaline. During infusion, record blood pressure every two minutes from the time the administration started until the desired blood pressure is obtained and then every five minutes thereafter if infusion continued. Constantly watch flow rate and never leave patient unattended.

Hypertension may eventually lead to acute pulmonary oedema, arrhythmia or cardiac arrest. Caution in patients receiving pressor amines with chloroform, enflurane or other halogenated anaesthetics (may cause serious cardiac arrhythmias) or any other cardiac sensitising agent or in patients who exhibit profound hypoxia or hypercarbia. Extreme caution in patients receiving monoamine oxidase inhibitors or within 14 days of cessation of such therapy and in patients receiving tricyclic antidepressants, adrenergic- serotoninergic drugs or linezolid. Overdoses or conventional doses in hypersensitive persons may cause severe hypertension with violent headache, photophobia, stabbing retrosternal pain, pallor, intense sweating and vomiting. The infusion site should be checked frequently for free flow. Care should be taken to avoid extravasation of noradrenaline tartrate into the tissues, as local necrosis might ensue due to the vasoconstrictive action of the drug (see SmPC for antidote for extravasation ischaemia). Blanching along the course of the infused vein warrants consideration of changing infusion site at intervals. Avoid administration via the veins of the leg in elderly patients or in those suffering from occlusive vascular diseases. Noradrenaline interacts with other medicinal products; some combinations are inadvisable or require additional precautions and close medical supervision – see SmPC. Undesirable effects: Anxiety, insomnia, confusion, weakness, psychotic state, transient headache, tremor, acute glaucoma, bradycardia, arrhythmia, electrocardiogram change, tachycardia, cardiogenic shock, stress cardiomyopathy, palpitations, increase in the contractility of the cardiac muscle resulting from the beta- adrenergic effect on the heart (inotrope and chronotrope), acute cardiac insufficiency, hypertension, peripheral ischaemia including gangrene of the extremities, plasma volume depletion with prolonged use, dyspnoea, respiratory insufficiency or difficulty, nausea, vomiting, paleness, scarification of the skin, bluish skin colour, hot flushes or skin redness, skin rash, hives or itching, retention of urine, extravasation, necrosis at injection site. Legal Category: POM Marketing Authorisation Number: PA2059/073/001 Marketing Authorisation Holder: Fresenius Kabi Deutschland GmbH; Else-Kröner Straße 1, 61352 Bad Homburg v.d.Höhe, Germany Further Information: See the SmPC for further details. Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517. Website: www.hpra.ie, E-mail: medsafety@hpra.ie. Adverse events should also be reported to Fresenius Kabi Limited via email Pharmacovigilance.GB@Fresenius-Kabi.com. Date of Preparation: January 2022 FPI-0041

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

Date of Prep: March 2022 Job Code: IE-IVF-2200006

10 News

Mental Health Impact on Hospital Workers anonymous survey of 377 Dublin healthcare staff during the third wave of the COVID-19 pandemic in early 2021, are: • 45% of respondents reported moderate or severe symptoms of post-traumatic stress disorder (PTSD) • 52% of respondents reported low mood • 13% of respondents reported thinking of ending their life over the previous week, and 5% reported planning to end their life.

The high levels of post-traumatic symptoms found in this study are higher than the current best international estimate for healthcare workers.

Findings from a research study exploring the mental health of Dublin’s general hospital staff during the COVID-19 pandemic revealed significant impacts on doctors, nurses and radiographers, including high levels of symptoms of posttraumatic stress disorder (PTSD), depression and suicidal thinking.

The COWORKER Study, developed to investigate the mental health impact of the pandemic on Dublin general hospital staff and to help inform appropriate responses, involved researchers from Trinity College Dublin, St Patrick’s Mental Health Services and RCSI University of Medicine and Health Services. It

was led by Declan McLoughlin, Research Professor of Psychiatry at Trinity and Consultant Psychiatrist at St Patrick’s Mental Health Services.

Staff in three large Dublin general hospitals (St James’s Hospital, Tallaght University Hospital and Beaumont Hospital) were invited to participate, with the study also aiming to provide an opportunity for doctors, nurses and radiographers to recognise if they have been experiencing mental health difficulties since the pandemic and to seek support if required.

Among the key findings, which came from a cross-sectional

Staff also reported high levels of moral injury, which is the psychological distress experienced when one is forced to witness or perform acts that go against one’s ethical beliefs.

This concept arose in military mental health research but has gained importance in research studying healthcare workers’ mental health due to COVID-19related scenarios. For example, healthcare workers may have had no option but to ration care when resources were scarce, or they may have had to stop family from visiting their loved ones due to restrictions.

Researchers also examined whether there were any differences in the levels of mental health difficulties between staff based on their roles. The findings show that doctors were significantly less likely to report symptoms of PTSD, low mood and moral injury than nurse or radiographers, while

radiographers were significantly more likely to report low mood.

Speaking about the impact of the findings, Declan McLoughlin, Research Professor of Psychiatry at Trinity and Consultant Psychiatrist at St Patrick’s Mental Health Services, said: “The pandemic has presented immense challenges for hospitals, their staff, patients and families. While there have been many studies internationally examining the psychological impact on hospital staff, this is the first to examine the impacts on those working in Dublin hospitals.

“We hope that the study’s findings will highlight potential areas of concern for hospital management and staff so that they can address this and seek support as required.”

Lead author of the study, Dr Conan Brady, Trinity College Dublin, said: “The results of the COWORKER study have shown the significant mental health impacts of the pandemic for those working in hospitals. While we do not know the full extent of the mental health experiences for hospital staff before COVID-19, there are many pandemic-related factors that may have impacted on this cohort’s mental health.

“In addition to the restrictions we’ve all faced, other reasons could be job stress or concerns about stigma from working in environments with high levels of COVID-19. There are few data on suicidal ideation in hospital staff internationally, and this warrants more investigation.”

The results of the peer-reviewed study have been published as an Open Access paper in the Irish Journal of Medical Science.

Chickenpox Vaccine Schedule The Health Information and Quality Authority (HIQA) has published the protocol for its newest health technology assessment (HTA) of the addition of the chickenpox (varicella) vaccine to the routine childhood immunisation schedule. The protocol describes the approach that HIQA's team will use to complete this piece of work.

HIQA agreed to undertake this

HTA following a request from the Department of Health. The request was supported by the National Immunisation Advisory Committee (NIAC).

Varicella-zoster virus can cause two clinical syndromes: chickenpox, as a result of primary (initial) infection, and shingles, which typically occurs in later life due to reactivation of the virus. Chickenpox is a common

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

infectious disease that mainly affects children; one case of chickenpox can potentially infect 10 to 12 people. Within EU/EEA countries, the annual incidence of chickenpox is typically equivalent to the birth cohort; the total number of births in Ireland annually is approximately 56,000.

Dr Conor Teljeur, HIQA's Chief Scientist said: “A vaccine for chickenpox was first developed

almost 50 years ago. Over the last 30 years, a growing number of countries around the world have added the chickenpox vaccine to their routine childhood immunisation schedules. In Ireland, the vaccine is currently recommended for non-immune individuals in certain risk groups.

Our assessment will examine the impact of adding the vaccine to the childhood immunisation schedule.”

News 11

Waiting Lists Continue to Increase The Irish Hospital Consultants Association (IHCA) has warned that the ongoing shortage of Consultants across many specialties in the North-East together with public hospital capacity deficits is restricting patients from accessing timely, high-quality medical and surgical care and is contributing massively to growing waiting lists and poorer health outcomes.

New analysis from the IHCA shows that between the period May 2015 to May 2022, an additional 7,966 (+31%) people have been added to outpatient waiting lists across the NorthEast, with 33,468 now waiting for assessment. A further 2,742 patients are on inpatient/day case waiting lists and another 2,144 are waiting for GI endoscopies.

This means there are 38,354 people across Counties Cavan, Monaghan, Louth and Meath waiting for public hospital inpatient/day case treatment, GI endoscopies or an outpatient appointment with a Consultant.

Our Lady’s Hospital Navan has experienced the largest growth, with the main waiting lists there having almost doubled since 2015 to 8,700. The number of ‘long waiters’ at Navan have increased significantly, with 91 patients now waiting longer than a year for inpatient or day case treatment compared with zero patients seven years ago.

The busiest hospital in the region, Our Lady of Lourdes in Drogheda, has seen its Outpatient waiting list increase by almost 3,500 (+30%) in the past seven years to almost 15,000. Drogheda consistently has one of the largest number of patients in any hospital who are medically fit for discharge but whose discharge is delayed. Patients presenting to

its Emergency Department also faced a 9-hour average waiting time for admission in May.

Dr Alan Irvine, President, Irish Hospital Consultant's Association

The worst affected Specialties Almost 4,500 additional people in the region waiting for an outpatient appointment with a hospital Consultant in four specialties, an increase of 41% since 2015, the analysis has revealed.

The four specialties of Orthopaedics, Dermatology, Gynaecology and Rheumatology have some of the largest waiting lists and combined they account for close to half (46%) of all those waiting to be assessed by a hospital Consultant in the region. These patients run the risk of either a delayed diagnosis of skin and other cancers or may be living with increased pain while awaiting hip or knee surgery or treatment for arthritis.

These lists (seen below) have also seen some of the largest increases since 2015 - an average increase of 41%.

Orthopaedics alone accounts for 15% (5,064) of the entire Outpatient waiting lists at the four North-East hospitals. Louth County Hospital in Dundalk has seen a 127% increase in its Orthopaedic Outpatient waiting list, with an additional 833 people added since 2015, while Our Lady's Hospital, Navan and Our Lady of Lourdes, Drogheda have both seen a 28% increase over the same period. Many of these people will later go on separate inpatient waiting lists if they require hip or knee replacements.

Commenting on the waiting lists, IHCA President Professor Alan Irvine, said, “The severe shortage of Consultants across the NorthEast is the main contributor to the unacceptable delays in providing care to patients. Growing waiting

lists demonstrate the impact of years of Consultant shortages and underinvestment in capacity across these public hospitals.

“We have a chronic recruitment and retention crisis with 22% of all approved Consultant posts nationally either vacant or filled on a temporary or agency – 838 posts in total. This increases to 26% in the North-East.

“The unprecedented level of Emergency Department presentations in recent months and the continued impact of the number of patients hospitalised with Covid-19 has meant further cancellations of surgical activity and outpatient appointments in the North-East and nationwide, which in turn will only increase the waiting lists further and lead to poorer clinical outcomes for patients. There were 281cancelled appointments in April alone at the four North East hospitals.

“In addition, just 68 (8%) of the 829 additional acute beds that were provided nationally over the past two-and-a-quarter

years were in the four hospitals in the North-East. Health service management needs to progress practical plans to significantly expand hospital capacity in the North-East, and throughout the country, at a much faster pace and without further delay.

“The Government must make good on its promise to provide the extra beds, extra Consultants and extra facilities which are badly needed to meet the healthcare needs of the 38,000 people currently on waiting lists at hospitals in the North-East.

“To achieve that end, the Consultant contract talks which resumed last week must honour the ‘unambiguous commitment’ made by the Minister for Health to end the pay discrimination imposed on Consultants contracted since 2012. This and more competitive terms and conditions are crucially important to recruit and retain the increased number of hospital Consultants required to provide timely care to the 902,000 people waiting for hospital care across the country.”

Specialty

North-East Outpatient Waiting Lists May 2015 North-East Outpatient Waiting Lists May 2022 Change

Orthopaedics

4,023

5,064

+26%

Dermatology

3,487

4,728

+36%

Gynaecology

2,712

3,420

+26%

Rheumatology 664

2,153

+224% - more than a 3-fold increase

Total

15,365

+41%

10,886

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

12 News

Pharmacy President Appointment Muireann Ní Shúilleabháin, President of the PSI

“COVID-19 had a huge bearing on the operational activities of the PSI and a significant amount of time and resources were engaged as part of the national response during 2021”

Former Hospital Pharmacist Muireann Ní Shúilleabháin has been re-appointed President of the Pharmaceutical Society of Ireland.

Minister for Health Stephen Donnelly has also appointed four public interest members to the Council of the PSI, the Pharmacy Regulator following an open call for applicants through the State Boards appointment process.

The new appointments are Dr Ann McGarry, Dr Paula Barry Walsh and Mr Peter Dennehy. Ms Dorothy Donovan has also been re-appointed for a second fouryear term.

Muireann Ní Shúilleabháin is a graduate of Trinity College Dublin and has 30 years’ experience, working in many facets of the pharmacy profession. She currently works in community pharmacy in Co. Kerry and she has spent more than twenty-five years as a hospital pharmacist, both in Ireland and the USA (California and Washington states). She has been in a Chief/Superintendent pharmacist role since 2001. Her overall remit is in medication

safety, and she has been an active advocate for quality and safety in medicines management at a local and national level. Muireann has experience in healthcare management, clinical governance, clinical pharmacy, consultancy pharmacy, accreditation processes, pharmacy practice and project leadership. She has a Black Belt in Lean Six Sigma, a Law degree and is currently pursuing a diploma in Corporate Governance.

Meanwhile, the Pharmacy Regulator has published its annual report for 2021, outlining the significant work undertaken by the agency to protect the health, safety and wellbeing of patients and the public by regulating pharmacists and pharmacies in Ireland.

It provides a detailed overview of the work undertaken so far in response to the ambitious targets of the PSI Corporate Strategy 2021-2023. Developed against the backdrop of the COVID-19 global pandemic and the significant threat posed to all sectors of society, the strategy, under the direction of the PSI Council,

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

identifies key strategic objectives, including building pharmacy resilience, adopting a “digital first” business approach and developing a robust regulatory model for community pharmacy settings, items the PSI sees as critical to ensuring pharmacy healthcare activity is regulated to a high and consistent standard.

While COVID-19 had a large impact on the pharmacy sector and the regulator’s work in 2021, the PSI continued to deliver on extensive responsibilities and make strong progress in strategic projects, critical to assuring public and patient trust in pharmacy healthcare and services.

Key activities for PSI during 2021 included: • Significant work to facilitate pharmacy participation in the national COVID-19 vaccination programme.

• Management of the registration of 6,846 pharmacists, 254 pharmaceutical assistants and 1,981 pharmacies as part of PSI’s regulatory remit to assure public trust in the standard of pharmacy care and services.

• Launch of a new registration portal for PSI applicants and registrants as the first phase of an ongoing digital transformation programme.

• Implementation of the amended qualification recognition and registration process for applicants with qualifications obtained in the United Kingdom, as a result of the UK’s departure from the European Union.

• Implementing a new organisation structure to improve organisational capacity, planning and delivery.

• Reviewing 120 expressions of concerns, as well as 80 formal complaints during the year, with 25 complaints during the period referred for further action.

• Responding to 607 pharmacy practice related queries from pharmacists and members of the public and implementing appropriate follow-up actions to deal effectively with queries.

Commenting on the publication of the annual report, Interim Registrar and Chief Officer Dr Lorraine Horgan said that the regulator had continued to deliver on its statutory remit to ensure public and patient trust in the country’s pharmacy services during the immensely challenging circumstances of the global pandemic.

“COVID-19 had a huge bearing on the operational activities of the PSI and a significant amount of time and resources were engaged as part of the national response during 2021. We had extensive engagement and collaboration with the Department of Health and others to progress the requisite legislation*, systems, guidance, training, and governance to enable the effective participation of pharmacists and pharmacies in the national vaccination programme.”

“Pharmacists and pharmacies played a key role during the pandemic and maintaining public trust in the sector was of critical importance. Throughout the pandemic, pharmacists combined their ‘everyday’ duties with the extra responsibilities and demands brought about by the pandemic, across practice settings. Over 600,000 COVID-19 vaccines were administered in community pharmacies in the course of 2021.

Our duty to ensure continued delivery of safe services remained and the ongoing implementation of the PSI’s COVID-19 Operational Standards, developed in 2020, was an important piece of work to provide guidance and support on the operating protocols for pharmacies during this period.”

If it’s out there... we can source it for you

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

14 Pharmacy

A Pharmacist Amongst Paramedics My experience with the National Ambulance Service Clinical Directorate Written by Edel Burton - Edel Burton is a second year Structured Population and Health-services Research Education (SPHeRE) scholar in University College Cork and a scholar on the Health Research Board(HRB) Collaborative Doctoral Programme in Chronic Disease Prevention(CDPCDP). Edel is also a Clinical Pharmacist in the Bons Secours Hospital Cork. As part of her PhD studies Edel carried out a placement in the National Ambulance Service (NAS) Clinical Directorate, in Dooradoyle, Limerick from March to May 2022. Edel’s placement supervisor was Mr. David Willis, Clinical Information Manager with NAS. Edel Burton, Pharmacist and PhD Scholar and David Willis, Clinical Information Manager with the National Ambulance Service Clinical Directorate

worked on a medication safety report which consisted of auditing the use of controlled drugs over a yearly period.

BACKGROUND We have all been told multiple times that a PhD is a marathon and not a sprint. If we are sticking with that analogy, my placement with NAS was like winning the gold medal. This opportunity allowed me to engage with a multidisciplinary team of prehospital care professionals, familiarise myself with the clinical data collected by NAS and become part of this dynamic empathetic team providing patientcentred care.

Due to the developing and everexpanding area of pre-hospital care I believe it is an exciting time for me to become involved with the ambulance service. From my clinical and research experience I have a clear understanding of medications, and protocols related to pre-hospital care and the importance of thorough handover between pre-hospital and acute care. The value of highquality, well-placed and rigorous clinical pre-hospital research and clinical practice initiatives is very

clear across my roles on a daily basis. Thus, as a pre-hospital care researcher and a practising pharmacist this opportunity allowed me to reflect on my research, my role as a pharmacist and continue to engage with stakeholders, procedures and practices in pre-hospital care.

REFLECTION – USING GIBBS REFLECTIVE CYCLE 1988 1. Description The team in the Clinical Directorate consists of a multidisciplinary group including the Clinical Director, The Clinical Information Manager, The Clinical Development Manager, The Covid - 19 and Winter Lead, Data Analysts, The PA to the Clinical Director and Audit Support staff.

During my time on placement, I primarily worked on two reports.

Firstly, in relation to optimising the process of exporting a medication list into the electronic patient care record used by ambulance staff. Secondly, I also

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Mornings usually consisted of data entry or report composition.

After that, the afternoon could look different every day.

Sometimes I might be asked to pharmaceutically analyse a report or offer an insight into a clinical/ research query. Everyday my supervisor would ensure we had a meeting to discuss the progress of my assigned tasks, ask any questions and work through any PhD-related queries. Outside of this time I would be analysing data or reviewing resources to include in my assigned reports.

2. Feeling Before I started my time with the ambulance service I was intrigued to learn more about their organisational structure, medication management strategies, team dynamic, protocols and procedures. I was eager to deepen my understanding of pre-hospital care and felt energized by the opportunity to immerse myself in this environment.

During my time in the Clinical Directorate, I felt that my comprehension and appreciation for integration across not only healthcare professions but also healthcare sectors deepened.

Written on the wall of the office of the Clinical Directorate is “ to serve the needs of patients and the public as part of an integrated health system through the provision of high quality, safe and patient centred ambulance services”. I believe that holistic and robust healthcare delivery is built on teamwork.

Written on the wall of the office of the Clinical Directorate is “ to serve the needs of patients and the public as part of an integrated health system through the provision of high quality, safe and patient centred ambulance services”. I believe that holistic and robust healthcare delivery is built on teamwork.

Different disciplines working together to deliver evidence-based care. Thus, every day I observed that statement on the wall and witnessed its principle in action I felt proud to be associated with this team. This statement also challenged me to continue to embody this statement in my own work and reflect on my own practices.

Furthermore, after the placement I now feel that from both a research and clinical perspective my perception of holistic care has greatly developed. This learning was facilitated by a dynamic team and familiarisation with ambulance service data. As my PhD work is focusing on pre-

15 hospital care, I am delighted that members of NAS will be involved throughout my studies. I strongly believe that my placement with the Clinical Directorate facilitated this collaboration, as it gave me the opportunity to understand the NAS processes and environment.

Consequently, I am motivated to continue my engagement and relationship with the service.

3. Evaluation I can honestly say that all aspects of my experience with NAS were positive. In particular the continued training and immersion in the pre-hospital culture I received by all members of the team. I was given the chance early on in the placement to review Pre-hospital Emergency Care Council Guidelines, Health Information and Quality Authority standards, and other documents related to pre-hospital care.

Due to my background, I was particularly interested in the medication related aspects of the documents. I was very engaged by the regulations surrounding the medications which an emergency medical technician, paramedic and an advanced paramedic can administer. The dosages and routes of administration included in the guidelines also caused me to reflect on the clinical significance of these aspects and their application.

Due to both my research and clinical background I also appreciated the opportunity to engage with the electronic platform operated by NAS. The method in which the current medications prescribed to the patient were captured and how these were handed over to those in acute care piqued my interest. I reflected on how the process of importing a validated medication list into this electronic platform could be optimised. This became one of the main bodies of work I completed during my time with NAS. As a result of the relationship I have developed with the Clinical Directorate team and the synergism between the service and my work NAS became involved in a recent international multidisciplinary event. The Collaborative Doctoral Programme in Chronic Disease Prevention annual Summer School was hosted in Galway on 14-15th June this year, facilitating shared discussion between national and international experts on chronic disease prevention. Mr. David Willis (Clinical Information Manager in NAS) was invited to speak about “National Ambulance Service – Ireland, Deployment of Pre-Hospital EHR” in the “Digital transformation: Irish trailblazers” session.

also in my clinical career. I believe my research helped to forge a link between pre-hospital care and researchers to optimise patient care and shared learning. I think the event was a great success in many ways, due to knowledge translation and informed critical discussion. Furthermore, David’s presentation and discussion allowed me to further develop my appreciation of the pre-hospital care environment and the role of all healthcare professionals in this sector. Additionally, I was left looking towards the future in terms of lessons learned and potential quality improvements initiatives.

4. Analysis For me the most meaningful aspect of this experience was appreciating the value of true stakeholder involvement in research. Previously my knowledge of the pre-hospital phase of care was limited to my practice in acute care and clinical research. As a result of engaging with NAS and involving at least one member of the team in each of my studies I have significantly improved my understanding of this environment. Having experienced the working environment of the Clinical Directorate I now know the finer detail of pre-hospital care practice. I also have gained further insight into the nature and scope of data captured by the service and its application in research and quality improvement.

Additionally, I really appreciated that the team valued my skills and experience as both a pharmacist and clinical researcher.

On reflection, I can see that this was a key facilitator for the success of the placement and a foundation for my future relationship with the team. At first, I did not know exactly how my skills and expertise would fit into the daily operations of the Clinical Directorate. However, as the placement continued, I began to notice how my portfolio and experience were complementary to that of other team members.

Once we spoke the same general language of patient centred care, the mix of different disciplines, experience and perspectives

enriched experiences and resulted in positive outcomes.

I can now see that the Summer School and co-authorship on PhD publications with members of the NAS team were only tangible examples of the mutualistic and collegial relationship we had built.

I contend that the collegiately, mutual respect and appreciation for transdisciplinary working that underpin these outcomes displayed the true value of the relationship. In my opinion this started with the immersive experience of placement, however continued mutual respect and shared interest allows the collaboration to flourish.

5. Conclusion In retrospect I believe my professional skills have developed in many regards. As I was tasked with composing reports I needed to understand how to present pharmaceutical information to a multidisciplinary audience. At first I found it daunting to write a report for use within NAS on a typically pharmaceutical area. In hindsight I can see that the apprehension was not required, and that I should have seen the opportunity as a chance to further develop my presentation and communication skills. The willingness of the team to engage with me and unpick the details of the report to ensure a useful and accessible document ensured a serviceable and constructive report.

In terms of technical skills, I was immersed in the datasets used by NAS, particularly those related to medications and clinical presentation. Initially, I questioned my ability to navigate and analyse these datasets due to their level of detail and volume. However, I have significantly improved my ability to analyse vast datasets due to working with members of the NAS team.

I can now see that maybe due to my clinical discipline and professional experience that I learn by engaging in an activity

and learning with and from my colleagues. Having applied my learning by working with the data I could understand its origin and day-to-day use. As a result, I could clinically appreciate the information gathered. Furthermore, as I am using similar data for my research, I could now analyse the data with more confidence and agility.

6. Action Plan I am very fortunate that my relationship with the Clinical Directorate continues and that I am considered part of the team. Working with the Clinical Directorate is a privilege, and I am grateful to all the team, my supervisors and SPHeRE for granting me this opportunity.

Going forward I hope to gain further hands-on experience with the electronic environment of the ambulance service by attending training sessions. I believe this will provide me with the skills to critically analyse the NAS dataset and also understand the value of this dataset in other areas of the health service.

Also, I can now see that pharmacists can have a significant role in pre-hospital care. Research such as Beatrous et al. 2021 highlights a pharmacist’s role in helping to drive patient safety and well-being in this sector. As a pharmacist, I welcome any opportunity to advocate for pre-hospital care in any of its forms, both from a clinical and research perspective.

CONCLUSION I can say with true confidence that this opportunity has challenged me to further explore the execution of integrated care and research.

I truly believe that my work with NAS has not only vastly improved the potential value of my research but also optimised my ability to provide holistic patient care. I am delighted that I did not need to say goodbye to the NAS team after placement. As I learned from my NAS colleagues; “Never Say Goodbye, Always Say Good Luck”

This event was a milestone for me, not only in my PhD journey but

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

16 News

Minister for Health launches ‘My Health, My Language’ Dr Sura Aldeen and Uzma Shakeen, pictured watching the ‘My Health, My Language’

The Minister for Health, Stephen Donnelly T.D., has launched a video series to help migrants navigate the Irish health system more easily and provide health information in multiple languages.

The series of multilingual videos on the Irish health service were developed to make health advice more accessible to people from migrant communities living in Ireland.

According to the 2016 Census, there are over 600,000 people in Ireland (13% of the overall

population) who are multilingual, speaking a language other than Irish or English at home. The videos, which have been produced in 17 different languages, offer clear information on important health topics such as how the Irish health system works, accessing different types of health care, services that are free and information on pregnancy, newborn and maternal health.

Healthcare systems vary significantly from country to country, and navigating an unfamiliar health service on arrival

English-language skills. We know from our work to reduce inequity in the health service that language and cultural differences can be barriers to people accessing the healthcare they need. These videos provide us with a powerful tool to speak to people living in Ireland in their native language and overcome some of these barriers. Very often, inclusivity benefits everyone.

in a new country has been shown to be a stressful experience and can result in a lack of access to essential services. These videos are presented in a personal, relatable and culturally appropriate manner, using simple language.

The videos are presented by native speakers, who are also healthcare workers based in Ireland. People are often reassured when they see a member of their own community delivering factual, trustworthy health information in the videos.

“The closed captions in the relevant language on each of the videos assist not only people watching in their native language, but also people who are deaf or have hearing impairments, as well as viewers watching with the sound off. We were delighted to have worked closely with Translate Ireland, ICGP and colleagues in the HSE in the development of these videos. Thanks to all the wonderful clinicians who took time out of their busy schedules during the Covid-19 pandemic and the recent Ukrainian crisis to participate in the videos.”

Dr Margaret Fitzgerald, Public Health lead for social inclusion, HSE National Social Inclusion Office says, “Understanding and navigating the health service has been made simpler through ‘My Health My Language’, a series of multilingual videos aimed at migrants and people with limited

These videos were produced by the HSE’s National Social Inclusion Office with support from Translate Ireland, the Irish College of General Practitioners (ICGP), and the HSE’s mychild.ie, National Immunisation Office (NIO), Sexual Health and Crisis Pregnancy Programme and other healthcare workers.

Cardiothoracic Ward opens at University Hospital Galway A new Cardiothoracic ward has opened at University Hospital Galway. The 13 bedded stateof-the-art ward is dedicated to cardiothoracic surgery.

The ward is built to the highest standard and accommodates three isolation rooms, 3 twobedded wards and a four-bedded ward depending on the needs of the patients.

The area includes a pre discharge lounge/ waiting area for patients waiting for admission. There is also a treatment room / pre assessment room where patients can be pre assessed prior to surgery.

Costing ¤4.71m to design, build and equip, the ward has a state-of-the-art monitoring facility with telemetry and in-room monitoring. This provides privacy to the patient when they are resting while allowing them to be

monitored by staff in the ward twenty four hours a day.

Consultant Cardiothoracic Surgeon for the Saolta University Health Care Group Mr Alan Soo welcomed the opening of the new ward. “I’m delighted to open this new ward to the patients requiring cardiothoracic care in the Saolta Hospital HealthCare Group. This state-of-the-art ward is built to the highest standard and regulations which I’m extremely proud of. It will allow us to provide patient care in a safe and clean environment at the same time giving adequate privacy to the patients to recover in their own time. Here, I would like to acknowledge all personnel involve in making this ward project a reality,” he added.

The Cardiothoracic Unit in UHG is the sole tertiary referral centre

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

for both cardiac and thoracic surgery in the West of Ireland.

The thoracic service is one of four designated NCCP lung cancer surgery centres in Ireland.

The department delivers both

elective and emergency services to all hospitals within the Saolta Hospital Health Care Group. It is also a designated training centre for junior surgeons, nurses and allied health professionals.

News 17 Paul Reid to step down as CEO Paul Reid, CEO of the HSE

The CEO of the HSE Paul Reid has advised the Chairman, the Board of the HSE and the Minister for Health that he will be stepping down from his position later this year.

He has agreed with the Chairman that he will step down in December 2022, facilitating a period to advance the process of selecting a successor. He said today that he has no immediate career plans.

In a message to staff today Mr Reid said that he was making the decision with a heavy heart, and that it was the hardest decision he had ever made in relation to his own career.

“Having previously worked in the private, not for profit, central and local government sectors, working in the HSE has been by far the greatest period in my career. It has been truly rewarding leading an organisation whose staff come to work every day to make people’s lives better.

“No organisation will ever match the commitment, dedication and relentless willingness to go

beyond the call of duty that I have witnessed as we battled multiple waves of Covid, a criminal cyber attack while driving a significant reform agenda. This has been truly inspirational for me to experience.”

He said his decision was influenced by two key factors: A desire to spend more time with his family who had made

many sacrifices to support him, and a belief that the HSE was entering a new phase and that the appointment of a new leader was now timely.

Paying tribute to Mr Reid the Chairman of the HSE Mr Ciarán Devane said, “It is with very great regret that I and the Board have heard of Paul’s decision. He has

led the health service through what has been the greatest challenge it has ever faced, and done so with relentless dedication and professionalism. We are very grateful that he will stay in his role for a further period to allow us progress the extremely difficult task of replacing him.”

Improvements in Opiod Agonist Treatment New research from RCSI University of Medicine and Health Sciences recommends that several measures implemented during COVID-19 to maintain access to opioid agonist treatment (OAT) led to improvements in the service and should be continued post-pandemic.

The study, led by researchers in the RCSI School of Pharmacy and Biomolecular Sciences, has been published in the International Journal of Drug Policy.

OAT is type of a treatment in which ‘opioid agonists’ – most commonly methadone – are prescribed for people who are dependent on opioids such as heroin. OAT helps to suppress heroin use, improves mental and physical well-being, and reduces risk of death including drug overdose deaths. A 2019 study showed there were over 10,000 people receiving OAT in Ireland.

Emergency contingency guidelines for opioid agonist treatment (OAT) were introduced in Ireland in March 2020, to ensure rapid and uninterrupted access to treatment while mitigating COVID-19 risk.

Certain measures, such as rapid assessments and telehealth, enabled services to overcome many of the usual barriers to providing treatment. As a result, waiting lists for OAT were drastically reduced, with over 11,000 people accessing treatment in 2021.

This study, consulted a panel of experts and stakeholders including psychiatrists, GPs and pharmacists, as well as people who were accessing OAT for opioid dependency, to identify which of the OAT contingency measures implemented as a result of COVID-19 should be continued.

The panel recommended 16 changes to be continued beyond COVID-19 in Ireland, rather than reverting to pre-pandemic practices. The agreed statements related to facilitating safe access to OAT with minimal waiting time, supporting patient-centred care to promote health and well-being, and preventing drug overdose.

Consensus was not achieved for OAT drug dosing and frequency of urine testing.

Dr Gráinne Cousins, Senior Lecturer in the RCSI School of Pharmacy and Biomolecular Sciences and the study’s principal investigator, commented on the findings, “The emergence of the COVID-19 pandemic transformed how OAT was delivered, in Ireland and internationally. While many authors have suggested that recent innovations should be continued beyond the pandemic, this is the first study

to seek consensus, among a wide range of stakeholders, on whether recommendations introduced in emergency clinical guidelines should be retained beyond the pandemic.

“These consensus recommendations are intended to inform future policy decisions and discussions regarding the delivery of OAT, identifying which changes should be considered for integration into care models beyond COVID-19. For example, all people on OAT should be prescribed and encouraged to take a supply of Naloxone (a medicine that rapidly reverses an opioid or heroin overdose), particularly during high-risk periods. They should also be trained on how to use Naloxone.”

This research was funded by the Health Research Board, Research Collaborative in Quality and Patient Safety [RCQPS-2020-016].

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

18

PEER REVIEW: OPHTHALMOLOGY Planning for our Future - Reconfigured Model of Eye Care Increases Specialist Care for Patients in the Community development of a regionalised model appears to be the best means of achieving this aim.

Central to the reconfigured Model of Eye Care is the implementation of the Integrated Eye Care Team which will extend the delivery of specialist ophthalmic care in the non-acute setting.

The ICO fully supports this policy for increased patient care in the community, with clear referral pathways to acute hospital care.

Priorities for the Integrated Eye Care Teams include the management of children referred from the screening programme, collaborating with screeners to improve the accuracy of the referrals and managing adult patients with a focus on medical retina, glaucoma and the delivery of pre and post operative cataract care. The teams will provide ongoing care for patients diagnosed in the community or ongoing care for patients transferred from the acute hospital.

‘Delivering Integrated Care in Ireland’ Pictured at the ICO Annual Conference 2022, which took place in the Kilkenny Convention Centre from May 16-18th were, Mr Tim Fulcher, President, Irish College of Ophthalmologists and Consultant Ophthalmic Surgeon, Mater Misericordiae with keynote speakers at the ‘Delivering Integrated Care in Ireland’ Symposium: Dr Margaret Morgan, Consultant Medical Ophthalmologist, Royal Victoria Eye and Ear Hospital, Dublin and CHO7; Prof William Power, Clinical Lead for Ophthalmology and Consultant Ophthalmic Surgeon, Royal Victoria Eye and Ear Hospital, Dublin; Ms Chriosa O’Conoor, Optometrist, Mater Misericordiae University Hospital, Dublin; Prof David Keegan, UCD Clinical Professor of Ophthalmology and Retina, UCD School of Medicine, University College Dublin. National Clinical Lead for Diabetic Retinopathy Screening.

The Irish College of Ophthalmologists (ICO) and the Clinical Programme for Ophthalmology continue to deliver the National Education Series for the Integrated Eye Care Team in 2022 in support of the expansion of specialist ophthalmic care to patients in the non-acute setting.

The National Education Series aims to support the implementation of the Integrated Eye Care Team model, highlighting the key rationale for establishing the team which is to deliver a health service that is patient focused, promotes evidence based practice, decompresses hospital based

eye services and improves timely access to care for patients.

The specialty of ophthalmology has experienced rapid advances and innovations over the last two decades which now provide prevention and treatment for a significant proportion of sight threatening diseases.

The anticipated five fold increase in the elderly population by 2040 coupled with advances in treatment has demanded a reconfiguration of eye services countrywide.

The ICO and the National Clinical Programme for Ophthalmology is working extensively with the

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Consultant Medical Ophthalmologists lead and work as part of the Integrated Eye Care team and are co-located across the acute and community setting, to ensure access to acute inpatients services if required, subspecialty resources for more complex cases and cross specialty multidisciplinary care.

HSE and with the Department of Health to ensure the existing and projected future demand for eye care services in our population can be delivered.

Allied health professionals working as part of the team include ophthalmic nurses, orthoptists, optometrists and ophthalmic technicians.

The Clinical Programme has determined that, in line with Government policy, the majority of services should be provided within the community setting. As such, integration of acute and community services is essential in order to allow for rebalancing of access and delivery of eye care services from acute hospitals to the community. The aim is to provide high-quality, consistent, efficient and effective care. The

The delivery of the model of care is underpinned by clinical governance oversight promoting patient safety and the sustainability of a patient-centered model.

ICO and Clinical Programme National Education Meeting Series for the Integrated Eye Care Team To support the implementation of the Model of Care recommendations, the ICO in

120mg and 180mg Film-coated tablets

A NEW generation antihistamine offering non-drowsy, long-lasting relief from allergy symptoms Abbreviated Prescribing Information Telfast 120 and 180 mg film-coated tablets Each tablet contains 120 or 180 mg fexofenadine hydrochloride.

Presentation: Telfast 120 mg: Peach, capsule-shaped, film-coated tablet with 012 on one side and a scripted e on the other side. Telfast 180 mg: Peach, capsule-shaped, film-coated tablet with 018 on one side and a scripted e on the other side. Indications for Telfast 120 mg: Telfast 120 mg is indicated in adults and children 12 years and older for the relief of symptoms associated with seasonal allergic rhinitis.

Indications for Telfast 180 mg: Telfast 180 mg is indicated in adults and children 12 years and older for the relief of symptoms associated with chronic idiopathic urticaria. Dosage: Adults and children aged 12 years and over: One tablet once daily before a meal. Not recommended for children under 12 years. Studies in special risk groups (elderly, renally or hepatically impaired patients) indicate that it is not necessary to adjust the dose of fexofenadine hydrochloride in these patients. Method of administration: Oral. Contraindications: Hypersensitivity to the active substance or any of the excipients. Warnings and precautions: There is limited data in the elderly and renally or hepatically impaired patients.

Fexofenadine hydrochloride should be administered with care in these special groups. Patients with a history of or ongoing cardiovascular disease should be warned that, antihistamines as a medicine class, have been associated with the adverse reactions tachycardia and palpitations. Interactions: Fexofenadine does not undergo hepatic biotransformation and therefore will not interact with other medicinal products through hepatic mechanisms. Coadministration of fexofenadine hydrochloride with erythromycin or ketoconazole has been found to result in a 2–3 times increase in the level of fexofenadine in plasma. The changes were not accompanied by any effects on the QT interval and were not associated with any increase in adverse reactions compared to the medicinal products given singly. Animal studies have shown that the increase in plasma levels of fexofenadine observed Distributed in Ireland by Clonmel Healthcare Ltd.

after coadministration of erythromycin or ketoconazole, appears to be due to an increase in gastrointestinal absorption and either a decrease in biliary excretion or gastrointestinal secretion, respectively.

No interaction between fexofenadine and omeprazole was observed.

However, the administration of an antacid containing aluminium and magnesium hydroxide gels 15 minutes prior to fexofenadine hydrochloride caused a reduction in bioavailability, most likely due to binding in the gastrointestinal tract. It is advisable to leave 2 hours between administration of fexofenadine hydrochloride and aluminium and magnesium hydroxide containing antacids. Fertility, pregnancy and lactation: Fexofenadine hydrochloride should not be used during pregnancy unless clearly necessary. Fexofenadine hydrochloride is not recommended for mothers breast-feeding their babies. No human data on the effect of fexofenadine hydrochloride on fertility are available. In mice, there was no effect on fertility with fexofenadine hydrochloride treatment. Driving and operation of machinery: On the basis of the pharmacodynamic profile and reported adverse reactions it is unlikely that fexofenadine hydrochloride tablets will produce an effect on the ability to drive or use machines. In objective tests, Telfast has been shown to have no significant effects on central nervous system function. This means that patients may drive or perform tasks that require concentration. However, it is advisable to check the individual response before driving or performing complicated tasks. Undesirable effects: Headache, drowsiness, dizziness, nausea. Refer to Summary of Product Characteristics for other undesirable effects. Pack size: 30 tablets. Marketing authorisation holder: Opella Healthcare, 82 Avenue Raspail 94250, Gentilly, France SAS T/A Sanofi. Marketing authorisation number: PA23180/003/002-003. Medicinal product subject to medical prescription. A copy of the SPC is available on request or visit www.clonmelhealthcare.ie.

Last revision date: March 2022.

2022/ADV/TEL/067H

20

PEER REVIEW: OPHTHALMOLOGY Care in Ireland” and “Planning for the Future” dedicated to the changing environment of eye care in Ireland and the future plans to manage the demand for services in light of our expanding and aging population, and the incredible new sight saving therapies available.

collaboration with the Clinical Programme for Ophthalmology introduced the National Education Series for the Integrated Eye Care Team in 2019.

The overarching aim of the series is to provide a platform for ongoing engagement and wider consultation with all key stakeholders to facilitate their contribution to the development, delivery and outcome evaluation of the reconfiguration of services.

The series is designed to inform stakeholders of the latest developments in the expansion of ophthalmic services, and to share examples and results from Community Healthcare Organisations (CHO’s) where the reconfiguration of services is being implemented.

The initial sessions concentrated largely on developments in the three Dublin CHOs (CHO6, CHO7 & CHO9) where new Consultant Medical Ophthalmologists have been appointed.

The series continued in 2020 and 2021 in a virtual format,

due to COVID 19 public health restrictions. A number of meetings are taking place throughout 2022.

The 2021 webinar provided an update from the ophthalmic consultant team on the progress for the development of regional ophthalmic services in Cork/ Kerry to integrate hospital and community service and plans for the future. The meeting was chaired by National Clinical Lead Prof. Billy Power.

The team discussed the new Community Centre in Ballincollig, due to open later this year with 20 clinical rooms, which can accommodate 36 newly recruited staff and will allow over 30,000 patients a year to be seen at the facility. Two dedicated purposebuilt injection clean rooms are designated for intravitreal injections, which will provide the potential for 280 injections per week. This future additional capacity would provide a threefold increase to current injection capacity. The new clinic will be an enormous benefit to the current congestion in the hospital and

community services, allowing access for patients with stable glaucoma, AMD and paediatric conditions to be seen, thereby restoring access for patients with surgical needs, including cataract, in the acute system.

Plans for the development of a second eye-theatre in South Infirmary Victoria University Hospital, Cork will also improve access for patients requiring cataract and other surgeries. A third dedicated eye theatre at the hospital, is in the business case plan for the expansion of services in 2021-2031, to accommodate ongoing growth in demand for cataract surgery.

The latest webinar in the National Education Series took place on April 28 this year, returning to Dublin with an update on the implementation of the Integrated Eye Care Team in CHO6 / Community Healthcare East.

ICO Annual Conference The ICO Annual Conference, held in May this year, included symposia on “Delivering Integrated

Despite the challenges of the past two years, much progress has taken place in the specialty of ophthalmology with investment into the new Integrated Eye Care Teams at community and hospital level, and the establishment of dedicated cataract theatres.

There is much more to be done to address the waiting lists in ophthalmology and the ICO focus, alongside the work of the National Clinical Programme, remains on delivering a service equipped to manage the areas of greatest patient demand.

Save the Date: Eye Care in Focus Conference The ICO is excited to announce plans for our first conference for the extended eye care team, which will take place in The Gibson Hotel, Dublin on Tuesday, October 4th, 2022.

The conference will be a full day meeting delivered via clinical symposia, guest lectures and panel discussion. The conference programme will be of interest to ophthalmologists, general practitioners, optometrists, orthoptists, nurses and technicians.

The conference programme and registration details will be shared via the ICO website www.eyedoctors.ie and Twitter @eyedoctorsirl over the coming weeks.

News - New Research on Willebrand Factor New research from RCSI University of Medicine and Health Sciences has found that high levels in the bloodstream of a key protein involved in blood clotting called von Willebrand Factor can lead to poorer outcomes for breast cancer patients.

The findings will help researchers and doctors to better understand and treat breast cancer to reduce the risk of life-threatening blood clots and cancer spread in patients.

Published in the Journal of Thrombosis and Haemostasis, the research found that patients with breast cancer had very high levels of von Willebrand Factor in their blood and that patients with the highest levels had the poorest outcomes. This work suggests that analysis of von Willebrand Factor levels may be useful to help predict clinical outcomes in patients with breast cancer.

The study also examined how breast cancer triggers high levels of von Willebrand Factor and found that breast tumour cells cause release of the clotting protein which helps the breast tumour cells to circulate in the blood stream and may aid breast tumour spreading to other organs in the body. Anticoagulant medication or blood-thinners which are already used to treat blood clots, could inhibit this effect by reducing levels of von Willebrand Factor and also preventing the spread of cancer cells in the blood stream.

The findings of the research will help doctors to better understand why patients with breast cancer have increased risk of blood clots and also why this may contribute to worse disease, cancer progression and spread throughout the body.

Dr Jamie O’Sullivan, Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI, said, "Our findings now show, for the first time, that this blood clotting may be caused by increased levels of a key pro-clotting protein, von Willebrand Factor and that the breast tumour cells directly interact with the blood vessel wall to promote release of this protein. Interestingly, this not only increases risk of blood clotting for these patients, but may also promote breast cancer cells spreading throughout the body via the circulation. Our work helps to better understand why patients with breast cancer have increased risk of blood clots and also why this may contribute to worse disease, cancer progression and spread throughout the body which will have a huge impact on the treatment of breast cancer and the outcomes for patients worldwide."

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

A FIXED COMBINATION OF

TREHALOSE

HYALURONIC ACID

BIOPROTECTION

HYDRATION

le Availabe on th GMS

CLINICALLY PROVEN1 TO

HYDRATE, LUBRICATE, REPAIR AND PROTECT THE OCULAR SURFACE 2

3

References 1. SchmidlD1 , SchmettererL et al. Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease., Cornea. 2015 Apr;34(4):421-6 2. Chiambaretta F. et al; A randomized, controlled study of the efficacy and safety of a new eyedrop formulation for moderate to severe dry eye syndrome Eur J Ophthalmol 2016 3.Matsuo T. Trehaloseprotects corneal epithelial cells from death by drying. B J Ophthalmol. 2001; 85(5)610–12

Théa Pharma ltd., Golden Mile Industrial Park, Breaffy Rd., Castlebar, Co. Mayo, F23 D299. T: 094 925 0290 www.theapharma.ie TP/22/041 Thealoz Duo Advert V1

22

PEER REVIEW: MEDICAL TRAINING

Advanced Training for Medical Workers The use of case method in the learning process of advanced training courses for medical workers in Ukraine and worldwide Written by Tatiana Iarmak – http:// orcid.org/0000-0001-5371-2958; iarmak.tat@gmail.com; Lecturer of the Department of Advanced Training of Junior Medical Specialists at the Municipal Health Care Institution “Kharkiv Regional Medical Vocational College”, Kharkiv, Ukraine.

Corresponding Author details: iarmak.tat@gmail.com

Key words: Case method, case study, interactive technologies, education, educational process, innovations, medical workers The aim of the study: Show the importance of applying the case method in the educational process of advanced training courses for health professionals as a method of correlation between theory and practice which activates and optimizes the educational process; develop an ability to analyze; to draw conclusions, make independent decisions in particular in critical, atypical situations; form critical thinking; build confidence in making responsible decisions which will result in improving the professional level of every health worker.

Brief summary: This article researches the use of case method in the learning process of advanced training courses for medical workers; displays the results of the optimization of the learning process using the case method and the prospects of their use in the learning process. The case method is an interactive technology aimed at forming new

qualities and skills in students.

Nowadays the case method is actively used in leading educational institutions in Europe and America and has its specifics of use in teaching of various disciplines. The case method is a specially prepared educational and methodical material which contains a structured description of situations taken from real practice. It is based on the solution of a specific problematic situation on the basis of a real case - a situational task. For medical workers, this is a real medical situation which is presented in the form of an educational task.

For example, a real clinical case where a doctor or a nurse needs to diagnose a patient - prescribe tests, examination methods, treatment. Or it can be a case from medical practice during surgery, childbirth etc. The case method activates mental activity, reveals and improves students' learning abilities, creates conditions for creativity, increases the ability to analyze information, develops professional competence, ability to solve various problems, expands the scope of understanding of real situations at work. Students learn how to communicate, discuss, express their opinion, find the most correct and effective solution to the problem. This method has a great educational potential.

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Background: The case method first originated in 1870 in Harvard Law School.

In 1912 the Harvard School of Business introduced a compulsory course - a method of situational analysis called "The Art of Doing Business". Students were given tasks and offered different solutions. It was necessary to choose the optimal one. The students were solving existing practical problems during classes.

In Harvard, this method is called "situational decision-making exercises". Today it is used in the educational process of many educational institutions around the world in almost all fields.

The Case Clearing House of Great Britain and Ireland (European Case Clearing House (ECCH) since 1991), established in 1973 at the initiative of 22 higher education institutions is the leader in collecting and distributing cases. ECCH is a non-profit organization that is affiliated with organizations located in different parts of the world which spreads and uses case studies. ECCH currently consists of about 340 organizations, including The Harvard Business School Publishing, the London Business School in England, INSEAD, Fontainebleau in France, the Institute for Management Development (IMB) in Lausanne, Switzerland, the School of Management in Cranfield IESE in Barcelona, Spain. Each of these organizations has its own collection of unique cases, which ECCH has the right to distribute.

Specialists of the School of Public Administration J. Kennedy of Harvard University at the National Academy of Public Administration under the President of Ukraine (formerly the Institute of Public Administration and Local SelfGovernment) presented the case method in Ukraine in 1992. In 1996, the Center for Innovation and Development introduced the case method into the Ukrainian

education system. In recent years, Ukraine has been paying more and more attention to innovative technologies in education. The need for innovative interactive approaches to learning is due to the intensity of information flows.

Innovation in the educational process is a necessity. Modern innovations help to increase the efficiency of the educational process. Interactive learning technologies are one of the most effective modern methods for improving the quality of education, so the introduction of the "case method" or "situational methodology" in the practice of modern education is very important. Case study is becoming one of the promising learning technologies as it is aimed at the development of professional competencies and improvement of professional skills. According to the Strategy for the Development of Higher Education in Ukraine for 2021-2031 "The mission of higher education is to ensure sustainable innovative development of Ukraine through the training of highly qualified specialists, the creation and dissemination of knowledge ..."; "Priority principles of higher education development in Ukraine: professionalism, focus on achieving the highest quality of education ...".

In medical education, at the training courses for health professionals, the essence of the method consists in the following - the students are offered a real clinical situation from their professional profile which can have several solutions. The main thing is to find the best, most effective, i.e optimal solution to the problem presented. Students are divided into groups. The group analyzes the situation, discusses possible solutions to the problem for that finds out the causes of certain symptoms, makes up a plan of examination, suggests laboratory diagnostics, suggests a possible preliminary diagnosis, prescribes the most effective treatment, develops preventive measures and makes optimal decisions. When

23 solving the problem the students are active, exchange their points of views, analyze, give advice which helps a group to come up with an optimal solution to the problem and accelerates the uptake of the material. The peculiarity of the case method is that the problematic situation is created on the basis of a real clinical case, so that the students gain practical experience in solving problems with further use in the work.

Thanks to the case method, the learning process is organized in a new way that students become active participants, motivated and involved in vivid discussions. It is a creative insightful process and at the same time a complex system, which includes modeling, method of a problem-based learning, imaginary experiment, method of description. The introduction of the case method or case study changes the role of the teacher – a teacher becomes an expert - assistant guiding students in solving the proposed tasks.

The case method as an interactive method of teaching promotes the formation and development of creative clinical thinking in medical professionals. This method allows to unleash the potential of a

doctor or nurse to think creatively from a professional point of view, considering the individual characteristics of each patient.

Today it is necessary to make decisions quickly, especially in critical situations, to have readyto-go methods of action, to own a situation. Every time prescribing treatment, examination diagnosing a patiant, the doctor solves the case. The nurse participates in the treatment of the patient together with the doctor. She performs all medical procedures and manipulations prescribed by a doctor and is responsible for the quality of their conduct, which depends on her competence, skills and abilities.Therefore, a nurse should be able to make her "nursing diagnosis" and prescribe "nursing treatment". Today, there are many definitions of a nursing diagnosis, which are recognized as a part of the professional activities of a nurse. “Nursing diagnosis” is “The patient's state of health established as a result of a nursing examination and requiring intervention by a nurse” (Carlson, Kraft, & McGure, 1982). The Classification of

Nursing Diagnoses (McLain) was first proposed in 1986. "A nurse must always perform her duties professionally, continuously improve their special knowledge and skills, improve their cultural level" (Article 3. "Code of Ethics for Nurses"). Competence, expertise, qualification of both the doctor and the the nurse allow to analyze clinical cases and situations in the best way and make an optimal decision. And the case method is of great help here.

Conclusions: The use of the case method or case study in the educational process of advanced training courses for health professionals is a necessity. It is very important in education for adults. Adults already have professional and life experience, skills, abilities, which contributes to a greater understanding of situational problems, their solution. The method allows to develop creative and critical clinical thinking in

both the teacher and students; activates, stimulates, motivates to learn. The method opens prospects to significantly improve the quality of education, to fill the educational process with creative content. Advantages of use - interactivity, efficiency, optimization of educational process. Advantages of the case method - it develops problemsolving and decision - making skills, initiative, individual and collective responsibility, working with the team, argument skills to defend one’s point of view, improves communication and presentation skills, makes everyone an active participant, increases interest in the material learned, links theory with practice.

The case study method brings novelty to the teaching and learning process and increases the efficiency of the educational process. The case method in the educational process performs such important functions as educational, analytical, research, training, prognostic.

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

24

PEER REVIEW: PATIENT SAFETY

Why is Healthcare Still not Safe?

Written by Dr Dale Whelehan, PhD in Behaviour Sciences, Trinity College Dublin, the University of Dublin

In the turn of the century a report was published recognising ‘to err is human’. It recognised the fallible nature of humans, and how error-making is a part of work. Nonetheless, ongoing discussions exist in the media and literature as to ‘why is healthcare still not safe?’.

In this article, I will give an executive overview, based on empirical evidence and broad disciplinary considerations, that such issues exist to a myriad of intertwining complex and historically associated variables.

There will be reference to the foundations of the safety for patients movement, the growing influence of medical bureaucracy, the flaws in research design and assessment of progress, and an overemphasis on leveraging change at the individual level and not the organisational level.

Foundations of patient safety First – we need to look back to fully understand the causal factors which led to the formation of focus on healthcare safety.

While this article questions why healthcare is still not safe, and could be argued from the lens of injury to practitioners in their work, the focus of this article is on the end user of healthcare work – the patient. Patient Safety is a healthcare discipline that emerged with the evolving complexity in health care systems and the resulting rise of patient harm in health care facilities. As a discipline it aims to prevent and reduce risks, errors and harm that occur to patients during provision of health care. A cornerstone of the discipline is continuous improvement based on learning from errors and adverse events.

Day to day adverse events create a burden of harm which can lead to safety issues for our patients.

These include things such as medication errors, diagnostic errors and health-care associated infections.

The issue of patient safety was first raised in 1847 by Semmelweiss who documented the difference in rates of medical harm across two wards of care. Coupled with disparate amounts of research over the coming decades, a seminal study conducted by Moser in the 1960’s called ‘Diseases of Medical Progress’ as well as the Harvard medical practice study first began to succinctly identify instances of safety concern in healthcare. This was the beginning of the research movement and founded with input from the safety sciences.

A successful application of this research, and considered a gold standard example to this day, was the application of human factors and safety science research to the discipline of Anaesthesia by a researcher called Jeff Cooper.

Large scale reductions in patient harm were recorded from this initial movement.

Alongside this stream of work, a parallel movement was forming, motivated by milestone cases relating to medical error.

Confounded by several variables, including media, these cases created a political uproar as each played on a different public fear.

Libby Zion, who died as a result of poor supervision and overworked staff. Willie King, whose wrong leg was amputated. Josie King, who went to a prestigious and highly rated hospital for cancer treatment and received a dose that was too high. Elaine Bromley, who went in for a routine nasal operation and died soon after. Growing hostility towards the healthcare

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

professions ensued, with large blame being placed on individuals within systems. There was a true desire to prevent such cases from ever happening again, leading to successful events such as the Annenberg 1 and 2 conferences.

These brought together a broad range of stakeholders under the impetus to make healthcare safe in the turn of the century.

A third movement emerged around this time, fuelled in part by both aforementioned movements, but also by publication of significant reports such as the ‘To Err is Human’ report which estimated 44,000-98,000 deaths/year U.S citizens died due to medical error every year. Political will to deal with these issues through ‘shaking up healthcare’ resulted, leading to application of managerialism style interventions. Medical practitioners became managers to deal with issues of safety, leading to the formation of an in-group thinktank for patient safety assurance.

Industralisation of medicine ensued, creating a corporate elite of healthcare staff who utilized superficial principles of evidencebased approaches from the safety sciences, in conjunction with Taylorism principles of scientific management, to create faux solutions which were branded as scientific interventions. This has become the dominant movement, and despite efforts, a 2016 John Hopkins Study concluded that little progress has been made and safety issues are the 3rd leading cause of death.

Research design A discourse has been ongoing in academic institutions since the biomedicalisation of patient safety research. A twenty year review has found that, using retrospective analysis of charts, there exists little shifts in the metrics previously used to define safety in healthcare – whether they be harm, adverse events, or medical error. The interchanging utilisation of these terms has meant the research is heterogenous, and often poorly understood. Utilisation of inappropriate research methods to make sweeping generalisation and conclusions has become a normal issue in the discipline of research, further conflating the

difficulty in truly understanding the effective interventions to make healthcare safer.

Along the journey since the publication of To Err is Human, we have lost one of the pivotal segments of the research puzzle – to involve the experts of safety sciences – the psychologists, anthropologists, human factor engineers – as our methodological experts. Instead we have biomedicalised the discipline, broadening its parameters to include aligned disciplines such as infection control, which has led to a forever squeezing of opportunity for the nonepidemiological disciplines. This positivist approach has meant many disciplines have been effectively silenced. A fundamental realignment to recognise that medicine needs these disciplines to make evidence-based interventions is important.

Organisational behaviourist Dr. Kathleen Sutcliffe has conducted extensive research on the issue of healthcare safety and concludes healthcare is a mindless and vulnerable system. She identifies a series of confounding variables influencing healthcare issues – ranging from micro-issues such as individual performance, mezzo issues such as interpersonal skills, as macro issues such as organisation design and culture.

These manifested themselves through behaviours which led to individualism, siloed ways of working, hierarchical governance, and inability to meet growing public service needs. The growing focus on performance science in recent decades from psychologists has also identified a link between staff wellbeing and patient safety.

While healthcare workers have always worked above and beyond their vocational requirements, the confounding role that COVID has played on levels of burnout in the healthcare workforce is likely to significantly influence healthcare safety efforts.

Culture One of the growing issues around patient safety is the risk of poor patient safety culture.

When individuals work together, in teams, and not just groups with individuals with personal

25 interests, then a richer and fuller understanding of phenomena can be achieved. Unfortunately healthcare has a long way to go in achieving this vision.

Ethnographic research conducted

by Dr. Sutcliffe identified that healthcare workers continue to perform well at the individual level, but fail to form a level of team cognition which would allow them to communicate at a system level, and thus towards the higher system-level requirement of patient safety assurance.

Leadership should be the focus going forward, at all levels, with a reduced emphasis on quality reporting as the only metric of safety evaluation, and instead increased effort on system resilience capability building.

Supporting such strategic endeavours is the need to build a culture of patient safety which is honest, reflective, constructive and ethically-driven. Viewing the blackbox analogy used in the airline industry as an example of opportunity to learn from adverse event causal effects instead of as an oversight regulatory intervention is where we need to get to in healthcare. To ensure that first, we need to build psychological safety in our teams, where blame culture is removed, and individuals are recognised as just one cog in a complex machine which attempts to make a system as hazardous free as possible.

Too long the blame has been on scapegoating the individual as the causal outcome of an egregious error, and instead system ownership to build authentic safety culture, away from biomedicalization and managerialism approaches is needed.

The Solution: A highly-reliable system So how do we build such desired states? We have two approaches

to safety. Safety 1, which focuses on accident causation in risk management. This identifies root causes which differ from normal work. It is managed through regulation. It is bio-medically driven and bureaucratically positivist and includes Heinrich’s pyramid and Swiss cheese models of linear sequential chain models.

This approach alone is problematic as it assumes relationships between causes but ultimately blames people for making healthcare not safe.

Safety 2 on the other hand, utilises aspects of accident and high reliability organisation theories. It is interpretative in approach, and focuses on making authentic risks and consequences more apparent, so that they can become reversible. This resilience engineering also enables capabilities in people to adapt to dynamic responses. It recognises that people are performing exceptionally well despite trying conditions. Instead of focusing on causal outcomes, accidents and errors are thought to happen naturally in complex systems. A high reliability organisation is one which can reduce such failures where they might be normally expected. Serious accidents in high risk and hazardous operations can be prevented through a combination of organizational design, culture, management, and human choice. High reliability organisations seek to organize in ways that increase the quality of attention across the organization, thereby enhancing people's alertness and awareness to details so that they can detect subtle ways in which contexts vary and call for collective mindfulness.

There are particular behaviours needed to build a HRO:

 Treat anomalies as symptoms of a problem with the system and building anticipation and learning opportunities.  Building situational awareness is extremely important  Refusing to simplify complex problems.  Commiting to resilience developing the capability to detect, contain, and recover from errors. Errors will happen, but we are not paralysed by them.  Deference to expertise - follow typical communication hierarchy during routine operations, but defer to the person with the expertise to solve the problem during upset conditions.

These behaviours are particularly important as safety is a dynamic non-event. It is dynamically preserved by human adjustment, and a non-event because successful outcomes aren’t visible.

Conclusion To conclude this article I rephrase the question from ‘why is healthcare still not safe’ to ‘how do complex healthcare organisations achieve safe, reliable, resilience performance under trying conditions’. This allows us to focus on the organisational and behavioural levers we need to pull to evoke effective change.

It is a fundamental rethinking of the patient safety discipline that is needed. A focus on not scrutinising the people within the system as the cause of safety issues, but the system itself. The "medicalisation" of the patient safety movement has

placed it under the hegemony of bureaucratic-industrialized medicine and rendered the movement with little hope of truly understanding the basis (social and psychological as opposed to medical) of accidents in healthcare delivery. If we want to make healthcare safe, we need to: 1. Achieve greater consilience and reducing scientific bureaucratic technocracy. Making the human factors the subject matter experts, and the healthcare workers the content experts 2. Focus on new behaviours and culture – rejecting approaches where rule bound organisations are considered safe, and instead focus on safety culture.

Reduce hubristic behaviours and build capability to prepare for the unknown. Safety is not an objective quality, but an activity created and destroyed every minute.

3. Reshift the research towards the evidence-base and not just cherry picking the parts of patient safety we like such as checklists. Redefine our understanding of what is patient safety research and what isn’t. Similarly, create greater understanding of different latent constructs such as medical harm, medical error – and understand the implications of these terminologies for media dissemination. Foster the energy of the patient safety movement and engage in meaningful patient engagement to design studies.

4. Start with understanding the dynamic nature of people and system interaction to influence safety. There is a need for focusing on supra organisational interventions which transcend both the individual behavioural and organisational levers of patient safety.

5. Be driven by science and not by popular movement.

Safety in healthcare has a fluid and fractured intellectual history. Vested interests, cognitive dissonance, and oversimplification of complex systems does nothing in the end to make healthcare safer.

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

26

PEER REVIEW: GOUT

Closing the Gap: Improving Pharmacist Knowledge of Gout Management Written by Dr. Emma Dorris (Scientist, UCD), Mariosa Kieran (Pharmacist, Mater Misericordiae University Hospital), Professor Nicola Dalbeth (Consultant Rheumatologist, University of Auckland) and Professor Geraldine McCarthy (Consultant Rheumatologist, Mater Misericordiae University Hospital/UCD) MSU crystals. The goal of urate lowering therapy is to reduce serum urate to a therapeutic target level, thereby permitting MSU crystals to dissolve, in addition to preventing further crystal formation and deposition.

Dr. Emma Dorris (Scientist, UCD)

Professor Geraldine McCarthy (Consultant Rheumatologist, Mater Misericordiae University Hospital/UCD)

Mariosa Kieran (Pharmacist, Mater Misericordiae University Hospital)

Professor Nicola Dalbeth (Consultant Rheumatologist, University of Auckland)

Gout is the most common form of inflammatory arthritis in adults. The incidence of gout is rising. People with gout have an increased risk of cardiovascular disease, and gout is associated with a number of comorbidities including diabetes and renal impairment. The increased incidence of gout together with increased cardiovascular risk and comorbidities is a significant public health challenge.

Unlike other common rheumatic diseases, the underlying cause of gout is well understood. Gout is caused by hyperuricaemia, too much uric acid in the body. This can occur due an underexcretion and/or overproduction of urate, which leads to monosodium urate (MSU) crystal formation and deposition in joints and tissues in susceptible individuals (figure 1). Acute gout flares occur as an inflammatory response to the

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

An important issue in urate lowering therapy is that paradoxically, initiation of urate lowering therapy can actually induce a gout attack.

This happens because the urate lowering therapy causes MSU crystals to be shed from the articular cartilage into the joint space, resulting in acute inflammation. To prevent this, a low dose of anti-inflammatory prophylaxis, such as colchicine, is recommended for at least the first three to six months following initiation of urate lowering therapy.

Community pharmacists are the most easily accessible members of a patient’s health care team.

Pharmacists are often a key source of information on disease management and patients have confidence in them. Pharmacists act as a critical resource for effective management of disease, particularly when chronic such as gout. Thus, open communication and education between the pharmacy and prescriber communities is essential to provide the most up-to-date and appropriate patient care.

However, pharmacists frequently report a lack of patient treatment plan information and clinical connection to other healthcare professionals as barriers to providing optimal care to patients.

The use of low dose colchicine as a prophylaxis is an example of this gap in knowledge translation.

Colchicine use in gout is most commonly used in the treatment of acute gout flares in a strictly time limited fashion. Legacy prescribing, whereby short or intermediate-term medications are

not appropriately discontinued, is prevalent. Patients, and indeed pharmacists, can be unsure whether the prescribed colchicine is intended as a prophylaxis or is a legacy prescription that was previously prescribed in case of flare. This confusion can be magnified by lack of clear, definitive statements on updated best practices from national bodies and the time lag in incorporating professional body recommendations into readily accessible drug information sources, e.g. the product Summary of Product Characteristics, the British National Formulary. Pharmacists have reported that the advice on use of colchicine as a prophylaxis in their typical reference manuals is poorly defined in comparison to its use for acute flares. This can lead to conflicting advice being given to patients from their pharmacists and rheumatologists about gout management, particularly in relation to colchicine use. This prompted research into the pharmacist knowledge of gout management, leading to the development of an educational intervention for pharmacists.

Our research showed that pharmacist-knowledge of gout management in Ireland was not in line with current European (EULAR) gout management guidelines.

However, we also demonstrated that pharmacists do not typically use disease management guidelines as standard sources of information. As such, there is a knowledge gap in the most up to date recommendations for gout management. Given the wide number of conditions encountered on a daily basis in community pharmacy, this is somewhat understandable.

As such, a dedicated effort must be made by prescribers and professional societies to communicate treatment standards to pharmacists.

27 In response to our initial findings, an education intervention was co-developed by two consultant rheumatologists and gout specialists, a pharmacist and general practitioner. We worked closely with the site founder of Pharmabuddy, the eLearning platform designed for and used by pharmacists. A thirteen minute video tutorial on the pharmaceutical management of gout was produced and is hosted on the Pharmabuddy eLearning platform. Nine months after the initial launch of the video, the impact of the educational intervention was assessed.

Pharmacists who had watched the tutorial had significantly greater knowledge of gout management than the pharmacists who had not. Importantly, pharmacists who had watched the tutorial had greater knowledge about colchicine and its use as prophylaxis following initiation of ULT. This demonstrates that low-cost educational interventions

can greatly improve pharmacist knowledge of gout management.

Gout management recommendations can be impeded if translation into pharmacy practice is neglected.

Our research acts as a proof of concept that a co-designed educational intervention on gout management is effective. The Pharmacy Act 2007 requires that all pharmacists in Ireland undertake continuing professional development (CPD). For wider implementation, our intervention could be integrated into a CPD for gout management. This could increase the reach of this information to pharmacists.

Pharmacists, particularly community pharmacists, have a hugely broad remit. The onus is on the rheumatology community to communicate to pharmacists and other health care providers about up-to-date recommendations for gout management. Improved pharmacist knowledge can in turn

empower patients to assume selfmanagement of gout.

The original research paper is available open access at BMC Rheumatology: Pharmacist knowledge of gout management: impact of an educational intervention. ER Dorris, M. Kieran, N. Dalbeth & G. McCarthy.

BMC Rheumatol 6, 30 (2022). https://doi.org/10.1186/s41927022-00259-x Figure 1: Pathophysiology of Gout Both the overproduction of urate and the underexcretion of urate can contribute to hyperuricaemia, leading to gout.

rate of crystal reduction is dependent upon both the total crystal load and reduction in serum uric acid. Urate lowering therapy initiation can cause rapid dissolution of crystal deposits and may lead to increased flare rate and associated pain due to the removal of protein deposits protecting the underlying surface from attack by inflammatory cells. Thus an anti-inflammatory prophylaxis, such as Colchicine, is recommended for the first six months following initiation of urate lowering therapy.

Image Copyright: Emma Dorris

The goal of urate lowering therapy is to reduce serum uric acid levels below its saturation point, thereby preventing crystal formation and deposition. The

Figure 1

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

28

PEER REVIEW: ERECTILE DYSFUNCTION

Management of Erectile Dysfunction in Ireland An interview with Theresa LowryLehnen (PhD), CNS, GPN, RNP, South East Technological University

syndrome and cardiovascular disease, cardiac assessment is warranted in men with symptoms of ED.” Aetiology of Erectile Dysfunction

Erectile dysfunction (ED) is a common condition occurring in males over 40 years of age, although it can occur earlier. It is estimated that at least 150 million men globally have ED. It is difficult to obtain accurate values for the true prevalence of erectile dysfunction however, as many patients fail to seek medical attention, and many clinicians are reluctant to ask patients about their sexual health.

We recently spoke to Theresa Lowry Lehnen, RGN, GPN, RNP, BSc, MSc, M. Ed, PhD Clinical Nurse Specialist and Associate Lecturer South East Technological University to understand more about this condition and its impact on males in Ireland.

ED can have a substantial negative impact on a man’s quality of life, Theresa reflects. She says, “Erectile dysfunction is the inability to achieve or maintain an erection for satisfactory sexual performance, and affects a considerable proportion of men at least occasionally. It is often treatable, however, if left untreated, ED can be a source of severe emotional stress for both the man and their partner.”

Theresa notes that erectile dysfunction is often an under recognised, yet important, cardiovascular risk factor. She says, “Owing to its strong association with metabolic

Although most men will experience periodic episodes of erectile dysfunction, it tends to become more frequent with advancing age.

“Many factors can contribute to sexual dysfunction in older men, including physical and psychological conditions, comorbidities and polypharmacy,” she adds. “Aspects of an ageing man’s lifestyle behaviour and androgen deficiency, most often decreasing testosterone levels, can affect sexual function.

“Studies have shown that the percentage of men who engage in some form of sexual activity, decreases from 73% in men aged 57–64 years to 26% for men aged 75–85 years. The aetiology for this decline in male sexual activity is multifactorial, and is in part related to female partners menopause at approximately 52 years of age, leading to a significant decline in female libido and desire to engage in sexual activity.”

While ED is associated with ageing, many studies and largescale surveys have concluded that ED is a major health concern among young men.

Theresa adds, “One study in 2013 reported that 1: 4 men seeking medical help for erectile dysfunction in the real-life setting, is < 40 years of age. Another study in 2016 concluded that 22.1% of men < 40 years of age had low (<21) Sexual Health Inventory for Men (SHIM) scores.

“In the past, erectile dysfunction was almost always considered a

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

psychogenic disorder. However, evidence now suggests that more than 80% of cases have an organic aetiology. While most patients with ED have organic disease, some do have a primary psychological cause, particularly younger men.

Even when ED is organic in nature, there are almost always psychological consequences regarding relationship issues, cultural norms and expectations, loss of self-esteem, shame, and anxiety and depression related to sexual performance.”

Erectile dysfunction is multidimensional in nature, and Theresa says it can be broadly divided into endocrine and nonendocrine causes.

“The condition can be caused by any disease process which affects penile arteries, nerves, hormone levels, smooth muscle tissue, corporal endothelium, or tunica albuginea. It is closely related to cardiovascular disease, diabetes mellitus, hyperlipidaemia, hypertension, and endothelial dysfunction,” she explains.

“Erectile dysfunction and vascular disease are thought to be linked at the level of the endothelium.

Endothelial dysfunction, results in the inability of smooth muscle cells lining the arterioles to relax and prevents vasodilatation. The endothelial cell is known to affect vascular tone and impact the process of atherosclerosis and impacting ED, CVD and peripheral vascular disease. Cardiovascular disease and hypertension are very significant risk factors for erectile dysfunction.”

Besides cardiovascular disease, there are strong correlations between ED and hyperlipidaemia, diabetes, hypogonadism, obesity, smoking, alcoholism, benign prostatic hyperplasia (BPH) with lower urinary symptoms (LUTS), depression, and premature ejaculation. Diabetes is a common aetiology of sexual dysfunction, because it can affect both the blood vessels and the nerves that supply the penis. Men with diabetes are four times more likely to experience erectile dysfunction, and on average, experience it 15 years earlier than men without diabetes.

“Obesity is also correlated to the development of several types of dysfunction, including a decrease in sex drive and an increase in episodes of ED,” she continues. “Neurogenic erectile dysfunction is caused by a deficit in nerve signalling to the corpora cavernosa. Such deficits can be secondary to spinal cord injury, multiple sclerosis, Parkinson disease, lumbar disc disease, traumatic brain injury, radical pelvic surgery and diabetes. Men being treated for prostate cancer with treatments such as radical prostatectomy, radiation therapy or the use of lutenising hormonereleasing hormone (LHRH) agonists and antagonists often experience ED.” Numerous medications are listed with erectile dysfunction and/ or a decreased libido as a side effect. Drugs that can cause ED include hydrochlorothiazide’s and beta-blocking agents.

Medications used to treat depression, particularly the SSRIs such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, can also contribute to ED. The severity of erectile dysfunction is often described as mild, moderate or severe according to the five-item International Index of Erectile Function (IIEF-5) questionnaire, with a score of 1–7 indicating severe, 8–11 moderate, 12–16 mild–moderate, 17–21 mild and 22–25 no erectile dysfunction.

The International Index of Erectile Function (IIEF-5) Questionnaire The IIEF is a multidimensional validated questionnaire with 15 questions in the five domains of sexual function (erectile and orgasmic functions, sexual desire, satisfaction with intercourse and overall sexual satisfaction), and there is also an abbreviated format of five questions in the Sexual Health Inventory for Men (SHIM).

Investigations and Diagnosis Theresa continues, “A thorough medical history, detailed sexual history, and physical examination are required before commencing treatment or further investigations.

It is important to distinguish between psychological and

S U S P E C T AT T R - C M ( T R A N S T H Y R E T I N A M Y L O I D C A R D I O M YO PAT H Y )

A L I F E - T H R E AT E N I N G D I S E A S E T H AT C A N G O U N D E T E C T E D Life-threatening, underrecognized, and underdiagnosed, ATTR-CM is a rare condition found in mostly older patients in which misfolded transthyretin proteins deposit in the heart.1-7 It is vital to recognize the diagnostic clues so you can identify this disease.

C O N S I D E R T H E F O L L O W I N G C L I N I C A L C L U E S , E S P E C I A L LY I N C O M B I N AT I O N , T O R A I S E S U S P I C I O N F O R AT T R - C M A N D T H E N E E D F O R F U R T H E R T E S T I N G

HFpEF INTOLERANCE DISCORDANCE DIAGNOSIS ECHO NERVOUS SYSTEM heart failure with preserved ejection fraction in patients typically over 60 years old5-7

to standard heart failure therapies (ACEi, ARBs, and beta blockers)8-10 between QRS voltage and left ventricular (LV) wall thickness11-13

of carpal tunnel syndrome or lumbar spinal stenosis3,8,14-20

showing increased LV wall thickness6,13,16,21,22

—autonomic nervous system dysfunction-including gastrointestinal complaints or unexplained weight loss6,16,23,24

L E A R N H O W T O R E C O G N I Z E T H E C L U E S O F AT T R - C M AT :

SUSPECTANDDETECT.IE

References 1. Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209-213.

2. Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135(14):1357-1377. 3. Connors LH, Sam F, Skinner M, et al. Heart failure due to age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290. 4. Pinney JH, Whelan CJ, Petrie A, et al. Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc. 2013;2(2):e000098. 5. Mohammed SF, Mirzoyev SA, Edwards WD, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2(2):113-122. 6. Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172.

7. González-López E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36(38):2585-2594. 8. Narotsky DL, Castano A, Weinsaft JW, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016;32(9):1166.e1-1166.e10. 9. Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS. Transthyretin cardiac amyloidosis in older Americans. J Card Fail. 2016;22(12):996-1003. 10. Castaño A, Drach BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163-178. 11. Carroll JD, Gaasch WH, McAdam KP. Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation. Am J Cardiol. 1982;49:9-13. 12. Cyrille NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol. 2014;114(7):1089-1093. 13. Quarta CC, Solomon D, Uraizee I, et al. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation. 2014;129(18):1840-1849. 14. Connors LH, Prokaeva T, Lim A, et al. Cardiac amyloidosis in African Americans: Comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. Am Heart J. 2009;158(4):607-614. 15. Nakagawa M, Sekijima Y, Yazaki M, et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23(1):58-63. 16. Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation.

2009;120(13):1203-1212. 17. Sperry BW, Reyes BA, Ikram A, et al. Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol. 2018;72(17): 2040-2050. 18. Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223-228. 19. Yanagisawa A, Ueda M, Sueyoshi T, et al. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol. 2015;28(2):201-207. 20. Sueyoshi T, Ueda M, Jono H, et al. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol.

2011;42(9):1259-1264. 21. Phelan D, Collier P, Thavendiranathan P, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart. 2012;98(19):1442-1448. 22. Ternacle J, Bodez D, Guellich A, et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging.

2016;9(2):126-138. 23. Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63-76. 24. Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22(2):123-131.

The health information contained in this ad is provided for educational purposes only.

Date of Preparation: February 2021 GCMA code: PP-RDP-IRL-0105

The International Index of Erectile Function (IIEF-5) Questionnaire

30

The severity of erectile dysfunction is often described as mild, moderate or severe according

Patient Name: _________________ to the five-item International Index of Erectile Function (IIEF-5) questionnaire, with a score of 1–7 indicating severe, 8–11 moderate, 12–16 mild–moderate, 17–21 mild and 22–25 no

Date of Birth __________________ erectile dysfunction.2, 4

PEER REVIEW: ERECTILE DYSFUNCTION

Date Completed: _______________ The International Index of Erectile Function (IIEF-5) Questionnaire 4,5

Sexual Health Inventory for

The IIEF is a multidimensional validated questionnaire with 15 questions in the five Mendomains (SHIM) of sexual function (erectile and orgasmic functions, sexual desire, satisfaction with the past 6 months: intercourse and Over overall sexual satisfaction), and there is also an abbreviated format of five 5 1. How do you rate your confidence Very 2 Inventory Moderate 4 Very high 5 questions inlow the1SexualLow Health for Men3(SHIM).High that you could get and keep an erection?

Sexual Health Inventory for Men (SHIM)

2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration?

Almost never/never 1

A few times (much less than half the time) 2

Sometimes (about half the time) 3

Most times (much more than half the time) 4

Almost always/always 5

3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?

Almost never/never 1

A few times (much less than half the time) 2

Sometimes (about half the time) 3

Most times (much more than half the time)4

Almost always/always 5

4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?

Extremely difficult 1

Very difficult 2

Difficult 3

Slightly difficult 4

Not difficult 5

5. When you attempted sexual intercourse, how often was it satisfactory for you?

Almost never/never 1

A few times (much less than half the time) 2

Sometimes (about half the time) 3

Most times (much more than half the time) 4

Almost always/always 5

IIEF-5 scoring: The IIEF-5 score is the sum of the ordinal responses to the 5 items.

22-25: No erectile dysfunction 17-21: Mild erectile dysfunction 12-16: Mild to moderate erectile dysfunction 8-11: Moderate erectile dysfunction 5-7: Severe erectile dysfunction https://www.urologypartners.co.uk/repository/originals/The_International_Index_of_Erectile_Function.pdf

Total Score __________

organic causes of ED, as well as to ensure that the patient has erectile dysfunction and not another disorder. History that points towards a psychological aetiology include, sudden onset of erectile dysfunction especially if it is related to a new partner or a major life-changing event, situational ED, normal erections with masturbation or a different partner, presence of morning erections and high daily variability in erectile rigidity.

“The main differential diagnosis for erectile dysfunction is hypogonadism, loss of libido, depression with low mood, and other psychological conditions. It may also be the first manifestation

Investigations and Diagnosis A thorough medical history, detailed sexual history, and physical examination are required commencing or further investigations.

It is important to distinguish of before diabetes or cardiovascular treatment inhibitors and calcium channel should be carefully inspected for disease as well as depression. blockers are the least likely to hypogonadism, signs infection,has between psychological and organic causes of ED, as well as to ensure that theof patient It is important to differentiate cause ED. Beta-blockers are the presence of penile fibrosis or erectile and not another disorder.

History a psychological between truedysfunction erectile dysfunction only a minor contributor, while that points plaques,towards and phimosis. and other sexual disorders such as premature ejaculation, and this is usually assessed by obtaining a good sexual history.

“A complete medication list including supplements should be checked with the patient. ED can be a result of prescription or other medications. Prescription drugs that can cause ED include, antidepressants especially SSRIs, cimetidine, ketoconazole, spironolactone, sympathetic blockers, thiazide diuretics, and other antihypertensives. ACE

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

alpha-blockers can improve erectile function.”

Vascular risk factors such as hypertension and diabetes and lifestyle factors such as smoking, activity level, alcohol intake, and the use of any recreational drugs should be assessed, Theresa adds.

A full general and cardiovascular examination should be undertaken, as erectile dysfunction can be the first symptom of underlying vascular disease. Peripheral pulses should be checked and blood pressure measured. The genitalia

Theresa continues, “The role of testosterone replacement therapy (TRT) as a potential to improve erectile function in ED remains an issue for clinicians who are comfortable treating androgen deficiency. Androgens are known to have a significant impact on the function of the smooth musculature within the corpus spongiosum.

“Testosterone supplementation is more effective as a treatment for low libido than for ED. For most men with both ED and

FOR YOURSELF, WOULD YOU CONSIDER

BOTH EFFICACY AND SAFETY?

Choose both efficacy and safety with ELIQUIS®

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

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

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

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

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

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

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

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

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

considered safe.6 Practice with the device improves outcomes and some degree of manual dexterity 32 is required. VCD devices are the most inexpensive long-term therapy for ED, and a non-invasive option for patients who deem it acceptable. While the efficacy rates of VCD devices are high, patient satisfaction rates are lower. 1

PEER REVIEW: ERECTILE DYSFUNCTION “Other second-line therapy malfunction and infection are rare, includes the use of either and patient satisfaction is high.” intracavernosal injection (ICI) Outlook or intraurethral suppositories (IUS). A small needle is used to Theresa told us that future inject the ICI medication into Therapies for ED Clinical studies the lateral aspect of the penis in gene therapy are looking through a small-gauge needle. towards replacing proteins that These vasoactive agents include may not be functioning properly prostaglandin E1, papaverine and in the penile tissue of men with phentolamine and sometimes erectile dysfunction. atropine, which work alone or in She says, “Replacement of these combination to elicit an erection. proteins may result in improvement Response is dose related, usually in ED. Experimental animal models occurs within 10– 15 minutes, and have demonstrated improvement does not require stimulation. A in erectile function with gene concern with ICI use is priapism, therapy. Human studies may and if this occurs the patient will demonstrate success with this need to seek urgent medical therapy in the future, however, attention. Bruising can also gene therapy in humans is occur, due to it being an injected controversial, and can take a long medication. The intraurethral time for regulatory approval and suppository consists of a tiny public acceptance. pellet of prostaglandin E1 inserted into the urethral meatus.

“Stem cell studies may also Response is dose related, and provide advancements in the onset usually occurs within treatment of ED in the future. The 2, 6 10–15 minutes. Patients need to mechanism of action of stem cells be trained on the technique of the is to generate angiogenesis with IUS before use, and should be subsequent increase in cavernosal advised that pain or burning may smooth muscle cells within the occur with this medication. corporal bodies.

sweating.

Other second-line therapy includes theLifestyle use modifications of either intracavernosal injection (ICI) or are considered first-line therapy hypogonadism, oral PDE5 inhibitors and men should be intraurethral suppositories (IUS).for A ED, small needle alone are recommended as encouraged to make is theused to inject the ICI medication into the the initial therapy. Testosterone necessary changes to benefit supplementation reasonable both atheir sexual function and lateral aspect of isthe penisinthrough small-gauge needle.

These vasoactive agents include men with proven hypogonadism their overall health. and ED who have already failed inhibitors are highly prostaglandin and“PDE5 phentolamine and sometimes atropine, which work alone PDE5 inhibitorEtherapy or who 1, papaverine effective and have an overall also have low libido. Hypogonadal success rate of up to 76%. PDE5 with borderline erectile or inpatients combination to elicit an erection. is dose related, usually occurs within 10– inhibitors Response are contraindicated rigidity are most likely to benefit in patients taking nitrates, but from testosterone supplementation. otherwise are safe A and effective. with ICI use is priapism, and if this 15 minutes, and does not require stimulation. concern “Testosterone replacement When PDE5 inhibitors are therapy may cause increased co-administered with nitrates, occurs theof haemoglobin patient willorneed to seek urgentsystemic medicalvasodilation attention. Bruising can also occur, due to levels pronounced haematocrit which is associated and severe hypotension can occur. with an increased risk of heart it being an injected medication.“PDE5 The inhibitors intraurethral suppository consists of a tiny pellet of and α-adrenergic attack, stroke and blood clots. receptor blockers, often used Testosterone treatment can also for treatment need toResponse is dose related, and onset cause an enlarged prostate or into the prostaglandin E1 inserted urethralof BPH, meatus. be taken at least 4 hours apart. other prostate disorders. During Among second-line therapies, TRT treatment, the prostate usually occurs within 10–15 Patients need to(VCDs) be trained on the technique of the IUS external vacuum devices specific antigen (PSA) will be minutes. are a good, non-surgical option measured to monitor for any patients with ED. VCDs are changes is particularly before use,and andthisshould be advisedfor that painchambers or burning clear plastic placedmay over occur with this medication. important in men over 45 years of age.

the penis, tightened against the lower abdomen with a mechanism to create a vacuum inside the chamber. This directs blood into the penis. If an adequate erection occurs inside the chamber, the patient slips a small constriction band off the end of the VCD and onto the base of the penis.

An erection beyond 30 minutes is not recommended. While cumbersome, these devices are considered safe.

“As a who result of In men failusing to testosterone respond to first or second-line therapy, or who are not interested in replacement, natural production of testosterone may be “In men who fail to respond to first “The clinical studies published conservative therapies, prosthesis implantation is available.

Peniletherapy, implants reduced. This may lead to penile a or second-line or who include to date provide encouraging reduction in sperm production are not interested in conservative results, with improvement of and fertility. Other side effects therapies, penile prosthesis sexual function reported with no malleable and inflatable devices, although most implants used are of the inflatable variety. of TRT include: weight gain, implantation is available. Penile side effects. Although pioneering, increased appetite, hot flushes, implants include malleable and 6 cell studies to date are acne, effects depression, restlessness, inflatable devices, although most Adverse including malfunction and infection are rare, and patient satisfaction is high.stem small scale, with a short follow irritability, aggression, tiredness, general weakness and excessive

implants used are of the inflatable variety. Adverse effects including

up period, various aetiologies of ED and without a control group. Melanocortin activators are drugs that act through the central nervous system, and have been shown in animal studies to produce an erection. Initial studies in humans suggest that the drug (PT-141) can be effective if given intranasally in men with psychological rather than physical causes, and mild to moderate ED. “Larger studies are necessary, however,to demonstrate the safety and overall effectiveness of these drugs. Another potential new treatment for ED, is penile lowintensity shock wave lithotripsy.

This consists of 1500 shocks twice a week for 3–6 weeks. The purpose is to stimulate neovascularisation to the corporal bodies with improvement in penile blood flow and endothelial function. The use of low-intensity shock wave lithotripsy may convert PDE5 inhibitor nonresponders to responders.”

Erectile Dysfunction. JAMA. 2016;316(17):1838. doi:10.1001/ jama.2016.12284

Erectile Dysfunction. JAMA. 2016;316(17):1838. doi:10.1001/jama.2016.12284 AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

33

PEER REVIEW: PSORIASIS

What is psoriasis?

Psoriasis is a common skin condition that is thought to affect between 2% and 3% of the population of the United Kingdom and Ireland. It is an immune condition which affects the skin but is also associated with a condition called psoriatic arthritis which affects the joints.

However, psoriasis is much more than just a skin condition. It can also affect people physically and psychologically.

When a person has psoriasis, the skin replacement process speeds up, taking just a few days to replace skin cells that usually take 21-28 days. This results in an accumulation of skin cells on the surface of the skin, in the form of psoriatic plaques. This process is the same wherever it occurs on the body.

Psoriasis affects men and women equally and can occur at any point in the lifespan, affecting children, teenagers, adults and older people. However, there seem to be two peaks: from late teens to early adulthood and between the ages of around 50-60. It is a long-term condition that may wax and wane.

Sometimes it can appear mild and other times it can be more severe. Although there is no cure, it can be managed and with the right treatment and advice, many people are able to live well with the condition.

Usually, a trigger is required for psoriasis to develop, and this could be a throat infection, an injury to the skin, certain medications or physical or emotional stress. There are also others, as triggers can vary from one person to the next.

People who are unfamiliar with the condition sometimes ask whether psoriasis can be transmitted from person to person through contact.

The answer is no. Nor can it be transferred from one part of the body to another. However, some people may have a family history of psoriasis and certain genes have been identified as being linked to the condition. Many genes need to be involved though and even if the right combination of genes has been inherited, psoriasis still may not appear.

Written by Laura Stevenson, Deputy Chief Executive, Psoriasis Association

or dark patches of skin, covered with silvery white scales. These scales are the buildup of skin cells waiting to be shed and the redness is caused by the increase in blood vessels required to support the increase in cell production.

Psoriasis can range in appearance from mild to severe.

sterile blisters usually on the hands and feet. Nail psoriasis can result in changes to the appearance and texture of nails. In sensitive areas, such as the armpits and groin, psoriasis is often red and shiny, with little or no scaling.

The plaques can appear in a variety of shapes and sizes, varying from very small to several centimeters in diameter. They have a well-defined edge, making it easy to tell where the psoriasis ends, and non-psoriatic skin begins. For some people, plaques may be thin or flat to the skin surface but for others they may be much thicker. It is not unusual for psoriasis to be itchy, and it can often feel painful or sore.

Traditionally psoriasis was thought to be a condition of the uppermost layer of the skin (the epidermis), but now it is known that the changes in the skin begin in the immune system when certain immune cells (T cells) are triggered and become overactive.

Around 80% of people with psoriasis have plaque psoriasis, with plaques appearing most often on the elbows, knees, lower back and quite often in the scalp.

However, there are several different types of psoriasis, and any area of the body can be affected.

What does it look like?

Guttate psoriasis, which is most often seen in children and teenagers, can result in small and scaly patches (often less than 1cm in diameter). These can be numerous and cover all areas of the body. This type of psoriasis can be triggered by a throat infection.

Patches of psoriasis, which are often called plaques, are raised red

Pustular psoriasis is different again and can take the form of small

What causes it?

The T cells produce inflammatory chemicals and act as if they were fighting an infection or healing a wound, which leads to the rapid growth of skin cells, causing plaques to form. As a result, psoriasis is sometimes referred to as an ‘auto-immune disease’ or ‘immune-mediated condition’. It is not yet clear what triggers the immune system to act in this way.

Links between severe psoriasis and conditions such as diabetes and heart disease have been found but this does not necessarily mean that psoriasis causes these conditions, or that these conditions cause psoriasis. Research is ongoing to try to understand the true nature of this link, why these conditions sometimes occur in the same people and if this is also true of mild or moderate psoriasis.

How can it be treated?

How psoriasis is treated is dependent upon the type and the severity, although the available treatments fall broadly into four main categories.

Topical therapies such as creams, lotions, ointments, foams and gels can be prescribed by a GP and are usually tried first by most people with psoriasis. These can include topical steroids, dithranol, vitamin A and D derivatives and coal tar preparations. If psoriasis is particularly widespread or doesn’t respond to topical treatment, a referral to a dermatologist can take place, who can then offer a wider range of treatment options.

Phototherapy treatment with ultraviolet light can be considered.

UVB is the most commonly prescribed although treatment with UVA and the use of a chemical agent called psoralen can also be prescribed. This is referred to as PUVA therapy. Phototherapy treatment can necessitate attendance at a phototherapy centre 2 to 3 times a week for several weeks.

Systemic treatments, which are treatments that are taken into the body, can also be used for moderate to severe psoriasis.

The main types used in the UK are methotrexate, ciclosporin and acitretin. All require ongoing monitoring with blood tests and blood pressure checks. They do

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

34

PEER REVIEW: PSORIASIS have potential risks and some cannot be prescribed in conjunction with other medications or if the individual is thinking of having children within the next two years.

Guttate Psoriasis

Finally, psoriasis treatment has been revolutionised over the last ten years with the increased use of biologics which can be used to treat severe psoriasis that has not responded to any of the abovementioned treatments. Biologics work by blocking the action of certain immune cells (T cells) or the chemicals released by them.

People with psoriasis can also be prescribed biologics if the systemic treatments mentioned above cause side effects which means the person should not take them, or if the person has another condition or medication which means that they should not take the other systemic treatments.

There are now over 13 biologics approved by the National Institute for Health and Care Excellence (NICE) for treating severe psoriasis currently available. Additionally, there are a number of biosimilars available for adalimumab, etanercept and infliximab.

Plaque Psoriasis

Managing psoriasis extends far beyond applying treatments and taking medications. Learning to

cope with a skin condition can take time as the psychological impact is not always related to the clinical severity of psoriasis.

It can be reassuring to hear about how other people cope with their psoriasis and live with their condition. The Psoriasis Association, a leading national charity for people affected by psoriasis in the UK, offers help in this regard by funding research, providing information and raising awareness of the condition. The tailored support offered by the charity’s helpline, and peer-to-peer support offered through its website forums and social media platforms can be invaluable.

Everyone has their own way of coping with psoriasis. Some people cover their skin, either with clothing or special skin camouflage make-up, whilst others are comfortable not covering up at all. Some may wear lighter clothes on the top half of their body to hide flakes from scalp psoriasis, whilst for others this is less of an issue. The most important thing is honesty with any healthcare professional offering treatment, especially if experiencing feelings of anxiety or distress due to the impact of psoriasis.

News - Off-Patent Medicines Industry ‘Vital’ The Medicines for Europe annual conference was held recently, during which the organisation launched a report to optimise market policies for the secure supply of medicines.

Health systems face tremendous challenges across Europe. The management of COVID-19, war in Ukraine and high inflation rates are challenging supply chains for the most essential medicines.

Off patent medicines account for 70% of those dispensed in Europe, treating severe conditions such as cancer, auto-immune conditions, respiratory diseases, and cardiovascular disease. These medicines are clearly part of the solution for resilient health systems.

Policy reforms are needed to strengthen health systems in Europe with off-patent medicines. When revising the EU pharmaceutical legislation, the EU must: • Encourage the use of generic, biosimilar and value-added medicines to increase patient access to medicines and ensure budgetary sustainability • Support the off-patent medicines industry response to inflation by revising procurement guidelines for medicines and safeguarding the medicines manufacturing sector in emergency response plans • Commit to durable supply chains and manufacturing for medicines, by allowing access to EU funds • Critically assess the IP infrastructure on medicines, taking action to eliminate abuses, and fully supporting the entry into force of the SPC manufacturing waiver on 01 July 2022.

At the Medicines for Europe annual conference, Elisabeth Stampa, President, Medicines for Europe commented, “The role of the EU in health policy took on a new life during the pandemic and should continue to do so if we want our health systems to be resilient. Europeans now expect strong EU leadership on health policy and our industry, as the biggest supplier of medicines to patients in Europe, is ready to play its part.

“We consistently bring solutions to improve access to medicines and reduce pressure on healthcare budgets.

“Today we are launching a report to optimise market policies for the secure supply of medicines. Our recommendations will ensure that medicines remain available, affordable, and accessible for patients, and also reduce the risk of medicines shortages and increase European strategic autonomy.”

Margaritis Schinas, Vice President of the European Commission for Promoting our European way of life, said, “We are revising the pharmaceutical legislation at EU level. The objectives are clear: having medicines at affordable conditions for all, and ensuring European industry remains an innovative world leader. These are not antagonistic objectives, on the contrary, both are possible, and we should make them a reality.”

The report titled ‘New pricing models for generic medicines to ensure long-term healthy competitiveness in Europe’ is available by visiting www. medicinesforeurope.com

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

INTRODUCING

FOR THE TREATMENT OF MODERATE TO SEVERE

atopic dermatitis

in adults and adolescents 12 years and older who are candidates for systemic therapy1

MARKETING AUTHORISATION HOLDER: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany.

Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; website: www.hpra.ie.

LEGAL CLASSIFICATION: POM (S1A).

Full Summary of Product Characteristics is available at www.medicines.ie Reference 1. RINVOQ Summary of Product Characteristics, available on www.medicines.ie ©2022 AbbVie Inc.

All rights reserved.

IE-RNQ_AD-220036 | March 2022

36

PEER REVIEW: PLEURAL EFFUSION

Malignant Pleural Effusion: Diagnosis and management Written by P. Ridge; D Breen - Interventional Respiratory Unit, Galway University Hospital Corresponding Author: Padraic Ridge, Galway University Hospital, Newcastle, Galway, Ireland Email: P.macaniomaire1@gmail.com Abstract: Malignant pleural effusion (MPE) is a common clinical entity affecting 40,000 people per year in the UK. MPE can occur with a primary pleural malignancy, typically mesothelioma or more commonly as a metastatic manifestation of a non pleural primary malignancy. In Ireland mesothelioma is an infrequent diagnosis and therefore the majority of cases of MPE represent advanced Stage IV malignant disease.1 In this paper we will review the diagnosis and subsequent management of MPE. This has important implications for staging and treatment of individuals.9

Dr Padraic Ridge

Dr David Breen

Introduction

The size of the effusion does not reliably predict a patients symptom burden as the fluid can accumulate gradually over time allowing the patient to compensate. Symptoms are more strongly correlated with the rate of fluid accumulation.7

Malignant pleural effusion (MPE) is defined by malignant cells within the pleural space.

The pleural space can be involved by malignancy through direct extension of tumour, haematogenous spread or through primary pleural malignancy (mesothelioma).2,3 While any cancer can metastasize to the pleural space the most common in descending order are lung, breast, lymphoma, ovarian and gastric cancer. These account for approximately 80% of MPE.4,5 The incidence of MPE In the UK is circa 40,000 people/year.

Median survival from diagnosis of MPE ranges from 3-12 months depending on the tumour type.5 Metastatic involvement of the pleural space by lung cancer is associated with the shortest median survival of 3 months, however novel targeted therapies may improve this prognosis.4 6 Presentation Patients may present with dyspnoea, orthopnoea or chest pain. Dyspnoea can be very severe and dramatically affect quality of life. However Individuals can often be relatively asymptomatic and MPE may only be incidentally picked up on routine imaging studies.4

Diagnosis It is important to note that 50% of pleural effusion in the setting of individuals with cancer are non-malignant.8 These may be caused by bronchial obstruction from tumour or benign causes such as congestive heart failure or infection. These are termed paramalignant or non-malignant pleural effusions. See Figure 1.

Figure 1 Fig 1.

Causes of paramalignant effusions Direct tumour effect: -Lymphatic obstruction -Bronchial obstruction -Trapped lung -Chylothorax -Superior vena cava obstruction Systemic effects: -Pulmonary embolism -Hypoalbuminemia Complications of therapy: -Radiotherapy -Chemotherapy

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Malignant pleural involvement should never be presumed and it is crucial to pathologically stage pleural effusions in the setting of malignancy. Malignant involvement of the pleural space implies stage 4 malignancy thus radical treatment options such as surgery are not an option. For those with para-malignant effusions radical, curative treatments may still be an option.10-12 Assuming malignant involvement in those with a paramalignant effusion could wrongly deny them potentially curative treatment.

Imaging Chest radiography (CXR): Is the initial imaging for most. The standard posterior-anterior (PA) CXR will only start to become abnormal in the presence of approximately 200ml of pleural fluid.13 The initial sign is costophrenic blunting, which may progress to opacification with a meniscus or even a full “white

out” with tracheal deviation away from the effusion.13,14 Lateral films are more sensitive and can detect pleural effusions of 50ml.13 Ultrasound (US): Ultrasound scanning has become the gold standard in diagnostic imaging for MPE. Ultrasound can differentiate pleural effusion from lung collapse or pleural thickening.4 USS outperforms CT at identifying pleural features such as: pleural thickness, nodules and adhesions.

Features consistent with malignant pleural effusion on USS include: nodules of the pleura or diaphragm, diaphragmatic thickening (>7mm) and pleural thickening (>1cm).

These findings on ultrasound have a sensitivity and specificity of differentiating benign from malignant effusions of 79% and 100% respectively. See Figure 2 15 Ultrasound has also developed a key role in pleural procedures. It has the benefit of not exposing the patient to radiation and being able to be performed at the bedside.

Figure 2: Ultrasound: Malignant pleural effusion with diaphragmatic nodules

37 Ultrasound should be used to “mark the spot” immediately prior to any form of pleural intervention. As pleural fluid can often be free flowing the patient should be advised to remain as still as possible from the moment of marking the spot until the pleural intervention takes place.

The method of marking the spot in the radiology department and then transferring back to the ward for pleural intervention is not recommended.4 For small effusions, or patients who are liable to move post marking, intervention can be performed under real time ultrasonography.5 Ultrasound guidance increases the accuracy and reduces the risk of inadvertent damage to surrounding organs and now is a fundamental requirement for any pleural service.16 Computed Tomography and PET: Standard CT and PET are important modalities to further investigate an effusion and in particular for further assessment for an underlying primary cancer, assessing extent of disease, and identifying alterative cause of the effusion such as bronchial obstruction, infection or pulmonary embolism. 17 If stage 4 disease is confirmed then PET scan is not pursued.

Signs of malignant pleural effusion on CT include pleural thickening, nodular pleural thickening, mediastinal pleural thickening and circumferential pleural thickening.18 Figure 3 CT is also useful for

Figure 3: Computed Tomography: Pleural thickening (*) and pleural nodule (N) on CT

helping the USS operator better conceptualize the pleural effusion.5 However, CT is not as sensitive at detecting pleural thickening or identifying internal septations in a pleural effusion.19 Sampling Aspiration: Pleural aspiration is the initial method of obtaining pathological confirmation of MPE. It should always be performed with US guidance. It can be performed at the bedside using a 21G needle and a 50ml syringe or as part of a therapeutic thoracentesis.4 The procedure should be performed aseptically and local anaesthetic should be administered particularly superficially and at the pleural surface.

The British Thoracic society recommend all pleural samples should be sent to biochemistry for LDH and protein (5ml), microbiology for culture, sensitivity and Acid Fast Bacilli (5ml), and cytology (~40ml). If there is a concern for pleural infection, pleural samples should be inoculated in blood culture bottles as this increases the microbiological yield.20 We also recommend the pH should be checked within an hour by the person performing the aspiration using a standard arterial blood gas (ABG) needle and ABG machine. In the case of MPE PH is predictive of future chemical pleurodesis rates and may add evidence to the diagnosis of MPE.4,5,21,22 For Para-malignant effusions, such as pleural infections, pH in

combination with USS features may indicate the need for a chest drain and therefore both are important point of care tests.4 It is important to note pleural aspiration gives a cytological sample. In malignancies such as mesothelioma, where histological samples are recommended, sensitivity of cytological samples can be low as 32%. 23 The overall sensitivity of aspiration for MPE is 60% (range 40-87%).4 Therefore in the right clinical context a negative aspiration should not out-rule MPE and further tests may be required.

One study looked at the benefit of repeating aspiration. This study achieved a yield of 65% from initial aspiration, a further 27% from a second aspiration and 5% from a third aspiration.24 Each aspiration meant a repeat procedure for the patient with all its associated risks and increased wait time for results. Also repeated interventions may make the pleural space more complex, making it more difficult to perform a definitive procedure in the future. Therefore, if local resources allow, we recommend proceeding to a more definitive procedure as an alternative to repeated aspirations. (See Figure 4 on page 36).

Biopsy For patients undiagnosed after initial less invasive methods a biopsy is required. This can be achieved by percutaneous or thoracoscopic methods.

Percutaneous pleural biopsy: CT guided biopsy has been the favoured method due to its superior sensitivity of 88%. 25 Prior to this blind percutaneous biopsy was traditionally performed with an Abram’s needle. This method is performed less now due to its low sensitivity of 57% and high complication rate. However, recent studies have shown that biopsies taken with an Abrahm’s needle in combination with USS guidance have comparable sensitivity and safety to CT guided pleural biopsies.26,27 Thoracoscopy biopsy: Thoracoscopy allows direct visualisation of the pleura and sampling of abnormal pleural patches. A medical thoracoscopy is performed by a respiratory physician. It can be performed in the endoscopy suite under conscious sedation.28 A Video assisted thoracoscopic surgery is performed by a surgeon and requires a general anaesthetic and single lung intubation. Therefore, a medical thoracoscopy is the preferred method for a frail patient.4 The sensitivity of medical thoracoscopy and VATS for malignancy is 92.6% and 95% respectively.4

An advantage of these procedures is that they can be therapeutic as well which we will outline below.

Management Once a diagnosis has been obtained, Multiple factors should be considered prior to deciding on definitive treatment such as: symptoms, need for future samples for tumour confirmation or molecular markers, rate of fluid accumulation, life expectancy, tumour type and predicted response to treatment. A potential algorithm is outlined in Figure 5.5 (See figure 5 on page 36).

Management should be delivered by a multidisciplinary team including respiratory physicians, oncology, radiation oncology, Thoracic surgeons, palliative care physicians and other supportive staff. Due to the limited life expectancy of those with MPE care should be delivered in a timely and convenient manner to the patient. We aim to provide pleural management in the outpatient setting as much as possible to achieve this goal.5 1) Conservative Monitoring For those who are asymptomatic we do not perform any invasive intervention as there is no benefit to the patient. We educate the patient, provide them with contact details and arrange regular follow up. If they develop symptoms at a future date then we offer a pleural intervention.

2) Systemic Therapy Response of the MPE depends on the histology of the primary tumour. Lymphoma, small cell lung carcinoma, germ cell tumours, prostate carcinoma and ovarian cancers typically have a favourable response to systemic chemo-radiotherapy.29 3) Therapeutic Thoracentesis Breathlessness in malignancy can be multifactorial and even in those with a MPE, it may be due to other causes such as lymphangitis carcinomatosa, bronchial obstruction, pulmonary embolism, chronic lung disease or even ischemic heart disease.4,30 Before proceeding with definitive pleural management one should always perform a therapeutic thoracentesis to assess for improvement in dyspnoea. The initial procedure can be both therapeutic and diagnostic.

Post thoracentesis, patients should be assessed for radiological expansion of the underlying lung and symptomatic benefit. When

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

38

PEER REVIEW: Figure 4 pleura. Talc is the most effective and most used agent in Ireland.32 For chemical pleurodesis to be effective the effusion needs to be drained and the lung expanded to allow the apposition of visceral and parietal pleura.4 Talc can be administered at the bedside via a chest drain (talc slurry). (See Figure 6 on page 37). It can also be administered at the time of thoracoscopy (talc poudrage). The thoracoscopy method is more invasive but allows one to examine and sample the pleura, lyse any adhesions and spread the talc more evenly on the pleura which may lead to better control. (See Figure 7 on page 37).

However, neither method has been shown to be superior. 33-35

Fig. 5 a lung does not fully expand to oppose the parietal pleura this is termed a trapped lung.

Only those who show an improvement in symptoms post thoracentesis should have a definitive pleural procedure performed. Those who do not show an improvement should be investigated for an alternative cause of their symptoms. 4 The minimal amount of fluid to remove to assess for clinical response is 500ml.30 Thoracentesis is associated with a risk of re-expansion pulmonary oedema (RPO). Standard practice is to remove 1.2L in one session.

However no maximal volume has ever been identified. Methods of minimising the risk of RPO include pleural manometry and monitoring for chest tightness, cough or dyspnoea during thoracentesis and stopping if they begin to develop. 5,31 As mentioned above, therapeutic thoracentesis allows the identification of individuals who have a trapped lung. This is important as those with a trapped lung do not derive benefit from chemical pleurodesis as there is no pleural opposition to allow this process to occur. Therefore an indwelling pleural catheter is the best option for these patients.

Fig. 5

4) Chest Drain Insertion and Complete Drainage Chest drain insertion and full drainage of the pleural effusion can be considered for those who accumulate fluid very slowly, have a short life expectancy or choose to not have a definitive procedure.

In particular it is a viable option in those who have a chemo-sensitive tumour that is expected to respond to systemic therapy.

5) Chemical Pleurodesis Chemical pleurodesis can be performed using talc, tetracycline or bleomycin. It induces pleural inflammation resulting in adhesion of the visceral pleura to the parietal

Talc administration can be associated with pain therefore lidocaine is always administered to the pleura beforehand and generous analgesia should be prescribed.36 A study has shown that non-steroidal antiinflammatories do not effect pleurodesis rates.37 It is not unusual for patients to have a temperature post administration due to a systemic inflammatory response.4 6) Indwelling Pleural Catheter An IPC involves tunnelling a catheter through the skin into the pleural space. This catheter can then remain in place for a prolonged period allowing a family member to intermittently drain the effusion at home using a vacuum bottle (usually every 2nd day). (See Figure 8 on page 37). The drain can be inserted in an outpatient setting and thus does not require admission. It can also be inserted at the time of diagnostic thoracoscopy with or without concomitant talc which is termed an accelerated pleurodesis. 38-40 7) IPC vs Chemical Pleurodesis An IPC is the only effective option in those with non-expandable or trapped lung where chemical pleurodesis has been shown to be ineffective.4 In those with expandable lung the two methods are comparable in terms of symptom control and safety.

Generally we discuss the benefits and drawbacks of each method of managing the pleural fluid with the patient and in turn allow them to make an informed decision based on evidence and personal preference.

Figure 5

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

39

Fig. 6 Guide to performing Talc slurry -Insert small bore chest tube -Drain pleural effusion completely -Confirm lung expanded and drain still in pleural space -Administer analgesia pre procedure -Instill lidocaine into pleural space (3 mg/kg; maximum 250 mg) -Instill 4-5g of sterile graded talc in 50 ml 0.9% saline into pleural space -Clamp drain for 1-2 hours -Remove chest drain within 24-48 hours

Figure 7

Fig. 7

Figure 6

The advantages of chemical pleurodesis are that it is a one-off procedure, if successful and there is no ongoing management of an indwelling drain for the patient.

However it requires chest drain insertion, hospital admission for a few days, can be painful and pleural infection has been reported.5 IPCs are associated with less repeated procedures and fewer days in hospital as it can be inserted as a day case.41 However, IPC insertion’s can be complicated by local skin infections, pleural infection and catheter blockage or fracture. Some patients do not like the burden of managing the drain long term.42 Ultimately the choice between chemical pleurodesis andvs IPC is usually made based on the patients preference for avoiding a hospital admission versuss the burden of the ongoing management of the IPC drain.41,42 8) Palliative

Fig. 8

Occasionally patients may be too unwell for an invasive procedure and optimal control of symptoms is best achieved through systemic opioid and benzodiazepine therapy guided by the palliative care services.5 Conclusion

Fig. 6 Guide to performing Talc slurry Figure 8

-Insert small bore chest tube -Drain pleural effusion completely -Confirm lung expanded and drain still in pleural space -Administer analgesia pre procedure -Instill lidocaine into pleural space (3 mg/kg; maximum 250 mg) -Instill 4-5g of sterile graded talc in 50 ml 0.9% saline into pleural space -Clamp drain for 1-2 hours -Remove chest drain within 24-48 hours

MPE are common, indicate advanced stage and are associated with a high morbidity and mortality. Diagnosis should always be prompt and confirmed pathologically.

MPE results in a major burden on the health service and account for significant inpatient days.

It’s for this reason that we have developed a pleural service in Galway University Hospital which has been in constant development since 2010. Our service has been pivotal in reducing inpatient days and reducing symptom burden in those suffering from MPE through the provision of the treatment strategies outlined in this review.

We believe management of patients with MPE should focus on symptom control, be delivered on an outpatient basis (when possible) and should always be led by patient preference.

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

40

PEER REVIEW: COLON CANCER

The Unintended Consequences of Centralisation of Colon Cancer Surgery Written by Mr Desmond Toomey MD, FRCSI, Consultant General & Colorectal Surgeon - Regional Hospital Mullingar & Mater Misericordiae University Hospital; UCD Associate Clinical Professor; RCSI (Hon) Clinical Senior Lecturer

Centralisation of cancer care into specific Model IV hospitals with the appropriate resources, skillsets, equipment and ethos improves outcomes and survival. In Ireland, rectal cancer was centralised to the eight cancer centres a decade ago and the benefits for this cohort of patients is evident. It has been proposed that colon cancer surgery should be similarly centralised.

Would this colon cancer policy be suitable for the Irish system or would it have unintended, negative consequences for other patients and Irish surgery? Could a colon cancer plan be tailored with lessons learned from rectal cancer and our experiences with hybrid working / colocation during the pandemic?

The population of colorectal patients is far greater than just those with cancer. There are many other colorectal diseases, such as inflammatory bowel disease and diverticular disease that dramatically impact on quality of life, often at a younger age and over a more chronic period. There is significant overlap between the skillsets for colorectal cancer surgery and complex benign disease. Surgery for these benign conditions can be more technically challenging than

many cancer cases and requires skilled, experienced surgeons and multidisciplinary input. The “C word” inspires such fear in people that cancer care tops the political and medical agendas despite the sustained burden of IBD on economic and societal metrics.

Are geographically rigid, cancer centric policies detrimental to care for other non cancer patients and possibly the health system as a whole?

In the Irish public healthcare system, services commonly have to be developed before resources are allocated – the cart is put before the horse. Consultants are being appointed and increasing amounts of cancer work are being done in the eight cancer centres.

However, the beds, theatres and other resources lag behind and it is difficult to see how the necessary development will be financed and staff recruited. As increasing numbers of cancer patients are centralised into these eight hospitals we already see the knock on detrimental effects on other patients, unscheduled care and the trolley count.

If we cannot resource these Model IV cancer centres sufficiently then

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

perhaps we should explore other options and capacity. We learned during the COVID pandemic to utilise remote and hybrid working models and this experience could be extrapolated to the cancer treatment system. Is the value of the cancer centre, particularly for the less complex cancer work, in the locating of these staff in a single geographical location or is it joint care and decision making from a cohesive team of high volume specialists? If the latter is true then why does all the surgery need to be performed in the same building?

Appropriate consultant surgeons should be collocated across Model III & IV hospitals, should be an integral part of the MDT and, subject to measures of the quality of their treatment, should be trusted to treat their patients in the right place at the right time making the most efficient uses of all the resources available.

There is a crisis in surgical recruitment and retention in Model III hospitals, in part due to the relocation of services to the cancer centres. Further geographical centralisation will likely exacerbate the draining of surgeons with complex colorectal skillsets away from these hospitals. This impacts on both cancer and non cancer colorectal patients.

Up to 30% of colon cancers present as an emergency needing urgent surgery or considered decision making by a surgical

oncologist. These are some of the most challenging cases and commonly present outside of the eight cancer centres. In the Model III hospital, the presence of a colorectal surgeon allows expedient, appropriate, surgical oncological intervention without the need to transfer to an already overloaded Model IV where the oncall surgeon may not even be colorectal. The skill drain also affects the non malignant cases who present emergently, who encounter intestinal difficulty during other procedures or abdominal complications while admitted under medical and other specialities. These patients have an equal right to the appropriate expertise and there are numerous examples of poor outcomes in such cases where the appropriate expertise was not available.

In my experience most patients would prefer not to travel long distances for care if an equivalent service was available locally. This in itself should not have a major bearing on policy decisions in a resource poor environment.

However, even when patients do travel for treatment in a cancer centre under the current system they frequently present back to the Model III if they encounter difficulties after stepdown or discharge. If the Model III hospital becomes downgraded by attrition of skilled staff then these complicated patients cannot be managed locally and face delay in their care with the associated detrimental outcomes. This staff attrition also prevents complex benign patients from accessing surgery locally and they are then de facto centralised to the cancer centres where they struggle to compete for resources.

If as a country and a health service we were to start again, then we would build the appropriate hospitals in the appropriate places with room and resources for all. We are not in that situation.

Centralisation of care is the correct thing to do but are we trying to ram a square peg into a round hole? Unless we can adequately resource our Model IV hospitals to service the needs of all of our colorectal patients then we should tailor our centralisation policy to maximally utilise the existing resources that are available to the benefit of all of our patients.

MAKE TIME for more moments that matter Extend overall survival for patients in 3rd line mCRC1

trifluridine/tipiracil Lonsurf® (Trifluridine/ tipiracil): Abbreviated Prescribing Information: Please refer to the Summary of Product Characteristics before prescribing. COMPOSITION*: Lonsurf 15 mg/6.14 mg: film-coated tablet containing 15 mg trifluridine and 6.14 mg tipiracil (as hydrochloride).

Lonsurf 20 mg/8.19 mg: film-coated tablet containing 20 mg trifluridine and 8.19 mg tipiracil (as hydrochloride). INDICATION*: As monotherapy for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents. As monotherapy for the treatment of adult patients with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction, who have been previously treated with at least two prior systemic treatment regimens for advanced disease. DOSAGE AND ADMINISTRATION*: Recommended starting dose: 35 mg/m2/dose taken orally twice daily on Days 1 to 5 and Days 8 to 12 of each 28-day cycle, within 1 hour after completion of the morning and evening meals (20mg/m2/dose for patients with severe renal impairment). Dosage calculated according to body surface area, not exceeding 80 mg/dose. Possible dosing adjustments based on individual safety and tolerability: permitted dose reductions to a minimum dose of 20 mg/m2 twice daily (15mg/m2/dose for patients with severe renal impairment), dose escalation not permitted after a dose reduction. CONTRAINDICATIONS*: Hypersensitivity to the active substances or to any of the excipients. WARNINGS *: Bone marrow suppression: Complete blood cell counts must be obtained prior to initiation of therapy, prior to each cycle and as needed. Treatment must not be started if absolute neutrophil count < 1.5 x 109/L, if platelet counts < 75 x 109/L, or if unresolved Grade 3 or 4 non-haematological clinically relevant toxicity. Patient should be monitored closely for infections, appropriate measures should be administered as clinically indicated. Gastrointestinal toxicity: anti-emetic, anti-diarrhoeal and other measures should be administered as clinically indicated, dose modifications should be applied as necessary. Renal impairment: not recommended if end-stage renal disease. Patients with renal impairment should be monitored closely; patients with moderate or severe renal impairment should be more frequently monitored for haematological toxicities. Hepatic impairment: not recommended if baseline moderate or severe hepatic impairment. Proteinuria: monitoring by dipstick urinalysis recommended prior to starting and during therapy. Excipients: contain lactose. INTERACTIONS*: Precautions: medicinal products that interact with nucleoside transporters CNT1, ENT1 and ENT2, inhibitors of OCT2 or MATE1, human thymidine kinase substrates (e.g. zidovudine), hormonal contraceptives. FERTILITY*. PREGNANCY AND BREASTFEEDING*: Not recommended. CONTRACEPTION*: For women and men, highly effective contraceptive measures must be used during treatment and for 6 months after stopping treatment. DRIVE & USE MACHINES*: Fatigue, dizziness or malaise may occur. UNDESIRABLE EFFECTS*: Very common: Neutropenia, leukopenia, anaemia, thrombocytopenia, decreased appetite, diarrhoea, nausea, vomiting, fatigue. Common: Lower respiratory tract infection, febrile neutropenia, lymphopenia, hypoalbuminaemia, dysgeusia, neuropathy peripheral, dyspnoea, abdominal pain, constipation, stomatitis, oral disorder, hyperbilirubinaemia, Palmar-plantarerythrodysaesthesia syndrome, rash, alopecia, pruritus, dry skin, proteinuria, pyrexia, oedema, mucosal inflammation, malaise, hepatic enzyme increased, blood alkaline phosphatase increased, weight decreased. Uncommon: Septic shock, enteritis infectious, lung infection, biliary tract infection, influenza, urinary tract infection, gingivitis, herpes zoster, tinea pedis, candida infection, bacterial infection, infection, neutropenic sepsis, upper respiratory tract infection, conjunctivitis, cancer pain, pancytopenia, granulocytopenia, monocytopenia, erythropenia, leukocytosis, monocytosis, dehydration, hyperglycaemia, hyperkalaemia, hypokalaemia, hypophosphataemia, hypernatraemia, hyponatraemia, hypocalcaemia, gout, anxiety, insomnia, neurotoxicity, dysaesthesia, hyperaesthesia, hypoaesthesia, syncope, paraesthesia, burning sensation, lethargy, dizziness, headache, visual acuity reduced, vision blurred, diplopia, cataract, dry eye, vertigo, ear discomfort, angina pectoris, arrhythmia, palpitations, embolism, hypertension, hypotension, flushing, pulmonary embolism, pleural effusion, rhinorrhoea, dysphonia, oropharyngeal pain, epistaxis, cough, enterocolitis haemorrhagic, gastrointestinal haemorrhage, pancreatitis acute, ascites, ileus, subileus, colitis, gastritis, reflux gastritis, oesophagitis, impaired gastric emptying, abdominal distension, anal inflammation, mouth ulceration, dyspepsia, gastrooesophageal reflux disease, proctalgia, buccal polyp, gingival bleeding, glossitis, periodontal disease, tooth disorder, retching, flatulence, breath odour, hepatotoxicity, biliary dilatation, skin exfoliation, urticaria, photosensitivity reaction, erythema, acne, hyperhidrosis, blister, nail disorder, joint swelling, arthralgia, bone pain, myalgia, musculoskeletal pain, muscular weakness, muscle spasms, pain in extremity, renal failure, cystitis noninfective, micturition disorder, haematuria, leukocyturia, menstrual disorder, general physical health deterioration, pain, feeling of body temperature change, xerosis, discomfort, blood creatinine increased, electrocardiogram QT prolonged, international normalised ratio increased, activated partial thromboplastin time prolonged, blood urea increased, blood lactate dehydrogenase increased, protein total decreased, C-reactive protein increased, haematocrit decreased. Post-marketing experience: interstitial lung disease. OVERDOSE*. PROPERTIES*: Trifluridine is an antineoplastic thymidine-based nucleoside analogue and tipiracil hydrochloride is a thymidine phosphorylase (TPase) inhibitor. Following uptake into cancer cells, trifluridine, is phosphorylated by thymidine kinase, further metabolised in cells to a deoxyribonucleic acid DNA substrate, and incorporated directly into DNA, preventing cell proliferation. However, trifluridine is rapidly degraded by TPase and readily metabolised by a first-pass effect following oral administration, hence the inclusion of the TPase inhibitor, tipiracil hydrochloride.PRESENTATION* Pack of 20 or 60 film-coated tablets. Marketing Authorisation Holder LES LABORATOIRES SERVIER, 50 rue Carnot, 92284 Suresnes cedex France. www.servier.com. Marketing Authorisation: EU/1/16/1096/001-006. Legal Classification for Supply: POM. Further information available from: Servier Laboratories (Ireland) Ltd., Second Floor, 19 Lr. George’s Street, Dun Laoghaire, Co. Dublin A96 ER84, Ireland, Tel (01) 6638110, www.servier.ie. *For complete information, please refer to the Summary of Product Characteristics available on medicines.ie. Date of last revision of text: January 2021 (Date of last approved SmPC: December 2020) Reference: 1. Lonsurf SmPC December 2020 Date of preparation of item September 2021. 2122c1LNPressAd A4

42

PEER REVIEW: LYMPHOEDEMA

Lymphoedema Treatment and Management Written by Dr Grainne Sheill, Clinical Specialist in Cancer Rehabilitation and Kelly Coghlan, Senior Physiotherapist, Early Detection Lymphoedema

Dr Grainne Sheill Cancer related lymphoedema is a chronic, progressive condition resulting from failure of the lymphatic system to drain fluid and proteins from tissue throughout the body and return it to the circulatory system. Lymphoedema usually affects a limb and can cause discomfort, pain, heaviness, limited motion, unsatisfactory appearance and impacts on quality of life. Cancer relatedlymphoedema is a well know side effect of surgery chemotherapy, radiation therapy and endocrine therapies, impacting up to 1490 new breast, gynaecological, melanoma, prostate and bladder cancers in Ireland annually.

Over 15,000 people in Ireland are living with lymphoedema.

Lymphoedema is progressive and if not treated, will become more complex with build up of fluid causing skin changes and reduced function which can lead to higher healthcare costs and hospitalization due to cellulitis.

Lymphedema Stages

earliest point possible in the patient detect those with sub-clinical changes in limb volume and start journey and monitors patients lymphoedema education and lymphoedema, and also lipoedema, exercises as early as possible. in the long term. Although treatment The service uses a state-of-the-art is not a cure it can improve quality Lymphoedema Treatment and Management SOZO Bioimpedance Spectroscopy of life and prevent complications (BIS) to get pre-operative such as cellulitis which reduces and detect Specialist sub hospital admissions.

Written by Dr measurements Grainne Sheill, Clinical inunnecessary Cancer Rehabilitation clinical changes in patients’ fluid The management of lymphoedema tissues after surgery. Patients involvesLymphoedema education, lymphatic Kelly Coghlan,and Senior Physiotherapist, Early Detection are provided with information drainage, the provision of garments early signs and and prescription of exercise.

Cancer related lymphoedema ison a managing chronic, progressive condition resulting from failure of the lymphatic symptoms of lymphoedema, 4 cornerstones system to drain fluid and proteins from skin tissue throughout tolymphoedema the circulatory including care advice. Theythe body and return itof Kelly Coghlan management: reviewed postoperative at system. Lymphoedema usually are affects a limb and can cause discomfort, pain, heaviness, limited motion, different time points based on • Skin Care: moisturising vital to unsatisfactory appearance and their impacts onrisk, quality of by life. is arisk well know level of triaged theCancer related-lymphoedema avoid cracks and reduce In Ireland, 70% of lymphoedema Senior Physiotherapist. of infection effect of surgery chemotherapy, radiation therapy and endocrine therapies, impacting up to 1490 careside should be provided in the primary setting with non• Exercise: important for Over 15,000 newcare breast, gynecological, melanoma, and bladder in Ireland annually.

The aimsprostate of this service are: cancers specialist services and 30% of muscle pump, weight control, in Ireland arecenters living with• lymphoedema.

Lymphoedema is progressive and if not treated, will Prevent lymphoedema in carepeople should be in specialist mental health at high risk skin changes and reduced function which can lead (community assessment, becomebased) morefor complex with buildpatients up of fluid causing • Compression: bandaging in complex patients and intensive • Empower patients intensive phase, garments long to higher costs and hospitalization duetototake cellulitis. treatment.

The healthcare structure of the greater control of their term. Correct garment helps national lymphoedema model of healthcare maintain/slow progression of Stages careLymphedema is depicted in Figure 1. condition • Move away from the traditional Early-Detection Lymphoedema • hospital centric model Stage 0: Subclinical/latent, undetectable by clinical examination. MLD: by a trained therapist, Service helps to reduce size of limb & Stage 1: Clinically visible oedema, spontaneously are soft, can have pitting. No pain • Piece together thereversible. fragmented Tissuesimprove skin condition. Also There is ongoing development of community services no skin changes & negative Stemmer’s sign.

SLD which is a modified form early detection services nationally. of MLD which patients perform therapy.

These services aim to detect • Providereversible, proactive planned Stage 2: Oedema is notsubspontaneously can be reversed with complete decongestive themselves. clinical lymphoedema which can be preventative care Pittingconservatively is difficult aswith tissues managed short are harder. Positive Stemmer’s sign.

• Data driven platforms at Once the symptoms of termStage use of3: compression garments, Irreversible, severe oedema with subcutaneous and connective tissue fibrosis, limb national level lymphoedema are controlled skin care, exercise and education, disfigurement & skin changes.

May include: hyperkeratosis, papillamatosis, pachydermia long term maintenance treatment and prevent chronic issues which • Cemented service based on all will begin with regular reviews, require complex treatment. stakeholder feedback measurement for new compression In Ireland, 70% of lymphoedema care should be provided in the primary care setting with non-specialist An early detection cancer garments at least every 6 months.

Lymphoedema Treatment lymphoedema service Ourbased) service for works with patients to services and 30%was of care shouldService be in specialist centers (community assessment, complex established at the physiotherapy ensure they can self-manage their patients and intensive treatment.

The structure of the national lymphoedema model of care is depicted The lymphoedema service in St department at St James’s Hospital lymphoedema which can often be James’s Hospital was established in 2020.

The service reviews in Figure 1. a life-long diagnosis. in 2003. This service provides patients before and after their References available on request assessment and treatment at the cancer treatment in order to

Stage 0: Subclinical/latent, undetectable by clinical examination.

Stage 1: Clinically visible oedema, spontaneously reversible. Tissues are soft, can have pitting. No pain no skin changes & negative Stemmer’s sign.

Stage 2: Oedema is not spontaneously reversible, can be reversed with complete decongestive therapy. Pitting is difficult as tissues are harder.

Positive Stemmer’s sign.

Stage 3: Irreversible, severe oedema with subcutaneous and connective tissue fibrosis, limb disfigurement & skin changes.

May include: hyperkeratosis, papillamatosis, pachydermia

Figure 1

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

(pembrolizumab) Infusion 25mg/ml

KEYTRUDA as monotherapy is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults.1 Survival results from KEYNOTE-006 An open-label, multicentre, randomised, controlled, phase 3 study of KEYTRUDA monotherapy vs Ipilimumab for patients with advanced Melanoma.1-3 7-Year Overall Survival in the intention-to-treat population*

In participants who completed 2 years of KEYTRUDA and achieved Stable Disease or better*

KEYTRUDA 37.8% vs Ipilimumab 25.3% HR 0.70 (95 % CI 0.58 to 0.83)

5-year Overall Survival was 92.9% 5-year Progression Free Survival was 70.1% 103/556 (18.5%) of patients obtained stable disease or better

In the as-treated population, any grade adverse events of any cause occurred in 442 (80%) of 555 participants in the pembrolizumab group and 190 (74%) of 256 participants in the Ipilimumab group. Grade 3 or worse adverse events of any cause occurred in 96 (17%) in the pembrolizumab group and 50 (20%) in the Ipilimumab group.

system can occur simultaneously. Immune-related adverse reactions are immune-related pneumonitis, immune-related colitis, immune-related hepatitis, immune-related nephritis, immune-related endocrinopathies (including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism), Immune-related skin adverse reactions (also including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)), Refer to SmPC for more information and management of immune-related adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with classical Hodgkin lymphoma undergoing allogeneic HSCT after previous exposure to pembrolizumab. Infusion-related reactions: Grades 1, 2, 3 or 4 infusion reactions including hypersensitivity and anaphylaxis, could be seen with pembrolizumab treatment. Refer to SmPC for more information and management of infusion-related reactions. Overdose: There is no information on overdose with pembrolizumab. In case of overdose, monitor closely for signs or symptoms of adverse reactions and treat appropriately. INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. No metabolic drug drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. Corticosteroids can be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. FERTILITY, PREGNANCY AND LACTATION Women of childbearing potential Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Pregnancy No data on use in pregnant women. Do not use during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Breast-feeding It is unknown whether pembrolizumab is secreted in human milk. A risk to newborns/ infants cannot be excluded. Fertility No clinical data available. SIDE EFFECTS Refer to SmPC for complete information on side effects. Pembrolizumab is most commonly associated with immune-related adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-and infusion-related adverse reactions. When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment. For additional lenvatinib safety information related to advanced RCC see the SmPC for Kisplyx and for advanced EC see the SmPC for Lenvima. Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, pruritus, rash, fatigue. Common: pneumonia, thrombocytopenia, neutropenia, lymphopenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, insomnia, dizziness, dysgeusia, pneumonitis, colitis, dry mouth, severe skin reactions, vitiligo, dry skin, alopecia, eczema, dermatitis acneiform, erythema, dermatitis, myositis, pain in extremity, arthritis, influenza like illness, chills, AST and ALT increases, increase in blood alkaline phosphatase, hypercalcaemia, blood bilirubin increased, blood creatinine increased, infusion related reaction. In combination with chemotherapy: Very Common: neutropenia, anaemia, thrombocytopenia, leukopenia, hypothyroidism, hypokalaemia, decreased appetite, insomnia, neuropathy peripheral, headache, dizziness, dysgeusia, dyspnoea, cough, nausea, diarrhoea, vomiting, abdominal pain, constipation, alopecia, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pyrexia, fatigue, asthenia, oedema, ALT increase, AST increased. Common: pneumonia, febrile neutropenia, lymphopenia, infusion related reaction, adrenal insufficiency, thyroiditis, hyperthyroidism, hyponatraemia, hypocalcaemia, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, pneumonitis, colitis, gastritis, dry mouth, hepatitis, severe skin reactions, erythema, dermatitis acneiform, dermatitis, dry skin, eczema, pain in extremity, arthritis, acute kidney injury, influenza-like illness, chills, blood creatinine increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased. In combination with axitinib or lenvatinib: Very Common: urinary tract infection, anaemia, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, diarrhoea, abdominal pain, nausea, vomiting, constipation, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pain in extremity, fatigue, asthenia, oedema, pyrexia, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, infusion-related reaction, adrenal insufficiency, hyperthyroidism, thyroiditis, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, dizziness, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, pancreatitis, gastritis, dry mouth, hepatitis, severe skin reactions, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, arthritis, nephritis, influenza like illness, chills, amylase increased, blood bilirubin increased, blood alkaline phosphatase increased, hypercalcaemia. PACKAGE QUANTITIES KEYTRUDA 25 mg/mL: 4 mL of concentrate in a 10 mL Type I clear glass vial. Legal Category: POM. Marketing Authorisation numbers EU/1/15/1024/002 Marketing Authorisation holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: May 2022. © 2022 Merck & Co., Inc., Rahway, NJ, USA and its affiliates.. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin, D18 X5K7 or from www.medicines.ie. II109_II117_II110 Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie.

Adverse events should also be reported to MSD (Tel: 01-2998700) References 1. KEYTRUDA (pembrolizumab) SmPC. Available at: www.medicines.ie. Accessed June 2022 2. Robert C, Carlino MS, McNeil C, et al. 7-Year Follow-Up of KEYNOTE-006: Pembrolizumab Versus Ipilimumab in Advanced Melanoma. Poster 104. Presented at the 18th International Congress of the Society for Melanoma Research; October 28-31, 2021; Virtual.

3. C. Robert, A. Ribas, J. Schachter et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 2019; 20: 1239-1251

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

IE-KEY-00588

KEYTRUDA® (pembrolizumab) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION KEYTRUDA 25 mg/mL: One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. INDICATIONS KEYTRUDA as monotherapy is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with Stage III melanoma and lymph node involvement who have undergone complete resection. KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults.

KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 with a ≥1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD L1 with a combined positive score (CPS) ≥ 10. KEYTRUDA as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 1. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic HNSCC in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy.

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma (RCC) in adults. KEYTRUDA, in combination with lenvatinib, is indicated for the first line treatment of advanced renal cell carcinoma in adults. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. KEYTRUDA as monotherapy is indicated for the first line treatment of metastatic microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in adults. KEYTRUDA as monotherapy is indicated for the treatment of the following MSI H or dMMR tumours in adults with (a) unresectable or metastatic colorectal cancer after previous fluoropyrimidine based combination therapy, (b) advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation, (c) unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy. KEYTRUDA, in combination with platinum and fluoropyrimidine based chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10. KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early stage triple negative breast cancer at high risk of recurrence. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple negative breast cancer in adults whose tumours express PD L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease. KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation. KEYTRUDA, in combination with chemotherapy with or without bevacizumab, is indicated for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD L1 with a CPS ≥ 1. DOSAGE AND ADMINISTRATION See SmPC for full details. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes. The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL is 2 mg/kg bodyweight (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. KEYTRUDA must not be administered as an intravenous push or bolus injection. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Treat patients until disease progression or unacceptable toxicity (and up to maximum duration of therapy if specified for an indication). For the adjuvant treatment of melanoma or RCC, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year. Refer to the SmPC for dosing in neoadjuvant and adjuvant treatment of locally advanced, or early stage triple-negative breast cancer at high risk of recurrence. KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued (a) For Grade 4 toxicity except for: endocrinopathies that are controlled with replacement hormones; or haematological toxicity, only in patients with cHL in which KEYTRUDA should be withheld until adverse reactions recover to Grade 0-1; (b) If corticosteroid dosing cannot be reduced to ≤10 mg prednisone or equivalent per day within 12 weeks; (c) If a treatment-related toxicity does not resolve to Grade 0 1 within 12 weeks after last dose of KEYTRUDA; (d) If any event occurs a second time at Grade ≥ 3 severity. Patients must be given the Patient Alert Card and be informed about the risks of KEYTRUDA. Special populations Elderly: No dose adjustment necessary. Renal impairment: No dose adjustment needed for mild or moderate renal impairment. No studies in severe renal impairment. Hepatic impairment: No dose adjustment needed for mild hepatic impairment. No studies in moderate or severe hepatic impairment. Paediatric population: Safety and efficacy in children below 18 years of age not established except in paediatric patients with cHL. CONTRAINDICATIONS Hypersensitivity to the active substance or to any excipients. PRECAUTIONS AND WARNINGS Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations. Immune-related adverse reactions Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. Most immune related adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Immune related adverse reactions have also occurred after the last dose of pembrolizumab. Immune-related adverse reactions affecting more than one body

Date of Preparation: June 2022

*This is a 7-year follow-up post-hoc analysis and no statistical conclusions can be drawn from these results

44

PEER REVIEW: BREAST CANCER

The importance of cancer clinical trials as illustrated by HER2+ breast cancer Then and Now: Cumulative effects of 30 years of Research: Targeting HER2, Breast Cancer and Beyond international ethical and scientific quality standard for the designing, conducting and reporting of trials that involve human participants.

Written by Dr Claire Brady. Oncology Clinical Trials Registrar, Cork University Hospital Cancer Clinical Trials Clinical trials are fundamental to advances in healthcare. COVID 19 and the development of effective vaccines have helped shine an important spotlight on the importance of clinical trials.

The recent ‘Just Ask 2022’ survey conducted by Cancer Trials Ireland (CTI) showed 78% of the the public surveyed agreed the pandemic has highlighted the importance of clinical trials.

The oncology community was one of many groups that celebrated International Clinical Trials Day “Then and Now” on the 20th May 2022. International Clinical Trials Day (ICTD) is held on/ around the 20th May of each year to commemorate the day when James Lind started his clinical trial on scurvy in 1747. This laid the foundation for modern clinical research and is the bedrock on which clinical medicine advancements are made.

Why cancer trials are important Clinical trials are the backbone of all progress seen in treatment of cancer. Medical oncology in particular, along with radiation oncology has helped to unite the disciplines of biology, basic research, genetics, immunology, pathology and pharmacology.

The collective input of these diverse disciplines has seen

the development of systemic treatments that has resulted in dramatically improved outcomes for patients. This is a dynamic and ever evolving field as shown by the recent ground breaking DESTINY 04 breast cancer trial results presented at the international American Society of Clinical Oncology (ASCO) annual meeting.

The National Cancer Control Program (NCCP) was established by the HSE in 2007 to lead in the development and implementation of cancer policies with the aim of standardising and improving national cancer care and patient outcomes.

In June 2022, the NCCP launched the Systemic Anti-Cancer Therapy (SACT) Model of Care. The report highlighted the growing incidence and prevalence of cancer in Ireland, with the number of cancers expected to double from 2015 to 2045. This will result in a projected 58-81% increase in the number of patients receiving SACT for cancer during this period. It has set out twenty five key recommendations to optimise SACT services.

One of its key recommendations is that ‘all patients should have access to a clinical trial where clinically appropriate’ and that ‘clinical trial services should be enhanced/developed in SACT services to support the availability of trials to all patients undergoing SACT.’ This recommendation is supported by the evidence that treatment on a clinical trial is regarded internationally as the gold standard of care. The report also notes there is evidence to suggest that outcomes for patients treated within the context of clinical trials are superior to those outside formal trials. The central role of clinical trials in cancer care has also being noted in the NCCP

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Cancer Strategy 2017-2026. One of its key performance indicators (KPI) is to increase patient participation in cancer therapeutic trials from 3% to 6% by 2020.

How cancer trials are conducted in Ireland Cancer Trials Ireland (CTI), established in 1996 (formally known as ICORG) is the leading cancer research trials organisation in Ireland. More than 15,000 Irish patients have particiapted in over 350 cancer trials. It is a not for profit registered charity and is partly funded by the Health Research Board (HRB) and Irish Cancer Society. It has developed strong links with international cancer research groups and has facilitated Irish patients being able to participate in internationally, practice changing clinical trials. It serves as the key link for strategic and coordinated support for the dedicated on site cancer trials units in hospitals across Ireland and the recently formed six cancer clinical trials groups. In 2021, the HRB invested ¤22 million to support the delivery of high quality cancer care in these six cancer trials groups (Children’s Health Ireland Cancer Trials Group, Beaumont Hospital – RCSI University of Medicine and Health Sciences Cancer Trials Group, Irish Research Radiation Oncology Trials Group, UCC Cancer Trials Group, Ireland East Hospital Cancer Trials Group, Trinity Academic Cancer Trials Group.)

Regulation of Clinical Trials The conduct of clinical trials is strictly regulated ensuring the fundamental importance of safety for all trial participants. All clinical trials must be conducted within strict national regulations and are underpinned by Good Clinial Practice (GCP). GCP is an

Before a clinical trial can be conducted, it must receive approval by a national ethics committee and/or the Ethics Committee of the hospital in which it is taking place. The recent establishment of the National Ethics Committee aims to streamline this process.

Furthermore, a clinical trial involving an investigational medicinal product (IMP) must be approved by the Health Products Regulatory Authority (HPRA). The HPRA ensures that trials are conducted in line with current Irish & EU legislation and standards for clinical research.

Clinical trials are subject to continuous data monitoring with strict criteria for reporting serious adverse events.

Pharmacovigilance compliance is monitored by HPRA. Study personnel All study personnel involved in the conduct of a study must have up to date GCP training and must receive specific training in relation to the particular study in which they are involved. Compliance with this standard provides public assurance that the rights, safety and wellbeing of people participating in cancer trials are protected and that the resulting clincal trial data is trustworthy.

Patient participation Patient participation in clinical trials is entirely voluntarily. It involves a detailed consent process. This involves dicussing both standard of care options in addition to the clinical trial. Armed with this knowledge, a patient can determine what the best treatment plan is for them.

Why Cancer Trials are Important – review of 30 years of progress in treating HER2+ breast cancer 15-20% of breast cancers overexpress the HER2 protein and are referred to as HER2+ breast cancer. Before HER2 directed therapy, this subset of breast cancer was recognised

MYLOTARGTM is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients age 15 years and above with previously untreated, de novo CD33‑positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia (APL)1,2

Add MYLOTARG™ to

REINFORCE YOUR

AML TREATMENT

FOR LONGER REMISSION COMPARED WITH STANDARD OF CARE CHEMOTHERAPY1,2 MYLOTARG™ significantly extends EFS and RFS* for patients with previously untreated de novo AML compared with the standard of care, chemotherapy with DNR and AraC1,2

▼ MYLOTARG® (gemtuzumab ozogamicin) PRESCRIBING INFORMATION Please refer to the Summary of Product Characteristics (SmPC) before prescribing MYLOTARG 5 mg powder for concentrate for solution for infusion.

Presentation: Each vial contains 5 mg gemtuzumab ozogamicin. After reconstitution the concentrated solution contains 1 mg/ mL gemtuzumab ozogamicin. Gemtuzumab ozogamicin is an antibody-drug conjugate composed of the CD33-directed recombinant monoclonal antibody humanized hP67.6; recombinant humanised immunoglobulin [Ig] G4, kappa antibody covalently linked to the cytotoxic agent N-acetyl gamma calicheamicin.

Indications: MYLOTARG is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients aged 15 years and above with previously untreated, de novo CD33-positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia (APL). Dosage: Administer under the supervision of a physician experienced in the use of cancer therapy and in an environment where full resuscitation facilities are immediately available.

MYLOTARG should be used only in patients eligible to receive intensive induction chemotherapy. The recommended induction dose of MYLOTARG is 3 mg/m2/dose (up to a maximum of one 5 mg vial) infused over a 2 hour period on Days 1, 4, and 7 in combination with DNR 60 mg/m2/day infused over 30 minutes on Day 1 to Day 3, and AraC 200 mg/m2/day by continuous infusion on Day 1 to Day 7. If a second induction is required, DNR should be infused at a dose of 35 mg/m2/ day on Day 1 to Day 2 and AraC at a dose of 1 g/ m2/every 12 hours on Day 1 to Day 3. MYLOTARG should not be administered during a second induction. For patients experiencing a complete remission (CR) following induction, defined as fewer than 5% blasts in a normocellular marrow and an absolute neutrophil count (ANC) of more than 1.0 × 109 cells/L with a platelet count of 100 × 109/L or more in the peripheral blood in the absence of transfusion, up to 2 consolidation courses of intravenous DNR (60 mg/m 2 for 1 day [first course] or 2 days [second course]) in combination with intravenous AraC (1 g/m2 every 12 hours, infused over 2 hours on Day 1 to Day 4) with intravenous MYLOTARG (3 mg/m 2/dose infused over 2 hours up to a maximum dose of one 5 mg vial on Day 1) are recommended. Dose modification of MYLOTARG may be required based on individual safety and tolerability.

Management of some adverse drug reactions may require dosing interruptions and/or dose reductions, or permanent discontinuation of MYLOTARG. See SmPC for dose modification guidelines for haematological and non haematological toxicities. Special populations: Hepatic impairment: No adjustment of the starting dose is required in patients with hepatic impairment defined by total bilirubin ≤ 2 × upper limit of normal (ULN) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN. Postpone MYLOTARG until recovery of total bilirubin to ≤ 2 × ULN and AST and ALT to ≤ 2.5 × ULN prior to each dose. Renal impairment MYLOTARG has not been studied in patients with severe renal impairment. Paediatric population: The safety and efficacy of MYLOTARG in patients less than 15 years has not been established. Contra-indications: Hypersensitivity to the active substance or to any of the excipients.

Special warnings and precautions for use: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Premedication with a corticosteroid, antihistamine and acetaminophen (or paracetamol) is recommended 1 hour prior to MYLOTARG dosing due to the potential for infusion related reactions. In patients with hyperleukocytic AML, leukoreduction should be considered with hydroxyurea or leukapheresis to reduce the peripheral WBC count to below 30,000/mm3 prior to administration of MYLOTARG to reduce the risk of inducing tumour lysis syndrome.

Appropriate measures to help prevent the development of tumour lysis-related hyperuricaemia, such as hydration, a d m i n i s t rat i o n o f a nt i hy p e r u r i ce m i c s (e.g., allopurinol) or other agents for treatment of hyperuricaemia (e.g., rasburicase) must be taken.

Hepatotoxicity: Hepatotoxicity, including severe, life-threatening, and sometimes fatal hepatic failure and VOD/SOS have been reported in patients treated with MYLOTARG. Adult patients who received MYLOTARG as monotherapy, either before or after a haematopoietic stem cell transplant (HSCT), and patients with moderate or severe hepatic impairment are at increased risk for developing VOD. Signs and symptoms of VOD/SOS should be monitored closely in all patients. For patients who develop abnormal liver tests, more frequent monitoring of liver tests and clinical signs and symptoms of hepatotoxicity is recommended. For patients who proceed to HSCT, close monitoring of

References 1. Pfizer MYLOTARG™ (gemtuzumab ozogamicin) Summary of Product Characteristics.

2. Pfizer Cytarabine Summary of Product Characteristics.

PP-MYL-IRL-0094 Date of preparation February 2022

liver tests is recommended during the post-HSCT period, as appropriate. Management of signs or symptoms of hepatic toxicity may require a dose interruption, or discontinuation of MYLOTARG (see section 4.2). In patients who experience VOD/SOS, MYLOTARG should be discontinued and patients treated according to standard medical practice.

Myelosuppression/cytopenias: Neutropenia, thrombocytopenia, anaemia, leukopenia, febrile neutropenia, lymphopenia, and pancytopenia, some life-threatening and some with complications, were reported. Blood counts should be monitored prior to dosing and signs of myelosuppression should be monitored during treatment. Infusion related reactions: Infusion should be interrupted immediately for patients who develop evidence of severe reactions, especially dyspnoea, bronchospasm, or clinically significant hypotension. Patients should be monitored until signs and symptoms completely resolve. Discontinuation of treatment should be strongly considered for patients who develop signs or symptoms of anaphylaxis, including severe respiratory symptoms or clinically significant hypotension. The efficacy of MYLOTARG has been shown in AML patients with favourable- and intermediate-risk cytogenetics, with uncertainty regarding the size of the effect in patients with adverse cytogenetics (see smPC section 5.1).

For patients being treated with MYLOTARG in combination with daunorubicin and cytarabine for newly diagnosed de novo AML, when cytogenetics testing results become available it should be considered whether the potential benefit of continuing treatment with MYLOTARG outweighs the risks for the individual patient (see smPC section 5.1) Fertility, pregnancy and lactation: Women of childbearing potential receiving this medicinal product, or treated male partners should use effective contraception during therapy and for at least 7 months or 4 months after completing therapy for females and males, respectively. There are no or limited amount of data from the use of MYLOTARG in pregnant women. Non-clinical studies have shown reproductive toxicity.

MYLOTARG must not be used during pregnancy unless the potential benefit to the mother outweighs the potential risks. The potential hazard to the foetus of MYLOTARG treatment must be explained to pregnant women, patients becoming pregnant while receiving treatment, or treated male partners of pregnant women. Because of the potential for adverse reactions in breast-fed children, women must not breast-feed during treatment with MYLOTARG and for at least 1 month after the final dose. Based on non-clinical findings,

male and female fertility may be compromised by treatment with MYLOTARG. Driving and operating machinery: MYLOTARG may cause fatigue and patients should exercise caution when driving or using machines. Undesirable effects: The overall safety profile of MYLOTARG is based on data from patients with acute myeloid leukaemia from the combination therapy study ALFA-0701, monotherapy studies, and from post-marketing experience. In the combination therapy study, safety data consisting of selected treatment emergent adverse events (TEAEs) considered most important for understanding the safety profile of MYLOTARG consisted of all grades haemorrhages, all grades VOD, and severe infections. The most common adverse reactions (> 30%) in the combination therapy study were haemorrhage and infection. In patients who received MYLOTARG in the combination therapy study ALFA-0701, clinically relevant serious adverse reactions were hepatoxicity including VOD/SOS (3.8%), haemorrhage (9.9%), severe infection (41.2%), and tumour lysis syndrome (1.5%). See relevant SmPC (Table 5) for full details on specific comprehensive list of AEs for combination therapy.

Instructions for reconstitution and dilution: Use appropriate aseptic technique for the reconstitution and dilution procedures. Following reconstitution and dilution, the solution should be protected from light and should be used immediately. If the product cannot be used immediately, the diluted solution may be stored up to 18 hours in a refrigerator (2°C–8°C) from the time of initial vial puncture with not more than 6 hours at room temperature (below 25°C).

Legal Category: S1A. Marketing Authorisation Number: EU/1/18/1277/001 – 5mg 1 vial. The Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@pfizer.com.

For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500. ▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Last revised: 11/2020 Ref: ML 4_0

*RFS is a secondary endpoint. Only EFS and RFS achieved significance in the ALFA-0701 study.1 AML, acute myeloid leukaemia; APL, acute promyelocytic leukaemia; AraC, Cytarabine; DNR, Daunorubicin; EFS, event-free survival; RFS, relapse-free survival.

46

PEER REVIEW: BREAST CANCER for its aggressive biology and poorer outcomes in comparison to hormone sensitive breast cancer.

Targeting HER2+ breast cancer has dramatically changed the natural history of this disease and is no longer associated with the dismal outcome of the past.

Identifying HER2 as an oncogene The discovery of the protooncogene HER2 as a driver of cancer, is a prime example of how this sparked a revolution in the management of cancers which overexpress this protein. It highlights the essential ecosystem that is bench to bedside/clinical research. Understanding this process is important for all health professionals and is critical to be able to evaluate and critically appraise trial results.

in rat neuroblastomas in 1984. It was noted to be similar in overall structure to EGF receptors. This was soon followed in 1985 by the cloning of the human neu counterpart by Ullrich’s group, which was called HER2 (Human E(GFR) Receptor 2) based on the similarity with EGFR receptor.

ERBB2 refers to the gene across both human and rodent species.

HER2 is one of the four members of the ERBB family of receptor tyrosine kinase inhibitors, which include EGFR (HER1), HER3 and HER4. HER2 mediates signalling pathways including PI3K/AKT/ mTOR and MAPK pathways, which regulate cellular processes of proliferation, motility and survival.

the interrogation of tumour cells provided from a human breast cancer tumour bank rather than cell lines. The Slamon group furthermore, idenitifed HER2 as a prognositic biomarker showing that women with overpression of HER2 in their tumours had a more aggressive phenotype with a substantially worse progress.

This provided strong evidence that HER2 was likely to play a role in driving tumorigenesis.

recommend initial assessment of HER2 status using IHC and a semi quantitative scoring system, followed by reflex ISH testing in all IHC score 2+ cases.

Understanding the nuances of this testing has become even more important in the context of the recent DESTINY 04 trial publication.

Prior to this trial, predictive HER status has been reported in a binary fashion (positive versus negative).

DESTINY 04 results defined a new predictive group called HER2 low expression.

Defining HER2 positive breast cancer: IHC & ISH Assessment of HER2 overexpression is with immunohistochemistry (IHC) and in situ hybridization (ISH) testing.

Correct pathological assessment of HER2 status is of the utmost importance, as it is the sole predictive marker for response to HER2 directed therapy. Reporting of IHC and ISH results is in accordance with the updated 2018 ASCO/CAP guidelines. Since 2007, ASCO/CAP guidelines

Hitting the bull’s-eye: HER2 as a predictive biomarker in breast cancer

Current algorithm for defining HER2+ breast cancer*

Finding the Receptor: Cell signalling & Nomeclature

Neu refers to the oncogene that was isolated by Weinberg et al

Discovering the role of HER2 in human cancer

In 1987, Dr Dennis Slamon, a physician/scientist at UCLA discovered that the HER2 gene was amplified in approximately 30% of breast cancers. This major breakthrough was achieved with

Preclinical research by Drs' Shepard and Ullrich led to the development of HER2 mouse monoclonal antibodies called ‘MoAb 4D5’ followed by the humanised monoclonal antibody 4D5, now known as trastuzumab.

In 2019, a New England of Medicine editorial by Professor

Current algorithm for defining HER2+ breast cancer* HER testing by validated IHC assay

Current algorithm for defining HER2+ breast cancer*

HER testing by validated IHC assay

Circumferential membrane staining that is complete, intense, and in >10% of tumour cells

Circumferential membrane staining that is complete, intense, and in >10% of tumour cells

Incomplete membrane staining that is faint/barely perceptible and in >10% of tumour cells IHC 1+

Weak to moderate complete membrane staining observed in >10% of tumour cells

IHC 3+

IHC 2+

Positive

Negative

Equivocal

IHC 3+

IHC 2+

Positive

Equivocal

No staining is observed

Incomplete membrane staining that is faint/barely perceptible and in >10% of tumour cells

Weak to moderate complete membrane staining observed in >10% of tumour cells

IHC 1+ Negative

or Membrane staining that is incomplete and is faint/barely perceptible and in ≤10% of tumour cells

No staining is observed or Membrane staining that is incomplete and is faint/barely perceptible and in ≤10% of tumour IHC 0 cells

Negative

IHC 0 Negative

Must order reflex ISH testing Must order reflex ISH testing

ISH Positive

ISH negative

HER2 Positive

HER2 Negative

ISH Positive

ISH negative

HER2 Positive

HER2 Negative

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

* Adapted from ASCO/CAP 2018 gu * Adapted from ASCO/CAP 2018 guidelines

47 Classes of HER2 Targeted Therapy Monoclonal Monoclonal antibodies antibodies Trastuzumab* Trastuzumab* (Herceptin & other (Herceptin & other brand names) brand names) Pertuzumab* Pertuzumab* (Perjeta) (Perjeta) Margetuximab Margetuximab (Margenza) (Margenza)

Antibody drug Antibody conjugatesdrug (ADC) conjugates (ADC) Ado-trastuzumab Ado-trastuzumab emtansine * emtansine * (Kadcyla) (Kadcyla) Fam-trastuzumab Fam-trastuzumab deruxtecan deruxtecan (Enhertu) (Enhertu)

Tyrosine kinase Tyrosine inhibitorskinase (TKI) inhibitors (TKI) Lapatinib (Tykerb)* Lapatinib (Tykerb)* Neratinib Neratinib (Nerlynx)* (Nerlynx)* Tucatinib (Tukysa) Tucatinib (Tukysa) * Reimbursed by NCCP * Reimbursed by NCCP

Daniel Hayes stated – “the terms ‘game changer’ and ‘blockbuster’ are worn, but in this case the ingenuity, vision and persistence of these collaborators justify these superlatives.” In 2019, Drs’ Slamon, Shepard and Ullrich were awarded the prestigious Lasker DeBakey Clinical Medical Research Award for their invention of Herceptin.

The discovery of trastuzumab led to a flurry of clinical trials which demonstrated not only its dramatic benefit in the advanced setting but also in the neo/adjuvant setting. For instance, the HERA trial reported in 2005, showed the addition of adjuvant Herceptin in HER2+ breast cancers halved the risk of cancer returning when it was added to chemotherapy. Irish patients had the benefit of participating in this trial ensuring they had the earliest access to treatment which ultimately proved to dramatically improve survival. There is no better example of how access to clinical trials can be truly life changing for patients.

Since those initial studies, the treatment landscape for HER2+ positive breast cancer has exploded, with 3 classes of HER2 targeted therapy now available.

HER2 also represents a potential opportunity for seeking tissue agnostic approval. These umbrella trials or basket trials enroll patients based on the genetic biomarkers of their tumours as determined with genomic sequencing, regardless of the pathological tissue of origin.

Examples of these trials include the TAPUR (Targeted Agent and Profiling Utilisation Registry), MATCH and MyPathway.

of patients. Further refinement and discussion regarding inter pathological variability in detecting HER2 low (IHC 1+) will be of even greater importance given this new therapeutic option, in addition to assessing risks and management of treatment related toxicities including pneumonitis.

Clinical trials are integral to providing the very best care for patients. One in two people will develop cancer in their lifetime. It is imperative that we strive to cure as many people as possible. This can only be achieved with access to high quality clinical trials that is embedded in health care planning.

Proposed algorithm for defining HER2- low breast cancer*

2022 – HER2+ Low Breast Cancer: A new predictive biomarker & treatment paradigm DESTINY 04 results which were presented at the plenary session at the annual ASCO congress in June 2022 were met with

*See www.cancertrials.ie for more information.

References available upon request

Proposed algorithm for defining HER2-low breast cancer* HER testing by validated IHC assay

IHC 3+

IHC 2+

POSITIVE

Equivocal

HER2 POSITIVE

ISH Positive HER2 POSTIVE

IHC 1+

ISH negative HER2 LOW

IHC 0

Negative

Negative

HER2 LOW

HER2 NEGATIVE

*Adapted from Tarantino et al. JCO 2020

HER 2+ Therapeutic Trials Open in Ireland (as of 1st July 2022)*

Beyond HER2+ Breast Cancer: In 2009, the TOGA (Trastuzumab for Gastric Cancer) Trial, showed a benefit of trastuzumab beyond breast cancer. The results of this phase III trial led to approval of trastuzumab for patients with HER2+ metastatic gastric or gastroesophageal cancer.

rapturous standing ovation by the packed audience. It is the first randomized trial to demonstrate that targeting HER2 for patients with metastatic HER2-low (IHC 1+ or IHC2+ and ISH negative) breast cancer had meaningful benefit. This phase three randomised trial, demonstrated that heavily pre-treated patients with advanced HER2 low expressing breast cancers as defined by conventional HER2 testing (previously defined as HER2 negative) had a 50% reduction in the risk of disease progression or death when treated with trastuzumab-deruxtecan as compared with treatment of physicians choice. With approximately 60% of HER2 negative breast cancers assessing low levels of HER2 expression; this represents a significant advancement for a large cohort

DESTINY- 12

• Disease site: breast • Indication: previously treated advanced HER2+ breast cancer, whose disease has progressed on prior HER2 based regimens • Phase: 3b/4, open-label, single arm • IMP: trastuzumab deruxtecan

DESTINY-05

• Disease site: breast • Indication: HER2+ primary breast cancer that do not achieve a complete pathological response after neoadjuvant chemotherapy and are at high risk of recurrence • Phase: 3, randomised, open label, active controlled study • IMP: trastuzumab deruxtecan vs trastuzumab emtansine

DESTINY DS8201-A-U306

• Disease site: Upper GI • Indication: HER2+ metastatic/and or unresectable gastric or GEJ cancer • Phase: 3, randomised, 2 arm, open label • IMP: trastuzumab deruxtecan vs ramucirumab + paclitaxel

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

2022 NOMINATIONS NOW OPEN

PROFESSIONAL PROFESSIONAL 100 100 Our annual listing celebrating innovation and excellence in healthcare is coming soon.

To request an entry or nomination form please

To request an entry or nomination form please contact: contact: kelly-jo@ipn.ie sarah@hospitalprofessionalnews.ie

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

CPD 90: POLYMYALGIA RHEUMATICA Continuing Professional Development

CPD 60 Second Summary Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disease which demonstrates a strong association with aging. In Ireland, 2% of the population will experience the condition at some time during their life.

Characteristic symptoms constitute bilateral hip and shoulder stiffness with an early morning predominance.

Inflammatory markers (ESR and CRP) are generally elevated, but not always markedly so.

Many other conditions can present with polymyalgia-like symptoms, with potential negative consequences if missed, therefore a thorough clinical assessment at initial presentation is crucial.

Symptom response to relatively modest doses of glucocorticoids, for example 15mg prednisolone, is usually dramatic. Long-term glucocorticoids are needed however, with a minimum of one year duration. Difficulties therefore arise due to the challenge of maintaining a good clinical response while minimising glucocorticoid related adverse events.

Careful navigation of these challenges has the potential to improve long term outcomes for people with PMR and close clinical monitoring is essential. There are several treatment options which now have evidence of efficacy for relapsing or refractory disease, including methotrexate, tocilizumab, and rituximab.

Adjunctive treatment for bone and gastro protection is crucial, as are patient education and careful management of emergent treatment or disease related complications.

49

AUTHOR: Dr Richard Conway, Consultant Rheumatologist, St. James Hospital; Clinical Associate Professor, Trinity College Dublin Richard Conway graduated from the Royal College of Surgeons in Ireland in 2006.

He completed rheumatology and general internal medicine training in Ireland in 2014, and a PhD in giant cell arteritis at University College Dublin in 2017. He is currently a consultant rheumatologist and physician at St. James’s Hospital and a clinical associate professor at Trinity College Dublin. He is the author of more than 150 peer-reviewed publications and 3 book chapters. His research interests include interstitial lung disease in systemic rheumatic diseases, vasculitis, and polymyalgia rheumatica.

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. Galapagos UK, has no editorial oversight of the CPD programmes included in these modules.

Management and Treatment of Polymyalgia Rheumatica Introduction Polymyalgia Rheumatica (PMR) is an inflammatory rheumatic condition. It has a striking age predilection, virtually never occurring prior to age 50 and becoming more common until a peak in the 70’s with a plateau thereafter. PMR is a common disease, with an incidence equivalent to rheumatoid arthritis (RA). It demonstrates a marked geographic preponderance being strikingly more common in Northern European populations than in other parts of the world.

This association seems to be genetically based rather than due to physical location with emigrant populations maintaining the risk of their ancestral origin. The lifetime risk of PMR in Ireland (extrapolated from similar populations) is 2.5% for women and 1.5% for men.1 The cause of PMR is unknown; the marked age association suggests a key role for immunosenescence.

It is hypothesised that a particular individual’s immune system may be primed, by aging and/or other factors, to develop PMR, and then a subsequent second hit triggers the disease. The nature of this trigger has been elusive, and this may reflect the fact that there is no specific trigger; rather it may be the case that anything that

stimulates the immune system can act in this role, this would correlate with the wide variety of infectious agents mooted as triggers, and indeed with the more controversial association with vaccines.

Clinical Presentation PMR is very much a disease defined by the word “usually”.

While there is a classic presentation, the individual components of which are seen in the majority of patients, the absence of these features does not rule out the diagnosis. By virtue of how common PMR is, it becomes relatively frequent to see patients with atypical presentations, where we run the risk of erroneously ruling out PMR. PMR typically presents with a sudden onset of symptoms. This can be dramatic; a patient can go to bed perfectly well and wake the subsequent morning unable to move. Patients will often report that “I became an old woman/ man overnight”. The symptoms are most often described as an ache or stiffness but may be referred to as pain. The typical sites affected are the proximal limb muscles – the shoulders and hips, and the neck. However, it is a myth that distal involvement rules out PMR, up to 50% of patients will have

involvement of the hands, wrists, or knees; frequently this is mild but can occasionally predominate.

PMR is classically a bilateral and symmetric condition. At initial onset one side may be affected in isolation, however it rapidly progresses to involve both sides.

While most patients will present with both shoulders and hips affected, they may not be equally involved, and a substantial minority of patients will report only shoulder or hip involvement in isolation.

Early morning predominance of symptoms is characteristic, this is described as early morning stiffness – a shared feature of all inflammatory arthritis conditions.

Patients will often also become stiff to a lesser degree after sitting for prolonged periods – not infrequently on the car journey to their clinic appointment or sitting in the waiting room! Patients with more severe symptoms will often not manifest the characteristic improvement during the day, they will wake with early morning stiffness which will then continue until they go to bed again.

Systemic symptoms such as weight loss, malaise, and anorexia are common. Fever however is unusual in isolated PMR and should prompt a search for one of the PMR mimics.

50

CPD 90: POLYMYALGIA RHEUMATICA

PMR Mimics It is perhaps more appropriate to consider PMR as a clinical syndrome rather than a specific disease, at least at initial presentation. This reflects the limitations of our nosological framework of disease categorisation. The entity we consider as PMR is likely composed of a number of different “diseases” which present in similar ways, sometimes this will differentiate into other defined conditions over time.

It is likely however that even in those who remain in the PMR diagnostic category that several different disease subsets and pathogeneses are represented.

This being the case, when a patient presents with a polymyalgic syndrome there are a number of important differentials to consider. PMR is frequently considered an easy diagnosis to make, I would argue that it is easy to mis-diagnose PMR given the many different conditions which can present with similar symptom complexes.

Probably the most frequent and important of these to consider is giant cell arteritis (GCA). While it is still debated, PMR and GCA are likely two ends of the spectrum of a single disease process. This is supported by shared pathogenic mechanisms, demographic associations, treatment responses, and particularly by the frequent co-occurrence of the two – 50% of GCA patients have polymyalgic symptoms, while 10-30% of people with PMR will ultimately develop GCA. All patients presenting with PMR should have a clinical assessment for GCA including examination of the temporal arteries and for large vessel arterial bruits. If the history or examination raise concern for GCA, further investigation with imaging and/or temporal artery biopsy should be pursued.

The second classic mimic of PMR is rheumatoid arthritis (RA). RA can present initially with proximal joint symptoms in the same distribution as PMR. This is particularly the case in elderly patients, the very group in whom PMR classically presents. Clues to the presence of RA can include synovitis in the hands and feet, and of course positive rheumatoid factor or anti-cyclic citrullinated peptide

antibodies (these are only present in 70% of rheumatoid arthritis patients however). Marked foot involvement in particular is almost never seen in true PMR. A number of other conditions can present with initial polymyalgic symptoms. These include ANCAassociated vasculitis (which can subsequently manifest severe organ damage) and idiopathic inflammatory myopathies (which more commonly present with muscle weakness rather than stiffness or pain). Non-rheumatic diseases are important mimics, these include hypothyroidism, Parkinson’s disease, myasthenia gravis, and non-inflammatory myopathies – all of these should particularly be considered in patients with no elevation in inflammatory markers.

The final mimics are those which are drilled into the minds of medical students and trainees the world over – paraneoplastic and infections (particularly infective endocarditis). It is of course vital not to miss these, however, it is unusual that these would present with symptoms of PMR in the absence of other consistent features.

Clinical Examination Given the predominant symptoms, the clinical examination in PMR will often be dominated by pain and restricted range of motion in the shoulders and hips. It is important to assess for synovitis clinically as this may be a clue as to the presence of rheumatoid arthritis. Palpation of the temporal artery for tenderness, swelling, hardening, or loss of pulsation is important to assess for cranial GCA. Auscultation of the carotid, subclavian, and axillary arteries to assess for vascular bruits may be a clue to large vessel GCA but can also be seen in atherosclerosis.

Stigmata of infective endocarditis or signs of an underlying malignancy should not be missed.

It is important in patients with known PMR to assess for clinical signs of GCA at each visit due to the high rate (10-30%) of development of GCA in patients with PMR. As diseases may evolve over time, it is also prudent to reassess the peripheral joints for synovitis at each visit, as a diagnosis of rheumatoid arthritis would change management.

Laboratory Investigations PMR is a systemic inflammatory rheumatic disease. As such acute phase reactants / inflammatory markers are characteristically but not invariably elevated. Erythrocyte sedimentation rate (ESR) is the traditional diagnostic test in PMR but actually, C-reactive protein (CRP) is the more useful test overall. CRP is elevated in 98-99% of patients with PMR. ESR can be normal in up to 20% of patients with untreated PMR. While having both a normal ESR and CRP does occur in PMR, this is distinctly unusual and should prompt reconsideration of the diagnosis. An important pitfall to avoid is being misled by the extent of the inflammatory marker elevation. While it sometimes occurs, PMR does not necessarily need to be associated with very high inflammatory markers, lesser elevations are also significant in the appropriate clinical scenario.

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

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

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

Imaging Imaging is rarely required to make the diagnosis of PMR. It sometimes reveals the disease when done for other reasons, either incidentally or when investigating unexplained inflammatory marker elevations.

Ultrasound, MRI, and PET scan can all demonstrate evidence of inflammation in periarticular structures. This typically consists of subdeltoid/subacromial bursitis and long head of biceps

tenosynovitis in the shoulders, and trochanteric bursitis and hamstring tendinitis in the hips. Capsular inflammation can also be seen.

Treatment It is a misconception that PMR is an easy disease to treat. It is relatively easy to get a rapid benefit in these patients, but longer-term management and maintenance of initial good responses is much trickier. Negotiation of treatment related adverse events is also a significant challenge.

Our treatment paradigm in PMR continues to be largely glucocorticoid based. In Ireland this will utilise prednisolone as the glucocorticoid of choice.

Enteric coated formulations may be associated with less adverse events in individual patients but there is little objective evidence they are beneficial for the wider group of people with PMR and dose tapering is complicated by the absence of lower strength doses of these formulations.

I recommend a starting dose of prednisolone 15mg daily in PMR; this will be sufficient for complete symptom resolution in most patients. There are a small percentage of PMR patients who will require a higher initial dose of 20mg or even 25mg; glucocorticoids are a weightbased medication, and this is more commonly seen in higher weight individuals. There are two benefits to starting with this relatively low glucocorticoid dose, the lower cumulative glucocorticoid exposure is self-evident. The second benefit is a diagnostic one; 15mg of prednisolone will generally completely resolve “true” PMR but will frequently be less effective in many of the mimics.

The glucocorticoid response is typically dramatic in PMR, some individuals will have symptom resolution in hours, and most will in 1-2 days; there are however a smaller percentage of patients where this may take 1-2 weeks, and the absence of a rapid response does not exclude PMR. Once glucocorticoids have commenced, it is prudent to review the response, either in person or by telehealth, at 2-4 weeks. This again helps to provide diagnostic confirmation. If a response is absent or suboptimal, the diagnostic process should be revisited. If a good response

51

Figure 2: Prognosis in PMR

has been achieved, this is now the time to formulate a long-term treatment plan. There are many ways in which the glucocorticoid dose can be tapered. My practice is to reduce glucocorticoids at monthly intervals; this obviates the need for the patient to change doses between pharmacy prescriptions – they receive 1 month supply at a time and stay at the same dose until they return for the next dispensing. After 1 month on 15mg, the dose reduces to 12.5mg for 1 month, then 10mg for 1 month, thereafter, reducing by 1mg a month until stopped. If a higher starting dose is needed (20 or 25mg), then this extra reduction should be added initially as extra months, I generally reduce by 5mg a month above 20mg, by 2.5mg a month between 20mg and 10mg, and 1mg a month under 10mg. It is absolutely vital during this process that the patient both knows to, and has the facility, to contact the treating physician if there is a recrudescence of their symptoms.

Relapse is common on glucocorticoid tapering, occurring in up to 50% of patients.3 Many relapses, particularly if addressed promptly will respond to an increase to the last prednisolone dose at which there were no

symptoms, while further delay will often lead to a necessity to return to the initial prednisolone dose. Subsequent tapering as per the original protocol, will generally be successful. If patients continually relapse at a particular glucocorticoid dose, alternative tapering strategies such as alternate day tapering (eg reduce from 5mg to 4mg/5mg on alternate days instead of directly to 4mg) or reducing the dose every two months rather than monthly, may be successful. Even with these strategies many patients will reach a “threshold” glucocorticoid dose below which relapse inevitably and persistently occurs. At this point consideration should be given to the alternative options of long-term maintenance glucocorticoids or addition of a second agent. This decision may be dependent on what the threshold glucocorticoid dose is; glucocorticoids have a multitude of adverse events related to dose and cumulative dose.

Generally, anything above 5mg daily of prednisolone is probably inadvisable, but even at lower doses there are increased rates of adverse events.4, 5 Methotrexate has been our traditional second line medication in PMR. There is randomised

nisolone tapering regimen in PMR 15mg daily x 1 month 12.5mg daily x 1 month 10mg daily x 1 month 9mg daily x 1 month 8mg daily x 1 month 7mg daily x 1 month 6mg daily x 1 month 5mg daily x 1 month 4mg daily x 1 month 3mg daily x 1 month 2mg daily x 1 month 1mg daily x 1 month Then stop

1/3 – smooth glucocorticoid reduction

Figure 2: Prognosis in PMR Methotrexate has been our traditional second line medication in PMR. There is randomised controlled trial evidence for a steroid sparing effect (6). However, in clinical practice this is ofte quite modest, and the efficacy of methotrexate in PMR does not approach its efficacy in rheum arthritis. For some patients this modest steroid effect, even if it only results in a reduction of a 8 milligrams in the dose, may however.

Within last year we no controlled trialdaily evidence for be a clinically meaningful, term benefits in PMR. Thethe place 6 have evidence fromeffect. three randomised trials of biologic disease antirheum steroid sparing However, controlled of these bDMARDs in the modifying PMR drugs (bDMARDs) to treat The IL-6 inhibitors tocilizumab and sarilumab, the latter not in clinical practice thisPMR. is often treatment algorithm is still under quite modest, the to efficacy of consideration.

While wouldeffect be in GCA (7). available in Ireland,and appear have excellent efficacy, mirroring theiritknown methotrexate in PMR does intuitively appealing tohas administer surprisingly perhaps, a single dosenot of rituximab at treatment initiation been shown to have approach efficacy in rheumatoid them up in front all treatment patients with term benefits its in PMR (8). The place of these bDMARDs the to PMR algorithm is still arthritis. For some patients this the aim to minimise cumulative consideration. While it would be intuitively appealing to administer them up front to all patien modest steroid effect, even if it glucocorticoid exposure as with theresults aim to minimise cumulative glucocorticoid exposure as much as possible, this would only in a reduction of a few much as possible, this would undoubtedly to the over-treatment patients who would have done just fine with milligramslead in the daily dose, may of many undoubtedly lead to the overglucocorticoid disadvantage of waitingofuntil relapses occur, is that by that t be clinicallymonotherapy. meaningful, The however. treatment many patients who Within the last year we now have would have done just fine with evidence from three randomised glucocorticoid monotherapy. controlled trials of biologic The disadvantage of waiting until disease modifying antirheumatic relapses occur, is that by that drugs (bDMARDs) to treat PMR. time a significant accumulation The IL-6 inhibitors tocilizumab of glucocorticoid adverse events and sarilumab, the latter not has already occurred. We need available in Ireland, appear to better predictive prognostic have excellent efficacy, mirroring markers in order to properly risk their known effect in GCA.7 More stratify patients. The role of shared surprisingly perhaps, a single dose decision making is also crucial, of rituximab at treatment initiation and the input of people with PMR has been shown to have longon the risks and benefits of various treatment strategies is crucial given that they will be the ones ultimately experiencing them.

Figure 1: Example of prednisolone tapering regimen in PMR

Adjunctive managements are important in all patients with PMR. These are largely directed at minimising glucocorticoid

ocorticoid tapering, occurring in up to 50% of patients (3). Many relapses, omptly will respond to an increase to the last prednisolone dose at which while further delay will often lead to a necessity to return to the initial

52

CPD 90: POLYMYALGIA RHEUMATICA

adverse events. Long term glucocorticoids, even at relatively modest doses, have a profound negative effect on bone, leading to glucocorticoid induced osteoporosis. All patients should be assessed for the need for calcium and vitamin D supplementation, and have it provided to those who have dietary calcium deficiency and low serum vitamin D respectively.

All patients receiving long-term glucocorticoids should receive an anti-resorptive agent, generally a bisphosphonate while on glucocorticoids. People with PMR are generally also in the age range where DXA screening for osteoporosis is recommended, but many will have not had this performed, if this is the case, it should be performed to guide the need for long-term bone protection after glucocorticoids have finished. Those receiving the initial glucocorticoid doses will generally also receive

gastroprotection with a proton pump inhibitor, this can usually be ceased as the glucocorticoid dose reduces. It is important to encourage people with PMR to maintain activity in order to limit glucocorticoid adverse events, particularly myopathy. Patients who have more significant myopathy, either due to disease or glucocorticoid related effects may benefit from physiotherapy.

Patient education is important both in terms of the management plan and as there are many pervasive myths around PMR.

References

1. Crowson CS, Matteson EL, Myasoedova E, Michet CJ, Ernste FC, Warrington KJ, et al. The lifetime risk of adultonset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis and rheumatism. 2011;63(3):633-9.

2. McCarthy EM, MacMullan PA, Al-Mudhaffer S, Madigan A, Donnelly S, McCarthy CJ, et al.

Plasma fibrinogen is an accurate marker of disease activity in patients with polymyalgia rheumatica. Rheumatology (Oxford). 2013;52(3):465-71.

Summary 3. Salvarani C, Cantini F, Niccoli L, Macchioni P, Consonni D, PMR is a common and disabling Bajocchi G, et al. Acute-phase condition. Dramatic initial reactants and the risk of relapse/ treatment responses are tempered recurrence in polymyalgia by longer term struggles with rheumatica: a prospective relapses and treatment related followup study. Arthritis and adverse events. Focused rheumatism. 2005;53(1):33-8. optimum management of PMR 4. Widdifield J, Bernatsky S, leads to dramatically improved Paterson JM, Gunraj N, Thorne patient outcomes.

JC, Pope J, et al. Serious infections in a population-based Figure 3: Adjunctive management in PMR cohort of 86,039 seniors with rheumatoid arthritis. Arthritis care & research. 2013;65(3):35361.

5. Kavanaugh A, Wells AF. Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis. Rheumatology (Oxford).

2014;53(10):1742-51.

6. Caporali R, Cimmino MA, Ferraccioli G, Gerli R, Klersy C, Salvarani C, et al.

Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial.

Annals of internal medicine.

2004;141(7):493-500.

7. Bonelli M, Radner H, Kerschbaumer A, Mrak D, Durechova M, Stieger J, et al.

Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial.

Annals of the rheumatic diseases. 2022;81(6):838-44.

8. Marsman DE, den Broeder N, van den Hoogen FHJ, den Broeder AA, van der Maas A. Efficacy of rituximab in patients with polymyalgia rheumatica: a double-blind, randomised, placebocontrolled, proof-of-concept Figure 3: Adjunctive management trial. The Lancet Rheumatology.

Summary in PMR 2021;3(11):e758-e66.

PMR is a common and disabling condition. Dramatic initial treatment responses are tempered by longer term struggles with relapses and treatment related adverse events. Focused optimum management of PMR leads to dramatically improved patient outcomes.

CPD Questions 1. The following are all common clinical features of polymyalgia rheumatica except a. Age ≥ 50 years b. Early morning stiffness c. Worse with activity d. Rapid response to glucocorticoids e. Shoulder and hip stiffness 2. Which of the following may be decreased in PMR? a. C-reactive protein b. Erythrocyte sedimentation rate c. Platelets d. Haemoglobin e. Fibrinogen 3. Standard adjunctive treatments for PMR include all of the following except

Bone protection

a. Bisphosphonate b. Calcium/vitamin D c. Statin d. Proton pump inhibitor e. Exercise

DXA

4. Which of the following is true regarding glucocorticoid treatment in PMR

PPI

Maintain activity Physiotherapy

Patient education

References 1.

Crowson CS, Matteson EL, Myasoedova E, Michet CJ, Ernste FC, Warrington KJ, et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis and rheumatism. 2011;63(3):633-9.

2.

McCarthy EM, MacMullan PA, Al-Mudhaffer S, Madigan A, Donnelly S, McCarthy CJ, et al.

Plasma fibrinogen is an accurate marker of disease activity in patients with polymyalgia rheumatica.

Rheumatology (Oxford). 2013;52(3):465-71.

a. Relapses are rare b. A treatment course of weeks is needed c. High dose steroid (eg 40mg prednisolone) is required initially d. At least a year of treatment is generally needed e. There are minimal adverse events 5. Potential options in refractory/relapsing PMR include all of the following except a. Methotrexate b. Non-steroidal antiinflammatory drugs c. Tocilizumab d. Rituximab e. Long-term low dose glucocorticoid

ew

N

IMMUNE With Extra Strength Vitamin D For Immune Support*

ud ied

IR V B P Sc t ien tifically S

Available Now Distributed by 14 Moneen Business Park, Castlebar, Co. Mayo, Ireland.

Tel: +353 94 9024000 Fax: +353 94 9022824 Email: info@pamex.ie

Your Sales Partner in Ireland

Contains the unique PB-VIR™ culture, a PrecisionBiotics strain *Vitamin D contributes to the normal function of the Immune System More information available at www.precisionbiotics.com

54

PEER REVIEW: OSTEOPOROSIS

Management and Treatment of Osteoporosis Written by Kevin McCarroll Dr Kevin McCarroll is a consultant physician and geriatrician specialising in osteoporosis at St James’s Hospital, Dublin where he is a Clinical Lead of the Bone Heath Unit. He also co-runs the orthogeriatric service and is a Clinical Senior Lecturer in Medical Gerontology at Trinity College. He is a co-investigator in the Trinity, Ulster, Dept Agriculture (TUDA) study of over 5000 patients in which research on bone health and vitamin D is being conducted.

Osteoporosis is common and affects an estimated 300,000 people poople in Ireland. It is defined as decline in bone mass associated with a microarchitectural deterioration in bone resulting in increased risk of fragility fracture.

In practise, the diagnosis can be made when the lowest T score on DXA is ≤-2.5 at any of three sites (total hip, neck of femur or lumbar spine). However, a clinical diagnosis of osteoporosis can also be made without bone mineral density (BMD) measurements in patients who have a fragility fracture of the hip or spine. Fragility fracture is one that occurs from a fall from standing height or due to trauma not normally expected to cause a fracture. Osteopenia is defined when the T score is between -1.0 to < -2.5. In premenopausal females and males aged under 50, a Z score < -2.0 indicates low bone mass which may due to osteoporosis though other causes such as osteomalacia need to be considered.

Who to treat?

Osteoporosis therapy may in general be initiated when there is: (1) clinical diagnosis due to low trauma hip or vertebral fracture (2) diagnosis based on DXA criteria (3) high fracture risk as calcuated using tools such as FRAX (4) osteopenia with high risk of fracture. The FRAX tool can be used to estimate 10 year fracture risk with or without BMD. The threshold to start therapy varies by country and guidelines.

The National Osteoporosis Guideline Group (NOGG) in the UK have established age dependent

thresholds. For example, in adults aged 70+, therapy is recommended when then 10 year fracture risk for hip is 5.4% and 20.3% for major osteoporostic fracture. In patients with no fracture history but with moderate osteopenia (T score < 1.5 -2.0) and on drugs causing bone loss (eg. aromatase inhibitors, steroids) antiresorptive therapy can be started.

Factors to consider Up to 50% of fragility fractures occur in patients with osteopenia as other factors influence risk.

While about 70% of bone strength relates to BMD, other factors collectively determining ‘bone quality’ are important, especially in the spine. For example, patients on steroids, aromatase inhibitors and androgen deprivation therapy have a higher risk of fracture independent of BMD resulting from their negative effects on bone quality. For recurrent fallers (≥2 per year), FRAX estimated fracture risk may be increased by 30%. Prior recent fracture (within 2 years) is a big predictor of imminent fracture.

The majority (70%) of vertebral fractures do not present clinically but are associated with increased incident vertebral fracture risk by a factor of 2-5. For this reason, any previous radiological imaging which includes the spine should be reviewed. In patients at very high risk of fracture (FRAX risk 60% above treatment threshold), T score ≤ -3.5 or recent vertebral fractures, parenteral or anabolic therapy should be considered.

Vitamin D / calcium and lifestyle

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

factors should be addressed including avoidance of smoking, alcohol in moderation and weight bearing exercise (at least 30 mins/day). Resistive exercises to improve muscle strength and balance are advised and where appropriate multidsiciplinary input to reduce falls risk. Secondary causes of osteoporosis should be looked for, especially in younger patients or those with very low T scores. Most trials of osteoporosis medications have included patients on vitamin D / calcium supplements. However, not everyone needs supplemental calcium and the dose should be tailored to the individual. In general, total calcium intake should be 1000 mg combining diet and and /or supplements.

Patients should have a serum 25-hydroxyvitamin D level of at least 50 nmol/l which can usually be achieved with 800-1000 IU of vitamin D per day.

Bisphosphonates First line therapy for osteoporosis is usually oral bisphosphonates which are also indicated for prevention of steroid induced osteoporosis. They reduce the risk of fractures of the hip and spine by up 50% an forearm by about 25%.

However, use is contraindicated in renal impairment (<35 ml/ min), GORD and oesophageal disorders (Barretts and achalasia).

Unfortunately, persistence with bisphosphonates is low at about 50% at one year, highlighting the importance of selecting the appropriate patients for treatment: avoid if difficulty remembering to take or comply with instructions (sit upright for at least 30 mins, full glass of water, no food) and if GI intolerance / malabsorption syndromes. Alendronate may have superiority over risedronate in BMD gains but there is no evidence of any difference in antifracture efficacy. Ibandronate can be taken once monthly as an alternative for some patients with mild GORD. Zolendronic acid is an alternative therapy when there are GI contraindications to oral bisphosphonates. It has also been recommended as a first line initial treatment for patients in hospital with a hip fracture and can be considered in those at very high fracture risk. It is given as a once yearly intravenous infusion

over 15-30 mins. It has similar antifracture efficacy at the hip and forearm but is superior at reducing vertebral fractures (about 70% reduction). Standard therapy is for 3 years though in patients with severe osteoporosis and high risk of fracture, it may be considered for up to 6 years. About 25% of patients experience a mild acute phase reaction after the initial infusion (musculoskeletal pain and fever) which usually resolves with simple analgesics within 72 hrs.

Drug holidays, when and for how long?

Bisphosphonates have a long half life in bone (10 years) with anti-resportive and anti-fracture effects persisting for a period after therapy cessation. For this reason, patients may have a break from treatment or 'drug holiday' though this needs to be closely monitored. Importantly, the concept of ‘drug holiday’ does not apply to other osteoporosis treatments where BMD drops after therapy cessation. Treatment with oral bisphosphonates is typically for 5 years and for 3 years with zolendronic acid, after which a ‘drug holiday’ should be considered. Drug holidays may be appropriate in patients who after treatment have a T score at the hip or spine of > -2.5, no recent fractures and are at lower risk of future fracture. However, in older patients at high risk of fracture (fallers, previous hip or recent fractures) or on drugs causing bone loss, therapy may need to be continued (up to 10 yrs for alendronate and 6 yrs for zoldenronic acid). Fracture risk can also be reassessed using FRAX and applying standard treatment thresholds. Drug holidays are typically for 1.5 to 3 years (18 -24 months with oral therapy and for up to 3 years with zolendronic acid) followed by repeat BMD assessment.

In patients where there is a significant decline in BMD or rise in bone markers, treatment may be need to be restarted.

Treatment failure This is not clearly defined but may be considered to occur when there is a decine in BMD, no improvement in bone markers or ≥2 fractures on therapy. It should always prompt an investigation into potential reasons including

55

greater in Asians and patients on steroids. Fractures often occur spontaneously or with minimal trauma and may be bilateral (25%).

As there is often a prodrome of pain in the groin/ thigh, patients on bisphosphonates for 5 or more years should have a femur x-ray if clincally indicated. This can identify ‘incomplete AFF’ which is generally an indication for prophylactic femoral nailing to prevent fracture propagation.

When AFF occurs, isphosphonates are generally stopped, with future AFF risk appearing to decline substantially. However, in those at high risk of fragility fracture due to their osteoporosis, the optimal future treatment strategy is unclear.

AFF have also been reported with denosumab though with a lower incidence. poor compliance, malabsorption and secondary causes (endocrine and medications).

Denosumab Denosumab is the most potent antiresorptive used in the treatment of osteoporosis and is administered by subcutaneous injection twice yearly. It can also be used for the prevention of bone loss in patients on aromatase inhibitors or androgen deprivation therapy. It's a monoclonal antibody that blocks the action of the cytokine (RANK), resulting in profound inhibition of bone resorption. It has a similar potency and antifracture efficay to zoledronic acid but can be used in renal impariment (eGFR< 30 ml/min). Treatment for 3 years reduces fracture risk in spine by 68%, 40% at the hip and 20% at nonverterbal sites. Therapy can be continued for up to 10 years (based on trial data) where there is sustained rises in BMD and antifracture efficacy. Serum calcium should be normal and vitamin D >50 nmol/l prior to starting so as to avoid hypocalcaemia.

Denosumab is associated with an increased risk of cellulits and possibly other infections and for this reason might not be as suitable for some patients.

Rebound bone loss and fracture risk on stopping denosumab Stopping denosumab results in rapid rebound bone loss, decline in BMD and increased vertebral fracture risk, occurring as early as 1-3 months after discontinuation.

In fact, all BMD gains from several years of treatment can be lost

within 24 months. For this reason denosumab must not be stopped unless patients are switched to alternative therapies. The greatest predictor of bone loss after stopping denosumab is duration of use. However, as data on safety and efficacy is lacking beyond 10 years , there are concerns about continuing therapy indefinitely.

Despite this, for patients already on denosumab and at high risk of fracture remaining on treatment may be the best option. If stopping denosumab, recent NOGG guidelines suggest transitioning to zolendronic acid with close montioring of bone turnover markers (BTM). Further zoledronic acid therapy at 6 months is advised if there is inadequate suppression of bone turnover, or in patients at higher risk of fracture when BTM are not accessible.

Alternatively, for patients, on densumab for shorter periods (2.02.5 years), oral bisphosphonate (if no contraindication) after 6 months of their last injection can be considered with BTM monitoring to ensure treatment efficacy. Despite bisphosphonate therapy, there is still a risk of bone loss for some patients. For these reasons, in younger patients and those with mild osteoporosis, starting denosumab may not be a good option. Conversely, in older patients with severe osteoporosis and /or life expectancy of up to 10 years, it is a good choice.

Teriparatide Teriparatide is a recombinant parathyroid hormone administered as a daily subcutaneous injection.

It should be considered as a first line therapy in patients with severe

osteoporosis of the spine and/or with low trauma or spontaneous vertebral fractures. It is the only anabolic therapy available in Ireland and reduces vertebral fracture risk by abut 70-80%.

However, it’s effect on hip BMD is modest where it is not shown to reduce fracture. Contraindications include unexplained raised ALP, Paget’s disease, prior radiotherapy hypercalcaemia, hyperparathyroidism, haematological or active malignancy and renal calculi. Most patients tolerate it well though adverse effects include nausea, dizziness, musculoskeletal pain, palpitations and low mood.

For patients who have severe osteoporosis of both the spine and hip, bisphosphonate treatment may be more appropriate followed by teriparatide. Alternatively, dual therapy with denosumab and teriparatide for two years may be considered in a specialised setting. Of note, switching from denosumab to teriparatide is associated with a decline in BMD at the spine (at 6 months) and hip (at 12 months) and is not advisable in patients with severe hip or spine osteoporosis. Importantly, teriparatide must be followed up with further treatment (typically bisphosphonates) to consolidate BMD gains.

Atypical fractures Atypical fractures are a rare and possible adverse effect of bisphosphonates (incidence of 1/ 1000 after 10 years of oral therapy).

They are a type of stress fracture of the subtranchanteric femur.

Though rare, the risk increases substantially after 5 years and is

Osteonecrosis of the Jaw (ONJ) This is a rare occurence in the treatment of osteoporosis and is more common with potent antiresorptives (denosumab and zoledronic acid). In the majority of cases, it is precipitated by dental surgery, particularly dental implants or extractions. However, poor dental hygiene, diabetes, and steroids are risk factors. If using these parenteral therapies it is advisable to maintain good dental hygiene and consider dental treatments (if required) prior to their initiation. When ONJ occurs, bisphoshonates may be stopped though this needs to balanced against risk of fracture. For patients on denosumab therapy who are at higher risk of ONJ, some guidelines suggest doing elective dental procedures between 5-6 months after administration of their last injection and to restart treatment 2- 4 weeks later. .

Osteoporosis in younger adults The majority of cases of osteoporosis in younger adults are associated with secondary causes including drugs, premature menopause, amenorrhoea, anorexia and endocrine disorders.

Osteomalacia resulting from vitamin D deficiency and/or low calcium intake will also result in low BMD and should not be mistaken for osteoporosis. In patients at very high risk of fracture and where other causes have been addressed or treated, bisphosphonates may be cautiously considered. However, females of child bearing age should be counselled on the potential risk of teratogenetcity and to avoid pregancy while on treatment.

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

ARDE AW A R DDE D AW

NOW BVBM NOW BVBM FOR 20MG FOR 20MG ADALIMUMAB ADALIMUMAB

BBVVBBM M

CITRATE CITRATE FREE FREE

ARDE AWWA R DDE D A

Amgevita® ®

Amgevita ®

Awarded value biologicmedicine medicine awardedbest best value biosimilar best value biologic medicine awarded best value biosimilar medicine a citrate free formulation of inAwarded aincitrate free formulation of adalimumab a citrate free formulation of in ain citrate free formulation of adalimumab adalimumab and is the only BVBM by the Medicines Management Programme adalimumab and is the only BVBM by the Medicines Management Programme awarded for 20mg adalimumab. awarded for 20mg adalimumab. ®

AMGEVIT ®® AMGEVIT WHAT’S BEHIND AMGEVITA WHAT’S BEHIND

HOW HOW AND AND WHE WHE

supply reliab supply reliilaitby ilit e y nc

AMGEVITA® AMGEVITA® is is injec injec aa specially designe specially designe

tent qual ity nsis co istent qu alit ns y co

ur ufact ing exc an el m facturing le exc u an el m le

e nc

Amgen has Amgen has >40 YEARS >40 YEARS BIOLOGICS BIOLOGICS EXPERIENCE

EXPERIENCE

ing innov t inu uing innao iv oant nt in ion co ont c

You You should should inject inject in in see diagram see diagram below below

The The medicine medicine trave that that are are inflamed a

Your Your doctor, doctor, pharm you or you or your parent/ injection. injection. It’s impor correctly correctly for it to w

PRESCRIBE PRESCRIBE AMGEVITA AMGEVITA®® BY

BY BRAND BRAND NAME

You You may may have the i at at home. home. You can g parent/carer parent/carer can do followed EOW starting one week after initial dose.≥ ≥3030kg: kg: clinical clinicalresponse. response.Paediatric PaediatricUC, UC,≥6 ≥6years: years:Moderately Moderately to to severely severely active active UC UC kg:kg: 2020 mgmg followed byby 2020 mgmg EOW starting one week after initial dose.

AMGEVITA® (adalimumab) Brief Prescribing Information AMGEVITA® (adalimumab) Brief Prescribing Information then EOW startingone oneweek weekafter afterinitial initialdose. dose.Reconsider Reconsider with withan aninadequate inadequateresponse responsetotoconventional conventionaltherapy therapyincluding including corticosteroids corticosteroids mgmg then 4040 mgmg EOW starting Please to the Summary of Product Characteristics (SmPC) before 40 40 Please referrefer to the Summary of Product Characteristics (SmPC) before injection injection is given ev treatment beyond weeks if no clinical response.

Safety has beenassessed assessed and/or and/or6-MP 6-MPororAZA, AZA, oror who who are are intolerant intolerant to to or or have have contraindications. contraindications. beyond 1616 weeks if no clinical response.

Safety has been prescribing Pharmaceutical Form: Single dose pre-filled syringe contains prescribing Pharmaceutical Form: Single dose pre-filled syringe contains 20 20 treatment paediatricpatients patientswith withplaque plaquepsoriasis psoriasisforfora amean meanofof1313months. months. Dosage: Dosage:<<40 40 kg: kg: Induction: Induction: 80 80 mg mg atat Week Week 00 and and 40 40 mg mg at at Week Week 2. mg adalimumab in 0.4 mg/mL) solution, adalimumab in 0.8 paediatric mg adalimumab in 0.4 mL mL (50 (50 mg/mL) solution, 40 40 mgmg adalimumab in 0.8 mLmL in in Hidradenitis suppurativa(HS), (HS),adults adultsand andadolescents adolescents≥ ≥1212years: years:Active Active Maintenance Maintenancestarting startingatatweek week4:4:40mg 40mgEOW. EOW. Dosage:≥≥ 40 40 kg: kg:may Induction: 160 160 mg/mL) solution or single dose pre-filled (SureClick ) contains Dosage: Induction: suppurativa doctor (50 (50 mg/mL) solution or single dose pre-filled penpen (SureClick ) contains 40 40 mgmg Hidradenitis doctor change moderateto tosevere severeHSHS(acne (acneinversa) inversa)with withinadequate inadequate response response toto mg mgWeek Week00and and80 80mg mgWeek Week2.2.Maintenance Maintenancestarting starting at at week week 4: 4: 80mg 80mg EOW. EOW. adalimumab in 0.8 mg/mL) solution.

Indications Dosage: please moderate adalimumab in 0.8 mL mL (50 (50 mg/mL) solution.

Indications andand Dosage: please conventional systemic therapy.

Dosage, adult: 160mg mgatatDay Day1,1,followed followedbyby Patients Patientsreaching reaching18 18 years years should should continue continue their prescribed prescribed maintenance maintenance refer to SmPC information. subcutaneous injection.

Treatment conventional their systemic therapy.

Dosage, adult: 160 refer to SmPC for for full full information.

ForFor subcutaneous injection.

Treatment works works for you.

Day day continue with mg everyweek weekoror8080mg mgEOW. EOW. dose. dose.Reconsider Reconsider treatment treatment beyond beyond 88 weeks weeks ifif no no clinical clinical response. response. No No should be initiated supervised specialist physicians experienced mgmg at at Day 15.15.

At At day 2929 continue with 4040 mg every should be initiated andand supervised by by specialist physicians experienced in in 80 80 ®

®

® ® Reintroduction after treatment interruption: mg every weekoror8080mg mgEOW. EOW. conditions which AMGEVITA is indicated.

Ophthalmologists should Reintroduction after treatment interruption: 4040 mg every week conditions for for which AMGEVITA is indicated.

Ophthalmologists should Dosage: adolescent kg): week then4040mg mgEOW EOWstarting startingatat consult an appropriate specialist before starting treatment.

Give patients Dosage: adolescent (≥ (≥ 3030 kg): 8080 mgmg at at week 00 then consult withwith an appropriate specialist before starting treatment.

Give patients week If response inadequate, consider increasingtoto4040mg mgevery everyweek week a Patient Reminder Card.

After training in injection technique, patients may week 1. 1.

If response is is inadequate, consider increasing a Patient Reminder Card.

After training in injection technique, patients may or 80 EOW. Dosage, adult and adolescent: Antibiotics maybebecontinued continuedif if self-inject medical follow-up as necessary.

Optimise other concomitant or 80 mgmg EOW. Dosage, adult and adolescent: Antibiotics may self-inject withwith medical follow-up as necessary.

Optimise other concomitant necessary.Use Useconcomitant concomitanttopical topicalantiseptic antisepticwash washonona adaily dailybasis. basis. therapies corticosteroids or/immunomodulatory agents).

Rheumatoid necessary. therapies (e.g.(e.g. corticosteroids andand or/immunomodulatory agents).

Rheumatoid Reconsidertreatment treatmentbeyond beyond1212weeks weeksif ifnonoimprovement. improvement.Periodically Periodically arthritis (RA), adults: In combination methotrexate (MTX) 1. Moderate Reconsider arthritis (RA), adults: In combination withwith methotrexate (MTX) for:for: 1. Moderate evaluate benefit and risk continued treatment.Crohn’s Crohn’sdisease disease(CD), (CD), to severe, active inadequate response to disease-modifying anti- evaluate thethe benefit and risk of of continued treatment. to severe, active RA RA withwith inadequate response to disease-modifying antiadults: Moderately to severely active CD with no response despite fulland and rheumatic drugs (DMARDs) including MTX; 2.

Severe, active and progressive adults: Moderately to severely active CD with no response despite a afull rheumatic drugs (DMARDs) including MTX; 2. Severe, active and progressive adequate course intolerance contraindication corticosteroidand/ and/ previously treated MTX. given monotherapy course of,of, intolerance to to or or contraindication forfor aa corticosteroid RA RA not not previously treated withwith MTX. CanCan be be given as as monotherapy if if adequate or an immunosuppressant therapy.

Dosage: Induction: 80 mg at Week 0, then intolerance to or when continued treatment with MTX is inappropriate. or an immunosuppressant therapy.

Dosage: Induction: 80 mg at Week 0, then intolerance to or when continued treatment with MTX is inappropriate. at Week a more rapid response: 160 mg Week0,0,then then8080mg mg Dosage: 40 mg every other week (EOW).

Continue concomitant MTX. mgmg at Week 2. 2.

ForFor a more rapid response: 160 mg atat Week Dosage: 40 mg every other week (EOW).

Continue concomitant MTX. In In 40 40 at Week 2; risk adverse events higher during rapid induction.Maintenance: Maintenance: monotherapy, patients require 40 mg every week or 80 EOW if there at Week 2; risk of of adverse events higher during rapid induction. monotherapy, patients maymay require 40 mg every week or 80 mgmg EOW if there dose EOW. Corticosteroids may tapered accordancewith withclinical clinical a decrease in clinical response.

Reconsider treatment beyond weeks mgmg dose EOW. Corticosteroids may bebe tapered in in accordance is a is decrease in clinical response.

Reconsider treatment beyond 12 12 weeks if if 40 40 guidelines.

If decrease clinical response, can increase mgevery everyweek week no clinical response.

Consider need for dose interruption, before surgery guidelines.

If decrease in in clinical response, can increase toto 4040mg no clinical response.

Consider need for dose interruption, e.g.e.g. before surgery or 80 EOW. If no response Week 4 there may benefit fromcontinued continued if serious infection occurs.

Polyarticular juvenile idiopathic arthritis (pJIA), or 80 mgmg EOW. If no response byby Week 4 there may bebe benefit from or iforserious infection occurs.

Polyarticular juvenile idiopathic arthritis (pJIA), therapy to week 12.

Reconsider treatment beyond 12 weeks if no clinical paediatrics ≥ 2 years: In combination with MTX for active pJIA with inadequate therapy to week 12. Reconsider treatment beyond 12 weeks if no clinical paediatrics ≥ 2 years: In combination with MTX for active pJIA with inadequate response. Paediatric CD, ≥ 6 years: Moderately to severely active CD with response to one or more DMARDs. given monotherapy response to one or more DMARDs. CanCan be be given as as monotherapy if if response. Paediatric CD, ≥ 6 years: Moderately to severely active CD with inadequate response intoleranceto toororcontraindication contraindicationtotoconventional conventional intolerance to or when continued treatment with MTX is inappropriate. inadequate response to,to, intolerance intolerance to or when continued treatment with MTX is inappropriate. therapy including primary nutrition therapy and a corticosteroid and/or an Dosage: 10 kg to < 30 kg: 20 mg EOW. ≥ 30 kg: 40 mg EOW. Reconsider therapy including primary nutrition therapy and a corticosteroid and/or an Dosage: 10 kg to < 30 kg: 20 mg EOW. ≥ 30 kg: 40 mg EOW. Reconsider immunomodulator. Dosage: < 40 kg: Induction: 40 mg at week 0 then 20 mg treatment beyond 12 weeks if no clinical response. Enthesitis-related arthritis immunomodulator.

Dosage: < 40 kg: Induction: 40 mg at week 0 then 20 mg treatment beyond 12 weeks if no clinical response. Enthesitis-related arthritis at week 2. For a more rapid response: 80 mg at week 0 then 40 mg at week 2; (ERA), paediatrics, ≥ 6 years: Active ERA with inadequate response to or at week 2. For a more rapid response: 80 mg at week 0 then 40 mg at week 2; (ERA), paediatrics, ≥ 6 years: Active ERA with inadequate response to or of adverse events higher during rapid induction. Maintenance starting at intolerance to conventional therapy. Dosage: 15 kg to < 30 kg: 20 mg EOW. riskrisk of adverse events higher during rapid induction. Maintenance starting at intolerance to conventional therapy. Dosage: 15 kg to < 30 kg: 20 mg EOW. week 4: 20 mg dose EOW. If insufficient response, consider 20 mg every ≥ 30 kg: 40 mg EOW. Ankylosing spondylitis (AS), adults: Severe active AS week 4: 20 mg dose EOW. If insufficient response, consider 20 mg every ≥ 30 kg: 40 mg EOW. Ankylosing spondylitis (AS), adults: Severe active AS week. Dosage: ≥ 40 kg: Induction: 80 mg at Week 0 then 40 mg at Week 2. For with inadequate response to conventional therapy. Axial spondyloarthritis week. Dosage: ≥ 40 kg: Induction: 80 mg at Week 0 then 40 mg at Week 2. For with inadequate response to conventional therapy. Axial spondyloarthritis a more rapid response: 160 mg at Week 0, then 80 mg at Week 2; risk of without radiographic evidence of AS (nr-axSpA), adults: Severe nr-axSpA with a more rapid response: 160 mg at Week 0, then 80 mg at Week 2; risk of without radiographic evidence of AS (nr-axSpA), adults: Severe nr-axSpA with adverse events higher during rapid induction. Maintenance starting at week 4: objective signs of inflammation (elevated CRP and/or MRI), and an inadequate adverse events higher during rapid induction. Maintenance starting at week 4: objective signs of inflammation (elevated CRP and/or MRI), and an inadequate 40 mg dose EOW. If insufficient response, consider 40 mg every week or 80 response to or intolerance to nonsteroidal anti-inflammatory drugs. Psoriatic 40 mg dose EOW. If insufficient response, consider 40 mg every week or 80 response to or intolerance to nonsteroidal anti-inflammatory drugs.

Psoriatic mg EOW. Reconsider treatment beyond 12 weeks if no clinical response. arthritis (PsA), adults: Active and progressive PsA with inadequate response mgUlcerative EOW. Reconsider treatment beyond 12 weeks if no clinical response. arthritis (PsA), adults: Active progressive PsA inadequate response colitis (UC), adults: Moderately to severely active UC with to DMARDs. Dosage (AS, and nr-axSpA, PsA): 40 mgwith EOW. Reconsider treatment Ulcerative colitis (UC), to, adults: Moderately to severely active UC with to DMARDs. Dosage PsA): 40 mg EOW. Reconsider treatment inadequate response intolerance to or contraindication for conventional beyond 12 weeks (AS, if no nr-axSpA, clinical response.

Psoriasis, adults: Moderate to severe inadequate response to, intolerance or contraindication for or conventional beyond 12 weeks if no clinical response.

Psoriasis, adults: Moderate to severe therapy including corticosteroids andto 6-mercaptopurine (6-MP) azathioprine chronic plaque psoriasis in candidates for systemic therapy. Dosage: 80 mg at therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine chronic plaque psoriasis in candidates for systemic therapy. Dosage: 80 mg at (AZA). Dosage: Induction: 160 mg at week 0 and 80 mg at week 2.

Week 0, followed by 40 mg EOW from Week 1. Reconsider treatment beyond (AZA).

Dosage: 40 Induction: 160 mg at weekmay 0 and 80 mg inataccordance week 2.

Week followed 40 mg EOW from Week 1. Reconsider treatment Maintenance: mg EOW. Corticosteroids be tapered 160, weeks if noby clinical response.

Refer to SmPC. Paediatric Plaque beyond Psoriasis, mg EOW. Corticosteroids may consider be tapered in accordance 16 weeks if no Severe clinical response.

Referpsoriasis to SmPC. Paediatric Plaque Psoriasis, with clinical 40 guidelines.

If insufficient response, increasing to 40 mg ≥ 4 years: chronic plaque with inadequate response to or if Maintenance: with clinical guidelines.

If insufficient response, consider increasing to 40 mg ≥ 4 topical years: Severe chronic plaque psoriasis with inadequate response to or if every week or 80 mg EOW. Do not continue treatment beyond 8 weeks if no therapy and phototherapies are inappropriate. Dosage: 15 kg to < 30 every week or 80 mg EOW. Do not continue treatment beyond 8 weeks if no topical therapy and phototherapies are inappropriate. Dosage: 15 kg to < 30

relevantuse useininchildren children<6 <6years. years.Uveitis, Uveitis,adults: adults:Non-infectious Non-infectious intermediate, intermediate, relevant posterior and and panuveitis panuveitis with with inadequate inadequate response response to to corticosteroids, corticosteroids, in posterior patientsininneed needofofcorticosteroid-sparing, corticosteroid-sparing,or orininwhom whomcorticosteroid corticosteroid treatment treatment patients inappropriate.Dosage: Dosage:80 80mg mgatatWeek Week 00 and and 40 40 mg mg EOW EOW from from Week Week 1.

1. isisinappropriate.

Thereisislimited limitedexperience experienceinininitiation initiationof oftreatment treatment with with adalimumab adalimumab alone. alone.

There Treatmentcan canbe beinitiated initiated inin combination combination with with corticosteroids corticosteroids and/or and/or with with Treatment othernon-biologic non-biologic immunomodulatory immunomodulatory agents. agents. Concomitant Concomitant corticosteroids corticosteroids other maybe betapered taperedstarting startingtwo twoweeks weeksafter afterinitiating initiatingtreatment treatment with with AMGEVITA AMGEVITA®®.. may Evaluateon on aa yearly yearly basis basis the the benefit benefit and and risk risk of of continued continued treatment. treatment.

Evaluate Paediatric uveitis, ≥ 2years: Chronic non-infectious anterior uveitis with with Paediatric uveitis, ≥ 2years: Chronic non-infectious anterior uveitis inadequateresponse response oror intolerance intolerance toto conventional conventional therapy, therapy, or or in in whom whom inadequate conventional therapy is inappropriate.

In paediatric uveitis, there is no conventional therapy is inappropriate. In paediatric uveitis, there is no experienceininthe thetreatment treatmentwith withAMGEVITA AMGEVITA®® without without concomitant concomitant treatment treatment experience with methotrexate.

Dosage: < 30 kg: 20 mg EOW in combination with MTX. with methotrexate. Dosage: < 30 kg: 20 mg EOW in combination with MTX. Dosage:≥≥30 30kg: kg:40 40mg mgEOW EOWinincombination combinationwith withMTX. MTX.AAloading loading dose dose of of 40 40 Dosage: mg(<(<30 30kg) kg)oror80 80mg mg(≥(≥30 30kg) kg)may maybe beadministered administered 11 week week in in advance advance of of mg maintenancetherapy. therapy.No Noclinical clinicaldata dataon onuse useof of loading loading dose dose in in patients patients << 66 maintenance years. Evaluate benefit and risk of continued treatment on a yearly basis. years. Evaluate benefit and risk of continued treatment on a yearly basis.

Contraindications: Hypersensitivity to the active substance or to any Contraindications: Hypersensitivity to the active substance or to any excipients; Active tuberculosis (TB) or other severe infections such as sepsis excipients; Active tuberculosis (TB) or other severe infections such as sepsis and opportunistic infections; Moderate to severe heart failure (NYHA class III/ and opportunistic infections; Moderate to severe heart failure (NYHA class III/ IV). Warnings and Precautions: Clearly record the name and batch number.

IV). Warnings and Precautions: Clearly record the name and batch number.

Infections: Patients taking TNF-antagonists are more susceptible to serious Infections: Patients taking TNF-antagonists are more susceptible to serious infections, especially if impaired lung function. Monitor for infections, before, infections, especially if impaired lung function. Monitor for infections, before, during and for 4 months after treatment. Do not initiate treatment during an during and for 4 months after treatment. Do not initiate treatment during an active infection, until infection is controlled. Consider risk/benefit prior to active infection, until infection is controlled. Consider risk/benefit prior to treatment in patients exposed to TB or who have travelled in areas of high risk treatment in patients exposed to TB or who have travelled in areas of high risk of TB or endemic mycoses. Evaluate new infections and monitor closely. Stop oftreatment TB or endemic Evaluateor new infections and monitor closely.

Stop if newmycoses. serious infection sepsis and treat.

Exercise caution in treatment if new serious of infection or infections sepsis andortreat. caution in patients with a history recurring who Exercise are predisposed to patients with a history of recurring infections or who are predisposed to infections, including the use of concomitant immunosuppressive medications.

6 infections, including the use of concomitant immunosuppressive medications.

Serious Infections: Consult SmPC for Serious infections, including 6 details. Serious Serious Infections: with Consult SmPC for details. those associated hospitalisation or death, were infections, reported inincluding patients those associated with or new death, were in patients receiving treatment.

TB:hospitalisation Reactivation and onset TB,reported both pulmonary and receiving treatment.

TB: Reactivation and new onset TB, boththerapy pulmonary and extra-pulmonary (disseminated). Screen all patients before initiation extra-pulmonary (disseminated). Screen all patients before therapy initiation

You need need to follow You healthcare healthcare team an you are not feelin ifif you

For full full and detaile For administer administer your AM instructions provide provide instructions

TA® AND ME ME TA® AND MAKES THE DIFFERENCE

MAKES THE DIFFERENCE

EN IS IT IT GIVEN? GIVEN? EN IS

cted under the the skin skin (a (a subcutaneous subcutaneousinjection) injection)with with cted under ed pen called SureClick® or using a pre-filled syringe. ed pen called SureClick® or using a pre-filled syringe. ® AMGEVITA®®40mg 40mgSureClick SureClick Pre-filledpen pen ® AMGEVITA Pre-filled

AMGEVITA®®20mg 20mgPre-filled Pre-filledsyringe syringe AMGEVITA

® ® AMGEVITA 40mgPre-filled Pre-filledsyringe syringe AMGEVITA 40mg

n the tummy, tummy, or or the the tops tops of of your your legs legs(thighs), (thighs), n the w. w.

els into your bloodstream bloodstream to to work work on onthe theareas areas and causing your your symptoms. symptoms.

Information for for Healthcare Healthcare Professionals Professionals Information

The Medicine Medicine Management Management Programme Programmerecommends recommends LEFT RIGHT macist or nurse will will show show ®® as LEFT nurse AMGEVITA as aaRIGHT citrate-free formulationof ofadalimumab. adalimumab. citrate-free formulation AMGEVITA /carer how to to give give the the Prescribing AMGEVITA®® has has lead lead to tosignificant significantsavings savingsfor for Prescribing rtant the injection is is given givenAMGEVITA injection 1,2,3 work. health service, service, in in the the order orderof ofmillions millionsof ofeuros euros1,2,3 the health

injection in hospital hospital or or give it to yourself yourself or or your your you.

Usually, o thisforforfor you.

Usually, the Store in ainrefrigerator (2°C – 8°C).

Do Do not not freeze.

Keep in the active detailed Autoimmune antibodies may form.

Stop treatment if if Precautions: Precautions: Store a refrigerator (2°C – 8°C). freeze.

Keep in the active or or inactive inactive (latent) (latent) TB. TB. Perform Performthe detailedmedical medicalassessment assessmentand and Autoimmune Autoimmuneprocesses: processes: Autoimmune antibodies may form.

Stop treatment carton in order to protect from light.

OutOut of the refrigerator, maymay be stored aa lupus-like syndrome with positive antibodies against doubleouter carton in order to protect from light. of the refrigerator, be stored appropriate screening screening tests tests for for TB TB inin all all patients patients and andresults resultsrecorded recordedon on development developmentofof lupus-like syndrome with positive antibodies against double- outer weeks, but your very 2appropriate weeks, but your to to 25°C for for up up to 14 days.

Legal Category: POM. Presentation andand patient Consider the long half-life of of AMGEVITA planned 25°C to 14 days.

Legal Category: POM. Presentation patient reminder reminder card. card. IfIf latent latent TB TB isis suspected, suspected, consult consult physician physicianwith with stranded strandedDNA. DNA.Surgery: Surgery: Consider the long half-life AMGEVITAforfor planned up up Authorisation Number.

AMGEVITA appropriate There is is limited safety 20 mg solution for injection Marketing Authorisation Number.

AMGEVITA appropriate expertise expertise Despite Despite prophylaxis, prophylaxis,TB TBreactivation reactivationhas hasoccurred occurredon on surgical surgical procedures.Monitor Monitorclosely closelyforforinfections. infections.

There limited safety Marketing 20 mg solution for injection AA procedures.

IfIf active TB do undergoing arthroplasty or or surgical procedures.

Elderly pre-filled syringe: EU/1/16/1164/001 – 1–pack: costcost AMGEVITA 40 mg to best suit what adalimumab. active TB isisdiagnosed, diagnosed, donot notinitiate initiateAMGEVITA AMGEVITA treatment. experienceininpatients patients undergoing arthroplasty surgical procedures.

Elderly in in pre-filled syringe: EU/1/16/1164/001 1 pack: AMGEVITA treatment. experience 40 mg e this adalimumab. suit what in in patients over 65,65, some of of which Other for for injection in in pre-filled syringe: EU/1/16/1164/003 – 2– pack patients:Serious Seriousinfections infectionswere werehigher higher patients over some which solution Other opportunistic opportunistic infections: infections: Opportunistic Opportunistic infections infections were were observed observedinin patients: solution injection pre-filled syringe: EU/1/16/1164/003 2 pack ®

®

®

®®

®

®

®

risk ofof infections in in these patients.

Interactions: Antibody patients mgmg solution for for injection in pre-filled pen:pen: EU/1/16/1164/007 werefatal. fatal.Consider Consider risk infections these patients.

Interactions: Antibody AMGEVITA patients receiving receiving adalimumab. adalimumab. Stop StopAMGEVITA AMGEVITA ininpatients AMGEVITA40 40 patientswith withsigns signsand and were solution injection in pre-filled EU/1/16/1164/007 ® ® AMGEVITA symptoms Marketing Authorisation Holder: Amgen Europe B.V.B.V. Minervum was given together with MTX rather formationwas waslower lowerwhen when AMGEVITA symptoms of of such such infections. infections. Consult Consult with with physician physician with with appropriate appropriate formation 2 pack.

Marketing Authorisation Holder: Amgen Europe Minervum was given together with MTX rather – 2– pack. ® expertise 4817 ZKZK Breda, TheThe Netherlands.

Further information is available fromfrom expertise for for diagnosis diagnosis and and administration administration ofof empiric empiric antifungal antifungal therapy. therapy. than 7061, 4817 Breda, Netherlands.

Further information is available than asasmonotherapy. monotherapy.Combination Combinationof ofAMGEVITA AMGEVITA®with withother otherbiologic biologic 7061, Hepatitis Ireland Limited, 21 21 Northwood Court, Santry, Dublin D09D09 TX31. is is notnot Amgen Hepatitis B B reactivation: reactivation:Reactivation ReactivationofofHBV HBVhas hasoccurred occurredininchronic chroniccarriers; carriers; DMARDs Amgen Ireland Limited, Northwood Court, Santry, Dublin TX31.

DMARDs(e.g. (e.g.anakinra anakinraand andabatacept) abatacept)or orother otherTNF-antagonists TNF-antagonists ® ® some is aisregistered trademark of Amgen Inc.Inc. Date of PI some cases cases were were fatal. fatal. Test Test patients patients for for HBV HBV infection infection before before initiating initiating recommended.

AMGEVITA recommended. Fertility, Fertility, pregnancy pregnancyand andlactation lactationOnly Onlyuse useduring during AMGEVITA a registered trademark of Amgen Date ofpreparation: PI preparation: treatment. of of childbearing age to to consider useuse of of December 2021 (Ref:IE-AMB-1121-00005) treatment. HBV HBV carriers carriers should should consult consultaaspecialist specialistphysician physicianand andbe beclosely closely pregnancy pregnancyif ifclearly clearlyneeded. needed.Women Women childbearing age consider December 2021 (Ref:IE-AMB-1121-00005) monitored thethe lastlast monitored for for reactivation reactivationof ofHBV HBVinfection infectionthroughout throughouttherapy therapyand andfor forseveral several adequate adequatecontraception contraceptionduring duringand andforforat atleast least5 5months monthsafter after months (e.g.

BCG) to to infants exposed to to months after after treatment. treatment. IfIf reactivation reactivation occurs, occurs, stop stop treatment treatmentand andinitiate initiate treatment. treatment.Administration Administrationofoflive livevaccines vaccines (e.g.

BCG) infants exposed Adverse reactions/events should be reported to the Health Products ® Adverse reactions/events should be reported to the Health Products ® utero is not recommended for 5 months following the mother’s appropriate appropriate antiviral antiviraland andsupportive supportivetreatment. treatment.Neurological Neurologicalevents: events:Caution Cautioninin AMGEVITA AMGEVITA in in utero is not recommended for 5 months following the mother’s Regulatory Authority (HPRA) using thethe available methods via via ® Regulatory Authority (HPRA) using available methods ® patients during pregnancy.

AMGEVITA bebe used during breastfeeding. patients with with pre-existing pre-existingor orrecent-onset recent-onsetcentral centralororperipheral peripheralnervous nervoussystem system last lastinjection injection during pregnancy.

AMGEVITAcan can used during breastfeeding. www.hpra.ie.

Adverse reactions/events should alsoalso be reported to to ® www.hpra.ie.

Adverse reactions/events should be reported demyelinating ® AMGEVITA have a a demyelinating disorders. disorders. Consider Consider discontinuation discontinuationififany anyofofthese thesedevelop. develop. Effects Effectson onability abilitytotodrive driveand anduse usemachines: machines: AMGEVITAmay may have Amgen Limited on on +44+44 (0) (0) 1223 436441 or Freephone 1800 535535 160.160.

Amgen Limited 1223 436441 or Freephone 1800 Perform onon the ability toto drive and use machines.

Adverse Reactions: Perform neurologic neurologic evaluation evaluation inin patients patients with with non-infectious non-infectiousintermediate intermediate minor minorinfluence influence the ability drive and use machines.

Adverse Reactions: uveitis Respiratory tract infections, leukopenia, anaemia, lipids uveitis prior prior to to initiation initiation of of treatment treatmentand andregularly regularlyduring duringtreatment. treatment.Allergic Allergic Very Verycommon common≥ ≥1/10: 1/10: Respiratory tract infections, leukopenia, anaemia, lipids reactions: anaphylaxis. and vomiting, elevated liver Amgevita Product Information Sheet. https://www.hse. reactions: Reports Reports of of serious serious allergic allergic reactions reactions including including anaphylaxis.For For increased, increased,headache, headache,abdominal abdominalpain, pain,nausea nausea and vomiting, elevated liver 1. 1. BVBM BVBM Amgevita Product Information Sheet. https://www.hse. ® serious musculoskeletal pain, injection site reaction.

Common ≥ 1/100 ie/eng/about/who/cspd/ncps/medicines-management/bestserious allergic allergic or or anaphylactic anaphylactic reaction, reaction,stop stopAMGEVITA AMGEVITA®immediately enzymes,rash, rash, musculoskeletal pain, injection site reaction.

Common ≥ 1/100 immediatelyand and enzymes, ie/eng/about/who/cspd/ncps/medicines-management/bestto < 1/10: Systemic infections, intestinal infections, skin and soft tissue initiate appropriate therapy.

Dry natural rubber: The needle cover of the pen value-medicines/best-value-biological-medicines/bvb-medicineto < 1/10: Systemic infections, intestinal infections, skin and soft tissue initiate appropriate therapy. Dry natural rubber: The needle cover of the pen value-medicines/best-value-biological-medicines/bvb-medicine® oral infections , reproductive tract infections , urinary (SureClick amgevita-product-information-sheet.pdf.

Accessed January 2022. infections,ear earinfections, infections, oral infections , reproductive tract infections , urinary (SureClick®)) is is made madefrom fromdry drynatural naturalrubber rubber(a(aderivative derivativeofoflatex), latex),which whichmay may infections, amgevita-product-information-sheet.pdf.

Accessed January 2022. cause tractinfections, infections,fungal fungalinfections, infections,joint jointinfections, infections,skin skincancer cancerexcluding excluding 2. 2. Oireachtas.ie, cause allergic allergic reactions. reactions. Malignancies Malignancies and and lymphoproliferative lymphoproliferativedisorders: disorders:AA tract Debates, December 2020, Written Answer by by Oireachtas.ie, Debates, December 2020, Written Answer possible melanoma, benign benign neoplasm, neoplasm, leucocytosis, leucocytosis, thrombocytopenia, thrombocytopenia, possible risk risk of of malignancy, malignancy,some somefatal, fatal,including includinglymphomas lymphomasand andleukaemia, leukaemia, melanoma, Minister for Health. https://www.oireachtas.ie/en/debates/ Minister for Health. https://www.oireachtas.ie/en/debates/ uric acid increased, blood sodium cannot be excluded (see SmPC). Examine all patients, especially those with a question/2020-12-10/373/. Accessed January 2022. hypersensitivity,allergies, allergies,hypokalaemia, hypokalaemia, uric acid increased, blood sodium cannot be excluded (see SmPC). Examine all patients, especially those with a hypersensitivity, question/2020-12-10/373/. Accessed January 2022. abnormal, hypocalcaemia, hyperglycaemia, hypophosphataemia, medical history of extensive immuno-suppressant therapy or psoriasis abnormal, hypocalcaemia, hyperglycaemia, hypophosphataemia, 3. medical history of extensive immuno-suppressant therapy or psoriasis Medicines Management Programme Best-Value Biological Medicines: dehydration, mood alterations , anxiety, insomnia, paraesthesia, migraine, patients with a history of PUVA treatment, for non-melanoma skin cancer prior 3.

Medicines Management Programme Best-Value Biological Medicines: dehydration, mood alterations , anxiety, insomnia, paraesthesia, migraine, patients with a history of PUVA treatment, for non-melanoma skin cancer prior Adalimumab 20 mg solution for injection. https://www.hse.ie/eng/ nerve root compression, visual impairment, conjunctivitis, blepharitis, eye to and during treatment. Melanoma and Merkel cell carcinoma have also been Adalimumab 20 mg solution for injection. https://www.hse.ie/eng/ nerve root compression, visual impairment, conjunctivitis, blepharitis, eye to and during treatment. Melanoma and Merkel cell carcinoma have also been about/who/cspd/ncps/medicines-management/best-value-medicines/ swelling, vertigo, tachycardia, hypertension, flushing, haematoma, asthma, reported. Caution in COPD patients, and in patients with increased risk for about/who/cspd/ncps/medicines-management/best-value-medicines/ swelling, vertigo, tachycardia, hypertension, flushing, haematoma, asthma, reported. Caution in COPD patients, and in patients with increased risk for best-value-biological-medicines/mmp-report-bvb-medicinedyspnoea, cough, GI haemorrhage, dyspepsia, gastroesophageal reflux malignancy due to heavy smoking. Consider the potential risk with the best-value-biological-medicines/mmp-report-bvb-medicinedyspnoea, cough, GI haemorrhage, dyspepsia, gastroesophageal reflux malignancy due to heavy smoking. Consider the potential risk with the adalimumab-20mg-march-2021.pdf. January 2022. disease, Sicca syndrome, worsening or new onset of psoriasis , urticaria, combination of AZA or 6-MP and AMGEVITA®®(hepatosplenic T-cell lymphoma adalimumab-20mg-march-2021.pdf. January 2022. disease, Sicca syndrome, worsening or new onset of psoriasis , urticaria, 4. combination of AZA or 6-MP and AMGEVITA (hepatosplenic T-cell lymphoma AMGEVITA® (adalimumab) summary of product characteristics. bruising , dermatitis, onychoclasis, hyperhidrosis, alopecia, pruritus, muscle has occurred). Caution in patients with a history of malignancy. Risk of 4.

AMGEVITA® (adalimumab) summary of product characteristics. bruising , dermatitis, onychoclasis, hyperhidrosis, alopecia, pruritus, muscle has occurred). Caution in patients with a history of malignancy. Risk of spasms , renal impairment, haematuria, chest pain, oedema, pyrexia, developing dysplasia or colon cancer unknown. Screen patients with UC, spasms , renal impairment, haematuria, chest pain, oedema, pyrexia, developing dysplasia or colon cancer unknown. Screen patients with UC, IE-AMB-0122-00003 coagulation and bleeding disorders, autoantibody test positive , blood lactate history of dysplasia or colon carcinoma, for dysplasia before and during IE-AMB-0122-00003 coagulation andincreased, bleeding disorders, autoantibody test positive , blood lactate history of dysplasia or colon carcinoma, for dysplasia before and during dehydrogenase Date of preparation: January 2022 impaired healing. Serious, including fatal, treatment. Haematologic reactions: Adverse events of the haematologic FRONT FRONT Date of preparation: January 2022 dehydrogenase increased, impaired healing.

Serious, including fatal, treatment.

Haematologic reactions: Adverse events of the haematologic adverse reactions have been reported including infections/sepsis, TB, system, including medically significant cytopenia, have been reported. Advise adverse reactions have been reported including infections/sepsis, TB, system, including medically significant cytopenia, have been reported.

Advise opportunistic infections, allergic reactions, HBV reactivation and malignancies. patients to seek immediate medical attention if signs and symptoms of blood opportunistic infections, neurological allergic reactions, HBV reactivation and malignancies. patients to seek immediate medical attention if signs symptoms of blood Serious haematological, and autoimmune reactions have also dyscrasias develop.

Vaccinations: Patients may and receive concurrent Serious haematological, neurological autoimmune reactions have also dyscrasias develop.

Vaccinations: Patients may receive been reported.

These include rare reportsand of pancytopenia, aplastic anaemia, vaccinations, except for live vaccines. Bring paediatric patients up to concurrent date with been reported.

These include rare reports of pancytopenia, vaccinations, except for live vaccines.

Bring paediatric patients up to date with central and peripheral demyelinating events and reports ofaplastic lupus, anaemia, lupusall immunisations prior to initiating treatment. Congestive heart failure: See centralconditions and peripheral demyelinating syndrome. events andOther reports lupus, and lupusall immunisations Caution prior to in initiating treatment.

Congestive failure: See related and Stevens-Johnson lessofcommon contraindications. mild heart failure (NYHA class heart I/II). Discontinue related conditions and reactions Stevens-Johnson OtherPharmaceutical less common and contraindications. in mild heart failure of (NYHA class I/II).

Discontinue rarely reported adverse are listedsyndrome. in the SmPC. treatment if new Caution or worsening symptoms congestive heart failure. rarely reported adverse reactions are listed in the SmPC. Pharmaceutical treatment if new or worsening symptoms of congestive heart failure. ®®

w the advice of of your your nd ask to speak speak to to them them ng well.

ed instructions instructions on on how how to to MGEVITA®, please read the please read the ed in ed in the the product product carton. carton.

®

BB

CC

®

58

PEER REVIEW: COPD

Eoisinophils as a Treatable Target in COPD Written by Dr Marie Talty, Specialist Registrar in Respiratory Medicine Beaumont Hospital. and Dr Breda Cushen, MB BCh BAO MRCPI PhD, Consultant Respiratory Physician, Beaumont Hospital

Dr Marie Talty

Dr. Breda Cushen

Introduction

Eosinophils in stable COPD

The role of eosinophils in airways inflammation has emerged as an important area of study and therapeutics development in respiratory disease over the last 20 years. COPD is a heterogenous condition which is associated with a large burden of illness, high hospitalisation rates and increased mortality. Classically deemed a neutrophilic disease there is increasing evidence that eosinophilic airway inflammation may be present both in stable COPD and during an exacerbation.

Classically, eosinophilic inflammation in obstructive lung disease has been considered suggestive of asthma rather than COPD. However, analysis of induced sputum in COPD patients demonstrates eosinophilic inflammation is present in in approx. 20-67% of COPD patients. Similar to asthma studies, correlation of blood and sputum eosinophil counts has also been demonstrated in COPD patients. The exact criteria for a diagnosis of “eosinophilic COPD” remain uncertain however with variable definitions, and blood and sputum count benchmarks used throughout the literature.

There remains ongoing debate as to the differentiation of this group from those with concomitant asthma or “asthma- COPD overlap syndrome” (ACOS).

Nevertheless, the identification of an “eosinophilic COPD” phenotype has important clinical and treatment implications. While the impact of airway eosinophilia on the rate of lung function decline in COPD remains unclear, larger studies such as ECLIPSE suggest that COPD patients with higher BEC have overall higher baseline mean FEV1 with lower symptom burden and improved quality of life, compared to the noneosinophilic COPD population.

However, an association between high BEC and increased exacerbations has been observed.

Clinical characteristics associated with elevated BEC include male gender and ex smoking status.

Eosinophils are produced in the bone marrow from multipotent haematopoietic stem cells. The eosinophil’s primary role is to regulate local immunity through innate and adaptive responses as well as supporting tissue metabolic haemostasis and inducing remodelling and fibrosis in inflammatory tissue. Eosinophils may be recruited and proliferated to lung tissue through a variety of cytokines and inflammatory mediators including IL-5 and eotaxin-2, which also have key roles in eosinophil survival and lung tissue recruitment. The eosinophil is recognised as a key mediator of inflammation in several respiratory conditions and is a treatment target in eosinophilic asthma, eosinophilic pneumonia, and eosinophilic granulomatosis with polyangiitis.

The effectiveness of eosinophiltargeted therapy in severe asthma in particular has led to it being considered in COPD as a potential biomarker to personalise therapy.

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Most notable to everyday practice, elevated BEC has been shown to be predictive of response to inhaled corticosteroid (ICS) therapy. Pascoe et al first demonstrated reduced exacerbation rates in patients with BECs >2% on ICS/LongActing Beta-2-Agonist (LABA) therapy vs LABA alone across two parallel randomised controlled trials. Whilst the IMPACT investigators demonstrated that once daily triple therapy with ICS/ LABA/Long-Acting Muscarinic Antagonist (LAMA) resulted in a lower number of exacerbations and hospitalisations across all BECs, a greater effect was observed in those with BEC ≥150 per μL. Further studies have demonstrated greater response to ICS therapy in stable COPD patients with BECs >150 per μL. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2022 now recommends considering ICS therapy in those with BEC >300 per μL or a previous diagnosis of asthma, and advises caution in those with BEC <100 per μL, in whom data suggests ICS have little or no effects.

Eosinophils in COPD exacerbation A significant subset of COPD patients has elevated sputum eosinophil counts during exacerbations. These have been identified as a separate subgroup to bacterial or viral exacerbations accounting for almost 30% of all exacerbations. Clear identification of eosinophilic exacerbations can be difficult to ascertain in routine clinical practice due to limited access to sputum or bronchoalveolar lavage (BAL) eosinophil counts, but blood eosinophilia is a very sensitive (<90%), albeit not as specific (60%), surrogate marker. As with stable COPD, several studies have shown that eosinophilic exacerbations are more likely to respond to corticosteroid therapy.

In one such study, BEC directed corticosteroid therapy reduced length of hospital stay in those with BEC ≥200 per μL. In the CORTI-COP trial, serial BECs on first 5 days of admission led to a treatment algorithm whereby oral corticosteroids were administered if BEC ≥300 per μL or held if below this cut-off. Omitting systemic corticosteroids from standard

treatment in those with low BEC was found to be non-inferior with regard to days alive and out of hospital. These studies are an important advance towards a more personalised approach to the treatment of COPD exacerbations.

Future therapies Monoclonal antibody therapy targeting the eosinophil has transformed severe eosinophilic asthma treatment. Subsequently anti-eosinophilic therapies have been studied in the exacerbating eosinophilic COPD population. Whilst the GALTHEA and TERRANOVA studies of benralizumab (an anti-IL5 receptor monoclonal antibody) in exacerbating COPD patients with BECs >220 per μL failed to show a significant reduction in annual exacerbation rate, subgroup analysis suggested that those prescribed triple inhaled therapy and had ≥3 exacerbations in the previous year were likely to benefit. The METREX and METREO studies of mepolizumab, (an anti-IL5 monoclonal antibody) demonstrated reduced moderate/ severe exacerbation rate in exacerbating COPD patients with BECs >300 per μL in the previous year and >150 per μL at study enrolment. Further studies of anti-eosinophilic therapies in the eosinophilic COPD population are ongoing to more clearly elucidate which subgroup of patients will benefit the most.

The role of benralizumab in acute exacerbations of COPD is also being examined in the ABRA trial which is currently in recruitment phase. In the coming years, further data is expected in this area.

Conclusion Evidence suggests that a substantial subgroup of COPD patients have eosinophilic inflammation which may represent a therapeutic target in this population. BECs are an acceptable surrogate for sputum and airway eosinophilia.

Knowledge of BEC can guide personalised treatment in both stable disease and acute exacerbations. Anti-eosinophilic monoclonal antibody therapies targeting IL-5 have shown promise and may become a viable treatment option for specific COPD patients in the future.

References on Request

59

PEER REVIEW: COPD

Pulmonary Hypertension in COPD Written by Dr Rosie Kelly, respiratory registrar and Professor Eddie Moloney, respiratory consultant Tallaght university hospital Chronic obstructive pulmonary disease (COPD) is a common, preventable, treatable disease that is characterised by persistent respiratory symptoms and airflow obstruction, usually caused by smoking. Approximately 10 percent of individuals aged 40 years or over have COPD, with estimates of over 500,000 people in Ireland having COPD, most undiagnosed and half of whom have moderate to severe disease, and prevalence increases with age. Disease course can vary from exertional breathlessness to progressive severe exacerbations requiring hospitalisation. COPD is diagnosed using spirometry with a measurement of forced expired air in one second (FEV1) over forced vital capacity (FVC), the total volume of air expelled in a forced effort. A persistent obstruction in airflow will result in FEV1/FVC ratio of < 70 percent with. FEV1 also used to measure the severity of disease. Pulmonary function testing in a pulmonary laboratory allows for measurement of lung volumes (air trapping and hyperinflation pattern usually seen in COPD) and diffusion capacity for carbon monoxide (DLco) between lung alveoli and pulmonary capillaries. DLco is usually reduced in COPD as a complication of alveolar destruction due to emphysema and maladaptive pulmonary vascular changes which result in pulmonary hypertension.

Pulmonary hypertension (PH) is a significant complication of COPD, seen commonly in moderate (FEV1 < 80 percent) to severe (FEV1 < 50 percent) disease, and the presence of PH has a significant impact on survival outcomes in COPD. Patients with PH are classified into 5 groups based on aetiology and classification, with group 3 pulmonary hypertension due to chronic lung disease and hypoxaemia, including COPD. Hypoxaemia from COPD results in pulmonary vascular endothelial cell injury promoting pulmonary vasoconstriction to try and maintain ventilation and perfusion balance, cellular proliferation and thrombosis.

Given that the majority of COPD patients at risk of PH (moderatesevere disease) will experience breathlessness, a principal symptom of both COPD and PH, it is important to be vigilant in clinical examination of COPD patients for signs attributable

to PH. Such findings include a loud second heart sound (P2), signs of right ventricular failure including a raised jugular venous pressure (JVP), an auscultatory third or fourth heart sound, a systolic murmur of tricuspid regurgitation, hepatomegaly, and peripheral oedema. If there is clinical suspicion, a number of non-invasive methods may give further clues. A six minute walk test will often show a rapid decline in oxygen saturations. A CXR may show right ventricular enlargement.

An ECG may show signs of right ventricular hypertrophy (right axis deviation, dominant R wave in V1, a peaked P wave in leads II/III/ AVF), or right ventricular strain (ST depression and - T wave inversion in leads V1-V3).

Transthoracic echocardiography (TTE) remains the investigation of choice due to its wide availability.

While there is an agreed upon consensus for the definition of PH on pulmonary artery catheterisation (mean pulmonary artery pressure > 20 mmHg), definitions for PH on TTE are less well defined. TTE evaluates the probability of PH using the tricuspid regurgitant jet velocity (TRV). TRV along with right atrial pressure (RAP) can be used to estimate the pulmonary artery systolic pressure (ePASP). PH is suggested echocardiographically when the ePASP exceeds 35 mmHg, and/or when the right ventricular size, wall thickness, and function are abnormal.

However, due to variability in RAP, ePASP may poorly correlate with values obtained by right heart catheterization (RHC).Thus, we support guidelines issued by the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) that propose use of the peak TRV together with echocardiographic findings of PH rather than ePASP to report the echocardiographic probability of PH. Regardless of whether the TRV or ePASP is used, these values should always be interpreted together with clinical suspicion and signs of RV dysfunction. When pulmonary dysfunction is severe enough to explain the degree of PH on echocardiography (eg, severe pulmonary dysfunction and mild PH), RHC is not indicated. RHC is usually reserved for those in whom the severity of PH on

Dr Rosie Kelly

Professor Eddie Moloney

echocardiography is not explained by the severity of their underlying CLD (eg, moderate to severe PH with mild lung disease) or for those in whom an alternate aetiology is suspected. If PH is present in the setting of a relatively normal or mildly impaired FEV1, but DLco disproportionately low, a CT Thorax should be considered to check for co-existing interstitial lung disease with COPD, or pulmonary embolic disease.

used correctly at a minimum of 15 hours per day, could slow progression of PH and reduce mortality. Unfortunately, correction of hypoxaemia at this point is unlikely to reverse vascular remodelling.

Should a diagnosis of group 3 PH be established, it is essential that the underlying disease process is managed as well as possible to prevent further progression.

This includes smoking cessation and pharmacological therapy to reduce symptoms and reduce frequency and severity of exacerbations. This will aim to optimise lung function and limit hypoxaemia. For specific therapies targeting PH, a recent systematic review showed minimal benefit in pharmacological therapies for COPD-PH. Vasodilator treatment resulted in reduction of measured PAH however this failed to translate into symptomatic improvement or survival benefit for patients with COPD. The only treatment option that showed both haemodynamic and clinical benefits was long term oxygen therapy (LTOT). Guidelines for commencing LTOT in patients with COPD recommend its use in those who show evidence of moderate hypoxaemia (Pa02 <8 mmHg) with pulmonary hypertension and/or polycythaemia (haematocrit >55 percent) or severe hypoxaemia (Pa02 <7.3mmHg). LTOT, when

COPD-PH is a significant complication with direct impact on outcomes in a disease that already has significant morbidity and mortality. Recognition of this complication requires vigilance in clinical examination and an awareness of clues on readily available investigations such as six minute walk test, ECG, CXR and pulmonary function testing.

Echocardiography can be used to diagnose PH but results should be interpreted in combination with the clinical picture, should results be incongruous referral for expert opinion for consideration of RHC should be sought. Management of COPD-PH remains focused on correction of hypoxaemia with targeted treatments to lower PAH showing minimal clinical benefits at this stage.

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

60

PEER REVIEW: ADDISON’S DISEASE

Management and Treatment of Addison’s Disease Written by Theresa Lowry-Lehnen (PhD), CNS, GPN, RNP, South East Technological University

adrenal glands; amyloidosis; and surgical removal of the adrenal glands.2, 3, 5 Secondary Adrenal Insufficiency

Addison’s disease (AD), often referred to as primary adrenal insufficiency or hypoadrenalism, is a rare endocrine disorder which occurs when the adrenal glands do not produce enough of the hormone cortisol and in some cases aldosterone. The disease is characterized by weight loss, muscle weakness, fatigue, hypotension, and sometimes darkening of the skin in both exposed and non-exposed areas of the body. It affects about 1 in 100,000 people, occurs in all age groups, but usually individuals aged 30-50 years and affects men and women equally. In rare cases, Addison’s disease has been noted to occur in families suggesting a genetic predisposition to developing the disorder.1, 3, 5, 11 Cortisol produced by the adrenal glands, located just above the kidneys belongs to a class of hormones called glucocorticoids, which affect almost every organ and tissue in the body. Cortisol’s main function is to help the body respond to stress. It also helps maintain blood pressure and cardiovascular function; slow the immune systems inflammatory response; helps balance the effects of insulin in breaking down sugar for energy; and help regulate the metabolism of proteins, carbohydrates, and fats.1, 3, 7 Aldosterone belongs to a class of hormones called mineralocorticoids also produced

by the adrenal glands. It helps maintain blood pressure and water and salt balance in the body by helping the kidney retain sodium and excrete potassium. When aldosterone production falls too low, the kidneys are unable to regulate salt and water balance, causing blood volume and blood pressure to drop.1, 3, 7 Primary Adrenal Insufficiency The commonest causes of Addison's disease are autoimmune disorders and tuberculosis.

While TB is the most common cause of Addison's disease in developing countries most cases of AD are caused by the gradual destruction of the adrenal cortex, the outer layer of the adrenal glands, by the body's own immune system. About 70 percent of reported cases of Addison’s disease are due to autoimmune disorders, in which the immune system makes antibodies which attack the body's own tissues or organs and slowly destroys them. Several autoimmune processes can lead to adrenal insufficiency either affecting the adrenal glands exclusively or as part of a more complex inherited autoimmune polyglandular syndrome. Other causes include certain medications, sepsis, and bleeding into both adrenal glands.

Less common causes of primary adrenal insufficiency are chronic infections, mainly fungal infections; cancer cells spreading to the

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Secondary adrenal insufficiency is caused by insufficient ACTH produced by the pituitary gland or CRH produced by the hypothalamus. It causes a drop in the production of cortisol but not aldosterone. A temporary form of secondary adrenal insufficiency can occur when a person receiving glucocorticoid hormones such as prednisone for a long time abruptly stops taking the medication.

Another cause of secondary adrenal insufficiency is the surgical removal of benign ACTHproducing tumours of the pituitary gland. Although less common, adrenal insufficiency can occur when the pituitary gland decreases in size or stops producing ACTH. This can result from tumours or infections of the area, loss of blood flow to the pituitary, radiation for treatment of pituitary tumours, or surgical removal of parts of the hypothalamus or the pituitary gland during neurosurgery.1, 2, 7 Addison's disease is associated with the development of other autoimmune diseases, such as type I diabetes, Hashimoto's thyroiditis, coeliac disease and vitiligo. Psychiatric symptoms such as mood disturbances, decreased motivation, and behavioural changes are also frequently associated with the condition.2, 3, 5 Hyponatremia and hyperkalemia are commonly associated with Addison's disease, while hypoglycaemia is uncommon.

The patient usually complains of gastrointestinal upset with anorexia, nausea, vomiting and diarrhoea and a craving for salty foods can occur due to salt loss. In women, menstrual periods may become irregular or stop. Adrenal calcification and enlargement are commonly seen in Addison's disease associated with tuberculosis.2 The symptoms of Addison disease increase in intensity over time and eventually lead to acute adrenal insufficiency, known

as adrenal crisis. Symptoms of addisonian crisis include sudden penetrating pain in the lower back, abdomen, or legs, severe vomiting and diarrhoea, followed by dehydration, low blood pressure and loss of consciousness.

Adrenal crisis is a medical emergency and must be treated immediately. It can cause cardiac arrest, CVA, hypovolaemic shock and hypoxia. If left untreated, adrenal crisis can be fatal leading to coma and death.1, 3 Diagnosis A suspected diagnosis of Addison’s disease is often based upon a detailed patient history, thorough clinical examination and identification of characteristic findings. A confirmed diagnosis is made through a series of specialised biochemical tests including the ACTH stimulation test and insulin-induced hypoglycemia test. X-ray examination of the adrenal and pituitary glands are also useful in helping to establish the diagnosis. Adrenal insufficiency can be difficult to diagnose in the early stages. Because symptoms progress slowly, the condition is often not detected until a stressful event or illness occurs.

In about 25 percent of patients, symptoms first appear during an addisonian crisis.3, 5. 10 ACTH Stimulation Test / Synacthen Stimulation Test ACTH stimulation test measures the ability of the adrenal cortex to respond to ACTH. Blood and/ or urine cortisol levels (short/ rapid ACTH test) are measured before and 30-60 minutes after a synthetic form of ACTH (Synacthen) is given by injection.

The normal response after an injection of ACTH is a rise in blood and urine cortisol levels.

Patients with either form of adrenal insufficiency respond poorly or do not respond at all. If the response to the short ACTH test is abnormal, a "long" ACTH stimulation test is carried out to determine the cause of adrenal insufficiency. ACTH is injected intravenously or intramuscularly over a 48- to 72-hour period,

61

therapy, which is ongoing for life.

Cortisol is replaced orally with hydrocortisone tablets, a synthetic glucocorticoid, taken once or twice a day. Other medicines used are prednisolone or dexamethasone, although these are less commonly prescribed. If aldosterone is also deficient, it is replaced with oral doses of a mineralocorticoid, called fludrocortisone acetate (Florinef), taken once a day and patients are usually advised to increase their salt intake. Patients with secondary adrenal insufficiency normally maintain aldosterone production, so do not require aldosterone replacement therapy. The doses of these medications are adjusted to meet the needs of individual patients.3, 5, 6, 8 During addisonian crisis, hypotension, hypoglycaemia, and hyperkalaemia can be life threatening, however, therapy with intravenous hydrocortisone, saline, and dextrose usually provide a rapid improvement.

When the patient can take fluids and medications by mouth, the amount of hydrocortisone is decreased until a maintenance dose is achieved. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.6, 7, 8

and blood and/or urine cortisol are measured the day before and during the 2 to 3 days of the injection. Individuals with primary adrenal insufficiency do not produce cortisol during the 48- to 72-hour period; however, those with secondary adrenal insufficiency have adequate responses to the test on the second or third day.2, 3, 10 Insulin-Induced Hypoglycemia Test Insulin-induced hypoglycemia is a reliable test to determine how the hypothalamus, pituitary and adrenal glands respond to stress.

Blood glucose and cortisol levels are measured, followed by an injection of fast-acting insulin and levels are measured again at 30, 45, and 90 minutes after the insulin injection. The normal response is for blood glucose levels to fall and cortisol levels to rise.2, 3, 10

Thyroid Function Tests may also be carried out as many people with Addison's disease have hypothyroidism.3 Other Diagnostic Tests Once a diagnosis of primary adrenal insufficiency has been made, x-ray of the abdomen may be taken to detect if the adrenals have any signs of calcium deposits which could indicate TB. If secondary adrenal insufficiency is determined to be the cause, a CT scan, producing a series of x-ray pictures giving a cross-sectional image may be used to check the size and shape of the pituitary gland. The function of the pituitary gland and its ability to produce other hormones are also tested.1, 8 Treatment In the majority of cases of Addison's disease, treatment will involve corticosteroid replacement

In most cases, underlying causes of Addison's disease can be treated. TB is treated with a course of antituberculous medication taken over a period of at least six months. Other infections may be treated with antibiotics or antifungal medication accordingly.

Autoimmune conditions can be treated, however, they cannot usually be cured.6, 7, 10 Patients with chronic adrenal insufficiency who require surgery under general anaesthesia are treated with hydrocortisone injections and saline. Injections commence the evening before surgery and continue until the patient is fully awake and able to take medication orally. The dosage is adjusted until the maintenance dosage given before surgery is reached.1 Women with Addison’s disease who are pregnant must be thoroughly monitored throughout their pregnancy to ensure the absence of complications.

Pregnant women with primary adrenal insufficiency are treated with standard replacement

therapy. If nausea and vomiting in early pregnancy interfere with oral medication, injections of the hormone may be necessary.

During delivery, treatment is similar to that of patients requiring surgery. Following delivery, the dose is gradually tapered and the usual maintenance doses of hydrocortisone and fludrocortisone acetate by mouth are not reached until about 10 days after childbirth.1 Patients with Addison’s disease should wear or carry a medical alert such as an id card, bracelet or necklace, be prescribed and carry an emergency injection kit at all times in case of adrenal crises. Each year, approximately 8% of people with Addison's disease experience adrenal crisis requiring extra steroid medication immediately, in the form of an emergency injection of intramuscular hydrocortisone (100mgs).

A person with Addison’s disease should also know how to increase medication during periods of stress or upper respiratory infections.4, 9 While Addison’s disease is a serious illness, the prognosis for many people living with the condition is good. Most people can expect to live relatively normal lives with a good life expectancy, if they receive on going good care and treatment.3, 8, 11 Assessment, monitoring, audit and evaluation for disease activity, progression, and effects of the therapeutic regime on a patient with Addison’s disease is a continuous process. By implementing person-centred care, monitoring and evaluating symptoms, outcomes and responses to therapy, clinicians play a pivotal role in managing the illness and improving the patient’s quality of life.

Addison's Ireland is the Irish branch of the Addison’s Disease Self-Help Group (ADSHG) with approximately 104 members from around the country both north and south. It works to raise awareness of Addison's in Ireland, support people and families affected by the condition and organises regular meetings in Dublin and around the country. For more information visit: https://www.addisons.org.uk/ articles.html/addisons-ireland/4 References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

62

PEER REVIEW: HEPATITIS C

Roadmap to Zero- The Elimination of Hepatitis C by 2030 Written by Nicola Perry, Secretary, Hepatitis C Partnership

Hepatitis C is an infection of the liver caused by the Hepatitis C virus, if left untreated it can cause permanent damage to the liver over many years. One in five people with liver damage associated with the virus will go on to develop Cirrhosis, which increases their risk of developing liver cancer.1 Most people become infected with the hepatitis C virus by sharing needles or other equipment used to prepare and inject drugs.

From 2004 to 2019, 15,700 people in Ireland have been diagnosed with Hepatitis C. Each year around 600 to 700 people find out they have Hepatitis C and there could be as many as 30,000 people in Ireland living with the virus.2 To date, over 5,000 patients in Ireland have been treated with highly effective Direct Acting Antiviral DAA’s for hepatitis C.3

Programme (NHCTP), established in 2015. The programme specifics and structure is available on HseLand, and also in the NHCTP Community Treatment Guidelines, originally published in 2019. The document outlines preferred community DAA prescriptions as: Sofosbuvir/Velpatasvir 400mgs/100mg (Epclusa®) one tablet daily with or without food.

Patient should be advised to take the medication at the same time every day. Pangenotypic 12-week course Suitable in all stages of hepatic impairment renally excreted (requires creatinine clearance > 30mls/min) Headache, fatigue and nausea are the most common side effects (> 10% of patients). They tend to be mild to moderate in severity. They are most likely to occur in the first four weeks of treatment.

In May 2016, the World Health Assembly adopted the first global health sector strategy on viral hepatitis, 2016-2021. Ireland is one of 194 Member States of the World Health Organisation committed to eliminating viral hepatitis as a public health threat by 2030.4 This ambitious strategy was made possible largely due to the introduction of Direct Acting Antiviral (DAAs) drugs in 2011.

With a cure rate of ~96% these highly effective drugs with minimal side effects transformed HCV care globally. These drugs provided an opportunity to scale treatment largely due to the reduced monitoring and the increased efficacy they afforded.

In Ireland the oversight of Hepatitis C treatment is carried out by the National Hepatitis C Treatment AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Glecaprevir/Pibrentasvir 100mgs/40mgs (Maviret®) three tablets once daily with or after food. Patient should be advised to take the medication at the same time every day. Pangenotypic 8-week course not suitable for Child Pugh’s stage B and C cirrhosis. Suitable in all stages of renal failure including dialysis Minimal side effects. Headache and fatigue most common.

Also potential for GI symptoms particularly if patients do not take their medication with or after food.

These treatments have >95% cure rate, for most patients are taken with minimal side effects, the drug cost is covered in the NHCTP. So why in some quarters does it appear Ireland, along with other EU countries is not on track to achieve the elimination of Hepatitis C by 2030?

A recent study done by Liver International in 2021 found, that out of 45 high-income countries, only 11 (Australia, Canada, France, Germany, Iceland, Italy, Japan, Spain, Sweden, Switzerland, and United Kingdom) countries are on track to meet the WHO’s global elimination strategy. Ireland, like 27 other member states, are predicted to achieve elimination by 2050, 20 years after the target date.5 Current data from the NHCTP suggests that Ireland has reached the 2020 targets and is on track to achieve 2030 WHO elimination targets.6 This is disappointing given the known risks of communicable diseases and the availability of highly effective curative treatments. The reasons for this are of course complex but in the simplest of terms, endemic barriers in the care cascade have resulted in many patients being lost to care.

We at the Hepatitis C Partnership (HCP) undertook a national scoping exercise during 2021 to try to better understand the experiences of healthcare providers and people directly affected by Hepatitis C. We hoped to learn what was working well, what could be improved and what those at the centre of the Hep C cascade of care thought.

The result of this extensive undertaking is “The Roadmap to Zero”, launched by the HCP on the 1st June of June 2022. The launch coincided with the opportunity to present the recommendations

For treatment of HIV-1

Make Doravirine a Part of Every Day DELSTRIGO® (100 mg doravirine/300 mg lamivudine/300 mg tenofovir disoproxil fumarate, equivalent to 245 mg of tenofovir disoproxil) is indicated for the treatment of adults infected with HIV-1 without past or present evidence of resistance to the NNRTI class, lamivudine, or tenofovir.1 PIFELTRO® (doravirine) is indicated, in combination with other antiretroviral medicinal products, for the treatment of adults infected with HIV-1 without past or present evidence of resistance to the NNRTI class.2 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions.

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

ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION Pifeltro: film-coated tablet containing 100 mg doravirine. Delstrigo: film-coated tablet containing 100 mg doravirine, 300 mg lamivudine and 300 mg tenofovir disoproxil fumarate, equivalent to 245 mg of tenofovir disoproxil. INDICATIONS Pifeltro: For use in combination with other antiretrovirals, for the treatment of HIV-1 without past or present evidence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). Delstrigo: For the treatment of HIV-1 without past or present evidence of resistance to NNRTIs, lamivudine or tenofovir. DOSAGE AND ADMINISTRATION Therapy should be initiated by a physician experienced in HIV infection management.

Pifeltro: One 100 mg tablet once daily. Delstrigo: One 100/300/245 mg tablet once daily. Pifeltro and Delstrigo: If co-administered with rifabutin or other moderate CYP3A inducers, increase doravirine dose to 100 mg twice daily (12 hours apart). Pifeltro: Elderly: No dose adjustment necessary. Renal impairment: No dose adjustment necessary. Hepatic impairment: mild to moderate: no dosage adjustment required; severe: use with caution. Delstrigo: Elderly: Special care advised. Renal impairment: estimated creatinine clearance (CrCl) ≥ 50 mL/min: no dose adjustment necessary; estimated CrCl <50 mL/min: not recommended. Hepatic impairment: mild to moderate: no adjustment required; severe hepatic: use with caution. CONTRAINDICATIONS Hypersensitivity to the active substance or excipients Co-administration with strong CYP3A inducers. PRECAUTIONS AND WARNINGS A residual risk of sexual transmission of HIV-1 cannot be excluded and precautions should be taken in accordance with national guidelines. Use with CYP3A inducers may reduce the exposure of doravirine. Autoimmune disorders (such as autoimmune hepatitis) and immune reactivation syndrome have been reported in patients treated with combination antiretroviral therapy which may require investigation and treatment. Contains lactose monohydrate. Delstrigo: Post-treatment exacerbation of HBV (including hepatic decompensation and liver failure) have been reported in patients co-infected with HIV-1 and HBV following discontinuation of lamivudine or tenofovir disproxil. Monitor patients co-infected with HIV-1 and HBV after discontinuation of Delstrigo and if appropriate initiate anti-HBV therapy. Renal impairment, including acute renal failure and Fanconi syndrome have been reported with tenofovir disoproxil. Assess estimated CrCl prior to initiation and during therapy. In patients at risk of renal dysfunction, serum phosphorus, urine glucose, and urine protein should also be assessed. Discontinue therapy if estimated CrCl declines below 50 mL/min. Avoid with concurrent or recent use of nephrotoxic medicinal products (e.g. high-dose or multiple NSAIDs). Evaluation of renal function is recommended for persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness. Assessment of bone mineral density should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms. Doravirine/lamivudine/tenofovir disoproxil must not be co-administered with other medicinal products containing lamivudine, tenofovir disoproxil, or tenofovir alafenamide or with adefovir dipivoxil. Doravirine/lamivudine/tenofovir disoproxil should not be administered with doravirine unless needed for dose adjustment (e.g. co-administered with rifabutin). Drug interactions: Refer to SmPC for full information on drug interactions. Pifeltro and Delstrigo: Doravirine is metabolized

primarily by CYP3A. Do not co-administer with strong CYP3A enzyme inducers. If co-administration with rifabutin or other moderate CYP3A inducers cannot be avoided, increase doravirine dose to 100 mg twice daily (taken 12 hours apart). Use with caution when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that have a narrow therapeutic window (e.g., midazolam, tacrolimus and sirolimus). Delstrigo: Do not administer with other antiretroviral medicinal products. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion may increase serum concentrations of lamivudine. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion via OAT1, OAT3 or MRP4 may increase serum concentrations of tenofovir. Avoid with concurrent or recent use of nephrotoxic medicinal products. Pregnancy and Lactation: Pifeltro and Delstrigo: Avoid use during pregnancy. An Antiretroviral Pregnancy Registry has been established. Breastfeeding is not recommended.

SIDE EFFECTS Refer to SmPC for complete information on side-effects. Pifeltro and Delstrigo: Common: abnormal dreams, insomnia, headache, dizziness, somnolence, nausea, diarrhoea, abdominal pain, flatulence, vomiting, rash, fatigue alanine aminotransferase increased. Uncommon: hypophosphataemia, nightmare, depression, suicidal ideation, paraesthesia, asthenia. Rare: hypomagnesaemia, blood creatine phosphokinase increased. Delstrigo: Common: cough, nasal symptoms, alopecia, muscle disorders, fever. Uncommon: neutropenia, anaemia, thrombocytopenia, pancreatitis, rhabdomyolysis, proximal renal tubulopathy (including Fanconi syndrome), aspartate aminotransferase increased. Rare: lactic acidosis, hepatitis, angioedema, myopathy, acute renal failure, renal failure, acute tubular necrosis, nephritis (including acute interstitial) and nephrogenic diabetes insipidus. Very Rare: pure red cell aplasia, peripheral neuropathy (or paraesthesia). Lactic acidosis Cases of lactic acidosis have been reported with tenofovir disoproxil alone or in combination with other antiretrovirals. Patients with predisposing factors such as patients with decompensated liver disease, or patients receiving concomitant medications known to induce lactic acidosis are at increased risk of experiencing severe lactic acidosis during tenofovir disoproxil treatment, including fatal outcomes. PACKAGE QUANTITIES Bottle of 30 tablets. Legal Category: POM. Marketing Authorisation numbers: Pifeltro: EU/1/18/1332/001. Delstrigo: EU/1/18/1333/001. Marketing Authorisation Holder: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: June 2020. © Merck Sharp & Dohme B.V., 2020. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 or from www.medicines.ie. Date of Preparation: April 2021. IB/0019.

References: 1. DELSTRIGO Summary of Product Characteristics, June 2020. 2. PIFELTRO Summary of Product Characteristics, November 2019.

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

Adverse events should also be reported to MSD (Tel: 01-2998700)

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

IE-DOV-00022

PIFELTRO® ▼ (Doravirine) DELSTRIGO® ▼ (Doravirine/Lamivudine/Tenofovir disproxil fumarate)

64

PEER REVIEW: HEPATITIS C

to the Oireachtas Joint health Committee, to discuss the current experiences of healthcare providers and their patients.

The report produced 7 key recommendations across three themes, they were: 1. Establish regional needs with regional experts Understanding the burden of Hepatitis C on a regional basis is important. Not all areas will have the same needs and it is important to work with regional stakeholders to: • Establish baseline prevalence and incidence data on as local a level as possible.

• Identify any specific challenges in different regional areas considering at-risk cohorts, likely burden of disease, accessibility, and resource needs across the Cascade of Care.

• Define agreed regional micro elimination targets, based on the current best evidence of the likely burden of disease in the region.

2. Set national and regional implementation plans • Have an explicit focus on elimination as defined by the World Health Organisation, and use the regional micro elimination targets as metrics for success.

• Set out how capacity is to be built in each regional area, as well as what actions will be undertaken at both national and regional levels to drive elimination.

location in the country and your characteristics as a patient. Every effort should be made to create a policy framework that is driven by the need to test and treat as flexibly and locally as possible, to realise the Slaintecare vision for equality in the context of liver care. There is also the potential for cross-policy engagement with the National Drug Strategy, and actions related to making services more accessible for people who use drugs.

Recommendations 3. Unblock existing policy barriers, and set policy to enable elimination • Remove the requirement that patients need to be engaged with opioid substitution treatment to be treated in the community by their GP. • Remove any barriers to community pharmacy management of Hepatitis C medications and ensure that community pharmacists can dispense medication where possible.

• Ensure an opt-out system for testing in all community-based addiction services, including section 39 agencies, is being implemented.

• Implement an opt-out system for testing and treatment in prison settings.

• Broaden the range of testing opportunities by enabling a diverse range of community testing initiatives, including mobile and outreach testing, dried blood spot testing, point of care testing, and at-home testing as appropriate.

• Assign ownership to a named role for delivery, both regionally and nationally, and set SMART objectives for implementation.

• Ensure PAG has appropriate structure and resources to monitor and drive implementation, including regional subgroups with representation from people with lived experience, statutory sector, and civil society representation which is representative of the challenges in the region.

2. Build pathways to support elimination in a sustainable way Rationale Now, there is an inequality in access to Hepatitis C care in that the care that you receive is largely dependent on your AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

• Provide training on Hepatitis C testing and care to staff project and support workers, peers, care and case managers, and nurses - in all community services working with people who are part of a population with higher seroprevalence, and resource those services to provide testing.

4. Build a community based, nurse and peer-led system to drive elimination • Utilise existing hospital-based consultant-led services in each regional area as hubs and existing community services (e.g., OST clinics, GP-led services) as spokes.

Recognising the pressures that both hospital and community professionals are under, support should be flexible and ad hoc, and leverage online tools (teleconferencing, emails) as a preference.

• Include paid peer workers with relevant lived experience to provide community-based testing, and patient support across the cascade, learning from the positive experience of the model in place at the Mater Hospital, and extending the same to other regions. Peer workers are vital in addressing Hepatitis C in our communities and should be paid, well trained, embedded in clinical teams/ services and provide flexible support (outreach, access supports) to patients determined by patient need.

• Include enhanced nursing supports to ensure a nurseled community service model, including nurse prescribing.

• Include properly resourced GPs who can treat Hepatitis C among any community-based

population who do not clinically require hospital-based treatment and who can support a nurseled model of community care.

• Include access to appropriate laboratory/testing facilities at each spoke, acknowledging the significant pressure on laboratories, including the National Virus Reference Laboratory arising from COVID, and supporting those services accordingly.

• Include access to community pharmacy dispensing at each spoke, and consider a strategic partnership with a suitable national pharmacy group to scale community access.

5. Ensure utility beyond Hepatitis C • Ensure that the system has a role in addressing longer-term liver care in Ireland after the initial push to eliminate Hepatitis C. • Consider whether the system can play a role in detecting / providing longer-term care around other liver care issues (such as Hepatitis B virus (HBV) / fatty liver disease (FLD) or around other healthcare issues that could be addressed primarily in the community.

3. Drive Hepatitis C Elimination Rationale When a suitable system is in place to drive elimination, we need to help people access it.

Some people who are treated for Hepatitis C will have ongoing liver care needs, and will continue to be exposed to risk factors post-treatment, or may have other issues in their lives around which they seek support. The drive to eliminate Hepatitis C should be seen as an opportunity to link people to other systems of care.

65 6. Find the ‘missing thousands’ • Ensure widespread and sustained public health promotion campaigns targeted at the ‘missing thousands’ who are currently living with undiagnosed Hepatitis C in our communities. These campaigns should include a strong peer-led outreach component and can focus on the positive impact of addressing Hepatitis C in the community as well as maximising opportunities for general hepatic health promotion.

• Ensure that frontline healthcare providers and, where needed, patients, are appropriately incentivized (if this is not already the case) through a staged incentivization approach and are recognized for reaching agreed targets around reaching, testing and treating people with Hepatitis C.

hepatic issues. Due to the nature of the transmission of Hepatitis C and high prevalence among people who do, or have, used drugs they often have co-occurring health issues, mental health challenges and frequently have experienced stigma in statutory settings.

Community based treatment, improvements to regional access and the use of trained peer support workers can help with the drive to elimination. Initiatives such as the NHCTPs planned roll out of the home testing kits for Hepatitis C, initially a 1000 kit pilot, should be implemented

and evaluated in a timely manner and if proven successful, fully implemented. Systemic and policy blockages should be resolved to maintain a flow of patients eligible for treatment, this improving health outcomes, future burden and quality of life.

Finally, there is a need to strategically align with the WHO goals and ensure that there is a consistent, visible, and clearly articulated metrics-based strategy focused on elimination.

The Hepatitis C Partnership (HCP) is a national collaborative network of stakeholders from across the public and NGO sector who lobby, educate and support those impacted by hepatitis C. Please go to the website for more information on our work, and access to the full report.

References on request

7. Focus on supporting good longer-term outcomes • Support people who access treatment and require additional inputs, such as around housing, employment, education, or psychosocial support to access those supports as needed Summary There is no doubt of the drive and commitment present in the healthcare provider cohort working with Hepatitis C and broader

News - Government Urged to Increase Availability of PrEP HIV Ireland has called on Government to increase funding and resources to ensure timely and barrier free access to PrEP services in Ireland. The call comes amid a reported doubling of the number of newly notified cases of HIV in Ireland compared to the first six months last year (293 v 145), as highlighted in the Weekly HIV and STI Report published by the Health Protection Surveillance Centre (HPSC).

Speaking ahead of a public seminar on the role of communities in memorialising HIV and AIDS, Executive Director of HIV Ireland Mr Stephen O’Hare said, “PrEP [pre-exposure prophylaxis] is highly effective at preventing a person who is HIV negative from acquiring HIV through sexual intercourse and is a vital component in our strategy to reduce HIV transmissions. Delays in access to services is detrimental to communities and will further reduce Ireland’s ability to meets its ambitious target of ending new HIV transmissions by 2030,” he added.

Research published in 2022 by HIV Ireland points to ongoing difficulties in accessing PrEP. The recently published EMERGE Study, conducted by the London School of Hygiene and Tropical Medicine in partnership with HIV Ireland’s MPOWER programme found that more than half of gay, bisexual and other men who have sex with men who reported difficulty in accessing STI services during COVID-19 restrictions were attempting to access PrEP. Adam Shanley, co author of the report and MPOWER Programme manager said, “The continued increase in waiting times risks eroding the high degree of enthusiasm for PrEP among gay, bisexual and other men who have sex with men in Ireland as frustration with the overburdened system sets in. A successful national HIV prevention strategy depends heavily on timely and barrier free access to services” he added.

“We know from other jurisdictions,” continued Mr Shanley, “that long waiting times for PrEP may be associated with increased vulnerability to acquiring HIV for those on waiting lists, and further risks entirely preventable onward transmissions.”

The warnings were issued ahead of a public event to mark Irish AIDS Day to discuss the Government’s recent public call for expressions of interest to design and construct a National HIV and AIDS Monument, located in the Phoenix Park, Dublin. The event “These Fragile Lives – The Role of Communities in Memorialising HIV and AIDS in Ireland” will hear from speakers and stakeholders with a long history in activism and of working at the coalface of the epidemic particularly during the height of the HIV and AIDS crisis in the 1980s and 1990s.

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

66

PEER REVIEW: MEDICAL IMAGING

An evaluation of information online on artificial intelligence in medical imaging Written by Philip Mulryan1, Naomi Ni Chleirigh2, Alexander T. O’Mahony2* , Claire Crowley1, David Ryan3, Patrick McLaughlin4, Mark McEntee2, Michael Maher1,2 and Owen J. O’Connor1,2

Background Artificial intelligence (AI) involves the use of computer algorithms to perform tasks typically associated with human intelligence.1 The role of AI in medical imaging has progressed to various stages of development, application and refinement over the past 10–15 years. Consequentially, publications on AI in medical imaging have exponentially increased from about 100–150 per year in 2007–2008 to 700–800 per year in 2016–2017.2 Several studies pertaining to dermatology, pathology, and ophthalmology have shown the potential and clinical utility of AI algorithms. For example, skin cancer, the most diagnosed malignancy worldwide, is primarily diagnosed visually.

Deep neural networks (DNN) have demonstrated equivalence with consultant dermatologist diagnostic ability.3 Hence the early evolution of AI has leaned towards the visual sciences and its application to radiology an extension of this.

Medical imaging interpretation requires accuracy, precision, and fidelity. At its essence it is a visual science whereby the interpreter translates either a single or series of images into a succinct report to answer a clinical question and guide evidence-based management. Studies report that on average a radiologist must interpret one image every 3–4 s in an 8-h workday to meet workload demands4 and with the compound annual growth rate (CAGR) of diagnostic imaging estimated to be 5.4% until 20275 increasing workloads are expected. Burnout has been ubiquitously reported among medical specialties (~ 25–60%)6, 7 with limited solutions being proposed and implemented; thus many key advantages may be conferred by the incorporation of AI into radiological practice. The applications of AI in radiology can be broadly divided into diagnostic and logistic. Computeraided diagnostics (CAD) may facilitate earlier detection of abnormalities, improve patient outcomes, reduce medico-legal exposure, and

decrease radiologist workload.

Logistic improvements would include optimization of workflow, prompt communication of critical findings and more efficient vetting and triage systems.

Historically, apprehension has existed concerning recruitment within the medical and radiological community as a result of AI. Focused assessment of individual stakeholder groups in relation to AI in radiology demonstrated a wide spectrum of opinion.

Studies of medical student perspectives in North America, Europe and the United Kingdom conveyed heterogenous opinions on the potential implications of AI on radiology possibly with geographical variation.8–10 A recurrent theme in early studies is the large educational gap in medical schools regarding the capability, utility, and limitations of AI. A European multi-centre study of both radiologists in training and consultants performed in France11 demonstrated an overall positive perspective; however, a majority expressed concerns regarding insufficient information on AI and its potential implications. Ten years ago, the end of radiology as a career was being heralded. Hence radiology residency applications reduced in response to concerns about the future of radiology as a career.12 Ten years ago, perception probably reflected local concerns in the absence of experience. It has been shown that more positive opinions have been expressed by those medical students with exposure to AI and radiology.9 The transition from discourse about the potential of AI to its integration and use should have modified opinions based on practice and experience.

Therefore, this paper aimed to quantify the proportion of positive, negative, balanced, and neutral viewpoints presented on the internet in relation to the impact of AI on radiology. The purpose of this was to determine the global and regional perception of AI in radiology, and thus, conclude as to where the future of radiology may lie.

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Methods Data collection Two search methods were used to evaluate information online relating to artificial intelligence in medical imaging. The first search method screened existing data on AI in radiology at the time of search. The second method identified a live stream of articles relating to AI as they were released on the web. Searches were carried out independently by two of the investigators.

Thirty-four key search phrases were established (Additional file 1: Appendix 1). Phrases were generated with input from a medical student, healthcare professional, non-consultant hospital doctor and prospective radiology trainee. These phrases were than validated by two consultant radiologists (M.M.M., O.J.O’C).

The phrases were chosen to reflect a broad range of search terms encompassing a multidisciplinary opinion to the impact of AI on the radiology service.

Data identification Existing data This search was performed on ‘All’ content in the Google search engine and was conducted over the period 25th January 2021–7th February 2021. The google search engine has over 90% of the market share and thus was felt to be reasonably representative of the population on a global scale.13 The google search was performed for the 34 key phrases in an identical manner. Results were limited to the English language and open access academia or where no financial stipulation was required to access the article. We reviewed the first two pages of Google results for these searches, as numerous studies on user behaviour have indicated that 95% of users choose websites listed on the first page of results, leaving only 5% reviewing results on any subsequent page.14–18 While date of publication was not a selection criterion all included articles from the google search were created within the past 5 years.

Live stream A Rich Site Summary (RSS) feed search strategy was used to evaluate the written incident information over a 3-week period (07/03/21–28/03/21) as a surrogate for postings on news media and social media. The same 34 key phrases were entered into Google Alerts. This provided a continuous search for new relevant online content appearing subsequently.

This content was then analyzed and organized appropriately.

Data sourcing The source of each relevant post was identified. The source website was then assigned a sub-type based on the ‘About Us’ section. The source subtypes were segregated as either journal, media, commercial, education or other if outside of these categories.

For published academia, it was noted whether it was from a peerreviewed and/or indexed journal (PUBMED). Where an identifiable author existed, it was subtyped into radiologist, journalist, nonradiologist doctor, radiographer and other. The geographical origin and date of issue was also noted, where available.

Data categorization The web pages identified by the dichotomized search strategy were analyzed by each investigator homogenously. Firstly, all Google advertisements were omitted.Each post was then categorized as either relevant or nonrelevant. Nonrelevant posts included those failing to provide information on AI in medical imaging (such as a journal calling for abstracts/submissions) or academia related posts that were not open access, duplicate posts or posts that were inaccessible.

Relevant posts were divided as either having an overall positive, negative, balanced, or neutral viewpoint. The assessment and categorization of this information was carried out by two senior authors (M.M.M., O.J.O.C), both of whom are academic consultant radiologists working in a large teaching hospital. The

BIKTARVY® offers long-term treatment success for a broad range of people living with HIV*1–5 PRESCRIBE WITH

A robust** regimen delivering long-term efficacy with 0 resistance in randomised clinical trials†‡1,2

TAKE WITH

A small STR with low potential for DDIs, simple dosing and no food requirements¶1

FOCUS ON

A well-tolerated regimen with low rates of discontinuation in randomised clinical trials§ll2,5–7

CONFIDENCE

EASE

LONG-TERM HEALTH

Made in Ireland Prescribing information can be found overleaf | UK-BVY-0701 | June 2022

Footnotes:

Prescribing Information:

*BIKTARVY® was assessed in four Phase 3, randomised clinical trials: two double-blind trials in treatment-naive adults through to 144 weeks (Study 1489 [BIKTARVY® vs ABC/3TC/DTG, n=629] and Study 1490 [BIKTARVY® vs DTG + FTC/ TAF, n=645]) and two in virologically suppressed adults through to 48 weeks (Study 1844 [double-blind trial, switching from DTG + ABC/3TC or ABC/3TC/DTG to BIKTARVY®, n=563] and Study 1878 [openlabel trial, switching from ABC/3TC or FTC/TDF plus boosted ATV or DRV to BIKTARVY®, n=577]).1 The primary endpoint of Studies 1489 and 1490 was HIV-1 RNA <50 copies/mL at Week 48, as defined by the US FDA snapshot algorithm, with a prespecified non-inferiority margin of –12%.3,4 The primary endpoint of Studies 1844 and 1878 was HIV-1 RNA ≥50 copies/mL at Week 48, as defined by the US FDA snapshot algorithm, with a prespecified noninferiority margin of 4%.5,6 Efficacy defined as viral load <50 copies/mL.1

Consult the Summary of Product Characteristics (SmPC) before prescribing.

**Defined as maintained efficacy, which is dependent on patient adherence.

Adherence is impacted by tolerability and simplicity of treatment.8–11 †At Week 144, in Study 1489 (BIKTARVY® [n=314] vs ABC/3TC/DTG [n=315]) efficacy was 82% vs 84% (95% CI: –2.6 [–8.5– 3.4]) and in Study 1490 (BIKTARVY® [n=320] vs DTG + FTC/TAF [n=325]) efficacy was 81% vs 84% (95% CI: –1.9 [–7.8–3.9]), with BIKTARVY® demonstrating noninferior efficacy vs comparator in both trials. 2 At Week 48, in Study 1844 (BIKTARVY® [n=282] vs ABC/3TC/DTG [n=281]) efficacy was 94% vs 95% (95% CI: –1.4 [–5.5–2.6]) and in Study 1878 (BIKTARVY® [n=290] vs ABC/3TC or FTC/TDF plus boosted ATV or DRV [n=287]) efficacy was 92% vs 89% (95% CI: 3.2 [–1.6–8.2]).1 ‡At Week 144, in pooled treatment-naïve patient data from Study 1489 (n=629) and Study 1490 (n=645), and Week 48 in Study 1844 (n=563), there were 0 cases of treatment emergent resistance to study regimens [BIKTARVY® (n=0/834), ABC/3TC/DTG (n=0/315) and DTG + FTC/ TAF (n=0/325)].2,5 At Week 24, in Study 1878 (n=577) one participant in the ABC/3TC plus boosted DRV group developed treatment-emergent resistance; no participants in the BIKTARVY® group developed treatmentemergent resistance through Week 48.6 § At Week 144, in patients receiving BIKTARVY®, the most frequently reported study-drug-related adverse reactions (≥5%) in Study 1489 were diarrhoea 6% (n=19/314), nausea 6% (n=18/314) and headache 5% (n=16/314); in Study 1490 they were headache 4% (n=14/320), diarrhoea 3% (n=10/320) and nausea 3% (n=10/320).2 ll 44-week data on AEs leading to study drug discontinuation % (n). Study 1489 (vs ABC/3TC/DTG): 0% (n=314) vs 2% (n=5 /315); Study 1490 (vs FTC/TAF + DTG): 2% (n=6/320) vs 2% (n=6/325).2 48-week data on AEs leading to study drug discontinuation % (n). No discontinuations due to weight gain in Study 1489 or Study 1490. Study 1844 (vs ABC/3TC/DTG): 2% (n=6/282) vs 1% (n=2/281); Study 1878 (vs boosted DRV or ATV + 2 NRTIs): 1% (n=2/290) vs <1% (n=1/287).5,6 ¶Small STR with flexible daily dosing. Each BIKTARVY® tablet is approximately 15 mm x 8 mm.1 References: 1. BIKTARVY® (BIC/FTC/TAF) Summary of Product Characteristics.

2. Orkin C, et al. Lancet HIV. 2020; 7: e389 e400.

3. Sax PE, et al. Lancet. 2017; 390: 2073–2082.

4. Gallant J, et al. Lancet. 2017; 390: 2063–2072.

5. Molina JM, et al. Lancet HIV. 2018; 5: e357–e365.

6. Daar ES, et al. Lancet HIV. 2018; 5: e347–e356.

7. Wohl D. et al. Patient. 2018; 11: 561–573.

8. US Department of Health and Human Sciences (DHHS). Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. June 2021. Available from: https://clinicalinfo.hiv. gov/sites/default/ files/guidelines/documents/ AdultandAdolescentGL.pdf (Accessed June 2021) 9. Cihlar T and Fordyce M. Curr Opin Virol. 2016; 18: 50–56.

10. Trottier B, et al. J Int AIDS Soc. 2014; 17(4 Suppl 3): 19765.

11. Orkin C, et al. HIV Med. 2018; 19: 18–32.

Abbreviations: 3TC, lamivudine ABC, abacavir AE, adverse event ATV, atazanavir BIC, bictegravir CI, confidence interval DRV, darunavir DTG, dolutegravir FDA, Food and Drug Administration FTC, emtricitabine PLWH, people living with HIV RNA, ribonucleic acid STR, single-tablet regimen TAF, tenofovir-alafenamide fumarate TFV, tenofovir TDF, tenofovir disoproxil fumarate US, United States

BIKTARVY® bictegravir 50mg/emtricitabine 200mg/ tenofovir alafenamide 25mg film-coated tablets.

INDICATION: Treatment of adults with HIV-1 infection without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir DOSAGE: Adults: One tablet, once daily, taken orally and whole with/without food. Elderly: No dose adjustment is required in patients ≥ 65 years. Renal impairment: Patients with estimated creatinine clearance (CrCl) ≥ 30 mL/min: No dose adjustment required. Patients with CrCl ≥ 15 mL/min and < 30 mL/min or Patients with end stage renal disease (ESRD, CrCl < 15 mL/min) who are not receiving chronic haemodialysis: Should be avoided. Patients with ESRD on chronic haemodialysis: No dose adjustment, but only use if potential benefit outweighs the potential risks. Hepatic impairment: Mild/moderate hepatic impairment: no dose adjustment required.

Severe hepatic impairment: not recommended. Paediatric population (<18 years): Safety and efficacy has not been established. Refer to SmPC for full information CONTRAINDICATIONS: Hypersensitivity to active substances / any excipients. Co-administration with rifampicin and St John’s wort. Refer to SmPC for full information. WARNINGS/ PRECAUTIONS: Should not be co-administered with other antiretroviral products. Limited safety and efficacy data in HCV co-infection. Tenofovir alafenamide is active against HBV. Co-infected HIV/HBV patients should be closely monitored for at least several months following discontinuation for symptoms of severe acute exacerbations of hepatitis. Should not be administered simultaneously with magnesium/aluminium-containing antacids or iron supplements under fasted conditions. See SmPC for more information on liver disease, weight and metabolic parameters, risk of mitochondrial dysfunction following exposure in utero, immune reactivation syndrome, opportunistic infections, osteonecrosis with CART therapy or nephrotoxicity and patients with ESRD on chronic haemodialysis. Co- administration: Biktarvy is not recommended for coadministration with atazanavir, carbamazepine, ciclosporin (IV or oral use), oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, or sucralfate. Excipients: Contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially ‘sodium free’. Refer to SmPC for full information on warnings and precautions. INTERACTIONS: See SmPC for full list.

PREGNANCY/LACTATION: Use only if potential benefit justifies the potential risk. Breast-feeding: not recommended. Refer to SmPC for full information. DRIVING/USING MACHINERY: dizziness has been reported.

SIDE EFFECTS: Refer to SmPC for full information Common (≥1/100 to <1/10): depression, abnormal dreams, headache, dizziness, diarrhoea, nausea, fatigue. Serious adverse events: suicidal ideation, suicide attempt behaviour (particularly in patients with a pre-existing history of depression or psychiatric illness), anxiety, sleep disorders, angioedema and Stevens-Johnson syndrome. LEGAL CATEGORY: POM. PACK: Bottle of 30 film-coated tablets. PRICE: UK NHS List Price - £879.51; Éire/ Ireland – POA. MARKETING AUTHORISATION NUMBER: Great Britain: PLGB 11972/0008 Ireland and United Kingdom (Northern Ireland: EU/1/18/1289/001 & EU/1/18/1289/002 FURTHER INFORMATION: Gilead Sciences Ltd, 280 High Holborn, London, WC1V 7EE, UK; Great Britain & Northern Ireland: +44 (0) 8000 113700, For Ireland: +353 214 825 999. E-mail: ukmedinfo@gilead.com. Biktarvy is a trademark. DATE OF PREPARATION: March 2021; UK-HIV-2021-03-0032.

Additional monitoring required.

Adverse events should be reported. For Great Britain and Northern Ireland, reporting forms and information can be found at www.mhra. gov.uk/yellowcard/ or via the Yellow Card app (download from the Apple App Store or Google Play Store). Adverse events should be reported to Gilead (safety_FC@gilead.com) or +44 (0) 1223 897500.

Adverse events should be reported. For Ireland, reporting forms and information can be found at www.hpra.ie and can be reported to HPRA on +353 1 6764971. Adverse events should be reported to Gilead (safety_FC@gilead.com) or +44 (0) 1223 897500.

UK-BVY-0701 | June 2022

Mulryan et al. Insights into Imaging

69 Page

(2022) 13:79

PEER REVIEW: MEDICAL IMAGING Total Data Points (n=680)

Fig. 1 Schematic of google search and results summary

Non Relevant (n=113)

Relevant and accessible (n=248)

Inaccessible (n=6)

assessment wasdone in tandem, and the final decision was arrived at by consensus.

Duplicates (n=313)

Relevance Positive

Posi ve (n=106) Balanced (n=95) Neutral (n=38) Nega ve (n=8) Positive viewpoints were themed as changes brought about by AI which would result in increased employment, service expansion, Fig. 1 Schematic of google search and results summary efficiency, fidelity of interpretation, radiologist doctors accounted can be seen in Additional file 1: Data analysis improved patient care, better Appendix 3.1 & 3.2. Commercial for the lowest proportion of quality assurance and more Data compilation and statistical web pages had the highest positive viewpoints (18.8%, n = job satisfaction. Additional analyses were performed using Table with percentage proportion of positive viewpoints 3). Four percent of web pages file 1: Appendix 2 provides a 1 Summary of categorization of posts by origin Microsoft Excel (Microsoft i.e., 66%, followed by media web authored by radiologists (n = 4) sample of positive viewpoints Corporation, n =of 248 Journal Redmond, Media pages at 52%, peer-reviewed Commercial or by those falling into the Education ‘Other’ as extracted from the data Washington, USA) and Google journals at 37% and educational category (n = 3) had negative included posts. Webpages that Sheets (1600 Amphitheatre n = 120 48.39% nweb = 75pages at 14%.

30.20% n = 32 12.90% n 21 8.

On the other viewpoints, followed by web=pages contained predominantly positive Parkway, Mountain View, hand, media web pages had the authored by journalists at 2% information and concluded with an California, United States).

Positive 44 36.67% 39greatest proportion 52.00% 65.63% 3 14 of negative 21 (n = 1). There were no negative overriding positive viewpoint were Descriptive statistics were used followed by 0 viewpoints0.00% identified in web categorized as ‘Positive’.

Negative 4 3.33% 4viewpoints at 5%, 5.33% 0 pages 0 to summarize data. Frequency peer-reviewed journals at 3%. authored by radiographers or Balanced 58 48.33% 24 32.00% 4 12.50% 9 42 analyses were performed for Negative Negative viewpoints were not non-radiologist doctors. Those categorical variables.11.67% Neutral 14 8identified among 10.67% 21.88%into the category 9 42 commercial, 7 authors falling Negative viewpoints were those educational, or other sources.

“Other” had the highest proportion Results that displayed a contrary theme Peer-reviewed journals had the of balanced viewpoints at 39.7% toMulryan the positive (see et al.viewpoint Insights into Imaging A (2022) Page 4 of 11the total of13:79 680 Google pages greatest proportion of balanced (n = 27), while journalists had Additional file 1: Appendix 2). relating to AI in medical imaging viewpoints at 48%, while greatest proportion of neutral educational were web identified. pages had the greatest proportion of of neutral at 34.7% (n = 16). See Addit Of these, 561 educational web pages had the viewpoints Balanced and neutral viewpoints at 34.7% (n = 16). See neutral viewpoints at 43%. pages were deemed relevant and greatest proportion file of neutral 1: AppendixAdditional 4.1 for tabulated summary file 1: Appendix 4.1 for (Fig. 2) Webpages categorized as accessible.

Duplicate pages were viewpoints at 43%. There were 130 tabulated summary (Fig. 2).in North Am An identifiable named author was displayed on 93% pages authored ‘Balanced’ listed comparable removed, leaving 248 pages An identifiable author amounts of positive and(n negative = 230) of for web pages, with radiologists responsible fornamed were 130 authored18 neutral expressing 60 There positive, 48 pages balanced, evaluation. displayed on 93% (n = 230) points without giving an38.7% overall (n = 89); journalists represented 20%was in North America expressing 60 (n = 49), of authors negative pages of content. In Europe Forty-three percent (n = 106) of Data Points of web pages, with 4 radiologists positive or negative viewpoint.

Total positive, 48 balanced, 18 neutral (n = 46); doctors working in other specialties reprethese pages expressed the overall were balanced, 9 ofneutral (n =21 89);positive, Webpages categorized as ‘Neutral’ (n=680)responsible for 38.7% and17 4 negative pages content. and 9 neg view would have a positiverepresented journalists4.8% represented 20%authored. of objectively presented information In Europe (n = 49), there were 21 had the g sented 6.9% (n =that 16);AIand radiographers pages The United Kingdom impact on the radiologist and the authors (n = 46); doctors working relating to artificial intelligence positive, 17 balanced, 9 neutral and (ndiscuss = 11). Other authors not falling aforemenest number of9 European authored pages, and radiology department; 3.2% into the in other specialties represented and radiology but did not negative pages authored. The (n = 8) made presented 6.9%(n (n = = 16); how this would impact, tioned be it categories up an theoverall remaining 29.6% 68).and radiographers expressed 9 positive, 10 balanced, 4 neutral and 0 n United Kingdom had the greatest (n=113) viewpoint; 38.2% (n = 95) represented 4.8% (n = 11). negatively or positively, Researchers, onNon the Relevantnegative number ofThe European authored of the rem Relevant and accessible lawyers, and marketing managers were tive opinions (n = 23). distribution a balanced viewpoint Other authors not falling into field of radiology. The fundamental Inaccessiblepresented (n=6) pages, and these expressed 9 amongst those the ‘Other’ category.a(n=248)the aforementioneding andin 15.3% (n = 38) presented pages from positive, Europe10was as follows: categories difference between the ‘Balanced’ balanced, 4 neutralNetherland Duplicates (n=313) neutral viewpoint Fig. 1). the remaining 29.6% and ‘Neutral’ categories isWeb that pages and 0 negative opinions (n =Belgium—5, 23). authored by(see journalists had made the up highest Germany—6, Italy—8, Ireland—4, (n = 68). Researchers, lawyers, balanced webpages explicitly The distribution of the remaining Forty-eight percent (n = 120) of the percentage of overall positive viewpoints (52%, n = 24). way—1, Switzerland—5, Austri and marketing managers were Denmark—1, discussed how aspects of artificial pages from Europe was as follows: relevant pages werepages from openthose in the ‘Other’ intelligence would impact the was followed This by web authoredamongst by radioloCyprus—3, Europe not specified—9.

Netherlands—6, Germany—6, Finally, a access peer-reviewed journals; field of radiology while neutral Italy—8, Ireland—4,Australia—11; Belgium—5, gists (46%, n30.2% = 41)(nand radiographers (45%,category. n = 5). Web cellaneous group including: Israe = 75) were from media webpages did not (see Additional Norway— Posi ve (n=106) sources; 12.9% Balanced (n=95) Neutral (n=38) by journalistsNega ve (n=8)1, Denmark—1, (n = 32) from Web pages authored pages authored by non-radiologist doctors accounted Asia—12; SouthSwitzerland—5, America—2, Africa—2; and Not a file 1: Appendix 2).

Austria—1, commercial websites and 8.5% (n had the highest percentage for the lowest proportion of positive viewpoints (18.8%, Cyprus—3, Europe not specified—9. able—14, expressed 19 positive, 18 balanced, 7 = 21) from educational sources. of overall positive viewpoints Finally, a miscellaneous group Table 1. Summarises allocated (52%,by n =radi24). This was n = 3).search Four percent of web the pages authored tral followed and 2 negative opinions in the pages that Fig. 1 Schematic of google and results summary including: Australia—11; Israel—4; categories of origin and viewpoint by web pages authored by ologists (n = 4) or by those falling into the ‘Other’ cat- authored. This Asia—12; frequency data is presented in Ta South America—2, radiologists (46%, n = 41) and conveyed. The type of media Table 1 Summary of categorization Africa—2; and Not available— egory (n = 3) hadalong negative viewpoints, followed by(45%,with corresponding percentages in Fig. 14, 3. radiographers n = 5). source with the details of of posts by origin with percentage expressed 19 positive, 18 balanced, Web pages authored by nonspecific commercial company

web pages authored by journalists at 2% (n = 1). There Radiologists in North America (n = 42) authore were no negative viewpoints identified in web pages positive, 18 balanced, 3 neutral and 2 negative v Journal Media Commercial authored by radiographers or non-radiologist doctors. points. In Europe, Education radiologists (n = 31) authore Those authors falling into the category “Other” had the positive, 12 balanced, 3 neutral 8.47% and 2 negative v n = 120 48.39% n = 75 30.20% n = 32 12.90% n = 21 highest proportion of balanced viewpoints at 39.7% points. UK radiologists authored four pages expre 44 (n = 27), while 36.67%journalists 39 had the greatest 52.00% proportion 21 65.63% 3 14.29%

Table 1 Summary of categorization of posts by origin with percentage n = 248

Positive Negative

4

3.33%

4

5.33%

0

0.00%

0

0.00%

Balanced

58

48.33%

24

32.00%

4

12.50%

9

42.86%

Neutral

14

11.67%

8

10.67%

7

21.88%

9

42.86%

educational web pages had the greatest proportion of neutral viewpoints at 43%.

of neutral viewpoints at 34.7% (n = 16). See| HPN Additional HOSPITALPROFESSIONALNEWS.IE • AUGUST 2022 file 1: Appendix 4.1 for tabulated summary (Fig. 2).

70

Mulryan et al. Insights into Imaging

(2022) 13:79

Page 5

PEER REVIEW: MEDICAL IMAGING 100 Fig. 2 Number of overall viewpoints presented by each author group.

N = 230

90 7 neutral and 2 negative opinions in the pages that were authored. This frequency data is presented in Table 2 with corresponding percentages in Fig. 3.

Radiologists in North America (n = 42) authored 19 positive, 18 balanced, 3 neutral and 2 negative viewpoints. In Europe, radiologists (n = 31) authored 14 positive, 12 balanced, 3 neutral and 2 negative viewpoints. UK radiologists authored four pages expressing two positive and two balanced perspectives. These data are presented in Table 3 and Fig. 4.

The Google Alerts RSS feed identified 5504 new posts over the 3-week period from 34 search terms. Of the alerts identified, 177 were deemed relevant and accessible. Sixty-five percent (n = 115) of the posts expressed an overall positive viewpoint; 11% (n = 20) a balanced viewpoint; 23% (n = 40) a neutral viewpoint; and Mulryan into Imaging 1% (n = et 2) al. anInsights overall negative viewpoint towards the potential impact of AI on radiology (Fig. 5).

13 80

70

60

32

12

4

27

50

40

16

(2022) 13:79 30

Page 6 of 11

5 1

3

Of the relevant posts, the majority were of media origin (86%, n 41 = 152); peer-reviewed journals 20 An identifiable named author was present on 85% accounted for 8% (n = 14); 4% (nof=viewpoints Table 2 Geographical origin 7) were from commercial websites; (n = 151) of the relevant webpages identified by the and 2.3% (n = 4)Number were from other Positive Negative Neutral Balanced 5 Google Alerts RSS feed. The majority of listed26authors sources. Commercial webpages 24 had the highest percentage of 10 Geographical origin were journalists (66%, n = 100).1 This was followed by overall positive viewpoints (85.7%, North 130 4 18 48 8 commercial authors (12.6%, n 5= 19), radiologists (4%, n = 6).America This was followed by 60 0 media webpages49(67%, n = 21 102), Europe 2 9 17 n = 6), researchers 0 4% (n = 6), 5and doctors working in peer-reviewed journals (35.7%, n UK 23 that fell 9under 0 4 10 other specialties3 3.3% (n = 5). Other authors not falling = 5), and webpages 0 the category ‘other’ (25%, n = 1).

Other 46 19 2 7 18 into the categories represented 9.9% (n = 15) of the conRadiologist Journalist Non-Radiologist Radiographers Other Forums, educational webpages, Doctor tributors. This is illustrated in Fig. 4. Marketing manand blogs composed the ‘other’ category. Peer-reviewed journals agers, media editors, and students were amongst those had the greatest percentage of Posi ve Nega ve Balanced Neutral balanced viewpoints webpages had the(21.4%, highest percentage of overall positive that made up the ‘other’ category. Webpages with a Fig. 2 Number of overall viewpoints presented by each author group.

N = 230 n = 3), followed by those that of overviewpoints (85.7%, n= 6). This (2022) was 13:79 followed by media commercial author had the highest percentagePage Mulryan al.category Insights into Imaging 6 of 11 fell underet the ‘other’ webpages n =article 102), peer-reviewed journals (35.7%, all positive viewpoints 84% (n = 16). This was followed (25%, n = 1).(67%, One (7%)

n = 5), and webpages that fell under the category ‘other’ two positive and two balanced perspectives. These data viewpoint; 23% (n = 40) a neutral viewpoint; and (25%, = 1). Forums, Table 2 n Geographical origin of educational webpages, and blogs Table 3 Geographical origin of are presented Table 3 and Fig. 4. (n = 2) an overall negativeradiologist viewpoint towards the po viewpoints and viewpoint composed the ‘other’ category.in Peer-reviewed jourThe Google Alerts RSS feed identified 5504 new posts tial impact AI on radiology (Fig. 5).

An identifiable named author was present on 85% Table 3 Geographical origin of radiologist and viewpoint Table 2 Geographical origin of viewpoints nals had the greatest percentage of balanced viewpoints over the 3-week period from 34 search terms.

Of the Ofrelevant the relevant posts, the majority were of media (n = 151) of the webpages identified by the (21.4%, n = 3), Number followed byidentified, thoseNegative that177 fellwere under the catOrigin Number Positive Negative Neutral Balanced Positive Neutral Balanced alerts deemed relevant and accesgin (86%, n = 152); peer-reviewed journals accounte Google Alerts RSS feed. The majority of listed authors egory ‘other’ (25%, nsible. = 1). Sixty-five One (7%)percent article(nfrom a peer= 115) of the posts expressed 42 8% (n =19 4%100). (n were commercial Geographical origin North 2 = 7) 3 from 18 wereAmerica journalists (66%,14); n= This was followed by web reviewed journal had an overall negative viewpoint, an overall positive viewpoint; 11% (n = 20) a balanced and 2.3% (n = 4) were from other sources. Comme North America 130 60 4 18 48 3 12 (4%, commercial 31 authors 14 (12.6%, 2n = 19), radiologists as did one (0.66%) of the media webpages. No negative Europe Europe 49 21 2 9 17 4 2 (n = 6),0 and doctors 0 2 n = 6), researchers 4% working in viewpoints were identified in the commercial category. UK UK 23 9 0 4 10 Other 12 3 (n = 5).1Other authors 3 5 falling other specialties 3.3% not See Table 4 for summary.

Other 46 19 2 7 18 into the categories represented 9.9% (n = 15) of the contributors. This is illustrated in Fig. 4. Marketing managers, media editors, and students were amongst those 50% | HOSPITALPROFESSIONALNEWS.IE AUGUST 2022 • HPN webpages had the highest percentage of overall positive that made up the ‘other’ category. Webpages with a 46%

as did one (0.66%) of the media webpages. No negative viewpoints were identified in the commercial category.

See Table 4 for summary.

Fig. 3 Geographical origin of viewpoint (percentage)

31

14

2

3

12

4

2

0

0

2

Other

12

3

1

3 71

5

50% 46% 45%

from a peerreviewed journal had an overall negative viewpoint, as did one (0.66%) of the media webpages. No negative viewpoints were identified in the commercial category. See Table 4 for summary.

Europe UK

40% 35%

43%

43%

41% 39%

39% 37% 35%

An identifiable named author 30% was present on 85% (n = 151) of the relevant webpages identified by the Google Alerts RSS feed. The majority of listed 25% authors were journalists (66%, n = 100). This was followed by commercial authors (12.6%, 18% 20% 17% n = 19), radiologists (4%, n = 6), researchers 4% (n = 6), 15% 14% and doctors working in other 15% specialties 3.3% (n = 5). Other authors not falling into the categories represented 9.9% (n 10% = 15) of the contributors. This is illustrated in Fig. 4. Marketing 4% managers, media editors, 4% 5% 3% and students were amongst those that made up the ‘other’ 0% category. Webpages with a 0% commercial author had the Posi ve Nega ve Neutral Balanced highest percentage of overall positive viewpoints 84% (n = 16).

This was followed by webpages North America Europe UK Other authored by journalists 64% (n = Fig. 3 Geographical origin of viewpoint (percentage) 64); nonradiologist doctors 60% (n = 3); ‘other’ authors 53% (n to provide the radiology community substantially since the early = 8); and radiologists 50% (n = webpage authored by a journalist 2000’s with the advent of machine with information on AI and a further 3). Researchers had the greatest (1%) and one authored by an learning (ML) and deep learning study by the ESR demonstrated percentage of balanced viewpoints author in the ‘other’ category (7%) 19 The number of AI (DL) algorithms. that there is a demand amongst the 67% (n = 4), while radiologists had had overall negative viewpoints. exhibitors at the annual meeting radiological community to integrate the greatest percentage of neutral This data summarized and of the Radiological Society of AI education into radiology viewpoints 33% (n = 2). One tabulated can be seen in Additional North America (RSNA) and the curricula and training programs file 1: Appendix 4.2 (Fig. 6).

European Congress of Radiology including issues related to ethics (ECR) has tripled from 2017 to legislation and data management.24 Discussion 2019.20, 21 Since 2016, the US Food The aim of the present paper was Opinions and forecasts concerning and Drugs administration (FDA) use internet activity to determine the role and impact of AI on has approved 64 AI ML-based current opinion on whether AI medical imaging have exploded medical imaging technologies with is a threat or opportunity to the in last number of years primarily 21 of these specializing in the field field as this will have impact on due to recent advancements in of Radiology.22 In Europe, 240 AI/ recruitment and resource allocation AI products for radiology. These ML devices have been approved to radiology. viewpoints can be positive, over the 2015–2020 period by We observed that a wide the Conformité Européene (CE) yan et al. Insights into Imaging (2022) 13:79 negative, balanced, or neutral in Page 7 of 11 diversity of commentators were their content. AI in medical imaging with 53% for use in radiology.23 engaged dialog pertaining to AI was first mentioned in the literature In 2019, The European Society of in radiology ranging from those Radiology published a white paper in the 1950’s and has evolved with professional and academic backgrounds to those with Fig. 4 Geographical origin and individual and organizational radiologist viewpoint percentage interests. While these authors predictably included healthcare Percentage professionals, there was also a 60% significant representation from 50% 50% those with media and commercial 45% 45% 50% backgrounds. Opinions on AI in 43% 42% 39% radiology were therefore gathered 40% from authors with a wide variety of occupations and backgrounds 25% 25% 30% including radiologists, nonradiology physicians, journalists, 20% 10% researchers, radiographers, 8% 7% 10% 5% 6% commercial managers, physicists, 0% 0% lawyers, computer scientist, data 0% officers, engineers’, students, and Posi ve Nega ve Neutral Balanced pharmacists. There was a relatively equal division of authorship North America Europe UK Other between North America and . 4 Geographical origin and radiologist viewpoint percentage HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

0%

10%

0%

Posi ve0%

72

5% 6%

Nega ve Posi ve

8% 0% 0%

Europe

UK

0%

Europe

Balanced

Neutral

Other

North America

Fig. 4 Geographical origin and radiologist viewpoint percentage

10%

Neutral

Nega ve

North America

7%

UK

Balanced

Other

Fig. 4 Geographical origin and radiologist viewpoint percentage

PEER REVIEW: MEDICAL IMAGING

Total Data Points Total Data Points (n=5,504)

Fig. 5 Schematic of live Google Alert RSS feed and results summary

(n=5,504)

Non Relevant (n=5,069) Non Relevant (n=5,069) Relevant & Accessible (n=177) Relevant & Accessible (n=177) Duplicates (n=258) Duplicates (n=258)

Posi ve (n=115)

Posi ve Balanced (n=115) (n=20) Balanced (n=20) Neutral (n=40) Neutral (n=40) Nega ve (n=2) Nega ve (n=2)

5 Schematic of live Google Alert RSS feed and results summary Fig. 5 Schematic of liveFig. Google Alert RSS feed and results summary

Table 4 Summary of categorization of posts by origin with percentage Table 4 Summary of categorization of posts by origin with percentage

Table 4 Summary of categorization of posts by origin with percentage n = 177

n = 177

Journal

Journal 14

7.91%

Positive

5 Negative

Negative

14

Media

Media

7.91%

152

85.88%

152

85.88%

35.71% 1

1027.14%

1 Balanced

7.14% 3

Balanced

3 Neutral

Neutral

5

Positive

Commercial

Commercial

7

3.95%

102

7

67.11%

3.95%

67.11% 1

60.66%

1 21.43%

0.66% 13

21.43% 5

1335.71%

35.71%

36

5

35.71%

Other

Other 4

2.

1

25

25.00% 1

25

6

4

85.71%

2.26%

85.71% 0

1 0.00%

08.55%

0.00% 0

1 0.00%

25.00% 1

25

36 8.55%

23.68% 0

1 0.00%

14.29% 1

1 25.00%

25

23.68%

1

14.29%

1

25.00%

by webpages authored by journalists 64% (n = 64); non- authored by a journalist (1%) and one authored b in the ‘other’ (7%) hadbyoverall radiologist doctors 64% 60% (n(n==64); 3); non‘other’ authors 53% authored by a author journalist (1%) andcategory one authored an neg by webpages authored by journalists viewpoints.

ThisA (7%) data tabulated ca = 8); 50% (n = 3). had recentsummarized editorial in the and In the long-term I think Europe. This distribution(n also andRadiographers author in thefuture, ‘other’ category had overall negative radiologist doctorswas 60% (n =radiologists 3); ‘other’expressed authors 53%Researchers Radiological Society of North demonstrated among radiologist that computers will seen take over the opinion that utilizing AI in Additional file 1: Appendix 4.2 (Fig. 6). the greatestthepercentage of balanced viewpoints 67% viewpoints.

This datafrom summarized tabulated (n = 8); pages and included radiologists (n = 3).could: Researchers had work Americaand (RSNA) highlightedcan a be authored in this 50%algorithms of image interpretation (n = 4), while radiologists had the greatest percentnumber of high-profile negative study.

This professional and humans, just as computers or seen in Additional file 1: Appendix 4.2 (Fig. 6). the greatest percentage of balanced viewpoints 67% ultimately lead to a reduction viewpoints made a number of geographic diversity of authors age of neutral viewpoints 33% (n = 2). One webpage machines have taken over so many

(n = 4),a more whilecomplete radiologists had greatest in thethe radiation exposurepercentwhile provides and maintaining the high quality of international sample of opinions on age of neutral viewpoints 33% (n = 2). One webpage the impact of AI on radiology.

medical images

Radiologists repeatedly expressed the opinion that inclusion of AI algorithms could help with labour intensive tasks, improve efficiency and workflow. They also opined against the potential of AI replacing radiologists. Numerous studies in the literature also argued against AI replacing radiologists.25, 26 An example of two comments made by radiologists included:

And

and that radiographers would be vital in building quality imaging biobanks for AI data bases.

Interestingly, radiographers also wrote that AI should be integrated into the medical radiation practice curriculum and there should be more emphasis on radiomics. Furthermore, radiographers expressed the belief that emotional intelligence not artificial intelligence is the cornerstone of all patient care and while the concept of ‘will a robot take my job’ may be a hot topic, they believe that patient’s will not accept their radiographs being taken by a robotic device.

Radiologists, the physicians who were on the forefront of the digital era in medicine, can now guide the introduction of AI in healthcare The time to work for and with AI in radiology is now

This study identified a total of ten negative viewpoints which included comments from radiologists—5, a lawyer— 1, a journalist—1 and a neuroscience Ph.D. student— 1.

Examples include:

The higher efficiency provided by AI will allow radiologists to perform more value-added tasks, becoming more visible to patients and playing a vital role in multidisciplinary clinical teams

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

tasks in our lives. The question is, how quickly will this happen?

And

Radiologists know that supporting research into AI and advocating for its adoption in clinical settings could diminish their employment opportunities and reduce respect for their profession. This provides an incentive to oppose AI in various ways And An artificially intelligent computer program can now diagnose skin cancer more accurately than a board-certified dermatologist and better yet, the program can do it faster and more efficiently And A.I. is replacing doctors in fields such as interpreting X-rays and scans, performing diagnoses of patients’ symptoms, in what can be described as a ‘consulting physician’ basis

years ago relating to the impact of AI on radiologists.27 This included an AI pioneer who was recently awarded the Association for Computing Machinery Turing Award, “We should stop training radiologists now”.27 Secondly a venture capitalist, Vinod Khsla proclaimed in 2017 ‘that the role of the radiologist will be obsolete in 5 years’ and replaced with ‘sophisticated algorithms’28 and furthermore an American ‘Affordable Care’ architect remarked at the 2016 American College of Radiology Annual meeting that radiologists will be replaced by computer technology in 4–5 years29 and that ‘in a few years there may be no specialty called radiology’.30

Interestingly, many of the opinions regarding timeframes during which AI were predicted to replace radiologists have already expired with a relatively minor uptake of AI in imaging interpretation and without signs of AI replacing radiologists at present. These

Mulryan et al. Insights into Imaging

(2022) 13:79

Page

73 Fig. 6 Number of overall viewpoints presented by each author group.

N = 151

120

100

27 80

8 1 60

40 64

20

2

Journalist

4 2

16

2 3

0

1 1 4 1 Researcher

1

Radiologist Posi ve

Commercial Nega ve

Balanced

2 3

8

Non-radiologist doctor

Other

1

Neutral

Fig. 6 Number of overall viewpoints presented by each author group. N = 151

information found in social media minimize this by using two senior Radiologists were found to be controversial viewpoints have news feeds, Twitter, and other potential to grab headlines but are radiologists as the assessors. the most common author group, withassess 21 of thesesites. specializing in the field that of Radiology Discussionmaking up 38.5% of all identifiable We did not quantitatively There is also potential a not without potential for negative 3-week alert have periodbeen may be AI/ML devices approved impact on the future of radiology Opinions and forecasts the role and impact of In readability of posts.

We Europe, only used240 single authors.

Theseconcerning webpages were biased by and media events and particularly on recruitment onenumber search engine and predominantly the 2015–2020 period bynews the Conformité Européene AI on medical imaging peer-reviewed have exploded in last of ‘Google’ that occurred during that time. of future radiologists, given that limited to just the English language journal papers and media articles. with 53% for use in radiology [23].

In 2019, The Euro years primarily due to recent advancements in AI prodstudies have shown that medical and to the first two pages of These findings highlight that In conclusion, authors of 43% of students are less likely toucts consider Society of Radiology published a white paper to pr for radiology.

These viewpoints canin be positive, negeach search term, a strategy radiologists are actively involved all pages evaluated expressed the pursuing a career in radiology following previous publications both AI-related research and online ative, balanced, or neutral in their content. AI in medical the radiology community overall opinionwith that AIinformation would have on AI because of the apparent threat of and backed by behavioral studies discussions relating to AI and the aby positive impact on the radiologist a further study the ESR demonstrated that ther first mentioned in the literature in the 1950’s AI to the specialty.8–10, 31 imaging wasfield which have indicated that 95% of of radiology. Radiologists and the radiology department; demand amongst the radiological community to users choose websites listed on have been encouraged to play and has evolved substantially since the early 2000’s with 38.3% presented a balanced This study found that the the first page of results, leaving role inlearning the development viewpoint; presented grate AI education into 15.3% radiology curricula and tra of active machine (ML) and deep learning overwhelming majority ofthe webadvent an only 5% reviewing results on any of applications of AI in medical a neutral viewpoint; and 3.2% pages assessed had favourable issues related to ethics legisl (DL) algorithms Theappropriate number of AI subsequent exhibitorspages. at programs including imaging[19]. to ensure presented a negative viewpoint. viewpoints with very few negative and data management [24].

The aimthat of the the present p implementation and validation the annual meeting of the Radiological Society of North We have demonstrated viewpoints identified. This finding We acknowledge that the list of 26, 33 of AI in clinical practice.

In Congress overall viewtopresented online is a is consistent with a recent social was use internet activity determine current opinio America (RSNA) and the European of Radiolsearch terms in Additional file 1: 2017, The American College of positive one that AI will benefit the media-based study showing Appendix 1 is not exhaustive and whether AI is a threat or opportunity to the field a ogy (ECR) has tripled from 2017 to 2019 [20, 21]. Since specialty. We should be excited Radiology established The Data that discussions around AI and is just a representative sample of and look forward to advancements Science partly with this 2016, the US FoodInstitute and Drugs administration (FDA) has will have impact on recruitment and resource alloc radiology were astoundingly actual terms that may be used in this technology which has the in mind.34 medical imagingthe positive, with an increasing toinradiology. approved 64purpose AI ML-based technologies when searching for AI medical potential to improve accuracy of frequency of positive discussions imaging but by using a broad The main limitation of this diagnosis in diagnostic radiology, identified over a 1-year period.32 range of terms and studying the study was the use of subjective reduce errors and improve Taken together, these findings first two pages of findings that assessment to qualify information efficiency in dealing with rapidly suggest a shift in opinion from these search results would yield into positive, negative, neutral, increasing workloads. a once negative view to a more the most relevant information. The and balanced. This introduces positive one.

References available on request RSS feed was used as a surrogate potential for observer bias in for incident information and may determining the overall viewpoint Of the webpages identified not be wholly representative of of posts, but it was attempted to using the Google search engine,

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

74

PEER REVIEW: CARDIOLOGY

Deactivation of Implantable Cardioverter Defibrillators in end-of-life situations – more progress needed Lack of discussion around ICD deactivation and subsequent shock therapy in end of life situations is a source of frustration for family members, can be distressing for them, the patient and health care providers.

When should discussion happen?

Written by Mr Paul Nolan, Clinical Lecturer & Cardiac Physiologist, Dept of Health and Nutritional Sciences, Atlantic Technological University

Introduction Implantable Cardioverter Defibrillators (ICDs) are a standard therapy to prevent sudden arrhythmic cardiac death. ICDs are proven to reduce mortality in both patients with documented ventricular arrhythmias secondary prevention, and those at risk of such an arrhythmia - primary prevention. An ICD monitors a patient’s heart rhythm and if they develop ventricular tachycardia, of a predetermined rate, or ventricular fibrillation, for typically 30 beats, the device will treat the arrhythmia. This is done in two ways, one a painless fast pacing therapy, called anti-tachycardia pacing (ATP), the other being defibrillation or “shock” therapy. Many of these devices are implanted in patients with heart failure and some of those patients may be implanted with a device which also improves the pumping efficiency of the heart, whilst also having the ability to defibrillate. These devices are referred to as Cardiac Resynchronisation Therapy devices or CRT. The batteries on these devices typically last seven to ten and one of the issues with ICDs is that patient life goals may change, particularly in the setting of the diagnosis of a terminal illness.

In this setting a patient may no longer wish to receive painful shock therapy, which may prolong duration, but not quality of life.

Given that the number of ICD implants in Ireland is increasing,

at approximately 1000 implants per year, and the duration they may remain implanted means that the number of patients with a terminal illness and an implanted defibrillator is increasing.

Despite the fact that consensus documents from the European Heart Rhythm Association1 and the Heart Rhythm Society2 in the US underline the fact that it is ethical, deactivation of shock therapy in ICDs and CRTs remains an issue, with a number of barriers resulting in suboptimal care to patients in end of life situations.

Why is this still important?

Previous studies have shown that in ICD patients in end of life situations, with a Do Not Resuscitate Order (DNR), over half still had the shock function of their device programmed on.

Nearly one quarter of patients had a shock in the last hour of life with over half of these receiving multiple shocks.3 More recent data from 2019 shows similar results with only one-third of patients having the shock function of their device deactivated and 20% of patients having at least one shock within a month of their death.4 It would appear that the consensus documents have not had a significant impact on deactivation rates. A Swedish study5 noted that there was no significant increase in rates of deactivation, likely related to the fact that two-thirds of deaths happened on non-cardiology wards.

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

The Heart Rhythm Society Consensus document states that discussion around the management of ICDs at end of life should be included as part of the pre-implant discussion but this is only happening in 4% of centres surveyed across Europe.6 One of factors leading to this maybe a healthcare providers perception that such discussion might influence a patient to decline the implant, although the majority of a group of patients interviewed would prefer this to be part of a discussion.7 What we do know is that healthcare providers within cardiology recognise the importance of having the discussion, but that how we currently do it is sub-optimal.

There is no consistent approach and that such conversations either do not happen, or happen late in the patient journey.7, 8 One might assume that advance care plans would be a tool which would naturally lead to a discussion around ICD shock deactivation, however the evidence suggests it is not. A systematic review of the literature review showed ICD deactivation was explicitly mentioned in only 1% of advanced directives,9 this is sobering considering that only 12% of heart failure patients even had documented advanced directives.10 The recent COVID-19 pandemic introduced another level of complexity to this issue but also crystalised the importance of when these discussions should happen.11 It is clear that it is best that they happen early in the patient’s ICD pathway, preferably before implant. It should certainly happen when the patient is clinically stable, should be an ongoing in nature but there are also clear identified triggers for discussion which will be outlined below. The requirement for the conversation to be ongoing is highlighted by the fact that

patients remember the benefits of ICD therapy as outlined to them pre-implant, but not issues around end-of-life care.7 What do Healthcare Professionals know and believe?

A 2009 survey of over five hundred US based cardiologists, electrophysiologists, internists and geriatricians, presented with 5 end of life case vignettes, found significantly more would discuss a DNR, rather than ICD deactivation, in 4 out of five cases being 20-30% higher. Despite the 2010 guidance, a 2021 Canadian survey showed that 24% of nurses, 10% of fellows and 7% of cardiologists still believed shock deactivation was unethical.13 Predictors of such beliefs were sociocultural, including profession, region of training and spiritual beliefs.

Despite clinicians stating that they would discuss ICD shock deactivation in certain circumstances, such as when signing a DNR, there is also an admission amongst noncardiology professionals that lack of knowledge can be a barrier.8 Other reasons quoted which result in clinicians rarely explicitly discussing ICD shock deactivation includes personal discomfort, lack of experience, time constraints and lack of guidance documentation.14 Given that 11% of the population over 50 years of age in Ireland suffer from two or more chronic diseases and many of our patients see different teams, and multiple members within the one team, as well as their own General Practitioner, the question of who should partake in discussions around ICD shock deactivation can be a difficult one. With potentially fragmented care, there can be a feeling that the responsibility lies elsewhere.8 In the UK, data would suggest that Cardiologists often focus on getting the patient better, and this perhaps results in the conversation not being had early enough. Cardiac Physiologists, who follow-up patients with devices, have opportunity to discuss but are reluctant because of lack of knowledge or confidence. In general terms, Heart Failure Nurses, feel they are already having those

75 end of life conversations but perhaps are not explicitly talking about ICD deactivation.7 The truth is that all teams, involved in the care of the patient, particularly at end of life, need to be aware of the issue of ICD shock deactivation and have the knowledge to initiate the discussion and empower the patient decision.

What do our patients know and believe?

For patients to be part of an informed discussion, they need a good understanding of

their device and the end of life issues. A 2014 study showed that over 25% of patients believed deactivation equated to euthanasia, the device had to be surgically removed or that it could not be reactivated if the patient improved15. Disappointingly, five years later, the percentage of patients with those misconceptions had increased to nearly 40%.16 Unsurprisingly the data around patient perceptions and attitudes

Ask about Experiences with Device (Shocks, ATP, etc.)

Explore the Meaning of the Device to the Patient

Address Patient Understanding of Options Concerning Device at End-of-Life

is varied, some feeling that such a discussions would give them a sense of control, but others feeling it would raise concerns.7 Data would suggest that up to 40% of our ICD patients do not wish to have a discussion around end of life issues, with no significant difference between those with and without heart failure.17 However it also informs us that those who have experienced shocks, have high anxiety levels or concerns about their device are more likely to have these discussions. It has also been shown that past discussion around disease progression were a predictor of openness to discuss ICD deactivation.18 The data is also telling us that 60% of our patients do want to have such conversations.

A really interesting paper from Stoevelaar in 2020 showed the nuances of patients’ knowledge and attitudes to the issues. Some were unaware it was an option, other were uncertain as to when it would be appropriate and that relatives would play an important role in the conversation. Most would want to get information from their healthcare provider, but not necessarily their cardiologist, feeling others might have more time. Some felt documenting their wishes would help but others had concerns about changing their mind as people adapt to their situations.19 What the evidence tells us is that we should have ongoing conversations with our patients, tailoring the information to their needs, their current situation and we should include close relatives.

Assess Readiness to Discuss End-of-Life Device Issues, including Deactivation Fig 1 Issues to discuss surounding ICD deactivation

What else can we do better?

The mix of patients’ views on ICD therapy at the end of life supports the need for more open communication and ongoing education on this topic for both patients and providers. A number of projects have aimed at improving either deactivation rates or documentation of patients wishes regarding same.

These have all included staff education, changes to end-of-life care and/or DNR documentation and other tools such as reminder posters for staff.20, 21 In one setting in the UK, education was targeted at all specialities and also on wards where missed deactivation opportunities had been identified by audit.22 What are the practicalities?

It is clear that discussion with patients need to include education around their device and end of life issues and that these need to be ongoing and developing, aligned to patients’ current disease trajectory. Despite that, there are some clear events which should trigger such a discussion.

These would include, significant disease progression, repeated hospitalisations, refractory symptoms, deterioration in quality of life or if a patient or relative requests same.

There are a number of issues to explore prior to discussion, in an effort to overcome the “guardian angel” view of the ICD. The evidence suggests it is desireable to include close relatives as part of the discussion if the patient consents. These include patients experience of their device and therapies, the meaning of the device to them, their understanding of the option regarding their device at end of life in an effort to assess their readiness to have the discussion (Fig 1).

When the discussion moves specifically to deactivation of shock therapy, a number of points must be emphasised, which address some of the misconceptions highlighted in the literature. We first must be careful about language and avoid using phrases such as “switching off the ICD”, rather we should state that we are turning off potentially painful shocks. We should ensure our patients and their close relations have a clear understanding of the deactivation

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

76

PEER REVIEW: CARDIOLOGY procedure. Firstly that this does no hasten death but simply allows for a peaceful, natural death.

Also important is the fact that deactivation is painless, similar to the procedure for a routine device check. It should also be made clear that shock therapy can be turned back on if the patients condition improves or they change their mind, and that the care they are receiving won’t change (Fig 2).

Once the decision has been made, contact should be made with the patient’s current followup centre. Most centres in Ireland have a policy and procedure for deactivating an ICD in end of life settings and will endeavour to facilitate same. This will generally involve some form of documentation, such as clear evidence of a shared decision in the notes, and/or a completed deactivation request form. Whilst it is preferable for this to be

Clear understanding Deactivation is painless Only shock is disabled Does not hasten death - allows for peaceful death

carried out in a planned manner, during a hospital admission or visit, this is not always possible, and whilst challenging, centres endeavour to support deactivation in the community. This may require the GP or a member of the primary team, for example palliative care, to meet a Cardiac Physiologist at the patient’s home.

In emergency situations where the device cannot be programmed in a timely manner a strong donut shaped magnet can be placed over the device. This disables shock therapy for as long as the magnet is over the device.

Conclusion The consensus documents from the Heart Rhythm Society and the European Heart Rhythm Society are clear that deactivation of the shock function of the ICD is appropriate and ethical in end of life situations. What is clear is that we are falling short in delivering this important aspect of care to our patients.

We need to increase awareness of the issues and the practicalities around management of ICDs in end of life situations to all our

Will get same care from team Can be reactivated as easily

Fig 2 Key Points to highlight in ICD Deactivation Discussion

colleagues, across all relevant specialities. We need to ensure that patients are educated around their device function and their potential options in an end of life situation. We need the conversation with patients, and their close relatives, to be ongoing, ideally prior to implant, tailored to our patients needs at that time and should develop over time.

In an Irish setting we need to develop an education programme for all relevant healthcare providers, especially those outside of cardiology, with clear referral pathways for timely deactivation.

The Irish Heart Foundation had, prior to COVID, put a working group together to progress these issues and one hopes that this process can be reinvigorated.

There is good data that local quality improvement projects can also have a significant impact on appropriate discussions, documentation and deactivation rates in end of life settings. It is over ten years since the consensus documents but as a healthcare community we have some progress to make on this issue.

About the author Paul Nolan is a Clinical Lecturer on the new MSc in Clinical Measurement Physiology in Atlantic Technological University and is a Cardiac Physiologist.

He is a Certified Cardiac Device Specialist by the Heart Rhythm Society and the European Heart Rhythm Association.

References available on request

News - Significant Developments in Women’s Health Minister for Health Stephen Donnelly has launched the National Women and Infants Health Programme’s Annual Report for 2021.

The National Women and Infants Health Programme was established in the HSE to lead the management, organisation and delivery of maternity, gynaecology and neonatal services, strengthening such services by bringing together work that is currently undertaken across primary, community and acute care. The Programme acts as a single central authority on maternity care and as a reference point and resource for women’s health issues within the HSE, providing for much needed coordinated oversight.

Minister Donnelly said, “Promoting Women’s Health is a priority for me and the government. The investment and developments we are seeing in women’s health demonstrate that this area is now receiving the focus and support it needs to provide timely and effective services to the women of Ireland.

“The National Women’s and Infants Health Programme has undertaken very important work in the development of women’s health services since its establishment in 2017, particularly in maternity services, but also in the areas of gynaecology, fertility and sexual assault treatment services. The effect of that work is reflected in this Report where we can clearly see the benefits for the women and families accessing health services.

“Women have more choice when it comes to maternity care in 2021, with 24% of pregnant women booked on the Supported Care Pathway.

More women could also access more services closer to home, with additional community midwifery services and Early Transfer Home services becoming available.

“We also saw brand new services coming online, with additional ambulatory gynaecology clinics, as well as the establishment of specialised endometrial and menopause clinics in Tallaght and the NMH. “2021 was a challenging year for the HSE, with the ongoing COVID-19 pandemic and the cyber-attack on HSE systems, but this Report shows that the Programme continued to make significant progress in 2021.

“In Budget 2022, I secured additional funding of almost ¤9 million for the implementation of the National Maternity Strategy. This will ensure the continued implementation of the Strategy into 2022 and beyond, in line with the revised Implementation Plan. As Minister, I have made it clear that I am determined to improve access, affordability and quality of women’s health services and as part of that, I want to ensure the ongoing development of safe, trusted, standardised, maternity care which supports better outcomes for women.”

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

If you would like to hear more from MSD and keep up-to-date with the most useful clinical content across all our therapy areas then register now for MSDConnect.ie

MSDCONNECT

➜ Scan the QR code to register an account with MSDConnect.ie ➜ Registering only takes two minutes ➜ Discover videos and product information in our portal that will help to support you and keep you informed

BRIDION® 100 MG/ML SOLUTION FOR INJECTION Sugammadex ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics (SmPC) before prescribing PRESENTATION Vials of 200mg (2 ml) or 500mg (5 ml). INDICATIONS Reversal of rocuronium (ROC) or vecuronium (VEC) induced neuromuscular (NM) block in adults. For routine reversal of ROC-induced block in children and adolescents aged 2 to 17 years. DOSAGE AND ADMINISTRATION I.V. as a single bolus injection administered rapidly (within 10 seconds), into an existing I.V. line, by/under the supervision of an anaesthetist. Use appropriate technique to monitor recovery of NM block. Dose depends on the level of block to be reversed, not the anaesthetic regimen. Adults: Routine reversal following ROC- or VEC-induced block: • 4 mg/kg if recovery has reached at least 1 2 post-tetanic counts (PTC). Median recovery time (T4/T1 = 0.9) ≅ 3 minutes. • 2 mg/kg if recovery has occurred up to at least T2 following ROC- or VEC-induced block. Median recovery time (T4/T1 = 0.9) ≅ 2 minutes. Median recovery time (T4/T1= 0.9) is slightly faster with ROC- than VEC-induced block. Immediate reversal of ROC-induced block: 16 mg/kg. Median recovery time (T4/T1 = 0.9) ≅ 1.5 minutes when 16 mg/kg is given 3 minutes after a bolus dose of 1.2 mg/kg ROC. Not recommended for immediate reversal of VEC-induced block. Re administration of sugammadex: For post-operative recurrence of block after an initial dose of 2 mg/kg or 4 mg/kg, repeat dose of 4 mg/kg is recommended. Following a second dose of sugammadex, monitor the patient closely to ascertain sustained return of neuromuscular function. Re-administration of ROC or VEC after sugammadex: Up to 4 mg/kg Sugammadex a waiting time of 5 minutes for re-use of 1.2 mg/kg ROC; 4 hours waiting time for re-use of 0.6 mg/kg ROC or 0.1 mg/kg VEC. With ROC onset of NM block may be prolonged and duration of NM block may shortened. After immediate reversal, 16 mg/kg sugammadex, a waiting time of 24 hours is recommended. See SPC for patients with mild or moderate renal impairment. Special populations: Renal impairment: For mild and moderate renal impairment use adult dose. Not recommended in severe renal impairment (including patients requiring dialysis). Elderly: Use adult dose although recovery times are slower. Obese: In obese patients, including morbidly obese patients (body mass index ≥ 40 kg/m2), adult dose based on actual body weight. Hepatic impairment: Caution in patients with severe hepatic impairment, or impairment with coagulopathy. Children and adolescents (2-17 years): Bridion 100 mg/ml may be diluted to 10 mg/ml to increase the accuracy of dosing in the paediatric population. Routine reversal: A dose of 4 mg/kg sugammadex is recommended for reversal of rocuronium induced blockade if recovery has reached at least 1-2 PTC. A dose of 2 mg/kg is recommended for reversal of rocuronium induced blockade at reappearance of T2. Immediate reversal: Immediate reversal in children and adolescents has not been investigated.

Term newborn infants and infants: Not recommended. CONTRA-INDICATIONS Hypersensitivity to sugammadex or to any excipients. PRECAUTIONS AND WARNINGS Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored following reversal of block.

Should block reoccur following extubation, adequate ventilation should be provided. The use of lower than recommended doses may lead to an increased risk of neuromuscular blockade after an initial reversal and is not recommended. Caution should be exercised when considering the use of sugammadex in patients receiving anticoagulation for a pre-existing or co-morbid condition. An increased risk of bleeding cannot be excluded in patients with hereditary vitamin K dependent clotting factor deficiencies; with pre-existing coagulopathies; on coumarin derivatives and at an INR above 3.5; using coagulants who receive a dose of 16mg/kg sugammadex. If re administration of ROC or VEC is required in patients with mild or moderate renal impairment after routine sugammadex reversal a waiting time for re-use of 0.6 mg/kg ROC or 0.1 mg/kg VEC should be 24 hours. If a shorter waiting time is required, the ROC dose for a new NM blockade should be 1.2 mg/kg within 30 minutes after Sugammadex administration.

For re-administration of ROC or VEC after immediate reversal a waiting time of 24 hours is recommended. If neuromuscular block is required before the recommended waiting time has passed, a nonsteroidal neuromuscular blocking agent should be used. The use in patients with severe renal impairment is not recommended including those requiring dialysis. If neuromuscular block is reversed, while anaesthesia is continued, additional doses of anaesthetic and/or opioid should be given as clinically indicated. Marked bradycardia with cardiac arrest have been observed within minutes after administration, closely monitor patients for haemodynamic changes during and after reversal. Treat with anti-cholinergic agents such as atropine if clinically significant bradycardia observed.Sugammadex has not been investigated in patients receiving ROC or VEC in the ICU setting.

Do not use sugammadex to reverse block induced by nonsteroidal blockers such as succinylcholine or benzylisoquinolinium compounds, or steroidal blockers other than ROC or VEC. Conditions associated with prolonged circulation time such as cardiovascular disease, old age, or oedematous state may cause longer recovery times. Be prepared for possible drug hypersensitivity reactions. This medicinal product contains up to 9.7 mg sodium per ml, equivalent to 0.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult. OVERDOSE No dose related adverse events nor serious adverse events were reported. Sugammadex can be removed using haemodialysis with a high flux filter. INTERACTIONS Toremifene and fusidic acid may displace rocuronium or vecuronium from sugammadex and delay recovery (no clinically relevant capturing interactions are expected). Interaction of sugammadex with hormonal contraceptives may lead to a decrease in progesterone exposure equivalent to one missed daily dose of oral contraceptive (no displacement interactions are expected). In general sugammadex does not interfere with laboratory tests, with the possible exception of the serum progesterone assay where interference is observed at sugammadex plasma concentrations of 100 µg/ml plasma. In a study doses of 4 mg/kg and 16 mg/kg sugammadex resulted in maximum mean prolongations of the activated partial thromboplastin time by 17 and 22% respectively and prothrombin time by 11% and 22% respectively. These were of short duration (≤ 30 minutes). In in vitro experiments pharmacodynamic interaction was noted with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran. PREGNANCY AND LACTATION Pregnancy and Lactation: Caution in pregnant women. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sugammadex therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. The effects on human fertility have not been investigated. SIDE EFFECTS Refer to SmPC for complete information on side effects Common (≥ 1/100 to < 1/10): Anaesthetic complications including movement of limbs or body or coughing during anaesthesia, grimacing, or suckling on the endotracheal tube, airway complication of anaesthesia, procedural hypertension and procedural complication.

Uncommon (≥ 1/1,000 to < 1/100): Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers. Other less common and rarely reported side effects are listed in the SmPC. In clinical studies with subjects treated with rocuronium or vecuronium, where sugammadex was administered using a dose labelled for the depth of neuromuscular blockade, an incidence of 0.2% was observed for recurrence of neuromuscular blockade as based on neuromuscular monitoring or clinical evidence. The use of lower than recommended doses may lead to an increased risk of recurrence of neuromuscular blockade after initial reversal and is not recommended. HANDLING See SmPC for details of compatability with infusion solutions. Physical incompatibility has been reported with verapamil, ondansetron and ranitidine. PACKAGE QUANTITIES 10 vials of 2 ml 10 vials of 5 ml LEGAL CATEGORY POM Marketing Authorisation Numbers EU/1/08/466/001-002 Marketing Authorisation Holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands Date of review of prescribing information: January 2022 © Merck Sharp and Dohme B.V., 2022. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin 18 or from www.medicines.ie. EMEA/H/C/000885/II/0042 Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie.

Adverse events should also be reported to MSD (Tel: 01-299 8700)

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

Date of preparation: March 2022. IE-XBR-00079

➜ Keep up-to-date with news, announcements and events

page 1 of 3. This is a paid advertisement sponsored by AbbVie, it is part of a 3-page advertisement. Prescribing information for RINVOQ can be found on page 1 and for SKYRIZI on page 3

HELP YOUR PATIENTS

THE ITCH & RASH OF MODERATE TO SEVERE ATOPIC DERMATITIS 1 RINVOQ demonstrated in an integrated analysis of the MEASURE UP 1 & 2 monotherapy studies at Week 16: • EASI 75 skin clearance rates of 76% and 65% for patients treated with RINVOQ 30 mg QD and 15 mg QD, respectively, vs 15% with placebo (p<0.001 for both comparisons)2 • Itch reduction (mean percent change from baseline in Worst Pruritus NRS) of –70% and –58% for RINVOQ 30 mg QD and 15 mg QD, respectively, vs –24% with placebo (p<0.001 for both comparisons)2

RINVOQ, the first and only oral JAK inhibitor indicated for the treatment of both

adults and adolescents ≥12 years* with moderate to severe Atopic Dermatitis in the EU2-4 PRESCRIBING INFORMATION (PI) RINVOQ® (upadacitinib) 15 mg and 30mg prolonged-release tablets.

Refer to Summary of Product Characteristics (SmPC) for full prescribing information. PRESENTATION: Each 15 mg prolonged-release tablet contains upadacitinib hemihydrate, equivalent to 15mg of upadacitinib. Each 30mg prolonged-release tablet contains upadacitinib hemihydrate, equivalent to 30 mg of upadacitinib. INDICATION: Treatment of moderate to severe active rheumatoid arthritis (RA) and active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. Treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy. DOSAGE AND ADMINISTRATION: Intended for use under guidance and supervision of a physician experienced in diagnosis and treatment of conditions for which upadacitinib is indicated. Dosage: RA, PsA and AS: The recommended oral dose is 15mg once daily. Consideration should be given to discontinuing treatment in patients with AS who have shown no clinical response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. AD (adults): The recommended oral dose is 15 mg or 30 mg once daily based on individual patient presentation. 30 mg once daily dose may be appropriate for patients with high disease burden and for patients with an inadequate response to 15 mg once daily. The lowest effective dose for maintenance should be considered. For patients ≥ 65 years of age, the recommended dose is 15mg once daily. AD (adolescents from 12 to 17 years): The recommended oral dose is 15mg once daily for adolescents weighing at least 30 kg. Adults and adolescents 12 years and older: Upadacitinib can be used with or without topical corticosteroids. Topical calcineurin inhibitors may be used for sensitive areas such as the face, neck, and intertriginous and genital areas. Consideration should be given to discontinuing upadacitinib treatment in any patient who shows no evidence of therapeutic benefit after 12 weeks of treatment. Special Populations: Elderly: For AD, doses higher than 15mg once daily not recommended in patients aged 65 years and older. Limited data for patients aged 75 and older. Renal: No dose adjustment required in mild-moderate renal impairment. Upadacitinib 15mg once daily should be used with caution in patients with severe renal impairment.

Upadacitinib 30 mg once daily is not recommended for patients with severe renal impairment. Upadacitinib has not been studied in subjects with end stage renal disease. Hepatic impairment: No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Should not be used in patients with severe (Child Pugh C) hepatic impairment. Paediatric Population: No data available in the following paediatric patient populations: children with AD below the age of 12 years; children and adolescents with RA, PsA and AS aged 0 to less than 18 years. CONTRAINDICATIONS: Hypersensitivity to active substance or excipients. Active tuberculosis (TB) or active serious infections. Severe hepatic impairment. Pregnancy. SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details. Immunosuppression: Combination use, with immunosuppressants e.g. azathioprine, ciclosporin, tacrolimus, and biologic DMARDs or other JAK inhibitors has not been evaluated in clinical studies and is not recommended as the risk of additive immunosuppression cannot be excluded. Serious infections: Serious and fatal infections have been reported. Caution when treating patients ≥65 years. Frequently reported – pneumonia and cellulitis. Bacterial meningitis has been reported. Opportunistic infections reported – TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis. Do not initiate treatment in patients with active, serious infection, including localised infections. Consider the risk/benefit of treatment in patients with: chronic or recurrent infection, history of serious or opportunistic infection, those exposed to TB, those who have resided or travelled in areas of endemic TB or endemic mycoses, those with underlying conditions that may pre-dispose patients to infection. Closely monitor patients and interrupt treatment if there are signs and symptoms of infection pre and post treatment. Tuberculosis: Pre-screen patients for active or latent TB. RINVOQ should not be given to patients with active TB. Consider anti-TB therapy in patients with previously untreated latent TB or in patients with risk factors for TB infection. Consult with a physician with experience in TB therapy to assess whether initiating anti-TB therapy is appropriate for an individual patient. Monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

Viral reactivation: Cases of herpes virus reactivation have been reported e.g. herpes zoster. If herpes zoster is reactivated, consider interruption of upadacitinib therapy until the episode resolves. Screen for viral hepatitis and monitor regularly for reactivation before starting and during therapy with upadacitinib. Patients, positive for hepatitis C antibody/hepatitis C virus RNA and hepatitis B surface antigen/hepatitis B virus DNA were excluded from clinical studies. If hepatitis B virus DNA is detected while receiving RINVOQ, a liver specialist should be consulted. Vaccination: Use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunisations, including

©2022 AbbVie Inc.

All rights reserved.

prophylactic zoster vaccinations prior to starting therapy, in agreement with current immunisation guidelines.

Malignancy: Immunomodulatory therapies may increase the risk of malignancies including lymphoma and nonmelanoma skin cancer in RA patients. Malignancies were observed in clinical studies. Periodic skin examination recommended for patients who are at increased risk for skin cancer. See SmPC for full details. Haematological abnormalities: Do not start therapy if Absolute Neutrophil Count <1 x 109 cells/L, Absolute Lymphocyte Count <0.5 x 109 cells/L and Hb <8 g/dL. Monitor patients and temporarily stop therapy if abnormal haematological parameters as specified are detected during routine patient management. Diverticulitis: Events of diverticulitis have been reported in clinical trials and post-marketing. Upadacitinib should be used with caution in patients with diverticular disease and especially in patients chronically treated with concomitant medications associated with an increased risk of diverticulitis. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis to prevent gastrointestinal perforation. Cardiovascular Risk: RA patients have an increased risk for cardiovascular disorders. Manage patient’s risk factors for e.g. hypertension, hyperlipidaemia as per usual standard of care. Lipids: Monitor total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) at 12 weeks and thereafter according to international guidelines. Elevated LDL in clinical trials decreased to pre-treatment levels in response to statin therapy, although evidence is limited. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

Hepatic transaminase elevations: Monitor liver enzymes at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. In such cases therapy should be interrupted until this diagnosis is excluded.

Venous thromboembolism: Deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAKi, including upadacitinib. Use therapy with caution in patients at high risk for DVT/PE. Risk factors should be determined by patients age, obesity and medical history of DVT/PE, patients undergoing major surgery and prolonged immobilisation. If clinical features of DVT/PE occur discontinue therapy, evaluate and treat promptly. INTERACTIONS: Upadacitinib is metabolised mainly by CYP3A4 and plasma exposures may be affected

by CYP3A4 inhibitors or inducers. Upadacitinib 15 mg once daily should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors. Upadacitinib 30 mg once daily dose is not recommended for patients receiving chronic treatment with strong CYP3A4 inhibitors. See SmPC for full details. FERTILITY, PREGNANCY AND LACTATION: Upadacitinib is contraindicated during pregnancy. Women of childbearing potential should be advised to use effective contraception during treatment and for 4 weeks following the final dose of upadacitinib. Female paediatric patients and/or their parents/caregivers should be informed about the need to contact the treating physician once the patient experiences menarche while taking upadacitinib.

Upadacitinib should not be used during breast-feeding. The effect of upadacitinib on human fertility has not been evaluated. ADVERSE REACTIONS: Refer to SmPC for full details on adverse reactions. Very common adverse reactions (≥1/10): upper respiratory tract infections, acne. Common adverse reactions (≥1/100 to <1/10): bronchitis, herpes zoster, herpes simplex, folliculitis, influenza, anaemia, neutropaenia, hypercholesterolaemia, cough, abdominal pain, nausea, urticaria, fatigue, pyrexia, increased blood CPK/ALT/AST, increased weight and headache.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; website: www.hpra.ie.

LEGAL CLASSIFICATION: POM (S1A). MARKETING AUTHORISATION NUMBER/ PRESENTATION: EU/1/19/1404/001 and EU/1/19/1404/006 – Calendar blister packs containing 28 prolonged-release tablets. MARKETING AUTHORISATION HOLDER: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany.

Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.

DATE OF REVISION: December 2021. PI-1404-005 Abbreviations: EASI – eczema activity and severity index; NRS – numerical rating scale; QD – once daily; EU – European Union. * The recommended dose of RINVOQ is 15mg once daily for adolescents weighing at least 30kg. The safety and efficacy of RINVOQ in children with atopic dermatitis below the age of 12 years have not been established. No data are available. No clinical exposure data are available in adolescents <40kg. The posology in adolescent patients 30kg to <40kg was determined using population pharmacokinetic modelling and simulation.2 Reference: 1. Langan S. et al. Atopic dermatitis. The Lancet. 2020;396(10247):345-360. DOI: https://doi.org/10.1016/ S0140-6736(20)31286-1. 2. RINVOQ Summary of Product Characteristics, available on www.medicines.ie 3. Baricitinib Summary of Product Characteristics, available on www.medicines.ie 4. Abrocitinib Summary of Product Characteristics, available on www.medicines.ie

IE-RNQ_AD-220017 | February 2022

page 2 of 3. This is a paid advertisement sponsored by AbbVie, it is part of a 3-page advertisement. Prescribing information for RINVOQ can be found on page 1 and for SKYRIZI on page 3

A MEETING ENTITLED “ABBVIE INNOVATIONS IN PSORIASIS AND ATOPIC DERMATITIS”* Thursday May 5th, 2022 AbbVie were delighted to host the first face-to-face symposium since 2019 at the Irish Association of Dermatologists Spring Meeting 2022 which took place on May 5th in the Grand Hotel, Malahide, Dublin.

Among the good news shared was the recent reimbursement of SKYRIZI for Psoriasis and RINVOQ for Atopic Dermatitis.

Keynote speakers on the evening were Prof. Caitriona Ryan who presented on IL23 inhibition in Practice: Clinical Case Studies and Dr. Andrew Blauvelt who presented on Challenging AD Expectations: Challenging treatment goals for patients with moderate to severe Atopic Dermatitis.

The interactive nature of both sessions was greatly received by all those in attendance.

L-R: Isobel Bird, Brand Manager, AbbVie; Dr. Andrew Blauvelt; Marie Kennedy, Senior Product Specialist, AbbVie; Deirdre Callaghan, Senior Product Specialist, AbbVie

L-R: Dr. Andrew Blauvelt and Prof. Caitriona Ryan

Dr. Andrew Blauvelt, President of Oregon Medical Research Center, a small business dedicated to performing high quality clinical research studies in dermatology.

* SKYRIZI for Psoriasis and RINVOQ for Atopic Dermatitis ©2022 AbbVie Inc. All rights reserved. IE-RNQ_AD-220057 | June 2022

Professor Caitriona Ryan, Consultant Dermatologist and Co-Founder at the Institute of Dermatologists and an Associate Clinical Professor at University College Dublin.

page 3 of 3. This is a paid advertisement sponsored by AbbVie, it is part of a 3-page advertisement. Prescribing information for RINVOQ can be found on page 1 and for SKYRIZI on page 3

When it comes to your patient’s psoriasis treatment goals

What means everything to the patient?

The potential for nothing left on their skin.1,2 * Nothing on the skin: Defined as 75% achievement of PASI90 at Week 16 and ≥50% achievement of PASI 100 at Week 52 in UltIMMa-1 and UltIMMa-2.1 High skin clearance matters to patients: Patients who achieve and maintain high levels of skin clearance (PASI 90-99 or PASI 100) have significantly better HRQoL than those with lower levels of skin clearance (PASI 75-89).2 Sustaining high skin clearance or complete skin clearance is associated with incremental and durable benefits in HRQoL and mental health of psoriasis patients.2

PRESCRIBING INFORMATION (PI). SKYRIZI®▼ (risankizumab) 75 mg solution for injection in prefilled syringe; Skyrizi 150 mg solution for injection in pre-filled pen and Skyrizi 150 mg solution for injection in prefilled syringe. Refer to Summary of Product Characteristics (SmPC) for full information before prescribing. PRESENTATION: Skyrizi 150 mg solution for injection in pre-filled pen/syringe: each prefilled pen/syringe contains 150 mg risankizumab in 1 mL solution. Skyrizi 75 mg solution for injection in pre-filled syringe: each pre-filled syringe contains 75 mg risankizumab in 0.83 ml mL solution. INDICATION: Plaque Psoriasis: For treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. Psoriatic Arthritis: alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs (DMARDs). DOSAGE AND ADMINISTRATION: Intended for use under guidance and supervision of a physician experienced in diagnosis and treatment of psoriasis. Dosage: The recommended dose of Skyrizi is 150 mg by subcutaneous injection at weeks 0, 4, and every 12 weeks thereafter (either as two 75 mg pre-filled syringe injections or one 150 mg pre-filled pen or pre-filled syringe injection).

Two 75mg pre-filled syringes should be injected for the full 150 mg dose. Consider discontinuation of treatment in patients showing no response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. Special Populations: Elderly: No dose adjustment required. Renal or hepatic impairment: No dose adjustment required. Paediatric Population: No data available. Overweight patients: No dose adjustment required. CONTRAINDICATIONS: Hypersensitivity to any of the active substances or excipients. Clinically important active infections (e.g. active tuberculosis). SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Skyrizi may increase the risk of infections. In patients with a chronic infection or history of recurrent infections, or known risk factors for infection, Skyrizi should be used with caution. Treatment with Skyrizi should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

Patients should be evaluated for tuberculosis infection prior to initiating treatment. Anti-TB therapy should be considered prior to initiating Skyrizi in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Completion of all appropriate immunisations should be considered prior to initiating therapy. If a patient has received live vaccination (viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment with Skyrizi. Patients treated with Skyrizi should not receive live vaccines during treatment and for at least 21 weeks after treatment. If a serious hypersensivity reaction occurs, administration of Skyrizi should be discontinued immediately and appropriate therapy initiated. Excipients with known effect (75

mg solution for injection only): Skyrizi contains 68.0 mg sorbitol and less than 1 mmol sodium (23 mg) per 150 mg dose. INTERACTIONS: The safety and efficacy of Skyrizi in combination with immunosuppressants, including biologics or phototherapy have not been evaluated. PREGNANCY AND LACTATION: Women of Childbearing potential: An effective method of contraception during treatment and for at least 21 weeks after treatment should be used. Pregnancy: Limited data available. It is preferable to avoid the use of Skyrizi during pregnancy as a precautionary measure. Lactation: It is not known whether Skyrizi is excreted in breast milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A decision should be made whether to discontinue/abstain from Skyrizi therapy, taking into account the benefit of breastfeeding to the child and the benefit of Skyrizi therapy to the woman. Fertility: The effect of Skyrizi on human fertility has not been evaluated. ADVERSE REACTIONS: See SmPC for full details on adverse reactions. Very common adverse reactions (≥1/10): Upper respiratory infections. Common adverse reactions (≥1/100 to <1/10): Tinea infections, headache, pruritus, fatigue and injection site reactions. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

LEGAL CLASSIFICATION: POM (S1A). MARKETING AUTHORISATION NUMBERS/PRESENTATIONS: Skyrizi 75 mg solution for injection in pre-filled syringe (Pack of 2 pre-filled syringes): EU/1/19/1361/001; Skyrizi 150 mg solution for injection in pre-filled pen: EU/1/19/1361/002; Skyrizi 150 mg solution for injection in prefilled syringe: EU/1/19/1361/003. Not all presentations may be marketed. Further information is available from: AbbVie Ltd., 14 Riverwalk, Citywest Business Campus, Dublin 24, D24XN32. DATE OF REVISION: November 2021 PI/1361/004 HRQoL, Health-Related Quality of Life; PASI, Psoriasis Area Severity Index.

REFERENCES: 1. Gordon KB, et al. Lancet 2018; 392: 650-661. 2. Ryan C et al. Poster presented at the 27th European Academy of Dermatology & Venerology (EADV) Congress 2018; September 12–16; Paris, France.

Skyrizi® Summary of Product Characteristics, available on www.medicines.ie.

Date of preparation: April 2022 | IE-RISN-220005

81

PEER REVIEW: EPILEPSY Contraceptive Choice in Women on Antiepileptic Drugs (AEDs) Introduction

efficacy of contraceptives while Written by Authors: Sarah Cullen and Benedetta Soldati some contraceptives affect the It is crucial to counsel all women efficacy of AEDs (see table below). of childbearing age about As a consequence, the rate of oral future pregnancies, since half contraceptive failure is expected to Contraceptive on Antiepileptic Drugs (AEDs) of all pregnanciesChoice happen in to Women be be much higher in women taking unplanned. This recommendation enzyme-inducing AEDs compared becomesby even moreCullen important Written Sarah andfor Benedetta to theSoldati general population. For women with epilepsy, where all women on enzyme inducing AEDs, pregnancies should be planned the World Health Organisation and preconception advice should (WHO) recommends against the Introduction be sought. Considering that 25% use of the combined hormonal of people with epilepsy in Ireland contraception (pill, patch, ring) or areischild-bearing only contraception It crucial to women, counselthis all womenprogesterone of childbearing age about future pregnancies, since half of all amounts to about 10,000 people (implant, mini-pill). The copper pregnancies happen to be unplanned.

This recommendation becomes even more important for women who we must consider the use of IUD, levonorgestrel IUD and the with epilepsy,for. where all pregnancies should be planned and preconception advice should be sought. contraceptives medroxyprogesterone acetateConsidering that 25% of people with epilepsy in Ireland are child-bearing women, this amounts to about depot injection (DMPA) are not What does contraception involve attenuated by contraceptives drug interactions, 10,000 people who we must consider the use of for. for a woman with epilepsy? and are therefore the suggested alternative for women on enzymeContraception can be divided into Sarah Cullen, (Pharmacy Intern, NMH) What does contraception involve for a woman inducing AEDs. with epilepsy? three main types: natural, barrier and hormonal methods. As natural Emergency contraception methods are notcan appropriate Contraception be divided into three main types – natural, hormonal and barrier methods. As natural choices while taking for women of child-bearing age Lamotrigine andnot Sodium methods are not appropriate for women of child-bearing they will be discussed enzyme-inducing AEDsage with epilepsy, with epilepsy, they will not be Valproate further. discussed further.

Levonorgestrel and ulipristal Lamotrigine levels are decreased acetate are the two types Barrier methods include condoms, by coil. combined hormonal of emergency hormonal and the copper Barrier methods include condoms, femidoms, diaphragms The copper coil is a good femidoms, diaphragms and the contraception. For women who contraception (EHC). These are copper coil. for The women copper coil is alternative searching forboth a long-term contraceptive solution without the hormonal effects. are taking the COC alongside heavily impacted by enzymea good alternative for women lamotrigine, this may result in a inducing medications.

The copper Condoms alone are not strongly recommended because of the risk of failure. searching for a long-term reduced efficacy of lamotrigine coil is a non-hormonal form of contraceptive solution without the during the pill cycle and an emergency contraception (EC) Hormonal methods include the following; combined contraceptive pillincrease (COC),in progesterone only pill hormonal effects.

Condoms alone lamotrigine levels and, as such, it is not affected by are not strongly recommended (mini-pill), contraceptive implant, patch, depot injection, hormonal coilduring and the thevaginal pill free ring. break.Hormonal This enzyme-inducing medications. because of the risk of failure. means women women may more contraceptive methods are the mostAs commonly chosen byinwomen, withbe epilepsy. women may present need including likely to experience loss in seizure Hormonal methods include the of EC, it is strongly recommended control during the pill cycle and following: combined contraceptive that, if EC is necessary, they are Enzyme-inducing AEDs and contraception experience lamotrigine toxicity on pill (COC), progesterone only pill referred to their doctor to avail their pill-free interval. (mini-pill), contraceptive implant, of the copper coil, as this is the Enzyme-inducing AEDs can interact with hormonal contraceptives.

Interaction types – some patch, depot injection, hormonal Sodium valproate hasvary caused safest and most effective form coil and the vaginal ring.

Hormonal birth defects in babies whose of emergency contraception in AEDs may affect the efficacy of contraceptives while some contraceptives affect the efficacy of AEDs contraceptive methods are the mothers had taken the drug during those taking enzyme-inducing (see below).

As abyconsequence, the rate of oral contraceptive failure is expected to be much higher mosttable commonly chosen women, pregnancy and, therefore, it is not medications. If it is not possible including women with epilepsy. in women taking enzyme-inducing for AEDs compared totouch the general population.

For women on enzyme recommended for the treatment of a patient to get in with epilepsy in women child-bearing their doctor, or (WHO) if they dorecommends not Enzyme-inducing AEDs and Health Organisation inducing AEDs, the World against the use ofofthe combined age. It is only to be considered if wish to avail of the copper coil, contraception hormonal contraception (pill, patch,levonorgestrel ring) or progesterone only (implant, mini-pill).

The there is no alternative and it must can be given at contraception Enzyme-inducing AEDs be used in conjunction with the double the usual dose (3mg).

There Copper IUD, levonorgestrel IUD and the medroxyprogesterone acetate-depot injection (DMPA), are can interact with hormonal ‘Valproate Pregnancy Prevention is no evidence to recommend the not attenuated Interaction by drug interactions, andofare therefore thefor suggested for women on itenzymecontraceptives. types use ulipristal acetate patients alternative Programme’.

As a result, is rarely vary: someAEDs. AEDs may affect the on enzyme-inducing medications. used in women with childbearing inducing

Submission Date: 24-06-2022

AEDs that decrease the serum levels of hormonal contraceptives Carbamazepine Oxcarbazepine Phenobarbital Phenytoin Topiramate (reduce ethinylestradiol only) Eslicarbamazepine Primidone Lamotrigine (reduces progesterone only)

Word Count: 907 + table

AEDs that do not affect the serum levels of hormonal contraceptives Levetiracetam Gabapentin Vigabatrin Pregabalin Zonisamide Sodium Valproate Tiagabine Lacosamide

AEDs whom levels have been reduced by hormonal contraceptives Lamotrigine Sodium Valproate

Benedetta Soldati, (Sr. Pharmacist, NMH)

potential. However, it is important to highlight that ethinylestradiol can modestly reduce its levels.

Conclusion In conclusion, the prevalence of women with epilepsy who are of childbearing age means it is important for healthcare professional to be aware of the considerations of contraception.

Furthermore, women taking AEDs may present looking for preconception advice. Healthcare professionals should advise women who wish to become pregnant while on AEDs to engage with their consultants to optimise their medications and begin a course of folic acid. It is recommended that women on AEDs begin taking 5mg of folic acid at least three months prior to conception and remain on this dose throughout the pregnancy. The HSE National Clinical Programme for epilepsy recommends that women with epilepsy who are considering becoming pregnant engage with preconception planning 12 months before conception.

Though this article focused on women of child-bearing age, it is important to remember that hormonal replacement therapy (HRT) can also interact with AEDs. Common medications used in HRT such as estradiol and dydrogesterone have similar effects to COCs, and while there is no longer a concern of pregnancy, the efficacy of both the HRT and the AED must be considered.

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

50mgs once daily

50mgs once daily

Her 10th shopping trip since the day she started BETMIGA1

Prescribing Information: Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation: Prolonged-release tablet, containing mirabegron 25mg/50mg. Indication: Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. Posology and method of administration: The recommended dose is 50 mg once daily. A lower dose of 25mg is recommended for specific patient populations (renal and hepatic impairment) as well as in specific patient populations in combination with strong CYP3A inhibitors such as itraconazole, ketoconazole, ritonavir and clarithromycin.

Renal impairment: End stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis): Not recommended. Severe renal impairment (GFR 15 to 29 mL/min/1.73 m2): Reduce dose to 25 mg. Severe renal impairment and concomitant strong CYP3A inhibitors: Not recommended. Moderate renal impairment (GFR 30 to 59 mL/min/1.73 m2): 50 mg. Moderate renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Mild renal impairment (GFR 60 to 89 mL/min/1.73 m2): 50 mg. Mild renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Hepatic impairment: Severe hepatic impairment (Child-Pugh Class C): Not recommended. Moderate hepatic impairment (Child-Pugh B): Reduce dose to 25 mg. Moderate hepatic impairment and concomitant strong CYP3A inhibitors: Not recommended. Mild hepatic impairment (Child-Pugh A): 50 mg. Mild hepatic impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. The tablet is to be taken once daily, with liquids, swallowed whole and is not to be chewed, divided, or crushed. It may be taken with or without food Contraindications: Hypersensitivity to the active substance or to any of the excipients (see the SPC for a list of excipients). Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg. Special warnings and precautions for use: Renal impairment: Betmiga has not been studied in patients with end stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis) and, therefore, it is not recommended for use in this patient population. Data are limited in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2); based on a pharmacokinetic study a dose reduction to 25 mg is recommended in this population.

This medicinal product is not recommended for use in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) concomitantly receiving strong CYP3A inhibitors. Hepatic impairment: Betmiga has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and, therefore, it is not recommended for use in this patient population. This medicinal product is not recommended for use in patients with moderate hepatic impairment (Child-Pugh B) concomitantly receiving

Date of preparation: June 2019

strong CYP3A inhibitors. Hypertension: Mirabegron can increase blood pressure. Blood pressure should be measured at baseline and periodically during treatment with mirabegron, especially in hypertensive patients. Data are limited in patients with stage 2 hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg). Patients with congenital or acquired QT prolongation: Betmiga, at therapeutic doses, has not demonstrated clinically relevant QT prolongation in clinical studies. However, since patients with a known history of QT prolongation or patients who are taking medicinal products known to prolong the QT interval were not included in these studies, the effects of mirabegron in these patients is unknown. Caution should be exercised when administering mirabegron in these patients. Patients with bladder outlet obstruction and patients taking antimuscarinic medicinal products for OAB: Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medicinal products for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with Betmiga; however, Betmiga should be administered with caution to patients with clinically significant BOO. Betmiga should also be administered with caution to patients taking antimuscarinic medicinal products for the treatment of OAB. Interactions: Pharmacokinetic interactions: Mirabegron is a substrate for CYP3A4, CYP2D6, butyrylcholinesterase, uridine diphosphoglucuronosyltransferases (UGT), the efflux transporter P-glycoprotein (P-gp) and the influx organic cation transporters (OCT) OCT1, OCT2, and OCT3. Pharmacokinetic interactions involving the potential for other medicinal products to affect mirabegron exposures: Increases in mirabegron exposure due to drug-drug interactions may be associated with increases in pulse rate. Strong CYP3A inhibitors See Posology and administration above for dose adjustments recommended during concomitant use of strong CYP3A inhibitors in patients with renal or hepatic impairment. Mirabegron exposure (AUC) was increased 1.8-fold in the presence of the strong inhibitor of CYP3A/P-gp ketoconazole. CYP2D6 inhibitors: No dose adjustment is needed for mirabegron when administered with CYP2D6 inhibitors (or in patients who are CYP2D6 poor metabolisers). Inducers: Inducers of CYP3A (such as rifampicin) or P-gp may decrease the plasma concentrations of mirabegron. No dose adjustment of mirabegron is required as this effect is not expected to be clinically relevant.

Pharmacokinetic interactions involving the potential for mirabegron to affect exposures to other medicinal products: Inhibition of CYP2D6: Moderate and time dependent inhibition of CYP2D6 by mirabegron may result in clinically relevant drug interactions. CYP2D6 activity recovers within 15 days after discontinuation of mirabegron. Caution is advised if mirabegron is co-administered with medicinal

products metabolized by CYP2D6 with a narrow therapeutic index such as thioridazine, Type 1C antiarrhythmics (e.g.flecainide, propafenone) and tricyclic antidepressants (e.g., imipramine, desipramine). Caution is also advised if mirabegron is co-administered with CYP2D6 substrates that are individually dose titrated. Inhibition of P-gp: Mirabegron is a weak inhibitor of P-gp. For patients who are initiating a combination of Betmiga and digoxin, the lowest dose for digoxin should be prescribed initially. Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect. The potential for inhibition of P-gp by mirabegron should be considered when Betmiga is combined with sensitive P-gp substrates e.g. dabigatran. Fertility, pregnancy and lactation: The effect of mirabegron on human fertility has not been established.

Betmiga is not recommended during pregnancy and in women of child-bearing potential not using contraception. Mirabegron should not be administered during breast feeding. Refer to SPC for full guidance. Driving and use of machines: Betmiga has no or negligible influence on the ability to drive and use machines.

Undesirable effects: Summary of the Safety Profile: the safety of Betmiga was evaluated in 8433 patients with OAB, of which 5648 received at least one dose of mirabegron in the phase 2/3 clinical program, and 622 patients received Betmiga for at least 1 year (365 days). In the three 12-week phase 3 double blind, placebo controlled studies, 88% of the patients completed treatment with this medicinal product, and 4% of the patients discontinued due to adverse events. Most adverse reactions were mild to moderate in severity. The most common adverse reactions reported for patients treated with Betmiga 50 mg during the three 12-week phase 3 double blind, placebo controlled studies are tachycardia and urinary tract infections.

The frequency of tachycardia was 1.2% in patients receiving Betmiga 50 mg.

Tachycardia led to discontinuation in 0.1% patients receiving Betmiga 50 mg. The frequency of urinary tract infections was 2.9% in patients receiving Betmiga 50 mg.

Urinary tract infections led to discontinuation in none of the patients receiving Betmiga 50 mg. Serious adverse reactions included atrial fibrillation (0.2%). Adverse reactions observed during the 1-year (long term) active controlled (muscarinic antagonist) study were similar in type and severity to those observed in the three 12-week phase 3 double blind, placebo controlled studies. The following adverse reactions were observed with mirabegron in the three 12-week phase 3 double blind, placebo controlled studies. The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be established from the available data) Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse events

References: 1. Freeman R, et al. Current Medical Research and Opinion 2017. https://doi.org/10.1080/03007995.2017.1419170.

are grouped by MedDRA system organ class. Infections and infestations: Common: urinary tract infection Uncommon: vaginal infection, cystitis Psychiatric disorders: Not known: Insomnia*, confusional state* Nervous system disorders: Common: headache* dizziness* Eye disorders: Rare: eyelid oedema Cardiac disorders: Common: tachycardia Uncommon: palpitation, atrial fibrillation Vascular disorders: Very rare: Hypertensive crisis* Gastrointestinal disorders: Common: nausea*, constipation*, diarrhoea* Uncommon: dyspepsia, gastritis Rare: lip oedema Skin and subcutaneous tissue disorders: Uncommon: urticaria, rash, rash macular, rash papular, pruritus Rare: leukocytoclastic vasculitis, purpura, angioedema* Musculoskeletal and connective tissue disorders: Uncommon: joint swelling Renal and urinary disorders: Rare: urinary retention* Reproductive system and breast disorders: Uncommon: vulvovaginal pruritus Investigations Uncommon: blood pressure increased, GGT increased, AST increased, ALT increased (*observed during post-marketing experience). Reporting of suspected adverse reactions: see below. Legal category: POM (S1B) Marketing Authorisation number: EU/1/12/809/003 - 25mg EU/1/12/809/010 - 50mg. Marketing Authorisation holder: Astellas Pharma Europe B.V. Sylviusweg 62, 2333 BE Leiden, The Netherlands. Further information is available from: Astellas Pharma Co., Ltd, 5 Waterside, Citywest Business Campus, Dublin 24. Phone: +3531 467 1555. Summary of Product Characteristics with full prescribing information available upon request. Job number: BET_2019_0002_IE Date of preparation of API: 27 May 2019.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance Astellas Pharma Co. Ltd Earlsfort Terrace, IRL - Dublin 2 Tel: + 353 1 467 1555 Tel: +353 1 6764971 E-mail: Irishdrugsafety@astellas.com Fax: +353 1 6762517 Website: www.hpra.ie E-mail: medsafety@hpra.ie.

Approval code: BET_2019_0004_IE

83

PEER REVIEW: BENIGN PROSTATIC HYPERPLASIA

Benign Prostatic Hyperplasia (BPH) Benign Prostatic Hyperplasia (BPH)

Written by Dr Stefanie Croghan - Specialist Registrar in Urology and Mr James Forde - Consultant Urologist Both prostatic enlargement Background and Definition Written

by Dr Stefanie Croghan - Specialist Registrar in Urology and Mr James Forde and consequent lower urinary The prostate gland is located just tract symptoms increase with Consultant Urologist, Blackrock Clinic inferior to the bladder, and typically age; prostate volume has been approximates the size of a walnut or chestnut in young adult men, weighing 18-20g.1,2 It is composed of a combination of fibromuscular stroma and glandular elements, and serves in the production and liquefaction of the ejaculate.1 Benign prostatic hyperplasia (BPH) refers to a non-malignant process resulting in enlargement of the prostate gland (Figure 1).

observed to increase at a rate of 0.6ml [-9.9-62.1ml] per year in one longitudinal study.6,7 The interplay of further potential risk factors is incompletely understood, however obesity, hypertension, obesity, diabetes, diets lacking in fruit, vegetables and fibre and sex hormone levels have been implicated in the development of BPH.8

Background and Definition

The prostate gland is located just inferior to the bladder, and typically approximates the size 1,2 It is composed Dr Stefanie18-20g.

Croghan, Mr James Forde,of a of a walnut or chestnut in young adult men, weighing Epidemiology

Specialist Registrar in Urology

Consultant Urologist

combination ofcommon fibromuscular stroma and glandular elements, and serves in the production BPH is an extremely Clinical Consequences

process. Figures quote prevalence (on pathological inspection) of ~50% in men aged >50 years and >80% in men aged >70.3

BPH may be asymptomatic, or may result in bladder outlet 1 obstruction, causing lower urinary tract symptoms (LUTS) or urinary retention, which may be acute or chronic.5,8 Chronic urinary retention risks increased bladder pressure with transmission to the upper urinary tracts, causing hydronephrosis and renal impairment. In addition, high residual volumes of urine within the bladder predispose a patient to urinary tract infections, which may progress to epididymoorchitis or pyelonephritis.5,8

Presentation

Haematuria may occur, but must

be fully investigated for other and liquefaction of the ejaculate. Benign prostatic hyperplasia (BPH) refers to a nonPatients may present with a variety of lower urinary tract symptoms, including a weak stream of urine, straining to void, intermittency of the urinary stream, a feeling of incomplete bladder emptying, urinary frequency and urinary urgency.

The extent of these symptoms and their impact on a patient’s quality of life may be quantified using the validated International Prostate Symptom Score (IPSS).9

causes before being ascribed to BPH. The presence of nocturnal enuresis (bed-wetting) is a sign of high-pressure chronic retention, and should be enquired about.

The presence of neurological symptoms may suggest a nonprostatic cause of LUTS. Clinical history taking should seek the presence of medical conditions

Pathophysiology & Risk Factors malignant process resulting in enlargement of the prostate gland (Figure 1).

BPH results from an increase in the number of epithelial and stromal cells in the region of the prostate surrounding the urethra.4 The enlarged prostate may exert an obstructive effect on the urethra via both dynamic (contraction of prostatic smooth muscle) and static (direct local influence of increased volume) effects.5

Figure 1 – Anatomy of Benign Prostatic Hyperplasia (BPH) Figure 1: Anatomy of Benign Prostatic Hyperplasia (BPH)

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

84

PEER REVIEW: BENIGN PROSTATIC HYPERPLASIA

that may contribute towards LUTS (e.g. diabetes/other endocrine disorders or diuretic requirements) or influence treatment options. In addition, lifestyle factors should be explored, in particular fluid and caffeine intake.5,10,11 Physical Examination A physical examination should be performed on male patients presenting with LUTS/suspected BPH. This should include suprapubic palpation (assessing for a distended bladder), penile examination (for penile lesions, meatal stenosis or a tight phimosis – potential causes of LUTS) and a neurological examination of the lower limbs. A digital rectal exam (DRE) should be performed to estimate prostatic size and to assess the surface contour and consistency of the palpable peripheral zone of the prostate, with firm/hard regions or nodules raising possibility of malignancy.8,12 Further Diagnostic Assessment Urinalysis can be performed at the time of the physical examination and is important to detect urinary tract infection, non-visible haematuria or evidence of renal dysfunction.12 Bloods should be taken for a renal profile. A prostate specific antigen (PSA) test may be considered at this time. PSA serves as a screening tool for prostate cancer and may also have some role in predicting prostatic volume;13 however patients should be counselled regarding the implications of PSA testing, and given the option to choose whether or not to proceed.8,12,14 Post-void residual volume (PVR) assessments (bladder scans) are imperative to evaluate for incomplete bladder emptying, with high volumes prompting the need for immediate catheterisation. Within urology services, uroflowmetry will be performed, which plots the velocity of urinary stream over time on a graph and can suggest potential obstruction.8 Cystourethroscopy may be required for a variety of reasons including the presence of haematuria or suspicion of a urethral stricture, and cystometrogram may be indicated for non-straightforward cases of male LUTS (such as young age, equivocal findings on

uroflowmetry, the presence of a neurological condition, a history of prior radical pelvic surgery or prior surgical intervention for BPH).5,8,12 Renal ultrasonography or alternative upper tract imaging is indicated in the presence of abnormal renal function or for other indications (haematuria, suspected calculi) but is not routine in the evaluation of LUTS.12 Management Options A number of management options exist for patients with BPH.5,8,12 i. Conservative Patients with mild or moderate symptoms and minimal bother may be observed.

They should be advised about lifestyle measures that may exacerbate LUTS or increase the risk of acute urinary retention (nocturnal fluid intake, caffeine, alcohol, constipation and overthe-counter nasal decongestants).

Patients should be advised of the risk of BPH progression; a 4 year longitudinal study of 400 men found approximately 1/3 to have experienced clinical progression and approximately 5% to have had an episode of acute urinary retention over the study period.15 ii. Medical • α1-adrenergic antagonists aim to cause relaxation of prostatic smooth muscle and the bladder neck, by blockade of α1 receptors located within.

Tamsulosin is the best known of these; Silodosin has been shown to exert more selectivity for α1A adrenoreceptors versus α1B adrenoceptors and may reduce the risk of postural hypotension in susceptible patients.16,17 The main adverse effect is retrograde ejaculation.

• Although less frequently prescribed for LUTS, phosphodiesterase type 5 inhibitors such as Sildenafil cause smooth muscle relaxation.

Regular use can result in an improvement of lower urinary tract symptoms in men with or without erectile dysfunction.18 • Another drug class is steroid 5α-reductase inhibitors (5ARIs), with examples of which are Finasteride and Dutasteride.

These may be prescribed alone or in combination

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

with an α1-adrenergic antagonists. 5ARIs block the conversion of testosterone to Dihydrotestosterone (DHT), with resultant shrinkage of the prostate. These drugs must be taken for 4–6 weeks for benefit to emerge, and 3–6 months of treatment are required for full efficacy.12 They are generally well tolerated, however possible adverse effects include loss of libido, sexual dysfunction and mood alteration. Whilst these generally resolve on drug cessation, there is emerging evidence that they may persist in a very small minority.19 Bladder outlet obstruction, particularly over time, can result in the bladder becoming unstable and causing symptoms of bladder overactivity. Men with these symptoms and low post-void residual volumes may benefit from the addition of muscarinic receptor antagonists of muscarinic receptor antagonists (e.g. Solifenacin, Tolterodine, Fesoterodine) or beta-3 adrenergic agonists (e.g.

Mirabegron) alongside medications targeting outlet obstruction can provide relief. This may increase the chance of urinary retention, but the risk appears low.5,8, 20 iii.Surgical / Interventional A number of surgical treatments exist for the management of symptomatic BPH. • The most frequently performed of these is surgical debulking of the adenoma. This may be performed via monopolar or bipolar electrocautery transurethral resection of the prostate (TURP) or using other technologies, such as LASER or water vapourisation. A more conservative modification, transurethral incision of the prostate (TUIP) which aims to widen the bladder outflow tract without the removal of tissue, may be suitable for a small subgroup of patients.8 • Urethral lift is a minimally invasive procedure that may be performed as a day-case and involves placement of small implants to compress or ‘lift’ the prostate away from the urethra and improve urinary flow. As a relatively new procedure, data on longterm outcomes are still somewhat lacking.

A main advantage, however, is a lower rate of ejaculatory

dysfunction as compared to other treatments.8,21 • Enucleation or adenectomy, the removal of all prostatic tissue off its capsule is another surgical option, generally reserved for very large prostates.

This may be performed by open or minimally-invasive prostatectomy or transurethral laser enucleation.8 iv. Interventional Radiological • Prostatic artery emobolization (PAE) involves selective embolization of the prostate’s arterial blood supply, with the aim of resultant tissue necrosis and shrinkage of the gland. Objective outcome data regarding efficacy are lacking compared to alternative treatments and it is uncommonly performed in Ireland. It may have some role in patients with large, vascular prostates who require a minimally invasive approach that does not require general anaesthesia.8,22 v. Catheterisation A final option, for patients with bothersome LUTS, high post void residual volumes or recurrent urinary retention, who have not benefitted from, have a preference to avoid, or are medically high-risk for, alternative treatment strategies is to have a long-term indwelling urethral catheter or to be educated in intermittent self-catheterisation.5 Conclusions BPH is a common condition affecting men and increases in prevalence with age. It may be asymptomatic or cause bladder outlet obstruction and related symptoms. The greatest risks are of acute urinary retention, urological infections and high pressure chronic urinary retention, which can result in irreversible renal impairment if undiagnosed.

Initial assessment includes examination of the external genitalia and a DRE, urinalysis, biochemical renal profile, postvoid residual volume measurement and uroflowmetry and, in addition, PSA in counselled patients wishing to proceed. Management options include observation, pharmacological treatment, surgery, and for a minority of patients, long-term catheterisation or intermittent self-catheterisation.

References on request

2022 NOMINATIONS NOW OPEN

PROFESSIONAL PROFESSIONAL 100 100 Our annual listing celebrating innovation and excellence in healthcare is coming soon.

To request an entry or nomination form please

To request an entry or nomination form please contact: contact: kelly-jo@ipn.ie sarah@hospitalprofessionalnews.ie

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

86

PEER REVIEW: RARE DISEASES

Designing rare disease care pathways in the Republic of Ireland: a co-operative model Written by A. J. Ward1, D. Murphy1, R. Marron1, V. McGrath2, M. Bolz Johnson3, W. Cullen4, A. Daly3, O. Hardiman5,6, A. Lawlor7, S. A. Lynch8,9, M. MacLachlan11,12, J. McBrien13, S. Ni Bhriain14, J. J. O’Byrne9,10,15, S. M. O’Connell16,17, J. Turner1 and E. P. Treacy1,9,10* 1 National Rare Diseases Office, Mater Misericordiae University Hospital, Eccles St, Dublin 7, Ireland. 2 Rare Diseases Ireland, Carmichael House, North Brunswick St, Dublin 7, Ireland. 3 European Organisation for Rare Diseases (EURORDIS), Paris, France. 4 Division of Urban General Practice, School of Medicine, University College Dublin, Ireland. 5 Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland.

6 Department of Neurology, Beaumont Hospital, Beaumont, Dublin, Ireland. 7 22Q11 Ireland, North Brunswick Street, Dublin, Ireland. 8 Clinical Genetics, Children’s Health Ireland (CHI) at Crumlin, Dublin, Ireland. 9 School of Medicine, University College Dublin, Dublin, Ireland. 10 School of Medicine, Trinity College Dublin, Dublin, Ireland. 11 Disability Services, Health Service Executive, Dublin, Ireland. 12 Psychology and Social Inclusion, Assisting Living and Learning Institute, Maynooth University, Maynooth, Ireland. 13 Department of General Paediatrics and Neurodisability, CHI at Temple Street, Dublin, Ireland.

14 Office of the National Lead for Integrated Care, Health Service Executive, Dr. Steeven’s Hospital, Dublin, Ireland. 15 National Centre for Inherited Metabolic Disorders, Mater Misericordiae University Hospital, Dublin, Ireland. 16 Department of Diabetes and Endocrinology, Children’s Health Ireland (CHI) at Crumlin, Dublin, Ireland. 17 Department of Paediatrics, Royal College of Surgeons of Ireland (RCSI), Dublin, Ireland.

Background In Europe, a rare disease (RD) is defined as a condition with less than five affected persons per 10,000.1 It is estimated that 300,000 people in Ireland are living with one of over 6000 known RDs.2 These conditions tend to be complex, serious, debilitating, chronic and multisystemic, often associated with physical, sensory and intellectual disability.

In many cases patients require follow-up care with management from multiple medical specialists and health and social care professionals, which necessitates a high level of integrated care and service coordination between hospital, community, social and primary care services.3

services can prolong the ‘diagnostic odyssey’ for many people with RDs.8 Health care professionals (HCPs) from primary through to tertiary care report a lack of access to RD educational opportunities and struggle to meet the needs of people with RDs.9–11 Care pathways and defined standards for rare conditions are lacking.12 Consequently, people with RDs access a disproportionate level of health care resources.13, 14 The COVID-19 pandemic has further highlighted existing healthcare challenges for people with RDs and the need for more resilient healthcare systems which incorporate telemedicine.15, 16

Development and implementation of RD care pathways strongly People with RDs experience aligns with Irish national health significant challenges in securing service priorities as outlined in the diagnoses and accessing Ward et al. Orphanet Journal of Rare Diseases (2022) Model of Care for 17:162 Rare Diseases appropriate coordinated services, 2019,17 with a focus on delivering care and treatment.4, 5 Patients/ more integrated care locally service users and carers/ through the national Sláintecare supporters report that lack of care Health Reform Programme 2021– coordination is a central barrier 2023.18 At a European Union level, to accessing timely interventions member states are committed to and has a major impact on health facilitating equitable access to and well-being.6, 7 Ineffective use timely assessment and diagnosis of resources due to fragmented

Condi on selec on and care pathway model design

Review of existent Clinical Prac ce Guidelines

Preliminary care pathways development

Iden fica on of clinical leads and mapping of preliminary CPs to Irish healthcare system

and high quality, cost-effective care for all people with RDs, and to incorporate rare diseases into social services and policies.19, 20 In 2017, 24 European Reference Networks (ERNs), virtual networks of healthcare providers across the European Union, were launched to improve RD patient outcomes by enhancing access to specialised education of healthcare professionals (HCPs), developing and endorsing best practice guidelines, providing virtual expert consultations for complex cases and promoting clinical research activity.21 The ERN Board of Member States (2019) considers the development of national RD patient care pathways as central in the integration of ERNs into member states.22 Care Pathways are complex interventions that organize care for a well-defined group of patients for a well-defined period.23 They can be at a system, service or individual care level, have varying levels of granularity and can be multi-professional typically incorporating multiple guidelines.24

Iden fica on of pa ent representa ves and workshops with 'Rare Diseases Ireland'

Fig. 1 Flow diagram illustrating the development process of the care pathways

Fig. 1 Flow diagram illustrating the development process of the care pathways AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Pa ent representa ve review

Integra on of pa ent representa ve feedback by clinical leads

Methodology for developing a care pathway Whilst there is internationally agreed best practice methodology for the development of Clinical Practice Guidelines (CPGs), there is no commonly recognised methodology for care pathways.

Achieving international consensus on care pathway design methodology is complicated by the heterogeneity of national healthcare systems. However, it is agreed that co-design with patient partners is essential.25, 26 ‘RarERN Path’ has defined a model for care pathway development that is based on capturing existing practice through a narrative medicine approach and achieving patient, carer and HCP consensus on an optimized pathway.27 Patients accessing evidencebased care have increased health outcomes and their care is more Page 3 of 14 cost effective.28, 29 Care pathways increase evidence-based care and improve care process coordination.23, 30 However, identifying robust CPGs for RDs can be challenging due to limited randomized control trial data.31

Wider stakeholder engagement eg. HSCPs, disability services

Final cinical lead and pa ent representa ve review

87

developed. Common components and themes across the different pathways were identified to produce a RD care pathway model template.

Clinical lead identification For most childhood-onset conditions requiring lifelong care, both paediatric and adult clinical leads were identified. Our findings identified a significant gap in adult service provision for neurodevelopmental conditions such as Neurofbromatosis Type 1. For certain conditions (e.g., Amyotrophic Lateral Sclerosis), an adult-only care pathway was relevant. The pathway for transition from paediatric to adult services was poorly developed for a number of services with reference to the recommended National Rare Diseases ‘Model of Care’.

Fig. 2 National Rare Disease Care Pathway Collaborative Elements Infographic This pilot study explored the optimal approach to developing Irish RD care pathways by focusing on 29 multi-systemic conditions. A secondary objective was to determine the resources needed to implement optimum care pathways at the national level although it was evident during the development of the project that the resourcing for this standard of care was not in place at many of the Centres of Expertise.

Methods Figure 1 summarises the methodology used in the care pathway development process.

Figures 2 and 3 summarise the collaborative elements of the pathways and the aims across the patient journey.

Core components of a care pathway Team (CDNT)’ category was added to the 22q11 deletion syndrome and Angelman syndrome care pathways to capture recently completed reconfiguration within children’s disability services in Ireland. The Amyotrophic Lateral Sclerosis (ALS) care pathway included a specific category called ‘Specialist MND Multidisciplinary Clinic’ to accurately reflect how services for ALS are currently delivered. A co-ordinating patient/ service user representative was identified for each condition by the Irish national patient rare disease alliance—‘Rare Diseases Ireland’ (RDI) in liaison with the national patient organisations listed on Orphanet. The patient/ service user representative co-

ordinators for each condition were sent the relevant care pathway document and asked to invite key patient advocates from their network to attend an online workshop jointly led by RDI and NRDO. The main objectives of these workshops were: to create a supportive space for collaboration and sharing of experiential knowledge; to better understand the common needs and interventions which patients with rare diseases prioritise; and to enhance the relevance and utility of the care pathways.

Whilst the output from Clinical Leads was heterogenous, core components necessary across all care pathways emerged.

• ‘Diagnosis’ section features included: clinical presenting features; diagnostic criteria; tests and investigations required for diagnosis detailed under the medical disciplines responsible to carry these out; red flags for GPs were included where possible.

Results Care pathways developed 29 co-produced optimal national rare disease care pathways were

Fig. 3 Rare Disease Care Pathway Patient Journey Infographic

The initial care pathway model structure was designed based on input from several hospital consultant medical lead collaborators, with four overarching key categories under which the medical and HSCP disciplines and interventions could be placed and detailed: a. Diagnosis b. Hospital-based specialist care c. Hospital and community-based care d. Primary and community-driven care For certain conditions, it was necessary to include an additional category to reflect service and support intervention delivery models. For example, a ‘Children’s Disability Network HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

88

PEER REVIEW: RARE DISEASES • ‘Care’ section features included: medical disciplines and interventions necessary for patient management; symptomatic and asymptomatic screening; triggers for onward referrals; essential HSCP interventions; delineation of the GP role; links to relevant patient organisation(s).

• ‘Information’ section features included: CPGs and references used to inform the care pathway, the Orphanet definition and link for each condition along with Orphacode(s), relevant ERN links and clinical leads information.

‘Resources’ sections were developed containing staff resources and linked services needed to deliver the expected level of care outlined in each pathway, to support their use as a service funding planning tool.

This resource section outlined the optimum resources required according for the predicted patient numbers.

‘Core’ vs ‘as required’ medical disciplines Clinical leads indicated the need to distinguish between core medical disciplines and interventions necessary for routine patient management and ‘as required’ (medical disciplines and interventions for patients with more complex clinical needs).

Key health & social care professional roles Clinical leads and patient/service user representatives identified a Nurse Specialist, Medical Social Worker, Psychologist and Registry Manager roles as being essential in all 29 pathways. Genetic counselling was considered a key role for 93% of pathways as these conditions have a major underlying genetic aetiology. Occupational Therapy, Physiotherapy, and/or Speech and Language Therapy were defined as key in 76% of the care pathways. 45% of pathways included dietetics as a key role.

Discussion A primary objective of this project was to develop an optimal process for the introduction of national RD care pathways into the Irish healthcare system in the absence of a commonly recognised best practice methodology. Consideration of such a broad range of conditions across 18 different ERNs enabled the identification of common components and roles and the development of a national Rare Diseases care pathway

model template, which was a fundamental aspect of this study.

The aim was to create an adaptable, interactive, and updatable model with the capacity to outline the coordinated interventions by multiple healthcare providers from pre-diagnosis across the entire life-long patient journey.

The model can be flexible to allow for inclusion of specific delivery models where they exist and ensuring adaptability to evolving service configuration.

For example, in Ireland, the interdisciplinary Children’s Disability Network Teams have recently been established, comprising over 20 HSCPs, to provide services and supports for children with complex disabilities.

Care pathways can be mapped to their respective patient journeys to evaluate if holistic needs of the affected patient population are adequately addressed.33 Active engagement with health service managers involved in service design, at all stages of care pathway development, facilitates accurate alignment with national service delivery models. Patient representatives emphasised the importance of a holistic approach to highly specialised care, with a key focus on access to psychosocial care. RD pathways can signpost patients to therapeutic interventions, psychological care and social services, thereby supporting patients and families to navigate education, employment and welfare supports.

For example, in the DMD care pathway the medical social worker section details respite care to promote awareness of and access to these support services.

This is consistent with findings from published surveys across the wider RD patient community which prioritise improved social inclusion, mental health and quality of life as a means to redress the detrimental impact on personal, professional and socioeconomic status experienced by so many people living with a RD.3, 7, 33 Patient representatives attributed high value to HSCP and psychosocial roles.

As many rare diseases start in childhood and do not yet have effective treatments, the need to optimise child development and function through therapeutic support was considered critical to optimising quality of life. Timely access to local community psychology services was prioritised by patients/ service users at key points in the

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

patient journey. Within the Irish healthcare landscape, provision of psychological interventions has tended to be limited to restricted scenarios and often hospitalbased; however, psychology services are now provided in each of the 91 Children’s Disability Network Teams that provide community-based services throughout Ireland.

Gaps in adult services Challenges in mapping adult Irish clinical experts for lifelong, childhood-onset neurodevelopmental conditions, such as NF1, 22q11 deletion syndrome and Angelman syndrome, revealed significant gaps in adult service provision due to a lack of clear transition pathways. Consequently, GPs are often left to coordinate ongoing management in an ad hoc manner.10 The lack of adult multidisciplinary care to address the complex medical and psychosocial needs of these patients is a primary concern for patients and carers, who often take on the role of care coordinator themselves.6 A focus on delivering adequate co-ordinated adult care for life-long neurodevelopmental conditions is required.34 Provision of genetic services Over 70% of RDs have a significant genetic basis.32 Also, for RDs with a non-genetic basis there can be significant heritability, indicating the likelihood of genetic susceptibility and/or rare genetic sub forms. Genetic counselling was considered a core discipline for most of the pathways. As the clinical genomics landscape evolves due to improving diagnostic methods and treatments, care pathways need to be flexible to adapt.42 The genetic counselling profession is uniquely placed to support these transitions in best practice and to ensure that ethical principles are followed that consider the implications for patients and their extended family members. As genomics promises to deliver powerful diagnostic solutions, national clinical genetic services struggle to absorb increased demand.43 Mainstreaming of genetic testing is the inevitable consequence. However, the inherent risks of misinterpretation of complex genomic data are evident even for HCPs with formal clinical genetics training and extensive genomic experience.44 Clinical Geneticists and Genetic Counsellors have a central role in education of non-Genetics HCPs to promote the safe delivery of genomic medicine.45

Conclusion This pilot study explored the development of an optimal process for national RD care pathway design in the absence of agreed, common, best practice methodology. Partnership with RD patient representatives and service users was central to the delivery of this study. The high level of engagement experienced from clinical leads and patient organisations highlights the strong endorsement of this care pathway initiative by key RD stakeholders.

RD patient needs and health care professional interventions common across all pathways were identified, highlighting the core roles of therapeutic HSCPs, Nurse Specialist, Psychology, Medical Social Work, Database Manager and Genetic Counselling for delivering optimum rare disease care.

Effective care pathways offer the best opportunity to translate best practice, evidence-based guidelines into local healthcare services leading to service redesign and more targeted resources to optimise patient health outcomes. It is intended that care pathways will prove to be effective educational, clinical and advocacy tools for general practitioners (GPs), hospital specialists, HSCPs, health service managers, patients and carers.

Future research examining the implementation of such care pathways is a priority.

This is a summary of the paper first published in the Orphanet Journal of Rare Diseases. You can read the full paper and see list of references via the ojrd biomedical website https://ojrd.biomedcentral. com/articles/10.1186/s13023-02202309-6

A combined force against LUTS and BPH

49% of men with LUTS report bladder and prostate symptoms1 VESOMNI treats the symptoms of both the bladder and prostate2 Abbreviated Prescribing Information - Vesomni 6 mg/0.4 mg modified release tablets. Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation: Each tablet contains a layer of 6 mg solifenacin succinate, corresponding to 4.5 mg solifenacin free base and a layer of 0.4 mg tamsulosin hydrochloride, corresponding to 0.37 mg of tamsulosin free base. Indication: Treatment of moderate to severe storage symptoms (urgency, increased micturition frequency) and voiding symptoms associated with benign prostatic hyperplasia (BPH) in men who are not adequately responding to treatment with monotherapy. Posology and method of administration: Adult males, including older people: One Vesomni tablet (6 mg/0.4 mg) once daily taken orally with or without food. The maximum daily dose is one Vesomni tablet. The tablet must be swallowed whole, intact without biting or chewing. Do not crush the tablet. Special populations (see also contraindications below): Renal impairment: Severe renal impairment (creatinine clearance ≤ 30 mL/min): Treat with caution, maximum daily dose in these patients is one Vesomni tablet.

Hepatic impairment: Moderate hepatic impairment (Child-Pugh score of 7-9): Treat with caution, maximum daily dose in these patients is one Vesomni tablet. In patients with severe hepatic impairment (Child-Pugh score > 9), the use of Vesomni is contraindicated. Concomitant treatment with moderate and strong inhibitors of CYP450 3A4: e.g. verapamil, ketoconazole, ritonavir, nelfinavir, itraconazole: Treat with caution, maximum daily dose should be limited to one Vesomni tablet.

Paediatric population: There is no relevant indication for use of Vesomni in children and adolescents.

Contraindications: Patients with hypersensitivy to the active substance(s) or to any of the excipients (see SPC). Patients undergoing haemodialysis. Patients with severe hepatic impairment. Patients with severe renal impairment who are also treated with a strong cytochrome P450 (CYP)3A4 inhibitor e.g. ketoconazole. Patients with moderate hepatic impairment who are also treated with a strong CYP3A4 inhibitor e.g. ketoconazole. Patients with severe gastrointestinal conditions (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma and patients at risk for these conditions.

Patients with a history of orthostatic hypotension. Special Warnings and Precautions for Use: Vesomni should be used with caution in patients with: severe renal impairment; risk of urinary retention; gastrointestinal obstructive disorders; risk of decreased gastrointestinal motility; hiatus hernia/ gastroesophageal reflux and/or who are concurrently taking medicinal products (such as bisphosphonates) that can cause or exacerbate oesophagitis; autonomic neuropathy. The patient should be examined in order to exclude the presence of other conditions, which can cause similar symptoms to benign prostatic hyperplasia. Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Vesomni is initiated. If a urinary tract infection is present, appropriate antibacterial therapy should be started. QT prolongation and Torsade de Pointes have been observed in patients with risk factors, such as pre-existing long QT syndrome and hypokalaemia, who are treated with solifenacin succinate. Angioedema with airway obstruction has been reported in some patients on solifenacin succinate and tamsulosin. If angioedema occurs, Vesomni should be discontinued and not restarted. Appropriate therapy and/or measures should be taken. Anaphylactic reaction has been reported in some patients treated with solifenacin succinate. In patients who develop anaphylactic reactions, Vesomni should be discontinued and appropriate therapy and/or measures should be taken. As with other alpha1-adrenoceptor antagonists, a reduction in blood pressure can occur in individual cases during treatment with tamsulosin, as a result of which, rarely, syncope can occur. Patients starting treatment with Vesomni should be cautioned to sit or lie down at the first signs of orthostatic hypotension (dizziness, weakness) until the symptoms have disappeared. The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract and glaucoma surgery in some patients on or previously treated with tamsulosin hydrochloride. IFIS may increase the risk of eye complications during and after the operation. Therefore, the initiation of therapy with Vesomni in patients for whom cataract or glaucoma surgery is scheduled is not recommended. Discontinuing treatment with Vesomni 1-2 weeks prior to cataract or glaucoma surgery is anecdotally considered helpful, but the benefit of treatment discontinuation has not been established. During pre-operative assessment, surgeons and ophthalmic teams should consider whether patients scheduled for cataract or glaucoma surgery are being or have been treated with Vesomni in order to ensure that appropriate measures will be in place to manage IFIS during surgery. Vesomni should be used with caution in combination with moderate and strong inhibitors of CYP3A4 and it should not be used in combination with strong inhibitors of CYP3A4, e.g., ketoconazole, in patients who are of the CYP2D6 poor metaboliser phenotype or who are using strong inhibitors of CYP2D6, e.g., paroxetine.

Interactions: Pharmacological interactions: Concomitant medication with other anticholinergic medicinal products may result in more pronounced therapeutic and undesirable effects. Allow approximately one week after stopping treatment with Vesomni before commencing any anticholinergic therapy. The therapeutic effect of solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Pharmacokinetic interactions: Pharmacokinetic interactions involving the potential for other medicinal products to affect Vesomni exposures: Interactions with CYP3A4 and CYP2D6 inhibitors: See Contraindications, Posology and administration and Special warnings and precautions above. Concomitant administration may lead to increased exposure to both solifenacin (ketoconazole 400 mg/day resulted in a 1.5-fold increase in Cmax and a 2.8-fold increase in AUC). and tamsulosin (ketoconazole 400 mg/day resulted in a 2.2-fold increase in Cmax and a 2.8-fold increase in AUC). Vesomni should be used with caution in combination with strong CYP3A4 inhibitors. Vesomni should not be given together with strong CYP3A4 inhibitors in patients who are also CYP2D6 poor metabolizer phenotype or who are using strong CYP2D6 inhibitors. See SPC for details of the effects of other CYP3A4 and CYP2D6 inhibitors. Inducers: Inducers of CYP3A4 (e.g. rifampicin) may decrease the plasma concentrations of solifenacin and tamsulosin. Information available for the individual active substances: Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as metoclopramide and cisapride. Solifenacin did not affect the pharmacokinetics of digoxin, or the pharmacokinetics or effect on prothrombin time of R- or S-warfarin. Co-administration of tamsulosin and other alpha1-adrenoreceptor antagonists could lead to hypotensive effects. Diclofenac and warfarin may increase the elimination rate of tamsulosin. No interactions have been seen when tamsulosin was given concurrently with atenolol, enalapril or theophylline. Fertility, pregnancy and lactation: The effect of Vesomni on fertility has not been established. Ejaculation disorders have been observed in short and long term clinical studies with tamsulosin. Events of ejaculation disorder, retrograde ejaculation and ejaculation failure have been reported in the post authorization phase.

Vesomni is not indicated for use in women. Driving and use of machines: No studies have been performed, however patients should be informed about the possible occurrence of dizziness, blurred vision, fatigue and uncommonly somnolence, which may negatively affect the ability to drive or use machines. Undesirable Effects: Summary of the safety profile: Vesomni may cause anticholinergic undesirable effects of, in general, mild to moderate severity. The most frequently reported adverse reactions during the clinical studies performed for the development of Vesomni were dry mouth (9.5%), followed by constipation (3.2%) and dyspepsia (including abdominal pain; 2.4%). Other common undesirable effects are dizziness (including vertigo; 1.4%), vision blurred (1.2%), fatigue (1.2%), and ejaculation disorder (including retrograde ejaculation; 1.5%). Acute urinary retention (0.3%, uncommon) is the most serious adverse drug reaction that has been observed during treatment with Vesomni in clinical studies. List of adverse reactions: the ‘Vesomni frequency’ below reflects adverse drug reactions that have been observed during the double-blind clinical studies performed for the development of Vesomni (based on reports of treatment-related adverse events, which have been reported by at least two patients and occurred with a frequency higher than for placebo in the double-blind studies). The ‘solifenacin frequency’ and ‘tamsulosin frequency’ below reflect adverse drug reactions (ADRs) previously reported with one of the individual components (as presented in the Summary of Product Characteristics (SmPCs) of solifenacin 5 and 10 mg and tamsulosin 0.4 mg respectively that may also occur when receiving Vesomni (some of these have not been observed during the clinical development program of Vesomni). The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). The adverse events are grouped by MedDRA system organ class preferred term (PT). Vesomni frequency: Nervous system disorders: Common: dizziness Eye disorders: Common: vision blurred Gastrointestinal disorders: Common: dry mouth, dyspepsia, constipation Skin and subcutaneous tissue disorders: Uncommon: pruritus Renal and urinary disorders: Uncommon: Urinary retention*** Reproductive system and breast disorders: Common: ejaculation disorders including retrograde ejaculation and ejaculation failure General disorders and administration site conditions: Common: fatigue Solifenacin 5mg & 10mg frequency#: Infections and infestations: Uncommon: urinary tract infection, cystitis Immune system disorders: Not known: anaphylactic reaction* Metabolism and nutrition disorders: Not known: decreased appetite*, hyperkalemia* Psychiatric disorders: Very rare: hallucination*, confusional state* Not known:

References: 1. Sexton CC, et al. BJU Int 2009; 103(Suppl 3): 12-23. 2. VESOMNI Summary of Product Characteristics.

Date of preparation: July 2019 Job code: VESOM_2019_0003_IE

delirium* Nervous system disorders: Uncommon: somnolence, dysgeusia Rare: dizziness*, headache* Eye disorders: Common: vision blurred Uncommon: dry eyes Not known: glaucoma* Cardiac disorders: Not known: palpitations*, Torsade de Pointes*, electrocardiogram QT prolongation*, atrial fibrillation*, tachycardia* Respiratory, thoracic and mediastinal disorders: Uncommon: nasal dryness Not known: dysphonia* Gastrointestinal disorders: Very common: dry mouth Common: dyspepsia, constipation, nausea, abdominal pain Uncommon: gastro-oesophageal reflux disease, dry throat Rare: vomiting*, colonic obstruction, faecal impaction, Not known: ileus*, abdominal discomfort* Hepatobiliary disorders: Not known: liver disorder*, liver function test abnormal* Skin and subcutaneous tissue disorders: Uncommon: dry skin Rare: pruritus*, rash* Very rare: urticaria*, angioedema*, erythema multiforme* Not known: exfoliative dermatitis* Musculoskeletal and connective tissue disorders: Not known: muscular weakness* Renal and urinary disorders: Uncommon: difficulty in micturition Rare: urinary retention***Not known: renal impairment* General disorders and administration site conditions: Uncommon: fatigue, perhiperal oedema Tamsulosin 0.4mg frequency#: Nervous system disorders: Common: dizziness Uncommon: headache Rare: syncope Eye disorders: Not known: vision blurred*, Intraoperative Floppy Iris Syndrome (IFIS)**, visual impairment* Cardiac disorders: Uncommon: palpitations Not known: atrial fibrillation*, arrhythmia*, tachycardia* Vascular disorders: Uncommon: orthostatic hypotension Respiratory, thoracic and mediastinal disorders: Uncommon: rhinitis Not known: dyspnoea*, epistaxis* Gastrointestinal disorders: Uncommon: constipation, nausea, diarrhea, vomiting Skin and subcutaneous tissue disorders: Uncommon: pruritus, rash, urticaria Rare: angioedema Very Rare: Stevens-Johnson syndrome Not known: erythema multiforme*, exfoliative dermatitis* Reproductive system and breast disorders: Common: ejaculation disorders including retrograde ejaculation and ejaculation failure Very rare: priapism General disorders and administration site conditions: Uncommon: asthenia. #: The ADRs from solifenacin and tamsulosin included are the ADRs listed in the summary of product characteristics of both products. *: from post-marketing reporting. Because these spontaneously reported events are from the worldwide post-marketing experience, the frequency of events and the role of solifenacin or tamsulosin and their causation cannot be reliably determined. **: from post-marketing reporting, observed during cataract and glaucoma surgery. ***: see Special warnings and precautions for use. Long-term safety of Vesomni: The profile of undesirable effects seen with treatment up to 1 year was similar to that observed in the 12-week studies. The product is well-tolerated and no specific adverse reactions have been associated with long-term use.

Description of selected adverse reactions: For urinary retention see Special warnings and precautions for use. Older people: The therapeutic indication of Vesomni, moderate to severe storage symptoms (urgency, increased micturition frequency) and voiding symptoms associated with BPH, is a disease affecting elderly men. The clinical development of Vesomni has been performed in patients 45 to 91 years of age, with an average age of 65 years. Adverse reactions in the elderly population were similar to the younger population. Reporting of suspected adverse reactions: see below. Overdose: Overdosage with the combination of solifenacin and tamsulosin can potentially result in severe anticholinergic effects plus acute hypotension. Refer to SPC for details of treatment of overdose. Legal Category: Prescription Only Medicine (SIB). Nature and contents of container: Aluminium blister packs containing 30 tablets. Product Authorisation Number: PA1241/016/001. Marketing Authorisation holder: Astellas Pharma Co. Ltd. Further information is available from: Astellas Pharma Co. Ltd, 5 Waterside, Citywest Business Campus, Naas Road, Dublin 24. Phone: +3531 467 1555. Summary of Product Characteristics with full prescribing information available upon request. Job number: VESOM_2019_0001_IE Date of preparation of API: 24 May 2019 Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance Astellas Pharma Co. Ltd Earlsfort Terrace, IRL - Dublin 2 Tel: + 353 1 467 1555 Tel: +353 1 6764971 E-mail: Irishdrugsafety@astellas.com Fax: +353 1 6762517 Website: www.hpra.ie E-mail: medsafety@hpra.ie.

90

PEER REVIEW: UROLOGY

Current Treatment Options for Benign Prostatic Hyperplasia Written by Charles O’Connor, Patrick Collins and Gregory Nason BPH are alpha-adrenergic blockers including tamsulosin, alfuzosin and doxazosin and 5-alpha reductase inhibitors (5-ARIs) including dutasteride and finasteride, combination therapy is also common in the form of tamsulosin/ dutasteride or “Combodart”.

Charles O'Connor

Patrick Collins

Gregory Nason

Introduction

Risk factors for BPH

Benign prostatic hyperplasia (BPH) is a histologic diagnosis of prostatic enlargement from benign proliferation of epithelial prostate cells as well as smooth muscle.

BPH prevalence increases with age with rates ranging from 50% to 75% for men older than 50 years of age to 80% in men 70 years of age and older.1 The average prostate volume is 20-30cc, patients with BPH will typically have a larger prostate volume than 30cc. BPH is often diagnosed with patients experiencing lower urinary tract symptoms (LUTS).

These can be broadly categorised in to storage and voiding LUTS. Storage LUTS include frequency, urgency, nocturia and occasional incontinence. Voiding LUTS include hesitancy to start flow, straining, intermittent ‘or stopstart’ flow and a sensation of incomplete emptying. An objective measure of LUTS severity is the use of the international prostate symptoms score (IPSS). This score is the same as the validated American urological associate symptom index (AUASI) score but it asks one more key question- “If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about this?”. The IPSS is shown in figure 1.2

Risk factors that are associated with BPH include age, lack of exercise, smoking, excessive alcohol consumption, obesity, hypertension, diabetes, hyperlipidaemia and a genetic disposition. Factors that tend to decrease the risk of BPH include increased physical activity, moderate or decreased alcohol intake and increased vegetable consumption.3 Thus, like with many conditions, the first steps to manage BPH should be in terms of lifestyle modification. Other methods of lifestyle modification to deal with LUTS secondary to BPH include cutting out factors that cause increased frequency or nocturia. This can include cutting out or limiting caffeine or medications that increase frequency e.g., diuretics. For patients who experience nocturia a practical first step to manage this is to limit fluid intake in the hours prior to sleeping.

Medical management of BPH

antigen (PSA) test to screen for prostate cancer. Guidelines suggest that PSA should only be checked in a patient with a life expectancy of 10 years or more and after discussion of the risks and benefits of screening. A digital rectal examination (DRE) should be carried to assess the prostate size and the presence of masses or nodules, although this examination tends to under-estimate prostate volume.4 Urinalysis can be performed to out rule the presence of a urinary tract infection (UTI).

The use of the IPSS score can assess severity of symptoms.

If bladder outflow obstruction (BOO) is suspected, laboratory tests including creatinine should be checked and an ultrasound performed of a patient’s bladder post-void to ensure sufficient emptying- generally termed PVR (post void residual). A uroflowmetry test can also be carried out which measures a patient’s maximum flow rate (Qmax), average flow rate and voided volume. The pattern of flow can give an insight into the aetiology of the symptoms.

Medical management of LUTS generally starts with a patient’s primary care physician. As a recent increase in LUTS can be associated with prostate cancer, consideration can be given to performing a prostate specific

Medical management for BPH can be initiated if a patients LUTS fall in to the moderate or severe class as per their IPSS score or if their mild LUTS are bothersome to them. The two main classes of medication for

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Alpha blockers work by blocking sympathetic nerve fibres which decreases contraction of smooth muscle at the bladder neck and improves emptying.

Symptomatic relief is generally noted after 1 week of use but may take up to 4 weeks. IPSS scores improve by 5-8 points by taking an alpha blocker. As alpha blockers were initially developed as antihypertensive agents, one of their main side effects is orthostatic hypotension. Other side effects of alpha blockers include headache, retrograde ejaculation and with tamsulosin especially a condition called ‘floppy iris syndrome’ after ophthalmic surgeons noted iris flopping or prolapsing during cataract surgery.

Men should not be started on an alpha blocker if planning this surgery. Notably, in contrast to tamsulosin, alfuzosin does not cause retrograde ejaculation and one recent systematic review confirmed that it may even improve ejaculatory function.5 Antimuscarinic medications work by blocking muscarinic receptors from the action of acetylcholine which mediates parasympathetic nerves. Alpha blockers can be combined with antimuscarinic mediations like solifenacin in men with BPH who have predominantly bladder storage systems. The EAU strongly recommends their use in this subset of patients and the risk of acute urinary retention is rare with these provided a patients’ PVR is less than 150mls.6 Beta-3 agonists like Betmiga similarly improve these storage symptoms and can be used in combination with alpha-blockers.

Both testosterone and DHT are implicated in the stimulation of prostatic tissue. The second

91 Figure 1. IPSS Scoring system [2]

Figure1: IPSS Scoring system2

Side effects of 5-ARIs with prolonged use include erectile dysfunction, decreased libido, and gynecomastia.

Surgical management of BPHwho should it be offered to?

Surgical management of BPH should be offered to patients who fail medical management, have refractory urinary retention, recurrent UTIs, persistent haematuria, bladder stones or renal insufficiency. This article aims to provide the reader with an outline of the various different surgical managements of BPH, outlining the pros and cons of each procedure. In recent years, minimally invasive technologies have emerged which may be an alternative to the traditional TURP for some patients.

Prior to proceeding with surgery Prior to proceeding with a surgical procedure, the AUA advocates estimation of prostate volume and shape delineation (presence or absence of median lobe).

Another consideration prior to proceeding with surgery is to perform urodynamics (or bladder pressures reading tests) in patients where there is diagnostic uncertainty, to identify if the symptoms are in fact due to BPH or perhaps due to conditions like detrusor underactivity or detrusor sphincter dyssynergia where there is a lack of co-ordination between bladder and sphincter stimulation.

However, it has been shown that routinely investigating patients with urodynamics does not reduce surgical rates and therefore this should be reserved for cases of diagnostic uncertainty.7 Minimally invasive techniques

class of BPH medication- (5ARIs) work by inhibiting the enzyme 5-alpha reductase which metabolises testosterone to dihydro testosterone (DHT). Less DHT means less prostate tissue stimulation and resulting atrophy and apoptosis. 5-ARIs should only be started in men with prostate volumes over 30cc or glands enlarged on clinical examination.

These medications reduce the prostate size by up to 25% and decrease the vascularity of the prostate. For this reason, they can be beneficial for patients prior to prostate surgery or who are experiencing bleeding from the prostate. In contrast to alpha blockers, 5-ARIs can take 2-6 months to take full effect. IPSS scores improve by 3-5 points

by taking a 5-ARI. The risk of urinary retention is decreased more significantly by taking a 5-ARI than an alpha blocker, and is decreased even more with combination therapy. After 6 months these medications should reduce a patient’s PSA by 50%.

It is important that every clinician knows this to prevent abnormal PSA readings not being detected.

Minimally invasive techniques used in Ireland include Rezum and Urolift. These procedures are particularly attractive to patients who wish to avoid the sexual dysfunction that can come with medical therapy and more definitive surgery. While these procedures are often compared to other surgical techniques, as more data becomes available these may be more commonly compared to medical therapy. These procedures offer a better maximum flow rate

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

92

PEER REVIEW: UROLOGY Figure 2: Illustrations & pictures of various BPH procedures

1. Small prostates TUIP/BNI

1A

This procedure uses an electrocautery knife to make an incision from the bladder neck towards the verumontanum in men without a median lobe and a prostate size less than 30ccs.

This acts to dilate the prostatic urethra and improve LUTs. This procedure shows similar efficacy to TURP in men with prostates less than 30ccs. This procedure is usually performed under general anaesthesia. A meta-analysis comparing TUIP to TURP demonstrated a lower rate of retrograde ejaculation (18.2% vs 65.4%) and need for blood transfusion (0.4% vs 8.6%) as the main advantages of TUIP over TURP.12 A drawback of TUIP is the higher rate of re-operation vs TURP (18.4% vs 7.2%).13 A patient information leaflet on BNI can be found on the BAUS website.14

1D

1B

1E 1C

2. “Average” sized prostates

1A: HoLEP 1B: TURP 1C: Bladder neck incision 1D: Urolift 1E: Rezum

TURP improvement and IPSS score decrease compared to medication and could be a cost-effective option, possibly rendering them a future first line option. The longer efficacy and durability of Urolift and Rezum are unknown.

Rezum Rezum is the brand name for convective water vapour energy (WAVE) ablation. This system uses radiofrequency power on a few drops of sterile water to create thermal energy in the form of water vapour. This steam causes prostate tissue necrosis. This procedure can be used for men with prostate volumes from 30-80ccs, with or without a median lobe. This procedure can be performed under local anaesthesia but currently is only performed under general anaesthesia in Ireland. A catheter is usually placed for a number of days post procedure. The 5 years follow up data comparing Rezum to sham was published in September 2021.

This shows durable results with the improvement in LUTS being sustained since the <3month follow up. IPSS scores reduced by 48%, Maxium flow rates improved by 44%. Surgical re-treatment remains quite low at 4.4%, while 11.1% resumed on BPH medications. There are no reports

of sexual dysfunction in patients treated with Rezum.8 BAUS published an information leaflet on Rezum in June 2021.9 Urolift Urolift is the brand name for prostatic urethral lift. This procedure involves inserting an implant which looks like a treasury tag into the prostatic capsule via a cystoscope to compress the lateral lobes of the prostate therefore dilating the prostatic channel.

This procedure can be used for men with prostate volumes from 30-80ccs, without a median lobe.

This procedure can be performed under local anaesthesia or general anaesthesia. Around 20% of patients will require catheter insertion usually for 1 day. 5 years follow up for Urolift published in June 2017, reported an IPSS score reduction of 36% and a maximum flow rate improvement of 44%. Surgical retreatment was 13.6% over 5 years, while 10.7% of patients resumed on BPH medications. Sexual function was not affected in these patients over 5 years of follow up.10 A consideration with the use of Urolift is the 15mm artefact extension noted on MRI from the implant. The impact of this artefact on prostate cancer detection by MRI is not well studied, however,

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

reports suggest that MRI protocol can be adjusted to minimise this. The British Association of Urological Surgeons (BAUS) published an information leaflet on Urolift in December 2021.11 Definitive BPH surgery Definitive BPH surgical procedures can be classed into a number of categories. Those for 1. Small prostates <30ccs, 2. Average sized prostates 30-80ccs, 3.

Large and very large prostates and 4. Any sized prostates.

TURP (Transurethral resection of prostate) is the standard and most common procedure for BPH to which these treatments are usually compared. Transurethral incision of the prostate (TUIP) also known as bladder neck incision or (BNI) is reserved for prostates less than 30ccs. Procedures like TURP and PVP (Photoselective vaporisation of the prostate- or “Greenlight laser”) are used most commonly for prostates between 30-80ccs, but can also be used for smaller prostates. Enucleation of the prostate with Holmium or Thulium lasers can be used on prostates of any size. Open and robotic simple prostatectomy is reserved for large prostates (80-150cc) or very large prostates (>150cc)

The initial TURP was a monopolar TURP traditionally performed in glycine. The standard TURP procedure is now the bipolar TURP which can be performed in saline. This has led to a greater side effect profile and has rendered TUR-syndrome (acute dilutional hyponatremia) an historic event. Patients require a catheter for 2-3 days post procedure until haematuria has settled. TURP results in an average 14-point improvement in IPSS score at 1 year with a Qmax improvement of 13.7 mL/s.15,16 While retrograde ejaculation/ejaculatory dysfunction is common after TURP (65-75%), erectile dysfunction is uncommon (3.5-8.5%).17,18 Similar to previous, a patient information leaflet on the procedure is available on the BAUS website.19 This is the most commonly performed BPH procedure.

“Greenlight laser”Photoselective vaporisation of the prostate The greenlight laser works by ablation or vaporisation of the prostate adenoma from the urethra towards the prostate capsule.

This procedure provides good haemostasis and is performed with saline irrigation. Meta-analyses comparing greenlight to TURP show similar outcomes. Greenlight takes significantly longer to

93 Figure 3. Surgical management of BPH algorithm

Figure 3: Surgical management of BPH algorithm

Prostate artery embolization (PAE)

perform but results in decreased length of stay, catheterisation times and bleeding.20 The EAU gives a strong recommendation to offer this procedure as an alternative to TURP.6 A reference to this procedure is found on the BAUS website.21 3. Large & very large prostates Open simple prostatectomy This is the oldest procedure described to treat moderate to severe LUTs due to bladder outlet obstruction (BOO). Open prostatectomy was initially described by two Irish surgeons (Terence Millin described the simple retropubic prostatectomy while Peter Freyer described the simple transvesical prostatectomy). This procedure is associated with high blood loss and a transfusion rate of between 7-14%. Open prostatectomy provides very durable and quick results with a decrease in IPSS points between 12.5-23.3, a significant increase in maximum flow (16.5-20.2 mL/s), and a large reduction in PVR between 86-98%. Efficacy is maintained for up to six years.22,23 Metaanalyses evaluating the efficacy of this procedure show comparable outcomes to those achieved with HoLEP, and in centres with an absence of HoLEP, open prostatectomy is a reasonable treatment choice for men with prostates >80mls.24 The frequency of this procedure in Ireland is

dwindling. A patient information leaflet for this procedure is also available from the BAUS website.25 Robotic simple prostatectomy Performing a simple prostatectomy robotically results in decreased length of stay, less blood loss and equivalent functional outcomes for patients.26 Most studies to date on this procedure are retrospective and there is need for high quality randomised controlled trials (RCTs). Results from our centre on 5 patients over a 12-month period show excellent results with a median (IQR) length of stay of 3(1) days. No patient required a blood transfusion.27 This is a challenging procedure and carries a significant learning curve. As experience from robotic prostatectomy grows, we anticipate this procedure to become more common.

4. Any sized prostates Holmium laser enucleation of the prostate (HoLEP) HoLEP is an endoscopic enucleation of the prostate using a laser commonly used to treat kidney stones. Three meta-analyses evaluating HoLEP vs bipolar TURP showed no difference in short term efficacy in terms of IPSS improvement, quality of life and maximum flow.28-30 A retrospective comparison of 2,869 HoLEP procedures vs 37,577 TURP procedures demonstrated longer operation times with HoLEP.

However, there were shorter hospitalisation times and less infectious complications. Overall complication rates were similar.31 One meta-analysis of 7 RCTs showed similar short and midterm erectile function scores between HoLEP and TURP, however long-term scores were significantly better in HoLEP patients.32 This procedure can be offered as an alternative to TURP or Millin prostatectomy.

The learning curve with this procedure is said to be steep with 50 procedures being quoted as the number required to become proficient. A patient information leaflet on HoLEP is similarly available on the BAUS website.33 Thulium:yttrium-aluminiumgarnet laser (Tm:YAG) enucleation of the prostate (ThuLEP) The Thulium laser is another laser which is used for treating kidney stones, with recent research and clinical experience demonstrating it to be significantly faster than the standard holmium (Ho:YAG) laser.

ThuLEP is performed in exactly the same way as HoLEP. A key visual difference in the procedure vs HoLEP is the carbonisation of prostate tissue during the procedure giving it a brown or burnt look. Current data shows similar efficacy between ThuLEP, HoLEP and TURP. ThuLEP seems to be faster to perform than HoLEP, although it is associated with a larger haemoglobin drop.34,35

PAE is a procedure which uses digital subtraction angiography to identify suitable prostatic arterial supply to embolize. This procedure can be performed as a day case under local anaesthesia with access via femoral or radial arteries. This procedure can be particularly useful in co-morbid patients who may be more suited to minimally invasive treatment.

This procedure seems to be less effective than TURP for objective improvement in functional outcomes. However, blood loss as well as catheterisation and hospitalisation time all favour PAE. This procedure is still under investigation and it is advised that it only be performed in centres where urologists work with trained interventional radiologists to select appropriate candidates.36 Summary Benign prostatic hyperplasia is a condition characterised by a prostate volume over 30mls.

This is predominantly a condition of older men. Patients with suspected BPH should be worked up by their physician with a history including LUTs (IPSS) and DRE. Patients should be first advised on lifestyle modifications to improve their condition. Reasonable first line investigations for LUTs include laboratory investigations including PSA, creatinine and urine for microscopy or culture and sensitivity. Common BPH medications to treat obstructive urinary symptoms include alpha blockers and 5-ARIs. Common BPH medications to treat storage urinary symptoms include antimuscarinics and beta-3 agonists. Uroflowmetry, urodynamics, ultrasound, flexible cystoscopy, and CT/MRI are all useful investigations for BPH. Shared decision making is important between clinician and patient when deciding on the necessity for, and the type of BPH procedure to be carried out. This decision should be guided by a patient’s co-morbidities, functional status, prostate size and shape as well as most importantly the patient’s treatment goals.

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

94

PEER REVIEW: PRESCRIBING

Nurse Prescribing in A Private Cardiology Outpatient Setting Written by Padraig Denn, Introducing Nurse Prescribing to Private Cardiology Practice

Introduction I am going to investigate the processes involved in the development of a nurse prescriber role in a cariology out-patient setting in a private facility in Munster. I will initially look at defining the nurse prescriber role in order to have a clear view of the role requirements. I will then look at the specific area for the new role and how the Irish Legal and Regulatory framework will impact on the role’s development. I will finally look at how accountability and ethical considerations will impact on the role and what skills and guidelines a nurse/midwife prescriber could use to ensure that the care they provide is not only effective but appropriate for each individual patient.

Definition In order to investigate the development of nurse prescriber role in an outpatient setting we should first identify the definition of the role. I will review the development of nurse prescribing in Ireland later but in short nurse prescribing is built on both a legal framework and associated regulations and rules. The prescriber must be registered on the appropriate prescribers register and only prescribe medications that are commonly used in their specific area of expertise. Despite a thorough search of relevant literature, I was unable to identify a specific definition for the nurse prescriber role. Therefore, I

propose the below definition of the role for the purposes of this article.

“Nurse/Midwife prescribing is a comprehensive process of amending an individual’s medical product regime by an appropriately educated and registered nurse/midwife prescriber within their scope of practice and area of expertise. This process encompasses effective assessment of the individual and their problem whilst adhering to local and national laws/ regulations/policies/guidelines as part of a patient centred care approach. The resultant prescription should adhere to best practice documentation guidelines and should be subject to comprehensive auditing to ensure consistency and accuracy.”

role to encompass the assessment and management of non-acute cardiology presentations, in conjunction with the lead cardiologist, to improve the throughput in out-patient clinics. A significant component of this role would be the active management of patient’s conditions which would involve effective prescribing of medicinal products.

Scope of Nursing for Prescribing

The out-patient services are based in a private healthcare facility in the Munster region and will be the first private clinic in Munster to have an Advanced Nurse Practitioner (ANP) role as part of the day-to-day management of the broad spectrum of non-urgent out-patients.

Based on the recommendations of theses report a review was commissioned in 2001 into the possibility of extending the role of nursing to include prescribing. The review was carried by a team from An Bord Altranais and the National Council for the Professional development of Nursing and Midwifery. There review was published after three and a half years of assessment in 2005.

This review recommended that prescriptive authority should be extended to nurses and midwives (Drennan et al., 2009).

The implementation process for nurse prescribing in Ireland had its infancy in two reports that were published in the late 1990’s early 2000. The commission of Nursing (Government of Ireland, 1998) and the Review of scope of Practice for Nursing and Midwifery (Final Report) (An Bord Altranais, 2000).

In this article I will look at the important components of effectively integrating this new advanced nurse role into a preexisting clinical setting whilst ensuring that national legal and registration guidelines are adhered too. I will also consider the personal considerations of taking on this new role in the Appendix 1 above setting.

The National Nursing and Midwifery board (NMBI) (registration authority in Ireland for Nurse Prescribers) and the Health Services Executive have laid out the rules and regulations for the nurse/midwife prescribing role in numerous publications. I will explore these in more detail later.

Clinical Setting I am currently the manager of an outpatient cardiology department which includes a nurse lead Acute Cardiology assessment unit, heart failure clinic, cardiac rehabilitation nurse led service and we are in the process of developing a cardiology nurse research post. It is planned to expand my current

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

Appendix 2 Practice Standards and Guidelines

Appendix 1

95 The then Minister for Health and Children, Mary Harney, brought the recommendations of the report to cabinet. The Minister’s rationale for the extension of prescriptive authority to nurses and midwives was to improve services to patients, reduce health service delays and deploy the education and expertise of nurses and midwives more efficiently (Creedon and O’Connell, 2009).

Once it was cleared by Government in 2006 it was signed into law in several legal acts in 2006 and 2007.

• The Irish Medicines Board (Miscellaneous Provisions) Act 2006 (Commencement) Order 2007.

• The Medicinal Products (Prescription and Control of supply) (Amendment) Regulations 2007.

• The Misuse of Drugs (Amendment) Regulations 2007.

Over the subsequent years the specifics of requirements for effective and safe nurse prescribing have been reviewed and amended accordingly. Initially the guidelines from An Bord Altranais (now called Nursing and Midwifery Board of Ireland, NMBI) and the Health Services Executive (HSE) identified that to ensure safe prescribing practices it needed to be identified by the individual prescriber and their clinical mentor which specific medications the prescriber would be allowed to prescribe, this was called the Collaborative Practice Agreement (CPA) and was a requirement for registration with the NMBI. This however is no longer a requirement in Ireland as it was found to be too restrictive for the prescriber particularly when you look at the frequency and number of changes that occur in medications over the years. Therefore, in 2018 this requirement for registration as a nurse/midwife prescriber was discarded. It was replaced with a recommendation that the prescriber’s area of clinical practice implement local policies and guidelines about the prescriptive authority of each individual prescriber.

Along with this change over the intervening years the restriction of Nurse/Midwife prescribers prescribing Controlled and Non-licensed medications has also been amended to allow for a more comprehensive list of medications available for everyone to add to their agreed list of medicinal products (ONMSD and HSE, 2020). These changes have been reflected in associated amendments to the legal framework supporting the prescriptive authority of nurses/midwives.

• Nurses and Midwives Act 2011 (S.I. No 41 of 2011) • Misuse of Drugs Regulations 2017 (S.I No. 173 of 2017).

• Nurses and Midwives Rules 2018 (S.I. No. 219/2018-Register of Nurses and Midwives, S.I. No 218/2018-Education and Training).

• Medicinal Products Control of Placing on the Market) Regulations 2018 (S.I. No. 529 of 2018).

With the regular amendments to the legal framework supporting the implementation and regulation of nurse/midwife prescribing there has been concurrent development and amendments to the clinical guidelines and practices overseeing the prescriptive authority of the nurse/midwife prescriber. The Office of Nursing and Midwifery Services Director and the Health Services Executive have identified the below as the core guidelines for nurse/midwife prescribing: (ONMSD and HSE, 2020) • Recording Clinical Practice Guidance to Nurses and Midwives (An Bord Altranais, (2002) • Guidance to Nurses and Midwives on Medication Management (An Bord Altranais, (2007).

• Requirements and Standards for Education Programmes for Nurses and Midwives with Prescriptive Authority (An Bord Altranais, 2007).

• Code of Professional Conduct and Ethics for Registered Nurses and Registered Midwives (NMBI, 2014) • Scope of Nursing and Midwifery Practice Framework (NMBI, 2015) • Practice Standards for Midwives (NMBI, 2015) • Practice Standards and Guidelines for Nurses and Midwives with Prescriptive Authority, 4rd edn (NMBI, 2019) According to the NMBI (2015) the scope of nursing practice is the range of roles, functions, responsibilities and activities which a registered nurse is educated, competent and has authority to perform. Therefore, with the removal of the requirement for a CPA for nurse/midwife prescribing the specifics of what an individual prescriber has the competency and authority to prescribe falls to the employer. This can be supported through addition or amendment of local clinical

policies and guidelines. Having these guidelines developed in collaboration with all relevant members of a multidisciplinary team will allow for easier implementation of practices that reflect the specific clinical setting rather than depending on generic national or international policies which would be difficult to implement in very specific clinic settings.

Implementation into Private Cardiology Out-Patient Clinic As mentioned above I am working in a cardiology out-patient service in a private healthcare setting in the Munster region. There is a development plan in place to improve patient throughput by implementing an advanced nurse practitioner role in the coming months. In order to ensure that this role is implemented in an efficient and effective manner it is imperative that all aspects for the role and how it fits into existing structures are examined.

International research has identified a wide variety of benefits to the implementation of the nurse prescriber role into the clinical setting with some reporting that it is the single greatest development in the nursing since it became a profession (Dowden, 2016).

Numerous authors have identified efficiency and patient benefits to the development of the nurse/ midwife prescriber role. These benefits vary from improved patient satisfaction, improved waiting times, maximising resources and improving patient access (Courtenay et al., 2010; Carey and Steiner, 2011; Ferro, 2011; Griffith, 2013 and Milligan, 2012) to improvements in prescribers self-perception of the effectiveness of their patient care journey along with extension of their knowledge base for both medicinal products and the legal/ administrative requirements that are associated with it. The research has shown that nurse/ midwives are as effective as their medical colleagues at prescribing effectively and appropriately and identifying/reporting adverse medication events (Morrison-Griffiths et al., 2003 and Black & Dawood, 2014).

However, despite the above dearth of research about the benefits of nurse/midwife prescribing in the effectiveness of the care they provide when compared with our medical colleagues some issues have been identified with implementing the practice.

Bradley et al. (2007) identified

that despite undertaking an appropriate educational programme and registering as a non-medical prescriber 26% (n=8) of their respondents had not yet prescribed any medicinal products.

Although this research is based on a small cohort the findings are significant. The authors elaborated on their qualitative research finding and identified several areas that the respondents believed limited their ability to prescribe once qualified. They noted that the perception of patient safety was a key factor. The respondents also noted that although having completed the pre-requisite educational component for registration they felt this was only a starting point in their theory training, this perception is supported research conducted

by Boreham et al. (2014) in their review of nurse prescriber training in Scotland.

Bradley et al. (2007) identified that a key component to effective nurse/midwife prescribing was the integration with the practice within existing clinical structures and the support of members of the multi-disciplinary team with the development of the role and their support in ongoing educational needs of the role. The absence of this component of nurse/ midwife prescriber training has been identified by Casey et al.

(2019) as a key barrier to effective implementation of the nurse/ midwife prescriber role.

There are national guidelines, produced by the NMBI to assist nurse/midwife prescribers in their day-to-day patient centred care processes. One central component for the safe and effective prescribing of medicinal products is the code of professional conduct and the associated five principles (See Appendix 1). Two further key components of effective prescribing were identified by the NMBI in the 4th edition of Guidelines for nurses and midwives with prescriptive authority (2019). These included the eleven practice standards for nurse/midwife prescribing (See Appendix 2) and a decisionmaking framework (See Appendix 3). These were seen as the key factors required for the effective implementation of Nurse/Midwife prescribing when first commenced in Ireland (HSE, 2007).

As mentioned earlier with the withdrawal of the need to have a CPA in practice there

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

96

PEER REVIEW: PRESCRIBING

is a requirement to have an established framework in place in the prescriber’s area of clinical practice to not only support them in their practices but also to ensure that any practices are evaluated and amended as required to ensure the practitioner is working within their scope of practice and are treating their patients with the most up to date interventions. This issue was identified above when the barriers to effective implementation of the nurse/midwife prescriber role were highlighted. In my area, as it is a new venture for the hospital a comprehensive review of current policies and practices was undertaken to identify what components needed to be amended. This process was overseen by my clinical mentor, the hospitals nurse prescribing supervisor and the hospitals Drugs and Therapeutics committee.

A possible benefit of this collaborative approach would be to ensure that all key stakeholders in the process have an input in the process and thus be more likely to support the prescriber in the day-to-day activities and their ongoing professional development, thus avoiding the potential barriers identified above regarding effective implementation of the role.

Accountability of Nurse Prescriber Role in Out-Patient Cardiology setting As mentioned earlier nurse-led clinic allow for timely treatments by nurse/midwife prescribers.

Appendix 2

Practice Standard 1 Practice Standard 2 Practice Standard 3 Practice Standard 4 Practice Standard 5 Practice Standard 6 Practice Standard 7 Practice Standard 8 Practice Standard 9 Practice Standard 10 Practice Standard 11

These clinics allow specialist nurses to develop advanced skills and manage specific caseloads with relative autonomy. With this autonomy comes increased risk and accountability is essential to Appendix 1 the protection of patients receiving care in nurse-led clinic (Griffiths, 2013). According to the ONMSD and HSE (2020) practicing in an accountable manner requires a sound knowledge base in order to ensure that the nurse/ midwife prescriber can justify their course of treatment or omission of treatment. In Ireland the code of conduct for nurses and midwives has as one of its five core principles professional accountability of actions and omissions in care (NMBI, 2021).

In Ireland the requirements for acceptance into the theoretical component of nurse/midwife prescriber training states that the participant needs to already have extensive experience in the specific area of practice (Lotto, 2018). The courses although generic in their application of theory expect the individual participant to apply the new knowledge to their area of practice. There is also a component of evaluation of course completion through a logbook of the implementation of the theory into clinic practice. This multifaceted approach to education of the nurse prescriber is designed to meet the standards set out by the ONMSD and HSE for effective theoretical training of nurse prescribers to ensure a sound knowledge base and associated

accountability of decisions made in practice. However, applying theory to practice may not be so straight forward.

In 2006 in the United Kingdom Jan Keenan, a leading cardiac nurse consultant, identified that the restrictive nature of specific formulary-based nurse prescribing was leading to impaired care delivery in nurse-led clinics (Keenan, 2006). This issue was formally recognised in Ireland with the removal of the CPA in 2018.

However, one must recognise that the presence of the CPA was a crutch to assist the newly qualified prescriber in their dayto-day decision-making process by providing a clear structure to their prescribing options. The removal of the CPA potentially limits the newly qualified prescriber to implement a treatment plan.

Casey et al. (2019) reported in their qualitative study that nurse prescribers reported low levels of confidence in their abilities to alter medications already prescribed by another member of the multidisciplinary team. The HSE and ONMSD also recognised the issue of removal of the CPA in their 2020 National Nurse/Midwife prescriber guidelines by recommending the utilisation of national prescribing guidelines and amending them to fit local practices to support front line nurse/midwife prescribers (ONMSD and HSE, 2020).

However, the newly qualified nurse/midwife prescriber must remember that available research has shown that nurse prescribing is as effective/appropriate as our

Appendix 2 Practice Standards and Guidelines

Clinical decision-making process Communication and history taking Documentation Prescription writing Prescribing for self, family and significant others Repeat prescribing Prescribing of off-label and exempt medicinal products Prescribing by means other than the original prescription Separation of responsibilities in the medication management cycle Influence of outside interests (relationships with pharmaceutical representation or similar organisations Continuing professional development and continued competency

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

medical colleagues, medications errors are often reduced, and nurse/midwife prescriptions are compliant with pre-established documentation guidelines (Carey and Steiner, 2011). As mentioned earlier the utilisation of a multidisciplinary approach to the development of a new nurse/ midwife prescribing service is essential to ensure appropriate structures are in place for safe practice. It should also be noted that this structure can also aide the prescriber in their decision-making processes (Bradley and Riley, 2013).

In practice the utilisation of a decision-making framework has also been shown to aide the process of effectively prescribing and this allows the prescriber to be more accountable for their decisions as they can reference this framework if any adverse events occur. Moore (2019) described the utilisation of such a framework in prescribing home oxygen for patients with chronic obstructive pulmonary disease who continued to smoke. The NMBI also have a decisionmaking framework in their Practice Standards for Nurses and Midwives with prescriptive authority, see appendix 3 (NMBI, 2019).

Therefore, in order to support a nurse/midwife prescriber in the management of a case load of patients a facility should ensure that there are appropriate local guidelines that would include a decision-making framework. There should also be appropriate support from members of the multidisciplinary team to ensure that the prescriber feels they can ask questions about their prescriptive decisions. The knowledge base, decision making framework, appropriate local policies and the support of colleagues will ensure that the nurse prescriber is accountable for their decisions and ensure the patients receives the most appropriate and effective level of care.

Ethical Considerations of Prescribing in a Cardiology Setting As mentioned above the work highlighted by Moore (2019) prescribing Oxygen therapy to a patient who continues to smoke brings with it some issues around safety for the patient.

Taking this one step further should we consider the ethical component of such a decision, is it in the patients’ best interests to commence oxygen therapy?

This can also ring through when we look at prescribing medicinal

97

Appendix 3

existing α-blocker treatment for his prostate issue and worsen his dizzy spells and result in an increased numbers of falls. This would result in a worsening quality of life as he would be restricted in his daily activities. Therefore, would it be ethically correct to improve this gentleman’s blood pressure readings whilst worsening his quality of life.

It must be remembered that any decision in healthcare will have an impact on another individual and usually that individual is the patient. Therefore, when we look at prescribing in any setting, we must first consider the patient, their needs, expectations and beliefs. O’Connor and O’Dea (2021) present a comprehensive introduction to the issue of Human Factors in the decision-making process. Although the patient is not the only Human factor to consider as per the diagram representing human factors (See Appendix 4) they are central to the process of decision making in healthcare.

Conclusion Although the role of nurse prescriber has been present in the Irish healthcare system as an entity for nearly twenty years it is an ever evolving practice. The role itself has been poorly defined and varies from setting to setting and even within individual healthcare settings. The benefits of the nurse prescriber role have been clearly described in various publications but the success of implementation has been reported to be varied and occasionally stagnated.

It has been clearly identified that to effectively implement a new prescribing process in a clinical setting requires effective support and defined frameworks to assist the new prescriber in the development of the skills and knowledge to safely treat a specific patient cohort. This framework and support structure needs to be developed through effective collaboration with various members of the multidisciplinary team. The aim of the process being to ensure that the new prescriber can safely, autonomously and ethically decide on the most appropriate medicinal regime for every individual within their defined patient cohort.

Therefore, for any ethical discussion to happen the first step is to involve the patient in the process. Allow them to be central to the decision-making process by educating them about the Appendix 4 risks and benefits of any potential treatment regime and allowing them the space to decide if the treatment is in their best interests.

Foundations of Human Factors in Healthcare

products for cardiac patients. In general, Cardiac patients will have concurrent co-morbidities due to the general cohort of patients being older and with increased age comes worsening health issues.

A prescriber needs to assess if the decision-making framework, local guidelines and national/ international recommended treatment for a specific problem is in the patient’s best interests?

As an example, a 65-yearold gentleman who is on pharmaceutical treatment for benign prostatic hypertrophy and presents to a cardiology clinic for newly diagnosed hypertension.

He is frail and has been prone to dizzy spells and recently fell and

cut his head due to this dizziness.

The guidelines would suggest that he is immediately commenced on antihypertensive therapy and ideally a dual medication approach (Williams et al., 2018).

However, when we assess the patient, we see significant concerns about his wellbeing with the initiation of treatment as per guidelines. The effect of the newly commenced antihypertensives could be potentiated by the

Patient/Service User Work Environment/Equipment Individual Team Organisation and management

Appendix 4: Foundation of Human Factors in Healthcare

Society, culture and regulatory influence

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

98 Clinical R&D 

DARZALEX® (DARATUMUMAB) APPROVED FOR REIMBURSEMENT IN IRELAND Janssen, the Pharmaceutical Companies of Johnson & Johnson has announced Darzalex® (daratumumab) in combination with bortezomib, thalidomide and dexamethasone (VTd) has been granted reimbursement in Ireland for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT).

The announcement follows EC approval of daratumumab based on results from Part one of the Phase 3 CASSIOPEIA (MMY3006) study, published in The Lancet5 in June 2019 and presented at the 2019 American Society of Clinical Oncology (ASCO) Meeting.



Professor Philip Murphy, Consultant Haematologist, Beaumont Hospital said, “For Irish patients newly diagnosed with multiple myeloma, the importance of early intervention with effective first-line treatments to maximise response cannot be emphasised enough. Improvements in the standard of care to provide patients with valuable extra time are vital. Data from the CASSIOPEIA study demonstrates that the addition of daratumumab in combination with VTd can lead to deep remissions and prolong PFS.” Dr Thorsten Giesecke, General Manager, Commercial Business, Janssen Sciences Ireland UC, said, “Janssen is committed to providing access for patients to daratumumab in earlier disease stages of multiple myeloma, a type of blood cancer that can have a devastating impact on the lives of those affected. Every year in Ireland about 350 people are diagnosed with this condition, and today’s reimbursement provides those who are newly diagnosed and transplant eligible, with a long-awaited additional frontline therapy.”6 The Phase 3 CASSIOPEIA trial is a two-part study. Results from this first part of the trial showed that after consolidation, the stringent complete response (sCR) rate was significantly higher in the daratumumab-VTd arm (29 percent) compared to VTd alone (20 percent) (Odds Ratio [OR] = 1.60; 95 percent confidence interval [CI], 1.21-2.12; P<0.0010).2 At a median follow-up of 18.8 months, PFS was significantly improved in the daratumumabVTd group compared to VTd alone (Hazard Ratio [HR] = 0.47; 95 percent CI, 0.33-0.67; P<0.0001), and the median PFS was not reached in either arm.2 The addition of daratumumab to VTd resulted in an 18-month PFS rate of 93 percent compared to 85 percent for VTd alone.2

The most common (≥10%) Grade 3/4 treatment-emergent adverse events (TEAEs) for daratumumabVTd and VTd, respectively, were neutropenia (28 percent vs. 15 percent), lymphopenia (17 percent vs. 10 percent), stomatitis (13 percent vs. 16 percent) and thrombocytopenia (11 percent vs.

7 percent).2 In the daratumumabVTd combination arm, infusionrelated reactions occurred in 35 percent of patients.2 91% OF IRISH ADULTS SUFFER FROM BACK PAIN Minister of State, Patrick O’Donovan, T.D., officially opened the new Spine Excellence clinic in Limerick, a collaboration between Mater Private Network and the Poynton Spine Care Institute, bringing advanced spine care directly to patients in Limerick and Munster. The new clinic is a centre of excellence delivering comprehensive assessment, diagnosis, treatment and rehabilitation of spine conditions.

Spinal pain is a complex and multifactorial condition that is often poorly understood, incorrectly assessed, and inadequately treated.

At Spine Excellence, the expert team have a deep understanding of all aspects of spinal pathology and work with patients to develop a bespoke plan.

The extent to which Irish people suffer from back pain was made clear in a survey commissioned in conjunction with the official opening of the clinic. Conducted

by Bounce Insights for Mater Private Network, the survey among 500 Irish adults (28% of whom were from the Munster region) Minister of State, Patrick O’Donovan TD with Spine Excellence Clinical Director and leading Irish spine surgeon, Mr. Ashley Poynton, David Slevin, Deputy Chief Executive of Mater Private Network

AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE

found that 91% of respondents suffered from back pain, while 46% reported missing either work or college because of their pain.

Furthermore, 61% percent of respondents said they have visited their GP as a result of back pain and 53% said that their pain has impacted personal time with family and friends.

Spine Excellence Clinical Director and leading Irish spine surgeon, Mr. Ashley Poynton, said, “I am incredibly proud of our team here at Spine Excellence. They will be able deliver a uniquely comprehensive approach to spine care in a stateof-the-art facility and rapid access to the Mater Private Network high tech spinal facilities in the Cork and Dublin hospitals, when needed.

Our team has a broad and deep knowledge of spinal pathology from highly complex surgical cases to the most challenging rehabilitation patients and everything in between.

“Most spinal pain can be treated successfully by regaining movement, flexibility, and strength, and building confidence in functional movement and exercise.

While many people with spinal pain do not need any intervention other than rehabilitation, others may have underlying conditions that require deeper intervention, up to and including surgery. At Spine Excellence in Limerick, we have assembled an expert team, from specialist consultants and surgeons to spine expert physiotherapists to deal with all eventualities and all spinal pathologies.

“Our philosophy is centred around the patient understanding the nature of the problem and building confidence in their own ability to recover.”

David Slevin, Deputy Chief Executive of Mater Private Network, said, “Mater Private Network is delighted to deepen our collaboration with the Poynton Spine Care Institute through the establishment of Spine Excellence

in Limerick. Along with our hospitals in Cork and Dublin, we already have a presence in Limerick as the operator of the Mid-Western Radiation Oncology Centre at University Hospital Limerick. We understand how important it is to make best in class healthcare services more accessible to patients in the region. We are delighted to be part of Spine Excellence in Limerick with outstanding surgeons Mr. Ashley Poynton, Mr. Deb Roy, Mr. Islam Gawish along with the expert team.”

GSK ON BEHALF OF VIIV HEALTHCARE LAUNCHES AND REKAMBYS VOCABRIA IN IRELAND





GSK Ireland on behalf of ViiV Healthcare is pleased to announce that eligible people living with Human Immunodeficiency Virus (HIV) in Ireland now have access to Vocabria (cabotegravir longacting injection) developed by ViiV Healthcare in combination with Rekambys (rilpivirine long-acting injection) developed by Janssen Sciences Ireland UC (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Vocabria and Rekambys is indicated for the treatment of HIV type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL), on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the non-nucleoside reverse transcriptase inhibitor (NNRTI) and integrase inhibitor (INI) class.1 This marks the first time that people living with HIV in Ireland can access a complete, longacting regimen once every two-months. This could reduce the number of days receiving treatment from 365 to 6 per year, when on the continuation injection phase of treatment.

Professor Sam McConkey, Head of the Department of International Health and Tropical Medicine at the Royal College of Surgeons said: “Over the last 20 years great progress has been made in developing effective treatments for HIV that can suppress the virus in the body to undetectable levels, however until now it has required daily treatment. The introduction of a long-acting injectable treatment means that eligible people living with HIV will only need to be treated every two months, rather than every day. This approach has the potential to help lessen the burden of treatment and reduce the worry and stigma that comes with having to take treatments daily. We have used IM cabotegravir in the context of a phase III clinical trial in Ireland

99 and the patients in the trial were delighted to participate.”

Dr Nneka Nwokolo, Head of Global Patient Affairs at ViiV Healthcare and honorary consultant in sexual health and HIV medicine said: “At ViiV Healthcare, our mission is to ensure that no one living with HIV is left behind and we recognise that there are still unmet needs in both the choice of medication they take, and how often they take it.

We understand that no medicine works for every individual living with HIV, so we are committed to offering innovative choices that help address their evolving needs.

We are delighted that the first and only complete long-acting injectable HIV medicine is now available in Ireland, allowing us to focus on the people living with the condition and provide them with treatment options that remove the need for regular daily HIV tablets.”

Outlining the need for a less frequent dosing regimen, the largest global HIV patient-reported outcomes study to-date conducted

by ViiV Healthcare, Positive Perspectives Wave 2, which included 50 Irish participants, found that when asked about their treatment aspirations and attitudes towards innovative medications, 55% (n=1306/2389) of participants said they would prefer not having to take medication every day, as long as their HIV stays suppressed.2 In addition, 58% (n=1394/2389) noted that taking daily HIV medication acts as a constant reminder of HIV in their lives, while up to 38% (n=906/2389) of participants reported anxiety around the fact that taking daily treatment could increase the chances of revealing their HIV status to others.3 Stephen O’Hare, Executive Director at HIV Ireland said: “HIV Ireland welcomes the option of longacting injectable antiretroviral treatment for people living with HIV. For those eligible, this choice of treatment could be game changing for people who struggle with their current regimens, by eliminating the daily pill burden. The impact of this new treatment option could greatly improve adherence and reduce the burden for marginalised and harder-to-reach communities who may prefer the 2-monthly regimen to a daily oral pill.”

SANOFI-GSK NEXTGENERATION COVID-19 BOOSTER DELIVERS STRONG IMMUNE RESPONSE AGAINST VARIANTS OF CONCERN, INCLUDING OMICRON Sanofi has reported data from two trials, VAT02 Cohort 2 and COVIBOOST VAT013, conducted with its new next-generation COVID-19 booster vaccine

candidate modelled on the Beta variant antigen and including GSK’s pandemic adjuvant.

SMARMORE CASTLE CLINIC GAINS MAJOR INTERNATIONAL ACCREDITATION

In the Phase 3 VAT02 Cohort 2 study, the Sanofi-GSK nextgeneration vaccine candidate induced (at day 15 postimmunization) a significant boost in antibody titers above baseline against multiple variants of concern (15-fold increase against D614 parent virus, 30-fold increase against Beta strain) in adults previously primed with mRNA COVID-19 vaccines.

In particular against Omicron, preliminary data show a 40-fold increase against BA.1. The SanofiGSK next-generation booster candidate generated double the number of neutralizing antibodies against Omicron BA.1 and BA.2 compared to the D614-based (original parent virus) booster.

Smarmore Castle Clinic, a 32-bed detox and addiction rehab clinic near Ardee, Co. Louth, has been awarded a major international accreditation recognising Excellence in International Best Practice, Legislation and Regulatory Standards.

In parallel, the independent COVIBOOST (VAT013) study conducted by the Assistance Publique – Hôpitaux de Paris (AP-HP) demonstrated that, following primary vaccination with two doses of Pfizer-BioNTech’s Comirnaty vaccine, the SanofiGSK next-generation booster candidate generated a higher immune response (as measured by neutralizing antibody titers) than Pfizer-BioNTech’s booster or the Sanofi-GSK first-generation booster, both of which target the original D614 parent strain.

The proportion of participants with at least a 10-fold increase in neutralizing antibody titers for the original D614 SARS-CoV-2 strain between day 0 and day 15 was: • 76.1% (95% CI 64.5–85.4) for the Sanofi-GSK next-generation booster, vs • 63.2% (95% CI 51.3–73.9) for the Pfizer BioNTech D614 booster, and • 55.3% (95% CI 43.4–66.7) for the Sanofi-GSK D614 (firstgeneration parent booster candidate).

The prestigious award was received from the Comparative Health Knowledge System (CHKS), a UK health organisation which provides independent recognition of commitment to quality improvement for boards, external regulators and patients. The CHKS award follows a comprehensive assessment by a team of external senior healthcare professionals which examined a range of activities undertaken at Smarmore Castle Clinic.

Located in a 13th century castle, and surrounded by 15 acres of gardens, Smarmore Castle Clinic offers an unrivalled environment in which patients can take the first steps on the road to recovery from addiction.

News of the recognition comes as the Health Service Executive (HSE) has entered into an agreement with Smarmore Castle Clinic to provide public funding for patients in need of inpatient detox and rehab from alcohol and drugs.

Moyra Amess, Director, Assurance & Accreditation at CHKS stated, “The accreditation process requires dedication and commitment. Every organisation we make this award to has proved to our external assessors that its standards and process meet international best practice standards. This is a significant achievement.”

For Keith Cassidy, Clinic Manager at Smarmore Castle Clinic, the recognition reflects its high standards of care and successful outcomes for patients. “We are

delighted to receive this esteemed award which recognises the tireless work undertaken in this clinic towards the rehabilitation of patients. Our healing and selfreflective approach seek to show both patients and their families that there is life after addiction. Lives can be rebuilt.

“Smarmore Castle Clinic has quickly become one of the leading addiction treatment centres in Ireland and we are committed to offering people freedom from addiction. We will continue to improve our services in the months and years ahead, with recovery front and centre of everything that we do.

“Considering six out of ten people have direct experience of addiction, we are also now particularly pleased to have the opportunity to work with the HSE and other agencies in addressing the challenge of addiction.”

Smarmore Castle Clinic’s medical team is led by two of Ireland’s leading addiction specialists, medical director Dr Hugh Gallagher and consultant psychiatrist, Professor Gerry Lynch.

The clinic provides a distinctive therapeutic and medical programme for those suffering from alcoholism, drug and behavioural addictions. The treatment plan offered is based on the successful Minnesota Model 12-step treatment programme.

The clinic also offers a much sought-after dual diagnosis programme that directly treats patients who have both addiction and mental health issues. Indeed, Smarmore’s on-site 24-hour medical team enables the clinic to offer a full medically managed detox where necessary.

Dr Hugh Gallagher, Medical Director and Keith Cassidy, Clinic Manager

In this study, which included 247 subjects, all the three vaccines also elicited neutralizing antibodies against the Omicron BA.1 variant, with highest responses generated by the Sanofi-GSK next-generation candidate. Results of COVIBOOST study are available on a pre-print server, pending publication in a peer-reviewed journal.

Across both studies, the SanofiGSK next-generation vaccine candidate was well-tolerated, with a favorable safety profile.

In the VAT02 cohort 2 study, low numbers (less than 4%) of Grade 3 reactions were reported, all transient and non-severe.

HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST 2022

Whether your patients’ moderate-to-severe AD is FIERCE or TAMER,

CIBINQO is a convenient once-daily oral JAK1 inhibitor for moderate-to-severe atopic dermatitis (AD) that offers1-4

Significant skin clearance at week 12, with sustained control at week 48 1,5

Rapid itch relief, superior to dupilumab + TCS at week 2 for CIBINQO 200 mg + TCS, with significant results as early as day 41,6

A once-daily pill available in multiple doses that can be used with or without medicated topical therapies so you can

tailor treatment to meet the individual needs of your patients

1-3,7,8

CONSISTENT SAFETY PROFILE: Rigorously studied in >3100 patients across 7 clinical trials, including one ongoing LTE PRESCRIBING INFORMATION CIBINQO® ▼ (ABROCITINIB)

Please refer to full Summary of Product Characteristics (SmPC) before prescribing Cibinqo®.

Presentation: Film-coated tablets containing 50 mg, 100 mg, or 200 mg abrocitinib. Each tablet contains 1.37 mg, 2.73 mg, and 5.46 mg of lactose monohydrate, respectively.

Indications: For the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. Dosage: Treatment should be initiated and supervised by a healthcare professional experienced in the diagnosis and treatment of atopic dermatitis. Posology: The recommended starting dose is 200 mg once daily. A starting dose of 100 mg once daily is recommended for patients ≥ 65 years of age. For other patients who may benefit from a starting dose of 100 mg, see sections 4.4 and 4.8 of the SmPC. During treatment, the dose may be decreased or increased based on tolerability and efficacy. The lowest effective dose for maintenance should be considered. The maximum daily dose is 200 mg. Can be used with or without medicated topical therapies for atopic dermatitis. Discontinuation of treatment should be considered in patients who show no evidence of therapeutic benefit after 24 weeks. Treatment initiation: Treatment should not be initiated in patients with a platelet count < 150 × 103/mm3, an absolute lymphocyte count (ALC) < 0.5 × 103/mm3, an absolute neutrophil count (ANC) < 1.2 × 103/mm3 or who have a haemoglobin value < 10 g/dL. Dose interruption: If a patient develops a serious infection, sepsis or opportunistic infection, dose interruption should be considered until the infection is controlled. Interruption of dosing may be needed for management of laboratory abnormalities. Missed doses: If a dose is missed, patients should be advised to take the dose as soon as possible unless it is less than 12 hours before the next dose, in which case the patient should not take the missed dose. Thereafter, dosing should be resumed at the regular scheduled time. Interactions: In patients receiving dual strong inhibitors of cytochrome CYP2C19 and moderate inhibitors of CYP2C9, or strong inhibitors of CYP2C19 alone (e.g., fluvoxamine, fluconazole, fluoxetine and ticlopidine), the recommended starting dose of Cibinqo should be reduced by half to 100 mg or 50 mg once daily. Treatment is not recommended concomitantly with moderate or strong inducers of CYP2C19/CYP2C9 enzymes (e.g., rifampicin, apalutamide, efavirenz, enzalutamide, phenytoin). Renal impairment: No dose adjustment is required in patients with mild renal impairment, i.e., estimated glomerular filtration rate (eGFR) of 60 to < 90 mL/min. In patients with moderate (eGFR 30 to < 60 mL/min) renal impairment, the recommended dose of Cibinqo should be reduced by half to 100 mg or 50 mg once daily. In patients with severe (eGFR < 30 mL/min) renal impairment, 50 mg once daily is the recommended starting dose. The maximum daily dose is 100 mg. Cibinqo has not been studied in patients with end-stage renal disease (ESRD) on renal replacement therapy.

Hepatic impairment: No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Cibinqo must not be used in patients with severe (Child Pugh C) hepatic impairment. Elderly: The recommended starting dose for patients aged 65 years or more 100 mg once daily. Paediatric population: The safety and efficacy of Cibinqo in children under 12 years of age have not yet been established. No data are available. Cibinqo has been studied in adolescents 12 to < 18 years of age.

However, because of bone findings in juvenile rats (comparable to a 3 month old human), additional long-term data in growing adolescents is needed to conclude that the benefits outweigh the risks. Method of administration: This medicinal product is to be taken orally once daily with or without food at approximately the same time each day. In patients who experience nausea, taking Cibinqo with food may improve nausea. Tablets should be swallowed whole with water and should not be split, crushed, or chewed because these methods have not been studied in clinical trials. Contra-indications: Hypersensitivity to the active substance or to any of the excipients. Active serious systemic infections, including tuberculosis (TB), severe hepatic impairment, pregnancy, and breast-feeding. Warnings and Precautions: Serious infections: Serious infections have been reported in patients receiving Cibinqo. The most frequent serious infections in clinical studies were herpes simplex, herpes zoster and pneumonia. Treatment must not be initiated in patients with an active, serious systemic infection. Risks and benefits of treatment prior to initiating Cibinqo should be considered. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with abrocitinib. A patient who develops a new infection during treatment should undergo prompt and complete diagnostic testing and appropriate antimicrobial therapy should be initiated. The patient should be closely monitored, and therapy should be temporarily interrupted if the patient is not responding to standard therapy. Tuberculosis: Patients should be screened for TB before starting treatment and yearly screening for patients in highly endemic areas for TB should be considered. Abrocitinib must not be given to patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, preventive therapy for latent TB should be started prior to initiation of treatment. Viral reactivation: Viral reactivation, including herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical studies. The rate of herpes zoster infections was higher in patients 65 years of age and older and patients with severe atopic dermatitis at baseline. If a patient develops herpes zoster, temporary interruption of treatment should be considered until the episode resolves. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy and during therapy. Patients with evidence of active hepatitis B or hepatitis C (positive hepatitis C PCR) infection were excluded from clinical studies. Patients who were hepatitis B surface antigen negative, hepatitis B core antibody positive, and hepatitis B surface antibody positive had testing for hepatitis B virus (HBV) DNA. Patients who had HBV DNA above the lower limit of quantification (LLQ) were excluded. Patients who had HBV DNA negative or below LLQ could initiate treatment; such patients had HBV DNA monitored. If HBV DNA is detected, a liver specialist should be consulted. Vaccination: No data are available on the response to vaccination in patients receiving Cibinqo. Use of live, attenuated vaccines should be avoided during or immediately prior to treatment. Prior to initiating treatment with this medicinal product, it is recommended that patients be brought up to date with all immunisations, including prophylactic herpes zoster vaccinations, in agreement with current immunisation guidelines. Thrombotic events including pulmonary embolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving abrocitinib. Cibinqo should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient’s risk for DVT/PE include older age, obesity, a medical history of DVT/PE, prothrombotic disorder, use of combined hormonal contraceptives or hormone replacement therapy, patients undergoing major surgery or prolonged immobilisation. If clinical features of DVT/PE occur, treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment. Malignancy (including non-melanoma skin cancers): Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical

studies with abrocitinib. Clinical data are insufficient to assess the potential relationship of exposure to abrocitinib and the development of malignancies. Long-term safety evaluations are ongoing. The risks and benefits of Cibinqo treatment should be considered prior to initiating in patients with a known malignancy other than a successfully treated NMSC or cervical cancer in situ or when considering continuing Cibinqo therapy in patients who develop a malignancy. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Haematologic abnormalities: Confirmed ALC < 0.5 × 103/mm3 and platelet count < 50 × 103/mm3 were observed in less than 0.5% of patients in clinical studies. Treatment with abrocitinib should not be initiated in patients with a platelet count < 150 × 103/mm3, an ALC < 0.5 × 103/mm3, an ANC < 1.2 × 103/mm3 or who have a haemoglobin value < 10 g/dL. Complete blood count should be monitored 4 weeks after initiation of therapy and thereafter according to routine patient management. Lipids: Dose dependent increases in blood lipid parameters were reported in patients treated with abrocitinib compared to placebo. Lipid parameters should be assessed approximately 4 weeks following initiation of therapy and thereafter according to the patient’s risk for cardiovascular disease. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Patients with abnormal lipid parameters should be further monitored and managed according to clinical guidelines, due to the known cardiovascular risks associated with hyperlipidaemia. In patients with a high burden of cardiovascular risk factors, the risks, and benefits of abrocitinib compared to that of other available therapies for atopic dermatitis should be considered. If abrocitinib is chosen, interventions to manage lipid concentrations should be implemented according to clinical guidelines. Elderly: The safety profile observed in elderly patients was similar to that of the adult population with the following exceptions: a higher proportion of patients 65 years of age and older discontinued from clinical studies and were more likely to have serious adverse reactions compared to younger patients; patients 65 years and older were more likely to develop low platelet and ALC values; the incidence rate of herpes zoster in patients 65 years of age and older was higher than that of younger patients. There are limited data in patients above 75 years of age. Immunosuppressive conditions or medicinal products: Patients with immunodeficiency disorders or a first-degree relative with a hereditary immunodeficiency were excluded from clinical studies and no information on these patients is available.

Combination with biologic immunomodulators, potent immunosuppressants such as ciclosporin or other Janus kinase (JAK) inhibitors has not been studied. Their concomitant use with abrocitinib is not recommended as a risk of additive immunosuppression cannot be excluded. Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Drug Interactions:Potential for other medicines to affect pharmacokinetics of abrocitinib: Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9 enzymes, and to a lesser extent by CYP3A4 and CYP2B6 enzymes, and its active metabolites are renally excreted and are substrates of the organic anion transporter 3 (OAT3). Therefore, exposures of abrocitinib and/or its active metabolites may be affected by medicinal products that strongly inhibit or induce theses enzymes and transporter. Dose adjustments, as appropriate, may be required. Co-administration with products which increase gastric pH: The effect of elevating gastric pH with antacids, H2-receptor antagonists (famotidine), or proton pump inhibitors (omeprazole) on the pharmacokinetics of abrocitinib has not been studied and may reduce the absorption of abrocitinib due to the low solubility of abrocitinib at pH above 4. Potential for Cibinqo to affect pharmacokinetics of other medicinal products: No clinically significant effects of Cibinqo were observed in drug interaction studies with oral contraceptives. Caution should be exercised for concomitant use of abrocitinib with dabigatran. Caution should be exercised as the levels of P-gp substrates with a narrow therapeutic index, such as digoxin, may increase. The exposures of medicinal products metabolised by CYP2B6 (e.g., bupropion, efavirenz) and CYP1A2 (e.g., alosetron, duloxetine, ramelteon, tizanidine) may be decreased and of those metabolised by CYP2C19 (e.g., S mephenytoin) may be increased initially and then decreased, when used concomitantly with abrocitinib. Fertility, pregnancy, and lactation: Women of childbearing potential: Women of reproductive potential should be advised to use effective contraception during treatment and for 1 month following the final dose of Cibinqo. Pregnancy planning and prevention for females of reproductive potential should be encouraged. Pregnancy: There are no or limited amount of data on the use of abrocitinib in pregnant women. Studies in animals have shown reproductive toxicity. Abrocitinib has been shown to cause embryo-foetal lethality in pregnant rats and rabbits, skeletal variations in the foetuses of pregnant rats and rabbits and to affect parturition and peri/postnatal development in rats. Cibinqo is contraindicated during pregnancy.

Breast-feeding: There are no data on the presence of abrocitinib in human milk, the effects on the breast fed infant, or the effects on milk production. Abrocitinib was secreted in milk of lactating rats. A risk to newborns/infants cannot be excluded and Cibinqo is contraindicated during breast feeding. Fertility: Based on the findings in rats, oral administration of Cibinqo may result in temporary reduced fertility in females of reproductive potential. The effects on female rat fertility were reversible 1 month after cessation of abrocitinib oral administration. Driving and operating machinery: Cibinqo has no effect on the ability to drive or use machines. Side Effects: The most commonly reported adverse reactions are nausea (15.1%), headache (7.9%), acne (4.8%), herpes simplex (4.2%), blood creatine phosphokinase increased (3.8%), vomiting (3.5%), dizziness (3.4%) and abdominal pain upper (2.2%). The most frequent serious adverse reactions are infections (0.3%) including herpes simplex, herpes zoster, and pneumonia. Refer to SmPC for further information on side effects. Legal Category: S1A. Marketing Authorisation Numbers: EU/1/21/1593/002 - Cibinqo 50 mg (28 film-coated tablets), EU/1/21/1593/007 - Cibinqo 100 mg (28 film-coated tablets); EU/1/21/1593/012 - Cibinqo 200 mg (28 film-coated tablets). Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

For further information on this medicine please contact Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 467 6500. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Last revised: December 2021.

Ref: CQ 1_0 IE.

References: 1. Bieber T, Simpson EL, Silverberg JI, et al. N Engl J Med. 2021;384(12):1101-1112. 2. Simpson EL, Sinclair R, Forman S, et al. Lancet. 2020;396(10246):255-266. 3. Silverberg JI, Simpson EL, Thyssen JP, et al. JAMA Dermatol.

2020;156(8):863-873. 4. Boeri M, Sutphin J, Hauber B, et al. J Dermatolog Treat. 2020 Nov 2:1-10. doi:10.1080/09546634.1832185. 5. Reich K, Silverberg JI, Papp K, et al. Presented at the Revolutionizing Atopic Dermatitis Virtual Conference; 13 June 2021. 6. Ständer S, Yosipovitch G, Simpson EL, et al. Presented at the American Academy of Dermatology Virtual Meeting Experience 2021; 23-25 April 2021. 7. Cibinqo Summary of Product Characteristics.

8. Blauvelt A, Silverberg JI, Lynde CW, et al. J Am Acad Dermatol. Published online 17 August 2021. doi: 10.1016/j.jaad.2021.05.075. 9. Cork MJ, Deleuran MS, Geng B, et al. Presented at the European Academy of Dermatology and Venereology Virtual Congress 2021; 29 September-2 October 2021.

Although some clinical trials included adolescents, please note that CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy.

TCS includes low- to medium-potency topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase 4 inhibitors, per protocol guidance in JADE COMPARE. Nonmedicated topicals were also required.1 AD=atopic dermatitis; JAK=Janus kinase; LTE=long-term extension. © 2022 Pfizer Inc. All rights reserved. July 2022. PP-CIB-IRL-0035

9