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Irish Research Council Researcher of the Year Awards

Researcher of the Year Awards

The Irish Research Council has announced its 2021 Researcher of the Year awards.

UCD Chair of Critical Care Medicine, Professor Alistair Nichol received a special commendation for his ‘exceptional contribution’ in the field of medical research, specifically in critical care clinical trials and especially in the global fight against the COVID-19 pandemic. On receiving the accolade, Professor Nichol said, “I am honoured that the IRC has recognised my work and that of my team over the last decade and particularly during the COVID pandemic, with their special commendation today. This represents many years’ work by a large team in Ireland and beyond. I am very grateful to my colleagues within UCD, the Irish Critical Care Community and our global network collaborators. “Ireland’s Intensive Care Units continue to be the front line in our ongoing war against COVID. Our research collaborations have allowed us to understand the COVID waves during the pandemic – allowing us clinicians to identify patients at the highest risk of death, and the genetic factors associated with death in the ICU, so we can identify novel therapies.” Professor Nichol is Director of the Irish Critical Care-Clinical Trials UCD Chair of Critical Care Medicine Professor Alistair Nichol with Minister for Further and Higher Education, Research, Innovation and Science

Network (ICC-CTN), which runs, and builds capacity for running, clinical trials in Irish Intensive Care Units (ICUs). Funded by the Health Research Board, the ICC-CTN has also become a world-leading coordination centre for major global clinical trials, including REMAP-CAP.

REMAP (Randomised, Embedded, Multifactorial, Adaptive Platform trial) is a global trial that determines and continuously updates the optimal set of treatments for communityacquired pneumonia. REMAPCAP has added trial domains so that the platform can respond rapidly to COVID-19, specifically (i) antiviral therapy and (ii) immune modulation therapy. To date, REMAP-CAP has identified three safe and effective treatments that reduce death and organ failure in critically ill COVID patients, namely steroids,

Osteoporosis: Keeping Safe at Home

Written by Louise Brent, Irish Hip Fracture Database (IHFD) and Major Trauma Audit (MTA) Manager for NOCA

Each year many injuries are sustained in the home due to falls, a lot of which could potentially be prevented. Data from the Irish Hip Fracture Database (IHFD) and the Major Trauma Audit (MTA) two national clinical audits governed by the National Office of Clinical Audit (NOCA) show year on year that the leading cause of people sustaining a hip fracture and major trauma injuries (which result in life threatening or life changing injuries) are falls typically from standing height or less and most occur in the home.

Over the course of both audits much has been done to raise awareness about home safety for the prevention of falls, however due to the unprecedented impact of the COVID-19 pandemic this has never been more important. Over the last two years we have all had to endure prolonged periods at home none more so effected than our older population. Indeed it was right to tell our older people to cocoon to protect themselves from the pandemic in the early stage but little has been done to support older people regain their confidence to go back outside and resume normal activities. This increased time at home will undoubtedly lead to a higher risk of falls at home owing to the increase in frailty associated with restricting ones mobility. In addition the social isolation, fear of going outside, decreased bone density, sarcopenia are all valid concerns as this pandemic refusing to abate. In the most recent Irish Hip Fracture Database Report advice was included about how people can remain active at home while being safe at home too.

IL6 receptor antagonists and anticoagulation, in ward patients. It has also determined that Hydroxychloroquine, Keletra, Hydroxychloroquine and Keletra in combination, convalescent plasma, Anakinra and anticoagulation do not improve outcomes in critically ill patients with COVID-19.

Professor of Zoology at Trinity College Dublin, Yvonne Buckley was named Researcher of the Year for work focused on the growth, reproduction and survival of plant and animal species. UCD’s Professor of Social Policy Michelle Norris was awarded the Impact Award for her proven record of research impact ‘beyond academia’ in the field of social housing policy. Postdoctoral researcher in the School of Psychology and Institute of Neuroscience at Trinity College Dublin, Dr Kathy Ruddy won the ‘Early Career Researcher of the Year’ award for her work using brain-computer interfaces to improve brain function. Postdoctoral researcher Dr Sara Delmedico, UCD School of Languages, Cultures and Linguistics, was awarded the IRC Maurice J Bric Medal of Excellence. Postdoctoral researcher Dr Marco Timpanella, UCD School of Mathematics and Statistics, was awarded the IRC Thomas Mitchell Medal of Excellence.

Strength of Balance

Indicated for the treatment of moderate to severe active rheumatoid arthritis in adults who have responded inadequately to, or are intolerant to one or more disease modifying anti-rheumatic drugs.1 May be used as monotherapy or in combination with methotrexate.1

Refer to Summary of Product Characteristics (SmPC) before prescribing, and for full prescribing information.

JYSELECA® filgotinib 100 mg or 200 mg film-coated tablets. Indication: Jyseleca is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease modifying anti rheumatic drugs (DMARDs). Jyseleca may be used as monotherapy or in combination with methotrexate (MTX). Dosage: Adults: 200 mg once daily. Taken orally with/without food. It is recommended that tablets are swallowed whole. Laboratory Monitoring: Refer to the SmPC for information regarding laboratory monitoring and dose initiation or interruption. Elderly: A starting dose of 100 mg once daily is recommended for patients aged 75 years and older as clinical experience is limited. Renal impairment: No dose adjustment required in patients with estimated creatinine clearance (CrCl) ≥ 60 mL/min. A dose of 100 mg of filgotinib once daily is recommended for patients with moderate or severe renal impairment (CrCl 15 to < 60 mL/min). Not recommended in patients with CrCl < 15 mL/min. Hepatic impairment: Mild/moderate hepatic impairment: no dose adjustment required. Severe hepatic impairment: not recommended. Children (< 18years): Safety and efficacy not yet established. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active tuberculosis (TB) or active serious infections. Pregnancy. Warnings/Precautions: See SmPC for full information. Immunosuppression: Combination use, with immunosuppressants e.g. azathioprine, ciclosporin, tacrolimus, or biologic DMARDs (bDMARDs) or other Janus kinase (JAK) inhibitors is not recommended as a risk of additive immunosuppression cannot be excluded. Infections: Infections, including serious infections such as pneumonia and opportunistic infections e.g. tuberculosis (TB), oesophageal candidiasis, and cryptococcosis have been reported. Risk benefit should be assessed prior to initiating in patients with risk factors for infections (see SmPC). Patients should be closely monitored for the development of signs and symptoms of infections during and after filgotinib treatment. Treatment should be interrupted if the patient is not responding to antimicrobial therapy, until infection is controlled. There is a higher incidence of serious infections in the elderly aged 75 years and older, caution should be used when treating this population. Tuberculosis: Patients should be screened for TB before initiating filgotinib, and filgotinib should not be administered to patients with active TB. Viral reactivation: Cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies (see SmPC). If a patient develops herpes zoster, filgotinib treatment should be temporarily interrupted until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed. Malignancy: Immunomodulatory medicinal products may increase the risk of malignancies. Malignancies were observed in clinical studies (see SmPC). Fertility: In animal studies, decreased fertility, impaired spermatogenesis, and histopathological effects on male reproductive organs were observed (see SmPC). The potential effect of filgotinib on sperm production and male fertility in humans is currently unknown. Haematological abnormalities: Do not start therapy, or temporarily stop, if Absolute Neutrophil Count (ANC) <1 × 109 cells/L, ALC <0.5 × 109 cells/L or haemoglobin <8 g/dL. Temporarily stop therapy if these values are observed during routine patient

JYSELECA – a preferential JAK1 inhibitor for moderate to severe RA1

JYSELECA shows more than 5x greater potency for JAK1 over JAK2/3 and TYK21* Balancing sustained efficacy2-6 with acceptable tolerability1,7

*This is based on biochemical assays, the clinical consequence of this is unknown. Common adverse events (≥1/100 to <1/10) include: nausea, upper respiratory tract infection, urinary tract infection, dizziness.1

Visit strengthofbalance.co.uk to learn more

management. Vaccinations: Use of live vaccines during, or immediately prior to, filgotinib treatment is not recommended. Lipids: Treatment with filgotinib was associated with dose dependent increases in lipid parameters, including total cholesterol, and high-density lipoprotein (HDL) levels, while low density lipoprotein (LDL) levels were slightly increased (see SmPC). Cardiovascular risk: Rheumatoid arthritis patients have an increased risk for cardiovascular disorders. Patients should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care. Venous thromboembolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors including filgotinib. Caution should be used in patients with risk factors for DVT/PE, such as older age, obesity, a medical history of DVT/PE, or patients undergoing surgery, and prolonged immobilisation. Lactose content: Contains lactose; patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take filgotinib. Pregnancy/ Lactation: Filgotinib is contraindicated in pregnancy. Filgotinib should not be used during breast-feeding. Women of childbearing potential must use effective contraception during and for at least 1 week after cessation of treatment. Driving/Using machinery: No or negligible influence, however dizziness has been reported. Side effects: See SmPC for full information. Common (≥1/100 to <1/10): nausea, upper respiratory tract infection, urinary tract infection and dizziness. Uncommon (≥1/1000 to <1/100): herpes zoster, pneumonia, neutropenia, hypercholesterolaemia and blood creatine phosphokinase increase. Serious side effects: See SmPC for full information Legal category: POM Pack: 30 film-coated tablets/bottle Price: UK Basic NHS cost: £863.10; Ireland: POA Marketing authorisation number(s): Jyseleca 100mg film-coated tablets EU/1/20/1480/001 EU/1/20/1480/002 Jyseleca 200mg film-coated tablets EU/1/20/1480/003 EU/1/20/1480/004 Further information: Galapagos UK, Belmont House, 148 Belmont Road, Uxbridge UB8 1QS, United Kingdom 00800 7878 1345 medicalinfo@glpg.com Jyseleca® is a trademark. Date of Preparation: January 2022 IE-RA-FIL-202112-00003

Additional monitoring required

Adverse events should be reported. For Northern Ireland, reporting forms and information can be found at yellowcard.mhra.gov.uk or via the Yellow Card app (download from the Apple App Store or Google Play Store). Adverse events should also be reported to Galapagos via email to Drug.safety.UK.Ireland@glpg.com or 00800 7878 1345 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 also be reported to Galapagos via email to Drug.safety.UK.Ireland@glpg.com or 00800 7878 1345

References: 1. JYSELECA SPC. Available at: www.medicines.org.uk / www.medicines.ie. Last accessed: January 2022. 2. Combe B, et al. Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2020-219214. 3. Genovese MC, et al. JAMA 2019;322 (4):315–325. 4. Westhovens R, et al. Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2020-219213. 5. Combe B, et al. Poster presented virtually at ACR, November 3–10, 2021. 6. Buch MH, et al. Poster presented virtually at ACR, November 3–10, 2021. 7. Genovese MC, et al. Poster presented virtually at the European League Against Rheumatism (EULAR) 2020 E-Congress, June 3–6, 2020.

Cardiac Rehabilitation: Is it important with Modern Interventional Reperfusion Techniques?

Reperfusion techniques have their origins in the work of Alexis Carrell in the early 20th century with his initial concepts regarding coronary perfusion and subsequent intrathoracic anastomosis of aorta and myocardial tissue in dogs. This eventually lead to a technique of attaching an adjunct artery into the myocardium of the left ventricle with the theorised result that collateral perfusion would be provided to the left anterior descending (LAD) coronary artery called the Veinberg procedure. This work was developed further when Ake Senning placed a patch over the left main stem (LMS) to improve blood flow. Modern coronary artery bypass grafting was eventually an option when Mason Sones inadvertently injected contrast dye into the right coronary artery (RCA) of a patient with rheumatic heart disease and mapped the coronary perfusion system allowing for direct identification of the coronary arteries. This discovery allowed conduit vessels to be attached directly to blocked arteries and thus “bypassing” the occlusions. This has been refined in the subsequent years to now being carried out very effectively utilising microsurgical techniques with various vascular conduits to bypass blockages in main coronary arteries as well as branch vessels. Such techniques allow for early discharge and reduced adverse events as a result.

Similarly, percutaneous interventional reperfusion has had significant improvements since the early work of the Italian Dr Gruentzig. From the initial treatments with balloons

Written by Padraig Denn, Clinical Nurse Manager 3, Mater Private Network

to most recent drug eluting stents and techniques allow those appropriately trained and experienced to treat the most complex of coronary disease including chronic total occlusions. Both Coronary Artery Bypassing Grafting (CABG) and Percutaneous Coronary Interventions (PCI) have a Level 1A recommendation from a multitude of international bodies. Figure 1 below identifies the type of patient that is best suited to the PCI versus CABG intervention.

However, this level of recommendation is only valid for proven ischaemic or flow limiting coronary disease. New research released initially in 2019 has proven that PCI and CABG have no additional benefit for the management of non-ischaemic coronary disease above medical therapy. Research has shown that utilisation of non-internal mammary vascular conduits for CABG have limited duration of patency especially if there is competitive flow from the native system. PCI techniques are limited to specific areas of coronary disease and care needs to be taken to prevent inadvertent occlusion of branch vessels which can cause on-going symptoms of angina after successful treatment of a significant coronary occlusion. One must also consider that both CABG and PCI reperfusion techniques are limited to the three main coronary arteries and a limited number of branch vessels. Therefore, when we look at Figure 2 we can see that the coronary perfusion system is far more elaborate than the three main arteries and main branches. Therefore, we can see why pharmacological treatment after initial intervention for the management of certain risk factors of coronary artery disease (CAD)is necessary. However, an individual’s tolerance of pharmacological treatments varies significantly and in the era of an ageing population with multiple co-morbidities the risk of polypharmacy needs to be considered and can

Figure 1: PCI Vs CABG

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. warfarin1 • Superiority demonstrated on major bleeding vs. warfarin1

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 fi brillation (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 fi rst 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 benefi t 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 signifi cant bleeding, hepatic disease associated with coagulopathy and clinically relevant bleeding risk, lesion or condition if considered a signifi cant risk factor for major bleeding, see SmPC for further details. Concomitant treatment with any other anticoagulant agent except under specifi c 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 fi brillation, 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 fi brillation and conditions that warrant mono or dual antiplatelet therapy, a careful assessment of the potential benefi ts against the potential risks should be made before combining this therapy with Eliquis. A clinical trial enrolled patients with atrial fi brillation 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 effi cacy of Eliquis have not been studied in patients with prosthetic heart valves, with or without atrial fi brillation. 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 fi brillation, 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 fi rst 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 benefi t 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 effi cacy 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 benefi ts 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 effi cacy 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 defi ciency 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 sulfi npyrazone) 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 specifi c 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 fi brillation. 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 benefi t of breast-feeding for the child and the benefi t 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*; specifi c haemorrhage such as gastrointestinal*, abnormal vaginal*, urogenital*, post procedural*, wound secretion*, incision site*, operative*. Rare: hypersensitivity*; anaphylaxis*; haemoptysis*; gingival bleeding*; specifi c haemorrhage such as eye (including conjunctival)*, rectal*, muscle*. Not known: angioedema*; specifi c 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; specifi c haemorrhage such as eye (including conjunctival)*, gastrointestinal*, rectal*. Uncommon: thrombocytopenia*; hypersensitivity*; anaphylaxis*; haemoptysis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); specifi c haemorrhage such as brain (encompassing intracranial, intraspinal)*, intra-abdominal*, haemorrhoidal*, mouth*, abnormal vaginal*, urogenital*, post procedural*, wound secretion*, incision site*, operative*, traumatic*. Rare: specifi c 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; specifi c haemorrhage such as gastrointestinal*, mouth*, rectal*, abnormal vaginal*, urogenital*. Uncommon: hypersensitivity*; anaphylaxis*; haemoptysis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); specifi c haemorrhage such as eye (including conjunctival)*, haemorrhoidal*, muscle*, post procedural*, wound secretion*, incision site*, operative*, traumatic*. Rare: specifi c haemorrhage such as brain (encompassing intracranial, intraspinal)*, respiratory tract*. Not Known: angioedema*; specifi c 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 fi lm-coated tablets 2.5 mg, 60 fi lm-coated tablets 2.5 mg, 56 fi lm-coated tablets 5 mg, 28 fi lm- coated tablets 5 mg. MARKETING AUTHORISATION HOLDER (SPC section 7): Bristol-Myers Squibb/Pfi zer 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

of the COVID 19 pandemic some facilities have had their nursing allocation decimated for prolonged periods due to the acute care service needs.

It is recommended that the CR programs be multidisciplinary to ensure all specialities expert knowledge is utilised to better educate the participants on how best to manage their condition independently in the community setting. It is this that is the cornerstone of the CR programs. CR phases one and two are designed to ensure that participant takes personal change of the management of their disease.

Figure 2: Representation of Coronary Perfusion

often complicate the decisionmaking processes of effective pharmacological treatment of the risks of CAD. service is overseen by the Irish Heart Foundation (IHF). CR in Ireland is recommended to be delivered on a phased basis. Figure 3 identifies the four phases of CR in Ireland. According to IACR information prior to the COVID 19 pandemic CR was delivered in thirty-seven centres across Ireland, mostly in the acute care setting. The services appeared to have stagnated over the previous ten years and were often provided by the nursing profession alone in each setting, despite national and international recommendations that CR be provided by a multidisciplinary team (MDT). The guidelines recommend that the MDT is made up of physiotherapists, social workers, occupational therapists, psychologists and administrative staff. Unfortunately, for periods

In phase I, according to the IACR guidelines, patients are usually hospitalised for two to five days after a significant cardiac event. It is at this time when the CR process should commence with the visit of a member of the CR team. The duration of stay is dependent upon the cause of the patient’s admission to hospital. The recommendation of the IACR guidelines is that this phase of the programme should involve • Give support and information to the patient and their families about heart disease • Assist the patient to identify personal cardiovascular risk factors We must also note that CAD causes are multifactorial (See • Discuss lifestyle modifications of personal risk factors and help Table 1) and many of them provide an individual plan to cannot be managed either support these lifestyle changes pharmacologically or with invasive interventions. Risk factors such as • Gain support from family increased body mass index (BMI), members to assist the increased alcohol consumption, poorly managed levels of stress patient in maintaining the necessary progress and smoking all require more • Plan a personal discharge complex interventions to ensure activity programme and that they are effectively encourage the patient to managed without worsening the adhere to this and commence risk of polypharmacy. daily walks

It is for the above, and many other, research guided reasons that Cardiac Rehabilitation (CR) has a Level 1A recommendation for all those who have a confirmed diagnosis of CAD without any restrictions from the initial causes or treatment modalities utilised for the management of the disease.

A Cochrane systematic review and meta-analysis has shown that participation in a CR programme reduces cardiovascular mortality, reduces hospitalisations and improves quality of life. International governing bodies Figure 2: Representation of Coronary Perfusion have recommended the utilisation of CR for the management of CAD leading to CR reported to We must also note that CAD causes are multifactorial (See Table 1) and many of them be utilised in nearly one-hundred and twenty countries worldwide. cannot be managed either pharmacologically or with invasive interventions. Risk factors CR in Ireland falls under the remit of the Irish Association of Cardiac such as increased body mass index (BMI), increased alcohol consumption, poorly manag Rehabilitation (IACR) and this levels of stress and smoking all require more complex interventions to ensure that they are effectively managed without worsening the risk of polypharmacy. It is for the above, and many other, research guided reasons that Cardiac Rehabilitation (CR)

Phase I: In hospital patient period Phase lI: Post discharge pre exercise period

Figure 3: Phases of Cardiac Rehabilitation

Cardiac Rehab

Phase III: Exercise and Education Programme Phase lV: Maintenance

• Inform patients regarding

Phase II and Phase III programmes, if available, and encourage their attendance The CR member who meets with the patient in this phase is dependent upon the structure of the programme in that specific setting. Ideally education on the components of the CR programme (e.g. disease process, medication management, exercise regime) should be provided by those with that specific expertise (e.g. CNS, Pharmacist, Physiotherapist). This phase is also an opportunity for the patient to become actively involved in their own care through completion of assessments and identification of their own risk factors for CAD. This will facilitate the patient to take ownership of their condition and its future management. The focus of this phase of the programme is to create an individualised plan of care for each patient. This involves assessments of the various components of CAD including psychological status, risk factor profile, activity level, smoking and others. Based on these assessments appropriate referrals should be made to relevant healthcare professionals. In Phase II the aim is to reinforce the education that was provided in Phase I and to maintain lifestyle changes. It happens after discharge but prior to the commencement of Phase III. It can occur in a wide variety of settings (e.g. phone contact, clinic reviews, patient’s own home or GP’s office). The patient should commence some degree of exercise in this phase which is often self-directed and is dependent upon the initiating event that caused the referral to the CR system. Phase III is a structured longitudinal exercise programme that entails regular attendance (most often twice weekly for six weeks) and each session involves a warm-up, aerobic and cool down phase. Some programmes may also include heart rhythm monitoring and resistance training. According to the IACR 2013 Guidelines Phase III comprises all the following: • Exercise prescription based on clinical status, risk stratification, previous activity and future needs

• Education for patient and family regarding: • Cardiac anatomy and physiology related to the cardiac event

• Recognition of cardiac pain and symptom management • Risk factor identification and management • Benefits of physical activity • Energy conservation/graded return to activities of daily living • Cardio protective healthy eating • Prescribed cardiac medication and importance of compliance with same

• Resumption of sexual activity • Benefits and entitlements • Stress management and relaxation techniques • Counselling and behaviour modification

• Smoking cessation • Vocational counselling This phase is dependent upon the expertise of the MDT to ensure that all components of the programme are met. Phase IV of CR is designed to consolidate the improvements in exercise levels and to reinforce the education provided in Phase III. The aim is to maintain lifestyle changes to best ensure long-term change. This can be facilitated in several settings if there are appropriately qualified and experienced providers of this phase of the programme. Unfortunately, this appears to be an area that is lacking in Ireland with only ten recognised providers of Phase IV CR and only one of the thirty-seven registered CR sites providing this phase within their facility. There is no published evidence as to what extent each of the thirty-seven sites for CR in Ireland adhere to these guidelines. The author was further unable to gain access to any official numbers of patients that attend each of the programmes. Similarly, there is no available information to the author regarding the short, medium or long-term benefits of CR programmes in Ireland as any information regarding this is generally maintained in site specific databases. The IACR have previously requested participating sites to complete Excel spreadsheets regarding numbers and outcomes for individual patients through each CR site but this information has not yet been made public. International research has shown that CR is inconsistently implemented not only between countries but within individual countries. Further research has shown that guideline implementation is often improved through the utilisation of Information and Communication Technologies (ICT). The use of such technologies may also assist as we migrate from previous group setting for CR to the new COVID restriction limitations on indoor group activities, allowing for remote interaction of groups. The CR team in the Mater Private Cork have managed to utilise Skype to allow for group exercise and education sessions to be facilitated without impinging on the restrictions in effect during this international pandemic. Further utilisation of ICT should be considered not only to assist the members of the MDT to effectively document the various components of CR programs but to subsequently assess the effectiveness of individual programs and potentially improve the effectiveness of programs. It is clear that the utilisation of CR for those who have a confirmed diagnosis of CAD is clearly beneficial for the longterm outcomes of patients irrespective of the interventional reperfusion method utilised for confirmed occlusive CAD. CR is designed to equip the participant with the skills and knowledge to best manage all aspects of their lifestyle to reduce symptoms of and progression of their CAD. It is also designed to create a support network for on-going management of symptoms and the psychological impact of a diagnosis of CAD. Therefore, Cardiac Rehabilitation should be considered a pivotal treatment modality for any individual with a diagnosis of coronary artery disease.

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