NCHD overtime dispute
David Lynch reports on the IMO’s recent frustration over the failure of the HSE to pay NCHDs agreed overtime rates
PAGE 12
Anna Wedderburn provides an overview of some notable examples of Irish Covid-19 research to date
CATHERINE REILLY
The HSE Workplace Health and Wellbeing Unit has obtained a legal opinion, which indicates there is no legal basis for occupational health to be involved in Covid-19 contact management/tracing of healthcare workers, the Medical Independent (MI) understands.
The area is considered to fall under public health rather than health and safety regulations, it is understood. The legal opinion was obtained earlier this year.
Occupational health was accorded this role at the onset of the pandemic when the healthcare service was in crisis response mode.
However, it has placed a considerable ongoing strain on under-resourced occupational health departments, many of which are struggling to undertake their core functions.
As previously reported by MI, the HSE
has substantially increased its expenditure on outsourced occupational health services during the pandemic. The HSE spent almost €794,786 on outsourced services in 2020, compared to €99,292 in 2019 and €297,413 in 2018.
Outside of healthcare, Covid-19 contact tracing/management is organised through the HSE’s contact management programme (CMP), but the occupational health departments are not part of the CMP and have poor IT capabilities.
Additionally, occupational health is generally not an evening/weekend service and its work in this area is not standardised nationally.
MI asked the HSE if there were data protection issues arising from this matter and about any plans to remove the function from occupational health departments.
“The legal opinion is under consideration and discussions are ongoing,” said a spokesperson.
Biases in clinical research have compromised the medical treatment of women for decades, writes Dr Sarah Fitzgibbon
PAGE 22
The head of the HSE’s organ donation and transplant section “corresponded directly” with the Executive Director of Sláintecare “to raise awareness of the potential risk to provision of transplant services in the future” due to the proposed consultant contract, the HSE has confirmed. Director of HSE Organ Donation and Transplant Ireland (ODTI) Prof Jim Egan wrote to the then Executive Director of Sláintecare, Ms Laura Magahy, in his capacity as Chair of the national organ donation and transplant advisory group (NODTAG).
At a meeting of NODTAG in May, it was agreed that proposed consultant salaries did not provide for the “onerous on call rotas” associated with transplantation, according to minutes obtained by the Medical
Independent (MI) under Freedom of Information law.
Proposed new pay structures for consultant staff were discussed during the meeting. According to minutes, Dr Colm Magee, Consultant Nephrologist at Beaumont Hospital in Dublin, commented that the “NHS have a similar model and recruitment is a major issue”.
An action arising from the meeting was that Prof Egan would discuss the issue with transplant surgeons to get their views on the proposed contract.
A spokesperson for HSE ODTI told MI: “Transplant surgeons expressed concerns on prospective recruitment to the speciality given the onerous nature of delivery of the service, which includes significant out-ofhours activity and call rota. The proposal is ‘one size fits all’, which does not take into account the scope of responsibility and intensity of work.”
Vimovo® is indicated in adults for the symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, in patients who are at risk for developing non-steroidal anti-inflammatory drug (NSAID) -associated gastric and/or duodenal ulcers and where treatment with lower doses of naproxen or of other NSAIDs is not considered sufficient.1
About 1957: That was when, was recently launched at the headquarters of the CAI in Merrion Square, Dublin.
Prof Cunningham served as Foundation Dean, Perdana University RCSI School of Medicine, Malaysia, before taking up his current role as Medical Director of the Galway Clinic.
The book was written to give “an insight into and an understanding of the great social, political, and sporting highlights” of the year 1957.
Pictured at the launch of Prof Cunningham’s book are (L-R): Mr Joe Cunningham, (brother of the author); Mr Martin McCormack, CEO, CAI; Ms Ann Cunningham, (wife of the author); and Prof Cunningham.
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.
XELJANZ® is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent.
XELJANZ® in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs.
XELJANZ® in combination with MTX is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy.
PP-XEL-IRL-0668
Date of preparation: September 2021
When the atypical is typical
Lipertance® (Atorvastatin,perindopril,amlodipine): Abbreviated Prescribing Information: Please refer to the Summary of Product Characteristics before prescribing. COMPOSITION*: Lipertance 10mg/5mg/5mg, 20mg/5mg/5mg, 20mg/10mg/5mg, 20mg/10mg/10mg, 40mg/10mg/10mg film-coated tablets contain 10 mg atorvastatin (ator)/5 mg perindopril arginine (per)/5 mg amlodipine (amlo), 20mg ator/5 mg per/5 mg amlo, 20mg ator/10 mg per/5 mg amlo, 20mg ator/10 mg per/10 mg amlo, 40mg ator/10 mg per/10 mg amlo. Contains lactose as excipient. INDICATIONS*: Substitution therapy for treatment of essential hypertension and/or stable coronary artery disease, in association with primary hypercholesterolaemia or mixed hyperlipidaemia, in adult patients adequately controlled with atorvastatin, perindopril and amlodipine given concurrently at the same dose level. DOSAGE AND ADMINISTRATION*: One tablet once daily before a meal in the morning. Lipertance is not suitable for initial therapy. If a change of posology is required, the dose could be modified or individual titration with free combination may be considered. Co-administration: with elbasvir/grazoprevir or letermovir, the dose of atorvastatin should not exceed 20 mg/day. Lipertance not recommended when letermovir co-administered with ciclosporin. Elderly and patients with renal failure: frequent monitoring of creatinine and potassium. Clcr < 60 ml/min: not suitable. Hepatic impairment: should be used with caution. Lipertance is contraindicated in patients with active liver disease. Children and adolescents: should not be used. CONTRAINDICATIONS*: Hypersensitivity to the active substances or to any other ACE inhibitor or dihydropyridine derivatives or statin or to any of the excipients, active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal, during pregnancy, while breast-feeding and in women of child-bearing potential not using appropriate contraceptive measures (see section PREGNANCY* and BREASTFEEDING*), concomitant use with the hepatitis C antivirals glecaprevir/pibrentasvir, severe hypotension, shock (including cardiogenic shock), obstruction of the outflow tract of the left ventricle (e.g., hypertrophic obstructive cardiomyopathy and high grade aortic stenosis), haemodynamically unstable heart failure after acute myocardial infarction, history of angioedema (Quincke’s oedema) associated with previous ACE inhibitor therapy, hereditary or idiopathic angioedema, concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73m²) (see section INTERACTIONS*), concomitant use with sacubitril/valsartan (see WARNING* and INTERACTIONS*), extracorporeal treatments leading to contact of blood with negatively charged surfaces (see INTERACTIONS*), significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney (see WARNINGS*). WARNINGS*: Special warnings and precaution for use: Liver effects: liver function tests should be performed periodically and in case of transaminase levels increased, the patient should be monitored until resolution. Stop treatment if jaundice or marked elevations of hepatic enzymes (serum transaminases exceeding 3 times the upper limit of normal) and in patients with active liver disease. Use with caution in patients with hepatic impairment, who consume alcohol and/or have history of liver disease. Skeletal muscle effects: stop treatment if elevation of CK levels > 10 x ULN or muscular symptoms with elevation of CK level > 5 x ULN occur, or if rhabdomyolysis is suspected. Caution should be exercice when Lipertance is used with certain medicinal products that may increase the plasma concentration of atorvastatin and then the risk of rhabdomyolysis such as potent inhibitors of CYP3A4 or transport proteins (e.g ciclosporine, ketoconazole, letermovir, ritonavir…). Increased risk of myopathy with concomitant use of gemfibrozil and other fibric acid derivatives, antivirals for the treatment of hepatitis C, erythromycin, niacin and ezetimibe. Co-administration with systemic fusidic acid or within 7 days of stopping the treatment is not recommended. If use essential, Lipertance should be discontinued during fusidic acid treatment. Interstitial lung disease: if suspected, treatment should be discontinued. Diabetes Mellitus: In diabetic patients, glycaemic control should be closely monitored during first month of treatment. Patients with cardiac failure: use with caution. Hypotension: monitor blood pressure, renal function and potassium in patients at high risk of symptomatic hypotension (volume depleted or who have severe renin-dependent hypertension) or with symptomatic heart failure (with our without renal insufficiency), or with ischaemic heart or cerebrovascular disease. A transient hypotensive response is not a contraindication to further doses once the blood pressure has increased after volume expansion. Aortic and mitral valve stenosis/hypertrophic cardiomyopathy: use with caution and see CONTRAINDICATIONS. Kidney transplantation: no experience in case of recent transplantation. Renovascular hypertension: Increased risk of hypotension and renal insufficiency in patient with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Diuretics may be a contributory factor. Loss of renal function may occur (minor changes in serum creatinine) even in patients with unilateral renal artery stenosis. Renal impairment: monitor potassium and creatinine; individual dose titration with the monocomponents recommended if Clcr < 60 ml/min. In patients with renal artery stenosis, blood urea and creatinine may increase; with renovascular hypertension, risk of severe hypotension and renal insufficiency. Amlodipine may be used at normal doses in patients with renal failure. Amlodipine is not dialysable. Haemodialysis patients: use with caution.
Hypersensitivity/Angioedema: stop treatment and monitor until complete resolution of symptoms. Angioedema associated with laryngeal oedema may be fatal. Combination with sacubitril/valsartan (contraindicated due to the increased risk of angioedema). Sacubitril/ valsartan must not be initiated until 36 hours after taking the last dose of perindopril therapy. Perindopril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan. Concomitant use of other NEP inhibitors (e.g. racecadotril) and ACE inhibitors may also increase the risk of angioedema. Concomitant use of mTOR inhibitors: Increased risk for angioedema. Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis: rarely, patients have experienced life-threatening anaphylactoid reactions, temporarily withhold treatment prior to exams. Anaphylactoid reactions during desensitisation: temporarily withhold treatment prior to exams. These reactions reappeared upon inadvertent rechallenge. Neutropenia/agranulocytosis/thrombocytopenia/anaemia: extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treated with allopurinol or procainamide, periodic monitor of white blood cell counts advised. Race: perindopril may be less effective and cause a higher rate of angioedema than in non-black. Cough: resolves after discontinuation. Surgery/Anaesthesia: stop treatment one day prior to surgery. Hyperkaliemia: frequent monitoring of blood potassium if renal insufficiency, worsening of renal function, age (>70 years), diabetes mellitus, dehydration, acute cardiac decompensation, metabolic acidosis, and concomitant use of potassium-sparing diuretics and potassium salts or supplements. Combination with lithium. not recommended Dual blockade of the renin-angiotensin-aldosterone system (RAAS): concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS is therefore not recommended. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Primary aldosteronism: Use not recommended in patients with primary hyperaldosteronism (not responding to drugs acting through inhibition of reninangiotensin system). Galactose intolerance/glucose- galactose malabsorption/total lactase deficiency: should not be taken. Sodium: ‘sodium-free’. INTERACTIONS*: Contraindicated: Aliskiren (in diabetic and impaired renal patients), Extracorporeal treatments, Sacubitril/valsartan, Glecaprevir/pibrentasvir. Not recommended: CYP3A4 inhibitors, aliskiren, concomitant therapy with ACE inhibitor and angiotensin-receptor blocker, estramustine, lithium, Co-trimoxazole (trimethoprim/sulfamethoxazole), potassium- sparing diuretics (e.g. triamterene, amiloride, eplerenone, spironolactone), potassium salts, dantrolene (infusion), grapefruit or grapefruit juice. Precautions: CYP3A4 inducers, digoxin, ezetimibe, fusidic acid, gemfibrozil / fibric acid derivatives, transport inhibitors, warfarin, antidiabetic agents (insulins, oral hypoglycaemic agents), baclofen, non-steroidal anti- inflammatory medicinal products (NSAIDs) (including aspirin ≥ 3 g/day), racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus), colchicine, colestipol, oral contraceptives, gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin), sympathomimetics, tricyclicantidepressants/antipsychotics/anesthetics, gold, digoxin, atorvastatin, warfarin or ciclosporine, tacrolimus, antihypertensive agents and vasodilators. PREGNANCY AND BREASTFEEDING*: Lipertance is contraindicated during pregnancy and lactation. FERTILITY*: Reversible biochemical changes of spermatozoa in some patients treated by calcium channel blockers. DRIVE AND USE MACHINES*: May be impaired if dizziness, headache, fatigue, weariness or nausea. Caution is recommended especially at the start of treatment. UNDESIRABLE EFFECTS*: Very common: Oedema. Common: nasopharyngitis, hypersensitivity, hyperglycaemia, somnolence, dizziness, headache, dysgeusia, paraesthesia, vertigo, visual impairment, diplopia, tinnitus, palpitations, hypotension (and effects related to hypotension), flushing, pharyngolaryngeal pain, epistaxis , cough , dyspnoea, nausea, vomiting, abdominal pain upper and lower, dyspepsia, diarrhoea, constipation, change of bowel habit, flatulence, rash, pruritus, joint swelling, ankle swelling, pain in extremity, arthralgia, muscle spasms, myalgia, back pain, asthenia, fatigue, liver function test abnormal, blood creatine kinase increased. Uncommon: Rhinitis, eosinophilia, hypoglycaemia, hyponatraemia, hyperkalaemia reversible on discontinuation, anorexia, insomnia, mood altered (including anxiety), sleep disorder, depression, nightmares, tremor, syncope, hypoaesthesia, amnesia, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), vision blurred, tachycardia, vasculitis, bronchospasm, dry mouth, pancreatitis, eructation, hepatitis either cytolytic or cholestatic, urticaria, purpura, skin discolouration, hyperhidrosis, exanthema, alopecia, angioedema, pemphigoid, photosensitivity reactions, neck pain, muscle fatigue, micturition disorder, nocturia, pollakiuria, renal failure, erectile dysfunction, gynecomastia, chest pain, pain, malaise, oedema peripheral, pyrexia, blood urea increased, blood creatinine increased, weight increase, white blood cells urine positive, weight decrease, fall. Rare: Thrombocytopenia, confusional state, neuropathy peripheral, cholestasis, psoriasis aggravation, stevens-johnson syndrome, toxic epidermal necrolysis, erythema multiforme, myopathy, myositis, rhabdomyolysis, muscle rupture, tendinopathy sometimes complicated by rupture, hepatic enzymes increased, blood bilirubin increased. Very rare: Leucopenia/neutropenia, agranulocytosis or pancytopenia, haemolytic anaemia in patients with a congenital deficiency of g-6pdh, haemoglobin decreased and haematocrit decreased, anaphylaxis, hypertonia, hearing loss, myocardial infarction secondary to excessive hypotension in high-risk patients, angina pectoris, stroke possible secondary to excessive hypotension in high-risk patients, eosinophilic pneumonia, gastritis, gingival hyperplasia, jaundice, hepatic failure, exfoliative dermatitis, lupus-like syndrome, renal failure acute. Not known: immune-mediated necrotizing myopathy, extrapyramidal disorder (extrapyramidal syndrome), Raynaud’s phenomenon. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be considered as a very rare complication associated with ACE inhibitor therapy. OVERDOSE*. PROPERTIES*: Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase. Perindopril is an inhibitor of the enzyme that converts angiotensin into angiotensin II (Angiotensin Converting Enzyme ACE). Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. PRESENTATION*: Box of 30 film-coated tablets for Lipertance 10mg/5mg/5mg, 20mg/5mg/5mg, 20mg/10mg/5mg, 20mg/10mg/10mg, 40mg/10mg/10mg.
The Dean of the RCPI Faculty of Occupational Medicine, Dr Robert Ryan, has confirmed to the Medical Independent (MI) that “concerns” have been expressed to the Faculty by some “senior” occupational medicine specialists about HSE national guidance on Covid-19 control measures to mitigate infection risk and protect staff in healthcare settings. Dr Ryan informed MI he is communicating with “stakeholders” on these matters.
This newspaper understands some specialists have strongly argued for additional measures, as well as swifter updates to national guidance for healthcare settings throughout the pandemic. Wider use of respirator masks and greater emphasis on ventilation are among the issues that have been raised.
“In response to some concerns from some senior occupational health physicians about the issue of mitigation measures, I am at the moment in a process of dialogue with other stakeholders… so that this concern is given sufficient exploration,” stated Dr Ryan, Specialist in Occupational Medicine and Managing Partner at Medmark.
In regard to protecting healthcare staff from workplace-acquired infection, Dr Ryan, who does not personally work in
The Department of Health has established a new climate change oversight group to act as a “platform” for interaction between the Department and Government “particularly through the climate action plan process”, this newspaper has been told.
The Medical Independent (MI) reported in February 2020 that a climate change oversight group had yet to be established by the Department more than three months after its own plan stated the group should meet “as soon as possible”. The Climate Change Adaptation Plan for the health sector (2019 – 2024), published in October 2019, called for an oversight group for the health sector to be established and charged with implementing the plan.
A Department spokesperson told MI that the oversight group was finally “launched” in September 2021, “with representation across a range of policy and business areas, including medical expertise”. MI requested a membership list, but no reply had been received by press time.
The group’s tasks include “coordination and coherence” of climate-related policy activity in the Department; acting as a platform for interaction between the Department and wider whole-of-Government climate action; linking research in respect of health-related climate policy areas with Ireland’s climate research programmes; identifying areas for future work along with resourcing requirements; and reviewing and progressing actions identified in the climate change adaptation plan.
The Department said one of the initial objectives of the group “will be to develop a state of play encompassing climate action across Ireland’s health sector, which will inform the development of a work programme going forward”.
A HSE spokesperson said it looked forward to “engaging” with the new group “once their work with external stakeholders commences”.
the HSE, said his observation was that the Executive had instigated a wide range of control measures.
“It seemed to me they reorganised the workplace, the working practices, they brought in the appropriate mitigation measures, provided the necessary equipment in terms of personal protection, to try and protect healthcare
workers.” However, the guidance should remain under constant scrutiny, he said.
More broadly, when asked if the Faculty could be more vocal on occupational health matters during the pandemic, Dr Ryan said “perhaps in retrospect we could have done more”. See news feature, p4-6.
This module will focus on certain aspects of analgesia, including distinguishing different types of pain, particularly chronic pain. A holistic approach to pain control is outlined, as well as pain’s impact on the patient, including its causes and treatment options.
Author: Eamonn Brady MPSIThe Covid-19 pandemic is far from over and the protection of healthcare workers will remain an issue of concern for some time to come. Catherine Reilly reports on continuing misgivings from some specialists about the control measures deployed in healthcare
The Dean of the Faculty of Occupational Medicine, RCPI, Dr Robert Ryan, has confirmed to the Medical Independent (MI) that “concerns” have been expressed to the Faculty by some “senior” occupational medicine specialists about Covid-19 control measures to mitigate infection risk and protect staff in healthcare settings, as outlined in HSE national guidance.
“In response to some concerns from some senior occupational health physicians about the issue of mitigation measures, I am at the moment in a process of dialogue with other stakeholders… so that this concern is given sufficient exploration. We work in a collaborative environment; we work with public health; we work with infectious diseases; we work with hospital management; we work with our colleagues,” according to Dr Ryan, Specialist in Occupational Medicine and Managing Partner at Medmark (Dr Ryan does not personally work in the HSE. Medmark provides services to HSE/public healthcare organisations).
In regard to protecting healthcare staff from
workplace-acquired infection, Dr Ryan said his observation was that the HSE had instigated a wide range of control measures.
“I think in any scenario such as this, more or better could always have been done, but that would be true in any set of circumstances. It seemed to me they reorganised the workplace, the working practices, they brought in the appropriate mitigation measures, provided the necessary equipment in terms of personal protection, to try and protect healthcare workers.”
According to Dr Ryan, it was appropriate that the guidance remained under constant challenge and scrutiny. “I think that conversation is an ongoing one, I don’t think it’s a static conversation, and the guidance has evolved over time and in particular with the arrival of the more transmissible variants.” (see panel).
The Covid-19 pandemic represents the greatest occupational health challenge of modern times with healthcare workers facing a disproportionate risk of infection compared with the general population. Unfortunately, the pandemic is far from over and the protection of healthcare workers will remain a live and dynamic is-
sue for the foreseeable future, particularly in the context of potential new variants that may be less susceptible to vaccines.
The proportion of healthcare worker cases has declined substantially in comparison with 2020, but the virus continues to pose a significant risk to the health and wellbeing of staff, as well as threatening service delivery. In early November, up to 3,500 health staff were reportedly absent from work due to Covid-19.
According to figures from the Health Protection Surveillance Centre (HPSC), between 12 September and 9 October 2021 there were 1,417 reported cases in healthcare workers, representing 3.8 per cent of the total cases in the population. A small proportion of the
healthcare worker cases were confirmed as “likely” workplace-acquired. During much of 2020 about one-third of cases in the population were in healthcare workers.
Since a notification requirement on employers was effected on 24 November 2020, under the biological agents regulations, the Health and Safety Authority (HSA) has received 724 reports covering 1,211 occupational cases of Covid-19 in employees in health and social care (as of 29 October).
“The Authority is also aware of 17 reports of healthcare workers who have reportedly died with Covid-19,” stated a HSA spokesperson. “The Authority have commenced investigations into these reports to ascer-
Healthcare workers have shown extraordinary commitment throughout the pandemic, Dr Robert Ryan, Dean of the Faculty of Occupational Medicine, RCPI, told the Medical Independent (MI)
He said they have adapted to rapidly changing work environments and practices, while facing a “personal risk” of Covid infection far higher than in the general population.
“I have to commend the leadership, and team members, of the occupational health service within the HSE, but also all the healthcare workers in hospitals and community facilities who pulled together,” added Dr Ryan, Specialist in Occupational Medicine and Managing Partner at Medmark.
Dr Ryan also noted the considerable workload for occupational health departments and the health service generally. The system was “probably stretched in its steady state” and the demands had intensified during the pandemic for many reasons, including Covid-related leave, international recruitment difficulties, and staff absences due to medical vulnerabilities, etc.
He said he was aware that one concern for occupational health departments is the additional workload in managing contact tracing/management of healthcare workers. Dr Ryan said this function was probably outside the specialty’s remit and had “stretched people tremendously”. “I understand that discussions are taking place to try to address that issue.”
[Separately, MI understands that the HSE Workplace Health and Wellbeing Unit has obtained a legal opinion,
which states that occupational health does not have a legal basis to be involved in contact management and contact tracing].
In regard to protecting healthcare staff from workplaceacquired infection, Dr Ryan said his observation was that the HSE had instigated a wide range of control measures. “I think in any scenario such as this, more or better could always have been done, but that would be true in any set of circumstances. It seemed to me they reorganised the workplace, the working practices, they brought in the appropriate mitigation measures, provided the necessary equipment in terms of personal protection, to try and protect healthcare workers.”
However, he said it was appropriate that the guidance remained under constant challenge and scrutiny.
Dr Ryan acknowledged that a number of specialists in occupational medicine have strongly argued for additional or swifter deployment of control measures in the health sector.
As reported by MI, some occupational health physicians say they have not been adequately consulted during the development of national guidance pertaining to occupational protection of healthcare workers.
“As regards whether occupational health physicians feel their voice is being heard, I honesty couldn’t comment,” said Dr Ryan. “I know in the various committees there is occupational health representation… what I would say, on a general point, is that occupational medicine has
always been a slightly hidden specialty, largely unknown outside our immediate circle…. I think one of the things that has happened during the pandemic is our role has become far more visible and our relevance has become far more evident. So, if you were to ask me my personal experience in the places I work, I think our voice has never been more clearly heard.”
However, Dr Ryan said that the Faculty was taking on board the concerns expressed by colleagues. “In response to some concerns from some senior occupational health physicians about the issue of mitigation measures, I am at the moment in a process of dialogue with other stakeholders… so that this concern is given sufficient exploration. We work in a collaborative environment; we work with public health; we work with infectious diseases; we work with hospital management; we work with our colleagues.” Where a concern arises, a position paper is one way of articulating that concern, acknowledged Dr Ryan. “But on this occasion I have chosen to engage with other stakeholders to advance the points being made. It may be more subtle, but it is designed to be collaborative and solution focused.”
According to the RCPI website, the Faculty of Occupational Medicine is the “authoritative body on all matters of educational, professional and public interest concerning occupational medicine”. Its functions include providing advice to Government and statutory bodies on occupational medicine matters.
tain the relevant facts.”
Six claims have been made against the HSE by healthcare workers due to illness arising from Covid-19 infection allegedly acquired in the workplace, according to the State Claims Agency. One claim has been made regarding the death of a healthcare worker.
In late October, the Irish Nurses and Midwives Organisation (INMO) stated that it had requested the HSA to “reinforce the risk mitigation requirements” of the biological agents directive, which was transposed into Irish law.
This Directive directs employers to ensure that all necessary measures, including vaccines, are made available to afford maximum protections to those exposed to Covid-19.
Speaking to MI, Mr Kevin Figgis, Divisional Organiser, SIPTU Health, underlined that the HSE must fulfil its duties “as an employer and not just as a health provider”.
One of the principal duties and responsibilities of occupational health physicians in the HSE is advising management on occupational health issues including the operation of health and safety law.
Under legal provisions, employers are required to conduct risk assessments where employees are at risk of exposure to a biological agent (such as SARS-CoV-2). Where it is not technically possible to prevent exposure, measures must be applied to ensure that “as far as technically practicable” the exposure level is reduced to “as low a level as necessary in order to adequately protect the health and safety of the employees concerned”.
Throughout the pandemic, MI understands that some occupational medicine specialists have argued for additional control measures in healthcare including a higher standard of respiratory protection and greater emphasis on ventilation, as examples. This advice has been based on scientific data on SARS-CoV-2 (and other viral
Asked by MI if the Faculty could be more vocal on occupational health matters during the pandemic, particularly in respect of healthcare workers, Dr Ryan commented: “I think it has been a challenge, and perhaps in retrospect we could have done more. We are a small Faculty, an all-island Faculty, and of course a lot of our Faculty members are working within the health sector, all dealing with the extraordinary demands that arose over the last 18 months.”
Dr Ryan’s predecessor as Dean, Dr Lynda Sisson, is the Clinical Lead of occupational health in the HSE. Ostensibly, this was not a favourable position from which to express any views that could upset the HSE, MI suggested.
In response, Dr Ryan commented: “I have seen how in very difficult circumstances she and all of that team responded to what was needed of them. I probably wouldn’t have a comment to make on whether others in the system might have felt there was a conflict of interest. I personally did not see evidence of this in practice.”
A longstanding issue for occupational health physicians in the health service is their lack of consultant status, despite holding specialist registration with the Medical Council. Dr Ryan said the Faculty is advocating for consultant status for these
transmission), uncertainties in the face of a novel pathogen, and health and safety law.
However, they say their advice was not reflected in national guidance and may not be adopted by managers. It was a “perfect storm in occupational health”, stated a specialist, who said they were tasked with implementing operational policies and then faced with, in their view, “the failure of those operational policies” in the form of long Covid, moral injury and post-traumatic stress, etc. At State level, “we are trailing behind [the virus] continuously” with community transmission seeping into healthcare settings.
use of surgical masks (for close patient care) was deemed appropriate with the exception of a defined set of ‘aerosol generating procedures’ where respirator masks were advised. It was September 2020 before guidance also required healthcare workers to wear a surgical mask when in “busy public areas of healthcare facilities, even if they do not expect to be within a distance of 2m of another person for 15 minutes or more”.
However, the level of protection afforded by surgical masks has been described by Prof Raymond Agius, a UK-based occupational medicine specialist, as akin to ‘wearing slippers on a building site’.
On social media, Prof Agius has also drawn attention to research published by the UK’s Health and Safety Executive in 2008 (‘Evaluating the protection afforded by surgical masks against influenza bioaerosols’), which focussed on the effectiveness of surgical masks against a range of airborne particles.
2,305 patients were on trolleys during the first week in November, the highest since the pandemic began, according to the Irish Nurses and Midwives Organisation.
While mask policy is only one element of the hierarchy of control measures, it is a key matter on which some occupational medicine specialists have advised a different approach – namely, much more widespread use of respirator masks in healthcare.
In early 2021, the HSE advised that respirator masks (FFP2) should be available for healthcare workers when in contact with possible or confirmed Covid-19 cases and contacts. The change came on foot of the emergence of the Alpha variant and pressure from the INMO. In advance of this update,
specialists. He said lack of consultant status for specialists in occupational medicine affects their standing in the health service. “It is important we have consultant status so those of us in the specialty have that status to express opinions, concerns, and ideas for improvement.”
“I think the time is long past for our specialist colleagues to be recognised at consultant status. They are recognised as specialists by the Medical Council, they have participated in a specialist training scheme like all other doctors coming through. I don’t see any argument. I think it would help the specialty. The choice of occupational medicine has become a more evident choice for young doctors.”
According to Dr Ryan, six doctors entered the occupational medicine training scheme this year, which is the largest ever intake. They are “the best and the brightest” and entitled to the same outcomes as trainees in other specialist training programmes. “I think [consultant status] will help the specialty in recruiting and retaining the brightest. I think it will help specialists, particularly perhaps in a large organisation where these things matter. I think it will help them in arguing the case for occupational medicine and for engaging with their
Using separate tests to measure levels of inert particles and live aerosolised influenza virus, the findings showed that surgical masks provided around a six-fold reduction in exposure. Live viruses could be detected in the air behind all surgical masks tested. By contrast, properly fitted respirators could provide at least a 100-fold reduction. During the pandemic, research has also emerged in support of the higher protection afforded by respirator versus surgical masks (eg, a paper released in June from Addenbrooke’s Hospital in Cambridge, demonstrating far higher protection afforded by FFP3 versus surgical masks for staff on Covid-19 wards).
In a statement to MI in November 2020, the HSE outlined that infection prevention and control (IPC) guidance was based on an assessment that SARS-CoV-2 was “in most circumstances” a contact- and droplet-transmit-
peers. I think they engage with their peers now, but it would strengthen their hand at doing that. It is long overdue.”
Earlier this year, in his capacity as Dean, Dr Ryan wrote to Minister for Health Stephen Donnelly requesting a meeting to discuss consultant status.
Dr Ryan acknowledged that doctors have representative bodies to negotiate contracts, but said it was important to convey the “moral argument” in support of consultant status for specialists in occupational medicine. Dr Ryan was “disappointed” to have not yet received a date for a meeting, but it remained on the Faculty’s agenda.
More broadly, in respect of the health and wellbeing of doctors in the health service, Dr Ryan expressed concern about a requirement placed on NCHDs, by some sites, to arrange their own cover when they are on sick leave.
“That is something I have concerns about, I think it encourages presenteeism, which may be unsafe,” stated Dr Ryan, who indicated this is a matter the Faculty will be examining.
The residual stress that the pandemic has foisted on the population, including healthcare workers, will remain a live issue into the future, he added.
46 per cent of applicants for core surgical training commencing July 2021 were female, according to the RCSI.
215 patients with Covid-19 were in ICUs in public adult hospitals in January 2021, the highest of any stage of the pandemic to date, stated the National Office of Clinical Audit (NOCA) report on ICU activity during the pandemic.
53 patients who were pregnant or recently pregnant were admitted to ICU with Covid-19 up to 31 October 2021. 58 per cent of these admissions were since 1 August 2021. Only one patient was fully vaccinated, stated the NOCA report.
28.3% – overall mortality for patients in ICU with Covid-19 since March 2020, which was comparable to ICU mortality rates in other developed countries, according to NOCA.
I think in any scenario such as this, more or better could always have been done, but that would be true in any set of circumstances
ted infection and “the evidence that surgical masks offer equivalent protection to respirator masks in this context”.
In recent months, the INMO has called on the HSE to instigate a number of additional measures, including urgent access to the booster vaccine (since approved by the Department of Health), that FFP3 respirator masks be a mandatory requirement for healthcare workers in direct contact for extended periods with Covid confirmed patients; confirmation that the requirements in the code of practice for biological agents would be adhered to; and serial testing in health facilities in high-risk areas.
However, MI understands that HSE Antimicrobial Resistance and Infection Control (AMRIC), led by Consultant Microbiologist Prof Martin Cormican, has robustly defended existing IPC/personal protective equipment (PPE) guidance following criticism from healthcare unions.
The HSE AMRIC has pointed out that, under the guidance, respirator masks (FFP2) should already be available to healthcare staff likely to be in contact with patients with Covid-19 and this is not restricted in terms of duration of contact. Furthermore, in practice, there was “no evidence” of any difference in protection against infection between FFP2 and FFP3 masks. HSE AMRIC has also maintained that there is access to testing for staff who are symptomatic and that the HSE tests asymptomatic staff where a public health policy or local risk assessment supports such a move. Moreover, there are pilots of serial testing underway in some settings.
Ms Orla Hegarty, Assistant Professor, School of Architecture, University CollegeDublin, does not consider that current national policy on ventilation and masking in healthcare settings is adequate.
According to Ms Hegarty, it was “clear from the research” that basic plug-in HEPA filtration in a patient’s room and staff respirator masking in patient and non-patient areas substantially cuts transmission risk.
“So if that was done everywhere, we would not have issues in hospitals and care homes.”
She said while there was “some information” on ventilation in HSE/HPSC guidance for healthcare settings, it was not sufficiently specific.
Ms Hegarty added: “If you are in a hospital building as a worker, you have to assume that, firstly, you need a respirator mask for airborne precautions, not a surgical mask, and secondly, staff need to be wearing that everywhere in a hospital, not just within two metres of patients. Because it is the same air throughout the hospital. The advice and policy have been unclear on that, and inevitably we are now seeing outbreaks in hospitals, infection of people in hospital for other [conditions], infection of healthcare workers and nursing home outbreaks.”
Ms Hegarty said health and safety law was “very clear” that it was the employer’s responsibility to do a risk assessment in the workplace, assess every risk and take appropriate precautions.
Recalling the experience of the construction sector in the 1990s, Ms Hegarty said there was very weak health and safety in the sector and annual fatalities. However, with advances in health and safety law, the standards in construction greatly improved. Healthcare operates as a workplace under the same regulations, she said.
“The policy for masking in hospitals seems
The Department of Health is currently evaluating the business case for the three elective-only hospitals due to be built in Dublin, Cork, and Galway under the Sláintecare implementation plan, this newspaper understands.
“The preliminary business case has been completed and is currently undergoing internal evaluation in the Department of Health,” a spokesperson told the Medical Independent (MI)
“If approved internally, the preliminary business case will be submitted to the Department of Public Expenditure and Reform for further review.”
The Department’s spokesperson added that if “all public spending code requirements are met, it is expected that a memo for Government seeking approval in princi-
ple to proceed to the next stage of the spending code would be brought.... If approved the project planning phase would be expected to commence soon after.”
In February, MI reported that the three planned ambulatory, elective-only hospitals will have 10 specialties represented and operate six days a week for 50 weeks of the year.
These 10 specialties are orthopaedics, general surgery, ophthalmology, urology, gynaecology, ENT, plastic surgery, gastroenterology, pain medicine, and vascular. Radiology facilities will also be included in the new centres.
At the annual conference of the National Clinical Programme in Surgery in early 2021, the joint Clinical Lead, Mr Kenneth Mealy, described the plan as “the most significant investment in scheduled care that has ever taken place in this country”.
to be ‘ask for a better mask if you think you need one’. In fact, speaking and breathing generates more aerosols than many aerosol generating procedures. That wouldn’t wash in construction, workers don’t decide what PPE they wear on site. Hospitals need to train staff and enforce the use of appropriate PPE.
“I can understand right at the start of the pandemic there was an issue with supplies and procurement, but there is no issue with supply of proper masks, production is widely available.”
Ms Hegarty said that, under current guidance, many healthcare staff may be reassured to remove their masks in empty toilets, lifts, and staff rooms, but she cautioned that these settings can represent a high risk for transmission as airborne virus particles can linger for hours in certain conditions.
While the legacies of under-engineered and over-occupied healthcare settings may have played a part in transmission, Ms Hegarty said this could be largely counteracted through provision and implementation of appropriate guidance.
“I don’t think it is even about re-engineering buildings at all, there is an element of that, but mostly it is about information and practical precautions.”
In July Ms Hegarty left a national ventilation advisory group, which reports to Government, as she considered that its advice was not being adopted. She believes the political establishment has failed to communicate and enforce evidence-based measures to mitigate transmission and instead focused on an out-dated understanding and on “individual” responsibility. In the past, she said, clean water and clean air made great strides in respect of public health “and it is now time to re-establish the importance of indoor air hygiene”.
She said that relatively straightforward actions such as a “really good masking policy”, if properly implemented, would have a profound impact on reducing transmission in healthcare settings.
According to a HSE spokesperson, its guidance on respirator mask use in healthcare “reflects current evidence”. They added that occupational medicine had worked, and will continue to work, with colleagues in IPC, public health and others across the HSE in the ongoing response to Covid-19.
In regard to air filtration devices, the spokesperson said: “There is no clinical evidence that air filtration devices reduce the incidence of infection with SARS-CoV-2. Existing evidence relates to removal of microbes from the air. Use of air filtration devices is not required by current HSE ARMIC guidance, but some healthcare facilities do opt to use them in particular settings based on their risk assessment.”
Vaccination
Vaccination has played a significant role in the decline in cases in healthcare workers, but there is widespread unhappiness about the time taken to announce the decision on a booster dose.
While some data has indicated a third dose of the Pfizer vaccine will reduce transmission, non-pharmaceutical interventions are likely to remain necessary for some time, particularly if variants emerge that are not as susceptible to the vaccines.
Despite such uncertainties and Covid’s impact on service delivery, there appear to be no strategies being developed at hospital or Hospital Group/Community Healthcare Organisation levels to optimise the protection of healthcare workers into 2022 and beyond.
PAUL MULHOLLAND AND VALERIE RYAN
The board of the Mental Health Commission (MHC) heard in September how the establishment of the Decision Support Service (DSS) was continuing to experience significant difficulties.
The DSS, which is due to be the fully established by June 2022, is a service for all adults who have difficulties with decision-making capacity. It was initially hoped that the DSS would be rolled out by 2018.
At the September board meeting of the MHC, the minutes of which were seen by the Medical Independent (MI), concern was expressed about “the extent of the work to be done before June 2022 and that decisions on various matters are still outstanding”.
These included a delay in getting the General Scheme to Cabinet; the knock-on impact of this delay to the regulations, the codes of practice and other matters; no reply to the urgent request for expediting the sanction of staff as requested in July; no substantive update on the fees to be paid to panel members; and no substantive update on the fee for services. It was agreed that
“a lot may hinge” on Budget 2022 and “how quickly matters shall be addressed following confirmation of same”.
“It was thought that there appears to be a lack of understanding and appreciation amongst stakeholders in relation to actions on the critical path,” according to the minutes.
It was agreed that positive and direct communication in relation to “the seriousness and urgency of the outstanding matters” needed to be communicated to the inter-departmental steering group and the Department of Children, Equality, Disability, Integration, and Youth (DCEDIY).
An additional €1.5 million for the DSS was announced in Budget 2022.
The heralded opening date of next June hinges on amendments to the Assisted Decision-Making (Capacity) Act to enable full commencement of the remaining sections of the legislation to go ahead next year.
A statement to MI from the DCEDIY confirmed that Minister Roderic O’Gorman intended to seek a Cabinet date in the coming weeks to bring forward a General Scheme and seek approval for drafting. “Priority drafting has been secured,” added the statement. See news feature, p10.
For COPD patients on treatment with ICS/LABA and at risk of exacerbation* 1
*A worsening of symptoms or a history of exacerbation treated with antibiotics or oral corticosteroids in the past 12 months
TRELEGY
**Moderate exacerbation is a worsening of symptoms or a history of exacerbation treated with antibiotics or oral corticosteroids. A severe exacerbation is a worsening in symptoms that required hospitalisation.
TRELEGY Ellipta (FF/UMEC/VI) 92/55/22 mcg OD is indicated for maintenance treatment in adult patients with moderate to severe COPD who are not adequately treated by a combination of an ICS and a LABA or a combination of a LAMA and a LABA1
▼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.
Co-primary endpoints were change from baseline in trough FEV1 and SGRQ at week 24 (n=1810). A subset of patients (n=430) remained on blinded study treatment for 52 weeks. Trelegy showed an improvement in trough FEV1 of 171mL versus budesonide/formoterol (p < 0.001, 95% CI 148,194) at week 24. Trelegy showed an improvement in health-related quality of life (SGRQ) of 2.2 units (p <0.001, 95% CI 3.5, 1.0) at week 24. At week 52 in a subset of patients Trelegy showed a 44% reduction in annualised rate of moderate/severe exacerbations versus budesonide/formoterol (95% CI 15,63, p=0.006, Absolute difference 0.16).
TRELEGY Ellipta is generally well tolerated. Common adverse reactions include: pneumonia, upper respiratory tract infection, bronchitis, pharyngitis, rhinitis, sinusitis, influenza, nasopharyngitis, candidiasis of mouth and throat, urinary tract infection, headache, cough, oropharyngeal pain, constipation, arthralgia, back pain1
FF, fluticasone furoate; ICS, inhaled corticosteroid; LABA, long-acting ß2-agonist; LAMA, long-acting muscarinic antagonist; OD, once-daily; UMEC, umeclidinium, VI, vilanterol
References: 1. TRELEGY Ellipta SmPC 2019. 2. Lipson DA et al. Am J Respir Crit Care Med 2017; 196:438–446. 3. Lipson DA et al.N Engl J Med 2018; 378:1671–1680.
Trelegy▼ Ellipta (fluticasone furoate/umeclidinium/vilanterol [as trifenatate]) Prescribing information.
Please consult the full Summary of Product Characteristics (SmPC) before prescribing Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol [as trifenatate]) inhalation powder. Each single inhalation of fluticasone furoate (FF) 100 micrograms (mcg), umeclidinium bromide (UMEC) 62.5 micrograms and vilanterol as trifenatate (VI) 25 mcg provides a delivered dose of 92 mcg FF, 55 mcg UMEC and 22 mcg VI. Indications: Maintenance treatment in adult patients with moderate to severe COPD who are not adequately treated by a combination of an inhaled corticosteroid (ICS) and a long-acting ß2-agonist (LABA) or a combination of a LABA and a long acting muscarinic antagonist. Dosage and administration: One inhalation once daily at the same time each day. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate & magnesium stearate). Precautions: Paradoxical bronchospasm, unstable or life-threatening cardiovascular disease or heart rhythm abnormalities, convulsive disorders or thyrotoxicosis, pulmonary tuberculosis or patients with chronic or untreated infections, narrow-angle glaucoma, urinary retention, hypokalaemia, patients predisposed to low levels of serum potassium, diabetes mellitus. In patients with moderate to severe hepatic impairment patients should be monitored for systemic corticosteroid-related adverse reactions. Eye symptoms such as blurred vision may be due to underlying serious conditions such as cataract, glaucoma or central serous chorioretinopathy (CSCR); consider referral to ophthalmologist. Increased incidence of pneumonia has been observed in patients with COPD receiving inhaled corticosteroids. Risk factors for pneumonia include: current smokers, old age, patients with a history of prior pneumonia, patients with a low body mass index and severe COPD. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Trelegy. Acute symptoms: Not for acute symptoms, use short-acting inhaled bronchodilator. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases. Therapy should not be abruptly stopped without physician supervision due to risk of symptom recurrence. Systemic effects: Systemic effects of ICSs may occur, particularly at high doses for long periods, but much less likely than with oral corticosteroids. Interactions with other medicinal products: Caution should be exercised with concurrent use of ß-blockers. Caution is advised when co-administering with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, cobicistat-containing products), hypokalaemic treatments or non-potassium-sparing diuretics. Co-administration with other long-acting muscarinic antagonists or long acting ß2-adrenergic agonists is not recommended. Pregnancy and breast-feeding: Experience limited. Balance risks against benefits. Side effects: Common (≥1/100 to <1/10): pneumonia, upper respiratory tract infection, bronchitis, pharyngitis, rhinitis, sinusitis, influenza, nasopharyngitis, candidiasis of mouth and throat, urinary tract infection, headache, cough, oropharyngeal pain, arthralgia, back pain. Uncommon (≥1/1,000 to <1/100): viral respiratory tract infection, supraventricular
tachyarrhythmia, tachycardia, atrial fibrillation, dysphonia, dry mouth, fractures. Rare (≥1/10,000 to <1/1,000): Hypersensitivity reactions, including anaphylaxis, angioedema, urticaria, and rash. Not known (cannot be estimated from the available data): vision blurred. Marketing Authorisation (MA) Holder: GlaxoSmithKline Trading Services Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. MA No. [EU/1/17/1236/002]. Legal category: POM B. Last date of revision: September 2020. Code: PI-6725. Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Campus, Dublin 24. Tel: 01-4955000.
Adverse events should be reported to the Health Products Regulatory Authority (HPRA) using an Adverse Reaction Report Form obtained either from the HPRA or electronically via the website at www.hpra.ie. Adverse reactions can also be reported to the HPRA by calling: (01) 6764971. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.
The College of Psychiatrists of Ireland (CPsychI) believes that physician-assisted suicide and euthanasia (PAS-E) is opposed to good medical practice and should not be introduced, according to a new position paper.
The College’s position paper, which was discussed at its Winter Conference earlier this month, also contended that PAS-E represented a detrimental and radical change in the practice of medicine and urged that it is not introduced.
In opposing PAS-E, the College stated: “Perhaps because regulations are difficult to enforce and perhaps because legalisation results in a cultural shift, the numbers dying from euthanasia and assisted suicide inevitably increase within a few years of its introduction.”
CPsychI considers the introduction of euthanasia and assisted suicide represented a fundamental and harmful
reversal in medical care.
PAS-E runs counter to the efforts of society in general, and psychiatrists in particular, to prevent deaths through suicide, the position paper stated. “In keeping with national and international experts in palliative medicine we are convinced that euthanasia is not necessary for a dignified death, and that, on the contrary, it diminishes personal dignity,” the paper added.
Members were requested to submit their views following the College’s submission in January to the Oireachtas Committee on Justice relating to the proposed Dying with Dignity Bill in 2020.
The submission, in turn, formed the basis of the position paper drafted by the CPsychI’s human rights and ethics committee.
The College believes that the “use of law to address complex ethical issues is problematic and can have unintended consequence”.
The pulmonary function laboratory at Cork University Hospital (CUH) has only worked at approximately a quarter of its capacity since the Covid-19 crisis began, a respiratory physician based at the hospital has told the Medical Independent (MI) Consultant Respiratory Physician Dr Michael Henry said the reduction in the laboratory’s capacity is due to a range of factors associated with the pandemic, such as the emergency department appropriating part of the workspace, the greater need for sterilisation, and the safety concerns of staff.
“The knock-on effect of it all is that we get less than a quarter of the number of tests done that we need to get done,” he told MI. “So if you have a lung cancer patient who needs an urgent part of their lung removed, we can’t get it done for weeks.
“Also, I run a lung fibrosis clinic that I’m doing this afternoon. I would have 20-something patients coming; most of them should have had their pulmonary function tests done. I would say I’d be lucky if three or four have them done.... Most of it, not all of it, is down to Covid. That has a huge impact on how we manage all of these complex respiratory patients.”
Medical Laboratory Scientists Association (MLSA) Chairperson Mr Kevin O’Boyle following the announcement that 94 per cent of medical scientists had voted in favour of taking industrial action.
The respiratory department’s outpatient space was also appropriated at the beginning of the pandemic. As a result, outpatient consultations have moved offsite and now take place in a local convent.
“The facility is just really poor and not fit for an outpatient service,” according to Dr Henry.
“And that is the direct result of the other area that was previously used now being taken for Covid pathways. To put it mildly, it has devastated our service here. It will be different in different hospitals. But I’m sure everybody will tell you the same thing. It is having a huge effect on how we are running our service. We are not running our service very well because of this.”
Dr Henry was speaking in advance of the Annual Scientific Meeting of the Irish Thoracic Society, which takes place virtually on 19 November. See meeting preview, p40.
Ireland has been tracking ahead of other Western European countries when it comes to this fourth wave of the pandemic. We are now starting to see a rise in incidence across the continent in line with our own recent experience.”
As part of a summary outlining 10 key points, the position paper maintained that a dignified death was the goal of all end-of-life care, and that this was possible with good palliative care.
Not only was euthanasia not necessary for a dignified death, but techniques used to bring about death could themselves result in considerable and protracted suffering. The College considers that PAS-E would place vulnerable people at risk, and that there would be unintended consequences.
Even when safeguards were introduced to ensure that the choice for induced death was made with clear knowledge and full consent, intentions regarding induced death could often fluctuate over short periods, according to the College.
Doctors should not be coerced to act against their values in the provision of euthanasia or assisted suicide, the paper underlined.
Female patients aged 16-to-44 receiving reimbursement support for sodium valproate (Epilim) prescriptions stood at 1,691 in 2020, a decline from 1,801 in 2019. The teratogenic drug is licensed for use in epilepsy and bipolar disorder.
The data provided by the HSE related to valproate reimbursements through the long-term illness and GMS schemes. In 2016, the number of females in this age group in receipt of valproate was 2,142 and in 2018 it was 1,909.
Valproate should only be initiated in a girl or woman of childbearing potential by a specialist in epilepsy or bipolar disorder and where there is no effective alternative. Patients are advised not to stop taking valproate without a consultation with their doctor.
“The HSE notes the reductions in reimbursed prescriptions over the period 2016–2020. The HSE plans to analyse the data available to inform any additional guidance to the health service on further actions. The HSE is very aware that for some patients the medicine is essential,” according to a spokesperson.
The HSE Clinical Programme in Neurology “provides surveillance mechanisms to monitor the utilisation of the Health Products
Covid-19 cases in hospitals mean fewer beds to treat nonCovid cases. Our waiting lists are already in an appalling state. We can’t afford to lose hospital staff and hospital beds to Covid-19.”
Regulatory Authority risk assessment form process, and guidance to the health service on further actions”, added the spokesperson.
“The infrastructure to support the surveillance data has been delayed secondary to the pandemic and cyberattack. The HSE remains committed to embedding this infrastructure to inform valproate prescribing in Ireland.”
The Executive was commenting amid concerns about suboptimal implementation of a pregnancy prevention programme (PPP) for women taking valproate, as required following a 2018 review by the European Medicines Agency. These concerns have been raised by Epilepsy Ireland and the Organisation for Anticonvulsant Syndrome Ireland, and were underlined by the findings of a recent State-funded study published in Expert Opinion on Drug Safety
In 2018 six specialist nursing posts were approved to support the implementation of the PPP. However, only two of these posts have been filled.
“To date there have been 5.8 whole-time equivalent posts recruited to support the service, this includes two advanced nurse practitioners appointed as part of the pregnancy prevent programme. The HSE has sought funding for the remaining four advanced nurse practitioners as part of the 2022 estimate process.”
The MLSA has taken full industrial action only once in its 60-year history, so this is a big step, but we are left with no alternative – our members strongly support action.”PAUL MULHOLLAND CATHERINE REILLY Chief Medical Officer Dr Tony Holohan speaking on 5 November about the continuing surge in Covid-19 cases. President of the IMO Dr Ina Kelly commenting as part of the Organisation’s call on the public to “redouble” efforts to combat spread of Covid-19
Paul Mulholland and Valerie Ryan report on latest developments in regard to rolling out the Decision Support Service, and the delays that have hampered the project
Long-standing custom and practices regarding people who need support with decision-making are due to undergo fundamental change as work continues on fully establishing the Decision Support Service (DSS) by June 2022. However, the project has been beset by delays and there are ongoing challenges in establishing the Service.
The DSS is a service for all adults who have difficulties with decision-making capacity. This may include people with an intellectual disability, mental illness or acquired brain injury, as well as people with age-related conditions who may need supports to make decisions.
Structured under the Assisted Decision-Making (Capacity) Act, the new legislation establishing the DSS – which will be operated by the Mental Health Commission (MHC) – was enacted in 2015. However, the Act was not fully commenced at the time and its introduction has been phased in over the past six years.
The heralded opening date of next June hinges on amendments to the 2015 Act before full commencement can take place next year, allowing the DSS to move into full operation.
Answering a series of questions from TDs in recent weeks, querying when the Act would be fully commenced, Minister for Children, Equality, Disability, Integration and Youth, Roderic O’Gorman, re-iterated that he expected the Assisted Decision-Making (Capacity) (Amendment) Bill to be enacted before the end of this year.
“I will shortly seek Government approval for the General Scheme of the Bill,” he told the Dáil last month.
A high-level steering group, chaired by the Department of Children, Equality, Disability, Integration and Youth (DCEDIY), was meeting monthly. “It is working towards commencement of the 2015 Act in June 2022, with the Decision Support Service opening for business immediately thereafter,” he added.
Identified as a priority in the current Programme for Government and backed by additional Exchequer funding of €1.5 million announced last month, the financial boost brings the total DSS 2022 budget to €7.3 million. The announcement on funding was welcome, given the numerous delays the project has experienced to date.
Delays
The establishment of the DSS was expected in 2018, but this deadline was not achieved.
The MHC then aimed to establish the Service in 2020. However, this was also not possible due to a range of factors.
As previously reported by the Medical Independent (MI), the MHC board heard in January 2020 that key issues relating to funding, the ICT project and governance had “not yet been fully addressed” and would
delay the roll-out of the initiative. The Covid-19 pandemic then caused further challenges in establishing the Service.
In May 2020, the Director of the DSS, Ms Áine Flynn, wrote to each political party to ensure that the commencement of the DSS was prioritised within any Programme for Government. The letter was co-signed by the Chair of the MHC.
“The 2015 Act is long-awaited, reforming, human rights-based legislation,” according to Ms Flynn.
“However, we are now approaching fourand-a-half years since the legislation was signed into law. It is critically important that those who will be most affected by the Act are provided with a clear roadmap for full commencement so we can all be assured and continue with the job of getting the service ready for operation.”
Ms Flynn explained that approximately one-third of the allocation applied for in the Estimates process was awarded to the DSS in the previous two Budgets.
“Recent engagement with the Department of Justice and Equality has been positive. The Decision Support Service has presented to the Department a draft time-bound, costed project plan to include the development of an essential ICT system. This plan has been favourably received. However, unless adequate funding is allocated in the coming budget, the DSS will not commence operations until after 2022. It is therefore, abso-
update on the fee for services. It was agreed that “a lot may hinge” on Budget 2022 and “how quickly matters shall be addressed following confirmation of same”.
“It was thought that there appears to be a lack of understanding and appreciation amongst stakeholders in relation to actions on the critical path,” according to the minutes.
It was agreed that positive and direct communication in relation to “the seriousness
legal and finance professionals through future practice under the terms of the assisted decision-making legislation.
A consultation process around a draft set of codes is to begin this month. Finalised codes are to be published once they receive Ministerial approval.
A “significant public information campaign” is also planned for 2022, designed to inform as many people as possible about the new service and legal provisions in relation to everyone’s rights to assistance in making decisions.
A new National Consent Policy is also due to be finalised shortly and is being framed to work alongside the decision-making support provisions of the Act.
The policy is being prepared by the HSE and the latest draft version is out for consultation with stakeholders at present.
First drawn up in 2013, the evolving National Consent Policy has been amended in line with developments in healthcare legislation, such as the Health (Regulation of Termination of Pregnancy) Act 2018.
Underscoring that the policy is to function in tandem with the Assisted Decision-Making Act, Co-Chairs of the HSE National Consent Policy advisory group, Prof Shaun O’Keeffe, Consultant Geriatrician, Galway University Hospitals, and Prof Mary Donnelly, School of Law, University College Cork, were also recently appointed Co-Chairs of the Assisted Decision-Making Act implementation steering group to provide advice on the implementation of the 2015 Act in the HSE and HSE-funded agencies.
Prof O'Keeffe told MI that they were “continuing to work to make sure we are aligned”. The final versions of draft codes of practice under the Act would modify the language of the National Consent Policy. Although the process was further delayed due to the Covid-19 pandemic, Prof O’Keeffe said it was now “full steam ahead” for the 2015 Assisted Decision-Making Act provisions.
lutely critical that the full commencement of the 2015 Act is prioritised in the new Programme for Government.”
Following the announcement of Budget 2021, Ms Flynn said the DSS was on track to open its doors in 2022.
However, difficulties continued to be experienced this year. In MHC board meeting minutes from September 2021, seen by MI, concern was expressed about “the extent of the work to be done before June 2022 and that decisions on various matters are still outstanding”. These included a delay in getting the General Scheme to Cabinet; the knock-on impact of this delay to the regulations, the codes of practice and other matters; no reply to the urgent request for expediting the sanction of staff as requested in July; no substantive update on the fees to be paid to panel members; and no substantive
and urgency of the outstanding matters” needed to be communicated to the inter-departmental steering group (IDSG) and the DCEDIY.
“This could include a top line on the report for the IDSG noting that the project is trending red and not on track to achieve its proposed commencement date,” the minutes stated.
At the meeting, Ms Flynn noted that the service delivery model workstream rather than the overall project is tracking red at the time.
Much of the detail about how the new legislation is to operate at a day-to-day level is awaited through codes of practice. The purpose of codes of practice is to guide doctors, decision supporters, and other healthcare,
“We have all accepted it is a complex piece of legislation but not in terms of general principles. The general principle remains the same, if people can make a decision themselves, they should be supported to do so.
“The new Act will provide greater legal clarity and a greater range of options for patients.” In particular, Prof O’Keeffe said it provided a hierarchy of interventions for decision-making and would allow a more nuanced approach for those who had difficulty making decisions than existed at present.
“We have not been doing enough advance healthcare planning in the past. The Assisted Decision-Making Act will introduce a tier of ways people can plan ahead using Enduring Powers of Attorney and advance healthcare directives, and directives refusing care will be legally binding.”
The MHC then aimed to establish the Service in 2020. However, this was also not possible due to a range of factors
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David Lynch reports on the IMO’s recent frustration over the failure of the HSE to pay NCHDs agreed overtime rates
NCHDs feel a sense of "disquiet and a sense of disrespect" over not receiving agreed overtime rates, the Medical Independent (MI) has been told. The issue has been recently raised with the HSE by the IMO and NCHDs on social media.
On the evening of 10 November, the IMO sent an update to NCHD members on the issue.
"After direct engagement, it has been confirmed to the IMO that the national payroll has been updated and the corrected overtime rate will be paid in pay runs from this week onwards," according to the IMO message to members, seen by this newspaper.
"In terms of arrears due – overtime underpaid since 1 July – a programme has been put in place, starting this weekend, to capture arrears and process those for payment as soon as practicable.
"Clearly, the delay in implementing this new rate has caused a considerable degree of anxiety for NCHDs.
"We received a high volume of communication in this regard and brought your concerns to the responsible senior officials in the HSE and insisted that this matter be addressed. This is a clear demonstration of the importance of NCHDs acting in unity through their union in order to defend contractual rights. It remains of vital importance that we remain united in the face of other breaches of contract."
The IMO added that it would encourage members to "check their payslip and ensure that they are paid appropriately".
"How do they expect to retain doctors in the system when they treat them like this?"
MI asked the HSE for a comment regarding the overtime payment, but no response was received by press time.
The overtime payment issue has been raised by NCHDs on social media, while the IMO said that in recent weeks it has received reports from NCHDs across the country of non-payment of "nationally agreed overtime rates".
In response to the feedback from members, the IMO wrote directly to Mr John Delamere, Assistant National Director HSE – National Employee Relations, at the end of last month (29 October). The letter refers to ‘Building momentum: A new public service agreement, 2021-2022’, where "it was agreed in Section 4.1.1, that overtime and other premia affected by the Haddington Road Agreement of July 2013 would be restored to the rates that prevailed prior to July 2013. This change was to be effective from 1 July 2021."
Speaking to MI immediately prior to this development, Mr Anthony Owens, IMO Director of Industrial Relations, Consultants and NCHDs, said: "What we have here is a national agreement that was agreed at the end of 2020 on overtime to be implemented in July 2021 and it is now November 2021 and the thing still hasn't been implemented."
"They [the HSE] can't say they haven't been warned. This has been nearly a year coming down the track and it is wholly unacceptable to the IMO. NCHDs whose working patterns, unfortunately, require them to do a lot of overtime are not being paid properly for the [overtime] hours they are working."
Mr Owens said the "HSE have to get this implemented immediately to ensure that everyone gets everything they are owed going back to July, that just has to happen. We began raising this with the HSE back in June."
He added that the HSE was "clearly" not ready to implement the agreement. "Now our members are coming to us and there really is an enormous sense of disquiet and a sense of disrespect that is being relayed to us about the HSE and it is 100 per cent true," said Mr Owens.
The IMO letter said that it "continues to receive reports from around the country that members have still not seen this change reflected in their payslips. Just this week, we’ve received reports of this type from Limerick, Naas, St James’s and others.... As discussed previously, given the rotational nature of their employment and the inexplicable delays, NCHDs will have significant difficulties in reconciling their overtime hours with wages received when they are finally paid appropriately."
Mr Owens also wrote to Ms Anne Marie Hoey, HSE National Director for Human Resources, on 3 November and stated the IMO had "engaged with individual sites in this regard and has been informed that the changed rates will be input into the HSE National SAP system with a view to being live for payment on the 25 November pay date".
"It is quite extraordinary that an overtime rate that was agreed as part of a national agreement in December 2020, to be implemented in July 2021, will only finally be implemented at the end of November 2021," wrote Mr Owens.
"Given the rotational nature of their employment, and tendency to work long hours, this delay cannot but lead to considerable anxiety among NCHDs as to whether they have indeed been paid properly. The HSE’s previous record in this regard does not inspire confidence.
"I would, therefore, seek your agreement that outstanding monies that are owed to NCHDs, as a result of national agreements, be paid in advance of 25 November, in recognition of the inordinate delays to date."
Clearly, the delay in implementing this new rate has caused a considerable degree of anxiety for NCHDs
Respimat® is a soft-mist inhaler - not a DPI or a pMDI.1,2
Respimat® is also reusable - using one Respimat® inhaler with six cartridges can reduce its carbon footprint by 71% vs using the inhaler with one cartridge every month for six months.3
Respimat® is a soft-mist inhaler - not a DPI or a pMDI.1,2 Respimat® (tiotropium) achieved greater lung deposition compared with tested DPIs.3* Respimat®
Since the beginning of the pandemic, Ireland has played its part in global efforts to understand SARS-CoV-2 and develop strategies for treatment and prevention. Anna Wedderburn provides an overview of some notable examples of Irish Covid-19
Although a small country, Ireland has already made important contributions to research crucial in the fight against the SARS-CoV-2 virus. Irish researchers have participated in global clinical trials and synthesised cohesive reports for the World Health Organisation (WHO), which have formed international guidelines. Ireland has also been commended by the Organisation for Economic Co-operation and Development (OECD) for its research into – and use of – behavioural science.
Global clinical trials
Ireland has been involved in a number of global clinical trial programmes, most of which were set up years in advance for pandemic preparedness.
Prof Alistair Nichol, Director of the Heart Research Board (HRB)-funded Irish Critical Care – Clinical Trials Network (ICCCTN), told the Medical Independent (MI) about three of the studies the network was involved in: REMAP-CAP, SPRINT-SARI, and GenOMICC.
REMAP-CAP was initiated in 2014, in the wake of the 2009 H1N1 pandemic. It was designed so that “it could pivot in the event of a pandemic to answer pandemic relevant questions”, Prof Nichol said. During non-pandemic times, REMAP-CAP carries out useful clinical research in ICU patients with community-acquired pneumonia, which accounts for a large percentage of sepsis presentations to the ICU. In the face of a novel pandemic, the protocols, legal agreements, ethical approval, and regulatory approvals of REMAP-CAP simply need to be adapted.
This meant that during the Covid-19 pandemic, research could be carried out in a timely manner. “One of the really big, important questions in Covid-19 was, are steroids beneficial or not?,” Prof Nichol said. Hydrocortisone had already been randomised in patients with pneumonia in the REMAP-CAP trial, meaning that almost immediately after Covid-19 was declared a public health emergency of international concern, the REMAP-CAP trial was able to start randomising patients with Covid-19 for hydrocortisone.
Over 9,000 patients have been included in the trial globally so far, with over 16,000 patient randomisations in over 330 hospital sites. In this way, REMAP-CAP is a “highly efficient design”, Prof Nichol said. Studies generally test one intervention at a time before moving on to another, whereas “the design of REMAP-CAP was for a pandemic” and answered multiple questions at the same time.
Overall, REMAP-CAP has determined three treatments that reduce mortality and morbidity in Covid-19 patients in ICU: Hydrocortisone, tocilizumab, and sarilumab, and these results are now part of international guidelines. Alongside this, REMAP-CAP has been able to demonstrate that many treatments were not effective or were even harmful, and therefore are no longer used. Prof Nichol stated that this trial has given “more definitive answers in the last 15 months than I’ve found out in the last five years of my research”.
The SPRINT-SARI concept was initiated seven years ago. It is an observational study of patients presenting to hospital and ICU with severe acute respiratory infection (SARI)
symptoms. Again, the ethical approvals were in place for this trial to pivot during a pandemic, and the team behind the study “had been doing a war game one week a year, every year”, Prof Nichol explained. When the pandemic began, they were “able to roll it out immediately”.
From this study, “we were able to describe the patients’ demographics, their symptoms, the treatments, and their length of stay in Irish hospitals”, said Prof Nichol. Up to
towards potential therapeutic targets based on these genetic discoveries.
Prof Nichol concluded that “these three studies all dovetailed together: SPRINT-SARI collected information on patients so we could describe the pandemic; GenOMICC was able to describe patients with genetically high risk, and identify potential therapeutic targets; and REMAP-CAP could then definitively answer the question of whether the therapeutic agents were effective”.
The WHO Solidarity trial also had participants in Ireland. Prof Joe Eustace, Director of the HRB Clinical Research Facility at University College Cork, led the Irish arm of this trial. Prof Eustace explained that prior to the emergence of the Covid-19 pandemic, the WHO had put together a research and development team to predict which bacteria or viruses may cause future pandemics, and which therapeutics might be used against these potential pandemic-causing pathogens. This meant that when the Covid-19 pandemic emerged, the WHO already had a good understanding of what type of drugs to trial. Within a few months after the emergence of SARS-CoV-2, the Solidarity trial was set up to examine the effectiveness of hydroxychloroquine, lopinavir, interferon beta, and remdesivir against the novel coronavirus.
fortnightly reports of this information were sent out to clinicians about the status of Covid-19 patients in Ireland. There were 400,000 participants in this trial globally, with over 2,000 from Irish hospitals.
Finally, GenOMICC, a study led by Edinburgh University, examined genetic factors that make patients more susceptible to critical illnesses such as Covid-19, and which may influence recovery. This study showed for the first time that genetics are important for determining outcomes in ICU patients and was able to point
The Solidarity trial is an adaptive trial, meaning “you’re going to start with your best candidates, do interim reviews, and then if the results aren’t there, you move on to the next best set of candidates”, according to Prof Eustace.
Ireland performed well for its size, contributing 1 per cent to the overall recruitment of the global Solidari -
Alongside this, REMAP-CAP has been able to demonstrate that many treatments were not effective or were even harmful, and therefore are no longer used
Coverdine® (perindopril arginine/indapamide/amlodipine) Abbreviated Prescribing Information: Please refer to the Summary of Product Characteristics before prescribing. COMPOSITION* Coverdine 5mg/1.25mg/5mg film-coated tablets contains 5 mg perindopril arginine (per)/1.25 mg indapamide (ind)/5 mg of amlodipine (amlo); Coverdine 5mg/1.25mg/10mg film-coated tablets: 5 mg per/1.25 mg ind/10 mg amlo; Coverdine 10mg/2.5mg/5mg film-coated tablets: 10 mg per/2.5 mg ind/5mg amlo; Coverdine 10mg/2.5mg/10mg film-coated tablets: 10 mg per/2.5 mg ind/10 mg amlo. INDICATIONS* Substitution therapy for treatment of essential hypertension, in patients already controlled with perindopril/indapamide fixed dose combination and amlodipine, taken at the same dose level. DOSAGE AND ADMINISTRATION* One tablet per day, preferably in the morning and before a meal. The fixed dose combination is not suitable for initial therapy. If a change of the posology is required, titration should be done with the individual components. Paediatric population: should not be used. CONTRAINDICATIONS* Dialysis patients. Patients with untreated decompensated heart failure. Severe renal impairment (Clcr < 30 mL/min). Moderate renal impairment (Clcr < 60 mL/min) for Coverdine 10mg/2.5mg/5mg and 10mg/2.5mg/10mg. Hypersensitivity to the active substances, to other sulfonamides, to dihydropyridine derivatives, any other ACE-inhibitor or to any of the excipients. History of angioedema (Quincke’s oedema) associated with previous ACE inhibitor therapy (see Warnings section). Hereditary/idiopathic angioedema. Second and third trimesters of pregnancy (see Warnings and Pregnancy and lactation sections). Hepatic encephalopathy. Severe hepatic impairment. Hypokalaemia. Severe hypotension. Shock, including cardiogenic shock. Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis). Haemodynamically unstable heart failure after acute myocardial infarction. Concomitant use of Coverdine with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60mL/min/1.73m2) (see Interaction section), concomitant use with sacubitril/valsartan (see WARNING* and INTERACTIONS*), extracorporeal treatments leading to contact of blood with negatively charged surfaces (see INTERACTIONS*), significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney (see WARNING*).WARNINGS* Special warnings: Dual blockade of the renin-angiotensin-aldosterone system (RAAS): ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Neutropenia/agranulocytosis/thrombocytopenia/anaemia: caution if collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or combination of these complicating factors, especially if pre-existing impaired renal function. Monitoring of white blood cell counts. Renovascular hypertension: increased risk of hypotension and renal insufficiency in patient with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Diuretics may be a contributory factor. Loss of renal function may occur (minor changes in serum creatinine) even in patients with unilateral renal artery stenosis. Hypersensitivity/angioedema, intestinal angioedema: stop treatment and monitor until complete resolution of symptoms. Angioedema associated with laryngeal oedema may be fatal. Concomitant use of mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus): patients may be at increased risk for angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment). Combination with sacubitril/valsartan (contraindicated due to the increased risk of angioedema). Sacubitril/valsartan must not be initiated until 36 hours after taking the last dose of perindopril therapy. Perindopril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan. Concomitant use of other NEP inhibitors (e.g. racecadotril) and ACE inhibitors may also increase the risk of angioedema. Anaphylactoid reactions during desensitization: Caution in allergic patients treated with desensitization and avoid if venom immunotherapy. Temporarily withdrawal of ACE- inhibitor at least 24 hours before desensitization. Anaphylactoid reactions during LDL apheresis: Temporarily withholding ACE-inhibitor prior to each apheresis. Haemodialysis patients: consideration to use dialysis membranes other than high flux or antihypertensive agents other than ACE inhibitors. Primary aldosteronism: use not recommended in patients with primary hyperaldosteronism (not responding to drugs acting through inhibition of the renin-angiotensin system). Pregnancy: no initiation during pregnancy, stop treatment and start alternative therapy if appropriate. Hepatic encephalopathy which can progress to hepatic coma: stop treatment. Photosensitivity: stop treatment. Precautions for use: Renal function: In certain hypertensive patients without pre-existing apparent renal lesions and for whom renal blood tests show renal insufficiency, stop treatment and restart at a low dose or with one constituent only. Monitoring of potassium and creatinine, after two weeks of treatment and then every two months during therapeutic stability period. If bilateral renal artery stenosis or single functioning kidney: not recommended. Risk of arterial hypotension and/or renal insufficiency (in cases of cardiac insufficiency, water and electrolyte depletion, in patients with low blood pressure, renal artery stenosis, congestive heart failure or cirrhosis with oedema and ascites): start treatment at low doses and increase progressively. Hypotension and water and sodium depletion: Risk of sudden hypotension in presence of pre-existing sodium depletion (in particular if renal artery stenosis): Monitoring of plasma electrolytes, re-establish blood volume and pressure, restart treatment at a reduced dose or with only one of the constituents. Sodium levels: More frequent monitoring in elderly and cirrhotic patients. Potassium levels: Hyperkalaemia: Monitoring of serum potassium if renal insufficiency, worsening of renal function, age (> 70 years), diabetes mellitus, intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis and concomitant use of potassium-sparing diuretics, potassium supplements or potassium salts, or other drugs associated with increases in serum potassium. Hypokalaemia: high risk for elderly and/or malnourished subjects, cirrhotic patients with oedema and ascites, coronary patients, patients with renal failure or heart failure, long QT interval: monitoring of serum potassium, may cause muscle disorders and rhabdomyolysis, may favour the onset of torsades de pointes, which may be fatal. Calcium levels: hypercalcemia: stop treatment before investigating the parathyroid function. Renovascular hypertension: if renal artery stenosis: start treatment at hospital at low dose; monitor renal function and potassium. Dry cough. Atherosclerosis: start treatment at low dose in patients with ischaemic heart disease or cerebral circulatory insufficiency. Hypertensive crisis. Cardiac failure/severe cardiac insufficiency: Caution if heart failure. Severe cardiac insufficiency (grade IV): start treatment under medical supervision with reduced initial dose. Aortic or mitral valve stenosis / hypertrophic cardiomyopathy: Caution if obstruction in the outflow tract of the left ventricle. Diabetic patients: If insulin dependent diabetes mellitus, start treatment under medical supervision with reduced initial dose; monitor blood glucose during the first month and/or in the case of hypokalaemia. Black people: higher incidence of angioedema and apparently less effective in lowering blood pressure than in non-blacks. Surgery / anaesthesia: stop treatment one day before surgery. Hepatic impairment: Mild to moderate: caution. Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. Stop treatment if jaundice or marked elevations of hepatic enzymes. Uric acid: hyperuricemia: Increased tendency to gout attacks. Elderly: testing of renal function and potassium levels before treatment start. Dosage increase with care. Excipients: sodium-free. Choroidal effusion, acute myopia and secondary angle-closure glaucoma: discontinue drug intake as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Athletes: may cause positive doping test. INTERACTION(S)* Contraindicated: Aliskiren in diabetic or impaired renal patients, Extracorporeal treatments, Sacubitril/Valsartan. Not recommended: Lithium, Aliskiren in patients other than diabetic or impaired renal patients, Concomitant therapy with ACE inhibitor and angiotensin-receptor blocker, Estramustine, Potassium-sparing drugs (e.g triamterene,amiloride,…), Potassium salts, Co-trimoxazole (trimethoprim/sulfamethoxazole), Dantrolene (infusion), Grapefruit or grapefruit juice. Special care: Baclofen, Non-steroidal anti- inflammatory medicinal products (included acetylsalicylic acid at high doses), Antidiabetic agents (insulin, hypoglycaemic agents), Non-potassium-sparing diuretics and Potassium-sparing diuretics (eplerenone, spironolactone), Racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus), Torsades de pointes inducing drugs, Amphotericin B (IV route), glucocorticoids and mineralocorticoids (systemic route), tetracosactide, stimulant laxatives, Cardiac glycosides, Allopurinol, CYP3A4 inducers, CYP3A4 inhibitors. To be taken into consideration: Imipramine- like antidepressants (tricyclics), neuroleptics, other antihypertensive agents and vasodilatators, tetracosactide, Allopurinol, cytostatic or immunosuppressive agents, systemic corticosteroids or procainamide, Anaesthetic drugs, Diuretics (thiazide or loop diuretics), Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin), Sympathomimetics, Gold, Metformin, Iodinated contrast media, Calcium (salts), Ciclosporin, Atorvastatin, digoxin, warfarin, Tacrolimus, Simvastatin. PREGNANCY AND BREASTFEEDING* Contraindicated during the second and third trimesters of pregnancy. Not recommended during the first trimester of pregnancy and lactation. FERTILITY* Reversible biochemical changes of spermatozoa in some patients treated by calcium channel blockers. DRIVE & USE MACHINES* May be impaired due to low blood pressure that may occur in some patients, especially at the start of treatment. UNDESIRABLE EFFECTS* Very common: oedema. Common: dizziness, headache, paraesthesia, vertigo, somnolence, dysgeusia, visual impairment, diplopia, tinnitus, palpitations, flushing, hypotension (and effects related to hypotension), cough, dyspnoea, abdominal pain, constipation, diarrhoea, dyspepsia, nausea, vomiting, change of bowel habit, pruritus, rash, rash maculo-papular, muscle spasms, ankle swelling, asthenia, fatigue. Uncommon: rhinitis, eosinophilia, hypersensitivity, hypoglycaemia, hyperkalaemia reversible on discontinuation, hyponatraemia, insomnia, mood altered (including anxiety), depression, sleep disorder, hypoaesthesia, tremor, syncope, tachycardia, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), vasculitis, bronchospasm, dry mouth, urticaria, angioedema, alopecia, purpura, skin discoloration, hyperhidrosis, exanthema, photosensitivity reaction, pemphigoid, arthralgia, myalgia, back pain, micturition disorder, nocturia, pollakiuria, renal failure, erectile dysfunction, gynaecomastia, pain, chest pain, malaise, oedema peripheral, pyrexia, weight increased, weight decreased, blood urea increased, blood creatinine increased, fall. Rare: confusional state, blood bilirubin increased, hepatic enzyme increased, psoriasis aggravation. Very rare: agranulocytosis, aplastic anaemia, pancytopenia, leukopenia, neutropenia, haemolytic anaemia, thrombocytopenia, allergic reactions, hyperglycaemia, hypercalcaemia, hypertonia, neuropathy peripheral, stroke possibly secondary to excessive hypotension in high-risk patients angina pectoris, myocardial infarction, possibly secondary to excessive hypotension in high risk patients, eosinophilic pneumonia, gingival hyperplasia, pancreatitis, gastritis, hepatitis, jaundice, hepatic function abnormal, erythema multiforme, Stevens-Johnson Syndrome, exfoliative dermatitis, toxic epidermal necrolysis, Quincke’s oedema, acute renal failure, haemoglobin decreased and haematocrit decreased. Not known: Potassium depletion with hypokalaemia, particularly serious in certain high risk populations, extrapyramidal disorder (extrapyramidal syndrome), myopia, vision blurred, acute angle-closure glaucoma, choroidal effusion, torsades de pointes (potentially fatal), rhabdomyolysis, muscular weakness, possibility of onset of hepatic encephalopathy in case of hepatic insufficiency, possible worsening of pre-existing systemic lupus erythematosus, electrocardiogram QT prolonged, blood glucose increased, blood uric acid increased. Raynaud’s phenomenon. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be considered as a very rare complication associated with ACE inhibitor therapy. OVERDOSE* PROPERTIES* Perindopril is an inhibitor of the angiotensin converting enzyme (ACE inhibitor) which converts angiotensin I to angiotensin II. Indapamide is a sulfonamide derivative with an indole ring, pharmacologically related to the thiazide group of diuretics. Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. PRESENTATION* Box of 30 tablets of Coverdine 5mg/1.25mg/5mg, 5mg/1.25mg/10mg, 10mg/2.5mg/5mg and 10mg/2.5mg/10mg.
Marketing Authorisation Holder: LES LABORATOIRES SERVIER, 50 rue Carnot, 92284 Suresnes cedex France. www.servier.com. PA0568/024/002-005. Legal Classification for Supply: POM. Local Representative in Ireland: Servier Laboratories (Ireland) Ltd. Second Floor, 19 George’s Street Lower, Dun Laoghaire, Co. Dublin A96 ER84, Ireland . Tel (01) 6638110, www.servier.ie.
*For complete information, please refer to the Summary of Product Characteristics for Coverdine on www.medicines.ie.
Date of last revision of text: July 2021 (Date of last approved SmPC: July 2021) Date of preparation: September 2021. 2122C1CDEPressADCBU.
References: 1. Tòth K, on behalf of the PIANIST Investigators. Am J Cardiovasc Drugs. 2014. DOI 10.1007/s40256-014-0067-2. 2. Pall D et al, Hypertonia és Nephrologia. 2012;16(3-4):119-123. 3. Coverdine SmPC July 2021.
ty study. Phase one helped identify medicines that did not work, and phase two aims help identify medicines that will go on to save lives. Prof Eustace said “it's only by everybody coming together working collectively that we can beat a pandemic. That’s the real learning to take from this.”
Evidence Synthesis Ireland
Evidence synthesis is another important area of research. “Evidence synthesis establishes the overall balance of information on a topic,” Dr Nikita Burke, Programme Manager at Evidence Synthesis Ireland (ESI), told MI
ESI supports individuals to develop practical skills in evidence synthesis methods. This allows them to gather all the evidence surrounding a topic to help others make healthcare decisions, instead of focusing on individual studies or trials which may be controversial or flawed.
ESI was set up in December 2018, and is an all-Ireland initiative funded by the HRB and the Health and Social Care, Research, and Development Division of the Public Health Agency in Northern Ireland. It aims to “build capacity in people” including researchers, clinicians, policymakers, and institutions. This comes in a variety of ways, such as training and education, Fellowships, and public engagement with the aim to “help people to have awareness of what evidence synthesis and systematic reviews are, so that they can find trustworthy evidence and that they can make better informed decisions about their health, or the health of their patients”.
trusted source, throughout the pandemic, as it wanted its work to be “of global relevance”. This most certainly was the case, as over the last two years ESI’s work has informed WHO guidelines on many issues. Furthermore, in October 2020, the WHO needed certain questions answered for their clinical guidance. The Organisation approached Cochrane to recommend a group to carry out work on quality assurance.
Following this, the Editor-in-Chief of Cochrane approached ESI and asked it to deliver a product. Within 21 days, Prof Valerie Smith, Prof Declan Devane, Prof Alistair Nichol, and Dr David Roche created a review on care bundles for Covid-19 patients in ICU, and this was “directly as a response to the need by the World Health Organisation, and they included that in their guidelines”, according to Dr Burke.
ESI was also involved in setting up Covid Network Meta Analysis (Covid-NMA), which is a “living map of all of the registered clinical trials on Covid and on the treatment and prevention of Covid” around the world.
“So you can go in next week and it'll be different slightly different to how it was today as it will contain the most up-to-date evidence,” she said.
“The World Health Organisation started using that as their primary resource for the treatment for data on treatment and prevention, and we know that the Department of Health in Ireland were using that as well”, Dr Burke said.
Perhaps one of the less talked about areas of research during this pandemic is behavioural science. Dr Pete Lunn is the founder and head of the Economic and Social Research Institute’s (ESRI) behavioural research unit, which is a group comprised of eight psychologists and behavioural economists.
In early March 2020, Dr Lunn told the ESRI Director that he wanted his team to “drop everything and write a review of how behavioural science could contribute to the Covid response”, as initially behaviour was the chief means of defence against the SARS-CoV-2 virus.
The Director agreed to this and ESRI funded the review, which was completed within two weeks and provided to the Department of Health. The review included everything from how to encourage handwashing and carry out emergency risk communication at a macro level. Soon after this, Dr Lunn was asked to join the behavioural subgroup of the national public health emergency team.
pandemic. All the studies Dr Lunn and his team carried out were published in academic journals.
Funding agencies
Research is key to successful handling of a pandemic but this requires funding. Dr Teresa Maguire, Director of Research and Strategy at the HRB, told MI that the Board “adopted the WHO pandemic response framework”, which states that medical countermeasures, social countermeasures, and population health services measures were all required in response to this virus.
She also highlighted that throughout this pandemic, funding agencies including the HRB had to become “real time” and implement “slick and quick” processes.
Covid-19 has demonstrated the importance of investment in infrastructure, Dr Maguire stated. “You can really see how it allows you to react quickly, respond with quality, have a powerful reach, and make a difference both at home and abroad.”
This is evident through the work of REMAP-CAP, Solidarity, and Evidence Synthesis Ireland, which are all either directly funded by the HRB, or were able to take place in Ireland due to the infrastructure the HRB has facilitated. Dr Maguire said that, over the years, people have asked if the money the HRB puts into infrastructure and clinical trials is necessary. She believes that Covid-19 has proven that it is.
“We can all fund project programmes,” Dr Maguire said, “but infrastructure, once you invest in an asset, a national asset, it’s for life.” She pointed out that Ireland is “one of the few countries in Europe” that does not even have a policy position, let alone legislation, on optimising the “sharing, the use, the reuse and the linkage” of data surrounding health and the population. She believes this is essential as currently, “you can’t link where the money goes with the workforce, with the services, with the needs, or with the outcomes.”
Ireland now has a Covid-19 Data Hub set up by the HRB, the Central Statistics Office (CSO) and the Department of Health. Up-to-date data on the Irish Covid-19 cases, tests, and hospitalisations, etc, can be found and accessed by approved researchers. The HRB is also currently in the process of establishing a National Covid Biobank to collect samples and patient information for research purposes.
Although a pandemic was not on the minds of those who created ESI, at the beginning of the Covid-19 crisis the Department of Health asked ESI to refocus its resources and team to do high quality systematic reviews on the subject. Dr Burke said this was necessary as “we are in an era of too much information, of overwhelming information”, particularly throughout this pandemic when so much new data was being produced each day.
Dr Burke explained that systematic reviews usually take two years to complete; however, ESI had been investigating “rapid reviews” since its inception. This was of particular relevance during the Covid era.
“There’s a balance between the timeliness and time needed, and the quality assurance of the end product,” she said.
During a pandemic it was clear that waiting two years for a systematic review would not be helpful, and so Dr Catherine Houghton and colleagues within the ESI network “got together and in 23 days had the very first Cochrane rapid qualitative evidence synthesis completed and published”, which Dr Burke stated was a “mammoth task”.
ESI worked with organisations, such as Cochrane, a
Going forward, the Department of Health commissioned the ESRI to examine the population response to the pandemic. Dr Lunn and his team investigated the messages to use to encourage social distancing, self-isolation, and response to various symptoms, and whether decision trees and flow diagrams could be of benefit.
They also pre-tested aspects of the Covid-19 app in regard to data protection information and risk perceptions (which uncovered that people were misinterpreting the difference between being indoors and outdoors in terms of viral spread). Research on vaccination found that misinformation was less important than whether people had absorbed how effective vaccines were.
These experiments by Dr Lunn and his team have “exactly the same structure as a clinical trial” in that people are randomised into groups and presented information in different ways. The participants believe, for example, they are there to give feedback on the information they are shown, but are also asked questions that inform researchers how the information has affected their decision making or planned behaviour. In a summary of one study, Dr Lunn said “we're randomising different people to see different messages and we’re seeing what impact it has on their plans for the coming week”.
This work, alongside other studies on behavioural science, was specifically mentioned by the OECD in a report about the use of behavioural research to tackle the
Dr Maguire hopes that these national hubs will act as a “proof of concept” for other areas outside of infectious disease, once the pandemic has passed, and that the infrastructure set up over the last two years can be scaled up within infectious disease and other areas of research. Alongside the HRB, other funding bodies have also played a role responding to the Covid-19 pandemic. Mr Peter Browne, Director of the Irish Research Council (IRC), told MI that “the research funding agencies, IRC, HRB, Science Foundation Ireland, and Enterprise Ireland, very quickly mobilised to make additional funding available to researchers to respond to the Covid crisis in a very rapid way”, with approximately 60 projects funded as part of the rapid response initiative.
Mr Browne also pointed out that this pandemic has really demonstrated the extent to which our research system is a “national asset”. He highlighted the expertise that the IRC has fostered over the years that has positively impacted the pandemic response. He added “the challenge for Ireland going forward is to continue to retain and develop really world-leading experts in a broad range of fields, so that we can be equipped to deal with crises, national or global, as they arise”.
Dr Maguire said that, over the years, people have asked if the money the HRB puts into infrastructure and clinical trials is necessary. She believes that Covid-19 has proven that it isMr Peter Browne Dr Teresa Maguire Dr Pete Lunn Dr Nikita Burke
The ONLY prefilled inhaler with visual and audible feedback for confirmed dose delivery1-4
Genuair - a simple to use inhaler for patients with COPD4
Abbreviated Prescribing Information
Eklira® Genuair® 322 micrograms inhalation powder. Please consult the Summary of Product Characteristics (SPC) for the full prescribing information. Presentation: Inhalation powder in a white inhaler with an integral dose indicator and a green dosage button. Each delivered dose contains 375 µg aclidinium bromide equivalent to 322 µg of aclidinium. Also, contains lactose. Use: Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).
Dosage: For inhalation use. Recommended dose is one inhalation of 322 micrograms aclidinium twice daily. Patients should be instructed on how to administer the product correctly as the Genuair inhaler may work differently from inhalers used previously. It is important to instruct the patients to read the Instructions for Use in the pack. No dose adjustments are required for elderly patients, or those with renal or hepatic impairment. No relevant use in children and adolescents. Contraindications: Hypersensitivity to aclidinium bromide or to any of the excipients. Warnings and Precautions: Stop use if paradoxical bronchospasm occurs and consider other treatments. Do not use for the relief of acute episodes of bronchospasm. Use with caution in patients with myocardial infarction in the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, or hospitalisation within the previous 12 months for heart failure functional classes III and IV. Dry mouth, observed with anticholinergic treatment, may be associated with dental caries in the long term. Use with caution in patients with symptomatic prostatic hyperplasia or bladder-neck obstruction or with narrow-angle glaucoma. Do not use in patients with rare hereditary problems of galactose intolerance, total lactose deficiency or glucose-galactose malabsorption.
Interactions: Do not administer with other anticholinergic-containing medicinal products. No other interactions expected. Please consult the SPC for more details. Fertility, pregnancy and lactation: No data on use in pregnancy. Risk to newborns/infants cannot be excluded. Consider risk-benefit before using during lactation. Unlikely to affect fertility at the recommended dose. Side-effects: Common (1-10%): Sinusitis, nasopharyngitis, headache, cough, diarrhoea, nausea. Uncommon (0.1-1%): Dizziness, blurred vision, tachycardia, palpitations, dysphonia, dry mouth, stomatitis, rash, pruritus, urinary retention. Rare (0.01-0.1%): hypersensitivity. Not known: angioedema, anaphylactic reaction. Pack sizes: Carton containing 1 inhaler with 60 unit doses. Legal category: POM Marketing Authorisation Number: EU/1/12/778/002
Marketing Authorisation holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd., Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924. Further information is available on request to A. Menarini Pharmaceuticals Ireland Ltd. or may be found in the SPC. Last updated: February 2020
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 to: 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 A. Menarini Pharmaceuticals Ireland Ltd. Phone no: 01 284 6744.
Date of item: November 2020. IR-BRI-09-2020
Abbreviated Prescribing Information Brimica® Genuair® 340 micrograms/12 micrograms inhalation powder. Please consult the Summary of Product Characteristics (SPC) for the full prescribing information. Presentation: Inhalation powder in a white inhaler with an integral dose indicator and an orange dosage button. Each delivered dose contains 396 µg aclidinium bromide (equivalent to 340 µg of aclidinium) and 11.8 micrograms of formoterol fumarate dihydrate. Also, contains lactose. Use: Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Dosage: For inhalation use. Recommended dose is one inhalation of 340 µg/12 µg twice daily. Patients should be instructed on how to administer the product correctly as the Genuair inhaler may work differently from inhalers used previously. It is important to instruct the patients to read the Instructions for Use in the pack. No dose adjustments are required for elderly patients, or those with renal or hepatic impairment. No relevant use in children and adolescents. Contraindications: Hypersensitivity to the active substances or to any of the excipients. Warnings and Precautions: Do not use in asthma. Stop use if paradoxical bronchospasm occurs and consider other treatments. Do not use for the relief of acute episodes of bronchospasm. Use with caution in patients with myocardial infarction in the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, or hospitalisation within the previous 12 months for heart failure functional classes III and IV. Discontinue if increases in pulse rate, blood pressure or changes in ECG occur. Use with caution in patients with a history of or known prolongation of the QTc interval or treated with products affecting the QTc interval. Use with caution in patients with severe cardiovascular disorders, convulsive disorders, thyrotoxicosis and phaeochromocytoma. Hypokalaemia may occur, is usually transient and supplementation not needed. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment. Use with caution in patients with symptomatic prostatic hyperplasia, urinary retention or with narrow-angle glaucoma. Dry mouth, observed with anticholinergic treatment, may be associated with dental caries in the long term. Do not use in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Interactions: Do not administer with other anticholinergic and/or long-acting β2-adrenergic agonist containing medicinal products. Caution in use with methylxanthine derivatives, steroids, non-potassium-sparing diuretics, β-adrenergic blockers or medicinal products known to prolong the QTc interval. Please consult the SPC for more details. Fertility, pregnancy and lactation: No data on use in pregnancy. Consider risk-benefit before using during lactation. Unlikely to affect fertility at the recommended dose. Side-effects: Common (1-10%): Nasopharyngitis, urinary tract infection, sinusitis tooth abscess, insomnia, anxiety, headache, dizziness, tremor, cough, diarrhoea, nausea, dry mouth, myalgia, muscle spasms, peripheral oedema, increased blood creatine phosphokinase. Uncommon (0.1- 1%): Hypokalaemia, hyperglycaemia, agitation, dysgeusia, blurred vision, tachycardia, electrocardiogram QTc prolonged, palpitations, angina pectoris, dysphonia, throat irritation, stomatitis, rash, pruritus, urinary retention, increased blood pressure. Rare (0.01-0.1%): Hypersensitivity, bronchospasm, including paradoxical. Not known: anaphylactic reaction, angioedema. Pack sizes: Carton containing 1 inhaler with 60 unit doses. Legal category: POM Marketing
Authorisation Number: EU/1/14/963/001 Marketing Authorisation holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd., Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924. Further information is available on request to A. Menarini Pharmaceuticals Ireland Ltd. or may be found in the SPC. Last updated: October 2019
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, 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 A. Menarini Pharmaceuticals Ireland Ltd. Phone no: 01 284 6744.
Due to the rise in Covid-19 cases, the IMO recently made a call for the public to redouble its efforts to combat the spread of the virus. President of the Organisation Dr Ina Kelly said the next couple of weeks will be critical, not only regarding the deteriorating Covid situation, but for the wider health service.
“Our GP surgeries, hospitals and ICU units are all under extraordinary pressure,” stated Dr Kelly.
“We are being hit by a perfect storm of high Covid numbers, the annual winter flu season and shockingly high numbers on waiting lists.”
Dr Kelly said that the public could help healthcare professionals by increasing their own vigilance and maintaining a strong sense of personal responsibility.
“People have done incredibly well over the past 18 months but the weeks leading to Christmas will be critical,” she said.
“For those who have yet to be vaccinated, please get the vaccine as a matter of urgency. For those who have been vaccinated, don’t treat the vaccine as a permission-slip to return to the old ways. Continue to exercise caution. Wear masks. Wash hands and keep your distance.”
Dr Kelly is a Specialist in Public Health Medicine and knows the measures necessary to curb the spread of the pandemic. But is there
a danger that those in power are let off the hook with these increasing calls for “personal responsibility”?
In the baseball-fantasy film, Field of Dreams , Kevin Costner’s character was repeatedly told, “if you build it, they will come.” In our all-too-real pandemic world, the Government would know after months of lockdown, “if you open it, they will come.” Well, at least if they have proof of vaccination. Vaccine passes are of course important but, as the current surge shows, are not sufficient in halting the spread of the more contagious Delta variant, especially given how open society currently is, and the level of congregation taking place. Other measures, such as those outlined by Dr Kelly, are necessary. Whether it should mainly be up to the public to protect themselves and others, or whether more guidance and policies are necessary, is a matter of debate and needs to be discussed in light of how the situation develops as Christmas approaches.
Personal responsibility is important. But so too is Governmental responsibility. It is all well and good telling people to be careful. But if the public do not see any change in direction at official level in order to reduce the burden on our health services in the coming weeks, it will make it harder to make the argument that they need to modify their individual behaviours.
8 NOVEMBER
"It is shocking, as Prof O'Shea points out in the article, that a major decision maker within the field still believes that 'eating less and moving more' would have an impact. Feels like a rollercoaster ride at times. So many positives and forward steps taken in field of obesity and then...." Bernadette Keenan, @JMBernK, 7 November
REACTION TO OUR LEAD NEWS STORY, 'PROBLEM OF SEXISM IN CARDIOLOGY', 8 NOVEMBER
"'Almost 80 per cent of female respondents said they had experienced sexism during their training... much higher than the UK survey that was published earlier this year, which reported 48 per cent.' Almost half of all heart trainees also experienced bullying.... This is not good." WiMIN, @WomenMedIreland, 5 November
"No, it’s not good. What’s encouraging though is that this is under the spotlight. Across several professions. We can support and learn from each other as we address these issues." Sonia McEntee, @SoniaMcEntee, 5 November
REACTION TO OUR NEWS INTERVIEW, 'A SURGEON DEDICATED TO ENDING OBSTETRIC FISTULA IN THE DRC', 8 NOVEMBER
"Great interview with Dr Lucien Wasingya Kasereka of @FistulaP in DRC. Having been trained by @RCSI_Irl Fellow Sr Dr Maura Lynch in #Uganda, Dr Lucien is now providing free fistula care to women in his home country of DRC." RCSI Institute of Global Surgery, @RCSI_GlobalSurg, 9 November
REACTION TO OUR NEWS STORY, 'PLANS FOR ALL-ISLAND CANCER RESEARCH INSTITUTE DISCUSSED', 8 NOVEMBER
"Plans for All-Island Cancer Research Institute discussed – article within Medical Independent – Thanks to the Joint Committee for Implementation of the Good Friday Agreement for giving us an opportunity to outline our vision for @AlCRIproject." Prof Liam Gallagher, @WaterfordMafia, 8 November
"No doubt this scheme was a game changer in its day for women.... But it is no longer fit for purpose and does not meet the needs of women (or the clinician by the looks of it). #timeforchange." Mary Curtin, @Marytcurtin, 29 October
"Seven years ago brought a proposal to the then COO in the HSE regarding the need to review the M&ICS. Should be prioritised in order to progress the national maternity strategy." Síle Ní Shiochrú, @sugrue_sheila, 30 October
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Type 2 diabetes mellitus
JARDIANCE is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise
- as monotherapy when metformin is considered inappropriate due to intolerance - in addition to other medicinal products for the treatment of diabetes
Heart failure
JARDIANCE is indicated in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction.
* In addition to glucose lowering, JARDIANCE (empagliflozin) demonstrated secondary benefits of reduction in weight and blood pressure although it is not licensed for this.1
† EMPA-REG OUTCOME® was a randomised, double-blind, placebo-controlled cardiovascular outcomes trial. Patients were randomised to receive either JARDIANCE 10 mg once daily, JARDIANCE 25 mg once daily or placebo, on top of standard of care. Primary endpoint was 3-point MACE: Time to first occurrence of cardiovascular death, non-fatal MI, non-fatal stroke. 14% relative risk reduction for combined endpoint of cardiovascular death, non-fatal MI, or non-fatal stroke (ARR 1.6%). JARDIANCE has an acceptable safety profile. 2
References
1. JARDIANCE (empagliflozin) Summary of Product Characteristics. Available at https://www.medicines.ie/medicines/jardiance-10-mg-and-25-mg-film-coated-tablets-32545/spc
2. Zinman B, Wanner C, Lachin JM et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-2128. (& Supplementary Appendix)
Prescribing Information (Ireland) JARDIANCE® (empagliflozin)
Film-coated tablets containing 10 mg or 25 mg empagliflozin. Indication: Type 2 diabetes mellitus: Jardiance is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise: as monotherapy when metformin is considered inappropriate due to intolerance; in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, refer to the Summary of Product Characteristics. Heart failure: Jardiance is indicated in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction. Dose and Administration: Type 2 diabetes mellitus: The recommended starting dose is 10 mg once daily. In patients tolerating empagliflozin 10 mg once daily who have eGFR ≥60 ml/min/1.73 m2 and need tighter glycaemic control, the dose can be increased to 25 mg once daily. The maximum daily dose is 25 mg. Renal impairment: The glycaemic efficacy of empagliflozin is dependent on renal function. Empagliflozin should not be initiated in patients with an eGFR <60 ml/min/1.73 m2 or CrCl <60 ml/min. In patients tolerating empagliflozin whose eGFR falls persistently below 60 ml/min/1.73 m2 or CrCl below 60 ml/min, the dose of empagliflozin should be adjusted to or maintained at 10 mg once daily. Empagliflozin should be discontinued when eGFR is persistently below 45 ml/min/1.73 m2 or CrCl persistently below 45 ml/min. No dose adjustment is required for patients with an eGFR ≥60 ml/min/1.73 m2 or CrCl ≥60 ml/min.
Heart failure: The recommended dose is 10 mg empagliflozin once daily. Renal impairment: For treatment of heart failure in patients with or without type 2 diabetes mellitus, empagliflozin 10 mg may be initiated or continued down to an eGFR of 20 ml/min/1.73 m2 or CrCl of 20 ml/ min. For patients with an eGFR <20 ml/min/1.73 m2 or CrCl <20 ml/min empagliflozin is not recommended. All indications: When used with sulphonylurea or insulin a lower dose of these may be considered to reduce the risk of hypoglycaemia. If a dose is missed, it should be taken as soon as the patient remembers; however, a double dose should not be taken on the same day. Renal impairment: Empagliflozin should not be used in patients with end stage renal disease (ESRD) or on dialysis. Hepatic impairment: No dose adjustment is required for patients with hepatic impairment. Not recommended in severe hepatic impairment. Elderly patients: No dose adjustment is recommended based on age. In patients 75 years and older, an increased risk for volume depletion should be taken into account. In patients aged 85 years and older, initiation of empagliflozin therapy is not recommended due to the limited therapeutic experience. Paediatric population: No data are available. Method of administration: The tablets can be taken with or without food, swallowed whole with water. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and
Precautions: Ketoacidosis: Rare cases of ketoacidosis, including life-threatening and fatal cases, have been reported in patients with diabetes mellitus treated with SGLT2 inhibitors, including empagliflozin. The risk of ketoacidosis must be considered in the event of nonspecific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Assess patients for ketoacidosis immediately, regardless of blood glucose level. In patients where ketoacidosis is suspected or diagnosed, treatment with empagliflozin should be discontinued immediately. Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute
serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of blood ketone levels is preferred to urine. Treatment with empagliflozin may be restarted when the ketone values are normal and the patient’s condition has stabilised. Before initiating empagliflozin, factors in the patient history that may predispose to ketoacidosis should be considered. Use with caution in patients who may be at higher risk of ketoacidosis. Restarting SGLT2 inhibitor treatment in patients with previous ketoacidosis while on SGLT-2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved. Jardiance should not be used for treatment of patients with type 1 diabetes. Renal impairment: Empagliflozin should not be used in patients with ESRD or in patients on dialysis. For type 2 diabetes mellitus, as glycaemic control depends on renal function, Jardiance should not be initiated in patients with an eGFR below 60 ml/min/1.73 m2 or CrCl <60 ml/min. In patients tolerating empagliflozin whose eGFR is persistently below 60 ml/min/1.73 m2 or CrCl <60 ml/min, the dose of empagliflozin should be adjusted to or maintained at 10 mg once daily. Empagliflozin is not recommended when eGFR is persistently below 45 ml/min/1.73 m2 or CrCl persistently below 45 ml/min. For heart failure, Jardiance is not recommended in patients with eGFR <20 ml/min/1.73 m2 Monitoring of renal function: Assessment is recommended prior to initiation and at least annually. Risk for volume depletion: Osmotic diuresis accompanying glucosuria may lead to a modest decrease in blood pressure. Therefore, caution should be exercised in patients with known cardiovascular disease, patients on anti-hypertensive therapy with a history of hypotension or patients aged 75 years and older. In case of conditions that may lead to fluid loss (e.g. gastrointestinal illness), careful monitoring of volume status and electrolytes is recommended. Temporary interruption of treatment with empagliflozin should be considered until the fluid loss is corrected. Elderly: See under Dose and Administration; special attention should be given to volume intake of elderly patients in case of co-administered medicinal products which may lead to volume depletion (e.g. diuretics, ACE-inhibitors). Complicated urinary tract infections: Temporary interruption of empagliflozin should be considered in patients with complicated urinary tract infections. Necrotising fasciitis: Cases of necrotising fasciitis of the perineum (Fournier’s gangrene), have been reported in patients with diabetes mellitus taking SGLT2 inhibitors. This is a rare but serious and potentially life-threatening event that requires urgent surgical intervention and antibiotic treatment. Patients should be advised to seek medical attention if they experience a combination of symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be aware that either uro-genital infection or perineal abscess may precede necrotising fasciitis. If Fournier’s gangrene is suspected, Jardiance should be discontinued and prompt treatment should be instituted. Lower limb amputation: An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term clinical studies with another SGLT2 inhibitor, counsel patients on routine preventative footcare. Hepatic injury: Cases of hepatic injury have been reported with empagliflozin in clinical trials. A causal relationship between empagliflozin and hepatic injury has not been established. Elevated haematocrit: Haematocrit increase was observed with empagliflozin treatment. Urine laboratory assessments: Due to its mechanism of action, patients taking Jardiance will test positive for glucose in their urine. Lactose: The tablets
PC-IE-101344
Date of preparation: September 2021
contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product. Interactions: Use with diuretics may increase the risk of dehydration and hypotension. Insulin and insulin secretagogues may increase the risk of hypoglycaemia therefore, a lower dose of insulin or an insulin secretagogue may be required. The effect of UGT induction (e.g. induction by rifampicin or phenytoin) on empagliflozin has not been studied. Co-treatment with known inducers of UGT enzymes is not recommended due to a potential risk of decreased efficacy. If an inducer of these UGT enzymes must be co-administered, monitoring of glycaemic control to assess response to Jardiance is appropriate. Interaction studies suggest that the pharmacokinetics of empagliflozin were not influenced by coadministration with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, torasemide and hydrochlorothiazide. Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically relevant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, simvastatin, warfarin, ramipril, digoxin, diuretics and oral contraceptives. Fertility, pregnancy and lactation: There are no data from the use of empagliflozin in pregnant women. As a precautionary measure, it is preferable to avoid the use of Jardiance during pregnancy. No data in humans are available on excretion of empagliflozin into milk. Jardiance should not be used during breast-feeding. No studies on the effect on human fertility have been conducted for Jardiance. Undesirable effects: Frequencies are defined as 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 common: hypoglycaemia (when used with sulphonylurea or insulin), volume depletion. Common: vaginal moniliasis, vulvovaginitis, balanitis and other genital infections, urinary tract infection (including pyelonephritis and urosepsis), thirst, constipation, pruritus (generalised), rash, increased urination, serum lipids increased. Uncommon: urticaria, angioedema, dysuria, blood creatinine increased/glomerular filtration rate decreased, haematocrit increased. Rare: necrotising fasciitis of the perineum (Fournier’s gangrene), diabetic ketoacidosis. Prescribers should consult the Summary of Product Characteristics for further information on side effects. Pack sizes: 10 mg; 28 tablets, 25 mg: 28 tablets. Legal category: POM. MA numbers: 10 mg/28 tablets EU/1/14/930/013; 25 mg/28 tablets EU/1/14/930/004. Marketing Authorisation
Holder: Boehringer Ingelheim International GmbH, 55216 Ingelheim am Rhein, Germany. Prescribers should consult the Summary of Product Characteristics for full prescribing information. Additional information is available on request from Boehringer Ingelheim Ireland Ltd, The Crescent Building, Northwood, Santry, Dublin 9. Prepared in July 2021
Adverse events should be reported. Reporting forms and information can be found at https://www.hpra.ie/homepage/about-us/report-an-issue. Adverse events should also be reported to Boehringer-Ingelheim Drug Safety on 01 2913960, Fax: +44 1344 742661, or by e-mail: PV_local_ UK_Ireland@boehringer-ingelheim.com
Ms Síle O’Dowd , Legal Counsel at Medisec Ireland CLG, addresses some of the key considerations when there are disagreements between guardians/ parents regarding treatment and the release of information in respect of minor patients
The starting point for considering any request for information relating to a minor patient, or a request to be involved in decisions regarding their care, is to consider the issue of legal guardianship.
What is legal guardianship and who is the legal guardian?
Guardianship represents the collection of rights and duties in respect of a child, and guardians are responsible for the moral, intellectual and physical wellbeing of the child, including decisions regarding their healthcare. Guardianship should not be confused with custody (responsibility for the day-today care of the child) and access (right of a person who does not live with the child to spend time with the child).
Guardianship can arise in a number of different forms including the following:
1. Automatic guardianship
Mother – The biological mother of a child, whether married or unmarried, is automatically a legal guardian of that child.
Married father – A child’s father also has automatic guardianship if he is married to the child’s mother; either before or after the birth of the child. Following a separation or divorce, both parents remain the child’s legal guardians, regardless of whether one or both parents have custody of the child.
Unmarried father meeting the prescribed co-habitation periods – following the introduction of the Children and Family Relationships Act 2015 (‘the 2015 Act’), an unmarried father can automatically become a legal guardian of his child if he has lived with the child’s mother for 12 consecutive months, including at least three months after the birth of the child.
It is important to note that the cohabitation period can only be calculated from the commencement date of the 2015 Act, ie, after 18 January 2016.
2. Guardianship by statutory declaration
Guardianship can also arise by way of statutory declaration. If both an unmarried mother and father are in agreement that the father should become the child’s joint legal guardian, the parents can complete a statutory declaration to that effect. A separate statutory declaration is required in respect of each individual child. At present, there is no central register or database for these declarations.
3. Guardianship by court order
A child’s father (unmarried to the child’s mother) can also apply to the local district court in order to be appointed joint legal guardian, regardless of whether his name appears on the child’s birth certificate or not. The court will make its decision based on the child’s best interests. There are other forms of guardianship which arise less frequently in day-to-day practice. These include adoption, non-parental, testamentary and temporary guardianship. A doctor may also be presented with a scenario where guardianship has been granted in another jurisdiction. The 2015 Act has helpfully confirmed that guardianship should be recognised when the equivalent rights and responsibilities are acquired in another jurisdiction.
Proof of guardianship
It is good practice to confirm the identity of a child’s legal guardians when registering them as a patient of the practice and to request proof of guardianship and formal identification before disclosing any minor patient information. The proof of guardianship should be kept on the child’s records for future reference. In some circumstances, such as guardianship on foot of the requisite “cohabitation period”, there
may be no written proof and it may be necessary to inquire about the relevant dates/periods of cohabitation.
Proof of guardianship can include one of the following:
A marriage certificate showing that the father was married to the child’s mother;
A copy of the statutory declaration;
A court order.
Records requests
As a general rule, there is a presumption of entitlement for legal guardians to have access to their children’s medical records (with any third party information redacted) unless a doctor believes that releasing the information would not be in the best interests of the child. The child’s best interests must be the doctor’s paramount consideration when dealing with any such requests. In situations where it may not be in the child’s best interests to release the information, there is potential for the decision to be interpreted as discrimination against the parent/guardian requesting the information. In these situations, it is advisable to err on the side of caution and consult with your professional indemnifier/insurer/legal advisor for further advice.
guardians with appropriate rights who share parental responsibility, it is usually sufficient for one guardian to give consent to day-to-day treatment and this is acknowledged in the HSE National Consent Policy. However, where decisions may have profound and/or irreversible consequences, it is advisable that both or all guardians are consulted. As a general rule of thumb, the more complex the decision, or the more serious the situation, the greater the need to include all guardians in your discussions.
Disagreement amongst guardians regarding treatment
Where there is reason to believe that the guardians may not be in agreement, you should seek the consent of all guardians with the exception of emergency situations. In emergency circumstances where a guardian is not contactable, the general doctrine of necessity applies. In all cases, the best interests of the child must be the paramount consideration.
If a doctor is aware that a child’s guardians do not agree with certain medical treatment, as an initial step, it is advisable to speak with the guardians together to go through the options and answer any questions they may have and see if agreement can be reached and documented on the patient’s file.
Where guardians cannot reach agreement, they can consider mediation and/or collaborative law and/or can apply to the court for direction. For example, where agreement cannot be reached on childhood vaccinations, one guardian can apply to the court for an order dispensing with the need for consent of the other. A court can use its discretion to dispense with a guardian’s consent if it is found to be unreasonably withheld, always making its decision based on the child’s best interests.
If there is any uncertainty regarding general issues of consent between guardians, it is advisable to try to obtain written agreement confirming that day-to-day routine care can be provided with the consent of one guardian. This will avoid any legal uncertainty and the treating doctor can provide medical treatment to the child as required.
In line with paragraph 18.1 of the Medical Council’s Guide to Professional Conduct and Ethics for Registered Medical Practitioners, if it is felt that the minor is sufficiently mature to understand the implications of the release of his or her records, then his or her consent should be obtained before allowing access. Part two of the HSE National Consent Policy considers the concept of a ‘mature minor’ noting that it is dependent on the child’s level of maturity, with no lower age limit defined in the document. It should be made clear in any dealings with minor patients that parents/guardians may be entitled to access their records up to 18 years and it is, therefore, important for the minor patient, despite their maturity, to understand that their confidentiality cannot be guaranteed.
The consent of a legal guardian is usually required to treat any patient under the age of 16 (or 18 in respect of psychiatric treatment). It is generally accepted that children under the age of 16 years should be involved in healthcare decision-making, but that the decision-making rests with the child’s guardians, bearing in mind the paramount responsibility on the doctor to act in the child’s best interests.
It is important to firstly clarify the precise role of the guardian and whether they have the necessary rights to consent on behalf of the child. Where there are two or more
The HSE has issued guidance, which is available on the Executive’s website, in respect of the roll-out of the Covid-19 vaccine to the under-16 age group, which specifically addresses situations where there is disagreement amongst parents/guardians. It advises that every reasonable effort should be made to avoid vaccination of a child where one parent/guardian has indicated that they object to vaccination. The onus, as per the HSE National Consent Policy, is on the objecting parent/guardian to make this objection known to the service in question. However, it notes that because of the way in which the vaccination roll-out is delivered for the 12-to-15 year old cohort, it is not possible to provide an absolute guarantee that notification of an objection will ensure that the child is not vaccinated.
As with all matters relating to the minor patient, if at any stage, you believe or have reasonable grounds for suspecting that a child is being harmed, has been harmed, or is at risk of harm through sexual, physical, emotional abuse or neglect, you should inform Tusla of your concerns without delay in line with your mandatory reporting obligations. Queries against the background of complex and contentious family law matters can often involve very specific individual circumstances. If you have any such queries, it is always advisable to contact your indemnifier/insurer/ legal advisor for advice and, if necessary, ask the parents to seek a court order.
In situations where it may not be in the child’s best interests to release the information, there is potential for the decision to be interpreted as discrimination against the parent/ guardian requesting the information.
Beacon Hospital’s Post - Covid Clinic was established in March 2021 in response to increasing numbers of patients presenting with lingering complaints long after their initial Covid-19 infection.
This highly specialised MDT clinic, the first of its kind in Ireland, o ers much needed care and support to these patients as they continue in their post-covid recovery journey.
Led by Prof Seamus Linnane, the Post-Covid Clinic has the support of the full service acute hospital including Ireland’s most technologically advanced radiology and diagnostics equipment.
For more information please see the Post-Covid Clinic section of our website - www.beaconhospital.ie or call 01 650 4860.
Patients can be referred by emailing covid.recovery@beaconhospital.ie
possibly be? What if the classic Levine chest-clutching sign is only found in less than half of the population?
Readmore by
Dr Sarah Fitzgibbon at www.mindo.ie @SarahFitzWiMINIf there’s one thing a doctor loves, it is a symptom that is “classical”. At med school, we learned multiple lists of physical complaints and experiences that were neatly boxed into diagnostic criteria, which helpfully corresponded to multiple lists of clinical syndromes and diseases. We loved the “easy” diagnoses, like the chest-clutching, sweaty, overweight gentleman, keeling over in his early 60s just like his father before him, with his waxy yellow xanthelasma-covered eyelids closing dramatically as he clutches the last breath from his cigarette-heavy lungs. A heart attack waiting to happen, as the whispered voices around him declare. Simple.
We do not love, on the other hand, the “atypical presentations”. The diagnoses that lurk at the back of our minds. Overlapping and intermingled signs and symptoms that could mean a brain tumour, or hypertension, or demyelination. Some of these we are regularly warned about – the ‘great pretenders’ such as syphilis, or lupus. The kind of illnesses that require head-scratching even from Dr House. We are conscious that there are complicated pathological conundrums and we hope that we are wise enough to recognise the times when we know that we do not know.
What if, however, the “atypical” presentation is one that occurs in more than half of the population? How could that
In 2016, an article in the British Medical Journal pointed out that myocardial infarctions which present without pain, but instead with breathlessness and abdominal pain, take longer to diagnose and therefore treat, with a resultant increase in mortality. It turns out that these symptoms are the most common presentation of cardiac ischaemia in women.
In medicine we are programmed to consider the male patient as the norm, and the female as the anomaly. We are all familiar with the “standard” patient, the quintessential Norm. According to the International Commission on Radiological Protection’s 1974 definition, “Reference man is defined as being between 20-to-30 years of age, weighing 70kg, is 170cm in height, and lives in a climate with an average temperature of from 10°C to 20°C. He is a Caucasian and is a Western European or North American in habitat and custom.” When I see that written down, I am aghast at the ridiculousness of it. Pharmaceutical companies have been using “standard” men in their clinical trials for decades. This has resulted in women and people of varied ethnicities and phenotypes being excluded and therefore the benefits and risks of a given drug or therapeutic intervention being insufficiently or improperly investigated. Drug companies have historically tested all of their new medications on groups of young white men, then marketed them to the full population without any recognition of the very high likelihood of variability in efficacy, metabolism, and side-effects between the genders and also between ethnic groups. We have become more familiar with ethnic-
ity-based therapeutic decision making when it comes to, for example, hypertension and the use of ACE inhibitors, but we are presented with much fewer alternative pathways when we consider pharmaceutical interventions for men and women.
There is a particularly irritating cohort of humans when it comes to prescribing medication; those “women of child-bearing age”. Or, even worse, the pesky pregnant ones. However, pregnancy is a cinch therapeutically speaking – just tell them they can’t have any medications at all. Or if they really must insist on treating their potentially life-threatening infection or hyperemesis, tell them “we can’t say for definite if the drugs will work or are safe, but we think they probably are because other pregnant women have had to make the choice to take a tablet that has not been rigorously tested in pregnancy and most of those women were okay afterwards, as far as we know”. Our old friend “anecdotal evidence” (an oxymoron if ever there was one). All those icky hormones and developing foetuses are very off-putting for the researchers, who would much rather ask Norm to pop in again to swallow a load of ondansetron, and see how his hyperemesis responds.
These gender gaps in research and data were highlighted by Caroline Criado-Perez in her book Invisible Women, where she also describes how car safety tests are all carried out using our friend Norm as a crash test dummy, meaning that women are 47 per cent more likely to be seriously injured in a car accident. Police stab vests, PPE, safety helmets, even mobile phones are all designed for a typical man, resulting in increased risks for other users.
Is it time to erase the word “atypical” from our lexicon?
Given growing concerns about medical crowdfunding, has the time come to instate gatekeepers to monitor the area?
GEORGE WINTERThe subjects of Thomas Grey’s Elegy Written in a Country Churchyard are “Far from the madding crowd’s ignoble strife”; journalist Douglas Murray has written of The Madness of Crowds (2019); and in a speech given at the University of Copenhagen in 1968 the author Arthur Koestler spoke of a depersonalised “kind of savagery generated by the groupmind, which is largely indifferent, or even opposed, to the interests of the individuals who constitute the group”.
Given these far-from-ringing endorsements of crowds, it is almost a relief to find Brian Appleyard, in his The Brain is Wider than the Sky (2011), citing writer James Surowiecki’s idea – articulated in The Wisdom of Crowds (2004) – that en masse we are not only cleverer than experts but “more decent than individuals or small groups”. Really?
Has the internet changed the nature of crowds? Previously passive members of an audience are now participants and this passive/active shift has extended the word “community” to include screen-mediated encounters with individuals we will never meet. For example, “GoFundMe announces its community has made more than 120 million donations, raising over $9 billion for people and causes” is a 2019 headline on the company’s website. And in relation to medical crowdfunding – using websites and social media to attract money from donors to pay for medical care – GoFundMe is not only “the leader in online medical fundraising”, but also raises more than £450 million annually. As a salesman might ask his favourite audience – a herd of independent minds – “what’s not to like?”
Well, while walking on eggshells, but not treading on toes, I suggest that not all cyber “communities” are braced for collision with ethical boundaries towards which their well-intentioned efforts may impel them. For example, writing in the JAMA (2018, 320: 1705–1706) Vox et al describe how, between November 2015 and December 2017, they identified campaigns posted in the United States and Canada on GoFundMe for the following treatments that are unsupported by evidence or are potentially unsafe: Homeopathy or naturopathy for cancer; hyperbaric oxygen therapy for brain injury; stem cell therapy for brain injury and spinal cord injury; and long-term antibiotic therapy for “chronic Lyme disease”. Over 1,000 medical crowdfunding campaigns for these treatments raised more than $6.7 million and the authors conclude “that a wide scope of campaigns for unsupported, ineffective, or potentially dangerous treatments are moderately successful in obtaining funding”.
More recently, Iqbal and Collins, writing in the Irish Journal of Medical Science (2021, 190: 1355–1361), considered ‘Crowdfunding for anticancer therapies: An analysis of non-US GoFundMe pages’. Of 150 pages identified between November 2019 and January 2020, most requestors had brain cancer, followed by breast cancer and ovarian cancer. The median amount of money requested was €48,205 (€1,171–€588,759) and the authors commented that “worryingly, a large proportion are requesting immunotherapy for unlicensed indications and alternative therapies with no evidence”.
But in an age where patient autonomy is asserted, and crowdfunding is widespread why should the hope of a patient and their family be stifled by the ethical reservations of others who suggest that such hopes may be beyond realistic reach? This false hope harms argument is addressed by ethicist Dr Marleen Eijkholt, who acknowledges in Bioethics (2020, 34:703–711) the importance of hope for patients’ self-identity as active agents but insists “that the
healthcare profession has an obligation to avoid collaborating or participating in, propagating or augmenting false hope in medicine”. By complying with unrealistic patient and family requests, including those “for rights to try resuscitative efforts in terminally ill patients, or other demands for non-beneficial treatments” harm can be done “on both individual and communal levels and cannot be ignored”.
Iqbal and Collins (2021) highlight concerns around queue jumping and the promotion of medical tourism; note possibilities for fraud and dishonesty; and suggest that “[p]ossible expert review panels containing doctors, nurses and other healthcare professionals could screen the content of new webpages for authenticity, appropriateness, and safety”.
Charlie Gard was an infant born with encephalomyopathic mitochondrial DNA depletion syndrome, and although crowdfunding was used to finance experimental nucleoside therapy, the treatment was ultimately not given. This case is considered in ‘Bioethics and the use of social media for medical crowdfunding’ by Kubheka in BMC Medical Ethics (2020, 21:96), noting both the role of the media in highlighting interventions by Donald Trump and Pope Francis, and that “GoFundMe donated $10,000 to Charlie’s campaign hosted on their platform, but had refused to waive platform fees on a campaign supporting victims of a Somali drought in 2017, raising ethical disquiet”. Here, it seems, is a for-profit company assuming a gatekeeper role and determining who gains access to care.
Should there be medical gatekeepers for medical crowdfunding, and, if so, might they make moral decisions that are derived from emotion, or even display moral blindness and call it tolerance? Possibly. However, those tempted to accuse gatekeepers of elitism by imposing on the public what they think is good for it, should remind themselves that gatekeepers are also the public… but are prepared to carry a can that others choose not to pick up.
TALZENNA is a proven alternative to chemotherapy* that provides patients with greater efficacy in a convenient, once-daily oral dose1
LONGER MEDIAN PROGRESSION-FREE SURVIVAL (PFS)
TALZENNA significantly prolonged median PFS vs chemotherapy: 8.6 months vs 5.6 months (HR=0.54 [95% CI: 0.41-0.71]; P<0.0001)1
DOUBLED OBJECTIVE RESPONSE RATE (ORR) ORR for TALZENNA was 62.6% (95% CI: 55.8-69.0) vs 27.2% (95% CI: 19.3-36.3) with chemotherapy (OR=4.99 [95% CI: 2.93-8.83]; P<0.0001)1†‡
CONVENIENT DOSING
TALZENNA provides convenient, once-daily oral dosing, with or without food1
Indication: TALZENNA is indicated as monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2-negative locally advanced or metastatic breast cancer. Patients should have been previously treated with an anthracycline and/or taxane in the (neo)adjuvant, locally advanced or metastatic setting unless patients were not suitable for these treatments (see section 5.1 of full SmPC). Patients with hormone receptor (HR)positive breast cancer should have been treated with a prior endocrine-based therapy, or be considered unsuitable for endocrine-based therapy.
CI=confidence interval; gBRCA=germline breast cancer susceptibility gene; HER2-=human epidermal growth factor receptor 2 negative; HR=hazard ratio; HR+=hormone receptor-positive; OR=odds ratio; RECIST=Response Evaluation Criteria in Solid Tumors.
PRESCRIBING INFORMATION
▼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. Refer to section 4.8 of the SPC for how to report adverse reactions.
Talzenna®▼0.25 mg and 1 mg hard capsules IE Prescribing Information:
Before prescribing Talzenna (talazoparib) please refer to the full Summary of Product Characteristics (SmPC). Presentation: Each 0.25 mg hard capsule contains talazoparib tosylate equivalent to 0.25 mg talazoparib. Each 1 mg hard capsule contains talazoparib tosylate equivalent to 1 mg talazoparib. Indications: Talzenna is indicated as monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2-negative locally advanced or metastatic breast cancer. Patients should have been previously treated with an anthracycline and/or a taxane in the (neo)adjuvant, locally advanced or metastatic setting unless patients were not suitable for these treatments. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine-based therapy, or be considered unsuitable for endocrinebased therapy. Dosage and Administration: Treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. Patients should be selected for the treatment of breast cancer with Talzenna based on the presence of deleterious or suspected deleterious germline BRCA mutations determined by an experienced laboratory using a validated test method. Genetic counselling for patients with BRCA mutations should be performed according to local regulations, as applicable. The recommended dose is 1 mg talazoparib once daily. Patients should be treated until disease progression or unacceptable toxicity occurs. Complete blood count should be obtained prior to starting Talzenna therapy and monitored monthly and as clinically indicated. To manage adverse drug reactions, interruption of treatment or dose reduction based on severity and clinical presentation should be considered (see SmPC section 4.2). Special populations: Hepatic impairment: See SmPC section 4.2. No dose adjustment is required for patients with mild, moderate or severe hepatic impairment. Renal impairment: See SmPC section 4.2. No dose adjustment is required for patients with mild renal impairment. For patients with moderate renal impairment, the recommended starting dose of Talzenna is 0.75 mg once daily. For patients with severe renal impairment, the recommended starting dose of Talzenna is 0.5 mg once daily. Talzenna has not been studied in patients with CrCL < 15 mL/min or patients requiring haemodialysis. Elderly: No dose adjustment is necessary in elderly (≥ 65 years of age) patients. Paediatric population: The safety and efficacy of Talzenna in children and adolescents < 18 years of age have not been established. Method of administration: Talzenna is for oral use. To avoid contact with the capsule content, the capsules should be swallowed whole, and must not be opened or dissolved. They can be taken with or without food (See SmPC section 5.2). Contraindications: Hypersensitivity to the active substance or to any of the excipients. Breast-feeding. Special Warnings and Precautions: Myelosuppression: Myelosuppression consisting of anaemia, leucopenia/ neutropenia, and/or thrombocytopenia, have been reported in patients treated with talazoparib (see section 4.8). Talazoparib should not be started until patients have recovered from haematological toxicity caused by previous therapy (≤ Grade 1). Precautions should be taken to routinely monitor haematology parameters and signs and symptoms associated with anaemia, leucopenia/neutropenia, and/or thrombocytopenia in patients receiving talazoparib. If such events occur, dose modifications (reduction or interruption) are recommended. Supportive care with or without blood and/or platelet transfusions and/or administration of colony stimulating factors may be used as appropriate. Myelodysplastic
PP-TAL-IRL-0038
Date of Preparation September 2021
* Capecitabine, eribulin, gemcitabine, or vinorelbine.
† Conducted in the intent-to-treat population with measurable disease at baseline. Per RECIST v1.1, confirmation of response was not required.1
‡ ORR is the proportion of patients who have a partial or complete response to treatment.
Reference: 1. TALZENNA Summary of Product Characteristics.
syndrome/Acute myeloid leukaemia: Myelodysplastic syndrome/Acute Myeloid Leukaemia (MDS/AML) have been reported in patients who received poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, including talazoparib. Overall, MDS/AML has been reported in 2 out of 584 (0.3%) solid tumour patients treated with talazoparib in clinical studies. Potential contributing factors for the development of MDS/AML include previous platinum-containing chemotherapy, other DNA damaging agents or radiotherapy. Complete blood counts should be obtained at baseline and monitored monthly for signs of haematologic toxicity during treatment. If MDS/AML is confirmed, talazoparib should be discontinued. Contraception in women of childbearing potential : Talazoparib was clastogenic in an in vitro chromosomal aberration assay in human peripheral blood lymphocytes and in an in vivo bone marrow micronucleus assay in rats but not mutagenic in Ames assay (see section 5.3), and may cause foetal harm when administered to a pregnant woman. Pregnant women should be advised of the potential risk to the foetus (see section 4.6). Women of childbearing potential should not become pregnant while receiving Talzenna and should not be pregnant at the beginning of treatment. A pregnancy test should be performed on all women of childbearing potential prior to treatment. A highly effective method of contraception is required for female patients during treatment with Talzenna, and for at least 7 months after completing therapy. Since the use of hormonal contraception is not recommended in patients with breast cancer, two non-hormonal and complementary contraception methods should be used. Male patients with female partners of reproductive potential or pregnant partners should be advised to use effective contraception (even after vasectomy), during treatment with Talzenna and for at least 4 months after the final dose. Interactions: Talazoparib is a substrate for drug transporters P-gp and Breast Cancer Resistance Protein (BCRP) and it is mainly eliminated by renal clearance as unchanged compound. Concomitant treatment with inhibitors of P-glycoprotein (P-gp): Strong inhibitors of P-gp may lead to increased talazoparib exposure. Concomitant use of strong P-gp inhibitors (including but not limited to amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, and verapamil) during treatment with talazoparib should be avoided. Co-administration should only be considered after careful evaluation of the potential benefits and risks. If co-administration with a strong P-gp inhibitor is unavoidable, the Talzenna dose should be reduced to 0.75 mg once daily. When the strong P-gp inhibitor is discontinued, the Talzenna dose should be increased (after 3-5 half-lives of the P-gp inhibitor) to the dose used prior to the initiation of the strong P-gp inhibitor. No talazoparib dose adjustments are required when co administered with rifampin. However, the effect of other P-gp inducers on talazoparib exposure has not been studied. Other P-gp inducers (including but not limited to carbamazepine, phenytoin, and St. John’s wort) may decrease talazoparib exposure. BCRP inhibitors: The effect of BCRP inhibitors on PK of talazoparib has not been studied in vivo. Co-administration of talazoparib with BCRP inhibitors may increase talazoparib exposure. Concomitant use of strong BCRP inhibitors (including but not limited to curcumin and cyclosporine) should be avoided. If co administration of strong BCRP inhibitors cannot be avoided, patient should be monitored for potential increased adverse reactions. Effect of acid-reducing agents: Population PK analysis indicates that co-administration of acid-reducing agents including proton pump inhibitors and histamine receptor 2 antagonists (H2RA), or other acid reducing agents had no significant impact on the absorption of talazoparib. Systemic hormonal contraception: Drug-drug interaction studies between talazoparib and oral contraceptives have not been conducted. Fertility, pregnancy and lactation: Fertility
There is no information on fertility in patients. Based on non-clinical findings in testes (partially reversible) and ovary (reversible), Talzenna may impair fertility in males of reproductive potential. Women of childbearing potential should not become pregnant while receiving Talzenna and should not be pregnant at the beginning of treatment. A pregnancy test should be performed on all women of childbearing potential prior to treatment. Women of childbearing potential must use highly effective forms of contraception prior to starting treatment with talazoparib, during treatment, and for 7 months after stopping treatment with talazoparib. Since the use of hormonal contraception is not recommended in patients with breast cancer, two non-hormonal and complementary contraception methods should be used. Male patients with female partners of reproductive potential or pregnant partners should be advised to use effective contraception (even after vasectomy) during treatment with Talzenna, and for at least 4 months after the final.
Pregnancy: There are no data from the use of Talzenna in pregnant women. Studies in animals have shown embryo foetal toxicity. Talzenna may cause foetal harm when administered to a pregnant woman. Talzenna is not recommended during pregnancy or for women of childbearing potential not using contraception. Breast-feeding: It is unknown whether talazoparib is excreted in human breast milk. A risk to breast-fed children cannot be excluded and therefore breast-feeding is not recommended during treatment with Talzenna and for at least 1 month after the final dose.
Undesirable Effects: The overall safety profile of Talzenna is based on pooled data from 494 patients who received talazoparib at 1 mg daily in clinical studies for solid tumours, including 286 patients from a randomised Phase 3 study with germline BRCA-mutated (gBRCAm), HER2-negative locally advanced or metastatic breast cancer and 83 patients from a nonrandomised Phase 2 study in patients with germline BRCA-mutated locally advanced or metastatic breast cancer. The most common (≥ 25%) adverse reactions in patients receiving talazoparib in these clinical studies were fatigue (57.1%), anaemia (49.6%), nausea (44.3%), neutropenia (30.2%), thrombocytopenia (29.6%), and headache (26.5%). The most common (≥ 10%) Grade ≥ 3 adverse reactions of talazoparib were anaemia (35.2%), neutropenia (17.4%), and thrombocytopenia (16.8%). Dose modifications (dose reductions or dose interruptions) due to any adverse reaction occurred in 62.3% of patients receiving Talzenna. The most common adverse reactions leading to dose modifications were anaemia (33.0%), neutropenia (15.8%), and thrombocytopenia (13.4%). Permanent discontinuation due to an adverse reaction occurred in 3.6% of patients receiving Talzenna. The median duration of exposure was 5.4 months (range 0.03-61.1). Very common adverse reactions (>1/10) are Thrombocytopenia, Anaemia, Neutropenia, Leucopenia, Decreased appetite, Dizziness, Headache, Vomiting, Diarrhoea, Nausea, Abdominal pain, Alopecia and Fatigue. Commonly reported adverse reactions (>1/100 to <1/10), are Lymphopenia, Dysgeusia, Stomatitis and Dyspepsia. Refer to SmPC section 4.8 for further information on side effects. Legal Category: Product subject to prescription which may not be renewed (A): S1A. Marketing
Authorisation Number: Talzenna 0.25 mg hard capsules – EU/1/19/1377/001004; Talzenna 1 mg hard capsules – EU/1/19/1377/005-006. 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 4676500.
Date of Preparation: 05/2021
Ref: TE 2_0
▼This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get to HPRA Pharmcoviglance, Earlsfort Terrace, Dublin 2, IRL. Tel: +353 1 676 4971, Fax: +353 1 676 2517, Website: www.hpra.ie, E-mail: medsafety@hpra.ie
When treating adult patients with gBRCA-mutated HR+/HER2or triple-negative locally advanced or metastatic breast cancer1
So this year’s Oxford Languages’ 2021 Word of the Year is “vax”. No surprise really that a pandemic-related word would top the poll. The use of “vax” – a word that first appeared in the 1980s – surged dramatically, occurring more than 72 times as frequently in September than a year earlier.
“All the other vaccine words increased, but nothing like ‘vax’,” says Fiona McPherson, a senior editor for new words at Oxford Languages, which publishes the Oxford English Dictionary (OED). “It’s a short, punchy, attention-grabbing word. And, speaking as a lexicographer, it’s also quite a productive one,” she continues. “You see it used in all sorts of combinations to make new words.”
According to the OED, the word “vaccine” was first recorded in English in 1799, following the British scientist Edward Jenner’s experiments with inoculation against smallpox. And although the shortened form “vax” did not appear until the 1980s, the term “anti-vax” – spelled “anti-vacks” – reared its head not long after Jenner’s discovery. “The anti-vacks are assailing me... with all the force they can muster in the newspapers,” Jenner wrote in an 1812 letter.
In a trend toward “expressive doubling”, the OED notes an extra ‘x’ has crept into some of the vax-related neologisms (such as “vaxxie”) that have become common.
Katherine Wu, science writer at the Atlantic wrote recently about how the novel coronavirus has prompted a huge shift in the way we talk with one another, and about one another. It has resulted in a good deal of linguistic “leakage”, she says. Language that was hitherto confined to medical wards and research labs has
Question 2
suddenly appeared in everyday discourse. And a less than smooth transmission has caused some confusion and misunderstanding.
Take the word “asymptomatic”, which scientists use to denote infections that never make people sick. However, many who start off their infection symptomless might not stay that way, and until someone is fully over coronavirus infection, it’s impossible to say whether they were truly asymptomatic or presymptomatic.
Then there is “quarantine”. “Two years into our run with Covid, that’s still one of the terms we most commonly mess up,” Wu writes. “Correctly used, ‘quarantine’ describes the period of time when people who think they’ve been exposed to SARS-CoV-2 are supposed to cloister themselves.” However, if you know you are infected thanks to a positive PCR test, then you’re heading into isolation, not quarantine.
(Interestingly, the term “quarantine” has been in use since the time when ships arriving from plague-stricken countries were cordoned off for 40 days before docking –hence the ‘quar’ part of the word.)
“Natural immunity” is another foster-phrase; long before the pandemic started, scientists used it to describe the protection left behind after an infection by a bona fide pathogen. But, Wu says, in the age of Covid, the phrase has become weaponised into a false binary: If infection-induced immunity is natural, does that mean that immunity obtained through different means must be unnatural – artificial, undesirable, a dangerous hoax, or even, for some people, a moral failure?
After cataract surgery, patients should be advised that
A. Ninety minutes is the average stay in hospital.
B. They should not bend over for one month.
C. New glasses should not be prescribed for at least three months.
D. If their vision in the operated eye fails rapidly, they should seek medical advice urgently.
E. About 20-30 per cent will develop an ‘after-cataract’ at some time.
Duodenal ulcers
A. Peak incidence in men is 30-to-40 years.
B. Tend to relapse and remit over a 10-to-25-year period.
C. Epigastric pain is clearly related to eating.
D. Recognised symptoms include heartburn.
E. Investigation of choice is barium meal.
Question 3
A. Episodes last on average four-to-six months.
B. Recurrence arises in about 70 per cent of cases.
C. Even if unilateral is a well-recognised cause of significant behaviour disorders.
D. Treated with grommets, will benefit from treatment for about one year.
E. Can be effectively treated with oral antihistamines.
Question 4
The following are recognised side-effects of thiazide diuretics
A. Sleep disturbance.
B. Flushing.
C. Impotence.
D. Hyponatraemia.
E. Renal impairment (especially in renal artery disease).
Question 5
Keratoacanthoma
A. Develop rapidly in size over a period of a few weeks.
B. Lesion is characteristically raised above the surrounding skin surface.
C. Have a keratin-filled centre.
D. Affect all areas of the skin equally.
E. Will not disappear spontaneously.
“But that dichotomy is scientifically nonexistent”, she asserts. “Inoculations are designed to mimic the microbes that cause infections, and often end up tickling pretty similar responses out of immune cells. The main difference is that vaccines deliver their defensive lessons safely, without risking disease.”
The false binary has led scientists to use terms such as “infection-acquired” and “vaccine-acquired immunity”. They have even started using another phrase –”hybrid immunity” – to refer to the heightened protection that’s afforded when people with a prior SARS-CoV-2 infection get vaccinated.
For those who are afraid of the ‘unknown’ technology of Covid vaccines, Wu offers the following: “Vaccines leverage and build on our inborn defences, in much the same way that glasses can enhance vision and good running shoes can speed up a person’s pace. They’re not an indictment of the immune system and its numerous powers, but a tribute to them.”
It’s a point worth remembering for us healthcare professionals. I have no doubt the confusion around Covid-19 terminology has fed into the hands of the anti-vaxxers. It gives them ammunition with which to influence vaccine hesitators, who are genuinely trying to deal with real anxieties around the novel vaccines.
But if we can influence the everyday language around immunisation and create reassuring images in patients’ minds, we can move it from a lexicographically interesting aside to an effective weapon in our public health armoury.
E. FALSE. Heal over a period of months leaving a small scar.
D. FALSE. Mainly areas exposed to sunlight.
C. TRUE. If this keratin plug becomes detached the lesion may look like an ulcerating epithelium.
B. TRUE. Often raised 0.5cm and 1-2 cm in diameter.
A. TRUE. Presents as a small papule which rapidly grows over at most 12 weeks.
ANSWER 5
E. FALSE. A risk with ACE inhibitors.
D. TRUE. And other electrolyte disturbances.
C. TRUE. And mild GI disturbances.
B. FALSE. Calcium channel antagonists may cause this.
A. FALSE. Can occur with a beta blocker.
ANSWER 4
E. FALSE. No evidence that any medication is of benefit in the longer term.
D. TRUE. Further year’s benefit if have adenoidectomy as well.
B. FALSE. Seven per cent.
A. FALSE. Two months.
ANSWER 3
E. FALSE. Endoscopy.
D. TRUE. Also bloating, fullness, early satiety.
C. TRUE. May make it worse or better.
B. TRUE. Symptoms for four-to-six weeks, then remission for three-to-six months.
A. FALSE. 40-to-50 in men; 50-to-60 in women.
ANSWER 2
E. TRUE. Opacification of the capsule with reduction in vision, glare and dazzle.
D. TRUE. First sign of post-operative endophthalmitis (usually two-to-five days after surgery).
C. FALSE. With modern cataract surgery can get glasses when need them.
B. FALSE. No need to avoid lifting weights either.
A. TRUE. Longer if have a general anaesthetic, but still a day case.
ANSWER 1
C. FALSE. Even in persistent bilateral glue ear any resulting speech, learning or behavioural disorders are mild and correct spontaneously with age.
ONLY CDK4/6i cited by all these 3 expert panels 1-3:
ESO-ESMO Advanced Breast Cancer Fifth International Consensus Conference (ABC5)1
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)2
Clinical Cancer Advances 2020: Annual Report on Progress Against Cancer from ASCO3
Only KISQALI + ET received an ESMO-MCBS clinical benefit score of 5 — for the first-line treatment of premenopausal women
Only KISQALI + fulvestrant received an ESMO-MCBS clinical benefit score of 4 — for the first-line treatment of postmenopausal women
ABC5 2019 was the ESO-ESMO Advanced Breast Cancer Fifth International Consensus Conference.
The ESMO-MCBS is a standardized tool that quantifies the likely magnitude of clinical benefit. Grades for efficacy, QoL, and overall benefit in the non-curative setting range from 1-5, with 4 and 5 denoting substantial benefit.4
NCCN GUIDELINES®: 3 Category 1 preferred recommendations for KISQALI2
First line: AI + Kisqali ^ (category 1)
First line: Fulvestrant + Kisqali (category 1)
Second Line: Fulvestrant + Kisqali (category 1)
The National Comprehensive Cancer Network ® (NCCN ®) confers a Category 1 designation if, based on high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. NCCN makes no warranties of any kind whatsoever regarding their content, use or application, and disclaims any responsibility for their application or use in any way.
^In premenopausal women Kisqali + AI used in combination with LHRH agonist
The only CDK4/6 inhibitor regimen recognised by ASCO’s Clinical Cancer Advances 20203
Ribociclib + ET was recognised among “the most important clinical research advances of the past year” based on a “clear overall survival benefit” demonstrated in pre and peri menopausal women.
Clinical Cancer Advances 2020: Annual Report on Progress Against Cancer highlights the most important clinical research advances of the past year, including the Advance of the Year, and identifies priority areas where ASCO believes research efforts should be focused moving forward.
References:
of Oncology e-Learning Session 511; January 23, 2020. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.5.2020. ©National Comprehensive Cancer Network, Inc. 2020. All right reserved. Published July 15, 2020. Accessed August 21, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org.
3. Markham MJ, Wachter K, Agarwal N, et al. Clinical cancer advances 2020: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2020;38(10):1081-1101
4. ESMO-Magnitude of clinical benefit scale scorecards. ESMO.org. Accessed August 25, 2020. https:// www.esmo.org/guidelines/esmo-mcbs/esmo-magnitude-of-clinicalbenefit-scale/scorecard-[6-1, 7-1, 8-1, 9-1, 158-1, 159-1, 160-1, 161-1]. aBC, advanced breast cancer; ASCO, American Society of Clinical Oncologists; ESMO, European Society for Medical Oncology; ESO, European Society of Oncology NCCN, National Comprehensive Cancer Network
ABBREVIATED PRESCRIBING INFORMATION
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
Kisqali ▼ (ribociclib) 200 mg film-coated tablets
Presentation: Film‑coated tablets (FCT) containing 200 mg of ribociclib and 0.344 mg soya lecithin.
Indications: Kisqali is indicated for the treatment of women with hormone receptor (HR)‑positive, human epidermal growth factor receptor 2 (HER2)‑negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine based therapy, or in women who have received prior endocrine therapy
In pre‑ or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone‑releasing hormone (LHRH) agonist.
Dosage and administration:
Adults: The recommended dose is 600 mg (3 x 200 mg FCT) taken orally, once daily for 21 consecutive days followed by 7 days off treatment, resulting in a complete cycle of 28 days.
Kisqali should be used together with 2.5 mg letrozole or another aromatase inhibitor or with 500 mg fulvestrant.
When Kisqali is used in combination with an aromatase inhibitor, the aromatase inhibitor should be taken orally once daily continuously throughout the 28‑day cycle. Please refer to the Summary of Product Characteristics (SmPC) of the aromatase inhibitor for additional details.
When Kisqali is used in combination with fulvestrant, fulvestrant is administered intramuscularly on days 1, 15 and 29, and once monthly thereafter. Please refer to the SmPC of fulvestrant for additional details.
Treatment of pre‑ and perimenopausal women with the approved Kisqali combinations should also include an LHRH agonist in accordance with local clinical practice
Management of severe or intolerable adverse drug reactions (ADRs) may require temporary dose interruption, reduction or discontinuation of Kisqali. Please see section 4.2 of SmPC for recommended dose modification guidelines. Kisqali can be taken with or without food (see section 4.5). The tablets should be swallowed whole and should not be chewed, crushed or split prior to swallowing.
Special populations: ♦Renal impairment: Mild or moderate:
No dose adjustment is necessary. Severe: A starting dose of 200 mg is recommended in patients with severe renal impairment. Kisqali has not been studied in breast cancer patients with severe renal impairment. Caution should be used in patients with severe renal impairment with close monitoring for signs of toxicity. ♦Hepatic impairment: Mild: No dose adjustment is necessary. Moderate or severe:
Novartis Ireland Ltd
Vista Building, Elm Park Business Pk, Merrion Road, Dublin 4, D04 A9N6
Dose adjustment is required, and the starting dose of 400 mg once daily is recommended. ♦Elderly (>65 years): No dose adjustment is required. ♦Pediatrics(<18 years): Safety and efficacy have not been established.
Contraindications: Hypersensitivity to the active substance or to peanut, soya or any of the excipients.
Warnings/Precautions: ♦Neutropenia was most frequently reported ADR A complete blood count (CBC) should be performed before initiating treatment. CBC should be monitored every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. Febrile neutropenia was reported in 1.4% of patients exposed to Kisqali in the phase III clinical studies. Patients should be instructed to report any fever promptly.Based on the severity of the neutropenia, Kisqali may require dose interruption, reduction, or discontinuation.
♦Hepatobiliary toxicity increases in transaminases have been reported. Liver function tests (LFTs) should be performed before initiating treatment. LFTs should be monitored every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. If grade 2 abnormalities are noted, more frequent monitoring is recommended.
Recommendations for patients who have elevated AST/ ALT grade 3 at baseline have not been established. Based on the severity of transaminase elevations, Kisqali may require dose interruption, reduction, or discontinuation.
♦QT interval prolongation has been reported with Kisqali.
The use of Kisqali should be avoided in patients who have already or who are at significant risk of developing QTc prolongation. The ECG should be assessed prior to initiation of treatment. Treatment with Kisqali should be initiated only in patients with QTcF values <450 msec. The ECG should be repeated at approximately Day 14 of the first cycle and at the beginning of the second cycle, then as clinically indicated. In case of QTcF prolongation during treatment, more frequent ECG monitoring is recommended Appropriate monitoring of serum electrolytes (including potassium, calcium, phosphorous, and magnesium) should be performed prior to initiation of treatment, at the beginning of the first 6 cycles, and then as clinically indicated. Any abnormality should be corrected before the start of Kisqali treatment. Based on the observed QT prolongation during treatment, Kisqali may require dose interruption, reduction, or discontinuation. Based on the E2301 study QTcF interval data, Kisqali is not recommended for use in combination with tamoxifen ♦Critical visceral disease. The efficacy and safety of ribociclib have not been studied in patients with critical visceral disease.
♦Severe cutaneous reactions Toxic epidermal necrolysis (TEN) has been reported with Kisqali treatment. If signs and symptoms suggestive of severe cutaneous reactions (e.g. progressive widespread skin rash often with blisters or mucosal lesions) appear, Kisqali should be discontinued immediately. ♦Interstitial lung disease/pneumonitis ILD/
pneumonitis has been reported with CDK4/6 inhibitors including Kisqali. Based on the severity of the ILD/ pneumonitis, which may be fatal, Kisqali may require dose interruption, reduction or discontinuation as described in
SmPC
Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough and dyspnoea and dose modifications should be managed in accordance with Table 5 (see section 4.2)
♦Blood creatinine increase ribociclib may cause blood creatinine increase – if this occurs it is recommended that further assessment of the renal function be performed to exclude renal impairment.
♦CYP3A4 substrates.ribociclib may interact with medicinal products which are metabolised via CYP3A4, which may lead to increased serum concentrations of CYP3A4 substrates (see section 4.5). Caution is recommended in case of concomitant use with sensitive CYP3A4 substrates with a narrow therapeutic index and the SmPC of the other product should be consulted for the recommendations regarding co‑administration with CYP3A4 inhibitors Pregnancy, Fertility and Lacation
♦Pregnancy: Pregnancy status should be verified prior to starting treatment as Kisqali can cause foetal harm when administered to a pregnant woman.
♦Women of childbearing potential who are receiving Kisqali should use effective contraception (e.g. double barrier contraception) during therapy and for at least 21 days after stopping treatment with Kisqali. ♦Breast‑feeding: Patients receiving Kisqali should not breast‑feed for at least 21 days after the last dose. ♦Fertility: There are no clinical data available regarding effects of ribociclib on fertility. Based on animal studies, ribociclib may impair fertility in males of reproductive potential.
♦Effects on ability to drive and use machines Patients should be advised to be cautious when driving or using machines in case they experience fatigue, dizziness or vertigo during treatment with Kisqali.
Interactions:
♦Concomitant use of strong CYP3A4 inhibitors should be avoided, including, but not limited to, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, verapamil, and voriconazole. Alternative concomitant medicinal products with less potential to inhibit CYP3A4 should be considered. Patients should be monitored for ADRs. If concomitant use of a strong CYP3A4 inhibitor cannot be avoided, the dose of Kisqali should be reduced (see section 4.2 of SmPC). ♦Grapefruit or grapefruit juice should be avoided. ♦Concomitant use of strong CYP3A4 inducers should be avoided, including, but not limited to, phenytoin, rifampicin, carbamazepine and St John’s Wort (Hypericum perforatum). An alternative medicinal product with no or minimal potential to induce
This medicinal product is subject to additional monitoring. Reporting suspected adverse reactions of the medicinal product is important to Novartis and the HPRA. It allows continued monitoring of the benefit/risk profile of the medicinal product. All suspected adverse reactions should be reported via HPRA Pharmacovigilance, website www.hpra.ie. Adverse events could also be reported to Novartis preferably via www.report.novartis.com or by email: drugsafety.dublin@novartis.com or by calling 01 2080 612.
CYP3A4 should be considered. ♦Caution is recommended when Kisqali is administered with sensitive CYP3A4 substrates with narrow therapeutic index (including, but not limited to, alfentanil, ciclosporin, everolimus, fentanyl, sirolimus, and tacrolimus), and their dose may need to be reduced.
♦Concomitant administration of Kisqali at the 600 mg dose with the following CYP3A4 substrates should be avoided: alfuzosin, amiodarone, cisapride, pimozide, quinidine, ergotamine, dihydroergotamine, quetiapine, lovastatin, simvastatin, sildenafil, midazolam, triazolam.
♦Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of drug transporters P gp, BCRP, OATP1B1/1B3, OCT1, OCT2, MATE1 and BSEP which exhibit a narrow therapeutic index, including but not limited to digoxin, pitavastatin, pravastatin, rosuvastatin and metformin.
♦Co administration of Kisqali with medicinal products with known potential to prolong the QT interval should be avoided such as anti arrhythmic medicinal products (including, but not limited to, amiodarone, disopyramide, procainamide, quinidine and sotalol) and other medicinal products known to prolong the QT interval including, but not limited to, chloroquine, halofantrine, clarithromycin, ciprofloxacin, levofloxacin, azithromycin, haloperidol, methadone, moxifloxacin, bepridil, pimozide and intravenous ondansetron. Kisqali is not recommended for use in combination with tamoxifen.
Adverse reactions: ♦Very common: Infections, neutropenia, leukopenia, anaemia lymphopenia, decreased appetite, headache, dizziness, dyspnoea, cough, nausea, diarrhoea, vomiting, constipation, stomatitis, abdominal pain, dyspepsia alopecia, rash, pruritus, back pain, fatigue, peripheral oedema, asthenia, pyrexia, abnormal liver function tests.
♦ Common:, thrombocytopenia, febrile neutropenia, hypocalcaemia, hypokalaemia, hypophosphataemia, vertigo, lacrimation increased, dry eye, syncope, dysgeusia, hepatotoxicity, erythema, dry skin, vitiligo, dry mouth, oropharyngeal pain, blood creatinine increased, electrocardiogram QT prolonged. ♦Please refer to SmPC for a full list of adverse events.
Legal Category: POM
Pack sizes: Unit packs containing 21, 42 or 63 FCTs. Not all pack sizes may be marketed.
Marketing Authorisation Holder : Novartis Europharm Limited Vista Building, Elm Park, Merrion Road, Dublin 4 Ireland
Marketing Authorisation Numbers EU/1/17/1221/003 & 005.
Full prescribing information is available on request from Novartis Ireland Ltd, Vista Building, Elm Park Business Park, Dublin 4. Tel: 01 2601255 or at www.medicines.ie
Prescribing information last revised : October 2020
Abbreviated Prescribing Information - Xtandi (enzalutamide) 40 mg film-coated tablets. Please refer to the Summary of Product Characteristics (SmPC), available on www.medicines.ie, before prescribing. Presentation: Xtandi 40 mg film-coated tablets each containing 40 mg of enzalutamide. Indications: The treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy. The treatment of adult men with high-risk nonmetastatic castration resistant prostate cancer (CRPC). The treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. The treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy. Posology and administration: Treatment with enzalutamide should be initiated and supervised by specialist physicians experienced in the medical treatment of prostate cancer. The recommended dose is 160 mg enzalutamide (four 40 mg film-coated tablets) as a single oral daily dose. The tablets should be swallowed whole with water, and can be taken with or without food. Medical castration with a luteinising hormone-releasing hormone (LHRH) analogue should be continued during treatment of patients not surgically castrated. If a patient experiences a ≥ Grade 3 toxicity or an intolerable adverse reaction, dosing should be withheld for one week or until symptoms improve to ≤ Grade 2, then resumed at the same or a reduced dose (120 mg or 80 mg) if warranted. For further details, please refer to the SmPC. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Women who are or may become pregnant. Special warnings and precautions for use: Risk of seizure: Use of enzalutamide has been associated with seizure. The decision to continue treatment in patients who develop seizures should be taken case by case. Posterior reversible encephalopathy syndrome: There have been rare reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving Xtandi. PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of Xtandi in patients who develop PRES is recommended. Second Primary Malignancies: Cases of second primary malignancies have been reported in patients treated with enzalutamide in clinical studies. In phase 3 clinical studies, the most frequently reported events in enzalutamide treated patients, and greater than placebo, were bladder cancer (0.3%), adenocarcinoma of the colon (0.2%), transitional cell carcinoma (0.2%) and bladder transitional cell carcinoma (0.1%). Patients should be advised to promptly seek the attention of their physician if they notice signs of gastrointestinal bleeding, macroscopic haematuria, or other symptoms such as dysuria or urinary urgency develop during treatment with enzalutamide. Concomitant use with other medicinal products: Enzalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products. A review of concomitant medicinal products should therefore be conducted when initiating enzalutamide treatment.
Concomitant use of enzalutamide with medicinal products that are sensitive substrates of many metabolising enzymes or transporters should generally be avoided if their therapeutic effect is of large importance to the patient, and if dose adjustments cannot easily be performed based on monitoring of efficacy or plasma concentrations. Co-administration with warfarin and coumarin-like anticoagulants should be avoided. If Xtandi is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted. Renal impairment: Caution is required in patients with severe renal impairment as enzalutamide has not been studied in this patient population. Severe hepatic impairment: An increased half-life of enzalutamide has been observed in patients with severe hepatic impairment, possibly related to increased tissue distribution. The clinical relevance of this observation remains unknown. A prolonged time to reach steady state concentrations is however anticipated, and the time to maximum pharmacological effect as well as time for onset and decline of enzyme induction may be increased. Recent cardiovascular disease: The phase 3 studies excluded patients with recent myocardial infarction (in the past 6 months) or unstable angina (in the past 3 months), New York Heart Association Class (NYHA) III or IV heart failure except if Left Ventricular Ejection Fraction (LVEF) ≥ 45%, bradycardia or uncontrolled hypertension. This should be taken into account if Xtandi is prescribed in these patients. Androgen deprivation therapy may prolong the QT interval: In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Xtandi. Use with chemotherapy: The safety and efficacy of concomitant use of Xtandi with cytotoxic chemotherapy has not been established. Co-administration of enzalutamide has no clinically
relevant effect on the pharmacokinetics of intravenous docetaxel; however, an increase in the occurrence of docetaxel-induced neutropenia cannot be excluded. Hypersensitivity reactions: Hypersensitivity reactions manifested by symptoms including, but not limited to, rash, or face, tongue, lip, or pharyngeal oedema have been observed with enzalutamide. Severe cutaneous adverse reactions (SCARs) have been reported with enzalutamide. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. Interactions: Potential for other medicinal products to affect enzalutamide exposures: CYP2C8 plays an important role in the elimination of enzalutamide and in the formation of its active metabolite. Strong inhibitors (e.g. gemfibrozil) of CYP2C8 are to be avoided or used with caution during enzalutamide treatment. If patients must be co-administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily. No dose adjustment is necessary when Xtandi is coadministered with inducers of CYP2C8. CYP3A4 plays a minor role in the metabolism of enzalutamide. No dose adjustment is necessary when Xtandi is co-administered with inhibitors or inducers of CYP3A4. Potential for enzalutamide to affect exposures to other medicinal products: Enzalutamide is a potent enzyme inducer and increases the synthesis of many enzymes and transporters; therefore, interaction with many common medicinal products that are substrates of enzymes or transporters is expected. Enzymes that may be induced include CYP3A in the liver and gut, CYP2B6, CYP2C9, CYP2C19, and uridine 5’-diphospho-glucuronosyltransferase (UGTsglucuronide conjugating enzymes). The transport protein P-gp may also be induced, and probably other transporters as well, e.g. multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein (BCRP) and the organic anion transporting polypeptide 1B1 (OATP1B1). In vivo studies have shown that enzalutamide is a strong inducer of CYP3A4 and a moderate inducer of CYP2C9 and CYP2C19. The full induction potential of enzalutamide may not occur until approximately 1 month after the start of treatment, when steady-state plasma concentrations of enzalutamide are reached, although some induction effects may be apparent earlier. Patients taking medicinal products that are substrates of CYP2B6, CYP3A4, CYP2C9, CYP2C19 or UGT1A1 should be evaluated for possible loss of pharmacological effects (or increase in effects in cases where active metabolites are formed) during the first month of enzalutamide treatment, and dose adjustment should be considered as appropriate. In consideration of the long half-life of enzalutamide (5.8 days), effects on enzymes may persist for one month or longer after stopping enzalutamide. A gradual dose reduction of the concomitant medicinal product may be necessary when stopping enzalutamide treatment. In vitro data indicate that enzalutamide may be an inhibitor of the efflux transporter P-gp. The effect of enzalutamide on P-gp substrates has not been evaluated in vivo; however, under conditions of clinical use, enzalutamide may be an inducer of P-gp via activation of the nuclear pregnane receptor (PXR). Medicinal products with a narrow therapeutic range that are substrates for P-gp (e.g. colchicine, dabigatran etexilate, digoxin) should be used with caution when administered concomitantly with Xtandi and may require dose adjustment to maintain optimal plasma concentrations. Based on in vitro data, inhibition of BCRP and MRP2 (in the intestine), as well as organic anion transporter 3 (OAT3) and organic cation transporter 1 (OCT1) (systemically) cannot be excluded. Theoretically, induction of these transporters is also possible, and the net effect is presently unknown. Since androgen deprivation treatment may prolong the QT interval, the concomitant use of Xtandi with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated. Fertility, pregnancy and lactation: There are no human data on the use of Xtandi in pregnancy and this medicinal product is not for use in women of childbearing potential. This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant. It is not known whether enzalutamide or its metabolites are present in semen. A condom is required during and for 3 months after treatment with enzalutamide if the patient is engaged in sexual activity with a pregnant woman. If the patient engages in sexual intercourse with a woman of childbearing potential a condom and another form of birth control must be used during and for 3 months after treatment. Enzalutamide is not for use in women. Enzalutamide is contraindicated in women who are, or who may become, pregnant. It is not known if enzalutamide is present in human milk. Enzalutamide and/or its metabolites are secreted in rat milk. Animal studies showed that enzalutamide affected the reproductive system in male rats and dogs. Driving and use of machines: Xtandi may have a moderate influence on the ability to drive and use machines as psychiatric and neurologic events including seizure have been reported. Patients should be advised of the potential risk of experiencing a psychiatric or neurological event while driving or operating machines. Undesirable effects: Summary of the safety profile: The most common adverse reactions are asthenia/fatigue, hot flush, hypertension, fractures, and fall. Other important adverse reactions include cognitive disorder and neutropenia.
XTANDI™ is indicated for the treatment of adult men with metastatic castrationresistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgendeprivation therapy, in whom chemotherapy is not yet clinically indicated.1
XTANDI is also indicated for the treatment of adult men with metastatic castration – resistant prostate cancer whose disease has progressed on or after Docetaxel.1
Seizure occurred in 0.5% of enzalutamide-treated patients, 0.1% of placebo-treated patients, and 0.3% in bicalutamide-treated patients. Rare cases of posterior reversible encephalopathy syndrome have been reported in enzalutamide-treated patients. List of adverse reactions: Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Adverse reactions identified in controlled clinical trials and post-marketing (Listed by MedDRA System organ class frequency and adverse reaction): Blood and lymphatic system disorders Uncommon: leucopenia, neutropenia; Not known*: thrombocytopenia Immune system disorders
Not known*: face oedema, tongue oedema, lip oedema, pharyngeal oedema
Psychiatric disorders
Common: anxiety; Uncommon: visual hallucination Nervous system disorders
Common: headache, memory impairment, amnesia, disturbance in attention, dysgeusia, restless legs syndrome; Uncommon: cognitive disorder, seizureҰ; Not known*: posterior reversible encephalopathy syndrome Cardiac disorders
Common: ischemic heart diseaseǂ; Not known*: QT-prolongation Vascular disorders
Very common: hot flush, hypertension Gastrointestinal disorders Not known*: nausea, vomiting, diarrhoea Skin and subcutaneous tissue disorders Common: dry skin, pruritus; Not known*: rash Musculoskeletal and connective tissue disorders Very common: fractures**; Not known*: myalgia, muscle spasms, muscular weakness, back pain Reproductive system and breast disorder Common: gynaecomastia General disorders and administration site conditions Very common: asthenia, fatigue Injury, poisoning and procedural complications Very common: fall. *Spontaneous reports from post-marketing experience. ҰAs evaluated by narrow SMQs of ‘Convulsions’ including convulsion, grand mal convulsion, complex partial seizures, partial seizures and status epilepticus. This includes rare cases of seizure with complications leading to death. ǂAs evaluated by narrow SMQs of ‘Myocardial Infarction’ and ‘Other Ischemic Heart Disease’ including the following preferred terms observed in at least two patients in randomized placebo-controlled phase 3 studies: angina pectoris, coronary artery disease, myocardial infarctions, acute myocardial infarction, acute coronary syndrome, angina unstable, myocardial ischaemia and arteriosclerosis coronary artery. **Includes all preferred terms with the word ‘fracture’ in bones. Description of selected adverse reactions: Seizure In controlled clinical studies, 22 patients (0.5%) experienced a seizure out of 4168 patients treated with a daily dose of 160 mg enzalutamide, whereas three patients (0.1%) receiving placebo and one patient (0.3%) receiving bicalutamide experienced a seizure. Dose appears to be an important predictor of the risk of seizure, as reflected by preclinical data, and data from a doseescalation study. In the controlled clinical studies, patients with prior seizure or risk factors for seizure were excluded. In the 9785 CL 0403 (UPWARD) single-arm trial to assess incidence of seizure in patients with predisposing factors for seizure (whereof 1.6% had a history of seizures), 8 of 366 (2.2%) patients treated with enzalutamide experienced a seizure. The median duration of treatment was 9.3 months. The mechanism by which enzalutamide may lower the seizure threshold is not known but could be related to data from in vitro studies showing that enzalutamide and its active metabolite bind to and can inhibit the activity of the GABA gated chloride channel.
Ischemic Heart Disease
In randomized placebo-controlled clinical studies, ischemic heart disease occurred in 3.7% of patients treated with enzalutamide plus ADT compared to 1.5% patients treated with placebo plus ADT. Fifteen (0.4%) patients treated with enzalutamide and 2 (0.1%) patients treated with placebo had an ischemic heart disease event that led to death. Legal category: POM/S1A. Marketing
Authorisation number: Xtandi 40 mg film-coated tablets: EU/1/13/846/002
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. Tel.: +353 1 467 1555. SmPC with full prescribing information available upon request. Job number: XTD_2021_0085_IE Date of preparation of API: May 2021
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the bene t/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
HPRA Pharmacovigilance Website: www.hpra.ie Astellas Pharma Co. Ltd. Tel: + 353 1 467 1555 E- mail: irishdrugsafety@astellas.com
Prostate cancer is the second most frequent cancer diagnosed in men and the fifth leading cause of death globally. Excluding non-melanoma skin cancer, prostate cancer is the leading cause of cancer in men internationally. In 2018, 1,276,106 new cases of prostate cancer were registered worldwide, representing 7.1 per cent of all cancers in men and 358,989 deaths, representing 3.8 per cent of all male cancer deaths.1
Prostate cancer incidence rates are highly variable worldwide with the variation likely to be attributed to prostate-specific antigen (PSA) testing levels. In Europe, prostate cancer is the most frequently diagnosed cancer among men, accounting for 24 per cent of all new cancers in 2018, with around 450,000 new prostate cancer cases detected in 2018. 3
Approximately 3,890 men are diagnosed with prostate cancer each year in Ireland, and one-in-seven men in Ireland will be diagnosed with prostate cancer during their lifetime.1,2 It accounts for 30 per cent of all newly-diagnosed cancers in Irish males and 11 per cent of all invasive cancers in Ireland.4
Risk factors
The most common risk factor for prostate cancer is increasing age. It usually affects men over the age of 50 years and almost two in every three prostate cancers are diagnosed in men over the age of 65. While one-in-350 men under the age of 50 will be diagnosed with prostate cancer, the incidence rate increases up to one-in-52 men for those aged 50-to-59 years. 2
In Ireland, the majority of cases are detected in men aged 65-to-84 years, with 37 per cent detected in men under 65 years of age. Genetic factors play a role. Family history is associated with an increased risk and men with a father or brother diagnosed with prostate cancer at age 50 years have an approximately two-fold increased risk of prostate cancer.1 Risk is higher in males with a relative who developed prostate cancer at a younger age and in males who have more than one relative with the disease.
Two genes, BRCA1 and BRCA2, have been linked to prostate cancer. Like women, men can have mutations in the BRCA1 and BRCA2 genes. The function of the BRCA genes is to repair cell damage and keep breast, ovarian, and other cells growing normally. Men carrying mutations in the BRCA2 gene have an increased risk of developing prostate cancer, and mutations in either gene can significantly reduce survival.7
Studies have revealed an association between hereditary susceptibility to prostate cancer and sequence variations in the RNASEL gene (ribonuclease L), which plays a role in maintaining immunity
against viral infections. A common RNASEL variant involves a mutation resulting in decreased activity of the encoded ribonuclease L protein, reducing the immune defence against viruses. Men who inherit this mutation have a significant increased risk of developing prostate cancer.7
It is estimated that about 20 per cent of patients with prostate cancer report a family history, which may develop not only because of shared genes, but also for a similar pattern of exposure to certain environmental carcinogens and common lifestyle habits. 9
Afro-Caribbean men have the highest incidence of prostate cancer of any group (231.9 per 100,000) while Asian men have the lowest risk.
Obesity and physical inactivity have been associated with higher-grade prostate cancers and studies have shown increased risk associated with various dietary intakes, including high levels of high-saturated fats and red meats and reduced intake of fish, fruit, and vegetables.1,2,9 Research is ongoing into the links between diet and prostate cancer and there is some evidence that a diet high in calcium is also linked to an increased risk of developing prostate cancer. 8 Although there are no studies that can sufficiently demonstrate the direct correlation between diet and nutrition with risk or prevention of prostate cancer development, many preclinical studies looking at links between certain eating behaviours and cancer suggest there may be a connection. 9
The aetiology of prostate cancer is the subject of numerous studies and remains largely unknown compared to other common cancers. While the exact causes of
Tumour (T) –size of the tumour
T1 The tumour is within the prostate gland. It is too small to be felt during a rectal exam.
T2 The tumour is still within the prostate gland. It is large enough to be felt during a rectal exam.
T3 The tumour can be felt throughout the prostate, and may have broken through the outer layer of the prostate.
T4 The tumour has spread to organs outside the prostate gland.
Node (N) – are the lymph nodes affected?
N Cancer is present in the lymph nodes.
prostate cancer are not fully understood, many cases do appear to be related to aberrant cell signalling that involves male androgen hormones, particularly testosterone and its metabolites. Within certain tissues, testosterone may be converted into one-oftwo active compounds, oestradiol or dihydrotestosterone. Oestradiol promotes the growth of prostate cancer cells and dihydrotestosterone inhibits apoptosis of those cells. Testosterone plays a central role in maintaining prostate cells and stimulating apoptosis when abnormal cells arise. However, the mechanism by which testosterone and its active derivatives contribute to the development of prostate cancer is not entirely understood.7 During the process of malignant transformation, cells gradually evolve from the benign to malignant phenotype. High-grade prostatic intraepithelial neoplasia (PIN) is the histological entity widely considered to be the most likely precursor of invasive prostatic cancer. It is characterised by cellular proliferation within pre-existing ducts and glands with cytological changes.2 Although other prostate lesions may be associated with even higher rates of carcinoma, PIN has been identified as the most likely progenitor of the majority of prostatic adenocarcinomas.9
Symptoms
When the prostate gland becomes cancerous, it can put pressure on the urethra, causing dysuria, a burning sensation and frequency of micturition. It can also cause hesitancy, a weak and intermittent flow, nocturia, haematuria, and impotence or sexual dysfunction. Other symptoms include swollen lymph nodes in the groin and pain in the pelvis, hips, back, or ribs. More advanced stage of the disease may present with urinary retention and back pain, as the axis skeleton is the most com-
N0 No cancer in the lymph nodes.
N1 Cancer has spread to one or more of the lymph nodes.
If diagnosed with early prostate cancer, N0 signifies that the cancer has not spread outside the prostate.
Metastasis (M) – has it spread outside the prostate?
M The cancer has spread to lymph nodes and/or other organs, commonly bones
M0 The cancer has not spread.
If diagnosed with early prostate cancer, M0 signifies that the cancer has not spread outside the prostate.
mon site of bony metastatic disease. Prostate cancer should not be confused with benign prostate hyperplasia (BPH), which has similar symptoms and often occurs in older men, but is not a type of cancer.7
Diagnosis
Prostate cancers usually grow very slowly, and symptoms may not occur for some time. If the prostate is enlarged, a preliminary diagnosis can be made by rectal examination or transrectal ultrasound (TRUS). A PSA blood test is used to detect prostate tumours in their earliest stages in high-risk individuals. Although originally introduced as a tumour marker for the detection of cancer recurrence, PSA testing became widely adopted as a screening tool for prostate cancer. However, it is not prostate cancer-specific and other prostate conditions, such as BPH or prostatitis, can also affect PSA levels. 2 If prostate cancer is suspected a biopsy is done to confirm the diagnosis.
When detected early, prostate cancer is very treatable. A large majority of prostate cancers are diagnosed either before they have spread or when they have spread only locally. Survival rates in these cases are very high.7
Staging 1
The TNM staging system refers to the size of the tumour (T), if the cancer has spread to the lymph nodes (N), and if the cancer has spread to other parts of the body- metastasis (M) (Figure 1).1
The Gleason Score
The Gleason Score is a grading system used to determine the aggressiveness of prostate cancer and can be used to choose appropriate treatment options. The Gleason Score ranges from 1-5 and describes how much the cancer looks like healthy or abnormal tissue. Most cancers score a grade 3 or higher. Since prostate tumours are often made up of cancerous cells that have different grades, two grades are assigned for each patient. A primary grade is given to describe the cells that make up the largest area of the tumour and a secondary grade is given to describe the cells of the next largest area. If the Gleason Score is written as 3+4=7, it means most of the tumour is grade 3 and the next largest section of the tumour is grade 4. If the cancer is almost entirely made up of cells with the same score, the grade for that area is counted twice to calculate the total Gleason Score. Typical Gleason Scores range from 6-10. The higher the Gleason Score, the more likely that the cancer will grow and spread quickly. Scores of 6 or less describe cancer cells that look similar to
normal cells and suggest that the cancer is likely to grow slowly. A score of 7 suggests an intermediate risk for aggressive cancer. Scoring a 7 means that the largest section of the tumour (primary score) scored a 3 or 4. Tumours with a primary score of 3 and a secondary score of 4 have a reasonably good outlook, whereas cancers with a primary Gleason Score of 4 and a secondary score of 3 are more likely to grow and spread. Scores of 8 or higher describe cancers that are likely to spread more rapidly and these cancers are often referred to as high grade or poorly differentiated.10
Treatment
Current management of prostate cancer involves a multidisciplinary approach, with input from primary care, radiology, pathology, urology, radiation oncology, and medical oncology.
Treatment options for patients with prostate cancer depend on the stage and grade of the cancer and include active surveillance, watchful waiting, hormone therapy, radical prostatectomy, external beam radiotherapy, and brachytherapy.1 In patients with localised prostate cancer, the choice of treatment depends on whether the disease is low-, intermediate-, or high-risk.2
Active surveillance involves a PSA blood test every three months and a digital rectal exam (DRE) every six months for the first year followed by a PSA blood test every six months and a DRE at least once a year. Prostate biopsies and imaging tests may also be done every one to three years.12 Because prostate cancers usually progress slowly, a ‘watchful waiting’ approach rather than immediate treatment may be recommended. This is especially true for patients who are elderly or in otherwise poor health.
It should be noted that the five-alpha reductase inhibitors finasteride and dutasteride will lower PSA levels and may mask PSA elevation secondary to prostate cancer. Finasteride lowers PSA levels by a median 50 per cent within six months of use and dutasteride has been reported to reduce PSA levels by 48-to-57 per cent.
In patients with intermediate- or highrisk localised prostate cancer with a real prospect of long-term disease control and those with locally-advanced disease, radical prostatectomy or radical radiotherapy should be offered. 2
Hormone therapy, also called androgen suppression or androgen deprivation therapy (ADT), attacks androgens that stimulate the growth of prostate cancer. ADT involves the use of LHRH analogs, or LHRH agonists, such as buserelin, goserelin, leuprorelin acetate or triptorelin that chemically block the production of androgens. It is important to note that ADT is associated with a wide range of side-effects, many of which impair quality-of-life, including reduced libido, sexual dysfunction, osteoporosis, gynaecomastia, and hot flushes. 2,7 Hormone therapy is the primary treatment for metastatic prostate cancer, but is also used for patients with locally-advanced, non-metastatic disease. For men with castration-resistant prostate cancer and bone metastases, treatment with zoledronic acid should be con-
sidered, and denosumab is an option for men in whom zoledronic acid is contraindicated or not tolerated.
Brachytherapy is a form of radiation therapy used to treat prostate cancer. Prostate brachytherapy involves placing radioactive seeds in the prostate gland which destroys the cancer cells while causing less damage to healthy tissue nearby. Prostate brachytherapy procedures vary based on the type. High-dose rate (HDR) brachytherapy is a temporary type of prostate brachytherapy that involves placing radioactive sources in the prostate gland and delivering a highdose of radiation over a few minutes before the sources are removed. Treatment may involve several sessions. Low-dose rate (LDR) brachytherapy is permanent and involves placing radioactive seeds in the prostate gland permanently, where they slowly release radiation over several months. Brachytherapy may be the only treatment used for early-stage prostate cancer that is less likely to spread beyond the prostate.
For larger prostate cancers or those that have a greater chance of spreading beyond the prostate, brachytherapy may be used along with other treatments, such as external beam radiation therapy (EBRT) or hormone therapy.1,11 In EBRT, beams of radiation are focused on the prostate gland from a machine outside the body. This type of radiation can be used to try to cure earlier stage cancers, or to help relieve symptoms such as bone pain if the cancer has spread to a specific area of bone.1
Surgery is usually only carried out if the cancer has not spread from the prostate. A radical prostatectomy may be considered if examination of the pelvic lymph nodes reveals that they are not cancerous. Surgical risks can include impotence and urinary incontinence.7 Robotic-assisted radical prostatectomy is now by far the commonest method used in the surgical treatment of prostate cancer, and its use continues to increase in Ireland. Transurethral resection of the prostate (TURP) can be used to relieve symptoms, but does not remove all of the cancer. TURP is often used in men who cannot have a radical prostatectomy because of advanced age or illness or in men who have a non-cancerous enlargement of the prostate.
In men who are unable to have traditional surgery, cryosurgery may also be used. In this procedure, a metal probe is inserted into the cancerous regions of the prostate and liquid nitrogen is then used to freeze the probe, killing the surrounding cells. If the cancer has spread from the prostate, radiation therapy may be used.
Bilateral orchidectomy should be offered to all patients with metastatic prostate cancer as an alternative to continuous LHRH agonist treatment. Removal of the testicles cuts off the supply of testosterone to the tumour, which the prostate cancer needs in order to continue growing. It can delay or stop the tumour growth and eliminates the need for other hormone therapy.
If surgery or hormone therapy fails, chemotherapy may be used. While chemotherapy can slow the growth of the tumour, it is not very effective in treating prostate cancer.7
To access the latest national guidelines on the diagnosis, staging and treatment of
patients with prostate cancer, the National Cancer Control Programme (NCCP) in conjunction with the National Clinical Effectiveness Committee (NCEC) has published a ‘National evidence-based Clinical Guideline on Prostate Cancer’, which is available at www.hse.ie/cancer
The outlook for prostate cancer is generally good because, unlike many other types of cancer, it usually progresses very slowly. If treated early, prostate cancer can often be cured. The survival rate is over 90 per cent and many men die with prostate cancer, rather than as a result of having it. Prostate cancer has one of the highest survival rates of any type of cancer. About 92 per cent of all prostate cancers are found when they are in the early stage, and almost 100 per cent of men who have local or regional prostate cancer will survive more than five years after diagnosis. For most with local or regional prostate cancer, the relative 10-year survival rate is 98 per cent and the relative 15-year survival rate is 96 per cent. Once prostate cancer has spread beyond the prostate, however, survival rates fall and about 7 per cent have more advanced prostate cancer at the time of diagnosis. For men with prostate cancer that has spread to other parts of the body, the five-year survival rate is 30 per cent.13,14
Prostate cancer presents a number of challenges for primary care clinicians. Many men with prostate cancer are asymptomatic until the tumour has progressed, and common symptoms have significant crossover with benign condi-
References
1. Irish Cancer Society (2021). Prostate Cancer. Irish Cancer Society. Available at: www.cancer.ie/cancer-information-andsupport/cancer-types/prostate-cancer
2. Tobin S. (2020). Prostate Cancer: An Overview. Medical Independent May 22, 2020. Available at: www. medicalindependent.ie/prostate-canceran-overview/
3. Rawla P. Epidemiology of Prostate Cancer. World J Oncol. 2019 Apr; 10 (2): 63–89. doi: 10.14740/wjon1191
4. Perdana N, Mochtar C, Umbas R, Hamid
A. The risk factors of prostate cancer and its prevention: A literature review. Acta Med Indones. 2016; 48 (3):228–238.
5. CDC (2021). Prostate Cancer. Centres for disease control and prevention. Available at: www.cdc.gov/cancer/prostate/basic_ info/what-is-prostate-cancer.htm
6. Rogers K (2021). Prostate gland anatomy. Encyclopaedia Britannica. Available at: www.britannica.com/ science/testis
7. Gaur A. (2021). Prostate cancer pathology. Encyclopaedia Britannica. Available at: www.britannica.com/science/ prostate-cancer
8. NHS (2018). Prostate Cancer Causes. National Health Service. UK. Available at: www.nhs.uk/conditions/ prostate-cancer/causes/
9. Rawla P. Epidemology of Prostate Cancer. World J Oncol. 2019 Apr; 10(2): 63–89. doi: 10.14740/wjon119
tions affecting the prostate. PSA-based testing for prostate cancer is very common, but remains controversial. The value of screening remains uncertain because the PSA test does not distinguish between benign and malignant disease, and there has been no proof that early treatment leads to increased cure rates. DRE alone is insufficient for screening as its positive predictive value is only 11-to-26 per cent. Current diagnostic tests have limitations in terms of significant false positive and false negative rates, however, research is ongoing into improved methods for diagnosing prostate cancer.
Understanding the underlying causes of prostate cancer, including genetics and pathogenesis, has improved substantially in recent years. Nanotechnology has shown initial success in prostate cancer disease diagnosis, imaging and treatment. A number of new tests and testing strategies are being trialled to improve the diagnosis of clinically significant prostate cancer and blood-based biomarkers for prostate cancer are also being extensively investigated.15,16 Because the value of PSA-based testing remains unclear, more genetic testing-based detection strategies are needed to identify individuals at highrisk of prostate cancer and novel drugs need to be evaluated to substantially improve the clinical care of patients with prostate cancer. Continued clinical and translational research in prostate cancer is important and could be key to the treatment and management of prostate cancer through leading improvements in prostate cancer imaging and diagnosis.16
10. PCEC (2021). Gleason Score. Prostate cancer grading and prognostic scoring. Prostate Conditions Education Council. Available at: www.prostateconditions. org/about-prostate-conditions/prostatecancer/newly-diagnosed/gleason-score
11. Mayo Clinic (2021). Prostate Brachytherapy. Available at: www. mayoclinic.org/tests-procedures/ prostate-brachytherapy/about/pac20384949
12. American Cancer Society (2021). Observation or active surveillance for prostate cancer. Available at: www.cancer. org/cancer/prostate-cancer/treating/ watchful-waiting.html
13. Bandukwala, N. (2020). Prostate cancer survival rates: What they mean. Web MD. Available at: www.webmd.com/ prostate-cancer/prostate-cancer-survivalrates-what-they-mean
14. Ellsworth P, Cunha J. (2020). What are prostate cancer survival rates by stage? MedicineNet. Available at: www. medicinenet.com/prostate_cancer/staging
15. Merriel S, Funston G, Hamilton W. Prostate cancer in primary care. Adv Ther 2018; 35(9): 1285–1294. doi: 10.1007/ s12325-018-0766
16. Tian J, Guo F, Zheng G, Ahmad A. Prostate cancer: updates on current strategies for screening, diagnosis and clinical implications of treatment modalities. Carcinogenesis, Volume 39, Issue 3, March 2018, Pages 307–317. doi: 10.1093/carcin/bgx141
In treating a broad range of women with HR+/HER2- mBC:1
Powerful clinical efficacy 1
Real-world experience2
Patient-reported outcomes3
Established safety profile1
One scheduled monitoring provision1 One capsule, Once daily 1
Indications:
IBRANCE® is indicated for the treatment of HR+/HER2- locally advanced or mBC:1
• In combination with an AI
• In combination with fulvestrant in women who have received prior ET
• In pre- or peri-menopausal women, the ET should be combined with an LHRH agonist
IBRANCE® (palbociclib) Prescribing Information:
Please refer to the Summary of Product Characteristics (SmPC) before prescribing IBRANCE 75 mg, 100 mg or 125 mg hard capsules.
Presentation: Hard capsules containing 75 mg, 100 mg or 125 mg palbociclib. Indications: Treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer: in combination with an aromatase inhibitor; or in combination with fulvestrant in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone releasing hormone (LHRH) agonist. Dosage: Therapy should be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products. The recommended dose is 125 mg of palbociclib once daily for 21 consecutive days followed by 7 days off treatment (Schedule 3/1) to comprise a complete cycle of 28 days. When coadministered with palbociclib, the aromatase inhibitor should be administered according to the dose schedule reported in the SmPC. Treatment of pre/perimenopausal women with the combination of palbociclib plus letrozole should always be combined with an LHRH agonist (see SmPC section 4.4). Capsules should be swallowed (should not be chewed, crushed, or opened prior to swallowing). They should be taken with food, preferably a meal to ensure consistent palbociclib exposure (see SmPC section 5.2). Palbociclib should not be taken with grapefruit or grapefruit juice (see SmPC section 4.5). Dose modification of IBRANCE is recommended based on individual safety and tolerability. Management of some adverse reactions may require temporary dose interruptions/delays, and/or dose reductions, or permanent discontinuation. For dose reduction guidelines for management of adverse reactions, haematologic and non-haematologic toxicities, refer to SmPC section 4.2. IBRANCE should be permanently discontinued in patients with severe interstitial lung disease (ILD)/pneumonitis. For patients who experience a maximum of Grade 1 or 2 neutropenia in the first 6 cycles, complete blood counts for subsequent cycles should be monitored every 3 months, prior to the beginning of a cycle and as clinically indicated. No dose adjustments of IBRANCE are required for patients with mild or moderate hepatic impairment (Child-Pugh classes A and B). For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg once daily on Schedule 3/1 (see SmPC section 5.2). No dose adjustments of IBRANCE are required for patients with mild, moderate or severe renal impairment (creatinine clearance [CrCl]
For more information visit www.pfizerpro.ie/product/ibrance
≥15 mL/min) (see SmPC section 5.2). No dose adjustment of IBRANCE is necessary in patients ≥65 years of age (see section 5.2). Contraindications: Hypersensitivity to the active substance or to any of the excipients (see SmPC section 6.1), use of preparations containing St. John’s Wort (see SmPC section 4.5). Warnings and Precautions: Ovarian ablation or suppression with an LHRH agonist is mandatory when pre/perimenopausal women are administered IBRANCE in combination with an aromatase inhibitor, due to the mechanism of action of aromatase inhibitors. Palbociclib in combination with fulvestrant in pre/perimenopausal women has only been studied in combination with an LHRH agonist. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia. Appropriate monitoring should be performed (see SmPC sections 4.2 and 4.8). Severe, life-threatening, or fatal ILD and/or pneumonitis can occur in patients treated with cyclin dependent kinase 4/6 (CDK4/6) inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical studies (PALOMA-1, PALOMA-2, PALOMA-3), 1.4% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3, and no Grade 4 or fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported. Patients should be monitored for pulmonary symptoms and IBRANCE treatment should be immediately interrupted in patients suspected to have developed ILD/pneumonitis, see SmPC section 4.2, 4.4 and 4.8. Since IBRANCE has myelosuppressive properties, it may predispose patients to infections. Infections have been reported at a higher rate in patients treated with IBRANCE in randomised clinical studies compared to patients treated in the respective comparator arm. Grade 3 and Grade 4 infections occurred respectively in 5.6% and 0.9% of patients treated with IBRANCE in any combination (see SmPC section 4.8). Patients should be monitored for signs and symptoms of infection and treated as medically appropriate (see SmPC section 4.2). Physicians should inform patients to promptly report any episodes of fever. Strong inhibitors of CYP3A4 may lead to increased toxicity (see SmPC section 4.5). Avoid concomitant use of strong CYP3A inhibitors during treatment with palbociclib. Coadministration should only be considered after careful evaluation of the potential benefits and risks. If coadministration with a strong CYP3A inhibitor is unavoidable, reduce the IBRANCE dose to 75 mg once daily. When the strong inhibitor is discontinued, the dose of IBRANCE should be increased (after 3–5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor (see SmPC section 4.5). Coadministration of CYP3A inducers may
lead to decreased palbociclib exposure and consequently a risk for lack of efficacy. Therefore, concomitant use of palbociclib with strong CYP3A4 inducers should be avoided. No dose adjustments are required for coadministration of palbociclib with moderate CYP3A inducers (see SmPC section 4.5). Women of childbearing potential or their male partners must use a highly effective method of contraception while taking IBRANCE (see SmPC section 4.6).
IBRANCE contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucosegalactose malabsorption should not take this medicinal product. Drug Interactions: The concomitant use of strong CYP3A inhibitors including, but not limited to: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole, and grapefruit or grapefruit juice, should be avoided (see sections 4.2 and 4.4).
No dose adjustments are needed for mild and moderate CYP3A inhibitors. The concomitant use of strong CYP3A inducers including, but not limited to: carbamazepine, enzalutamide, phenytoin, rifampin, and St. John’s Wort should be avoided (see SmPC sections 4.3 and 4.4). No dose adjustments are required for moderate CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) may need to be reduced when coadministered with IBRANCE as IBRANCE may increase their exposure. Based on in vitro data, palbociclib is predicted to inhibit intestinal P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) mediated transport. Therefore, administration of palbociclib with medicinal products that are substrates of P-gp (e.g., digoxin, dabigatran, colchicine, pravastatin) or BCRP (e.g., rosuvastatin, sulfasalazine) may increase their therapeutic effect and adverse reactions. Based on in vitro data, palbociclib may inhibit the uptake transporter organic cationic transporter OCT1 and then may increase the exposure of medical product substrates of this transporter (e.g., metformin). Pregnancy & Lactation: Females of childbearing potential who are receiving this medicinal product, or their male partners should use adequate contraceptive methods (e.g., doublebarrier contraception) during therapy and for at least 3 weeks or 14 weeks after completing therapy for females and males, respectively (see SmPC section 4.5). There are no or limited amount of data from the use of palbociclib in pregnant women. Studies in animals have shown reproductive toxicity (see SmPC section 5.3). IBRANCE is not recommended during pregnancy and in women of childbearing potential not using contraception. Based on male reproductive
organ findings (seminiferous tubule degeneration in testis, epididymal hypospermia, lower sperm motility and density, and decreased prostate secretion) in nonclinical safety studies, male fertility may be compromised by treatment with palbociclib (see SmPC section 5.3). Thus, men may consider sperm preservation prior to beginning therapy with IBRANCE. Driving and Operating Machinery: IBRANCE may cause fatigue and patients should exercise caution when driving or using machines. Side Effects: The most common (≥20%) adverse reactions of any grade reported in patients receiving palbociclib in randomised clinical studies were neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anaemia, diarrhoea, alopecia, and thrombocytopenia. The most common (≥2%) Grade ≥3 adverse reactions of palbociclib were neutropenia, leukopenia, anaemia, fatigue, infections, alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased. Dose reductions or dose modifications due to any adverse reaction occurred in 38.4% of patients receiving IBRANCE in randomised clinical studies regardless of the combination. Very common adverse events (>1/10) are neutropenia, infections, leukopenia, fatigue, anaemia, asthenia, pyrexia, nausea, stomatitis, alopecia, diarrhoea, thrombocytopenia, vomiting, rash, decreased appetite, dry skin, AST increased, ALT increased and aspartate aminotransferase (AST) increased. Commonly reported adverse events (>1/100 to <1/10), are, dysgeusia, epistaxis, ILD/pneumonitis, lacrimation increased, vision blurred, dry eye, febrile neutropenia. Refer to SmPC for further information on side effects. Refer to section 4.8 of the SmPC for further information on side effects, including description of selected adverse reactions. Legal Category: S1A. Marketing
Authorisation Numbers: EU/1/16/1147/001 – 75 mg (21 capsules); EU/1/16/1147/003 – 100 mg (21 capsules); EU/1/16/1147/005 – 125 mg (21 capsules). 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.
Last revised: 07/2021
Ref: IB 9_0
Every
Chemical and physical in-use stability has been demonstrated for up to 24 hours at ≤ 30˚C and for up to 30 days at 2˚C to 8˚C from the time of preparation. From a microbiological point of view, the prepared solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2˚C to 8˚C or 8 hours at ambient temperature (≤ 25˚C) unless dilution has taken place in controlled and validated aseptic conditions.2
*A study examined the exposure-response relationship between TECENTRIQ’s efficacy and safety in patients with non-small cell lung cancer using data from pooled Phase I and III studies in non-small cell lung cancer and urothelial carcinoma. Population pharmacokinetic-simulated exposures for the 1680mg Q4W were compared with the previously approved 1200mg Q3W. The results from the study support the interchangeable use of 1200mg Q3W and 1680mg Q4W dosing regimens for atezolizumab, as they are anticipated to demonstrate comparable efficacy and safety profiles while offering patients greater flexibility and convenience in their treatment.1
TECENTRIQ as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. Patients with EGFR mutant or ALK-positive NSCLC should have received targeted therapies before receiving TECENTRIQ.2 2L, 2nd line.
References:
1. Morrissey, K.M et al. Cancer Chemother Pharmacol 2019; 84: 1257–1267. 2. TECENTRIQ 840 mg concentrate for solution for infusion, TECENTRIQ 1,200 mg concentrate for solution for infusion, Summary of Product Characteristics 20 September 2021, available on www.medicines.ie. Date of item: November 2021. M-IE-00000918. ABRIDGED PRESCRIBING INFORMATION (API). For full prescribing information refer to the Summary of Product Characteristics [SmPC]. Tecentriq® (atezolizumab)▼1,200 mg concentrate for solution for infusion (One 20 ml vial of concentrate contains 1,200 mg atezolizumab) and 840 mg concentrate for solution for infusion (One 14 ml vial of concentrate contains 840mg of atezolizumab). ▼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 box below for details on how to report. Therapeutic Indications: Tecentriq 1,200mg and 840mg: As monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) after prior platinum-containing chemotherapy, or who are considered cisplatin ineligible and whose tumours have a PD-L1 expression ≥ 5%. As monotherapy for the first-line (1L) treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have a PD-L1 expression ≥ 50% tumour cells (TC) or ≥ 10% tumour-infiltrating immune cells (IC) and who do not have EGFR mutant or ALK-positive NSCLC. As monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC after prior chemotherapy. Patients with EGFR mutant or ALK-positive NSCLC should also have received targeted therapies before receiving Tecentriq. Tecentriq 1,200mg: In combination with bevacizumab, paclitaxel and carboplatin for the 1L treatment of adult patients with metastatic non-squamous NSCLC. In combination with bevacizumab, paclitaxel and carboplatin, for patients with EGFR mutant or ALK-positive NSCLC, is indicated only after failure of appropriate targeted therapies. In combination with nab-paclitaxel and carboplatin, for the 1L treatment of adult patients with metastatic NSCLC who do not have EGFR mutant or ALK-positive NSCLC. In combination with carboplatin and etoposide, for the 1L treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). In combination with bevacizumab, is indicated for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy Tecentriq 840mg: In combination with nab-paclitaxel for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumours have PD-L1 expression ≥ 1% and who have not received prior chemotherapy for metastatic disease. Posology and Method of Administration: The initial dose must be administered over 60 minutes and if well tolerated, subsequent infusions may be administered over 30 minutes. It must not be administered as an intravenous push or bolus. For instructions on dilution and handling, refer to SmPC. For combination therapies refer to the full prescribing information for the combination products. Recommended to treat patients until loss of clinical benefit or unmanageable toxicity for (2L) NSCLC, 2L UC and HCC; or until disease progression or unmanageable toxicity for 1L NSCLC, 1L UC, 1L ES-SCLC and TNBC. Atypical responses (i.e., an initial disease progression followed by tumour shrinkage) have been observed with continued Tecentriq treatment after disease progression. Treatment beyond disease
progression may be considered at the discretion of the physician, for 1L NSCLC (Tecentriq in combination therapy) and 1L ES-SCLC. Administer Tecentriq as soon as possible if a planned dose is missed and adjust administration schedule to maintain a regular schedule. Dose reduction is not recommended. Dose delay or discontinuation may be required based on individual safety and tolerability, refer to SmPC. The safety and efficacy of Tecentriq in children and adolescents (< 18 years) has not been established, and no posology recommendation can be made. PD-L1 testing: Tecentriq monotherapy: Patients with 1L (cisplatin ineligible) UC and 1L NSCLC should be selected for Tecentriq treatment based on the tumour expression of PD-L1 by a validated test (1L (cisplatin ineligible) UC: PD-L1 ≥ 5%, 1L NSCLC: PD-L1 ≥ 50% TC or >10% IC). Tecentriq in combination therapy: Patients with previously untreated TNBC should be selected for treatment based on the tumour expression of PD-L1 ≥1% confirmed by a validated test. Refer to Tecentriq SmPC. UC, 1L NSCLC and 2L NSCLC: Tecentriq monotherapy: 1,200mg administered intravenously every three weeks, or 840mg administered intravenously every 2 weeks, or 1,680 mg administered intravenously every 4 weeks. 1L NSCLC: Tecentriq in combination with bevacizumab, paclitaxel, and carboplatin: Induction phase recommended dose of Tecentriq is 1,200 mg administered by intravenous infusion, followed by bevacizumab, paclitaxel, and then carboplatin every 3 weeks for 4 or 6 cycles; followed by a maintenance phase without chemotherapy in which 1,200 mg Tecentriq followed by bevacizumab, is administered by intravenous infusion every 3 weeks. Tecentriq in combination with nabpaclitaxel and carboplatin: Induction phase recommended dose of Tecentriq is 1,200 mg administered by intravenous infusion, followed by nab-paclitaxel and carboplatin every three weeks for 4 or 6 cycles. For each 21-day cycle, Tecentriq, nab-paclitaxel, and carboplatin are administered on day 1. Nab-paclitaxel is administered on days 8 and 15. The induction phase is followed by a maintenance phase without chemotherapy in which 1,200 mg Tecentriq is administered by intravenous infusion every three weeks. ES-SCLC: Tecentriqincombinationwithcarboplatinandetoposide: Induction phase recommended dose of Tecentriq is 1,200 mg administered by intravenous infusion followed by carboplatin, and then etoposide administered by intravenous infusion on day 1. Etoposide is also administered by intravenous infusion on days 2 and 3. This regimen is administered every three weeks for four cycles; followed by a maintenance phase without chemotherapy in which 1,200 mg Tecentriq is administered by intravenous infusion every three weeks. TNBC: Tecentriqincombinationwithnab-paclitaxel:The recommended dose of Tecentriq is 840 mg administered by intravenous infusion, followed by 100mg/m2 nab-paclitaxel. For each 28-day cycle, Tecentriq is administered on days 1 and 15, and nab-paclitaxel is administered on days 1, 8, and 15. HCC: Tecentriq in combination with bevacizumab: The recommended dose of Tecentriq is 1,200 mg followed by bevacizumab 15 mg/kg of body weight, administered by intravenous infusion every three weeks. Contraindications: Hypersensitivity to Tecentriq or to any of the excipients listed in the SmPC. Special Warnings and Precautions for Use: Refer to Tecentriq SmPC for full description of Special Warnings and Precautions. Tecentriq is associated with immune-related adverse reactions. For suspected immune-related adverse reactions, thorough evaluation should be performed to confirm aetiology or exclude other causes. Based on the severity of the adverse reaction, Tecentriq should be withheld and corticosteroids administered. Upon improvement to Grade ≤ 1, corticosteroids should be tapered over ≥ 1 month. Permanently discontinue treatment with Tecentriq for any recurrent Grade 3 immune-related adverse reactions, and for any Grade 4, except for endocrinopathies that are controlled with replacement hormones. Immune-related pneumonitis: Monitor patients for signs and symptoms of pneumonitis and causes other than immune-related pneumonitis should be ruled out. Treatment with Tecentriq must be permanently discontinued for Grade 3 or 4 pneumonitis. Immune-related colitis: Monitor patients for signs and symptoms of colitis. Treatment with Tecentriq must be permanently discontinued for Grade 4 (life threatening; urgent intervention indicated) diarrhoea or colitis. Immune-related hepatitis: Monitor patients for signs and symptoms of hepatitis, transaminase and bilirubin elevation. In patients without HCC, treatment with Tecentriq must be permanently discontinued for Grade 3 or Grade 4 events (ALT or AST>5.0 x ULN or blood bilirubin>3xULN). In patients with HCC, treatment with Tecentriq must be permanently discontinued if ALT or AST increases to > 10 x ULN or total bilirubin increases > 3 x ULN. Immune-related endocrinopathies: Monitor patients for clinical signs and symptoms of endocrinopathies. Thyroid function should be monitored prior to and periodically during treatment with Tecentriq. Treatment with Tecentriq should be permanently discontinued for Grade 4 hypophysitis. Immune-related meningoencephalitis: Monitor patients for clinical signs and symptoms of meningitis or encephalitis. Treatment with Tecentriq must be permanently discontinued for any grade of meningitis or encephalitis. Immune-related neuropathies: Monitor patients for symptoms of motor and sensory neuropathy. Treatment with Tecentriq must be permanently discontinued for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome. Immune-related pancreatitis: Monitor patients closely for signs and symptoms suggestive of acute pancreatitis. Treatment with Tecentriq should be permanently discontinued for Grade 4, or any grade of recurrent pancreatitis. Immunerelated myocarditis: Monitor patients for signs and symptoms of myocarditis. Treatment with Tecentriq must be permanently discontinued for Grade 3 or 4 myocarditis. Immune-related nephritis: Monitor patients for changes in renal function. Treatment with Tecentriq must be permanently discontinued for Grade 3 or 4 nephritis. Immune-related myositis: Monitor patients for signs and symptoms of myositis. Treatment with Tecentriq should be permanently discontinued for Grade 4 or 3 recurrent myositis. Other immune-related adverse reactions: Other potential immune-related adverse reactions may occur, including noninfective cystitis. Evaluate all suspected immune-related adverse reactions to exclude other causes. Monitor patients for signs and symptoms of immunerelated adverse reactions and, based on the severity of the reaction, manage with treatment modifications and corticosteroids as clinically indicated, refer to SmPC. Infusion-related reactions (IRRs): Severe IRRs have been observed. Tecentriq must be permanently discontinued for grade 3 or 4 IRRs. Immune-related severe cutaneous adverse reactions (SCARs): (SCARs), including cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients receiving Tecentriq. Monitor patients for suspected severe skin reactions and other causes should be excluded. For suspected SCARs, refer patients to a specialist for further diagnosis and management. Based on the severity of the adverse reaction, Tecentriq should be withheld for Grade 3 skin reactions and treatment with systemic corticosteroids at a dose of 1-2 mg/kg/day of prednisone or equivalent should be started. Treatment may be resumed if the event improves to ≤ Grade 1 within 12 weeks, and corticosteroids have been reduced to ≤ 10 mg prednisone or equivalent per day. Treatment with Tecentriq should be permanently discontinued for Grade 4 skin reactions, and corticosteroids should be administered. Tecentriq should be withheld for patients with suspected SJS or TEN. For confirmed SJS or TEN, Tecentriq should be permanently discontinued. Caution should be used when considering the use of Tecentriq in a patient who has previously experienced a severe or life-threatening skin adverse reaction on prior treatment with other immune-stimulatory anticancer agents. Tecentriq in combination with bevacizumab, paclitaxel and carboplatin in metastatic NSCLC: Carefully consider the combined risks of the four-drug regimen of Tecentriq, bevacizumab, paclitaxel, and carboplatin before initiating treatment, refer to SmPC. Tecentriq in combination with nab-paclitaxel in metastatic TNBC: Neutropenia and peripheral neuropathies occurring during treatment with Tecentriq and nab-paclitaxel may be reversible with interruptions of nab-paclitaxel. Consult the nab-paclitaxel SmPC for specific precautions and contraindications. Tecentriq in combination with bevacizumab in HCC: Severe gastrointestinal haemorrhage, including fatal events, were reported. Screening for and subsequent treatment of oesophageal varices should be performed as per clinical practice prior to starting treatment. Bevacizumab should be permanently discontinued in patients who experience Grade 3 or 4 bleeding with the combination treatment. Diabetes mellitus can occur. Monitor blood glucose levels prior to and periodically during treatment. Please refer to the bevacizumab SmPC. Tecentriq as monotherapy for 1L treatment in metastatic NSCLC: The delayed onset of Tecentriq effect should be considered before initiating 1L treatment as monotherapy in patients with NSCLC. A higher number of deaths within 2.5 months after randomisation followed by a long-term survival benefit was observed with Tecentriq compared with chemotherapy. No specific factor(s) associated with early deaths could be identified, refer to SmPC. Special Populations: Patients excluded from clinical trials included; baseline performance status ≥ 2, history of autoimmune disease and pneumonitis, active brain metastasis, HIV, hepatitis B or C infection (for non-HCC patients), significant cardiovascular disease and patients with inadequate hematologic and end–organ function, patients who were administered a live attenuated vaccine within 28 days prior to enrolment, systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medicinal products within 2 weeks prior to study entry; therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Use Tecentriq with caution in these populations, refer to SmPC for full list of specific precautions. Interactions: No formal pharmacokinetic drug interaction studies have been performed. Since Tecentriq is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected. The use of systemic corticosteroids or immunosuppressants should be avoided before starting Tecentriq. However systemic corticosteroids or other immunosuppressants can be used to treat immune-related adverse events after starting Tecentriq, refer to SmPC. Fertility, Pregnancy and Lactation: The effect of Tecentriq on fertility and pregnancy is unknown. Women of childbearing potential must use effective contraception methods during and for 5 months after treatment with Tecentriq. Tecentriq should not be used during pregnancy, unless the clinical condition of the woman requires treatment. It is not known whether Tecentriq is excreted in human milk. A risk to newborns/infants cannot be excluded. Effects on ability to drive and use machines: Tecentriq has minor influence on the ability to drive and use machines. Advise patients experiencing fatigue not to drive and use machines until symptoms abate Undesirable Effects: Tecentriq monotherapy: Very common (≥ 1/10): cough, decreased appetite, headache, dyspnoea, musculoskeletal pain, nausea, vomiting, diarrhoea, urinary tract infections, rash, pruritus, arthralgia, back pain, pyrexia, fatigue, asthenia. Common (≥1/100 to <1/10): thrombocytopenia, hypothyroidism, hyperthyroidism, hypokalaemia, hyponatremia, hyperglycaemia, hypotension, pneumonitis, hypoxia, nasal congestion, nasopharyngitis, abdominal pain, colitis, dysphagia, oropharyngeal pain, infusion–related reaction, AST increased, ALT increased, hepatitis, dry skin, blood creatinine increased, influenza like illness, chills Tecentriq in combination therapy: Very common (≥ 1/10): anaemia, thrombocytopenia, neutropenia, hypothyroidism, lung infection, leukopenia, decreased appetite, peripheral neuropathy, dyspnoea, nausea, diarrhoea, back pain, constipation, rash, pruritus, alopecia, arthralgia, pyrexia, oedema peripheral, headache, hypertension, fatigue, musculoskeletal pain, vomiting, cough, asthenia. Common (≥1/100 to <1/10): hypokalaemia, hyponatremia, dysgeusia, dysphonia, stomatitis, sepsis, infusion-related reaction, hypomagnesaemia, dizziness, lymphopenia, hyperthyroidism, syncope, AST increased, ALT increased, proteinuria, blood creatinine increased, blood alkaline phosphatase increased. Not known: cystitis noninfective (includes reports of cystitis noninfective and immune-mediated cystitis). Immunogenicity: 13.1%-54.1% of patients developed treatment-emergent anti-drug antibodies (ADAs), refer to SmPC for details. Tecentriq in combination with bevacizumab, paclitaxel and carboplatin: Other clinically significant adverse events which were observed more frequently in the Tecentriq, bevacizumab, paclitaxel, and carboplatin arm were epistaxis, haemoptysis, cerebrovascular accident, including fatal events. Refer to SmPC for full listings of adverse events. Refer to SmPC section 4.8 for instructions on reporting of suspected adverse events. Legal Category: Product subject to medical prescription which may not be renewed (A). Presentation(s) and Marketing Authorization Number(s): 1,200 mg of atezolizumab in 20 mL, pack of one vial (EU/1/17/1220/001); 840 mg atezolizumab in 14 ml, pack of one vial (EU/1/17/1220/002). Marketing Authorisation Holder: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany. Tecentriq® is a registered trademark. Further information is available from Roche Products (Ireland) Limited, 3004 Lake Drive, Citywest, Naas Road, Dublin 24. Telephone: (01) 4690700. Date of API Preparation: October 2021.
▼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.
In the event of a suspected adverse reaction, The Drug Surveillance Centre
Roche Products (Ireland) Limited
Telephone: (01) 4690700
Email: ireland.drug_surveillance_centre@roche.com
Or alternatively,report to: HPRA Pharmacovigilance
Website: www.hpra.ie
Tecentriq® Summary of Product Characteristics [SmPC] is available on www.medicines.ie. API M-IE-00000902 based onTecentriq SmPC dated 20 September 2021
DR AUSTIN DUFFY, Associate Professor of Translational Oncology, UCD, and Consultant Medical Oncologist, Mater Misericordiae University Hospital, DublinAlmost two years ago, just before Christmas, I had one of those conversations with a patient of mine, which I really would have liked to postpone, or better yet, not have at all. Monica had pancreatic cancer and had been on chemotherapy for the better part of a year. It had been a good year, her husband told me. They’d finally got around to marrying, they went on walks, spent time with friends, even travelled a little, to London, the west, and one final time to Montpelier where they used to go each summer. (There she swam in the Mediterranean and said a quiet goodbye to their house and the landscape she loved. Her husband told me that before leaving for the airport she stood gazing for a while down the valley from Arboras. Sitting into the car she said: “I'll probably never see it again – and that's enough sentimentality – let's drive.”)
But now things had taken a bit of a turn. She hated being in hospital, away from their home, but I managed to talk her into coming in for some fluids and to adjust her pain meds and introduce her to the palliative care consultant. I also wanted to get a scan, even though I already knew what it would show; I could more or less visualise it. I also knew how the next couple of weeks would go. In my job you don’t want to be right a lot of the time, predicting the future is like an unwanted ability that’s been foisted on you.
We met at her bedside. Her husband knew something was up when he had seen my missed call. Christmas isn’t helpful for these types of conversations. A family reunion was planned for Donegal. Was there not something we could give her? Well, there was, but it was only a long shot.
Earlier that summer I had mentioned to her about a promising new treatment for pancreatic cancer. Promising in that it worked in mice, but also in a man who similarly had been through chemotherapy. The researchers used two different pills, trametinib and hydroxychloroquine, both of which were available in Ireland, but which you would never ordinarily use together. I printed off a copy of the paper, but it was scientifically quite dense; there were sections I didn’t fully understand myself. I got advice from my former boss in America. He’d had some luck with these pills himself. A patient of his had had a decent response to them. The problem was that the benefit appeared to be transient. Although the pills were able to shrink the tumours, (no small thing in pancreatic cancer), the shrinkage didn’t seem to last for very long.
Nevertheless when I spoke to Monica she wanted to give the pills a try. We saw an improvement in her bloods almost straight away. Her liver had been under an enormous amount of pressure, an ominous sign in pancreatic cancer, but this improved dramatically – her bilirubin normalised in fact. They were able to make it to Donegal for Christmas, after all, and she was feeling well enough to enjoy it.
Pancreatic cancer has a bit of a reputation. This has even entered the public psyche. People who don’t know anything about cancer generally have the sense that it’s not one of the good ones to get. Perhaps they sense it in the reaction of their neighbours. Plenty of famous people have had pancreatic cancer and it’s hard to think of any who made a full recovery. Pavarotti had it. Patrick Swayze. Ruth Bader Ginsberg. The comedian Bill Hicks. Alan Rickman. Aretha Franklin. Alex
Trebek, the host of the gameshow Jeopardy. John Hurt.
We hear all the time about advances in cancer treatment. People like me are always going on about them, but beyond all the hype and marketing it really is true that there has been some genuine progress made. But pancreas cancer has stood largely apart.
In an era where we are trying to move away from old-fashioned cytotoxic chemotherapy (and all its side-effects) the biggest recent advance in the treatment of pancreatic cancer has been a simply more intense version of the same old-fashioned cytotoxic chemotherapy.
they grow the organoids but they bring to bear the power of modern computational techniques to analyse them on a systems level when exposed to drugs. Simply put, it allows us to look under the hood, to see what’s happening in the cancer cell when it is treated. Getting the likes of Walter and Boris involved in the treatment of patients with pancreatic cancer is called bench-to-bedside.
For me, a clinician, this type of approach is a no-brainer, the only way we will make progress. Only then can we potentially answer the question that is as infuriating as it is agonising: why does a treatment work so well and then stop working? Answering this question requires the sort of outside-the-box investment and resources that can only come from research grants, many of which are government funded or by philanthropy and charities. These grants are the oil in the research machine, allowing research staff to be hired and materials to be bought; they can change the focus of a laboratory and bring basic scientists into the same room as clinicians like me, forcing us to get along, even speak a common language.
From bench to bedside in Ireland
Pat Smullen was a jockey. A nine-time champion jockey, who brought home nearly 2000 winners, including the Epsom Derby in 2016. Pat Smullen had a wife and three children and he was only 43 when he died of pancreatic cancer. After he was diagnosed Pat, along with his family and friends, organised a legends race at the Curragh in aid of pancreatic cancer trials and research. They raised over €2 million, which they entrusted to Cancer Trials Ireland.
Why has progress been slow? One of the main reasons is a matter of pure practicality. It’s very difficult to get tissue samples for research, and the animal models of pancreatic cancer that were traditionally used simply weren’t very good. They didn’t mimic the human disease well enough, and if you don’t have a good model it is hard to come up with new treatments. The situation improved with the availability of genetically-engineered mice who could be induced to develop pancreatic cancer that was, if not human, human-ish. But even these were imperfect (to say nothing about any of the ethical considerations).
All of this means that scientists and drug developers have been working largely in the dark. And when we find a new treatment that works well but, maddeningly, only for a short period of time – as was the case with the pill combination I prescribed for Monica – we aren’t in a position to work out why resistance has set in and how we might go about treating it.
This looks set to change though. A new technology has recently been developed where so-called organoids are generated. Organoids are essentially 3D models of the patient’s tumour which are able to be derived from biopsies and induced to grow in the laboratory. They seem to mimic the human in-body situation quite well. Best of all, because they’re simply in a plastic dish and no animals are involved, you can do limitless experiments on them.
As it turns out one of the leading groups in the world doing this type of research are based in Dublin, in the laboratories of Walter Kolch and Boris Kholodenko in Systems Biology Ireland, UCD. Not only do
A call was sent out for research ideas, the result of which means that we can open a proper clinical trial of the pills I had prescribed Monica. This by itself is important. We will now be able to test the treatment directly, in a properly-run and monitored clinical trial.
But we’re also going to go one step further than this. The funding will enable us to generate individual organoids for each of the patients participating on the study. The patients will get the pills, but so will the organoids, which will be like miniature avatars of their cancer. Because there will be many of these avatars we will be able to interrogate them using the powerful tools that Walter and Boris have in their lab out in UCD.
It will of course be devoutly hoped for that the people on the study benefit from the treatment. Certainly we will be willing them on, open-minded regarding the possibility of the extraordinary, hoping for the wind to be fully at their backs. Knowledge in this business is hard won, not always what you want it to be, but hopefully worth it.
In Monica’s case the treatment certainly helped. She made it to Donegal and was also well enough to host a group of friends for New Year’s at home. (Her husband told me she sparkled, disguised the fact that she barely touched her glass of wine, and stayed up till 3am.)
But ultimately it fell far short of what we wanted for her. Such is the reality of this disease, which tends to set the tempo, forcing conversations on us that we don’t particularly want to have, like the ones I had with Monica and her husband and that Pat’s doctor would have had with him. But here at least is a way forward so that those coming behind will be able to benefit from the efforts of those who went before them.
Real research progress is now being made for this difficult to treat cancer, including in Ireland
The researchers used two different pills, trametinib and hydroxychloroquine, both of which were available in Ireland, but which you would never ordinarily use together
OYAVAS®
SIMPLY CONVINCING – with similar efficacy, safety and quality to the reference product*2
SIMPLY RELIABLE – with European production supported by over 20 years of biosimilars experience†
SIMPLY DEDICATED – with a continuously expanding oncology portfolio
ABBREVIATED PRESCRIBING INFORMATION Oyavas 25 mg/ml concentrate for solution for infusion. Each ml contains 25 mg of bevacizumab. Each 4 ml vial contains 100 mg of bevacizumab. Each 16 ml vial contains 400 mg of bevacizumab. Presentation: Glass vial. Indications: 1) Oyavas in combination with fluoropyrimidine based chemotherapy is indicated for treatment of adult patients with metastatic carcinoma of the colon or rectum. 2) Oyavas in combination with paclitaxel is indicated for first line treatment of adult patients with metastatic breast cancer. 3) Oyavas in combination with capecitabine is indicated for first line treatment of adult patients with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. Patients who have received taxane and anthracycline containing regimens in the adjuvant setting within the last 12 months should be excluded from treatment with Oyavas in combination with capecitabine. 4) Oyavas in addition to platinum-based chemotherapy is indicated for first line treatment of adult patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology. 5) Oyavas in combination with erlotinib, is indicated for first line treatment of adult patients with unresectable advanced, metastatic or recurrent non squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations. 6) Oyavas in combination with interferon alfa 2a is indicated for first line treatment of adult patients with advanced and/or metastatic renal cell cancer. 7) Oyavas in combination with carboplatin and paclitaxel is indicated for the front line treatment of adult patients with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. 8) Oyavas in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel is indicated for treatment of adult patients with first recurrence of platinum sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. 9) Oyavas in combination with topotecan or pegylated liposomal doxorubicin is indicated for the treatment of adult patients with platinum resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. 10) Oyavas in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix.
Dosage: Refer to Summary of Product Characteristics. Method of administration: Oyavas is for intravenous use. The initial dose should be delivered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion may be administered over 60 minutes. If the 60 minute infusion is well tolerated, all subsequent infusions may be administered over 30 minutes. Contraindications: Hypersensitivity to the active substance or excipients, hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies, pregnancy. Warnings and precautions: GI perforations and fistulae, GI vaginal fistulae, non-GI fistulae, wound healing complications, hypertension, posterior reversible encephalopathy syndrome, proteinuria, arterial thromboembolism, venous thromboembolism, haemorrhage, pulmonary haemorrhage/haemoptysis, aneurysms and artery dissections, congestive heart failure, neutropenia and infections, hypersensitivity reactions/infusion reactions, osteonecrosis of the jaw. Oyavas is not formulated for intravitreal use. Eye disorders, systemic effects following intravitreal use, female fertility impairment. Interactions: Refer to Summary of Product Characteristics. Fertility, pregnancy and lactation: Women of childbearing potential have to use effective contraception during (and up to 6 months after) treatment. Oyavas is contraindicated in pregnancy. Women must discontinue breast-feeding during therapy and not breast-feed for at least six months following the last dose of bevacizumab. Repeat dose toxicity studies in animals have shown that bevacizumab may have an adverse effect on female fertility. Long term effects of the treatment with bevacizumab on fertility are unknown. Driving and operation of machinery: Bevacizumab has no or negligible influence on the ability to drive and use machines. However, somnolence and syncope have been reported with bevacizumab use. If patients are experiencing symptoms that affect their vision or concentration, or their ability to react, they should be advised not to drive and use machines until symptoms abate. Undesirable effects:
Very common: Febrile neutropenia, leukopenia, neutropenia, thrombocytopenia, anorexia, hypomagnesaemia, hyponatraemia, peripheral sensory neuropathy, dysarthria, headache, dysgeusia, eye disorder, lacrimation increased, hypertension, thromboembolism (venous), dyspnoea, rhinitis, epistaxis, cough, rectal haemorrhage, stomatitis, constipation, diarrhoea, nausea, vomiting, abdominal pain, wound healing complications, exfoliative dermatitis, dry skin, skin discolouration, arthralgia, myalgia, proteinuria, ovarian failure, asthenia, fatigue, pyrexia, pain, mucosal inflammation, weight decreased. A copy of the SmPC is available upon request or go to www.clonmel-health.ie Pack size: 1 vial of 4 ml or 16 ml. Marketing authorisation holder: STADA Arzneimittel AG, Stadastrasse 2-18, 61118 Bad Vilbel, Germany. Marketing authorisation number: EU/1/20/1510/001-002. Medicinal product subject to medical prescription. Date last revised: May 2021. *Avastin® (bevacizumab) †STADA founded Bioceuticals Arzneimittel AG in 2000 1. Oyavas® SmPC (Apr. 2021). 2. Oyavas® EPAR Public Assessment Report. Available at: https://www.ema.europa.eu/en/documents/ assessment-report/oyavas-epar-public-assessment-report_en.pdf. Last accessed Apr. 2021. 2021/ADV/OYA/027H.
oyavas.ie
PRISCILLA LYNCH priscilla@mindo.ie
An Australian research team has observed positive long-term outcomes in a majority of patients with metastatic melanoma treated with anti-PD1-based therapy who remain progression-free at one-year by RECIST (Response Evaluation Criteria in Solid Tumours)/ clinical grounds, and particularly in 75 per cent of patients who achieve a complete metabolic response (CMR) on FDG-PET. The study team has previously shown the utility of FDG-PET to assess CMR in patients with metastatic melanoma treated with anti-PD1-based therapy (+/-CTLA4), reporting that 75
per cent of patients who have not progressed by one year on RECIST or clinical grounds have CMR, including two-thirds of patients with RECIST partial response on CT. Patients with CMR have excellent medium-term survival, with progression seldom seen in two years.
In the latest article, published in the Annals of Oncology, they report extended follow-up to explore the five-year outcomes based on PET response and the impact of early treatment discontinuation on long-term outcome.
The authors explained that due to the mechanism of action
of immune checkpoint inhibitors, the use of RECIST criteria can be challenging in response interpretation. FDG-PET scans, which capture the metabolic activity at a tumour site, have shown an additional value over CT for staging in patients with melanoma and although a CT scan remains standard-ofcare, FDG-PET can be used synergistically in the assessment of treatment response and post-treatment surveillance.
In this study, the authors performed a retrospective analysis in 104 patients with baseline and one-year PET and CT.
At median follow-up of 61 months (range, 58-64) from oneyear PET, 94 per cent remained alive and all but one had discontinued treatment after 23 months (median range, 1-59). Disease progression occurred in 19 patients (18 per cent); in 10 (53 per cent) while on treatment, and in 12 (63 per cent) in solitary sites for which eight (67 per cent) received local treatment.
RECIST PFS rate at five years after PET was higher in those with CR compared to partial response (PR)/stable disease (SD) (93 per cent vs 76 per cent, respectively) and CMR compared to non-CMR (90 per cent vs 54 per cent, respectively). In patients with PR, five-year PFS rate was superior in CMR (88 per cent and 59 per cent).
In total, 35 (34 per cent) patients (14/29 in CR, 31/78 in CMR) discontinued treatment within 12 months, largely due to toxicity, with no impact on PFS rate compared to those that continued (84 per cent vs 78 per cent).
Despite progression events, the overall survival (OS) rate at five-years was excellent and similar in patients with CR and PR/SD (100 per cent vs 91 per cent, respectively), CMR and non-CMR (96 per cent vs 87 per cent, respectively).
The authors concluded that five years after one-year PET, sustained responses are observed in the majority of patients, particularly those with CMR. PET continues to predict progression better than CT, particularly in those patients with residual disease on CT.
Anew study has found that a direct-to-consumer machine learning model for detecting skin cancers incorrectly classified rare and aggressive cancers, such as Merkel cell carcinoma (MCC) and amelanotic melanoma, as low-risk.
The findings suggest that making apps based on such models available directly to the public without transparency on performance metrics for rare, but potentially life-threatening skin cancers is ethically questionable.
The breakthrough study was presented during the recent 30th European Academy of Dermatology and Venerology (EADV) Congress, which took place on 29 September – 2 October 2021, in Lugano, Switzerland.
Glomerulonephritis has been reported in patients receiving lgrastim and peg lgrastim.
Generally, glomerulonephritis resolved after dose reduction or withdrawal of lgrastim and peg lgrastim. Urinalysis monitoring is recommended. Capillary leak syndrome has been reported after G-CSF administration and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. Generally asymptomatic cases of splenomegaly and cases of splenic rupture, including some fatal cases, have been reported following administration of peg lgrastim. Spleen size should be carefully monitored (e.g. clinical examination, ultrasound).
leukaemia and myelodysplastic syndromes). Dosage and Administration: Pelgraz therapy should be initiated and supervised by physicians experienced in oncology and/or haematology. Posology: One 6 mg dose (a single pre- lled injector) of Pelgraz is recommended for each chemotherapy cycle, given at least 24 hours after cytotoxic chemotherapy. Safety and e cacy of Pelgraz in children and adolescents has not yet been established and no recommendation on a posology can be made. No dose change is recommended in patients with renal impairment, including those with end-stage renal disease. Method of administration: Pelgraz is for subcutaneous use. The injections should be given subcutaneously into the thigh, abdomen or upper arm. See SmPC for instructions on handling of the medicinal product before administration.
Contraindications: Hypersensitivity to peg lgrastim or any of the excipients in Pelgraz.
Warnings and precautions: To improve the traceability of biological medicinal products, the trade name of the administered product should be clearly recorded. The long-term e ects of peg lgrastim have not been established in acute myeloid leukaemia (AML); therefore, it should be used with caution in this patient population. Granulocyte-colony stimulating factor (G-CSF) can promote growth of myeloid cells in vitro and similar e ects may be seen on some nonmyeloid cells in vitro. The safety and e cacy of peg lgrastim have not been investigated in patients with myelodysplastic syndrome, chronic myelogenous leukaemia, and in patients with secondary AML; therefore, it should not be used in such patients. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from AML. The safety and e cacy of peg lgrastim administration in de novo AML patients aged < 55 years with cytogenetics t(15;17) have not been established. The safety and e cacy of peg lgrastim have not been investigated in patients receiving high dose chemotherapy. This medicinal product should not be used to increase the dose of cytotoxic chemotherapy beyond established dose regimens. Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported after G-CSF administration. Patients with a recent history of pulmonary in ltrates or pneumonia may be at higher risk. The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological signs of pulmonary in ltrates, and deterioration in pulmonary function along with increased neutrophil count may be preliminary signs of Adult Respiratory Distress Syndrome (ARDS). In such circumstances peg lgrastim should be discontinued at the discretion of the physician and the appropriate treatment given.
A diagnosis of splenic rupture should be considered in patients reporting left upper abdominal pain or shoulder tip pain. Treatment with peg lgrastim alone does not preclude thrombocytopenia and anaemia because full dose myelosuppressive chemotherapy is maintained on the prescribed schedule. Regular monitoring of platelet count and haematocrit is recommended. Special care should be taken when administering single or combination chemotherapeutic medicinal products which are known to cause severe thrombocytopenia.
Sickle cell crises have been associated with the use of peg lgrastim in patients with sickle cell trait or sickle cell disease. Therefore, use caution when prescribing peg lgrastim in patients with sickle cell trait or sickle cell disease, monitor appropriate clinical parameters and laboratory status and be attentive to the possible association of this medicinal product with splenic enlargement and vasoocclusive crisis. White blood cell (WBC) counts of 100 x 10 /L or greater have been observed in less than 1% of patients receiving peg lgrastim. No adverse reactions directly attributable to this degree of leukocytosis have been reported. Such elevation in WBCs is transient, typically seen 24 to 48 hours after administration and is consistent with the pharmacodynamic e ects of this medicinal product. Consistent with the clinical e ects and the potential for leukocytosis, a WBC count should be performed at regular intervals during therapy. If leukocyte counts exceed 50 x 10 /L after the expected nadir, this medicinal product should be discontinued immediately. Hypersensitivity, including anaphylactic reactions, have been reported with peg lgrastim. Permanently discontinue peg lgrastim in patients with clinically signi cant hypersensitivity. Do not administer peg lgrastim to patients with a history of hypersensitivity to peg lgrastim or lgrastim. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. StevensJohnson syndrome (SJS), which can be life-threatening or fatal, has been reported rarely in association with peg lgrastim treatment. If the patient has developed SJS with the use of peg lgrastim, treatment must not be restarted at any time. As with all therapeutic proteins, there is a potential for immunogenicity. Rates of generation of antibodies against peg lgrastim is generally low. Binding antibodies do occur as expected with all biologics; however, they have not been associated with neutralising activity at present. Aortitis has been reported after lgrastim or peg lgrastim administration in healthy subjects and in cancer patients. The symptoms experienced included fever, abdominal pain, malaise, back pain and increased
in ammatory markers (e.g. C-reactive protein and WBC count). In most cases aortitis was diagnosed by CT scan and generally resolved after withdrawal of lgrastim or peg lgrastim. The safety and e cacy of Pelgraz for the mobilisation of blood progenitor cells in patients or healthy donors has not been adequately evaluated. Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive boneimaging ndings. This should be considered when interpreting bone- imaging results. This medicinal product contains 50 mg sorbitol in each unit volume, which is equivalent to 30 mg per 6 mg dose. Pelgraz contains less than 1 mmol (23 mg) sodium per 6 mg dose, that is to say essentially ‘sodium-free’. The needle cover contains dry natural rubber (a derivative of latex), which may cause allergic reactions. Pregnancy and Lactation: Peg lgrastim is not recommended during pregnancy and in women of childbearing potential not using contraception. A decision must be made whether to discontinue breastfeeding or to discontinue/ abstain from peg lgrastim therapy taking into account the bene of breastfeeding for the child and the bene of therapy for the woman. Adverse Events include: Adverse events which could be considered serious include: Common: Thrombocytopenia. Uncommon: Sickle cell crisis, capillary leak syndrome, glomerulonephritis, hypersensitivity reactions (including angioedema, dyspnoea, anaphylaxis), splenic rupture (including some fatal cases), Sweet’s syndrome (acute febrile dermatosis), pulmonary adverse reactions including interstitial pneumonia, pulmonary oedema and pulmonary brosis have been reported. Uncommonly cases have resulted in respiratory failure or ARDS which may be fatal. Rare: Aortitis, pulmonary haemorrhage, Stevens-Johnson syndrome. Other Very Common adverse events: Headache, nausea, bone pain. Other Common adverse events: Leukocytosis, musculoskeletal pain (myalgia, arthralgia, pain in extremity, back pain, musculoskeletal pain, neck pain), injection site pain, non-cardiac chest pain. See SmPC for details of other adverse events. Shelf Life: 3 years. Store in a refrigerator (2°C – 8°C). Pelgraz may be exposed to room temperature (not above 25°C ±
Researchers in London created a dataset of 116 images of MCC and amelanotic melanoma, both of which are rare but particularly aggressive cancers that tend to grow fast and require early treatment, and of the benign lesions seborrhoeic keratosis and haemangiomas, and assessed these images with two machine-learning models.
The first model studied was a certified medical device, directly sold to the public via the App store and advertised as being able to diagnose 95 per cent of skin cancers (Model 1). The second model was available for research purposes only and used as a reference (Model 2).
The results showed that Model 1 incorrectly classified 17.9 per cent of MCCs and 22.9 per cent of amelanotic melanomas as low-risk. In turn, 62.2 per cent of benign lesions were classified as high risk. For detecting malignancy, Model 1’s sensitivity was 79.4 per cent [95% CI 69.3-89.4%] and specificity was 37.7 per cent [95% CI 24.7-50.8]. For Model 2, MCC was not included in the top five diagnosis for any of the 28 MCC images analysed, raising the possibility that the model had not been trained that this disease class exists.
The high false-positive rate of Model 1 has potentially negative consequences on a personal and societal level. The results pose a bigger question of the safety of other artificial intelligence (AI) models for detecting skin cancer available on the market.
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 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, in combination with platinum and fluoropyrimidine based chemotherapy, is indicated for the first-line treatment of patients with 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. 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. 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. Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. Recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. For the adjuvant treatment of melanoma, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year.
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. Data from patients ≥ 65 years are too limited to draw conclusions on cHL population. Data are limited in patients ≥ 75 years for pembrolizumab monotherapy in patients with resected Stage III melanoma and MSI-H or dMMR CRC; for pembrolizumab in combination with axitinib in patients with advanced RCC; for chemotherapy combination in patients with metastatic NSCLC and oesophageal carcinoma; for pembrolizumab (with or without chemotherapy) in patients receiving first line treatment for metastatic or unresectable recurrent HNSCC. 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 system can occur simultaneously. See SmPC for full details. Immune-related pneumonitis: Patients should be monitored for signs and symptoms of pneumonitis.. Suspected pneumonitis should be confirmed with radiographic imaging and other causes excluded. Refer to SmPC for information on management of immune-related pneumonitis. Immune-related colitis: Patients should be monitored for signs and symptoms of colitis, and other causes excluded. Consider the potential risk of gastrointestinal perforation. Refer to SmPC for information on management of immune-related colitis. Immune-related hepatitis: Patients should be monitored for changes in liver function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and symptoms of hepatitis, and other causes excluded. Refer to SmPC for information on management of Immune-related hepatitis. Immune-related nephritis: Patients should be monitored for changes in renal function, and other causes of renal dysfunction excluded. Refer to SmPC for information on management of immune-related nephritis. Immune-related endocrinopathies: Severe endocrinopathies, including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism have been observed with pembrolizumab treatment and patients should be monitored for these endocrinopathies. Refer to SmPC for information on management of immune-related endocrinopathies. Immune-related skin adverse reactions: Patients should be monitored for suspected severe skin reactions and other causes should be excluded. Cases of Stevens-Johnson syndrome
a RFS was estimated by the Kaplan-Meier method.3
b The HR and its confidence interval (CI) were estimated using the Cox model stratified by stage provided at randomization.3
c Regardless of investigator attribution.4
(SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving pembrolizumab. If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued. Other clinically significant immune-related adverse reactions: The following additional clinically significant, immune-related adverse reactions, have been reported in clinical studies or in post-marketing experience: uveitis, arthritis, myositis, myocarditis, pancreatitis, Guillain-Barré syndrome, myasthenic syndrome, haemolytic anaemia, sarcoidosis, encephalitis, myelitis, vasculitis, cholangitis sclerosing and gastritis. Refer to SmPC for information on management of significant immune-related adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Allogeneic HSCT after treatment with pembrolizumab: 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. Allogeneic HSCT prior to treatment with pembrolizumab: In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with pembrolizumab. Infusion-related reactions: For Grades 3 or 4infusion reactions including hypersensitivity and anaphylaxis, stop infusion and permanently discontinue pembrolizumab. With Grades 1 or 2 infusion reactions, infusion may continue with close monitoring. Premedication with antipyretic and antihistamine may be considered. 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. Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, rash, pruritus, fatigue. Common: pneumonia, thrombocytopenia, neutropenia, lymphopenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, thyroiditis, 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, hypercalcaemia, increase in blood alkaline phosphatase, blood bilirubin increased, blood creatinine increased, infusion related reaction. Combination with chemotherapy: Very Common: pneumonia, anaemia, neutropenia, thrombocytopenia, hypothyroidism, hyponatraemia, hypokalaemia, decreased appetite, insomnia, dizziness, neuropathy peripheral, headache, dyspnoea, cough, alopecia, nausea, diarrhoea, vomiting, abdominal pain, constipation, rash, pruritus, musculoskeletal pain, arthralgia, pyrexia, fatigue, asthenia, oedema, blood creatinine increased. Common: febrile neutropenia, leukopenia, lymphopenia, infusion related reaction, hyperthyroidism, hypocalcaemia, dysgeusia, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), vasculitis, hypertension, pneumonitis, colitis, dry mouth, gastritis, hepatitis, severe skin reactions, dry skin, erythema, dermatitis, myositis, pain in extremity, arthritis, acute kidney injury, influenza-like illness, chills, hypercalcaemia, ALT increase, AST increased, blood alkaline phosphatase increased, blood bilirubin increased. Combination with axitinib: Very Common: hyperthyroidism, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, dysphonia, diarrhoea, abdominal pain, nausea, vomiting, constipation, palmar-plantar erythrodysaesthesia syndrome, rash, pruritus, musculoskeletal pain, arthralgia, pain in extremity, fatigue, asthenia, pyrexia, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, anaemia, neutropenia, leukopenia, thrombocytopenia, infusion related reaction, hypophysitis, thyroiditis, adrenal insufficiency, hypokalaemia, hyponatraemia, hypocalcaemia, insomnia, dizziness, lethargy, neuropathy peripheral, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, dry mouth, gastritis, hepatitis, severe skin reactions, dermatitis acneiform, dermatitis, dry skin, alopecia, eczema, erythema, myositis, arthritis, tenosynovitis, acute kidney injury, nephritis, oedema, influenza like illness, chills, blood alkaline
PSUSA-202009-II-097
References:
1. https://www.hse.ie/eng/services/list/5/cancer/profinfo/chemoprotocols/melanoma/melanoma%20protocols.html
2. Keytruda Summary of Product characteristics, available from www.medicines.ie
3. Eggermont
Irish Osteoporosis Society, Annual Medical Conference for Health Professionals, virtual, 23 October 2021
Amoving and uplifting presentation by a patient detailing her remarkable journey from being diagnosed with severe osteoporosis in her early 40s to full recovery was one of the highlights of this year’s Irish Osteoporosis Society (IOS) Annual Medical Conference for Health Professionals, which took place virtually on 23 October.
Ms Sarah Buckley, 48, from Dublin, shared her story about how she recovered from severe osteoporosis in her spine to achieve full bone health over a period of six years with a combination of medication, exercise, diet and lifestyle changes, and a full commitment to following professional healthcare advice.
She was initially diagnosed with osteoporosis in her lumbar spine at the age of 41, following a DXA scan and blood tests as part of an investigation for suspected early menopause.
“My GP described it as mild and not requiring specialist care and prescribed a bisphosphonate (alendronic acid) and calcium and vitamin D supplements. The diagnosis was a shock as I’d believed that I was fit and healthy – I was very active, sporty, had a balanced diet and was health conscious. I thought that osteoporosis was something that affected only old women and not something to be worried about at my age. This really highlights that just because a person eats healthy and exercises, everyone needs to remember that it's a silent condition that can affect all ages, including fit and healthy people.”
Though her GP advised that he would treat her, Ms Buckley was concerned about her spinal health because she has scoliosis and had had 12 vertebrae fused as part of corrective surgery when she was a teenager. She was thus referred to a rheumatologist, who she said took her off her alendronic acid, advising it was not necessary due to her age, low risk of fracture, and the fact she was not on a contraceptive pill.
Despite continuing to maintain a healthy diet and lifestyle, with good calcium and vitamin D intake, over the next two years her yearly DXA scans showed the osteoporosis continued to deteriorate until it became severe with a T-score of -3.6 in the lumbar spine, which was an average of the four vertebrae. The rheumatologist prescribed a bisphosphonate (risedronate) and advised Ms Buckley to start taking a contraceptive pill, and reduce her exercise regime, which was difficult as she was very active with cycling. Dissatisfied at being told she could at best expect her bones to remain stable, and being advised against using injections to treat her condition, Ms Buckley decided to seek further intervention.
A new direction
“A work colleague recommended that I go and see Prof Moira O’Brien for a second opinion and this was when things really started to change for the better in my journey back to bone health. Before the first consultation, I had a DXA scan, full bloods and completed a very comprehensive questionnaire to identify risk factors, covering medical history, diet, exercise etc. At the consultation, the Prof went through all my results in detail with me, including explaining DXA scan scores in my spine and hip, something that my GP and previous consultant hadn’t done. She confirmed that I had severe osteoporosis in my lumbar spine with two stress fractures and osteoarthritic changes, often seen in cyclists, as well as moderate osteopenia in my hips.”
Ms Buckley was taken off risedronate and moved onto teriparatide, a daily injectable form of parathyroid hormone which improves bone density, to be taken for two years, along with continuing the calcium and vitamin D supplements. She also saw a dietician to make sure her diet was supporting bone health.
The plan after the first consultation was to have repeat blood tests every six months and a repeat DXA every year. She was also given very clear advice on her exercise regime. “I was to stop the long-distance cycling completely
Sarah Buckleysix months after starting teriparatide, so took the two drugs together for a period of 18 months until the teriparatide course was complete.
Remarkable results
“My DXA scan after year one of treatment under the care of the Professor showed a strong improvement. In my spine, I had improved from severe osteoporosis to marked osteopenia, with no additional fractures, and my hips improved from moderate to mild osteopenia. I was absolutely delighted with such a marked improvement and felt that all the sacrifices and hard work had really been worth it.
“For the next three years my DXA results remained stable, with no change, which was very positive. I was happy that I was on an even keel and that things were under control. I am currently still on Prolia, taking this every six months, as well as the calcium and vitamin D supplements, as I had improved on the DXA scan, but my bone markers showed I was still losing bone. I maintained the lifestyle changes and increased exercise to about an hour and a half per day, following the same programme and taking care not to over-exercise. I started back cycling again last year, covering shorter distances and not pushing as hard. The only additional change was starting to take a vitamin K2 supplement last year.”
Her latest DXA results in January 2021 were quite remarkable.
“I am now completely osteopenia- and osteoporosis-free in my spine and hips and have recovered to normal bone density. I never would have believed that this was possible at the start of my journey, having been told that the best I could hope for was that my bone density could be held where it was, in osteoporosis, and that the risk of fracture would increase as I got older.
“I was looking at a life in fear of breaking bones, pain, losing mobility and a loss of my active life that was so important to me. With the right consultant, treatment and lifestyle changes – which were hard and took a lot of motivation and dedication – I got a result much better than I could ever have hoped for. I’m very positive about the future and intend to maintain the lifestyle changes to which I’ve now become accustomed. I look forward to a long and active life with continued bone health. Thank you to Prof O’Brien and the Irish Osteoporosis Society for your support with my journey.”
while recovering; focus on weight-bearing exercise; and avoid over-exercising, doing a maximum of one hour per day. She [Prof O’Brien] recommended that I see a chartered physiotherapist with an osteoporosis specialism to get a programme of strength and conditioning exercises tailored for bone health.
“Though it was very upsetting to be told to give up the cycling – something that I loved – and I worried about my mental health as a result, the Prof warned that if I didn’t do it, things could really deteriorate and I could be in serious trouble later in life mobility-wise. When I heard that, I knew that I had to follow the advice and do exactly what I was told, whether I liked it or not, and my motivation to get better long-term outweighed the short-term sacrifices.”
Another issue that needed to be addressed was her high cortisol levels, which were affecting her bone health, and lifestyle changes she could make to reduce stress. High cortisol continued to be an issue picked up in blood tests, in spite of lifestyle changes, so Ms Buckley was referred to an endocrinologist. No clinical features of cortisol excess were found and the high levels were attributed to being on one of the combined oral contraceptive pills (COCP), which increases cortisol-binding globulin. She was changed onto a different oral contraceptive pill and her cortisol levels slowly came down to normal levels.
The next stage in treatment was starting on a second osteoporosis drug, denosumab, taken as a six-monthly injection, as Ms Buckley's bone markers showed she needed it in order to get the maximum benefit from the teriparatide. She started denosumab
Speaking to the Medical Independent, Ms Buckley noted that osteoporosis is a complex condition and identifying the causes is key to putting the right treatment plan in place and reversing it, where possible.
“In my case, a risk factor assessment indicated that the causes included over-exercising and doing non-weight bearing exercise only (cycling), an eating disorder in my teens, genetics (my Mum and sister also have it) and high cortisol, caused by being on the COCP, which increases cortisol-binding globulin.”
She believes that the key to her recovery was the combination of interventions: Medication; changing her exercise routine to focus on weight-bearing and strength exercises under physio care; changing the contraceptive pill she was on; and full commitment to following the treatment plan.
“It's really important to find the right consultant and get the right treatment, even if it means getting second opinions and not settling for one medical point of view.”
Ms Buckley stressed that clinicians need to be aware that younger women can also be affected by osteoporosis and that prevention of fractures is less painful and more cost-effective than treating multiple fractures. “The key message I would give is that young and healthy people can get osteoporosis; it is preventable and curable with the right treatment; and early treatment is definitely a better option than a life with multiple fractures, pain, and mobility issues in later life.”
It's really important to find the right consultant and get the right treatment, even if it means getting second opinions and not settling for one medical point of view
Irish Osteoporosis Society, Annual Medical Conference for Health Professionals, virtual, 23 October 2021
Osteoporosis patients on denosumab, the twice-yearly injectable monoclonal antibody, must be adequately educated on the risks of treatment non-compliance, such as rapid rebound bone loss and increased fracture risk, the Irish Osteoporosis Society (IOS) 2021 Annual Medical Conference heard.
Dr Kevin McCarroll, Consultant Physician and Geriatrician specialising in bone health and osteoporosis at St James’s Hospital, Dublin, strongly advised against ‘drug holidays’ of denosumab, which had been a particular issue during Covid-19 despite guidelines being in place to continue and facilitate scheduled denosumab injections as a priority. Research has shown that follow-on denosumab administered after nine-to-12 months versus the advised six months results in a 50 per cent decrease in bone mineral density (BMD) gains, with rapid BMD loss even after one month, and early risk of vertebral (x five) and, later, other fractures, Dr McCarroll told the conference. “The single biggest predictor [for a fracture after denosumab delay/stoppage] is probably previous vertebral fracture, the next biggest being duration of therapy….”
Giving an overview of the benefits of denosumab in eligible osteoporosis patients, Dr McCarroll said that it is the most powerful antiresorptive bone mass agent currently available, and has better persistence than oral bisphosphonates, with its use continuing to rise in Ireland.
Patient studies have shown more satisfaction and preference for denosumab than weekly or monthly bisphosphonates. In addition, it has been proven to be cost-effective, with a potential cost saving in over 75s, those with previous fracture, and higher-risk patients, he said.
Patients at high risk of fracture should probably continue denosumab therapy indefinitely, Dr McCarroll stated, emphasising the need to replace denosumab with a bisphosphonate “to close it off” and to continue checking bone markers if it is stopped. However, BMD loss can continue despite taking zoledronic acid after denosumab; and the risk of vertebral fracture may still be 5-to-10 per cent (in high-risk patients) after stopping despite bisphosphonate use.
“So it won’t eliminate fracture risk”, Dr McCarroll stated. Quoting the results of a newly published Irish study on denosumab compliance, which looked at older patients new-
ly prescribed oral bisphosphonates or denosumab during 2012–2017 from 44 general practices in Ireland, Dr McCarroll noted that denosumab continuation (persistence) at two years was 53.8 per cent in the 1,615 reviewed patients. Only 5.7 per cent switched to alternative therapy (83 per cent of them transitioned to an oral bisphosphonate). Predictors of lower discontinuation of denosumab included having an osteoporosis diagnosis and being a medical card holder.
Dr McCarroll said patients and clinicians need to be made aware of the risks of denosumab treatment stoppage, to help improve compliance.
Strategies to improve compliance include multi-component education, pharmacist support, shared decision-making, and he noted that treatment satisfaction is important for persistence. He also suggested that recall systems to remind GPs and patients of when the next dose of denosumab is due are useful, as has been shown by research in Australia and other countries.
“So, in conclusion, denosumab persistence is suboptimal, 70 per cent at two years. Doses should not be missed by more than one month. What is key and crucial is education of patients and doctors about not stopping the injection….”
Vitamin D deficiency in the Irish population is high, and there should be a national strategy to address the issue, including consideration of mandatory food fortification, according to Prof Bernard Walsh, Clinical Professor, Trinity College Dublin (TCD) and Mercer’s Institute St James's Hospital (SJH), Dublin.
SJH recently completed a vitamin D geo-mapping study of Ireland, which investigated vitamin D status in a population of GP-requested samples within the SJH catchment area between 2014-2018. The study aimed to explore the effects of gender, age, geolocation, and season on vitamin D status over a five-year period.
The findings reveal that nearly 40 per cent of the geo-mapping study population were either vitamin D deficient (<30nmol/L) or insufficient (31-50nmol/L) - (25 per cent in summer and 50 per cent in winter <50 nmol/l), and levels remained stable over the five years.
Interestingly, more detailed research into children under 17 years (1,269 in study) show they had the same level of deficiency and insufficiency as adults, during a crucial time for bone development.
According to the results, those at greatest risk of low vitamin D are young males in lower socio-economic areas in winter.
Only 16.7 per cent of the study’s South-Asian group had a 25(OH)D status greater than 50nmol/L, and 66 per cent of this
Asian group were deficient <30mol/l.
Those exceeding 125nmol/L were rare (3 per cent) of the total number in the SJH geo-mapping study of 36,466.
The study, as well as other similar research, highlights the need for a national public health strategy to mandate for fortification to address this widespread deficiency, Prof Walsh maintained.
He noted that all children require an oral intake of vitamin D 400 units (10mcg) a day and adults need 800 (20mcg) units a day to ensure a vitamin D >50nmol/l.
Low vitamin D levels are also strongly associated with severe disease in patients with Covid-19, as well as COPD incidence, Prof Walsh added.
Male incontinence affects one-in-eight men, significantly affecting quality-of-life, the IOS 2021 Annual Medical Conference heard.
However, there are effective treatment strategies and a more proactive approach and increased awareness could help relieve the impact of this condition,
Ms Aoife Ni Eochaidh, Chartered Physiotherapist, Clinical Specialist Physiotherapist, Women’s and Men’s Health and Continence, Bon Secours Consultants Clinic, Galway, gave a comprehensive presentation on the risk factors and latest treatment approaches to male incontinence. Her clinic’s main patient cohort in this area are men who have had a radical or robotic prostatectomy, men with benign prostate enlargement, and men with a history of prostatitis.
“Pelvic floor muscle dysfunction and osteoporosis are linked, which you might be surprised to hear, and we have good evidence to support this in women, (I know we are talking about men today). But as osteoporosis unfortunately progress, with spine flexure, the tummy protrudes, the ribs can end up resting on the pelvis, and that pressurises the pelvic floor muscles and the woman or man can have incontinence. Urge incontinence is of course a falls risk,
so just keep that in mind,” she commented.
Bladder retraining is the recommended treatment and will cure urinary incontinence in 75 per cent of cases: “You could have the best pelvic muscle floor function, but if you have poor bladder habits the man is still going to have issues.”
“Pelvic floor muscle training from the pelvic physio side of things is the gold standard for treatment,” Ms Ni Eochaidh reported, while other male incontinence treatments include electrical stimulation, bulking agents, male slings, artificial sphincters, and other devices.
She stressed the importance of early intervention and “pre-rehab for men undergoing prostate cancer surgery”, praising her urology colleagues in Galway for referring such cases to her before surgery to begin training.
Ms Ni Eochaidh also discussed an online pelvic floor muscle training solution her clinic developed during Covid-19, which facilitated the continuation of services, and continues to be particularly useful given that clients are referred from all areas of the country and there is a national shortage of pelvic physiotherapists.
In relation to digital rectal examination (DRE), she said it gives GPs a great opportunity to assess pelvic floor muscle function when they are carrying out a prostate check or assessing piles, etc.
The Irish Osteoporosis Society (IOS) 2021 Annual Medical Conference for Health Professionals took place online on 23 October and featured a stellar line up of expert speakers discussing the latest prevention, diagnosis and treatment strategies for this common disease.
There was also a very uplifting presentation from Prof Jim Lucey, Clinical Professor of Psychiatry at Trinity College, Dublin, and Consultant Psychiatrist at St Patrick's University Hospital, based on his new book, A whole new plan for living: Achieving balance and wellness in a challenging world. Prof Lucey discussed strategies for improving wellbeing, self-care, and stress management, with an emphasis on being mindful – to stay focussed, and flexible – to deal with change.
Speaking to the Medical Independent, President of the IOS Prof Moira O’Brien said: “We were delighted with the turnout, especially for a Saturday. The highlights were the take-home messages of the importance of screening people for risk factors for bone loss as only 19 per cent are diagnosed, and monitoring patients is essential. A DXA scan result is
only part of the clinical evaluation to determine the most effective treatment for an individual and in an ideal world vitamin D levels would be taken annually, especially in senior citizens.”
Young Investigators Award
Secondary hyperparathyroidism and its relationship to bone mineral density and bone markers
Dr Finlay Brennan, St James’s Hospital, Dublin
Best Overall Scientific Abstract
High prevalence of hypercalciuria in patients attending a bone health clinic– implications for treatment
Dr Finlay Brennan, St James’s Hospital
Best Poster
Proton pump inhibitors associated with hyperparathyroidism and higher bone turnover
Dr Kevin Moloney, St James’s Hospital
Most Interesting Clinical Case x 1
Indolent systemic mastocytosis- a rare cause of osteoporosis
Dr Jonathan O'Toole, St James’s Hospital
PROLIA® (denosumab) Brief Prescribing Information
Please refer to the Summary of Product Characteristics (SmPC) before prescribing Prolia. Pharmaceutical Form: Pre-filled syringe with automatic needle guard containing 60 mg of denosumab in 1 ml solution for injection for single use only. Contains sorbitol (E420). Indication: Treatment of osteoporosis in postmenopausal women at increased risk of fractures. Dosage and Administration: 60 mg Prolia administered as a subcutaneous injection once every 6 months. Patients must be supplemented with calcium and vitamin D. No dosage adjustment required in patients with renal impairment. Not recommended in paediatric patients under 18 years of age. Give Prolia patients the package leaflet and patient reminder card Re-evaluate the need for continued treatment periodically based on the benefits and potential risks of denosumab on an individual patient basis, particularly after 5 or more years of use. Contraindications: Hypocalcaemia or hypersensitivity to the active substance or to any of the product excipients. Special Warnings and Precautions: Traceability: Clearly record the name and batch number of administered product to improve traceability of biological products. Hypocalcaemia: Identify patients at risk for hypocalcaemia Hypocalcaemia must be corrected by adequate intake of calcium and vitamin D before initiation of therapy. Clinical monitoring of calcium levels is recommended before each dose and, in patients predisposed to hypocalcaemia, within 2 weeks after the initial dose. Measure calcium levels if suspected symptoms of hypocalcaemia occur. Renal Impairment: Patients with severe renal impairment (creatinine clearance < 30 ml/ min) or receiving dialysis are at greater risk of developing hypocalcaemia. Skin infections: Patients receiving Prolia may develop skin infections (predominantly cellulitis) requiring hospitalisation and if symptoms develop then they should contact a health care professional immediately. Osteonecrosis of the jaw (ONJ): ONJ has been reported rarely with Prolia 60 mg every 6 months. Delay treatment in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventative dentistry and an individual benefit:risk assessment is recommended prior to treatment with Prolia in patients with concomitant risk factors. Refer to the SmPC for risk factors for ONJ. Patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups and immediately report oral symptoms during treatment with Prolia. While on treatment, invasive dental procedures should be performed only after careful consideration and avoided in close proximity to Prolia administration. The management plan of patients who develop ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ. Osteonecrosis of the external auditory canal: Osteonecrosis of the external auditory canal has been reported with Prolia. Refer to the SmPC for risk factors. Atypical femoral fracture (AFF): AFF has been reported in patients receiving Prolia. Discontinuation of Prolia therapy in patients suspected to have AFF should be considered pending evaluation of the patient based on an individual benefit risk assessment. Longterm antiresorptive treatment: Long-term antiresorptive treatment may contribute to an increased risk for adverse outcomes such as ONJ and AFF due to significant suppression of bone remodelling. Concomitant medication: Patients being treated with Prolia should not be treated concomitantly with other denosumab containing medicinal products. Warnings for Excipients: Patients with rare hereditary problems of fructose intolerance should not use Prolia. Interactions: Prolia did not affect the pharmacokinetics of midazolam, which is metabolized by cytochrome P450 3A4 (CYP3A4). There are no clinical data on the co-administration of denosumab and hormone replacement
therapy (HRT), however the potential for pharmacodynamic interactions would be considered low. Pharmacokinetics and pharmacodynamics of Prolia were not altered by previous alendronate therapy. Fertility, pregnancy and lactation: There are no adequate data on the use of Prolia in pregnant women and it is not recommended for use in these patients. It is unknown whether denosumab is excreted in human milk. A risk/benefit decision should be made in patients who are breast feeding. Animal studies have indicated that the absence of RANKL during pregnancy may interfere with maturation of the mammary gland leading to impaired lactation post-partum. No data are available on the effect of Prolia on human fertility. Undesirable Effects: The following adverse reactions have been reported: Very common (≥ 1/10) pain in extremity, musculoskeletal pain (including severe cases). Common (≥ 1/100 to < 1/10) urinary tract infection, upper respiratory tract infection, sciatica, constipation, abdominal discomfort, rash, alopecia and eczema. Uncommon (≥ 1/1000 to < 1/100): Cellulitis, ear infection and lichenoid drug eruptions. Rare (≥ 1/10,000 to < 1/1,000): Osteonecrosis of the jaw, hypocalcaemia (including severe symptomatic hypocalcaemia and fatal cases), atypical femoral fractures, and hypersensitivity (including rash, urticaria, facial swelling, erythema and anaphylactic reactions). Very rare (< 1/10,000): Hypersensitivity vasculitis. Please consult the Summary of Product Characteristics for a full description of undesirable effects. Pharmaceutical Precautions: Prolia must not be mixed with other medicinal products. Store at 2°C to 8°C (in a refrigerator). Prolia may be exposed to room temperature (up to 25°C) for a maximum single period of up to 30 days in its original container. Once removed from the refrigerator Prolia must be used within this 30 day period. Do not freeze. Keep in outer carton to protect from light. Legal Category: POM. Presentation and Marketing Authorisation Number: Prolia 60 mg: Pack of 1 pre-filled syringe with automatic needle guard; EU/1/10/618/003. Price in Republic of Ireland is available on request. Marketing Authorisation Holder: Amgen Europe B.V., Minervum 7061, NL-4817 ZK Breda, The Netherlands. Further information is available from Amgen Ireland Limited, 21 Northwood Court, Santry, Dublin DO9 TX31. Prolia is a registered trademark of Amgen Inc. Date of PI preparation: July 2021 (Ref: IE-PRO-0721-00001) Adverse reactions/events should be reported to the Health Products Regulatory Authority (HPRA) using the available methods via www.hpra.ie. Adverse reactions/events should also be reported to Amgen Limited on +44 (0)1223 436441 or Freephone 1800 535 160.
References:
1. Prolia® [denosumab], Summary of Product Characteristics.
2. Cummings SR et al, N. Eng. J Med 2009;361:756-765.
3. Holzer G et al, J Bone Miner Res 2009;24(3):468-74.
4. Poole K et al; J Bone Miner Res 012; 27 (suppl1):S44 abstract 1122.
5. Bone HG, et al; Lancet Diabetes Endocrinol. 2017;5:513-23;3-23.
6. Tsourdi E, et al. Bone. 2017;105:11–7. 7. Hernlund E, et al. Arch Osteoporos. 2013;8:136;
Irish Thoracic Society, Annual Scientific Meeting, virtual, 19 November 2021
Paul Mulholland speaks with Consultant Respiratory Physician Dr Michael Henry about the upcoming Irish Thoracic Society Annual Scientific Meeting at a time when respiratory services are struggling with the continuing Covid surge
It had been hoped, until recently, that the upcoming Irish Thoracic Society (ITS) Annual Scientific Meeting, which will take place on 19 November, would be a face-toface event. However, according to Consultant Respiratory Physician, Cork University Hospital (CUH), Dr Michael Henry, the ITS believed this was too great a risk given the deteriorating Covid situation in the country. Instead, the meeting, which will feature an impressive range of speakers, will be held virtually for the second year running.
Covid-19, of course, is not just affecting educational meetings, but the day-to-day working lives of medical professionals across the country. Dr Henry told the Medical Independent (MI) that three specialties have been most negatively impacted by the current crisis: Infectious disease; intensive care; and respiratory medicine.
“And all three services, particularly respiratory and intensive care – you see it on the news every day – are struggling badly,” he said.
Advocacy
One of the key roles of the ITS, especially at the current time, is to advocate for patient safety. In terms of Covid-19, this includes the promotion of healthcare guidelines, such as handwashing and mask-wearing. It also means agitating for more resources for the specialty and the protection of staff working in respiratory medicine. Regarding the latter, the roll-out of the booster Covid-19 vaccine for healthcare workers, which was recently announced by Government, is “massively important”, according to Dr Henry.
“Most healthcare workers are young and healthy and they are not going to get very sick,” he said.
“But they will be off work. And if they are off work from a service that is already struggling, then you are really going to struggle to provide services for everybody with respiratory disease. So we need to highlight that as much as we can.”
Covid-19 has had a direct impact on the staff working in the respiratory medicine department in CUH. Dr Henry himself was diagnosed with Covid in January, and two of the other three consultant respiratory physicians have also been infected, in addition to the majority of registrars. While thankfully none of these infections led to serious illness, the need for such a high number of staff to take time off work has severely hampered the service, he said.
The department has been struggling not only in terms of staff, but also due to a lack of resources. Dr Henry has not seen much evidence in CUH of the additional funding that has been released to cope with the pandemic.
“The extra resource that has been put in
to deal with Covid amounts to one Covid ward that is staffed to just look after Covid patients,” he said.
“But you have no choice but to do that. Every hospital has to have an isolation ward where Covid patients go. Other than that, access to extra staff, diagnostics, treatment, I would say, if anything, has gotten worse, not better, over the last 12 months.”
Covid impact on respiratory services
While Dr Henry said the effect of the cyberattack was as bad, if not worse, than the pandemic, services for other conditions have been “devastated” over the past year-and-half because of Covid-19. To take one example: CUH’s pulmonary function laboratory has only worked at approximately a quarter of its capacity since the Covid crisis began. This is due to a range of factors, such as the emergency department appropriating part of the workspace, the greater need for sterilisation, and the safety concerns of staff.
“The knock-on effect of it all is that we get less than a quarter of the number of tests done that we need to get done,” he told MI.
“So if you have a lung cancer patient who needs an urgent part of their lung removed, we can’t get it done for weeks. It shouldn’t be holding up the process at all. Also, I run a lung fibrosis clinic that I’m doing this afternoon. I would have 20-something patients coming; most of them should have
different hospitals. But I’m sure everybody will tell you the same thing. It is having a huge effect on how we are running our service. We are not running our service very well because of this.”
While there is disappointment about not having a face-to-face meeting, Dr Henry said the event will still be crucial in having members come together, albeit virtually, and hear about the latest developments in their fields.
“Because very few of us have had the opportunity to travel to international educational meetings,” he explained.
The meeting will also hear from Prof John Cryan, Professor and Chair, Department of Anatomy and Neuroscience, University College Cork. The title of Prof Cryan’s talk is ‘Gut microbiome: Our inner friends with benefits’.
“If you know anything about the [Department of Anatomy and Neuroscience] here in Cork, it is one of the top five international research centres in the world. He is looking at the gut microbiome and its effect on the lung. That might sound very highfaluting, but I think that is going to be very exciting for us.”
The international speakers include Prof Thierry Troosters, Professor in Rehabilitation Sciences, KU Leuven, Belgium, who will speak about pulmonary rehibition; and Prof Dirk-Jan Slebos, Professor of Interventional Pulmonology, University Medical Centre Groningen, Netherlands, who will speak about bronchoscopic interventions for COPD and chronic bronchitis. Both are world leaders in their respective fields.
According to Dr Henry, one of the highlights of the meeting will be a talk on lung cancer screening to be delivered by Prof Harry de Koning, Professor of Public Health and Screening Evaluation, Erasmus University Medical Centre, Rotterdam, Netherlands. The title of the lecture is ‘Implementation of lung cancer screening: Prime time!’.
“There is a lot of work around the world on screening for lung cancer,” according to Dr Henry.
“And clearly that is really topical. It hasn’t really reached prime time in Ireland yet. He is one of the leads in a very big European lung cancer screening trial. And he is going to bring us up to date on that. And hopefully that will push the agenda in Ireland on screening for lung cancer in the same way we screen for breast cancer, colon cancer, etc. We don’t, as of yet, have that programme here. But I think these types of people speaking in Ireland to Irish audiences will help promote that.”
had their pulmonary function tests done. I would say I’d be lucky if three or four have them done. This is how you monitor if patients are getting better or worse. Most of it, not all of it, is down to Covid. That has a huge impact on how we manage all of these complex respiratory patients.”
The department’s outpatient space was also appropriated at the beginning of the pandemic. As a result, outpatient consultations have moved off-site, and now take place in a local convent.
“The facility is just really poor, and not fit for an outpatient service. And that is the direct result of the other area that was previously used now being taken for Covid pathways. To put it mildly, it has devastated our service here. It will be different in
“There’s been no opportunity really. Some of it has been online and we have been trying to keep up to date. But it is critical for our own continuing development in medical education that we have these programmes coming online or face-toface regularly so we can keep up to date as to what is going on.”
Dr Henry emphasised the annual meeting will have “great speakers”, both national, and international.
On the national side, Prof Cormac McCarthy, Consultant Respiratory Physician, St Vincent’s University Hospital, Dublin, will speak about diffuse cystic lung diseases.
“That’s going to be really good; he is a world leader in that area,” according to Dr Henry.
In conclusion, Dr Henry said the huge challenges in dealing with the pandemic make events such as the ITS Annual Scientific Meeting particularly important.
“I think it is really critical for health workers that we all, at least, have the chance to get together, even if it is virtually. That we get a chance to meet as a community to try and keep a certain degree of solidarity going, encourage each other, and promote, not just Covid research and development, but other areas as well. Because it is important, as a respiratory community, that we don’t lose touch with each other in this era of Covid. That we stay in touch, and try to promote proper respiratory health values in the situation we find ourselves in.”
To put it mildly, [Covid-19] has devastated our service here. It will be different in different hospitals. But I’m sure everybody will tell you the same thing
*Anoro Ellipta compared to tiotropium/olodaterol showed statistical superiority on pre-specified secondary endpoint of trough FEV1 at 8 weeks in the Intent to Treat population. ITT population n=236 (180mL vs. 128mL in trough FEV1; Difference 52ml (p<0.001, 95% CI:28,77).
The primary endpoint of non-inferiority on trough FEV1 at Week 8 in the PP population was met. Non-inferiority was met for the primary endpoint at Week 8 in the PP population (n=227) (175mL Anoro Ellipta and 122mL tiotropium/olodaterol, 95% CI: 26, 80; p<0.001)1
Anoro Ellipta is contraindicated for patients who are hypersensitive to the active substances or to any of the excipients. Anoro Ellipta is not indicated for the treatment of acute episodes of bronchospasm. Cardiovascular events, such as cardiac arrhythmias, may be seen after the administration of muscarinic receptor antagonists and sympathomimetic agents, including umeclidinium/vilanterol. Therefore, Anoro Ellipta should be used with caution in patients with severe cardiovasular disease. Due to antimuscarinic activity (i.e. LAMA class activity), umeclidinium/vilanterol should be used with caution in patients with urinary retention or with narrow-angle glaucoma.2
An 8-week, randomised, open-label, two-period crossover in symptomatic patients with moderate COPD (post bronchodilator FEV1 ≤70% and ≥ 50% of predicted value, mMRC≥2) and not receiving ICS at inclusion.1
COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; LABA, long-acting beta2-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council scale; ITT, intent to treat; PP, per protocol.
Anoro Ellipta 55/22mcg is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD)2
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.
Anoro®▼ Ellipta® (umeclidinium bromide/vilanterol [as trifenatate]) Prescribing information (Please consult the full Summary of Product Characteristics (SmPC) before prescribing)
Anoro® Ellipta® 55/22mcg (umeclidinium bromide/vilanterol [as trifenatate]) inhalation powder. Each single inhalation of umeclidinium bromide (UMEC) 62.5 micrograms (mcg) and vilanterol (VI) 25mcg provides a delivered dose of UMEC 55mcg and VI 22mcg. Each delivered dose contains approx. 25 mg lactose. Indications: COPD: Maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. Dose and administration: Inhalation only. COPD: One inhalation once daily at the same time of the day. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate and magnesium stearate).
Precautions: Anoro Ellipta should not be used in patients with asthma. Treatment with Anoro Ellipta should be discontinued in the event of paradoxical bronchospasm and alternative therapy initiated if necessary. Cardiovascular effects may be seen after the administration of muscarinic receptor antagonists and sympathomimetics therefore Anoro Ellipta should be used with caution in patients with severe cardiovascular disease. Anoro Ellipta should be used with caution in patients with urinary retention, narrow angle glaucoma, convulsive disorders, thyrotoxicosis, hypokalaemia, hyperglycaemia and severe hepatic
References:
impairment. No dose adjustment is required in renal or mild to moderate hepatic impairment. Patients with rare hereditary problems of galactose intolerance, the Lapp total lactase deficiency or glucose-galactose malabsorption should not use Anoro Ellipta. Acute symptoms: Anoro Ellipta is not indicated for acute episodes of bronchospasm. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases, a re-evaluation of the patient and of the COPD treatment regimen should be undertaken. Interactions with other medicinal products: Interaction studies have only been performed in adults. Avoid β-blockers. Caution is advised when co-administering with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, itraconazole, ritonavir, telithromycin). Anoro Ellipta should not be used in conjunction with other long-acting β2-adrenergic agonists or medicinal products containing long-acting muscarinic antagonists. Caution is advised with concomitant use with methylxanthine derivatives, steroids or non-potassium-sparing diuretics as it may potentiate possible hypokalaemic effect of β2adrenergic agonists. Fertility, pregnancy, and breast-feeding: No available data. Balance risks against benefits. Side effects: Common: Urinary tract infection, sinusitis, nasopharyngitis,
1. Feldman G.J et al. Adv Ther. 2017 Nov;34(11):2518-2533. 10.1007/s12325-017-0626-4.
2. Anoro Ellipta Summary of Product Characteristics. Available from: www.medicines.ie. Accessed April 2021.
ANORO ELLIPTA was developed in collaboration with ©2021 GSK group of companies. All rights reserved.
pharyngitis, upper respiratory tract infection, headache, cough, oropharyngeal pain, constipation and dry mouth. Uncommon: Hypersenstivity reactions including rash, tremor, dysgeusia, dysphonia, atrial fibrillation, supraventricular tachycardia, rhythm idioventricular, tachycardia, supraventricular extrasystoles and palpitations. Rare: Anaphylaxis, angioedema, urticaria, vision blurred, glaucoma, intraocular pressure increased, paradoxical bronchospasm, urinary retention, dysuria and bladder outlet obstruction. Frequency not known: Dizziness. Marketing Authorisation (MA) Holder: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. MA Nr: 55/22mcg 1x30 doses [EU/1/14/898/002]. Legal category: POM B. Last date of revision: January 2021. Job Ref: PI-3826. Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Campus, Dublin 24, Tel: 01-4955000.
Adverse events should be reported directly to the Health Products Regulatory Authority (HPRA) on their website: www.hpra.ie. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.
Anoro and Ellipta are registered trademarks of the GlaxoSmithKline group of companies
PM-IE-UCV-ADVT-210001
Date of Preparation: April 2021
Irish Thoracic Society, Annual Scientific Meeting, virtual, 19 November 2021
08.00-09.00
Moderated Poster Review –
Chairs: Dr Aidan O’Brien and Dr Michael Henry
1. ILD and Miscellaneous
09.00-09.30
Guest Lecture I - Diffuse cystic lung diseases
Prof Cormac McCarthy, Consultant Respiratory Physician, St Vincent’s University Hospital, Dublin
Chairs: Dr Michael Henry and Dr David Curran
09.30-09.45 Break
09.45-10.45
Moderated Poster Review –
Chairs: Dr Katherine Finan and Dr Martin Kelly
2. Lung cancer and bronchoscopy/cystic fibrosis and pulmonary infections
10.45-11.15
Guest Lecture II – Joint ITS ERS guest Llecture: Update in pulmonary rehabilitation
Prof Thierry Troosters, Professor in Rehabilitation Sciences, KU Leuven
Chairs: Ms Siobhan Healy and Dr John Kiely
11.15-11.30 Break
11.30-12.00
Guest Lecture III – Gut microbiome: Our inner friends with benefits
Prof John Cryan, Professor and Chair, Department of Anatomy and Neuroscience, University College Cork
Chairs: Dr Oisin O’Connell and Prof Barry Plant
12.00-13.00
Moderated Poster Review –
Chairs: Dr Breda Cushen and Dr Silke Ryan
3. COPD/asthma and sleep
13.00-14.00 Lunch
14.00-14.45
Moderated Poster Review –
Chairs: Dr Emer Kelly and Dr Katherine Finan
4. Covid-19
14.45-15.30
Guest Lecture IV – Implementation of lung cancer screening: Prime time!
Prof Harry de Koning, Professor of Public Health and Screening Evaluation, Erasmus University Medical Centre, Rotterdam
Chairs: Dr Marcus Kennedy and Prof Terry O’Connor
15.30-15.45 Break
15.45-17.25
5. Oral Presentations –
Chairs: Dr Marcus Kennedy and Dr Desmond Murphy
17.25-18.15
Guest Lecture V – Bronchoscopic interventions for COPD and chronic bronchitis
Prof Dirk-Jan Slebos, Professor of Interventional Pulmonology, University Medical Centre Groningen, Netherlands
Chairs: Dr Liam Doherty and Dr Breda Cushen
Irish Endocrine Society, Annual Meeting, virtual, 19/20 November 2021
The Irish Endocrine Society 45th Annual Meeting 2021 is due to take place on 19 and 20 November 2021 on a virtual basis. The meeting will include local and international keynote speakers, basic science and clinical research, and clinical cases in adult and paediatric endocrinology.
Prof Eberhard Nieschlag, University of Münster, will deliver two talks. Prof Nieschlag is a specialist in internal medicine, endocrinology and andrology. His clinical and research activities concentrate on reproductive endocrinology and andrology, especially treatment of infertility,
Friday 19 November 2021
9.25 INTRODUCTION: Prof J Gibney
testosterone substitution, the aging male and hormonal male contraception.
The first of his talks, which will be delivered at the beginning of the meeting, is titled ‘Testosterone substitution: For whom, when and how?’. The second is the keynote Hadden Lecture at the end of the first day, which is titled ‘The cultural and medical history of testosterone and the testes’.
On the second day, the Paediatric Lecture, titled ‘Congenital hypopituitarism: Novel insights into management', will be given by Prof Mehul Dattani, UCL Great
9.30 – 11.00 MEET THE PROFESSOR: Prof E Nieschlag, University of Münster. Testosterone substitution: For whom, when, and how?
11.00- 11.30
BREAK/PHARMA INDUSTRY PRESENTATIONS
11.30 – 12.50 POSTER VIEWING (VIRTUAL)
12.55 WELCOME AND INTRODUCTION: Prof B Kinsley
13.00 – 13.30 INVITED POSTER PRESENTATIONS
13.00 – 13.05 P1. Impact of IGF-1 and GH assay type on the interpretation of growth hormone day curve results in the assessment of acromegalic disease activity
13.05 – 13.10 P2. HbA1c testing following transition of people with uncomplicated type 2 diabetes from outpatient diabetes clinics to general practice
13.10 – 13.15 P3. Hypoglycaemia in a metastatic gastrin secreting pancreatic NET on insulin pump therapy
13.15 – 13.20 P4. Case report: Transient postpartum hypopituitarism
13.20 – 13.25
13.25 – 13.30
13.30 – 15.30
13.30 – 13.45
P5 Case report: Subacute thyroiditis post viral vector vaccine for Covid-19
P6. U500 insulin in the management of severe insulin resistance in pregnancy
ORAL COMMUNICATIONS
OC1 Liquid-chromatography-tandem-mass-spectrometry (LC-MS/MS) demonstrates greater aldosterone/renin ratio in unselected Africanorigin compared to matched European-origin participants, but a similar proportion of abnormal results
Ormond Street Institute of Child Health.
The other keynote talk, the McKenna Lecture, will be delivered by Prof Hilary Hoey, Emeritus Professor and past Head of the Department of Paediatrics, Trinity College Dublin, on the subject of ‘Challenges and opportunities in endocrinology’.
The meeting will also feature oral research presentations and a formal poster session.
This online event is supported by the Pillar Centre for Transformative Healthcare in the Mater Misericordiae University Hospital, Dublin.
16.25 – 16.40 OC 9 In type 1 diabetes, lipidomic profiling demonstrates differing phosphatidylcholine concentrations in participants with increased carotid intima media thickness (CIMT)
16.40 – 16.55 OC10 Diabetic model development and investigation of the therapeutic effect of MSC-scaffold bio-complex
13.45 – 14.00
14.00 – 14.15
14.15 – 14.30
14.30 – 14.45
14.45 – 15.00
15.00 – 15.15
15.15 – 15.30
15.30 – 16.25
OC2 Changes in vitamin D concentration and deficiency in the West of Ireland during the Covid-19 lockdown
OC3 Transcutaneous electrical neurostimulation of dermatome T6 lowers glucose and blood pressure: A randomised controlled study
OC4 Pre-frailty in working middle-aged and older adults with and without diabetes and its association with fear of health limiting their ability to work and early retirement plans: A European overview
OC5 Metabolic effects 15 years after haematopoietic stem cell transplant
OC6 Mucosal associated invariant T-cells are associated with insulin resistance in childhood obesity and can disrupt insulin signalling via interleukin-17
OC7 Relative contribution of oral and inhaled glucocorticoid exposure to risk of adrenal insufficiency in asthma treated with fluticasone propionate
OC8
Outcomes of a national cohort of 1,000 pregnancies in women with pre-gestational diabetes type 1 and type 2: 2015-2020
BREAK/PHARMA INDUSTRY PRESENTATIONS
16.25 – 16.55 ORAL COMMUNICATIONS
Saturday 20 November 2021
17.00 – 17.45 IES HADDEN LECTURE: Prof E Nieschlag, ‘The cultural and medical history of testosterone and the testes’ 08.55
– 9.45 ORAL COMMUNICATIONS
9.00 – 9.15 OC11 HDL structure and function in people with Type 1 diabetes differ compared to those with Type 2 diabetes as well as lean and overweight people without diabetes
9.15 – 9.30 OC12 Endothelial colony forming cells as an autologous cell therapy to treat diabetic and non-diabetic critical limb ischaemia
9.30 – 9.45 OC13 Improving outcomes for young adults living with type 1 diabetes in Ireland: Results of the D1 NOW pilot randomised controlled trial
9.45 – 10.30 PAEDIATRIC S LECTURE: Prof Mehul Dattani, UCL Great Ormond Street Institute of Child Health, ‘Congenital hypopituitarism: Novel insights into management’
10.30 – 11.00
11.00 – 11.30
11.30 – 13.00
11.30 – 11.45
11.45 – 12.00
12.00 – 12.15
12.15 – 12.30
12.30 – 12.45
12.45 – 13.00
IES MCKENNA LECTURE: Prof Hilary Hoey, Emeritus Professor and past Head of Dept of Paediatrics Trinity College Dublin, ‘Challenges and Opportunities in Endocrinology’
BREAK/PHARMA INDUSTRY PRESENTATIONS
ORAL COMMUNICATIONS
OC14
Sex-specific differences in HDL function and composition in patients with and without metabolic disease
OC15 Forty years’ experience of neonatal thyroid stimulating hormone screening in NI
OC16 Reproductive health disturbance in the era of the Covid-19 pandemic
OC17 The novel Aphonopelmachalcodes tarantula venom-derived peptide, ΔTRTX-Ac1, possess insulinotropic actions and augments GLP-1 induced reductions of appetite
OC18 The endocrine management of differentiated thyroid cancer at St James’s Hospital, Dublin, 2005-2020
OC19 Abnormal glucose tolerance in women diagnosed with gestational diabetes mellitus using the International Association of the Diabetes and Pregnancy Study Groups criteria 10 years after an affected index pregnancy compared to women with normal glucose tolerance in the same period
13.00 Presentation of Irish Endocrine Society O’Donovan Medal (best oral presentation) and Montgomery Medal (best poster presentation)
Ozempic® provided a significant 26% risk reduction of MACE# in people with type 2 diabetes* and cardiovascular disease.1,2,§
This includes a 39% relative risk reduction in non-fatal stroke.1,2,‡
Ozempic® also has superior blood glucose and weight-loss efficacy across all head-to-head clinical trials in the SUSTAIN program.1-9,†,‡
* 26% CV risk reduction in patients with type 2 diabetes and high CV risk, compared to placebo, in addition to standard treatment.
# Major Adverse Cardiovascular Events
† Results apply to Ozempic® across SUSTAIN trials, which included placebo, sitagliptin, dulaglutide, canagliflozin, exenatide PR and glargine U100.1-9 § p=0.02 for superiority ‡ p<0.05
Ozempic® is recommended by the ADA/EASD Consensus Report for people with type 2 diabetes who have established atherosclerotic cardiovascular disease10
PR = Prolonged Release; ADA = American Diabetes Association; EASD = European Association for the Study of Diabetes.
SUSTAIN = Semaglutide Unabated Sustainability in treatment of Type 2 Diabetes.
*SUSTAIN was the phase 3 clinical trial programme investigating the effects of once weekly semaglutide versus other anti-diabetic agents.
ABBREVIATED PRESCRIBING INFORMATION
Ozempic®t semaglutide
Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Ozempic® 0.25 mg solution for injection in pre-filled pen. Ozempic® 0.5 mg solution for injection in pre-filled pen. Ozempic® 1 mg solution for injection in prefilled pen. One ml of solution contains 1.34 mg of semaglutide (human glucagon-like peptide-1 (GLP-1) analogue). Indication: Ozempic® is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise • as monotherapy when metformin is considered inappropriate due to intolerance or contraindications • in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1 of the Ozempic® SmPC. Posology and administration: Administered once weekly at any time of the day, with or without meals. Injected subcutaneously in the abdomen, thigh or upper arm. Starting dose: 0.25 mg once weekly. After 4 weeks the dose should be increased to 0.5 mg once weekly. After at least 4 weeks with a dose of 0.5 mg once weekly, the dose can be increased to 1 mg once weekly to further improve glycaemic control. When Ozempic® is added to existing metformin and/or thiazolidinedione therapy or to an SGLT2 inhibitor, the current dose of metformin and/or thiazolidinedione or SGLT2 inhibitor can be continued unchanged. When Ozempic® is added to a sulfonylurea or insulin, a reduction in dose of sulfonylurea or insulin should be considered to reduce the risk of hypoglycaemia. Blood glucose selfmonitoring is necessary to adjust the dose of sulfonylurea and insulin, particularly when Ozempic® is started and insulin is reduced. A stepwise approach to insulin reduction is recommended. Children: No data available. Elderly: No dose adjustment required, therapeutic experience in patients age ≥75 is limited. Renal impairment: No dose
adjustment is required for patients with mild, moderate or severe renal impairment. Experience in patients with severe renal impairment is limited. Not recommended for use in patients with end-stage renal disease. Hepatic impairment: No dose adjustment is required for patients with hepatic impairment. Experience with severe hepatic impairment is limited. Caution should be exercised when treating these patients with semaglutide. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special warnings and precautions for use: Should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Not a substitute for insulin. Diabetic ketoacidosis has been reported in insulin-dependent patients whom had rapid discontinuation or dose reduction of insulin. There is no experience in patients with congestive heart failure NYHA class IV and is therefore not recommended in these patients. Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions. This should be considered when treating patients with impaired renal function as nausea, vomiting, and diarrhoea may cause dehydration which could cause a deterioration of renal function. Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, semaglutide should be discontinued; if confirmed, semaglutide should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Use of semaglutide in combination with a sulfonylurea or insulin may have an increased risk of hypoglycaemia, therefore consider reducing the dose of sulfonylurea or insulin when initiating treatment with Ozempic®. In patients with diabetic retinopathy treated with insulin and semaglutide, an increased risk of developing diabetic retinopathy complications has been observed. Caution should be exercised when using semaglutide in patients with diabetic retinopathy treated with insulin. These patients should be monitored closely and treated according to clinical guidelines. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy, but other mechanisms cannot be excluded. When
semaglutide is used in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines. Fertility, pregnancy and lactation: Women of childbearing potential are recommended to use contraception when treated with semaglutide. Should not be used during pregnancy or breast-feeding. Discontinue at least 2 months before a planned pregnancy. Effect on fertility unknown. Undesirable effects: Very common (≥1/10): Hypoglycaemia when used with insulin or sulfonylurea, nausea, diarrhoea. Common (≥1/100 to <1/10): Hypoglycaemia when used with other oral antidiabetic medications, decreased appetite, dizziness, diabetic retinopathy complications, vomiting, abdominal pain, abdominal distension, constipation, dyspepsia, gastritis, gastro-oesophageal reflux disease, eructation, flatulence, cholelithiasis, fatigue, increased lipase, increased amylase, weight decreased. Uncommon (≥1/1,000 to <1/100): Hypersensitivity, dysgeusia, increased heart rate, acute pancreatitis, injection site reactions. Rare (≥1/10,000 to <1/1,000): Anaphylactic reaction. Not known (cannot be estimated from available data): Angioedema. The SmPC should be consulted for a full list of side effects. MA numbers: Ozempic® 0.25 mg pre-filled pen EU/1/17/1251/002. Ozempic® 0.5 mg prefilled pen EU/1/17/1251/003. Ozempic® 1 mg pre-filled pen EU/1/17/1251/005. Each pre-filled pen delivers 4 doses and includes 4 disposable NovoFine® Plus needles. Legal Category: POM. For complete prescribing information, please refer to the SmPC which is available on www.medicines.ie or by email from infoireland@novonordisk.com or from the Clinical, Medical and Regulatory Department, Novo Nordisk Limited, 1st Floor, Block A, The Crescent Building, Northwood Business Park, Santry, Dublin 9. Date last revised: March 2021.
tAdverse events should be reported to the Health Products Regulatory Authority. Information about adverse event reporting is available at www.hpra.ie. Adverse events should also be reported to Novo Nordisk on Tel: 1850 665 665 or complaintireland@novonordisk.com
References: 1. Ozempic® Summary of Product Characteristics www.medicines.ie 2. Marso SP, et al; Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. (SUSTAIN 6) N Engl J Med. 2 2016;375:1834-1844. 3. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(suppl1):S1-S108. 4. Lingvay I et al, Once weekly Semaglutide vs Canagliflozin in type 2 diabetes (SUSTAIN 8) : a double blind phase 3 randomised control trial: Lancet Diabetes Endocrinol 2019; 7: 834–44. 5. Ahmann AJ et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial. Diabetes Care 2018;41:258-266. 6. Aroda VR et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol 2017;5: 355–66. 7. Sorli C et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol 2017; 5: 251–60. 8. Ahrén B et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol 2017; 5: 341–54. 9. Pratley RE et al. Semaglutide versus dulaglutide once-weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6275-286. 10.Buse JB et al. 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020 Feb; 43(2):487-493.
Ozempic® is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise • as monotherapy when metformin is considered inappropriate due to intolerance or contraindications • in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1. of the SmPC.1 tThis medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.
Novo Nordisk Limited, First Floor, Block A, The Crescent Building, Northwood Business Park, Santry, Dublin 9, D09 X8W3, Ireland. Tel: 01 8629 700, Fax: 01 8629 725, Lo call: 1 850 665665. infoireland@novonordisk.com www.novonordisk.ie
Ozempic® and the Apis bull logo are registered trademarks owned by Novo Nordisk A/S.
Date of preparation: October 2021. IE21OZM00098
OUR NEW ADDRESS
Q1 Which nation won cricket’s Twenty20 international this month?
Q2 Snooker’s first Triple Crown event, the UK Championships, cues off next weekend. Who is the defending champion?
Q3 Who has replaced Steve Bruce as Newcastle United manager?
Q4 Which golf course will host the 2022 Irish Open?
Q5 Who became boxing’s undisputed Super Middleweight World Champion after claiming the WBC belt earlier this month?
Q6 Who will face off in this season’s FAI cup final?
18
The winner of the 28 October 2021 Sporting Quiz Competition is Dr Siobhan McCourt, Co Dublin
The winner of the 28 October 2021 Crossword is Dr Jessica Creaner, Dublin 15
Q1 Who is the manager of the Ireland senior men’s soccer team? A: Stephen Kenny
Q2 Name the British tennis player who won his first 1,000 series Masters title at Indian Wells this month? A: Cameron Norrie
Q3 Name the Northern Ireland snooker player who recently won the Northern Ireland Open? A: Mark Allen
Q4 Rory McIlroy claimed victory in the CJ Cup a couple of weeks ago. How many PGA titles has he now won? A: 20
Q5 The Irish rugby team will play autumn test matches against New Zealand, Argentina, and which other nation? A: Japan
Q6 Who was recently sacked as manager of Newcastle United? A: Steve Bruce
DOWN
1 Pair (6)
2 Drug that treats a disease (8)
3 Rustic (5)
5 Public collection of books (7)
6 Too; in addition (4)
7 Device that detects a physical property (6)
8 Person who gives something (11)
13 Thoroughly conversant with (8)
14 Grow more mature (7)
15 State of mental strain (6)
16 Way of standing (6)
17 Part of the leg (5)
19 Equitable (4)
- Part of the leg (5)
RESULTS FROM LARGE REAL-WORLD SAFETY STUDY IN ZOELY▼ PUBLISHED
Theramex, a global women’s health company, together with Consilient Health Ireland have announced that the safety results from the PRO-E2 real-world safety study for Zoely (NOMAC-E2) have been published in the European Journal of Contraception and Reproductive Health Care (EJCRH)
The post-authorisation safety study (PASS), known as PRO-E2, was a large, prospective, non-interventional controlled cohort study of over 101,000 women. PRO-E2 compared the risks of using NOMAC-E2 versus COCs containing levonorgestrel (COC-LNG), a commonly prescribed contraceptive.
The primary objective of the real-world study was to assess and compare the risk of cardiovascular events in NOMAC-E2 users with COC-LNG users. For the main clinical outcome, the risk of VTE was as least as low with NOMAC-E2 as with COC-LNG, consistent with findings of previous studies (0.59 Hazard Ratio [HR] 95 per cent confidence interval [CI], 0.25-1.35).
PRO-E2 also demonstrated that contraceptive failure (the risk of unintended pregnancy), a key secondary outcome, was statistically significantly lower with NOMAC-E2 compared with COC-LNG (0.45 HR, 95 per cent CI, 0.34-0.60, [p<0.0001]). Further analyses showed that the lower rate of unintended pregnancy with NOMAC-E2 was even more pronounced in women under 35 years of age. The shorter hormone-free interval with NOMAC-E2, its longer halflife, and monophasic regimen may all contribute to fewer unintended pregnancies.
These results will be pub-
lished in the EJCRH later this month.
All 14 secondary outcomes of the study were met, with the risk of severe adverse events and depressive disorders or changes in weight or acne score with NOMAC-E2 comparable to COC-LNG.
Dr Deirdre Lundy, GP, Bray Women’s Health Centre, Bray, Co Wicklow, said: “We as prescribers welcome any quality research that confirms pill safety. I use Zoely regularly – it is a favoured COCP for younger patients because it has the non-EE oestrogen and the short pillfree interval.”
Consilient Health Country Manager Ms Deirdre Kelly said: “The PRO-E2 study results will build further confidence in what has already been shown to be a reliable and effective birth-control option. As a company dedicated to improving women’s health, we are delighted that the wealth of evidence from this safety study can help clinicians and women make informed decisions about contraception.”
The safety and efficacy publications were accepted by the EJCRH in September. The publication on safety results is available online: www.tandfonline.com/doi/ 10.1080/13625187.2021.
1987410
The efficacy publication will be available online. Both publications will be available in the printed journal in December
Results have also been submitted to the European Medicines Agency (EMA) and will be presented at the European Society of Gynecology congress in November this year.
Minister for Health Stephen Donnelly has welcomed the publication of a new national clinical effectiveness guideline to help healthcare professionals manage chronic obstructive pulmonary disease (COPD).
This new guideline was developed by a multidisciplinary guideline development group supported by the HSE National Clinical Programme for Respiratory. The guideline development group was chaired since 2020 by Dr Des-
ment of exacerbations and often causes premature death.
The development of this national clinical guideline for COPD aims to ensure that COPD patients across the country receive consistent and standardised care, based on the best available evidence.
The guidance was quality assured by the Department’s national clinical effectiveness committee and has received Ministerial endorsement as a high-quality guideline to be implemented across the health service.
Supporting the publication, Minister Donnelly said: “I am pleased to endorse this national clinical guideline in relation to the management of chronic obstructive pulmonary disease, which will be implemented across the health service to help support safe, high-quality care for patients.”
He said the guideline development had been informed by a full public consultation and reviewed by international experts.
Dr Desmond Murphy, Chair of the guideline development group and Clinical Lead, HSE National Clinical Programme for Respiratory, commented: “The NCEC doc-
ument for COPD represents the culmination of a lot of work, by a lot of people, to develop a framework to support the provision of optimal care for COPD patients in Ireland.
“The document has been reviewed by multiple different elements within the Irish healthcare provider system and also by patient advocacy groups, with feedback incorporated. Furthermore, it has been reviewed by recognised international experts in COPD. It is a pleasure to see the document launched. I believe this represents significant progress for patients with COPD in Ireland.”
Dr Tony Holohan, Chief Medical Officer, said he “greatly welcomes” this latest national clinical guideline. “Making the evidence available in an accessible way to healthcare professionals is critical in enabling evidence-based practice and safe, high-quality patient care.”
The guideline is available at the following link: www.gov.ie/en/publication/5df41-national-clinical-guideline-no27-management-of-chronic-obstructive-pulmonary-disease-copd/
cent worried about developing Alzheimer’s and over one-quarter of those surveyed (28 per cent) responding that they have concerns about developing depression later in life.
Commenting on the research, Mr Paul Reid, Managing Director, Pfizer Healthcare Ireland, said: “It’s clear from the research that people have put off going to their doctor and it is really important that anyone with an ongoing health issue visits their GP to seek help. It is understandable that people are worried about having a stroke or getting cancer, however, scientific advancement and health outcomes are getting better and with early diagnosis and access to treatments, patients have a better chance of a positive outcome.”
Ms Rachel Morrogh, Director of Advocacy & External Affairs, Irish Cancer So-
ciety, added: “Covid-19 has presented many health system challenges, which have made it more difficult for the public to access non-Covid care. This year’s research reveals that the public is concerned that this may have impacted their health. The findings underscore the importance that if anyone is worried about missing an appointment or if they have not sought medical advice yet, to make an appointment with their GP or clinician as soon as possible.
“It’s so important for anyone who is concerned about their health generally or who feels they may have neglected a lump or a mole to reach out for a referral. When it comes to cancer, early detection and early intervention is proven to save lives. It’s vital to seek medical attention quickly if a potential symptom is identified.”
A team at St James’s Hospital in Dublin has received a ‘Cheers Award’ from the Institute for Safe Medication Practice (ISMP), a USbased non-profit organisation devoted to preventing medication errors.
mond Murphy, and previously by Prof Tim McDonnell.
COPD is the most prevalent respiratory disease in adults and is a major cause of morbidity and mortality. At least 1,500 patients die each year of this disease and over 15,000 patients are admitted to hospital.
The condition has considerable impact on the quality-of-life of patients, families and carers. It involves ongoing medical care, frequent hospital admissions for treat-
New research from Pfizer shows that one-in-five people (21 per cent) are worried about potential delayed diagnosis and treatments due to the pandemic, with around 50 per cent either cancelling medical appointments or missing scheduled appointments. Hospital-initiated cancellations were higher among older age groups with 28 per cent of over-65s having a hospital appointment cancelled compared to 16 per cent of 25-34-year-olds. Meanwhile, slightly more than one-in-10 (11 per cent) of adults did not seek treatment despite feeling unwell during this period.
However, the annual Pfizer Health and Science Index reveals that people are less worried about visiting the hospital compared with last year, with almost one-fifth (18 per cent) of respondents very or quite worried and would not visit a hospital – a nine-point drop compared to 27 per cent in 2020. Similarly, this year’s findings show that just 16 per cent of people
are very or quite worried and would not visit their GP. Despite this drop compared to 2020, 43 per cent of people believe they experienced a negative health implication of the pandemic with mental health, diet and weight, and a lack of exercise predominating.
The research also shows that people are anxious about their long-term health and the prospect of developing a variety of serious illnesses in the future, with cancer the most significant concern. Of those who state they were concerned about cancer as they age (50 per cent), some 21 per cent of respondents (41 per cent of women) said they were concerned about getting breast cancer, 18 per cent had concerns about contracting cervical cancer (35 per cent of women) and 39 per cent were concerned about all other forms of cancer.
The Pfizer Index shows that respondents have similar concerns about getting other diseases, with 40 per cent concerned about heart disease; 37 per
The St James’s team’s ‘Medication Safety Minute’ is an innovative education tool that has been developed to promote the safe prescription of medication to patients. The project emerged from the review of real-world medication errors and discussions about how to optimally communicate the learning points to prescribers in the age of information overload.
The initiative is based on the concept of ‘microlearning’ which involves the delivery of concise nuggets of information that are presented in a question and answer, two-slide format, which recipients can review and digest within one minute or less. Each week a new minute is distributed to recipients, allowing for the easy digestion of complex information.
The project is the only European initiative to be awarded a ‘Cheers Award’ at the 24th annual awards ceremony. The Cheers Awards take place each year and seek to highlight institutions and individuals that ensure that the implementation of medication safety strategies stretch far beyond a few in-
dividuals or a single department and are fully integrated into their organisation’s culture and clinical practice.
During its more than 25-year history, ISMP has helped make a difference in the lives of millions of patients and healthcare professionals.
The Medication Safety Minute is a collaborative project undertaken by Dr Barry O’Connell, Dr Una Kennedy, and Medication Safety Facilitator, Dr Eileen Relihan, all of St James’s Hospital.
The project resources are currently used by 24 hospitals in Ireland and by a number of university undergraduate and postgraduate programmes.
The material has also been made available as a free online access resource in the form of a digital flipbook as well as being published weekly on a dedicated Twitter page, @ medsafetymin
The virtual awards ceremony is set to take place on Tuesday, 7 December.
Since the beginning of the hybrid revolution, I’ve been asked many times about a diesel version and here we are with the first I’ve tested, the MercedesBenz GLC 300 de 4MATIC. Could this be the holy grail for Irish car buyers, searing for a diesel, crossover, hybrid?
The plug-in hybrid GLC has been available on the continent for some time, but is relatively new to Irish shores, having only arrived within the past year. On offer in Ireland are both a PHEV petrol and diesel model, and I’m going to bet my hat on the vast majority of Irish buyers opting for the diesel version.
My test car had a two-litre four-cylinder diesel engine, backed up by a 122hp electric motor claiming combined fuel consumption figures of 1.8-2.0 l/100km and CO 2 figures of 49g/km. The engine felt nice and powerful to drive, while also being refined. It didn’t have that rough diesel feel that can be so irritating to live with; in fact, it’s very smooth on the motorway, thanks in part to its nine-speed automatic transmission, which also effortlessly glides between hybrid and diesel power. The combined power output of 194hp brings the GLC from 0-100kmh in a very respectable 6.2 seconds, which is right in the sweet spot for merging onto
the motorway like a competent motorist.
Inside the GLC you will find the expected, refined, Mercedes feel, with all of the leathers and plastics having a premium look and touch. It’s a comfortable space to spend time, wrapped in a cocoon of ARTICO leather in black-anthracite. The infotainment system is Apple- and Android-equipped, which means you don’t have to spend much time dealing with the Mercedes infotainment system. However, you still might have to deal with the touch pad mouse setup, which isn’t my favourite solution. Believe it or not, I actually like it less than Mazda’s infotainment system. Other than that, it’s a pretty good car and one that I feel will sell well.
Despite the heavy battery in the back, the GLC doesn’t feel like a behemoth and its 4 MATIC all-wheel drive system means that this hybrid will be able to get through any future beastly snowstorms we may be faced with. You can also charge it at home in around two hours 30 minutes if you have a 7kW wall box. The GLC kicks off at €62,300, which is right in the sweet spot for premium crossovers. Irish people love Mercs, diesels, crossovers, and hybrids, so I feel these GLCs will sell extremely well.
If you love a bit of the black stuff, but also want to save the world, then this diesel hybrid is for you.
Inside the GLC you will find the expected, refined, Mercedes feel, with all of theleathers and plastics having a premium look and touch
MERCEDES-BENZ GLC 300 DE
4MATIC €62,300
Model: GLC 300 de 4MATIC
Version: GLC 300 de 4MATIC AMG Line
Exterior/Exclusive Line Interior
Engine: 1,950cc, 4-cylinder,194hp. Electric motor 122hp.
0-100km/h in 6.2 seconds,
Top speed of 230km/h
Fuel consumption (combined):
1.8 – 2.0 l/100km
Fuel Type: Diesel plug-in hybrid
CO2: 49 g/km
Road Tax: €140 (VRT Band 1 7 per cent VRT)
Transmission: 9G-TRONIC automatic
transmission
Colour: High-tech silver metallic
Upholstery: ARTICO Leather in black/anthracite
MERCEDES-BENZ GLC 300 DE
4MATIC
Standard Equipment: 2 USB ports in the rear
Four-way lumbar support
Acoustic ambient protection
Active brake assist
Adaptive brake lights
Advantage package
AMG bodystyling consisting of:
Two visible tailpipe trim elements integrated into the bumper
AMG front apron with sporty air intakes and chrome trim element
Charging cable for domestic socket, 5m, straight
Charging cable for wallbox and public charging stations, 4m, straight
Communications module (LTE) for the use of Mercedes me connect services
Cruise control
Dashboard and door beltlines in ARTICO leather
Digital radio
Double cup holder
DYNAMIC SELECT
EASY-PACK tailgate + load compartment cover
Electrically folding exterior mirrors Entry/exit lighting in the exterior mirrors
EXCLUSIVE interior
Extended MBUX functions
Hard-disc navigation
Heated front seats
Heat-insulating dark-tinted glass
Interior light package
Interior mirror and driver’s exterior mirror automatically dimming
KEYLESS GO starting function
Kneebag
LED high performance headlamp
MBUX multimedia system
Mercedes-Benz emergency call system
Mirror package
Multifunction leather sports steering wheel
Navigation connectivity package
Parking package with reversing camera
PARKTRONIC parking assist
Remote services
Reversing camera
Roof liner in crystal grey fabric
Seat comfort package
Smartphone integration
(Android Auto + Apple CarPlay)
Steering wheel shift paddles
THERMATIC automatic climate control
Touchpad
Velour floor mats
Windscreen wipers with rain sensor
Mercedes-Benz GLC 300 de 4MATIC €62,300
Optional extras
Night package €220
19 inch AMG 5-twin-spoke light-alloy wheels in high-gloss black with a high-sheen finish
Beltline trim strip and window line trim in high-gloss black
Door panelling (cladding) in black with inserts in high-gloss black
Exterior mirror housings painted in black
Heat-insulating dark-tinted glass starting from the B-pillar
Radiator grille with diamond grille with silver-coloured pins and louvre in high-gloss black
Roof rails in black
Underguard at front and rear apron in black
Trim in Black
Open-pore Ash Wood €323
Mercedes-Benz GLC 300 de 4MATIC
Price €62,843
Nurse required for practice nurse position in our North Dublin GP surgery. Flexible hours to include mornings, experience preferable in childhood immunisations, phlebotomy, and cervical smear services. Role supported by healthcare assistants and our GP team.
Surgery located on Navan Road, Dublin, in a modern purpose-built GP practice.
Competitive permanent package available along with training opportunities supported.
Enquiries should be sent to info@milligan.ie or call 087 125 1815
Practice nurse required for GP surgery in Dublin 5
Tonlegee Medical Practice
Flexible hours. Two-doctor practice Helix practice manager software
Candidate would ideally be confident in adult and childhood immunisations, phlebotomy, and the taking of cervical smears would be an advantage.
Previous experience in a GP clinic an advantage. Active NMBI registration (RGN) required. Friendly colleagues and pleasant working environment.
Applicants to kindly forward CV and details with a cover letter telling us about you and your nursing experience.
Job types: Full-time, Part-time, Permanent Salary: €38,000.00-€45,000.00 per year
Schedule:
• Eight-hour shift
• Monday to Friday
• No weekends
Please email CV to dranthonycrosse@gmail.com
Long established two-doctor GP training practice North Meath area seeks assistant. Flexible options available. Fully computerised, supported by excellent nursing and administrative staff. Excellent package including genuine partnership opportunity if desired.
Please email cv to drjameskeenan@gmail.com or phone 086 814 0136 for informal enquiries
GP REQUIRED
Vocationally trained GP required for Sutton Cross Surgery. 4–6 sessions. Flexible, friendly, coastal, Dublin teaching practice with a mix of GMS/ private patients. We are fully computerised using Health One software and 15-minute appointments. Supported by excellent nursing and administrative staff. An attractive package is available for suitable candidates.
Enquiries or CVs to manager@suttoncrosssurgery.ie or 01 832 6438
GP REQUIRED
Well-established GP practice requires a GP for 6+ sessions per week with a view to full-time employment in Donegal Town. Group practice/fully computerised/full ancillary staff. Email enquires to millrowfamilypractice@gmail.com
SHANE O’TOOLE
Specialist Medical Accountant, RCSI Lecturer and author of Fit money - the key to financial freedom
Now offering:
• Monthly Profit Growth Model
• Annual Accounts and Tax Returns
• Outsourced Bookkeeping and Payroll
• Support in Selling and Buying a Practice
Contact 01 801 3116 for help and support
GP REQUIRED
GP required for a well-established practice in East Galway (6-8 Sessions). 20-minute commute from Oranmore.
Fully computerised with Socrates and great practice support. Generous remuneration available to the right candidate.
Contact our Practice Manager Mary on 091 842144 or 087 2035825 or email your CV to maryhoran.mh@gmail.com
Applications are invited for the College of Psychiatrists of Ireland accredited National Higher Training Schemes in: (i) Child and Adolescent Psychiatry and (ii) Specialties of Adult Psychiatry
Applicants are also invited to apply for a part-time/flexible training. Details on how to apply are available on the College’s website www.irishpsychiatry.ie
The Competition will open for applications on Friday 26th November and will close on Friday 14th January 2022
Shortlisting will apply and will be based on information supplied by applicants on their application form.
Successful applicants must be entered on the Trainee Specialist Division of the Medical Register maintained by the Medical Council of Ireland by 11th July 2022 to take up their appointment.
Interviews for shortlisted candidates will take place in February 2022 for both Adult and CAP.
On the Medical Council of Ireland’s “Your Training Counts” National Trainee Survey, training in Psychiatry has received the highest D-RECT score (overall Trainee satisfaction) for the last two years.
If you have anything you would like to share, please email: info@mindo.ie
A round-up of news and oddities from left field by Dr Doug
Witherspoon
Up to the 1800s, doctors traditionally wore black or beige coats during the course of their work. When exactly this changed is a matter of discussion, but around the beginning of the 19th Century, the white coat was introduced as the standard 'uniform' for doctors. Not because of the most ob-
vious reason that all kinds of unpleasantness could be concealed by a black coat – rather, it was to distinguish doctors from dodgy snake-oil salesmen who would dupe members of the public with their 'medical expertise'. Around this time, the role of bacteria in the transmission of disease also began to be recognised and so the doctor's white coat was born.
Saturday,
Speakers
The first to don the white coat were surgeons, followed by other hospital doctors, and finally GPs. But is there a chance that wearing that symbol of medical expertise might actually make you just a little bit more sharp and/or intelligent? There have been many studies on how what we wear affects how we are perceived, but there haven't been as many to examine the effects it has on the wearer.
However, a 2017 study suggests wearing a lab coat may actually confer a cognitive benefit. Researchers at Northwestern University in the US organised a series of three experiments, the first of which featured 58 undergraduate students, half of whom wore a white lab coat. All participants were then asked to undertake the Stroop test, in which they were shown random differently-coloured words and asked to name the colour, rather than pronouncing the word itself. Some of the words were presented in an incongruent manner. For example, the word 'red' may have been presented with blue-coloured letters.
The people wearing the white coats were found to make approximately 50 per cent less errors than their plainclothed counterparts.
But was it the white coat itself, or the medical connotation that made the participants perform better? To address this question, the researchers did another experiment with 99 students. In this one, one-third of the group were told they were wearing a doctor's coat; another one-third were told it was a white coat worn by an artist whilst painting; and the rest were in plain clothes, but had what they were told was a white doctor's coat placed on the desk in front of them.
All were asked to write a brief essay on what a coat like that signified for them, after which they underwent four visual tests, whereby two almost identical pictures were presented to them and they were asked to write down the differences between the images as quickly as possible.
Agenda
Session 1 | 9 am – 10:25 am
Why Muscles Hurt and What You Can Do About It
– Dr. Dominic Hegarty
New Technologies Addressing the Pain of Knee Arthritis
– Mr. Pádhraig O’Loughlin
Modern Management of Hip & Knee Pain
– Mr. Karuppiah Mahalingam
Presentations followed by Panel Discussion / Q&A –moderated by Dr. Sonu Rathi (GP · Carrigaline, Co Cork) & Dr. Emer Byrne (GP · Kells, Co Meath)
Registration on www.materprivate.ie/news-events/events/ For more information, email events@materprivate.ie
Session 2 | 10:25 am – 11:45 am
Virtual Back Pain
– Mr. Derek Cawley
Stratified Physiotherapy
Treatment for Low Back Pain
– Ms. Martina O’Reilly
Rheumatology Case History
Miscellany
– Dr. Barry Sheane
The results showed that all groups took roughly the same time to finish the tests. But the participants who were informed that they were wearing a doctor's coat spotted more differences than their peers who were wearing an 'artist's' coat. The ones in plain clothes scored somewhere in between the two other groups.
Whilst the results are curious and novel, they also raise perhaps more questions than they answer, said the lead researchers Adam Galinsky and Hajo Adam. For example, “does wearing the robe of a priest or judge make people more ethical?” they wrote. “Does putting on the uniform of a firefighter make people act more courageously? And perhaps even more interestingly, do the effects of physically wearing a particular form of clothing wear off over time, as people become habituated to it?”
They termed this phenomenon 'enclothed cognition'. But why choose a doctor's coat for the test? It is “the prototypical attire of scientists and doctors. Wearing a lab coat thus signifies a scientific focus (and conveys) the importance of paying attention to the task at hand and not making errors,” wrote Adam and Galinsky. “The main conclusion that we can draw from the studies is that the influence of wearing a piece of clothing depends on both its symbolic meaning, and the physical experience of wearing the clothes,” they summarised. “There seems to be something special about the physical experience of wearing a piece of clothing.”
Of course, there is the other burning question of whether patients prefer doctors to wear white coats or not, but research into that will be reported in another Dorsal View
