With a new model of care and planned developments in hospital and primary care, David Lynch looks at the future of obesity services
The Irish Blood Transfusion Service’s Medical and Scientific Director Dr Stephen Field speaks with Pat Kelly about the challenges of maintaining blood supply during Covid-19
PAGE 10-12
Results of a study, released at the recent 72nd Irish Cardiac Society (ICS) Annual Scientific Meeting and AGM, suggest a significant degree of sexism and bullying in Irish cardiology.
The study, titled ‘Perceptions of equality, flexible working and mentorship amongst Irish cardiology trainees and consultants’, was presented at the meeting by Dr Bethany Wong, Cardiology SpR, during her talk on behalf of the ‘women in cardiology subgroup’.
Dr Wong and her colleagues distributed a survey to all ICS trainees and consultants in both the North and Republic of Ireland.
Almost 80 per cent of female respondents said they had experienced sexism during their training.
“This is much higher than the
UK survey that was published earlier this year, which reported 48 per cent,” said Dr Wong.
When asked if they felt they had missed out on professional opportunities due to their sex, 84 per cent responded ‘No’.
“But of the 16 per cent who said ‘Yes’, there was a statistically significant difference between females and males, with more women missing professional opportunities than their male counterparts,” she told the conference.
Also, Dr Wong said the results showed how women had higher childcare responsibilities, which had an impact on their careers.
“There is a high workload in cardiology,” she told the meeting. “This can sometimes make it difficult to manage childcare responsibilities, and one potential solution is working less than fulltime… an equal amount of males
and females said they would like to go less than full-time training, with the main reason being family and work-life balance.”
However, 63.83 per cent of respondents said they did not think their department would be supportive of them working less than full-time, while 20.21 per cent said they would be supported, and 15.96 per cent were ‘unsure’.
More than 48 per cent of respondents said they had experienced bullying during their training or career, with no difference between males and females.
There were 94 respondents, comprising almost one-third of all ICS trainees and consultants, over a two-week period. Fifty per cent females and 50 per cent males responded to the survey, which was supported by the ICS. See P32-36 for full conference coverage.
There has been no significant change in the past six months in the number of consultants employed by the HSE who are not on the Medical Council’s specialist register.
As of 11 October, there were 105 consultants employed by the HSE not on the specialist register, according to new information provided to the Medical Independent (MI). The figures are the first available since late April as the cyberattack disrupted the DIME (Doctors Integrated Management E-system) from which the data is extracted.
The 105 figure represents a small decrease from 109 at the end of April, which was previously reported in MI . Following HSE site visits in 2018/2019, some 153 consultants were found not to be specialist-registered.
“Currently there are 3,723 consultant application advisory committee-approved consultant posts,” said a HSE spokesperson. “DIME is dependent on clinical sites inputting details on their consultant workforce and therefore there may be variances and gaps in the data supplied to that held within clinical sites.”
General medicine accounts for the highest number of doctors not on the specialist register, at 32. This is followed by psychiatry with 23, surgery with 17, anaesthesiology with 11, emergency medicine with seven, obstetrics and gynaecology with five, paediatrics with four, radiology with four, and pathology with two.
In terms of Hospital Groups/Community Healthcare Organisations (CHOs) with consultants not on
the specialist register, Saolta University Health Care Group and South/South West Hospital Group are joint top with 22; followed by Dublin Midlands Hospital Group with 11; RCSI Hospital Group and CHO 8 have nine consultants each; and Ireland East Hospital Group and University of Limerick Hospital Group have seven each. The remaining Hospital Groups and CHOs have fewer than seven consultants each not on the specialist register.
In July, a HSE spokesperson told MI that when the Regulated Professions (Health and Social Care) (Amendment) Act 2020 is commenced, “it is expected the number of consultants not on the specialist division will continue to reduce.”
They said the HSE had “put in place protocols to ensure the number of consultants not on the specialist division do not increase”. In addition, “monthly monitoring” of the number is taking place.
Writing in MI last month on the eve of the IHCA annual conference, Association Secretary General Mr Martin Varley stated that the consultant “recruitment crisis has also manifested itself” in the appointment of doctors to consultant posts who are not on the Medical Council specialist register.
“This is a serious indictment of Government policy and is gravely damaging the delivery of timely, quality care to patients, as outlined by the former President of the High Court, Justice Peter Kelly, to then Minister Simon Harris and health service management in May 2018,” according to Mr Varley.
“The issue has more recently been described as ‘very serious’ by the HSE in terms of the risk it poses to patient safety and quality of care.”
Covid-19 has exacerbated the over-production of research, according to Prof Seamus O’Mahony
PAGE 20
CV risk LDL-C target
High** <1.8mmol/L
Very High* <1.4mmol/L
Lipocomb® (rosuvastatin (as zinc)/ezetimibe) Abbreviated Prescribing Information: Please refer to the Summary of Product Characteristics before prescribing. COMPOSITION* Lipocomb 10 mg/10 mg: hard capsule containing 10 mg rosuvastatin (as zinc) and 10 mg of ezetimibe. Lipocomb 20 mg/10 mg: hard capsule contains 20 mg rosuvastatin (as zinc) and 10mg of ezetimibe.
INDICATIONS*As adjunct to diet for treatment of primary hypercholesterolemia as substitution therapy in adult patients adequately controlled with the individual substances given concurrently at the same dose level as in the fixed dose combination, but as separate products. DOSAGE AND ADMINISTRATION*
Recommended daily dose is one capsule of the given strength with or without food. Lipocomb is not suitable for initial therapy. Treatment initiation or dose adjustment if necessary, should only be done with the monocomponents and after setting the appropriate doses the switch to the fixed dose combination of the appropriate strength is possible. Lipocomb 10 mg/10 mg and 20 mg/10mg hard capsules are not suitable for the treatment of patients requiring 40 mg dose of rosuvastatin. Children and adolescents: < 18 years should not be used. Elderly (age>70 years), moderate renal impairment (Clcr < 60 ml/min), race (Asian ancestry) and predisposing factors to myopathy: Start dose of 5 mg rosuvastatin is recommended. Mild to moderate renal impairment: no dose adjustment. Severe renal impairment (Clcr <30 ml/min): contraindicated. Hepatic impairment: Mild hepatic impairment (Child Pugh score 5 to 6): no dose adjustment. Moderate (Child Pugh score 7 to 9) or severe (Child Pugh score >9) liver dysfunction: not recommended. Active liver disease: contraindicated. Genetic polymorphisms: a lower daily dose is recommended. Co-administration: contraindicated with ciclosporin, not recommended with combinations of ritonavir with atazanavir, lopinavir, and/or tipranavir (full list in section INTERACTIONS* below). CONTRAINDICATIONS* Hypersensitivity to the active substances (rosuvastatin, ezetimibe) or to any of the excipients, active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 times the upper limit of normal (ULN), during pregnancy and breast-feeding and in women of childbearing potential not using appropriate contraceptive measures, severe renal impairment (creatinine clearance <30 ml/min), myopathy, concomitant ciclosporin. (see WARNINGS* INTERACTIONS* and PROPERTIES*). WARNINGS *Skeletal Muscle
Effects: Stop treatment if muscular symptoms with elevation of CK level > 5 xULN occur or if muscular symptoms are severe and cause daily discomfort (even if CK levels are ≤ 5 x ULN). Caution should be exercised when Lipocomb is used with fibric acid derivatives including gemfibrozil, ciclosporin, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Increased risk of myopathy with concomitant use of gemfibrozil. Co-administration with gemfibrozil is not recommended. Co-administration with systemic formulations of fusidic acid or within 7 days of stopping the treatment is not recommended. If the use is essential, Lipocomb
should be discontinued during fusidic acid treatment. Liver effects: Liver functions tests should be carried out 3 months following the initiation of rosuvastatin treatment. Stop treatment or reduce the dose if jaundice, hepatitis or marked elevation of hepatic enzymes (serum transaminases exceeding 3 times the upper limit of normal). Lipocomb use is not recommended in patients with moderate to severe hepatic impairment. Renal effects (proteinuria): Monitoring by dipstick testing recommended for patients treated with higher doses of rosuvastatin, in particular 40 mg. Race: Lipocomb may cause an increase in exposure in Asian subjects compared with Caucasians. Protease inhibitors: Concomitant use with certain protease inhibitors is not recommended unless adjustment. Interstitial lung disease: If suspected, treatment should be discontinued. Diabetes mellitus: Patients at risk (fasting glucose 5.6 to 6.9 mmol/L, BMI > 30 kg/m2, raised triglycerides, hypertension) should be monitored. Fibrates: If cholelithiasis is suspected in case of concomitant use with fenofibrate, treatment should be discontinued. Anticoagulants: If Lipocomb is added to warfarin, another coumarin anticoagulant, or fluindione, the INR should be appropriately monitored. Ciclosporin: Lipocomb is contraindicated in patients receiving concomitant ciclosporin. Paediatric population: not recommended in children < 18 years. Liver disease and alcohol: Use with caution in patients who consume excessive quantities of alcohol and/or have history of liver disease. INTERACTION(S)*Contraindicated: Ciclosporin. Not recommended combinations: protease inhibitors (e.g.atazanavir / ritonavir), transporter protein inhibitors (hepatic uptake transporter OATP1B1 / efflux transporter BCRP), gemfibrozil and other lipid-lowering products (fibrates and niacin(nicotinic acid)), fusidic acid. Precautions: Antacid, erythromycin, cytochrome P450 enzymes(inhibitor / inducer), vitamin K antagonists (e.g. warfarin or another coumarin anticoagulant), oral contraceptive/hormone replacement therapy (HRT), colestyramine, statins (atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin or rosuvastatin), other medicinal products(dapsone, dextromethorphan, digoxin, glipizide, tolbutamide, midazolam, cimetidine). PREGNANCY AND BREASTFEEDING*: Lipocomb is contraindicated in pregnancy and breastfeeding. FERTILITY* CONTRACEPTION* Women of childbearing potential should use appropriate contraceptive measures. DRIVE & USE MACHINES* Dizziness may occur. UNDESIRABLE EFFECTS* Common: Diabetes mellitus, headache, dizziness, constipation, nausea, abdominal pain, diarrhoea, flatulence, myalgia, asthenia, fatigue, ALT and/or AST increased. Uncommon: Decreased appetite, paraesthesia, hot flush, hypertension, cough, dyspepsia, gastrooesophageal reflux disease, dry mouth, gastritis, pruritus, rash, urticaria, arthralgia, muscle spasms, neck pain, back pain, muscular weakness, pain in extremity, chest pain, pain, oedema peripheral. Rare: Thrombocytopenia, hypersensitivity reactions including angioedema, pancreatitis, myopathy (including myositis), rhabdomyolysis, lupuslike syndrome, muscle rupture. Very rare: Polyneuropathy, memory loss, jaundice, hepatitis, arthralgia, haematuria, gynecomastia. Not Known: Hypersensitivity
(including anaphylaxis and angioedema), depression, peripheral neuropathy, sleep disturbances (including insomnia and nightmares), dyspnea, cholelithiasis, cholecystitis, Stevens Johnson syndrome, erythema multiforme, immune-mediated necrotising myopathy, tendon disorders, sometimes complicated by rupture. OVERDOSE*. PROPERTIES* Rosuvastatin is a selective and competitive inhibitor of HMG CoA reductase, the rate-limiting enzyme that converts 3-hydroxy3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. Ezetimibe is in a new class of lipid-lowering compounds that selectively inhibit the intestinal absorption of cholesterol and related plant sterols. PRESENTATION* Packs of 30hard capsules. Marketing Authorisation Holder: EGIS Pharmaceuticals PLC, Kereszturi ut 30-38, H-1106 Budapest, Hungary. Marketing
Authorisation Number: PA1470/004/001002. Legal Classification for Supply: POM. Local Representative in Ireland: Servier Laboratories (Ireland) Ltd, Second Floor, 19 Lr. George’s Street, Dun Laoghaire, Co. Dublin A96 ER84, Ireland. Tel (01) 6638110, www.servier.ie.
*For complete information, please refer to the Summary of Product Characteristics available on www.medicines.ie
Date of last revision of the text: June 2021 (Date of last approved
SmPC: March 2019) Date of Preparation September 2021, 2122 C1 LCB Press Ad CBU.
* For complete information, please refer to the complete Summary of Product Characteristics for Lipocomb® at www.hpra.ie
1. Mach et al. 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias, European Heart Journal (2019) 00, 1-78’ * Patients with: documented CVD, Diabetes Mellitus with organ damages, Severe CKD (chronic kidney disease), a calculated 10 year risk of fatal CVD ≥ 10%, Familial Hypercholesterolaemia with CVD/risk factor. **Patients with: Markedly elevated single risk factors (in particular cholesterol > 8mmol/L or BP ≥ 180/110 mmHg), Familial Hypercholesterolaemia, Diabetes Mellitus, Moderate CKD (chronic kidney disease), a calculated 10 year risk of fatal CVD ≥ 5% and <10%.
Get your patient’s LDL-C down even lower to <1.8mmol/L1
Women’s health would currently be the most suitable addition to the chronic disease management (CDM) programme for general practice, the Chair of the IMO GP committee has said.
Dr Denis McCauley said the “vast majority” of GPs had opted into the CDM programme agreed between the IMO, HSE and Department of Health in 2019.
The current programme covers specific chronic diseases including type 2 diabetes, asthma, chronic obstructive pulmonary disease, and cardiovascular disease.
Dr McCauley said if the programme was to be expanded in the future, he believed women’s health should be next. This could be followed by psychiatric and psychological care. He told the Medical Independent (MI) he considered there were insufficient support services for patients with obesity for this area to be added to the programme.
The CDM programme in general practice was “a very good system”, stated Dr McCauley.
“It is a system we would have been advocating for many years as part of the IMO GP deal that involved its introduction and the beginning of the process of the reversal of FEMPI,” Dr McCauley told MI. He added from a workforce
A “national approach” is required for the safe return to practice for interns following extended leave, heard a meeting of the Medical Intern Board (MIB).
There have been five interns over the past 10 years who have sought to return to intern training after taking extended leave, which is mainly taken for personal reasons, the HSE informed the Medical Independent Currently each case is dealt with on an individual basis by the relevant medical school and associated Intern Training Network.
At a MIB meeting in May, Clinical Lead Dr Gozie Offiah advised of queries received regarding interns returning to internship following extended leave. A meeting had been arranged with the Medical Council to discuss this further.
According to minutes, it was agreed at the MIB meeting that “a process for safe return to practice needs a national approach and integrating back into the system is resource intensive”. While there were return to work options at postgraduate level, this was not the case at intern level.
At intern stage, any pathway would have to take account of “potential patient safety issues and evidence regarding the individual knowledge, skills and professionalism of candidates who have never been in clinical practice for an adequate minimum period of time”.
Meanwhile, the MIB’s meeting in July heard that plans to implement a “health passport” for interns to allow them to declare health issues (similar to a UK model) had been discussed with the HSE Workplace Health and Wellbeing Unit.
However, this proposal “has not been supported as the policy currently is that interns should not be treated differently to other groups of employees”, for whom there were supports available and a process through occupational health to declare any issues.
The MIB meeting agreed that interns needed support in the transition from student to doctor and it was decided a brief would be prepared.
point of view, the reversal of FEMPI would “hopefully stabilise general practice to the extent of being able to attract young GPs in”.
“But if you look at it from a patient point of view, it makes sense that all chronic disease management starts in gener-
al practice... remember this was always done in an ad-hoc basis, but this [programme] makes it more formalised and there is more evidence base behind it. I think the reception from doctors and from patients has been very positive.” See news feature, p4-5.
A. Menarini Pharmaceuticals Ireland Ltd. wish to remind healthcare professionals of the necessary precautions to avoid the risk of photosensitivity reactions with Fastum Gel.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) undertook a safety review of topical ketoprofencontaining medicines in 2010 and recommended that doctors should strictly follow the contraindications when prescribing topical ketoprofen. CHMP also recommended that doctors and pharmacists should inform patients on how to use these medicines appropriately to prevent the occurrence of serious skin photosensitivity reactions. A series of risk minimisation measures for Fastum Gel was agreed with the Health Products Regulatory Authority. The Summary of Product Characteristics and the Patient Information Leaflet were updated accordingly and may be found on www.medicines.ie and www.hpra.ie.
Patients should be reminded to wash their hands thoroughly after application of the product and to protect treated areas from sunlight by wearing clothing. They should avoid exposing the treated areas to sunlight, even if cloudy, or UVA from sunbeds or solarium during use and for 2 weeks after discontinuation. In addition they should be advised to avoid using Fastum Gel under occlusive bandages and to discontinue Fastum Gel immediately and contact their doctor should any skin reaction develop, including cutaneous reactions after co-application of octocrylene-containing products.
A copy of the patient educational leaflet is available from A. Menarini on 01 284 6744 or 1800 283045 or is available at www.hpra.ie
A. Menarini would like to remind healthcare professionals that any suspected adverse reactions associated with the use of Fastum Gel should be reported to the Health Products Regulatory Authority at www.hpra.ie or by e-mailing medsafety@hpra.ie. Adverse reactions can also be reported to A. Menarini’s Pharmacovigilance Department on 01 284 6744.
‘National
With a new model of care and planned developments in both hospital and primary care settings, David Lynch looks at the future of obesity services in Ireland
With the health service consumed by the pandemic since March 2020, it is understandable that many doctors fear that their own particular specialty will struggle to garner attention and funding during the crisis.
“I thought when the pandemic began that ‘now that’s it, obesity is off the table for progress on policy for the next few years’,”
Prof Donal O’Shea, HSE National Clinical Lead for Obesity and Consultant Endocrinologist and Physician, told the Medical Independent (MI)
“But quite the opposite has happened. Because of the link between being overweight, obesity and poor outcomes with Covid-19, it seemed to have hit the policymakers in the face, with the need to address both prevention and treatment.”
The feedback from ICUs was that Covid-19 patients with obesity “were staying in the ICU longer and their outcomes are poorer and their rehab takes longer”.
Prof O’Shea said that because obesity has been linked to poor outcomes with Covid, it has proven “a wake-up call” for many in health management.
The public health challenge posed by obesity was recognised prior to the onset of the Covid crisis. According to HSE figures, 60 per cent of adults and 20 per cent of children in Ireland are living with overweight or obesity.
While there are serious issues around funding, policy formation and resources, Prof O’Shea warned that stigma remains a particular concern within obesity care.
Last month, the HSE hosted a virtual event titled ‘Overweight and Obesity... Let’s Talk!’. It was organised by the HSE Obesity Management Clinical Programme, the As-
be done,” Prof O’Shea said. While “there has been some progress”, there is a “widely held bias” towards patients with obesity that is found across society, including in medicine.
“Patients with obesity experience almost the most discrimination in the health system,” he told MI. “We have to get in at undergraduate level [in medical schools]. The ICPO and the ASOI are really looking for this to happen.
“Then within the HSE, greater awareness also needs to happen with a new module for addressing overweight and obesity, specifically and especially the stigma and judgement that goes with it.”
self-discipline and lack of motivation. But that is just not the case. The reality is that your body tries to protect its fat stores to maintain your highest weight – meaning that managing obesity is a lifelong process. Genetics are increasingly recognised to be a major contributor to body weight.”
The battle against stigma is not just about creating awareness and education, he underlined.
“I think the biggest push has to be around treatment,” said Prof O’Shea. “If you are actively treating the condition, people begin to see it as a disease. Not because their attitude changes to the disease, but because they see people who have been treated and they see how well they are.
“They realise that it wasn’t because they [the patient with obesity] didn’t want to get well. They realise that body weight is not a person’s choice and I think that is the big move in how we are trying to destigmatise the condition. If body weight was a choice, we would not have people living with severe and complex obesity.”
that an end-to-end approach is adopted, defining the way health services are developed over time”. He said it would “ensure that the right care is delivered to individuals with overweight and obesity at the right time and in the right place”.
However, currently bariatric surgery figures remain low (see panel). In the community, primary care has witnessed important changes in recent years with the roll-out of a new chronic disease management programme, which GPs can opt into. The first phase of the programme targeted GMS patients, aged over 75 years, with specific chronic diseases including type-2 diabetes, asthma and chronic obstructive pulmonary disease (COPD). Cardiovascular disease is also part of the programme and includes heart failure; ischaemic heart disease; cerebrovascular disease (stroke/ transient ischemic attack); and atrial fibrillation.
sociation for the Study of Obesity in Ireland (ASOI) and the Irish Coalition for People Living with Obesity (ICPO). The event was for the public and healthcare professionals “to share the science behind obesity” and to “continue to break the stigma of obesity through sharing lived experiences and explore conversations about weight and health in healthcare settings”.
“There is massive education work to
Such a module will form part of the HSE’s Make Every Contact Count programme, added Prof O’Shea.
Stigma
“Obesity is a complex chronic disease for which there are a lot of different causes,” he commented.
“Many people believe that obesity is a lifestyle choice, which is due to poor
Treatment of obesity is primed for a significant shake-up with the publication of the new HSE Model of Care for the Management of Overweight and Obesity in Ireland on World Obesity Day in March. This model of care sets out how healthcare for children, young people and adults living with overweight and obesity in Ireland should be organised and resourced, now and into the future.
Speaking earlier this year, Minister of State with responsibility for Public Health, Wellbeing and the National Drugs Strategy, Frank Feighan, said the model “will ensure
Obesity is noted by its current absence. However, the HSE has given some indication through the publication of the new model of care that it may feature in the programme in the future.
“The HSE National Service Plan 2021 seeks to take forward plans to implement the end-to-end obesity model of care with a joined-up approach towards delivering weight management and obesity treatment,” Ms Sarah O’Brien, National Lead, Healthy Eating and Active Living Programme, HSE Health and Wellbeing, said recently. “A structured programme for chronic disease management and prevention for all general medical/GP visit card patients will be introduced over time.”
Patients with obesity experience almost the most discrimination in the health systemProf Donal O’Shea
“Investment in community services will see community weight management services, delivered by dietitians, available in many areas. Training for healthcare staff to help them talk with patients living with overweight and obesity about healthy lifestyles will be available as part of Making Every Contact Count by the end of the year.”
GPs’ views
So, what do GPs think? “Chronic disease management is a good idea if general practice can have a significant input into that,” Dr Denis McCauley, Chair of the IMO GP com-
mittee, told MI
The Donegal GP said the “reception from doctors and from patients” to the current chronic disease management programme
“has been very positive”.
Dr Denis McCauleyHowever, he drew attention to the need for availability of other services to undertake a successful programme for obesity care in general practice.
“Say you don’t have access to a dietitian,
To date in 2021, there were 42 bariatric surgeries in St Vincent’s University Hospital (SVUH), Dublin and 18 bariatric surgeries in St Michael’s Hospital, Dún Laoghaire. During the same period (up until October) there were 13 bariatric procedures at University Hospital Galway (UHG), according to figures provided to the Medical Independent
All elective surgery has been hit hard by the disruption caused by the pandemic, but bariatric surgery figures were regarded as low prior to Covid-19.
“Ireland is way behind the curve,” said Prof Donal O’Shea, HSE National Clinical Lead for Obesity. “We have averaged between about 12 and 20 surgeries per million of our population over the last 10 years and other countries are sitting at 140 or a 180 per million. So we are hoping to build up to 1,200 surgeries per year. That will build it up to a low level of respectability.”
With the approval of the new model of care and the “prioritising of obesity” in the HSE Corporate Plan, he is hopeful that surgeries will increase.
“Obesity surgery needs to happen in the context of a multi-disciplinary team,” he said. “So you cannot do it properly
if you don’t have the right dietitian, the right psychological support, GP funding.”
Speaking in March on World Obesity Day, Dr John Conneely, Consultant Surgeon specialising in bariatric surgery at the Mater Private Network, Dublin, warned that Covid-19 is likely to increase the incidence of obesity in Ireland.
Dr Conneely urged the Department of Health and HSE to urgently address the challenges that patients with obesity experience when trying to access weight loss and weight management care.
“For those with chronic obesity waiting for bariatric surgery, waiting lists have grown and their condition has worsened,” he said in March. “We have incontrovertible evidence from global experience that bariatric surgery can be transformative for patients and prevent or reduce the incidence of other conditions, such as diabetes or heart disease, making them also more costeffective for our health services.
“As we begin to emerge from Covid-19 our health services now must plan and adequately resource the services patients suffering from obesity need to quickly access supports to achieve and maintain a healthy weight.”
One of the most high-profile public health measures introduced in recent years was the Sugar Sweetened Drinks Tax (SSDT), which came into effect on 1 May 2018 and was applied to waterand juice-based drinks, which have added sugar and a total sugar content of five grams or more per 100 millilitres (from 2019 it also applies to certain categories of plant protein drinks and drinks containing milk fats).
Prof Donal O’Shea, HSE National Clinical Lead for Obesity, reflected that “in its short time it has generated income and driven reformulation... loads of sugar sweet drinks have less sugar... and that’s fantastic.”
But he said it was a “huge disappointment” that the money raised from the SSDT “wasn’t ringfenced or wasn’t parked to go into obesity treatment and prevention, even though it was an opportunity when the tax was
introduced a few years ago”.
If he had a magic wand and could introduce any other public health policy, what would it be?
“I think calories posting on menu boards is a fantastic educational tool. It has been agreed, it has been approved, but the legislation is still stuck. It’s 10 years since we started actively looking for calorie posting.” Prof O’Shea made reference to “massive industry opposition to it.”
As well as major public policy reforms, Prof O’Shea also pointed to the more subtle art of influence.
“I think of the likes of [Cristiano] Ronaldo earlier in the year pushing the Coke to one side [during a press conference] and bringing the water in. I think if you could have significant influencers demonstrating just where industry is not behaving, I think that reaches a big audience.”
to a metabolic clinic, to surgery, we would sort of be sitting there saying [to the patient], ‘It’s really good to see you, but I’m not so sure what I can do for you, more than give you supportive care and general advice regarding diet and exercise’.
“So yes, I think if we were given ‘weapons’ to use and we had access to services in relation to the treatment of obesity and if we had further education on that, I think it would be very successful.”
However, Dr McCauley told MI that obesity would most likely not be the next area to be added to the chronic disease programme. If the programme was to be expanded in the future, he believes women’s health should be next, then possibly psychiatric and psychological care. He argued there are insufficient support services for patients with obesity to facilitate its addition to the programme.
“The thing with the introduction of the other diseases [on the current programme] was there were well-established pathways, well-established principles of treatment. Does the same format exist for obesity yet? No.
“Does it exist in regards women’s health and, say, some psychological and psychiatric disorders? Yes – although even in psychiatric care you are getting some fraying [in services] as well.”
In summary, if obesity is added to the chronic disease programme, it would have to be in the context of “availability of evidence-based treatments that would help”.
Dr McCauley said that current waiting lists for dietitians “are very long” and the lack of specialised obesity clinics in the country is another challenge. “So if suddenly GPs were told they were looking after it, they would say ‘where’s the clinic?’ and there is a waiting list of two years. That isn’t a great start.”
Despite the challenges, the shifting of chronic disease, including obesity, towards primary care is widely supported across medicine and “is beginning to happen already”, Prof O’Shea said.
He said the trend is in alignment with the goals of Sláintecare. Prof O’Shea pointed to the recruitment of more dietitians and the development of an adult weight management programme and a pre-diabetes programme in the community, as examples of progress.
“They are incredibly positive steps towards acknowledging that obesity is a chronic disease and that we need to address it, not just by telling somebody that they need to eat less and move more.”
Despite recent changes in attitudes towards obesity care and a renewed focus on the issue, Prof O’Shea added that he still encounters old ways of thinking.
“I was at a very senior meeting about three or months ago now, while we were on a final push about estimates, and I was met with the line ‘It’s a pity, because we do know if they just ate less and moved more’ [obesity would not be such an issue],” he recounted.
“And I was struck by that. In 2021 a senior health official who was important in decision-making [saying that] and I thought to myself, ‘God, other healthcare systems are moving beyond that’.”
Prof O’Shea said that the coming weeks and months will reveal much as to whether the model of care will be fully implemented.
10,000 safeguarding concerns were notified to the HSE in 2020, which is a 9 per cent decline on the figure for 2019, according to the 2020 National Safeguarding Office Report.
51,000 concerns were notified to the HSE safeguarding teams between the years 2016-2020.
20 million euro in new development funding is to be made available for cancer services in Budget 2022.
1 -in-five people in Ireland know the most vital action to take in the event of a stroke, according to a new poll conducted by the Irish Heart Foundation.
43 per cent of people are unaware of any of the four key warning signs of stroke.
320,000 Covid-19 vaccines have been administered by pharmacies since July, according to a statement from the Irish Pharmacy Union on 20 October.
The latest analysis of future demand for GPs has estimated an increase from approximately 200 to over 500 trainees annually is required in general practice over the next five years, not accounting for doctor emigration.
The updated report, titled Demand for medical consultants and specialists to 2028 and the training pipeline to meet demand: A high level stakeholder informed analysis, described general practice as unique in its requirements for
a substantial growth in trainee numbers in order to move towards policy changes advocated within Sláintecare.
The analysis published by HSE National Doctors Training and Planning (NDTP) “represents the views of NDTP stakeholders rather than the HSE or HSE NDTP itself”.
Overall, according to the ICGP, there are 866 trainees enrolled on the GP training programme in 13 schemes across four regions. The number of new training places will increase to 255 for 2022, up from 233 places for 2021.
The NDTP analysis calculated that the GP workforce
Document size: 250mm x 346mm (WxH)
needed to grow from the current number of 3,989 to 5,649 in the future in order to roll-out universal free GP care.
“Estimates do not factor in more nurse-led care in the community, which may reduce this demand estimate somewhat. More research is needed in this area once plans for primary care and general practice developments are more fully formed, in line with Sláintecare policy,” added the report. In general practice, demand estimates were based on consideration of rolling out free GP care to the under-18s and over-70s as well as universal free GP care.
On Saturday 16 October, the board of the ICGP gave formal approval to the transfer of general practice training from the HSE to the ICGP.
Developing further cohorts of community paramedics (CPs)
Allergic rhinitis relief fluticasone furoate
The incidence of epistaxis during long term treatment was higher than 10% but was generally mild to moderate in intensity1
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once daily) and reduce back down to 55 micrograms daily dose once control is achieved. Contraindication:
Hypersensitivity to active substance or excipients. Special warnings and
precautions: Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).
Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. Consider additional systemic
corticosteroid cover during periods of stress or elective surgery. Caution when prescribing concurrently with other corticosteroids. A reduction in growth velocity has been observed in children treated with fluticasone furoate 110 micrograms daily for one year. Therefore, children should be maintained on the lowest possible efficacious dose which delivers adequate symptom control. It is recommended that growth of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. Consider referring to a paediatric specialist. May cause irritation of the nasal mucosa. If a patient presents with visual disturbance they should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma, central serous chorioretinopathy. Contains benzalkonium chloride; long-term use may cause oedema of the nasal mucosa. Drug interactions: Caution is recommended when co-administering fluticasone furoate with potent CYP3A inhibitors including cobicistat-containing products as an increase in the risk of systemic side effects is expected. Co-administration should be avoided unless the benefit outweighs the increased risk. Co-administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate. Pregnancy and Lactation: No adequate data available. Recommended nasal doses result in minimal systemic exposure. It is unknown if fluticasone furoate nasal spray is excreted in breast milk. Only use if the expected benefits to the mother outweigh the possible risks to the foetus or child. Side effects: Very common (≥1/10): epistaxis. Epistaxis was generally mild to moderate, with incidences in adults and adolescents higher in longer-term use (more than 6 weeks). Common (≥1/100 and <1/10): headache, dyspnoea, nasal ulceration. Uncommon (≥1/1000 and <1/100): rhinalgia, nasal discomfort (including nasal burning, nasal irritation, and nasal soreness), nasal dryness. Rare (≥1/10,000 and <1/1000): hypersensitivity
reactions including anaphylaxis, angioedema, rash, and urticaria. Very rare (<1/10,000): Nasal septum perforation. Not known: transient ocular changes, vision blurred, bronchospasm, growth retardation. Marketing Authorisation (MA) Holder: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. MA Number: EU/1/07/434/003. Legal category: POM B. Last date of revision: January
“is not appropriate” until the required regulatory framework is in place, the HSE has informed the Medical Independent (MI)
The same situation applies to deploying the role of critical care paramedic, the Executive confirmed.
Some 11 CPs are employed by the HSE at present. These paramedics are “considered to be a vanguard group working under the authorisation of the National Ambulance Service (NAS) Clinical Director”, according to the HSE.
“The Pre-Hospital Emergency Care Council (PHECC) is the professional regulator of paramedic practice and it is understood that primary legislation changes are required to enable PHECC to register and regulate this new specialist level of paramedic practice.”
Community paramedicine involves pre-hospital emergency care practitioners operating in expanded roles supporting public health, primary healthcare and preventive services in the community.
The NAS community paramedic service aims to provide broader options for patient care with a focus on treating patients at home. The patients are referred via the National Emergency Operations Centre (NEOC) from 999 calls and GP referrals (received via NEOC). CPs are “autonomous practitioners practicing within an expanded scope of practice”, which was developed and agreed by the Clinical Directors of the NAS, Northern Ireland Ambulance Service and Scottish Ambulance Service in 2017.
The service was implemented by the NAS following a ‘proof of concept’ project supported by Cooperation and Working Together and funded by the Special European Union Project Board.
The 11 CPs, who are registered advanced paramedics, are deployed in counties Donegal, Cavan/Monaghan, Dublin, Cork, and Limerick.
Mr Richard Lodge, Director of PHECC, said a legislative deficit is an impediment to the development of this new branch of paramedicine.
More broadly, for several years PHECC has highlighted with the Department of Health (DoH) that legislative deficiencies restrict its ability to adequately regulate pre-hospital emergency services.
“As the absence of adequate legislation is currently the greatest risk to PHECC, and due to its urgency and significance in our Strategic Plan, DoH officials have been informed that the matter will remain as a standard agenda item on all Council and PHECC/DoH meetings going forward,” Mr Lodge informed MI
A Department spokesperson said officials are considering “a number of options to strengthen the regulatory framework governing the delivery of pre-hospital care in Ireland”.
*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
Plans for the establishment of an All-Island Cancer Research Institute (AICRI) have been outlined at the latest meeting of the Oireachtas committee on the implementation of the Good Friday Agreement.
First proposed in 2020, support for this cross-border initiative has grown significantly over the last 12 months, AICRI Co-Lead Prof William Gallagher told committee members.
Envisaged as a virtual institute for cancer research, from the laboratory bench to the hospital setting, Prof Gallagher outlined: “We are currently putting together an ambitious, comprehensive, and cross-cutting cancer research programme involving multiple stakeholders. These stakeholders include academic, clinical and industry partners, as well as patients, funders, and government agencies.”
“Ten academic institutions have agreed to partner to fulfil the All-Island Cancer Research Institute vision. Representatives from these institutions, along with pa-
tient advocates from both jurisdictions, are members of the All-Island Cancer Research Institute steering committee, which was established in February 2021. They are joined by the Director of the HSE’s National Cancer Control Programme and the CEO of Cancer Trials Ireland.”
Prof Gallagher said the AICRI would focus on four key themes: Cancer prevention; cancer diagnostics; cancer treatment; and survivorship/quality-of-life.
A wide range of projects relating to these thematic areas had already been garnered from the cancer research community across the island.
Prof Gallagher said the basis for their current mission had been the All-Ireland Cancer Consortium, which arose from the Good Friday Agreement.
A surveillance robot project deployed by the HSE for processing Covid-19 data has been developed further “to process Covid-19 whole genome sequencing results and case vaccination data”, this newspaper has been told.
In October 2020, the Medical Independent (MI) reported on the robot project deployed by the HSE for Covid-19 data processing. At the time, the HSE said there were plans for the project to be deployed for other respiratory infections during future influenza seasons.
However, a spokesperson told MI that the project will not be deployed during the influenza season and will continue to be used for the ongoing pandemic.
“The Covid-19 surveillance robot has not been tested for use on influenza notification processing,” said the spokesperson.
“In accordance with pandemic response priorities, the robot has been developed further to process Covid-19 whole genome sequencing results and case vaccination data....”
Chief Medical Officer Dr Tony Holohan on the rising incidence of Covid-19 cases. Dr Holohan stressed the importance of “individual, institutional and sectoral attention to risk mitigation” at this point in the pandemic.
According to a report in the September 2020 edition of Epi-Insight , a project team led by the HSE and the Health Protection Surveillance Centre explored the possibility of a robotic solution to relieve some of the burden of Covid-19 data processing.
“Through site visits to HSE Departments of Public Health, stakeholder workshops, business process analysis, a set of processing rules were agreed nationally and reference files for hospitals and community care areas were delivered,” outlined the Epi-Insight report.
“The robot was programmed by Deloitte to apply these rules and navigate the CIDR [computerised infectious disease reporting] system by replicating human behaviour.”
The live trial results of the project included “a successful degree of automation (ie, the robot could perform the processing just like a human), successful time-saving in processing time and the ability to operate outside of core hours to maximise its benefit”.
A tripartite cancer research and training agreement, first signed in 1999, had been reinvigorated on 16 March through a revised memorandum of understanding signed by Minister for Health Stephen Donnelly; Northern Ireland Minister for Health Robin Swann; and Director of the US National Cancer Institute Dr Norman Sharpless.
The committee also heard from Prof Maeve Lowery, Professor of Translational Cancer Medicine at Trinity College Dublin and Consultant Medical Oncologist at St James’s Hospital, Dublin, who commented: “There are so many questions that arise when we map the clinical care pathways for prevention, diagnosis, and treatment of cancers that really can be solved quicker and better through innovative and focused cancer research. And the key part of that is that we don’t work in silos.”
The meeting was also attended by Prof Mark Lawler, Queen’s University Belfast; Mr Ciaran Briscoe, Northeast Cancer Research and Education Trust; and Ms Eibhlín Mulroe, Cancer Trials Ireland, who discussed the latest proposals.
The HSE National Hepatitis C Treatment Programme (NHCTP) is looking to establish a pilot online hepatitis C testing service.
The service would be integrated with existing public treatment sites, according to tender documents.
The aim of the project is to improve access to hepatitis C testing in treatment sites through the availability of free home testing via an online system. As reported by the Medical Independent last month, the HSE plans to commence home testing for hepatitis C in the first quarter of 2022.
The proposed system should facilitate the online ordering of hepatitis C tests and provide clinical governance, results management, and remote clinical support to service users.
The NHCTP will establish a steering group comprising representatives from the programme and relevant partners to support and oversee the service’s initiation and progression.
The NHCTP will confirm the number of treatment sites in agreement with the online provider and the project working group after
While our Covid-19 vaccination programme has been exceptionally successful by international standards, its roll-out also required deployment of a new system to support its implementation. The absence of a digital system to manage not just Covid-19 vaccinations, but all vaccination programmes was notable.”
the tender has been awarded.
It is expected that the successful online service provider would be an experienced provider of “online hepatitis C health services with appropriately qualified staff”.
The project should be led by a senior registered medical doctor, with appropriate qualifications and experience.
“The remainder of the team are expected to hold a relevant degree in medicine, nursing and midwifery or other relevant discipline,” according to the tender.
The provider would be expected to ensure secure mechanisms for interaction with treatment sites, sharing patient data, and referral mechanisms.
While the geographical locations and treatment sites will be later confirmed by the HSE, tenderers should give consideration as to how geographical restrictions could be applied to the treatment site areas.
The provider would also be required to establish a system for ordering and delivery of hepatitis C tests and establish partnerships with laboratories.
The deadline for response to the tender is 17 November.
A combination of higher levels of social contact, a move to socialisation indoors and a collective relaxing of basic public health behaviours combined has led to this surge of infection.”
The funding provided will support the delivery of direct patient services throughout the cancer pathway – from prevention and early detection to diagnosis and treatment –leading to better outcomes for patients.”HIQA’s Director of Health Information and Standards Ms Rachel Flynn speaking at the launch of the Authority’s report calling for reform of the health information system for health and social care. Director of the National Cancer Control Programme Prof Risteárd Ó Laoide welcoming the announcement that new development funding of €20 million will be made available for cancer services in Budget 2022. Prof William Gallagher
2 CPD Hours
Authors: Dr Jayne Doherty, SpR in Gastroenterology, and Dr Garret Cullen, Consultant Gastroenterologist, Centre for Colorectal Disease, St Vincent’s University Hospital, Dublin
1.5 CPD Hours
Author: Eamonn Brady MPSI
2 External Credits
Authors: Dr Rehman Faryal, Prof Fionnuala Ní Áinle, Dr Barry Kevane, Department of Haematology, Mater Misericordiae University Hospital
The Irish Blood Transfusion Service Medical and Scientific Director Dr Stephen Field speaks with Pat Kelly about the challenges of maintaining blood supply during Covid and the Service’s recently published annual report
The nature of the functions of the Irish Blood Transfusion Service (IBTS) meant the impact of Covid-19 restrictions and safety measures was severe. The Service was forced to adapt at lightning speed to the rapidly evolving situation and introduced an appointments system almost overnight.
However, the IBTS continued to run clinics throughout the country by implementing new work rosters, enabling hundreds of staff to work remotely, adjusting the roles of other staff, sourcing personal protective equipment, and developing guidelines to support staff, among other measures. The Service also had to deal with hundreds of queries from concerned donors, which in itself placed inordinate strain on staff and the provision of services.
Even before Covid, the IBTS had begun the consultation process for its new strategic plan, Connections that Count: Developing the IBTS 2021-2025 , and notwithstanding changing circumstances due to the outbreak, work on this continued and was approved by its board.
The re-organisation of research will enable IBTS staff to make important contributions to scientific literature in the field of transfusion medicine, including the introduction of next-generation sequencing methodology. This will provide better resolution of highly polymorphic and complex human leukocyte antigen (HLA) genes, according to the IBTS.
at a time when we really didn’t know very much about what Covid really was,” said Dr Field.
“We also needed to cut back on the blood supply, because the hospitals had closed-up too, and so less blood was actually required. So, the first thing was that we needed to be sure we didn’t over-collect blood, because there’s nothing worse than having to discard blood on an expiry date because it’s not needed.”
It was necessary to rapidly adapt to a new system whereby all new donors had to make an appointment as the IBTS switched its focus to existing donors during that period, said Dr Field.
“It was more difficult to process new donors in 2020 because we needed to do pre-screening; they needed to make an appointment over the phone and then come and take it up; and it’s a lot easier to do that with existing donors. We suffered as a result of that, because as our donor panel gets older, some of them will need to stop donating as they get to a certain age or get illnesses, and they need to be replaced with younger people. The consequence is that we have a backlog on recruiting those new donors, so that’s where our emphasis is at the moment.”
In spite of these difficulties, the appointments system worked well, as donors knew when they were coming to the clinic and a lot of pre-screening work was done over the telephone to eliminate anybody who was not eligible to donate, he explained.
“Having said that, we now need to develop our software,” said Dr Field.
“We have a dedicated IT system, which is a specialist proprietary blood transfusion information system, which is called a blood establishment computer system, or BECS.” The IBTS uses the eProgesa system, which is a software application that has been specifically developed to meet functional requirements of blood banks and blood transfusion centres.
Dr Stephen FieldDr Stephen Field, Medical and Scientific Director at the IBTS, spoke with the Medical Independent (MI) about how the Service was forced to evolve during Covid, the strategic plan, and the ongoing drive for clinical innovation. Regarding the annual report, Dr Field commented: “I think the biggest take-home message from it was we have a new Chief Executive [Ms Orla O’Brien],” he said.
“There was great work done by [Mr] Andrew Kelly for the previous 19 years. The Service was in a bad place when he took the hot-seat but he has handed over the mantle of CEO to a really competent person and we are thriving under her leadership.”
In any discussion about healthcare provision in the current climate, it is difficult to avoid the topic of how Covid has affected care.
“When Covid came about, we obviously had to take a very careful approach to protect both staff and donors,
“We now need to develop a portal to make the appointments system a little bit tighter and more linked-in to the system itself. At the moment, we are just using a system we developed to see us through the crisis period.”
He described the early “chaotic” days of the outbreak: “Firstly, we had to know a little more about the virus,” said Dr Field.
“The thing that became rapidly apparent is that being a respiratory virus, it was not going to be transmitted through blood transfusion. But having said that, and knowing what we do about the emergence of viruses in the past and the havoc they can cause with transfusion, we obviously took a very careful approach.” This involved deferring those donors who had Covid before they could donate and this all had to be reconsid-
ered when the vaccines were rolled out, Dr Field explained. This also involved introducing a short deferral period after a donor had been vaccinated.
Another necessary measure was to introduce processes at clinics to ensure distancing and mask-wearing.
“Of course, the policies around masks changed quite a lot in those early days –were they effective, were they not effective, did people need to have them on all the time? There was a policy at one time whereby people needed to have them on during the queuing process, but when we were actually dealing with them on the donation couch, we needed to have their masks off so that we could pick up on any reactions the donor might suffer more quickly,” said Dr Field.
“Then it became apparent that it was preferred that people should wear masks all the time. We very quickly learned to pick up on people who were
having adverse events relating to the donation in other ways.
“All of those things needed to be worked out – we needed to look at the science, the national policy, to make sure that we were compliant.”
Whereas it was possible for some medical specialties to see patients during lockdowns and assess them via virtual consultations, the nature of blood donation meant that the IBTS did not have that luxury.
“We needed to rely on the donors truthfully filling-in their health questionnaire, which looks at risks and so on, but they had been basically doing that for years anyway, so there was nothing new there, but we had never done telephone pre-screenings before,” Dr Field said.
When Covid came about, we obviously had to take a very careful approach to protect both staff and donors, at a time when we really didn’t know very much about what Covid really was
When a DPP-4 inhibitor is needed
UNIQUE CONVENIENCE through always one dose, once daily 1 5mg once daily
Demonstrated CV AND KIDNEY SAFETY PROFILE 2,3
for adults with T2D 1,4
References:
1. TRAJENTA® (linagliptin) Summary of Product Characteristics. SmPC available at: https://www.medicines.ie/
2. Rosenstock J, et al. JAMA. 2019;321:69–79
3. Rosenstock J, et al. Cardiovasc Diabetol. 2018;17:39
4. McGill JB, et al. Diabetes Care. 2013;36:237–44
Prescribing Information (Ireland) TRAJENTA® (Linagliptin)
Film-coated tablets containing 5 mg linagliptin. Indication: Trajenta is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control as: monotherapy when metformin is inappropriate due to intolerance, or contraindicated due to renal impairment; combination therapy in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. Dose and Administration: 5 mg once daily. If added to metformin, the dose of metformin should be maintained and linagliptin administered concomitantly. When used in combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin, may be considered to reduce the risk of hypoglycaemia. Renal impairment: no dose adjustment required. Hepatic impairment: pharmacokinetic studies suggest that no dose adjustment is required for patients with hepatic impairment but clinical experience in such patients is lacking.
Elderly: no dose adjustment is necessary based on age. Paediatric population: the safety and ef cacy of linagliptin in children and adolescents has not yet been established. No data are available. The tablets can be taken with or without a meal at any time of the day. If a dose is missed, it should be taken as soon as possible but a double dose should not be taken on the same day.
Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and Precautions: Linagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Hypoglycaemia: Caution is advised when linagliptin is used in combination with a sulphonylurea and/or insulin; a dose reduction of the sulphonylurea or insulin may be considered. Acute pancreatitis: Acute pancreatitis has been observed in patients taking linagliptin. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, Trajenta should be discontinued. If acute pancreatitis is con rmed, Trajenta should not be restarted. Caution
should be exercised in patients with a history of pancreatitis. Bullous pemphigoid: Bullous pemphigoid has been observed in patients taking Linagliptin. If bullous pemphigoid is suspected, Trajenta should be discontinued. Interactions: Linagliptin is a weak competitive and a weak to moderate mechanism-based inhibitor of CYP isozyme CYP3A4, but does not inhibit other CYP isozymes. It is not an inducer of CYP isozymes. Linagliptin is a P-glycoprotein substrate and inhibits P-glycoprotein mediated transport of digoxin with low potency. Based on these results and in vivo interaction studies, linagliptin is considered unlikely to cause interactions with other P-glycoprotein substrates. Effects of other medicinal products on linagliptin: The risk for clinically meaningful interactions by other medicinal products on linagliptin is low. Rifampicin: Multiple co-administration of 5 mg linagliptin with rifampicin, a potent inductor of P-glycoprotein and CYP3A4, decreased linagliptin steady state AUC and Cmax. Thus, full ef cacy of linagliptin in combination with strong P-glycoprotein inducers might not be achieved, particularly if administered long term. Coadministration with other potent inducers of P-glycoprotein and CYP3A4, such as carbamazepine, phenobarbital and phenytoin has not been studied. Effects of linagliptin on other medicinal products: In clinical studies linagliptin had no clinically relevant effect on the pharmacokinetics of metformin, glibenclamide, simvastatin, warfarin, digoxin or oral contraceptives (please refer to Summary of Product Characteristics for a full list of interactions and clinical data). Fertility, pregnancy and lactation: The use of linagliptin has not been studied in pregnant women. As a precautionary measure, avoid use during pregnancy. A risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from linagliptin therapy taking into account the bene t of breastfeeding for the child and the bene t of therapy for the woman.
No studies on the effect on human fertility have been conducted
for linagliptin. Undesirable effects: Adverse reactions reported in patients who received linagliptin 5 mg daily as monotherapy or as add-on therapies in clinical trials and from post-marketing experience. Frequencies are de ned 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) or very rare (<1/10,000). Adverse reactions with linagliptin 5 mg daily as monotherapy: Common: lipase increased. Uncommon: nasopharyngitis; hypersensitivity; cough; rash; amylase increased. Rare: pancreatitis; angioedema; urticaria; bullous pemphigoid. Adverse reaction with linagliptin in combination with metformin plus sulphonylurea: Very common: hypoglycaemia. Adverse reaction with linagliptin in combination with insulin: Uncommon: constipation. Prescribers should consult the Summary of Product Characteristics for further information on side effects. Pack sizes: 28 tablets. Legal category: POM. MA number: EU/1/11/707/003. Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, D-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 September 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
In conjunction with the change of CEO, the new strategic plan for the IBTS was introduced following extensive consultations between different areas of the Service to identify what needs to be looked at more closely in transfusion medicine in Ireland. “It’s an evolving field,” Dr Field told MI. “In 2019, we looked at the issue of Creutzfeldt-Jakob disease (CJD) in the context of our donors who had ever lived in the UK. We examined all the scientific evidence and came to the conclusion that the risk is actually tiny and we could remove that risk factor. That has also opened up the way for us to use Irish plasma in a different way. For 20 years we discarded plasma – when we produce our red cells, which is the primary part that is transfused, we had not used the plasma. In fact, we sold it off at very cheap rates to companies that want to make controls for their blood reagent test kits, for example.”
However, there is now a worldwide shortage of intravenous immunoglobulin and the rest of the world is largely dependent on supplies from the US to produce this particular fractionated medical product, explained Dr Field.
“By changing the vCJD [variant CJD] rules, we are now able to look at the plasma market once again. We have imported plasma for the past 20 years to meet the fresh frozen plasma demands in our hospitals – there is a pathogen reduction process that kills-off any viruses, etc, within the plasma,” he said.
“We have the option of sending our own plasma for that process, or we have the option of doing it ourselves using another patented process, which is currently under procurement. So we do now have options.”
The excess from the process, according to Dr Field, can now be sent to fractionation plants for the production of items such as intravenous or other immunoglobulin or albumin, for example. This creates a revenue stream for the IBTS to allow them to look at pathogen reduction in platelets, for example, which is a costly process.
“We are hoping that we can look at the health economics of that,” said Dr Field. “Although it is expensive, it does add another layer of safety to our system, which is very safe as it is, but there is always the remote chance of something breaking through. And if we can implement that, of course, we have to make sure that we are using taxpayers’ money appropriately.”
Sickle cell
Dr Field also touched on a plan to recruit donors of African ancestry, many of whom have lived in malaria-endemic areas of the world, in an effort to improve Rh matching of blood required for sickle cell patients.
“We do need donors of African ancestry. We have an ever-growing cohort of patients in our hospitals, particularly Crumlin and St James’s Hospitals, who have sickle cell anaemia,” explained Dr Field. “The African blood group con -
figuration for Rh is slightly different to that of Irish and Caucasian populations.
In the simplest terms, the Rh system is a complex of three different antigen types: C, D and E, and D and E are not compatible with the normal Rh-positive Irish donors, but they are compatible with Rh-negative donors,” he said.
“So we need to collect blood [C- and E-antigens] from African donors who are Rh-positive. But the difficulty is that there is a risk of malaria,” said Dr Field.
“In the UK, there are tests with malaria and we have now validated those tests here in Ireland, and we are in the last stages of getting that ready. It’s simple enough to do the tests, but we need to get the software to transfer the results
that funding stopped some years ago, in that those projects were complete. We then needed to re-look at our own R&D, which needed a little more facilitation and organisation.
“I’m very pleased to say that about a year ago, we appointed Dr Allison Waters as our R&D facilitator,” he continued. “She has really put the IBTS on the map in this regard and she has developed a full R&D strategy, which is available on our website and is well worth a look.” As a result, the IBTS is now examining the prospect of placing its staff into higher degree courses. This is an area the Service has always encouraged, but organising it within a department allows all the assistance a staff member
In addition to all of these activities, the IBTS conducted a seroprevalence study on donors throughout the pandemic and the results are due to be published later in 2021.
“We got some interesting results from that and it has gone in for publication,” said Dr Field. “There was something about it splashed in one of the newspapers a few weeks ago, but we need to be quite careful in how we report our findings before they are published elsewhere.” The research is currently out on peer review, he added. However, Dr Field was able to say that a number of studies have been conducted on donors by the IBTS and the antibodies relating to Covid-19 and the results will be published shortly.
Dr Field and his team are anxiously awaiting the result of the peer review, but the process may be slower than normal, as “there is a lot of literature on Covid out there at the moment and a lot of competition for publication space”.
He also spoke briefly about the introduction of next-generation sequencing (NGS) methodology that has been used in the tissue typing (HLA) laboratory, which enables better matching of stem cell donors to patients who require a transplant.
“It’s a very specialist field, state-ofthe-art in tissue typing, so that does guarantee better matching for our patients who need transplants for leukaemia or other haematological disorders,” said Dr Field.
“It enables the best-quality match and puts our registry on the map worldwide in terms of having the top standard in HLA typing available to us. It uses more molecular sequencing processes to get right down to the core DNA sequences of the particular HLA type, and we hope that we can expand that in time to do red-cell genotyping. That will make the matching of our donors with patients a lot more specific.
from the test platform into the eProgesa system. That requires some configuration, but we are just about ready to test that and we are hoping to get a small group of people of African ancestry to come and give us samples so that we can test the system.”
The strategy also addresses the re-organisation of research work at the IBTS, which Dr Field has previously stated will enable the Service’s staff to make significant contributions to the scientific literature in the field of transfusion medicine.
“One per cent of our turnover is put into research and development,” he explained to MI. “In recent years, that money has been spent externally, outside the IBTS, looking at regenerative medicines, and has been run through NUI Galway. We funded a number of regenerative medicine projects, but
needs to put a project in place.
“We will also be working with many academic institutions and we are looking at a PhD project with our partners at St James’s and Trinity College to look at cellular therapies,” said Dr Field.
“We are also looking at a joint research project with Technological University Dublin on a PhD for someone who will eventually come into the field of transfusion science. We are also hoping to try to encourage a senior registrar in haematology to come and do a research Fellowship and get an MD degree, and that’s in the process of being looked at now. If we can have trainee haematologists coming through the Service, and if we can get one of them to do a Fellowship, it may entice them into the sub-specialty of transfusion medicine, because we are very short of people in that area.”
“We are in the genomics era, and we need to start thinking about how we are going to use our knowledge of genetic sequences and how we can pick up the different blood group antigens of our donors and make sure they are matched appropriately with our patients,” he stated.
“However, we also have to be aware of the power of DNA sequencing and certain information contained in it. What we don’t need to know, we don’t need to look at.” This would include mutations contained within blood groups.
“My term of office is coming to an end,” Dr Field told MI, whilst noting the many significant changes that have taken place within the Service in recent years.
“There has been tremendous change and hopefully under a new Medical and Scientific Director, that will continue, and we can move into other areas, such as cellular therapies – I think they are the way forward for the Blood Transfusion Service, in conjunction with our transplant or haematology units treating patients with malignant disease. I believe there is a big area to be developed there.”
We are in the genomics era, and we need to start thinking about how we are going to use our knowledge of genetic sequences…
For patients not adequately controlled on dual therapy with moderate to severe COPD
Significant protection against exacerbations*
TRIXEO Aerosphere is indicated as a maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting beta2-agonist or combination of a long-acting beta2-agonist and a long-acting muscarinic antagonist.1
*Significant reductions in the rate of moderate or severe exacerbations vs LAMA/LABA (24%, n=2137 vs n=2120, annual rates 1.08 vs 1.42, 95% CI 0.69–0.83; p<0.001) and ICS/LABA (13%, n=2137 vs n=2131, annual rates 1.08 vs 1.24, 95% CI 0.79–0.95; p=0.003).1,2 COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting beta2-agonist; LAMA, long-acting muscarinic antagonist. In the clinical trial programme for TRIXEO, LAMA/LABA refers to glycopyrronium/formoterol fumarate and ICS/LABA refers to budesonide/formoterol fumarate. ©AstraZeneca 2021. All rights reserved.
ABRIDGED PRESCRIBING INFORMATION
TRIXEO AEROSPHERE® 5 micrograms/7.2 micrograms/160 micrograms pressurised inhalation, suspension (formoterol fumarate dihydrate/ glycopyrronium/ budesonide)
Consult Summary of Product Characteristics (SmPC) before prescribing.
Indication: Trixeo Aerosphere is indicated as a maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid and a long acting beta2 agonist or combination of a long-acting beta2 agonist and a long acting muscarinic antagonist. Presentation: Pressurised inhalation, suspension. Each single actuation (delivered dose, ex-actuator) contains 5 micrograms of formoterol fumarate dihydrate, glycopyrronium bromide 9 micrograms, equivalent to 7.2 micrograms of glycopyrronium and budesonide 160 micrograms. This corresponds to a metered dose of 5.8 micrograms of formoterol fumarate dihydrate, glycopyrronium bromide 10.4 micrograms, equivalent to 8.2 micrograms of glycopyrronium and budesonide 182 micrograms. Dosage and Administration: The recommended and maximum dose is two inhalations twice daily (two inhalations morning and evening). If a dose is missed, take as soon as possible and take the next dose at the usual time. A double dose should not be taken to make up for a forgotten dose. Special populations: Elderly: No dose adjustments required in elderly patients. Renal impairment: Use at recommended dose in patients with mild to moderate renal impairment. Can also be used at the recommended dose in patients with severe renal impairment or end-stage renal disease requiring dialysis, only if expected benefit outweighs the potential risk. Hepatic impairment: Use at recommended dose in patients with mild to moderate hepatic impairment. Can also be used at the recommended dose in patients with severe hepatic impairment, only if expected benefit outweighs the potential risk. Paediatric
Population: No relevant use in children and adolescents (<18 years of age).
Method of administration: For inhalation use. To ensure proper administration of the medicinal product, the patient should be shown how to use the inhaler correctly by a physician or other healthcare professional, who should also regularly check the adequacy of the patient’s inhalation technique. Patients who find it difficult to coordinate actuation with inhalation may use Trixeo Aerosphere with a spacer to ensure proper administration of the medicinal product. Contraindications: Hypersensitivity to the active substances or to any of the excipients. Warnings and Precautions: Not for acute use: Not indicated for treatment of acute episodes of bronchospasm, i.e. as a rescue therapy.
Paradoxical bronchospasm: Administration of formoterol/glycopyrronium/ budesonide may produce paradoxical bronchospasm with an immediate wheezing and shortness of breath after dosing and may be life threatening.
Treatment should be discontinued immediately if paradoxical bronchospasm occurs. Assess patient and institute alternative therapy if necessary.
Deterioration of disease: Recommended that treatment should not be stopped abruptly. If patients find the treatment ineffective, continue treatment but seek medical attention. Increasing use of reliever bronchodilators indicates worsening of the underlying condition and warrants reassessment of the therapy. Sudden and progressive deterioration in the symptoms of COPD is potentially life threatening, patient should undergo urgent medical assessment.
Cardiovascular effects: Cardiovascular effects, such as cardiac arrhythmias, e.g. atrial fibrillation and tachycardia, may be seen after the administration of muscarinic receptor antagonists and sympathomimetics, including glycopyrronium and formoterol. Use with caution in patients with clinically significant uncontrolled and severe cardiovascular disease such as unstable ischemic heart disease, acute myocardial infarction, cardiomyopathy, cardiac arrhythmias and severe heart failure. Caution should also be exercised when treating patients with known or suspected prolongation of the QTc interval (QTc > 450 milliseconds for males or > 470 milliseconds for females), either congenital or induced by medicinal products. Systemic corticosteroid effects: May occur with any inhaled corticosteroid, particularly at high doses prescribed
for long periods. These effects are much less likely to occur with inhalation treatment than with oral corticosteroids. Systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, cataract and glaucoma. Potential effects on bone density should be considered particularly in patients on high doses for prolonged periods that have co existing risk factors for osteoporosis. Visual disturbances: May be reported with systemic and topical corticosteroid use. If patient presents symptoms such as blurred vision or other visual disturbances, consider ophthalmologist referral for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR). Transfer from oral therapy: Care is needed in patients transferring from oral steroids, since they may remain at risk of impaired adrenal function for a considerable time. Patients who have required high dose corticosteroid therapy or prolonged treatment at the highest recommended dose of inhaled corticosteroids, may also be at risk. These patients may exhibit signs and symptoms of adrenal insufficiency when exposed to severe stress. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery. Pneumonia in patients with COPD: An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been observed in patients with COPD receiving inhaled corticosteroids. Remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations. Risk factors for pneumonia include current smoking, older age, low body mass index (BMI) and severe COPD. Hypokalaemia: Potentially serious hypokalaemia may result from β2-agonist therapy. This has potential to produce adverse cardiovascular effects. Caution is advised in severe COPD as this effect may be potentiated by hypoxia. Hypokalaemia may also be potentiated by concomitant treatment with other medicinal products which can induce hypokalaemia, such as xanthine derivatives, steroids and diuretics.
Hyperglycaemia: Inhalation of high doses ofβ2-adrenergic agonists may produce increases in plasma glucose. Blood glucose should be monitored during treatment following established guidelines in patients with diabetes. Co-existing conditions: Use with caution in patients with thyrotoxicosis. Anticholinergic activity: Due to anticholinergic activity, use with caution in patients with symptomatic prostatic hyperplasia, urinary retention or with narrow-angle glaucoma. Patients should be informed about the signs and symptoms of acute narrow-angle glaucoma and should be informed to stop using this medicinal product and to contact their doctor immediately should any of these signs or symptoms develop. Co-administration of this medicinal product with other anticholinergic containing medicinal products is not recommended. Renal impairment: Patients with severe renal impairment (creatinine clearance of <30 mL/min), including those with end-stage renal disease requiring dialysis, should only be treated with this medicinal product if the expected benefit outweighs the potential risk. Hepatic impairment: In patients with severe hepatic impairment, use only if the expected benefit outweighs the potential risk. These patients should be monitored for potential adverse reactions. Drug Interactions: Co-treatment with strong CYP3A inhibitors, e.g. itraconazole, ketoconazole, HIV protease inhibitors and cobicistat-containing products are expected to increase the risk of systemic side effects. Should be avoided unless the benefit outweighs the increased risk, in which case patients should be monitored for systemic corticosteroid adverse reactions. This is of limited clinical importance for short-term (1-2 weeks) treatment. Since glycopyrronium is eliminated mainly by the renal route, drug interaction could potentially occur with medicinal products affecting renal excretion mechanisms. Other antimuscarinics and sympathomimetics: Co-administration with other anticholinergic and/or long-acting β2-adrenergic agonist containing medicinal products is not recommended as it may potentiate known inhaled muscarinic antagonist or β2-adrenergic agonist adverse reactions. Concomitant use of other beta-adrenergic medicinal products can have potentially additive effects. Caution required when prescribed concomitantly with formoterol. Medicinal product-induced
hypokalaemia: Possible initial hypokalaemia may be potentiated by xanthine derivatives, steroids and non potassium sparing diuretics. Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides. β-adrenergic blockers: β-adrenergic blockers (including eye drops) can weaken or inhibit the effect of formoterol. Concurrent use of β-adrenergic blockers should be avoided unless the expected benefit outweighs the potential risk. If required, cardio-selective β-adrenergic blockers are preferred. Other pharmacodynamic interactions: Concomitant treatment with quinidine, disopyramide, procainamide, antihistamines, monoamine oxidase inhibitors, tricyclic antidepressants and phenothiazines can prolong QT interval and increase the risk of ventricular arrhythmias. L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta2sympathomimetics. Concomitant treatment with monoamine oxidase inhibitors, including medicinal products with similar properties such as furazolidone and procarbazine, may precipitate hypertensive reactions. Elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.Pregnancy and Lactation: Administration to pregnant women/women who are breast-feeding should only be considered if the expected benefit to the mother justifies the potential risk to the foetus/ child. Ability to Drive and Use Machines: Dizziness is an uncommon side effect which should be taken into account. Undesirable Events: Consult SmPC for a full list of side effects. Common (≥ 1/100 to < 1/10): Oral candidiasis, pneumonia, hyperglycaemia, anxiety, insomnia, headache, palpitations, dysphonia, cough, nausea, muscle spasms, urinary tract infection. Uncommon (≥ 1/1,000 to < 1/100): Hypersensitivity, depression, agitation, restlessness, nervousness, dizziness, tremor, angina pectoris, tachycardia, cardiac arrhythmias (atrial fibrillation, supraventricular tachycardia and extrasystoles), throat irritation, bronchospasm, dry mouth, bruising, urinary retention, chest pain. Very Rare (< 1/10,000): Signs or symptoms of systemic glucocorticosteroid effects, e.g. hypofunction of the adrenal gland, abnormal behaviour. Not known: Angioedema, vision blurred, cataract, glaucoma.
Legal Category: Product subject to prescription which may be renewed (B)
Marketing Authorisation Number: EU/1/20/1498/002 120 actuations
Marketing Authorisation Holder: AstraZeneca AB, SE-151 85, Södertälje, Sweden.
Further product information available on request from: AstraZeneca Pharmaceuticals (Ireland) DAC, Block B, Liffey Valley Office Campus, Dublin 22.
Tel: +353 1 609 7100.
TRIXEO and AEROSPHERE are trademarks of the AstraZeneca group of companies.
Date of API preparation: 07/2021 Veeva ID: IE-2842
Adverse events should be reported directly to; HPRA Pharmacovigilance, Website: www.hpra.ie Adverse events should also be reported to AstraZeneca Patient Safety on Freephone 1800 800 899
1. TRIXEO AEROSPHERE 5 micrograms/7.2 micrograms/160 micrograms pressurised inhalation, suspension. Summary of Product Characteristics. Available at www.medicines.ie
2. Rabe KF et al. Triple inhaled therapy at two glucocorticoid doses in modeate-to-very-severe COPD. N Engl J Med. 2020;383:35–48. doi: 10.1056/ NEJMoa1916046 COPD. N Engl J Med. 2020;383:35–48. doi: 10.1056/NEJMoa1916046
For decades healthcare workers have been putting their lives on the line in conflict zones. In the first of a new series titled ‘On the frontlines’, Bette Browne tells the story of one of them, Dr Lucien Wasingya Kasereka
When he was just three days old, medicine became the life mission of Lucien Wasingya Kasereka. Today he is a surgeon in his native Democratic Republic of Congo (DRC) helping to end the agony of obstetric fistula for thousands of women.
“The decision of doing medicine as a career came from my late father, Lusenge Kalwahali Gaudens. He told me the decision was made when I was three days old,” Dr Wasingya Kasereka told the Medical Independent (MI)
“I had a febrile disease and my life was saved by MSF [Médecins Sans Frontières] doctors. He promised them that his son would be a doctor and save millions of lives. That’s how I was given my mission.”
Today, 37 years later, as an obstetric fistula surgeon and founder and Director of the fistula programme in the DRC, Dr Wasingya Kasereka is fulfilling his father’s promise.
In 2012, he began his medical studies as an undergraduate at Univesité Catholique du Graben in the North Kivu city of Butembo, in the eastern part of DRC, where he qualified as a medical doctor. Two years later, he decided to go to Uganda for further studies at Uganda Martyrs University where he qualified as a general surgeon in 2017.
Inspiration
But Dr Wasingya Kasereka is quick to credit others for his success, especially the late pioneering Irish surgeon Sr Dr Maura Lynch of the Medical Missionaries of Mary, an RCSI Fellow, whom he met while in Uganda where she was a founding member of the Association of Surgeons in Uganda. That meeting would inspire the next stage in his life’s mission in medicine.
“Dr Lynch is the pioneer of obstetric fistula surgery in Uganda. She stayed in that country for 30 years and more than 7,000 women were operated on free of charge by her and her team at Kitovu Missionary Hospital in Masaka in Uganda.
“She is the one who motivated me to join her team at Kitovu Missionary Hospital. She trained me on how to repair obstetric fistula and inspired me to love these life-changing operations that restore the dignity of suffering women. From there, I decided to help these women with obstetric fistula for the rest of my life.”
In 2020, Dr Wasingya Kasereka decided to return home to the DRC to devote himself to fistula surgery. “I decided to go back to my home country to continue serving obstetric fistula victims free of charge. I created my own charity, Fistula Programme DRC, and opened the first
dedicated obstetric fistula hospital in the region, Butembo Fistula Hospital.
“Ninety patients have been operated on free of charge in DRC under the sponsorship of the Fistula Foundation US, the International Federation of Gynaecology and Obstetrics, and the United Nations Population Fund (UNFPA).”
The UNFPA, which is leading a global campaign to end fistula by 2030, describes it as one of the most serious and tragic childbirth injuries. It occurs when a hole, or fistula, is caused between the birth canal and bladder and/ or rectum due to prolonged, obstructed labour without access to timely,
living far from medical services and those for whom services are not accessible, affordable or acceptable.”
It estimates that hundreds of thousands of women and girls in Africa, Asia, Arab states, Latin America, and the Caribbean are living with fistula, with new cases developing every year.
“Yet fistula is almost entirely preventable,” UNFPA emphasises. “Its persistence is a sign of global inequality and an indication that health and social systems are failing to protect the health and human rights of the poorest and most vulnerable women and girls.”
Without emergency intervention,
range of other physical ailments, including frequent infections, kidney disease, painful sores, and infertility. The physical injuries can also result in social isolation and psychological harm. Women and girls with fistula are often unable to work and many are abandoned by their husbands and families and ostracised by their communities, driving them further into poverty.
Fistula in the DRC
In the DRC alone, according to Dr Wasingya Kasereka, between 5,000 and 10,000 women and girls suffer every year with fistula with no access to proper care. “Cases of obstetric fistula are on the rise in the Democratic Republic of Congo and Uganda with few fistula surgeons and few facilities which are able to provide fistula care,” Dr Wasingya Kasereka told the MI
The fistula programme, he explained, “was born in a particular context where Congolese women have lived in conditions of advanced vulnerability for several decades, following a very unstable socio-political situation.”
“The context of socio-security crises creates massive displacements of populations, making women the first-line victims. Health crises only worsen an already precarious situation. These include the resurgence of the Ebola epidemic, but also the cholera pandemic in several regions of the country, not to mention the coronavirus that has claimed victims at all levels for more than a year now.
“To all this can be added the health conditions, which are below standards in several regions of the country. This affects women in general, not only in terms of their fundamental rights, but also in terms of their health.”
Fistula Programme DRC is mainly interested in maternal and reproductive health, specifically in women with obstetric fistula problems, Dr Wasingya Kasereka said. Its main objective is to restore the dignity of women.
high-quality medical treatment.
“It leaves women leaking urine, faeces or both and often leads to chronic medical problems, depression, social isolation, and deepening poverty.”
Obstetric fistula has been virtually eliminated in industrialised countries through the availability of timely and advanced medical treatment for prolonged and obstructed labour, namely Caesarean section, UNFPA notes.
“Today, obstetric fistula occurs mostly among the poorest and most marginalised women and girls, especially those
obstructed labour can last for days, resulting in death or severe disability. The obstruction can cut off blood supply to tissues in the woman’s pelvis. When the dead tissue falls away, she is left with a fistula in the birth canal.
Tragically, there is a strong association between fistula and stillbirth, with research indicating that approximately 90 per cent of women who develop obstetric fistula end up delivering a stillborn baby, according to the UNFPA.
Left untreated, obstetric fistula causes chronic incontinence and can lead to a
“Some obstetric fistula patients can be easily treated with non-surgical intervention, but the most common treatment is surgery. However, women with obstetric fistula are often from low-income families with no financial support and suffer from severe stigmatisation within their communities,” Dr Wasingya Kasereka said on the 2020 United Nations Day to End Obstetric Fistula.
“Many in sub-Saharan Africa consider obstetric fistula to be a divine punishment. Women are therefore stigmatised. They are rejected by their family, divorced by their husbands, and abandoned within their community in the belief they must pay for their ‘sins’.”
The DRC, which was formerly Zaire, is located in Central Africa. It is the sec -
From there, I decided to help these women with obstetric fistula for the rest of my life
ond-largest country in Africa, after Algeria, with a population of more than 90 million.
Its history has largely been one of exploitation and suffering, especially under Belgian rule. The country achieved independence from Belgium in 1960, but was subsequently consumed by decades of conflict.
Nine African countries and around 20 armed groups became involved in a war from 1998 to 2003, which resulted in the deaths of over five million people. The human rights situation in the country remains dire, according to Human Rights Watch, with more than 5.2 million people internally displaced and nearly a quarter of the population living in severe food insecurity. The poverty rate is well above average, with about 60 per cent of the population living on less than $2 a day.
In a report last year, UN High Commissioner for Human Rights Ms Michelle Bachelet said she was appalled by the increase in brutal attacks on innocent civilians by armed groups, and by the reaction of the military and security forces who had also committed grave violations, including killings and sexual violence.
“Violence and political instability continue to plague the Democratic Re -
educating Congolese communities on obstetric fistulas.”
Fistula is not only a debilitating physical condition; it also presents huge psychological and societal issues for women and girls, Dr Wasingya Kasereka emphasised.
these camps, we can carry out around 30-to-60 obstetric fistula treatments for free, while allowing a greater number of women to access the service. Through media engagement on radio and TV, as well as through church announcements and ambassadors, we can inform a wide number of people of the fistula camps.”
Dr Wasingya Kasereka told MI that the battle to end obstetric fistula is under serious threat due to the Covid-19 pandemic. “My worst experience was to do obstetric fistula camps during the pandemic in low resource facilities with-
out enough PPE [personal protective equipment].”
But despite such challenges on the frontlines, Dr Wasingya Kasereka said the rewards for such work are enormous and he would encourage more doctors to consider practising fistula surgery.
“The reward we get is that joy and hope that patients experience after healing from obstetric fistula. We feel happy and satisfied when we see the happiness of these patients. I would encourage more doctors to join us and restore women’s dignity.”
public of Congo,” the Fistula Foundation says, “effectively crippling its limited maternal healthcare infrastructure and abandoning women who are suffering with fistula. These grinding conditions prompted author and humanitarian Ms Lisa Shannon to call it the worst place on earth to be a woman.’’
Conflict
Dr Wasingya Kasereka grew up in North Kivu, a tumultuous region in the northeast of the country. “The horrors of war and violence have been permanent for over 18 years now, which has significantly affected maternal and child health,” he explained. “Our vision is to restore the fistula victims’ dignity in DRC after a long period of political instability.”
Such political instability, in a country in which rape has been widely documented as a widespread weapon of war among armed groups, prompted a visit to the North Kivu capital Goma in 2013 by former Irish President Mary Robinson on a UN peace mission.
Dr Wasingya Kasereka said there is an urgent need to train more doctors and nurses for obstetric fistula care and such training is a central part of the work of the fistula programme. “Fistula Programme DRC is engaged in the training of nursing staff and health providers on fistula care and prevention as well as in
“Most of our patients meet our teams after suffering for many years. They leak urine or stool all the time and they are stigmatised by their families or communities. They lose their dignity and hope. Most of them are from poor families and are vulnerable and needy. Every year we meet more than 50 women who had been suffering for many years without any help or hope.
“These women suffering with obstetric fistula isolate themselves, they are stigmatised, rejected and some of them get psychosis and others are depressed, stressed, and traumatised. When we take care of them we consider surgery, psychotherapy and socio economical reintegration. By the time they are discharged they have hope and joy because their dignity has been restored.
“Of course, we face many challenges. Some patients get information about fistula care but they hide in the community and they don’t easily accept the treatment. There is a need to increase awareness in the community. Women who have undergone obstetric fistula care have become ambassadors of the service we provide, helping to raise awareness and increase knowledge of obstetric fistula in the community.”
To spread the word even further, Dr Wasingya Kasereka and his team carry out fistula camps each year. “Through
Up to three million women and girls, mainly in 55 developing countries across Asia and Africa, are living with untreated obstetric fistula.
The UN is campaigning to end this agonising condition by 2030. Since 2013 it has designated 23 May each year as International Day to End Obstetric Fistula, promoting global action towards treatment and prevention.
Obstetric fistula is caused by a very long or obstructed labour when women do not have access to quality obstetric care services.
It can largely be avoided by delaying the age of first pregnancy, ending harmful traditional practices, and timely access to quality obstetric care, especially Caesarean section.
Most genital fistula can be repaired surgically. But there are numerous challenges facing those providing fistula repair services in developing countries, including a dearth of available surgeons with specialised skills, operating rooms, equipment and funding from local or international donors to support both surgeries and post-operative care.
More women and girls will be at risk of obstetric fistula due to overburdened health systems. During Covid-19, fistula repairs have been widely suspended as they are deemed to be non-urgent and hospitals have diverted resources to care for patients with Covid-19.
It is expected that 13 million more child marriages could take place by 2030 than would have otherwise, because the economic fallout from the pandemic is more likely to cause families to ‘marry off’ daughters to alleviate the burden of caring for them.
The UN’s target to end fistula by 2030 will not be obtainable, experts say, unless sufficient resources are mobilised so that affected countries can develop their own sustainable eradication plans, including access to safe delivery and emergency obstetric services.
The main treatment remains corrective surgery, but due to a global shortage of fistula surgeons, current treatment rates indicate that only one woman in 50 receives a fistula repair.
(Sources UN, WHO, International Federation of Gynaecology and Obstetrics)
Every year we meet more than 50 women who had been suffering for many years without any help or hope
Since its opening in November 2020, the UPMC Sports Medicine Clinic at the WIT Arena has attracted many athletes of all levels. “At UPMC, we strive to offer advanced, comprehensive care for athletes and active people,” said Mr Patrick Carton, MD, FRCS (Tr and Orth), FFSEM, director of orthopaedic sports medicine for UPMC in Ireland. “With a focus not only on recovery, but also injury prevention, the UPMC Sports Medicine Clinic is equipped and staffed to provide evidence-based, quantitative measurements of strength and performance for optimal care.”
Dr Dualtach MacColgáin, BSc, MSc (Sports Medicine), MBChB, MISCP, MICGP, MFSEM, and Mr Carton collaborate closely with their colleagues in Ireland and Pittsburgh to grow UPMC’s sports medicine programme, giving athletes across the country timely access to trusted diagnostics and treatment.
The clinic houses a wide variety of equipment and services unique to the region, including:
The South East’s only AlterG® Antigravity Treadmill™, which allows for pain-free lower extremity rehabilitation by reducing gravitational forces in a fall-safe environment.
Biodex technology, which guides return to play with validated, quantitative outcomes data obtained through computerised measurement of muscle function and output.
Blood flow restriction rehabilitation, which uses a specialised tourniquet system to reduce blood flow to an extremity, with the goal of increasing strength using lower weight loads to mimic training at high loads.
Winback and shockwave therapy, two non-invasive, evidence-based treatments that accelerate healing from sports-related injuries.
UPMC Sports Medicine is also one of the primary concussion treatment centres in Ireland. As part of the UPMC Concussion Network and under the direction of Derek O’Neill, the clinic offers athletes evidence-based testing and rehabilitation following a concussion injury to optimise recovery and return to play.
UPMC Sports Medicine Clinic Research
High impact field sports where rapid changes in direction and acceleration/deceleration at speed are required can predispose players to lower limb injuries. One such injury common in multi-directional sports is hip impingement. This is a mechanical issue caused by a build-up of bone on the ball and socket components of the hip joint. As these bony prominences become bigger, the repetitive contact results in associated labral tears and damage to the cartilage, potentially increasing the risk of osteoarthritis.
Advanced surgical treatment and new insights have expanded the understanding of this issue for athletes, with the dissemination of information on an international level.
Earlier this year (March 2021)
Mr Carton and team published a study1 in the Orthopaedic Journal of Sports Medicine
In this study, 760 athletes competitively involved in Gaelic football, hurling, soccer, or rugby were followed over a 2.2-year period. All cases underwent surgical correction for symptomatic hip impingement previously unalleviated by conservative management alone. For these athletes there was a significant improvement in their pain- and activity-related outcomes, which was maintained two years later. The range of movements in the previ-
ous stiff hips had significantly improved. Furthermore, twoyears post-op, 84 per cent of cases were continuing to play their main sport with 80 per cent of cases continuing to play at their pre-injury level, highlighting the effectiveness of this surgical procedure for these high performing athletes.
In this same study, the team at UPMC Whitfield Hospital were able to demonstrate that for cases with initial symptom duration greater than six months prior to undergoing surgery, outcomes were poorer at follow-up compared to those with symptoms <6 months. Additionally, athletes with longer symptom duration were less likely in their ability to continue with sport, even after undergoing this preservation surgery.
As team-based sports and activities resume (through Covid-19) it is vitally important to look after athletes in every aspect of their player wellbeing. This includes both physical and emotional aspects of overall health.
In February 2021, the team published a paper addressing the implications beyond the physical disability which chronic hip impingement may have on an athlete. Their study2 was published in Arthroscopy: The Journal of Arthroscopic and Related Surgery. This large study of 486 male athletic cases, showed that although excellent restoration of physical functioning and ability to continue playing twoyears following surgical correction was reported by the athletes, the emotional toll of carrying a chronic hip injury may not be such an easy fix. It is therefore important to be aware that limited ability to engage fully in the physical demands of these sports may have ongoing and lasting impact on players’ overall mental health.
Establishing an accurate diagnosis and undertaking the most optimal course of treatment for the athlete suffering from hip and groin pain can be complex. The guidelines for treatment often become even more blurred when there is a suspicion that symptoms could be originating from different areas.
One of the most common diagnoses for groin pain in the athlete is what is referred to as Gilmore’s groin, and the treatment of choice has primarily been through surgical groin-specific repair. New research 3 from our team published in April 2021 in The American Journal of Sports Medicine investigated the relationship between the classic signs and symptoms of groin pathology among cases with coexisting evidence of hip impingement.
With an awareness of this associated biomechanics, in this study of 113 competitive male athletes, the hip deformity and associated pathology was prioritized for treatment in the first instance using arthroscopic corrective surgery. In almost nine out of 10 cases (89.2 per cent) this
single, minimally invasive hip arthroscopic procedure was successful in managing both hip- and groin-specific symptoms, avoiding the need for unnecessary groin surgery. This study concludes, and adds to the growing body of evidence, that an underlying hip pathology may be the primary cause of secondary injury of the surrounding anatomic structures and correcting this primary pathology may avoid the need for unnecessary groin operations.
UPMC Concussion Network – Understanding the importance of VOMS
Recent research has determined that vestibular abnormalities are frequent following a concussion and can delay healing. Vestibular and/or ocular motor impairments (VOMS) present as dizziness and are often reported as one of the earliest symptoms of concussion. Should an athlete report dizziness following a suspected concussion, immediate removal from play and assessment is required. Failure to do so risks protracted recovery time from typically 19 days to over 40 days or more.
A clinical examination of the vestibular system and ocular motor system maybe one of the most appropriate methods to detect early symptoms of concussion. The Vestibular Ocular Motor Screening, developed at the internationally-accredited UPMC Concussion Network in Pittsburgh, assesses vestibular and ocular motor impairments via patient-reported symptom provocation after each assessment. The VOMS assesses five domains of vestibular (balance) and ocular (visual) motor impairments. These include: (1) smooth pursuit, (2) horizontal and vertical saccades, (3) convergence, (4) horizontal vestibular ocular reflex (VOR), and (5) visual motion sensitivity (VMS). The assessment is a brief, five-minute exam.
To supplement the VOMS assessment, a neuro-vestibular assessment is also useful in determining concussion and can be carried out pitch-side. This assessment challenges proprioception with and without visual input. A simple tandem stand with eyes open and closed on the sideline may be sufficient to determine issues with the vestibular system. The management of concussion has changed dramatically with increased understanding of the condition. Traditionally, rest, preferably in a dark room would have been prescribed, however we now know that exertion is an important factor in optimal rehabilitation. In fact, simply resting may prolong recovery time. Research suggests that two to three days following a concussion, sub-maximal exercise can be undertaken. As symptoms lessen, the level of exertion may be increased under clinician guidance. Before return to play clearance, athletes must be symptom free at rest, at maximal exertion and have baseline levels of neurocognitive function on the concussion ImPACT test.
For more information on UPMC Sports Medicine, visit UPMC.ie/sportsmed.
Reference Publications:
1. Mullins K, Filan D, Carton P. Arthroscopic correction of sports-related femoroacetabular impingement in competitive athletes: Two-year clinical outcome and predictors for achieving minimal clinically important difference. Orthopaedic Journal of Sports Medicine. March 2021. doi:10.1177/2325967121989675
2. Filan D, Carton P. Chronic hip injury has a negative emotional impact on the male athlete with femoroacetabular impingement. Arthroscopy. 2021 Feb;37(2):566-576. doi: 10.1016/j.arthro.2020.10.035. Epub 2020 Oct 24. PMID: 33239184
3. Carton P, Filan D. Arthroscopic correction of femoroacetabular impingement for concomitant inguinal disruption in athletes with dual pathology. The American Journal of Sports Medicine. April 2021. doi:10.1177/03635465211007144
Fictional patient, for illustrative purposes only
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 Ellipta provides your patients with statistically superior improvements in lung function and health-related quality of life, and reduction in annualised rate of moderate/ severe exacerbations** vs. budesonide/formoterol***1–3
**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.
▼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.
(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
patients on TRELEGY Ellipta
expect
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.
Start TRELEGY Ellipta was developed in collaboration with
The need to improve Ireland’s healthcare information system has been known for some time. However, Covid-19 and the recent cyberattack have highlighted deficits in the current infrastructure, and the impact on patient care.
On the back of these crises, HIQA has published a new position paper that has called for urgent reform in the area. The paper states that the health service’s ICT infrastructure, as it stands, is “fragmented with major deficits”.
Regarding Covid-19, the report says the “lack of maturity” of Ireland’s health information system made it even more challenging to respond to the pandemic. The past year-and-ahalf has underscored the importance of “high-quality, standards-based” health information, which can be communicated across acute and community settings.
“Covid-19 has particularly highlighted challenges of managing and delivering an effective public health service in Ireland in the absence of fit-for-purpose, integrated information systems in relation to infectious disease surveillance, public health case management and immunisation,” according to the report.
Despite the efforts made by the HSE in rapidly delivering health information systems for the management of Covid-19, there are still serious deficits in our overall health information landscape.
For instance, the report points to the lack of a fully operational individual health identifier and the impact of this on roll-out of systems, such as the Covid-19 case tracker, test and assessment appointment scheduler, and Covid referrals.
The report adds that the cyberattack “has had a severe and immediate im-
pact on health services and has strongly emphasised the need for continuous investment and strengthening of our security infrastructure”.
HIQA says political commitment is required to deliver a new national health information strategy. This strategy should have achievable and timebound objectives that are aligned with Sláintecare. The report points out the strategy “needs to be assigned appropriate funding to ensure that its objectives can be fully achieved”.
“There is a need for a clear policy direction for health information, and a clear roadmap on how the different agencies within health and broader governmental organisations are coordinated, to deliver an integrated approach to health information and support the health and social care system in Ireland,” according to the Authority.
To complement this work, the existing e-health strategy, which was published in 2013, is outdated and should be revised to reflect more recent technological developments, according to the HIQA report. E-Health Ireland has not been established as was originally intended, as a separate entity with responsibility for overall governance around e-health implementation.
However, HIQA adds that an “operational function” for developing and supporting systems required for the delivery of care should continue to exist in the Executive.
“The remit of this entity should be broader than e-health and include the centralised coordination and governance of national data collections and the secondary uses of health information at a national level.”
Developing such strategies at a time when the health service is still tackling an unprecedented crisis will not be easy. But the cost of not doing so will be too high.
"Biggest problem here is that exhausted GPs and practice staff are so snowed under with clinical work that they do not have time to review and query claims regularly. PCRS depending on this." Dr Sarah Sheehan, @sarahmsheehan1, 28 October
"Great article." Jeannine Webster, @flowepower66, 28 October
"Modern maternity care. *Just six visits to primary care provider allowed for during pregnancy* One visit (only for baby!) at two weeks and one visit for new mum at six weeks. That’s it. A 50-year-old M&I scheme. No structured State-delivered care in first postpartum year." Dr Mark Murphy, @DrMarkMurphy, 28 October
"Reply to @DrMarkMurphy: Agree – We need increased structured State support, with a recognition of the difficulties of the fourth trimester + increased support and education – having been on both sides of the fence recently we do not know enough!"
Dr Aodhnait O'Neill, @OAodhnait, 28 October
"The PCRS was, according to one Dublin GP, engaged in a 'game of attrition' with GPs. Deep into a grave national pandemic, GPs have enough on our plates than to be arguing with an anonymous, self-determining bureaucracy."
Dr Stephen Murphy, @stevemur67, 28 October
"It was a privilege to contribute to this article, thank you @CathyReilly. GPs appreciate advancements in things that make our lives easier, but trust is fragile and if incomes are undermined, change is disincentivised. Communication is the key."
laucullen, @laucullen1, 28 October
REACTION TO OUR NEWS STORY, 'PRIVATE NURSING HOMES’ CLINICAL GOVERNANCE GAPS "POSE HEALTH RISK"', 28 OCTOBER
"HSE risk reg 'There is a risk to the health and wellbeing of the residents of private nursing homes as a result of the current policy and regulatory framework, governance, including clinical governance… and model for private nursing home provision in Ireland.' #SafeguardingLawsNow."
Celine O'Connor, @CelineOConnor12, 27 October
REACTION TO OUR NEWS STORY, 'SURGICAL TRAINING "WILL BE PROLONGED" WITHOUT PROTECTIONS', 28 OCTOBER
"A good piece by @CathyReilly. The same can be said for anaesthesiology training too – anaesthesia training should be protected, especially in the context of greater demands on ICU."
Dr Eoin Kelleher, @EoinKr, 27 October
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While the prospect of raising concerns about issues affecting patient safety can feel intimidating, doing so promptly and in the right way can prevent patients coming to harm and allow colleagues in difficulty to be offered the help and support they need. Healthcare professionals have a duty to speak up, but an organisational culture needs to be fostered allowing individuals to feel confident in coming forward.
One of the most common reasons given by hospital doctors for keeping quiet about working conditions, including issues such as staffing levels, is that raising concerns would not make any difference. A study from the Journal of Health Organisation and Management analysed a national cross-sectional survey of over 5,000 (with a 20 per cent response rate) hospital doctors in Ireland in 2019.
In answer to the question, “If you had concerns about your working conditions, would you raise them?”, 450 respondents said they would, 208 were unsure and around 25 per cent (227) said they would not. Apathy was the most common factor in the reasons provided, including those who felt there was no potential for change, that they wouldn’t be listened to, or that they simply did not have “the time or energy”. Some respondents were fearful for their reputations, career progression, or job security.
However, the authors note that a culture of silence could have a “negative effect on patient outcomes and safety and human resources”. It is, therefore, important for doctors and patients that doctors are empowered to speak out.
Raising concerns is an ethical duty
The Medical Council’s Guide to Professional Conduct and Ethics is currently being updated, but the importance of promoting patient safety and raising concerns is unlikely to alter. It states that you have a duty to raise concerns “if you believe patients are either at risk of, or suffering harm as a result of” systems or matters outside of your control.
Doctors in management roles have additional responsibilities to promote patient safety. This includes ensuring systems are in place and publicised that encourage staff to promptly raise concerns about patient safety. Crucially, the guidance emphasises that staff members who raise concerns in good faith should never be subjected to disciplinary action as a result.
However difficult it feels, your duty to raise honestly held concerns takes precedence over any barriers you might perceive. Remember, you may need to explain or justify not raising concerns and could even face criticism if you fail to speak up about something you were aware of, which affected patient safety.
Raising concerns effectively –MDU advice
Do not be afraid to speak up.
Read and follow your organisation’s policy on raising concerns – a doctor will usually be expected to raise concerns within their own organisation as a first step.
Time can sometimes be an important factor, so it may be necessary to speak to a senior colleague as soon as possible to prevent future or further harm.
Consider whether any of your colleagues have also raised concerns and consider speaking up as a group.
Be honest, open objective, and be able to support your concerns if asked.
Do not make it personal if it concerns a colleague you do not get on with.
Be specific. If possible, provide examples of how patient safety has been affected or may be affected.
Get advice from your medical defence organisation if you are considering escalating concerns beyond your own organisation.
If you have concerns about the safety of patients, or that of yourself or your colleagues, you should inform an appropriate person or authority. The Medical Council provides some examples, such as:
Unsafe systems and service structures. These could include handover arrangements, controlled drugs, and rotas.
Resource constraints, such as the provision of suitable healthcare resources and facilities. Doctors have a duty to advocate for patients if these are unsuitable.
Colleagues with health or competency issues. The Medical Council says that you should usually first discuss your concerns with the doctor themselves “in a sensitive and discreet way” and encourage them to seek professional help. This
might not always be possible, particularly if the colleague is more senior to you, in which case you should identify another suitable person in your organisation to report your concerns to. However, if you are concerned that a colleague may be putting the safety of patients at risk, you must raise concerns with the relevant authorities without delay, which may include the Medical Council.
How to raise a concern
If you have concerns about the safety of patients, or that of yourself or your colleagues, follow your organisation’s procedures. For most hospital doctors, you will need to raise issues with your clinical or medical director in the first instance. If the concern is not investigated or acted on appropriately, it may become necessary to escalate the matter. In all but the most exceptional cases, this should usually be done in stages and within the organisation, ending up (if necessary) at the level of the chief executive or the hospital’s board of directors. Seek advice from your medical defence organisation before escalating concerns beyond your own organisation.
A doctor can make a ‘protected disclosure’ under the Health Act 2004 (as amended) or the Protected Disclosures Act 2014. There are procedural steps that need to be followed to ensure that doctors will be protected from detriment as a result of making a disclosure and you may need advice from your trade union to ensure you know what these are. The HSE website sets out the procedure to be followed.
For more information, visit www.themdu.com/ireland or follow us on Twitter @the_mdu
Think how you would deal with the following, fictional scenario, which is based on those on the Medical Defence Union’s files:
Keep notes of any incidents that concern you, ensuring you do not breach patient confidentiality.
Be clear about the outcome to you personally, such as acknowledgement of receipt of the concerns and a commitment to investigate and take necessary action.
Keep a record of all the steps you have taken. This will be of help if you are subsequently asked to make a statement or be interviewed about the concerns you raised.
A colleague complains to you that a medical specialist trainee on your ward is unhelpful, difficult to work with, and unsupportive of juniors. You have not personally noticed any concerning behaviour and explain this to the colleague. However, later that week, you witness the doctor in question saying they are too busy to see an elderly patient who is complaining of chest pain following admission for the investigation of unexplained falls. You overhear them instructing an intern over the phone to administer 10mg of intravenous morphine despite being advised that the patient has very
low blood pressure and respiratory difficulties. When the patient suffers a cardiac arrest, the specialist trainee documents in the chart that he spoke directly with the junior doctor and advised him to treat the patient’s pain with morphine. However, he notes in the chart that he advised starting at 2mg and titrating up to 10mg if the patient coped, and also to give aspirin and sublingual GTN before calling the on-call cardiology team. You are immediately worried, as you know this was not the case.
You speak to your consultant promptly and tell her about the trainee’s inaccurate records. As a result, probity concerns are now raised, and a formal disciplinary investigation into the doctor’s actions begins.
However difficult it feels, your duty to raise honestly held concerns takes precedence over any barriers you might perceive
Read more by Prof Seamus O’Mahony at www.mindo.ie
The dictum that “you can’t be too rich or too thin” is commonly attributed to Wallis Simpson, but was almost certainly coined by Babe Paley, socialite and daughter of Harvey Cushing. The academic equivalent to this would be that you can’t publish too many papers. A 2018 Nature paper by John Ioannidis, Richard Klavans and Kevin Boyack, entitled ‘Thousands of scientists publish a paper every five days’ questions this assumption. Ionnnidis is a Greek American professor at Stanford University, a founder of the discipline of meta-research – that is, research about research. He and his colleagues searched the literature for authors who had published more than 72 papers (one paper every five days) in any one calendar year between 2000 and 2016, a figure, they wrote, “that many would consider implausibly prolific.” They were careful to point out, however, that “we have no evidence that these authors are doing anything inappropriate”.
They found 9,000 such individuals, 7,888 (86 per cent) of whom were physicists. (It is recognised within physics that these ‘authors’ are simply members of very large teams.) Of the remaining 1,112, 909 authors were Chinese. They were excluded because Chinese universities openly grant cash rewards for publishing papers. In 2016, the average bonus for a lead author of a paper in one of the top journals (such as Nature and Cell ) was $44,000, which is five times the average professorial salary. This left 265
hyperprolific authors, whose number grew twenty-fold between 2001 and 2014. About half of these authors were in medical and life sciences. “We emailed all 265 authors,” they wrote, “asking for their insight about how they reached this extremely productive class.” Eighty-one replied, citing reasons such as hard work, love of research, mentorship of many young researchers, leadership of a research team, extensive collaboration, working on multiple research areas, and “sleeping only a few hours per day”. The median number of full papers was 677.
The authors came from several countries, including the United States (50), Germany (28) and Japan (27). Malaysia (13) and Saudi Arabia (7) were disproportionately represented; both countries, wrote the authors, “incentivise publication with cash rewards”. The Erasmus University in Rotterdam had more hyperprolific authors (9) than any other institution. Eleven authors worked on one large project – the European Prospective Investigation on Cancer and Nutrition. Hyperprolific authors were also concentrated in cardiology. I looked up the publication record of a prominent UK-based professor of cardiovascular medicine and found that he has already published 114 papers in 2021 (up to 15 October): That’s one every 2.5 days. (I would be happy if I read – as opposed to skimmed through – a scientific paper every 2.5 days.)
Authorship of a scientific publication means taking credit and responsibility. The Vancouver criteria for authorship specify that authors must do the following four things to qualify: Play a part in designing or conducting experiments or processing results; help to write or revise the manuscript; approve the published version; and take responsibility for the article’s contents. Although supervision, mentoring and sourcing grant money are not sufficient for authorship, many authors only became hyperprolific when
us wherever we go. These groups were vital in the early days of the emergency that gripped the country. They provided fast evidence-based information. This was necessary as guidelines changed from one hour to the next and they are still valuable resources of ‘just-intime’ information.
they became heads of department, suggesting that they become co-authors regardless of their contribution. Ioannidis emailed a survey on authorship to 81 hyperprolific researchers, of whom 27 replied. Most admitted that they did not fulfil all four Vancouver criteria.
The Covid-19 pandemic has only exacerbated research over-production. In December 2020, Nature reported that four per cent of global research output in 2020 was devoted to coronavirus, and that 2020 also saw a sharp increase in article submission on all subjects to journals. Submissions to the publisher Elsevier’s journals (such as The Lancet) were up by 58 per cent compared to 2019. The journal speculated that this rise might be because researchers had to stay at home, and so concentrated on writing papers. Many papers (an estimated 17-to-30 per cent of all Covid-19 articles) were published as preprints on sites such as medRxiv.org . We have also witnessed the phenomenon of ‘epistemic trespassing’ – scientists from other disciplines, who have no background in virology, epidemiology of infectious disease or vaccine development, have begun to publish papers on Covid-19. A similar phenomenon was observed after the 11 September attacks in 2001, when unqualified researchers, attracted by the large grants available, began to publish on terrorism.
I have known a few hyperprolific researchers – I do not envy them. To be identified as one should be a cause for concern, not a badge of honour. That their emergence is the inevitable consequence of the publish-or-perish culture that has dominated academic medicine for decades. Over-production is incentivised because candidates for senior academic posts and applicants for research grants are judged by these metrics. But these figures are now increasingly meaningless: The published product of medical research is now a devalued currency.
Last Tuesday evening, I had a choice between joining our local CME group online for a business meeting, followed by an educational session on adolescent mental health, or a menopause webinar resourced by the informative Dr Deirdre Lundy. I donned my blue light filter glasses and chose the menopause webinar, along with over 200 like-minded GPs.
The following evening, up to 2,000 GPs signed in to the regular ICGP webinar. Initially weekly, these webinars, following a recent survey of members, and despite large attendances, now take place fortnightly. Those who do not join can watch the recorded version at a time of their choosing. Later, that same week, the ICGP hosted a fourhour online Global Health Conference, with an interesting and relevant programme. As most GPs were in their surgeries at that time, I have no doubt that many, like myself, decided to listen in their leisure time.
Online education exploded into our consciousness with the onset of the pandemic in March 2020 and has been a constant for most GPs ever since. Alongside webinars and meetings, WhatsApp groups have mushroomed for GPs with special interests. Our phones, once used for social communication and entertainment have become workstations, which we carry with
I am currently registered with four such groups: ‘Covid Group,’ ‘START,’ ‘Sth Tipp GP News,’ and a more recently formed group called ‘HRT Prescribers in GP’, hosted on the Telegram platform, which has over 700 members. I know that other groups exist, but I can just about manage these. Being able to post a question to a group of experienced peers, who are uncommonly generous with their time and expertise, and receive a prompt answer that helps me deliver best possible care for a patient, is a great help for my day-to-day practice.
I am grateful for this technology and the shared expertise. These groups are active day and night and while there is no need to read every post, I often find myself spending up to 30 minutes scanning, skimming, pinning, and starring posts that I know I will need at some future date when I will have forgotten the details. So far, so good. But what is the effect of being ‘always on’? It takes more than blue light filter glasses to mitigate the effects of 12-to-14-hour working days. And no matter how much we try to convince ourselves that out-of-hours webinars are not work, they are certainly not leisure. Leisure, for those of us who have forgotten, is when we nourish ourselves. It can be conversation with family or friends, listening to music, reading for the pure pleasure of the words on the page, sitting staring into space thinking about nothing or daydreaming. It can be walking, swimming, cycling, or painting.
Leisure is not paying attention at meetings and webinars, even if we do this from our own fireside, kitchen table, or bed.
And what about the expert GPs who give freely of their time and expertise? Many have invested heavily in further education and training and are happy to help their colleagues free-gratis . But would we expect that same service from any other specialist?
There is also an uneasy feeling that arises when we have not checked in for a while. What are we missing? And how do those GPs who do not participate at all feel?
Are we raising the bar for all GPs, putting pressure on ourselves and others to take on more complicated cases, simply because there is no specialist service available?
(I am thinking in particular about specialist menopause clinics that I know are in the pipeline, but will probably be confined to the Dublin area initially, leaving a lot of rural GPs, like myself, struggling alone.) The demand for menopause expertise has escalated recently and I find myself, with the support of the group, tentatively managing cases that previously I would not have been keen to manage. I wonder at times if I am taking on too much risk and responsibility.
I sometimes think that by engaging with this ‘always on’ culture, GPs are carrying out a major intervention on themselves. What started as a response to a crisis has become the norm. But what are we doing to our brains, our neural networks, our general health? Are we better informed, but less compassionate? Are we less present to ourselves, our families, and our patients? Is it possible to sustain this level of engagement without adequate time to recharge and recover? I do not have answers. Only time will tell.
Question 1
A. Are always yellow.
B. Are umbilicated.
C. Are soft to touch.
D. Are an allergic reaction to the faeces or eggs of an insect.
E. Invariably resolve within a few months.
Question 2
A. Is first seen as an arc at the superior limbus.
B. Is separated from the limbus by a clear zone of cornea.
C. Is invariably associated with hypercholesterolaemia.
D. May be effectively treated with intraocular steroid drops.
E. Is a recognised cause of presbyopia.
Question 3
A. Is defined as any sugar less than 6mmol/l.
B. Primary features are more likely to be behavioural than autonomic (pallor, hunger, sweating).
C. Awareness is heightened compared to adults.
D. In the conscious child is most appropriately treated with chocolate.
E. Does not respond to glucagon.
Question 4
A. Dementia.
B. Untreated injuries in various stages of healing.
C. Inadequate clothing.
D. Sudden changes to will.
E. Unexplained fear.
Question 5
A. Affects males and females equally.
B. Is the common name for the osteoarthritic changes of the first metatarsophalangeal joint.
C. Pain is mainly felt in the ball of the foot.
D. Initial treatment should consist of the use of wide-fitting shoes with soft leather uppers.
E. Main indication for surgery is cosmetic.
E. FALSE. Not if it is the only complaint, but only if the deformity is significant with big toe pronated and overlapping the second toe.
D. TRUE. Remember foot size is one size greater at the end of the day, due to swelling.
C. FALSE. If in ball of foot, diagnosis is metatarsalgia.
B. FALSE. This is hallux rigidus.
A. FALSE. Most patients are female with a family history of the condition.
ANSWER 5
E. TRUE. Or sudden change in or development of unusual behaviour.
D. TRUE. Or signed cheques when older person unable to write.
C. TRUE. Poor personal hygiene, lice or sores.
B. TRUE. And dehydration, soiled clothes.
A. FALSE. Risk factor for it, not sign of it.
ANSWER 4
E. FALSE. Use IM500μgm for those <25kg; 1mg for those >25kg.
D. FALSE. Slowly absorbed compared to three glucose tablets, 100ml of sugar containing cola; or hypostop.
C. FALSE. Can be hypoglycaemic unaware and reach more severe stages of coma with little warning.
B. TRUE. Changes of mood, tiredness, irritability, headache.
A. FALSE. No consistent definition, but usual rule is less than four (four is the floor).
ANSWER 3
E. FALSE. Causes no visual abnormality.
D. FALSE. No treatment required.
C. FALSE. May be, but usually just a part of ageing.
B. TRUE. A 1mm band.
A. FALSE. At inferior limbus then at superior and both arcs extend to meet, forming complete ring.
ANSWER 2
E. FALSE. Often persist for years.
D. FALSE. Thought to follow some minor trauma such as an insect bite.
C. FALSE. Are small, firm nodules.
B. FALSE. On squeezing, a small dimple may be seen on the surface.
A. FALSE. May vary from yellow to brown.
ANSWER 1
Attendees at UCD’s Charles Institute Seminar Series heard a presentation by Prof Karin U Schallreuter of the University of Bradford and University of Greifswald on the current understanding of vitiligo
The Charles Institute, Ireland’s national dermatology research and education centre, hosts a range of guest speakers who cover a variety of topics ranging from skin cancer to psoriasis, among others. The series, which is sponsored by RELIFE (part of the A.Menarini group), is designed to provide expert advice from a range of distinguished national and international experts in their respective fields and is chaired by Prof Desmond Tobin, Full Professor of Dermatological Science at UCD School of Medicine and Director of the Charles Institute of Dermatology. The seminars are broadcast to attendees with a special interest in dermatology and cutaneous science in other locations, who access the talks remotely via an audio-visual link.
The seminar was held using a hybrid model, combining in-person attendance with interactive online access.
Attendees heard a presentation by physician-scientist Prof Karin U Schallreuter, Emerita Professor at the University of Bradford, UK, and University of Greifswald, Germany, on the topic ‘Vitiligo: From Bench to Bedside’.
Prof Schallreuter, a clinical and experimental dermatologist, has spent decades advancing research into skin disorders, including the biochemistry and molecular biology of pigmentary skin disorders. Among a huge range of academic achievements, Prof Schallreuter has published more than 300 peer-reviewed articles and many book chapters. She developed the pseudo-catalase treatment for vitiligo, which she has used to treat thousands of patients. She successfully extended this treatment modality with climatotherapy at the Dead Sea in Israel and Jordan.
Prof Schallreuter pointed out to attendees that vitiligo, which is characterised by an acquired loss of skin colour, is the most common depigmentation disorder worldwide. While its exact cause is yet unknown, there is an accumulating body of evidence to suggest there is a massive epidermal oxidative stress, via H 2 O 2 and peroxynitrite, in those affected by this disease.
Prof Schallreuter and colleagues have shown through extensive research that vitiligo appears to represent a complex reaction pattern or syndrome that involves multiple aetiological factors, some of which work in concert. She explained that in the initial stages of the disease course, there is an accumulation of H 2 O 2 in the mM range in the epidermal compartment of these patients. These high H 2 O 2 levels affect many pathways.
She provided a brief overview of the many clinical types of vitiligo, including the vulgaris , segmental, inflammatory and mixed (segmental and vulgaris) types and the body sites they can affect. Prof Schallreuter told the seminar that vitiligo should not be underestimated or treated as a ‘cosmetic’ problem. “According to the WHO, vitiligo is a disease, and not a bland cosmetic problem or condition,” she said, adding that “it is characterised by a sudden, spontaneous loss of the inherited skin colour.” This can affect the entire body or may be localised, as on the face, neck, axillae, hands, feet or upper and lower extremities, palms and soles, the hips, ano-genital area, abdomen and sacral area, mucosa, or even hair.
The initial diagnosis of vitiligo may seem obvious. But Prof Schallreuter told the attendees that there are other leucodermas mimicking vitiligo. Therefore, the correct diagnosis should always be made using a Wood’s light (351nm). Vitiligo shows a characteristic yellowish/bluish fluorescence, which is absent in leucoderma of other origins. The fluorescence is based on the presence of the H 2 O 2 -mediated oxidation of the important cofactor
6R- tetra -hydro-biopterin (6BH4) and the presence of oxidised 7R- tetra-hydro- biopterin. “Epidermal H 2 O 2 affects 6BH4- synthesis and recycling. 6BH4 is the co-factor for phenylalanine-, tyrosine-, tryptophan-hydroxylases, catecholamine synthesis and beta 2 adrenoceptor signalling, as well as for the nitric oxide reductases,” she said.
She showed the attendees examples of skin viewed with the naked eye compared to when a Wood’s light is used and provided slides to document the fluorescence. This method also allows the physician to detect old or new pigment. She then discussed the physical implications, the psychological impact of the loss of pigment (skin colour) of vitiligo, which can be extremely serious and affect mental health and quality-of-life.
“Vitiligo has an unpredictable course, which is a most scary out-of-control moment,” said Prof Schallreuter. “People are conditioned to think that what is beautiful is therefore ‘good’. A number of studies show that 85.7 per cent of patients with vitiligo experience staring and questions about it from other people, and some are asked by strangers if it is contagious, or even if it is leprosy.”
In terms of incidence, she commented: “There are no difference in incidence between different skin colours, and there is no significant gender difference. However, there is a positive family history in 30-to-45 per cent of patients and onset can occur at any stage of life. It seems more frequent in puberty, pregnancy and menopause, pointing to some hormonal influence in the pathogenesis.”
The pathogenesis of vitiligo is still a clinical conundrum, Prof Schallreuter explained, and there are several theories, including autoimmune causes, cytotoxic factors, biochemical or genetic causes, or even virus. “Together with my colleagues and students, I have demonstrated a body of evidence for the presence of oxidative stress by H 2 O 2 and peroxynitrite and its many consequences,” she said.
“Based on a plethora of in vitro and in vivo research and computer modelling, we demonstrated that the pigment-producing melanocyte is not the only target in vitiligo,” she said. “There is evidence for epidermal H 2 O 2 accumulation in the mM range, as shown by FT-Raman spectroscopy. Epidermal lipid peroxidation in untreated acute vitiligo affects the entire epidermal compartment as a consequence of H 2 O 2 . Moreover, there is evidence for H 2 O 2 -mediated oxidation for many proteins and peptides, leading to impaired function, including deactivation of catalase and other H 2 O 2 -degrading enzymes such as thioredoxin reductase, glutathione reductase and glutathione peroxidase,” she said, pointing out that patients with vitiligo show signs of DNA damage in their skin as well as in their plasma. “This leads us to a paradox in vitiligo,” said Dr Schallreuter. “There is DNA damage, but there is no evidence for increased incidence of solar-induced skin cancer.” Her group discovered that this patient group holds an upregulated wild-type functioning p53 expression which totally
escapes H 2 O 2 -regulation. This p53 can directly repair DNA damage. Interestingly, after topical application with activated pseudocatalase PC-KUS, they lowered DNA damage in the plasma, said Prof Schallreuter. She concluded that her findings strongly support the transfer from epidermal H 2 O 2 into the system and strengthen the generation of H 2 O 2 in the epidermis in vitiligo.
Besides a wide range of proven intrinsic H 2 O 2sources, the skin also has to cope with many exogenous sources of H 2 O 2 , including from sunlight/radiation, chemical compounds such as hydroquinone, Q10, phenols, curcumin and chlorine, and hormones like oestrogen and androgens.
Therefore, it seemed a realistic overall aim to reduce the excessive levels of epidermal H 2 O 2 , she said. “Topical application of an active pseudocatalase PC-KUS leads to reduction of epidermal H 2 O 2 , leading in turn to a) a cessation of the depigmentation process; b) to a recovery in epidermal catalase protein expression and enzyme activities; and c) to repigmentation of the white vitiligo patches,” she told the attendees. Prof Schallreuter displayed slides to show the before-and-after recovery of epidermal catalase protein expression in vitiligo after treatment with pseudocatalase PC-KUS. Moreover, she showed the seminar slides to illustrate some remarkable improvements of vitiligo after three months of treatment, with stable disease for 10 years after ending the treatment.
“It’s important to note that the duration of the disease has no influence on repigmentation,” she told the attendees. “Also, repigmentation of vitiligo is independent of skin colour.” She presented another case study showing a dramatic improvement in segmental vitiligo before and after 12 months of treatment with pseudocatalase PC-KUS, including the recovery of eyelash colour. This particular patient had stable disease and repigmentation more than 20 years after treatment, she explained.
“One important message for anxious parents: Repigmentation of vitiligo in children is independent of a positive family history and the extent of the disease,” said Prof Schallreuter. “There is also evidence to show a significant improvement in patients’ quality-of-life during and after treatment, especially after combined climatotherapy at the Dead Sea in a group of patients with this disease.”
She concluded with a brief recap of currently-used old and novel therapies for vitiligo, including topical and systemic immunomodulation via pharmacological therapies, climatotherapy at the Dead Sea, light therapy, photo-chemo-therapy and systemic antioxidants.
During an interactive Q&A session following the presentation, Prof Tobin remarked on how, regardless of the duration of vitiligo, the chances of repigmentation do not change. “On the question of when does ‘late’ become ‘too late’, I think that’s quite interesting, particularly in relation to the population of stem cell melanocytes and the loss of that reservoir.” He cited research which shows that there may be a population of melanocytes that are so immature that they do not get caught up in the disease process in vitiligo. “That may explain why as long as the melanocyte is not expressing a targetable differentiation protein, the cells is not therefore ‘recognised’ by whatever is happening around it,” he commented.
RELIFE has had no input into the content of this article or series of seminars
RELIFETM. MY SKIN SAYS HOW I FEEL.
ECZEMA, DERMATITIS, SENSITIVE SKIN & BABY CARE.
DRY, VERY DRY, ROUGH AND CRACKED SKIN.*
OILY, BLEMISHED AND ACNE PRONE SKIN.
HYPERPIGMENTATION AND MELASMA.
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
CASE STUDY 1
A 70-year-old male patient presented for review of a chronic cough. He had a history of childhood asthma but had not been treated for asthma as an adult. He had worked in the navy previously.
He described a chronic cough for two years productive of small amounts of sputum. He had been treated with several courses of antibiotics with no improvement.
A CT chest demonstrated some minor atelectasis but lung fields were otherwise clear. Pulmonary function tests were consistent with a diagnosis of asthma - within normal limits but with a significant response to bronchodilator.
CASE STUDY 2
A 43-year-old woman presented with exertional dyspnoea. Her past medical history was significant for Hashimoto’s thyroiditis and allergic rhinitis, and both her father and cousins had a history of asthma. She had had pertussis as a young child and had a frequent dry cough until the age of six but was never diagnosed with asthma and was well for the remainder of her childhood. She grew up on a farm around animals and hay. Occasionally during her 20s she would find it hard to catch her breath and would develop a wheeze with exercise.
Since having a lower respiratory tract infection eight years prior to presentation she had had episodes of nocturnal dyspnoea and wheeze; a year prior to presentation she was commenced on budesonideformoterol but did not experience any symptomatic improvement.
At the time of assessment she was having symptoms of dyspnoea and wheeze two-to-three days a week, with nocturnal dyspnoea and a wheeze with exercise. PFTs demonstrated a mild obstructive deficit with a significant response to bronchodilator, consistent with a diagnosis of asthma. Skin prick testing was negative for all allergens, and a serum IgE was normal, thus there was no evidence of associated atopy. She was switched to fluticasone-salmeterol, initially two puffs BD, and upon review had no symptoms of asthma, did not require her PRN salbutamol and was able to take up running again with no exacerbation of symptoms. The combination preventer therapy has now been reduced to one puff BD.
A 29-year-old female patient was referred for assessment of intermittent chest pain and nocturnal dyspnoea. She had never been diagnosed with asthma although described recurrent bronchitis as a child which resolved when she reached adulthood. There was no family history of asthma or atopy.
Three months prior to presentation she had had a short febrile illness, following which she developed nocturnal chest heaviness associated with some dyspnoea and occasional wheeze.
On examination chest was clear to auscultation. She was commenced on budesonide-formoterol and PRN salbutamol, but after eight weeks of regular preventer therapy she continued to complain of ongoing symptoms of chest tightness and discomfort for which she was still requiring regular salbutamol (which provided immediate relief). She was switched to a novel therapeutic combination of glycopyrronium, mometasone and indacaterol, which significantly reduced her requirement for PRN salbutamol. Repeat PFTs demonstrated a significant improvement, with an increase in FEV1 of almost 750mL.
Asthma is defined as a chronic disease of variable airway obstruction due to mucous hypersecretion and bronchial hyperreactivity.1 The diagnosis is made on pulmonary function tests (PFTs) demonstrating a significant response to bronchodilator (defined by the American Thoracic Society as greater than 200ml and 12 per cent increase in FEV1 after bronchodilator).1
Although asthma is often diagnosed in childhood, there is also a subset who are diagnosed in adulthood. This diagnosis is often delayed due to an atypical presentation.
Therapy is individualised based on severity of symptoms and is then up- or down-titrated depending on response. Therapy is becoming increasingly focused on phenotype and there are a number of adjunctive therapies available.
Patient education remains paramount, particularly with respect to daily monitoring of peak flow and symptoms, and with respect to correct technique with inhaler therapy. This is particularly important in older patients with asthma and suboptimal control, in whom poor inhaler technique may contribute significantly to lack of improvement with therapy. Regular review is important to ensure therapy remains appropriate for both severity and level of control.
Most asthma begins in childhood, with 95 per cent of asthma patients having had their first epodes before the age of six years. The main risk factors in asthma beginning in childhood are: Genetic predisposition/a family history of allergy/asthma, viral respiratory infections, bacterial colonisation, allergic sensitisation, and tobacco exposure.2 Patients with childhood asthma tend to have a Th2-predominant inflammatory pattern and a good response to corticosteroids.3,4 Asthma that begins in adulthood is often non-atopic, more severe and associated with a faster decline in lung function.1,2 It often requires treatment with high doses of inhaled and/or oral steroids.3 In recent years phenotypic types of asthma have begun to emerge. In the Severe Asthma Research Programme, five clusters were identified, and 80 per cent of those studied could be divided into a subtype using three variables: Baseline FEV1; maximum FEV1 after bronchodilator; and age of onset of asthma. The cluster with the most severe phenotype was largely made up of patients with a diagnosis in adulthood.2
The factors associated with adult-onset asthma are less well-known. It appears to mainly affect females, has a low remission rate, and is less associated with allergy/atopy.2,3,5 Additionally, individuals who had asthma as a child may redevelop symptoms in adulthood.5 There appears to be a large number of possible triggers associated with adult-onset asthma including
respiratory tract infections, moulds, cigarette smoke, occupational exposure, and environmental pollutants.4 Obesity is a risk factor for adult-onset asthma and increases the risk by up to 50 per cent.3 One study has examined long-term outcomes in adult-onset asthma and changes in asthma severity over time. Practically all, 95 per cent, of the patients in the study had ongoing active asthma five years after diagnosis, and half had moderate to severe disease.2 In a study assessing severity of adult-onset asthma, those with severe disease were less likely to be sensitised to common allergens, had more nasal symptoms, and were more likely to have a history of nasal polyposis.4
Several phenotypic patterns appear in the context of adult-onset asthma (see Figures 1 and 2). These have been described based on presentation (allergic, non-allergic, occupational), airway inflammation (eosinophilic and non-eosinophilic), and severity.6 Of these, presence or absence of eosinophilic inflammation (Th2- or non-Th2-associated) is a key phenotypic differentiator.5
Studies suggest low levels of eosinophilia in obesity-related asthma.3 Obesity is associated with low-level systemic inflammation, with increases in many inflammatory markers including CRP, IL-6, TNF-alpha, and leptin, which may play a role in the link between obesity and adult-onset asthma.3 However, patients with severe asthma appear to have higher levels of both blood and sputum eosinophilia than
Adult-onset asthma has distinct phenotypic variants that require specific investigations and often a different therapeutic approach than childhood asthmaFigure 1: Key phenotypes and risk factors for late-onset asthma6
those with mild-to-moderate asthma.4 Women are significantly more likely to develop asthma following puberty, and have more severe disease.2,3 Asthma is 20 per cent more common in females than in males over the age of 35 years.2 It appears that it is the non-allergic asthma that has a higher incidence in women of reproductive age, whereas there is no similar difference seen in the incidence of allergic asthma.2 Phases of the menstrual cycle have also been associated with asthma severity and atopy in women.3 Thus there appears to be a hormonal role, possibly oestrogenic, although the exact link remains unclear. Whilst there remains considerable debate about the exact definitions and phenotypic subtypes of adult-onset asthma (and asthma in general), studies have begun to identify various groups of patients that have different risk factor profiles, but also very different responses to treatment. The Seinajoki Adult Asthma Study of patients with new-onset adult asthma identified five phenotypes: non-rhinitic asthma, smoking asthma, female asthma, obesity-related asthma, and early-onset atopic adult asthma.6 In a study by Amelink et al,4 patients were classified into three groups: Patients with severe eosinophilic inflammation-predominant asthma and persistent airflow limitation despite high-intensity anti-inflammatory treatment; obese women with frequent symptoms, need for frequent medical care, and low sputum eosinophils; and patients with mild-moderate, well-controlled asthma with normal lung function and low inflammatory markers.
As phenotypic variants become increasingly identified, this assists healthcare practitioners to focus on specific assessments and subsequently to individualise therapy.
In adult-onset asthma associated with the Th2 phenotype and related to rhinosinusitis, it is important to identify the phenotype early, as pulmonary function is poor from onset and exacerbations occur frequently5 – (see Figure 3). Thus utilising a biomarker, such as fractional exhaled nitric oxide (FENO) that identifies Th2-type inflammation may be highly useful.5
Th2-type biomarkers including blood eosinophils, FENO, and periostin are used to identify those patients with Th2-driven adult-onset asthma.5 These biomarkers are particularly useful to assess asthma/COPD overlap syndromes, and may assist with prediction of response to corticosteroids.5
Management
In childhood-onset allergic asthma, treatment with daily corticosteroids combined with long-acting beta-agonists is usually very effective.
In contrast, many patients with adult-onset asthma do not have a good response to corticosteroids.2,5 Specifically, non-Th2type adult-onset asthma may require other treatment strategies including macrolides, diet/weight loss and smoking cessation.5
In addition to avoidance of exposure to known precipitants such as cigarette smoke and occupational sensitisers, targeted treatments based on phenotype are now being increasingly developed.
Omalizumab
Omalizumab is a humanised antibody against IgE. It was originally developed to treat severe allergic asthma, but has been shown to have efficacy on non-allergic asthma and nasal polyps, so may be of benefit to certain patients with adult-onset asthma,2 although its efficacy appears to be greater for early-onset asthma.5
Mepolizumab
Mepolizumab is a humanised monoclonal antibody against IL-5 that selectively targets and inhibits eosinophilic airway inflammation. In some recent studies it has been shown to be effective and safe as a treatment for patients with severe eosinophilic asthma; it has also been demonstrated to have efficacy in treatment of severe nasal polyposis.2
Lebrikizumab
Lebrikizumab is a humanised monoclonal antibody that binds to IL-1.3 It has been shown to be useful for patients with mod-
erate asthma, particularly the subset who had circulating levels of periostin above the median with a high Th2 phenotype.2
Reslizumab
Reslizumab is a humanised monoclonal antibody against IL-5, which has been shown to reduce exacerbations and improve lung function to a greater degree in those with adult-onset asthma than childhood asthma.5
Bronchial thermoplasty is a bronchoscopic procedure during which controlled thermal energy is applied to the airway wall, decreasing the amount of smooth muscle.2
It may offer one of very few therapeutic options for patients with adult-onset non-eosinophilic severe asthma. Studies have shown improvement in lung function, airway hyperresponsiveness, quality-of-life, and symptom scores, with a reduction in exacerbations and hospitalisations. 2
Bariatric surgery
For obese patients with non-eosinophilic asthma, the only treatment option at present is significant weight loss, and a study has demonstrated improved asthma control following bariatric surgery in this cohort of patients.2
Conclusion
In summary, asthma investigation and management is becoming increasingly individualised. Adult-onset asthma has distinct phenotypic variants that require specific investigations and often a different therapeutic approach than childhood asthma, with less reliance on inhaled corticosteroids and an increased focus on lifestyle modifications and targeted monoclonal therapies.
References
1. Tommola M, Won HK, Ilmarinen P, et al. Relationship between age and bronchodilator response at diagnosis in adult-onset asthma. Respir Res 2020; 21:179. doi: 10.1186/ s12931-020-01441-w
2. De Nijs SB, Venekamp N, Bel EH. Adult-onset asthma: is it really different? Eur Respir Rev 2013; 22:44-52. doi: 10.1183/09059180.00007112
3. Ilmarinen P, Tuomisto LE, Kankaanranta H. Phenotypes, risk factors, and mechanisms of adult-onset asthma. Mediators of Inflammation 2015. doi: 10.1155/2015/514868
4. Amelink M, de Groot JC, de Nijs SB, et al. Severe adult-onset asthma: A distinct phenotype. J All Clin Immunol 2013; 132(2): 336-341. doi: 10.1016/j.jaci.2013.04.052
5. Hirano T, Matsunaga K. Late-onset asthma: current perspectives. J Asthma Allergy 2018; 11: 19-27. doi: 10.2147/JAA. S125948
6. Quirce S, Heffler E, Nenasheva N, et al. Revisiting late-onset asthma: Clinical characteristics and association with allergy. J Asthma Allergy 2020; 13: 743-752 doi: 10.2147/JAA.S282205
1x daily
ENERZAIR® BREEZHALER® is indicated as a maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta2-agonist and a high dose of an inhaled corticosteroid who experienced one or more asthma exacerbations in the previous year.2
Abbreviated Prescribing Information
Please refer to Summary of Product Characteristics (SmPC) before prescribing. Enerzair® Breezhaler® (indacaterol (as acetate), glycopyrronium bromide, mometasone furoate) inhalation powder, hard capsules.
Presentation: Hard capsules for inhalation each containing 150 mcg of indacaterol (as acetate), 63 mcg of glycopyrronium bromide equivalent to 50 mcg of glycopyrronium and 160 mcg of mometasone furoate. Each delivered dose contains 114 mcg of indacaterol acetate, 46 mcg of glycopyrronium and 136 mcg of mometasone furoate. Indications: Maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta2-agonist and a high dose of an inhaled corticosteroid who experienced one or more asthma exacerbations in the previous year. Dosage and Administration: One capsule once daily, administered at the same time of the day each day, using the Enerzair Breezhaler inhaler. No dose adjustment is required in elderly patients, in patients with mild to moderate renal impairment, or in patients with mild or moderate hepatic impairment. Caution should be observed in patients with severe renal impairment or end-stage renal disease requiring dialysis. No data available for patients with severe hepatic impairment, only use in these patients if the expected benefit outweighs the potential risk. The safety and efficacy in paediatric patients below 18 years of age have not been established. Contraindications: Hypersensitivity to the active substances, lactose monohydrate or magnesium stearate. Warnings/Precautions: Deterioration of disease: Should not be used to treat acute asthma symptoms, including acute episodes of bronchospasm. Treatment should not be stopped abruptly. Hypersensitivity: Immediate hypersensitivity reactions have been observed after administration. If signs suggesting allergic reactions occur, in particular angioedema, urticaria or skin rash, treatment should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm: If paradoxical bronchospasm occurs, treatment should be discontinued immediately and alternative therapy instituted. Cardiovascular effects: Like other medicinal products containing beta2-adrenergic agonists, may produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms. Use with caution in patients with cardiovascular disorders (coronary artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension), convulsive disorders, thyrotoxicosis, and in patients who are unusually responsive to beta2-adrenergic agonists. Long acting beta2-adrenergic agonists (LABA) or LABA containing combination products such as Enerzair Breezhaler should be used with caution in patients with known or suspected prolongation of the QT interval or who are being treated with medicinal products affecting the QT interval.
Hypokalaemia: Beta2-adrenergic agonists may produce significant hypokalaemia in some patients, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. In patients with severe asthma hypokalaemia may be potentiated by hypoxia and concomitant treatment, which may increase the susceptibility to cardiac arrhythmias. Hyperglycaemia: Inhalation of high dose of beta2-adrenergic agonists and corticosteroids may produce increases in plasma glucose. Upon initiation of treatment, plasma glucose should be monitored more closely in diabetic patients. Anticholinergic effect related to glycopyrronium: use with caution in patients with narrow-angle glaucoma or urinary retention. Prevention of oropharyngeal infections: In order to reduce the risk of oropharyngeal candida infection, patients should be advised to rinse their mouth or gargle with water without swallowing it or brush their teeth after inhaling the prescribed dose. Systemic effects of corticosteroids: Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. Should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections. Excipients: Contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicinal product. Interactions: No specific interaction studies
December 2020 | 103207
ONCE DAILY
Indacaterol acetate / glycop yrronium bromide / mometasone furoate inhala tion p owder
were conducted with indacaterol/glycopyrronium/mometasone furoate. Information on the potential for interactions is based on the potential for each of the monotherapy components. Medicinal products that prolong QTc interval: Should be administered with caution in patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or medicinal products known to prolong the QT-interval. Hypokalaemic treatment: Concomitant treatment with methylxanthine derivatives, steroids, or nonpotassium sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists. Beta-adrenergic blockers: Should not be given together with beta-adrenergic blockers unless there are compelling reasons for their use. Where required, cardioselective beta-adrenergic blockers should be preferred, although they should be administered with caution. CYP3A4 and P-glycoprotein inhibitors: Inhibition of CYP3A4 and P-gp has no impact on the safety of therapeutic doses of Enerzair Breezhaler. Cimetidine and inhibitors of organic cation transport: No clinically relevant drug interaction is expected when glycopyrronium is co-administered with cimetidine or other inhibitors of the organic cation transport. Other long-acting antimuscarinics and LABAs: Co-administration with other medicinal products containing long-acting antimuscarinics or LABAs is not recommended. Fertility, Pregnancy and Lactation: Should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus. No information available on the presence of indacaterol, glycopyrronium or mometasone furoate in human milk, on the effects on a breast-fed infant, or on the effects on milk production. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Studies do not indicate a concern regarding fertility in either males or females. Undesirable Effects: Very common (≥1/10): nasopharyngitis, asthma (exacerbation). Common (≥1/100 to <1/10): upper respiratory tract infection, candidiasis, urinary tract infection, hypersensitivity, headache, tachycardia, oropharyngeal pain, cough, dysphonia, gastroenteritis, musculoskeletal pain, muscle spasms, pyrexia. Uncommon (≥1/1,000 to <1/100): hyperglycaemia, cataract, dry mouth, rash, pruritus, dysuria. Please consult the Summary of Product Characteristics for a detailed listing of all adverse events before prescribing. Pack Size(s): Single pack containing 30 x 1 hard capsules, together with one inhaler. Pack containing 30 x 1 hard capsules, together with 1 inhaler and 1 sensor. The sensor and App are not required for administration to the patient. The sensor and App do not control or interfere with delivery of the medicinal product using the inhaler. Legal Category: POM. Product (Marketing)
Authorisation Number(s): EU/1/20/1438/002 & 003. Product (Marketing) Authorisation Holder: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland. Full prescribing information is available upon request from: Novartis Ireland Limited, Vista Building, Elm Park Business Park, Elm Park, Dublin 4. Tel: 01-2601255 or at www.medicines.ie. Detailed information on this product is also available on the website of the European Medicines Agency http://www.ema.europa.eu Prescribing Information last revised: July 2020.
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.
References: 1. European Medicines Agency CHMP Press Release. Available at: https://www.ema. europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-28-30-april-2020
Date accessed: January 2021. 2. ENERZAIR® BREEZHALER®. Summary of Product Characteristics. Available at www.medicines.ie Date accessed: January 2021. 3. Propeller® Sensor for Enerzair® Breezhaler® Instructions for Use. Available in each pack of Enerzair® Breezhaler® plus Sensor.
Respiratory syncytial virus (RSV) is a common, ubiquitous and contagious viral pathogen that infects the respiratory tract of most children by two years of age. RSV is an RNA pneumovirus of the Paramyxoviridae family, and humans are the only natural host.
RSV is primarily a childhood infection; however, it may occur at any age and can be most severe in infants under one year of age, the immunocompromised, and in people aged 65 years and older.3,7 It infects 90 per cent of children within the first two years of life and frequently re-infects older children and adults.10
RSV infection can present as a variety of clinical syndromes including upper respiratory tract infections, bronchiolitis, pneumonia, exacerbations of asthma and viral-induced wheeze.1 Worldwide, it is estimated that RSV is responsible for approximately 33 million lower respiratory tract illnesses, three million hospitalisations, and up to 199,000 childhood deaths annually. The majority of deaths are in resource-limited countries.10 In medium and high resource countries, the RSV mortality rate in infants is almost nine times that of influenza.7
RSV has been shown to account for 22 per cent of all episodes of acute lower respiratory tract infection in children globally, with the greatest burden of severe disease requiring hospitalisation in infants under one year and particularly those under six months of age.2,5
For most babies and young children the infection is mild, presenting with cold-like symptoms which usually last one to two weeks, but for a small percentage, RSV infection can lead to serious and sometimes life-threatening problems, such as pneumonia or bronchiolitis.4 The chance of developing severe infection is highest for premature babies, children less than 10 weeks old, children aged under two years with congenital heart or chronic lung disease, and infants and young children with a weak immune system or who are immunocompromised.3,4
Adults with weakened immune systems and those aged 65 years and older are also at increased risk of developing severe RSV disease. Approximately one-in-20 older people develop RSV infection each year. Overcrowding, smoking and passive smoking are recognised risk factors for infection.3
RSV infection has been a notifiable disease in Ireland since January 2012, and RSV activity in Ireland is monitored by the Health Protection Surveillance Centre (HPSC).3 According to the HPSC (2020), nearly all children have been infected with RSV at least once, by two years of age. Most cases are not specifically diagnosed as RSV; however, the infection causes 80 per cent of bronchiolitis and 20 per cent of pneumonia cases in young children and RSV is a significant cause of infection and outbreaks in hospitals, neonatal units, day units, and nursing homes.3
RSV infections occur in a seasonal pattern in temperate climates with epidemics from October to April.7 Outbreaks typically occur in the winter months with the highest numbers of infections usually reported in December and January every year. The sharp winter peak varies little in timing or size from year to year, in contrast to influenza.3
There is only one serotype of RSV, but it is classified into two strains, A and B, with differences consisting of variation in the structure of several structural membrane proteins, most especially the attachment protein.10 One of the two major antigenic subgroups of RSV A or B, usually predominates each season.7 RSV typically spreads via hands, fomites and the airborne aerosol route. It spreads from person to person by aerosol droplets through coughing or sneezing, and is also spread through direct contact by touch. RSV can survive on surfaces and objects for 24 hours and spread can occur indirectly through contact with contaminated hands.1,4 Handwashing is the most effective infection control procedure.
The incubation period for RSV-infected individuals ranges from three-to-eight days, but immunocompromised patients with
severe infection may shed virus for up to four weeks. The frequent occurrence of mild or asymptomatic infection in otherwise healthy individuals makes infection control challenging.7
After inoculation into the nasopharyngeal or conjunctival mucosa, the virus rapidly spreads into the respiratory tract, where it targets its preferred growth medium, apical ciliated epithelial cells. There it binds to cellular receptors using the RSV-G glycoprotein and uses the RSV-F fusion glycoprotein to fuse with host cell membranes and insert its nucleocapsid into the host cell to begin its intracellular replication.10
Symptoms include: Fever, rhinorrhoea, pharyngitis, nasal congestion, sneezing, coughing which can be croupy or barking in nature, tachypnoea, sore throat, wheeze, decreased appetite, and ear infections in children. In very young infants, irritability, decreased activity and breathing difficulties may be the only symptoms of infection.
Lower respiratory tract infections, such as pneumonia or pneumonitis, are most likely to occur during a child's first infection with RSV and may develop in 30-to-70 per cent of those with a first infection. Typically, only between 1 and 3 per cent of infected infants require hospitalisation.7
The infectious period lasts from shortly before onset to one week post the onset of symptoms. Most children recover in eight-to-15 days. Even after recovery, however, very young infants and children with weakened immune systems can continue to spread the virus for one-to-three weeks. Immunity is incomplete and short-lived. Repeated RSV respiratory infections can occur, although these are usually mild and become less common with increasing age.3,7
Bronchiolitis is an inflammatory process in the small airways of the lungs and is the most common clinical syndrome associated with RSV infection. It typically presents in infants under one year of age, but may be diagnosed in children up to two years old, and is characterised by a short history of low-grade fever, cough, coryza, dyspnoea, and reduced feeding. The symptoms usually peak in clinical severity between day three and five of the illness. RSV bronchiolitis presents a significant clinical burden. In the UK, infection with RSV is responsible for up to 80 per cent of all cases of bronchiolitis, similar to that of 65-to-70 per cent in the US.3,8
In older children, RSV typically presents as an upper respiratory tract infection, viral pneumonia, episodic viral-induced wheeze or an acute exacerbation of asthma. Viral pneumonia is a common illness with five million cases reported globally in children annually. A meta-analysis of nine studies involving over 4,000 children investigating viruses identified by polymerase chain reaction (PCR), found that RSV was the causative organism in 11 per cent of community-acquired pneumonia cases.6
Diagnosis of RSV includes a thorough medical history and a physical exam. A chest x-ray may be requested and blood and urine tests may be carried out to rule out a bacterial infection or other conditions. Differential diagnosis can include asthma, bronchiolitis, influenza, croup, bronchitis and pneumonia.10 Respiratory viral testing may be used in a clinical setting to increase confidence in the diagnosis of a viral, rather than bacterial, cause for respiratory illness. RSV can be detected in nasopharyngeal aspirate, broncho-alveolar lavage, sputum, or swabs from the nose and throat by using real-time PCR, immunofluorescence, ELISA and growth in cell culture. Reverse transcriptase-PCR (RT-PCR) assays are currently the gold standard in RSV testing and are available commercially. These are more sensitive than antigen detection and virus isolation methods. The sensitivity of antigen detection tests ranges from 80-to-90 per cent in children, but is less sensitive in adults. Serological tests are used less for routine diagnosis and more for seroprevalence and epidemiological studies.3,7
Vaccination
There is currently no vaccine available against RSV infection. Palivizumab, which is a humanised mouse monoclonal
antibody specific for the F protein of RSV, provides passive immunity against RSV. Palivizumab inhibits RSV binding to host cells and prevents fusion of infected cells with adjacent cells. It is authorised in Ireland for the prevention of serious lower respiratory tract disease requiring hospitalisation caused by RSV in children at high risk for RSV disease.7
Palivizumab prophylaxis reduces the absolute risk of RSV hospitalisation from about 10-to-5 per cent for premature babies, infants with chronic lung disease and haemodynamically significant congenital heart disease, particularly when complicated by large left-to-right shunts, and pulmonary hypertension. It does not reduce mortality or the need for mechanical ventilation.7,3
Palivizumab is given as an intramuscular injection monthly (up to five doses) during the RSV season. As it is very expensive and has a half-life of 18-to-21 days, meaning monthly injections are required to maintain protective titres, cost-benefit analyses limit its use to only the most vulnerable infants, those born prematurely with moderate or severe BPD, haemodynamically significant, acyanotic congenital heart disease, severe combined immunodeficiency or infants with other severe chronic lung conditions or requiring long-term ventilation.9 Differences in epidemiology, practice setting, healthcare systems and drug cost have resulted in variability in palivizumab recommendations and use nationally and internationally.
The mainstay of treatment for the vast majority of RSV infections is supportive including rest, fluids and paracetamol, but passive preventive immunisation is available for at-risk children, including premature infants and infants with a history of cardiac, pulmonary, or neuromuscular diseases. Those with severe respiratory illness require hospitalisation, oxygen therapy, IV fluids and ventilatory support in the form of a high-flow nasal cannula, CPAP, or intubation, and mechanical ventilation.7,10
Ribavirin is the only licensed antiviral medication for the specific treatment of RSV infection, but due to drug toxicity, including bone marrow suppression and potential carcinogenicity and teratogenicity and minimal clinical benefit, it has not been recommended for routine clinical use.9 Ribavirin may be considered for a small number of patients and treatment of RSV with ribavirin must be done under the supervision of an infection specialist, such as a consultant microbiologist or an infectious disease specialist.3
Other treatment modalities for bronchiolitis have been tried in the past and have failed to show broad, reproducible efficacy on clinically significant outcomes in RSV and bronchiolitis. These include albuterol, epinephrine, steroids, hypertonic saline, antibiotics, and chest physical therapy, and routine use of these interventions is not recommended.10 Antibiotics are not effective against RSV and it is important that unnecessary antibiotics are discontinued once a diagnosis is confirmed, to avoid adverse drug reactions and antibiotic resistance.3
Although palivizumab may help prevent serious complications of RSV infection, it is not used to treat RSV infection.
Infants who are recovering from RSV bronchiolitis can continue to have respiratory symptoms including cough and post-bronchiolitis wheeze for several weeks/months. There is no evidence for the use of steroids, montelukast or other medications in preventing these symptoms, but the acute episodes often respond to anti-asthma medication.9 Highrisk infants with other co-morbidities may require longer admission and some may even require mechanical ventilation. However, the majority of children with RSV make a full recovery and have an excellent outcome. The majority of children who need hospital admission are usually discharged in several days. Some infants with RSV may develop wheezing, but recent studies do not show an increased risk of asthma.10
* Relvar Ellipta is indicated for the regular treatment of asthma in adults and adolescents aged 12 years and older where use of a combination medicinal product (long-acting β 2-agonist and inhaled corticosteroid) is appropriate: patients not adequately controlled with inhaled corticosteroids and ‘as needed’ inhaled short acting β 2-agonists or patients already adequately controlled on both inhaled corticosteroid and long-acting β 2 - agonist 2
For Healthcare Professionals only. Images used are for illustrative purposes only. Relvar is well tolerated. Most common adverse events are nasopharyngitis and headache2 PM-IE-FFV-ADVT-210002 September 2021
Relvar Ellipta was developed in collaboration with
References:
1. Bernstein DI et al. J Asthma 2015; 52: 1073-1083. 2. Relvar Ellipta SmPC, 2021, available on www.medicines.ie
Relvar® Ellipta® (fluticasone furoate/ vilanterol [as trifenatate]) Prescribing information
(Please consult the full Summary of Product Characteristics (SmPC) before prescribing) Relvar® Ellipta® (fluticasone furoate/vilanterol [as trifenatate]) inhalation powder. Each single inhalation of fluticasone furoate (FF) 100 micrograms (mcg) and vilanterol (VI) 25mcg provides a delivered dose of 92mcg FF and 22mcg VI. Each single inhalation of FF 200mcg and VI 25mcg provides a delivered dose of 184mcg of FF and 22mcg of VI. Indications: Asthma: Regular treatment of asthma in patients ≥12 years and older where a long-acting β2-agonist and inhaled corticosteroid combination is appropriate and where patients are not adequately controlled on inhaled corticosteroids and “as needed” short-acting inhaled β2-agonists, or where patients are already controlled on both inhaled corticosteroid and long-acting β2-agonist. COPD (Relvar 92/22mcg only): Symptomatic treatment of adults with COPD with a FEV1<70% predicted normal (post-bronchodilator) and an exacerbation history despite regular bronchodilator therapy). Dosage and administration: Inhalation only. Asthma: Patients with asthma should be given the strength of Relvar Ellipta containing the appropriate fluticasone furoate (FF) dosage for the severity of their disease. Prescribers should be aware that in patients with asthma, FF 100 mcg once daily is approximately equivalent to fluticasone propionate (FP) 250 mcg twice daily, while FF 200 mcg once daily is approximately equivalent to FP 500 mcg twice daily. Adults and adolescents ≥12 years: one inhalation once daily of: Relvar 92/22mcg for patients who require a low to mid dose of inhaled corticosteroid in combination with a long-acting β2-agonist. If patients are inadequately controlled then the dose can be increased to one inhalation once daily Relvar 184/22mcg. Relvar 184/22mcg can also be considered for patients who require a higher dose of inhaled corticosteroid in combination with a long-acting β2-agonist. Regularly review patients and reduce dose to lowest that maintains effective symptom control. COPD: one inhalation once daily of Relvar 92/22mcg. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose
monohydrate & magnesium stearate). Precautions: Pulmonary tuberculosis, severe cardiovascular disorders, heart rhythm abnormalities, thyrotoxicosis, uncorrected hypokalaemia or patients predisposed to low levels of serum potassium. chronic or untreated infections, diabetes mellitus. Paradoxical bronchospasm – substitute alternative therapy if necessary. In patients with hepatic with moderate to severe impairment 92/22mcg dose should be used. 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. Asthma-related adverse events and exacerbations may occur during treatment. Patients should continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of Relvar. Systemic effects: Systemic effects of inhaled corticosteroids may occur, particularly at high doses for long periods, but much less likely than with oral corticosteroids. Possible Systemic effects include: Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract, glaucoma. More rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Increased incidence of pneumonia, including pneumonia requiring hospitalisation, has been observed in patients with COPD receiving inhaled corticosteroids. If a patient presents with visual disturbance they should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma, or rare diseases such as central serous chorioretinopathy. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations. Risk factors for pneumonia include: current smoking, older age, low body mass index and severe COPD. The incidence of pneumonia in patients with asthma was common at the higher dose of Relvar (184/22mcg). Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption
should not use Relvar. Interactions with other medicinal products: Interaction studies have only been performed in adults. Avoid β-blockers. Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir, cobicistat-containing products). Concomitant administration of other sympathomimetic medicinal products may potentiate the adverse reactions of FF/VI. Relvar should not be used in conjunction with other longacting β2-adrenergic agonists or medicinal products containing long-acting β2-adrenergic agonists. Pregnancy and breast-feeding: Experience limited. Balance risks against benefits. Side effects: Very Common (≥1/10): Headache, nasopharyngitis. Common (≥1/100 to <1/10): Candidiasis of the mouth and throat, pneumonia, bronchitis, upper respiratory tract infection, influenza, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, muscle spasms, fractures, pyrexia. Uncommon (≥1/1,000 to <1/100): Hyperglycaemia, vision blurred, extrasystoles. Rare (≥1/10,000 to <1/1,000): Hypersensitivity reactions including anaphylaxis, angioedema, rash and urticaria; palpitations, tachycardia, tremor, anxiety, paradoxical bronchospasm. Marketing authorisation (MA) Holder: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. MA Nrs: 92/22mcg 1x30 doses [EU/1/13/886/002]; 184/22mcg 1x30 doses [EU/1/13/886/005].
Legal category: POM B. Last date of revision: January 2021. Code: PI-2046. 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.
Prevention and patient education is key, and frequent, careful handwashing is the most important measure in preventing the spread of RSV. Respiratory etiquette should be properly maintained and people with cold/flu-like symptoms should cover their nose and mouth preferably with a tissue or cough and sneeze into their elbow and wash their hands afterwards for at least 20 seconds or use an alcohol-based rub/gel. Used tissues should be properly disposed of. Sharing utensils with persons who have RSV illness should be avoided and cleaning contaminated surfaces such as door handles may help stop the spread of RSV.3 Parental
smoking is a known risk factor for RSV infection in infancy, and parents or carers who smoke should be offered smoking cessation advice and encouraged to stop smoking. Breastfeeding also offers some protection against RSV infection.9 Persons with RSV should not attend crèches, school, work and non-residential institutions until well. It is important to prevent young infants, frail older persons and immunocompromised people coming into contact with individuals with respiratory infection.9
In the hospital setting, RSV transmission can be prevented by managing children with RSV together in the same ward, paying strict attention to handwashing guidelines, using barrier precautions and avoiding overcrowding through
This CPD module is focused on asthma in all its forms and the treatment opportunities. On completion of this module, it is expected that the reader will have an enhanced understanding of the causes, prevalence and distinctions between different severities of asthma, as well as evidence on the most effective treatment options.
restriction of visitors.3 Several studies have shown that strict infection control practices including hand hygiene, the use of personal protective equipment when necessary, timely detection and isolating or cohorting infants with RSV infection can reduce nosocomial RSV infection rates by 39-to-67 per cent.9
RSV research and outlook
The management of RSV disease in infants and children is primarily supportive with antiviral medications reserved for the most vulnerable.10 Palivizumab continues to be the only effective prophylactic medication licensed for use, however, its high cost prevents it from being used in all infants. The development of a well-tolerated, clinically effective and cost-effective RSV vaccine and therapeutic agent remains a global health priority. It is likely that a licensed RSV vaccine is several years away, however, given the burden of RSV infection and the associated costs globally there is much ongoing research into the development of a well-tolerated and effective vaccine. The main target populations for vaccination include infants, school-age children, pregnant women and older adults. Multiple different vaccine approaches are being considered including live-attenuated chimeric, whole-inactivated, particle-base, subunit, nucleic acid, and gene-based vectors. There are also ongoing efforts to develop long-acting monoclonal antibodies for infants.2
Three agents; ribavirin, IVIG and palivizumab, have been extensively used and investigated as antiviral treatments for RSV. To date none have proven unequivocally beneficial, and effective treatments and research continues into future therapies. At least 14 anti-RSV treatment products are undergoing phase 1 and 2 clinical trials, of which five have included paediatric patients. Novel therapeutic molecules developed to date include fusion inhibitors, non-fusion inhibitors, polymerase inhibitors, antibodies, nucleoside analogues, small-interfacing RNAs, and a benzodiazepine. They have various targets on RSV, such as the F protein, RNA polymerase, nucleoprotein, and nucleocapsid mRNA. It is hoped that one of these products will become a licensed treatment for RSV infection in children and adults over the coming years.2
The development of a successful treatment or prophylactic agent has the potential to revolutionise the care and outcome for severe RSV infections in the world’s most vulnerable infant population.
References
1. Shi T, McAllister DA, O’Brien KL, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: A systematic review and modelling study. Lancet 2017; 390; 946–958
2. Barr R, Greene C, Sande CJ, Drysdale SB. Respiratory syncytial virus: diagnosis, prevention and management. Ther Adv Infect Dis January 2019. doi:10.1177/2049936119865798
3. HPSC (2020). Respiratory Syncytial Virus (RSV). Health Protection Surveillance Centre. Ireland. Available at: www.hpsc.ie/az/ respiratory/respiratorysyncytialvirus/factsheet/
4. Dunkin M. (2021). Respiratory Syncytial Virus (RSV). WebMD Medical Reference. Available at: www.webmd.com/lung/ rsv-in-babies
5. Bont L, Checchia PA, Fauroux B, et al. Defining the epidemiology and burden of severe respiratory syncytial virus infection among infants and children in western countries. Infect Dis Ther 2016;5(3):271-298. doi:10.1007/s40121-016-0123-0
6. Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet 2011; 377: 1264–1275. doi: 10.1016/ S0140-6736(10)61459-6
7. HSE (2019). 18a Respiratory Syncytial Virus. Available at: Health Service Executive. Ireland. Available at: www.hse.ie/eng/health/ immunisation/hcpinfo/guidelines/rsvch18a.pdf
8. Taylor S, Taylor RJ, Lustig RL, et al. Modelling estimates of the burden of respiratory syncytial virus infection in children in the UK. BMJ Open 2016;6:e009337. doi: 10.1136/bmjopen-2015-009337
9. Drysdale S, Greene C, Sande C. Best practice in the prevention and management of paediatric respiratory syncytial virus infection. Ther Adv Infect Dis. 2016 Apr; 3(2): 63. doi: 10.1177/2049936116630243
Free CPD – now accessible on android, iPhone and tablet
10. Schweitzer JW, Justice NA. Respiratory syncytial virus infection. StatPearls Publishing. Available from: www.ncbi.nlm.nih.gov/books/ NBK459215/
Irish Cardiac Society 72nd Annual Scientific Meeting and AGM, virtual, 7-9 October 2021
The Irish Cardiac Society (ICS) 72nd Annual Scientific Meeting and AGM was held recently and saw a range of distinguished national and international experts in their fields deliver a number of presentations relevant to the specialty, which ranged from devices, to disease prevention, to heart failure. The meeting, which was held on a virtual platform, also featured the prestigious Brian Maurer Young Investigator Award. The meeting also incorporated the Meeting of the Irish Nurses Cardiovascular Association and Meeting of Irish Cardiac Physiologists.
The event was introduced by ICS President Prof Vincent Maher, who was joined by co-Chairs Dr Deirdre Ward and Dr Patricia Campbell, who welcomed the first speaker, Prof Perry Elliot. Among a number of prestigious positions he holds, Prof Elliot is Professor of Cardiovascular Medicine at University College London and he spoke on the topic, ‘Genetics of Dilated Cardiomyopathy in 2021’.
In his opening address, Prof Maher acknowledged the importance of partnership with the pharmaceutical industry in enabling the ICS to host such a valuable and educational scientific meeting.
Prof Elliot emphasised that he wanted his presentation to be directly relevant to clinical practice, and said he has “never experienced such an exciting time in [treating] cardiomyopathy, particularly in relation to therapeutic innovation”. He focused on dilated cardiomyopathy and said: “It’s certainly the case that some viral infections can initiate an exaggerated immune response, which can result in acute damage to the heart, and sometimes chronic damage. Less well-appreciated, but seen in everyday practice, is the association between dilated cardiomyopathy and autoimmune disorders,” he said. “We often see it clustering in families who have thyroid disease, diabetes, rheumatoid arthritis, and so on.”
Prof Elliot presented case studies involving both young and old patients and provided an overview of medication options in dilated cardiomyopathy. He told the attendees: “It’s not just about the ejection fraction. Even in the broader phenotype of heart failure, such as preserved ejection fraction, mid-range ejection fraction and reduced ejection fraction, research has shown
that there are genetic ‘hits’. If your primary diagnosis is cardiomyopathy, there is a 15-fold chance that you will find a pathogenic mutation. We are starting to see some convergence in the way we assess patients clinically between the genetic paradigm and the heart failure with reduced ejection fraction paradigm.”
Prof Elliot concluded: “What we in the cardiomyopathy space can learn from heart failure is that we have to prove two very important hypotheses – the first is that it’s out there. If you go to any heart failure clinic in any town or city, you will find this stuff, but we have to prove that. The second thing we have to prove is that by making one of these diagnoses, there is some actionable implication. If you go to a heart failure clinic and look for genetic disease, infiltration or inflammation, you will find it, but there must be a cost-effective way of doing it,” he said.
“My proposal would be that MRI becomes more important,” he continued. “I know there are accessibility issues with MRI, but with short sequences and GAD imaging, that actually triages a lot of patients. I think genotyping may also have to become part of the screening protocol.” If a familial aspect is identified, it is possible to spot pre-symptomatic individuals, he added.
The next keynote speaker at the ICS 72nd Annual Scientific Meeting and AGM was Mr Norman Briffa, Consultant Cardiologist and Reader at the University of Sheffield Medical School, UK. Mr Briffa is also a surgeon with vast experience in performing surgical aortic valve replacement (AVR). In a session chaired by Prof Ian Menown, Consultant Cardiologist and Director of Invasive Cardiology at the Craigavon Cardiac Centre, Northern Ireland, Mr Briffa spoke on the topic, ‘TAVI vs surgical valve replacement: The best approach?’
Mr Briffa presented an overview of current guidelines and challenged the hypothesis that the automatic treatment of choice for all patients with calcific aortic stenosis is transcatheter aortic valve implantation (TAVI). “The perfect prosthetic heart valve should open with minimal effort and require minimal LV power,” he told the meeting. “It should also have an adequate orifice area when the leaflets fully open, it should be competent when the leaflets are closed, it should be thromboresistant in the absence of anticoagulants, it should be resistant to infection, and the leaflets should never degenerate,” he said. “So the perfect prosthetic valve should be most like the healthy native valve. These are important things to keep in mind because at the end of the day, a TAVI device is like a surgically-implanted tissue heart valve – it is just a type of prosthetic heart valve.”
In his talk, he addressed what he calls the increasingly “default thinking” in this area, and PICO, European and US guidelines, and he provided a brief review of evidence, as well as the need for durability and medium-term evidence of outcomes after TAVI, and how “weaknesses in surgery can be mitigated”.
PICO, he explained, is an acronym used by research teams in clinical trials,
and stands for ‘Population’, ‘Intervention’ (TAVI), ‘Comparator’ (surgical aortic valve replacement with a tissue prosthesis), and ‘Outcome’. He presented a case study to illustrate how PICO is used to assess the predicted healthy life span of a patient following surgery or TAVI, depending on the health profile, as well as whether the procedure is advisable in certain patients. He
presented case studies to show how US and European guidelines are very different from each other. “There are different criteria, which I think confuses matters, and it is possible to have a patient in their mid-70s who has a very low risk of dying or suffering serious morbidity after surgical AVR.”
He presented up-to-date research on surgical mortality and told the attendees: “The ability to have a good look into the aortic route is a big advantage of surgery. The surgeon ensures that any debris that could embolise is removed and ensures, with their own eyes, that there is a good fit for a prosthesis.”
The downside of TAVI, he explained, lies in the device and how it is deployed, irrespective of patient risk, “whereas the downside of surgery is means- or procedure-based, ie, surgical complications, and we know that these are dependent on age and risk. The difference in five-year risk of disabling stroke or death after surgery or TAVI will probably be wider in the lower-risk patients, compared to the intermediate- or high-risk ones.” There is now growing experience of completing surgical AVR through less-invasive incisions, he said, and these approaches lead to less bleeding and shorter hospital stays, as well as reduced admissions.
“Whichever side of the argument you are on, I think everybody would agree that adopting a multidisciplinary approach where multiple treatment strategies are available is sensible,” said Mr Briffa. He quoted US surgeon Mr Michael Riordan, who stated: “We have to figure out what we think our patient’s survival is going to be versus what we think the valve’s survival is going to be.”
Mr Briffa added: “I would go further and wouldn’t just say survival, but patients’ healthy survival if the AS is treated successfully. I think TAVI is an amazing technology and because of it, we have been able to treat patients who previously were not treated at all. But when it comes to younger patients, I think considerations beyond the seduction of no anaesthetic and early mobilisation and early hospital discharge must be taken into account.
“This idea that avoiding surgery as the primary outcome in the treatment of a patient is a fallacy and serves neither the patient or the healthcare system,” he continued. “Despite all this, I think the scenario where the patient will demand a non-surgical solution will increase and it’s up to us to make sure we have the right information to help the patient make the right decision.”
Mr Briffa concluded: “Expectations and guidelines are running way beyond what the evidence says. Also, the guidelines are inconsistent and TAVI in the lower-risk patient is probably not a good thing for the patient and healthcare in general. Multidisciplinary teams need to be encouraged and supported by hospital administration to ensure they work well and more evidence and good decision aids to help doctors and patients make the right decision are urgently needed and, in time, AI and machine learning will help us and our patients to make the right decisions.”
The ability to have a good look into the aortic route is a big advantage of surgery. The surgeon ensures that any debris that could embolise is removed and ensures, with their own eyes, that there is a good fit for a prosthesis
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 Summary of Product Characteristics (SmPC) for how to report adverse reactions. Xarelto 2.5 mg/ 10 mg / 15 mg / 20 mg film-coated tablets and 1mg/ml granules for oral suspension (Rivaroxaban). Presentation: 2.5mg/10mg/15mg/20mg rivaroxaban tablet (contains lactose) & 1mg/ml granules for oral suspension. Indication(s): 2.5mg, Xarelto, co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine, is indicated for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers. Xarelto is co-administered with acetylsalicylic acid (ASA) in prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischaemic events.10mg Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery. Treatment of deep vein thrombosis (DVT) & pulmonary embolism (PE), & prevention of recurrent DVT & PE in adults (see W&P for haemodynamically unstable PE patients). 15mg/20mg Prevention of stroke & systemic embolism in adult patients with nonvalvular atrial fibrillation with one or more risk factors such as congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, prior stroke or transient ischaemic attack (SPAF).
Treatment of DVT & PE, & prevention of recurrent DVT & PE in adults (see W&P for haemodynamically unstable PE patients). Paediatrics: 1mg/ml – Treatment of VTE and prevention of VTE recurrence in term neonates, infants & toddlers, children, & adolescents aged less than 18 years after at least 5 days of initial parenteral anticoagulation treatment.
Treatment of VTE & prevention of VTE recurrence in children & adolescents aged less than 18 years & weighing from 30kg to 50kg (for 15mg) / above 50kg (for 20mg) after at least 5 days of initial parenteral anticoagulation treatment. Posology & method of administration:
2.5mg – Oral b.d. dose. For ACS: patients should also take a daily dose of 75 – 100mg ASA or a daily dose of 75 – 100mg ASA in addition to either a daily dose of 75mg clopidogrel or a standard daily dose of ticlopidine. Start Xarelto as soon as possible after stabilisation, including revascularisation for ACS; at the earliest 24 hours after admission & at discontinuation of parenteral anticoagulation. If dose is missed take next dose, do not double the dose. For CAD/PAD: the recommended dose is 2.5 mg b.d. Patients taking Xarelto 2.5 mg b.d. should also take a daily dose of 75 – 100 mg ASA. In patients after a recent successful revascularisation procedure of the lower limb (surgical or endovascular including hybrid procedures) due to symptomatic PAD, treatment should not be started until haemostasis is achieved. Duration of treatment should be determined for each individual patient based on regular evaluations and should consider the risk of thrombotic events versus the bleeding risks.
In patients with an acute thrombotic event or vascular procedure and a need for dual antiplatelet therapy, the continuation of this treatment should be evaluated depending on the type of event or procedure and antiplatelet regimen. Dual antiplatelet therapy has not been studied in combination with Xarelto 2.5 mg b.d. in patients with CAD 10mg – hip or knee replacement surgery: Oral o.d. dose; initial dose taken 6 to 10 hours after surgery provided haemostasis established. DVT & PE: When extended prevention of recurrent DVT and PE is indicated (following completion of at least 6 months therapy for DVT or PE), the recommended dose is 10 mg o.d. In patients in whom the risk of recurrent DVT or PE is considered high, such as those with complicated comorbidities, or who have developed recurrent DVT or PE on extended prevention with Xarelto 10 mg o.d., a dose of Xarelto 20 mg o.d. should be considered. 15mg/20mg – Take with food SPAF. 20 mg orally o.d. DVT & PE: 15 mg b.d. for 3 weeks followed by 20 mg o.d. for continued treatment & prevention of recurrent DVT & PE.
Children & adolescents – calculate dose based on body weight: body weight <30kg refer to the SmPC for Xarelto 1mg/ml granules for oral suspension; body weight 30-50kg take 15mg o.d.; body weight >50kg take 20mg o.d. Monitor child’s weight & review regularly. All strengths - Refer to SmPC for full information on duration of therapy & converting to/from Vitamin K antagonists (VKA) or parenteral anticoagulants. Special populations: Patients undergoing cardioversion: Xarelto 15mg/20mg can be initiated or continued in patients
Reference: 1. Xarelto® (rivaroxaban). Summary of Product Characteristics.
who may require cardioversion. Patients with non-valvular atrial fibrillation who undergo PCI (percutaneous coronary intervention) with stent placement: There is limited experience of a reduced dose of 15 mg Xarelto once daily (or 10 mg Xarelto once daily for patients with moderate renal impairment [creatinine clearance 30 – 49 ml/min]) in addition to a P2Y12 inhibitor for a maximum of 12 months in patients with non-valvular atrial fibrillation who require oral anticoagulation & undergo PCI with stent placement. Renal impairment: mild (creatinine clearance 50-80 ml/min) – no dose adjustment; 2.5mg /10mg - moderate (creatinine clearance 30-49 ml/min)– no dose adjustment. 15mg/20mg – adults with moderate (creatinine clearance 30-49 ml/min) & severe (creatinine clearance 15-29ml/ min) - SPAF: reduce dose to 15mg o.d., DVT & PE: 15 mg b.d. for 3 weeks, thereafter 20mg o.d. Consider reduction from 20mg to 15mg o.d. if patient’s bleeding risk outweighs risk for recurrent DVT & PE; children & adolescents - Due to no clinical data available in children 1 year or older with moderate or severe renal impairment (glomerular filtration rate < 50 mL/ min/1.73 m2) or in children younger than 1 year with serum creatinine results above 97.5th percentile - Xarelto is not recommended. All strengths – Severe impairment: limited data indicate rivaroxaban concentrations are significantly increased, use with caution. Creatinine clearance <15 ml/min - not recommended. Hepatic impairment: Contraindicated in patients with coagulopathy & clinically relevant bleeding risk including cirrhotic patients with Child Pugh B & C Paediatrics: Only for treatment of VTE & prevention of VTE recurrence. Contra-indications: Hypersensitivity to active substance or any excipient; active clinically significant bleeding; lesion or condition (e.g. malignant neoplasm) considered to confer a significant risk for major bleeding (refer to SmPC); concomitant treatment with any other anticoagulants except under specific circumstances of switching anticoagulant therapy or when unfractionated heparin is given at doses necessary to maintain an open central venous or arterial catheter; hepatic disease associated with coagulopathy & clinically relevant bleeding risk including cirrhotic patients with Child Pugh B & C; pregnancy & breast feeding. 2.5mgconcomitant treatment of ACS with antiplatelet therapy in patients with a prior stroke or transient ischaemic attack; concomitant treatment of CAD/PAD with ASA in patients with previous haemorrhagic or lacunar stroke, or any stroke within a month. Warnings & precautions (W&P): Clinical surveillance in line with anticoagulant practice is recommended throughout the treatment period. There is no need for monitoring of coagulation parameters during treatment with rivaroxaban in clinical routine, if clinically indicated rivaroxaban levels can be measured by calibrated quantitative anti-Factor Xa tests. Discontinue if severe haemorrhage occurs. Increasing age may increase haemorrhagic risk. Xarelto should be discontinued at the first appearance of a severe skin rash, or any other sign of hypersensitivity in conjunction with mucosal lesions. Not recommended: In patients with severe renal impairment (creatinine clearance <15 ml/min); in patients with an increased bleeding risk (refer to SmPC); in patients with prosthetic heart valves; for patients with a history of thrombosis diagnosed with antiphospholipid syndrome; Xarelto should not be used for thromboprophylaxis in patients having recently undergone transcatheter aortic valve replacement (TAVR); Cancer: The individual benefit of antithrombotic treatment should be weighed against risk for bleeding in patients with active cancer. Tumours located in the gastrointestinal or genitourinary tract have been associated with an increased risk of bleeding during rivaroxaban therapy. Contraindicated in patients with malignant neoplasms (patients with cancer) at high risk of bleeding; 1mg/ml oral suspension - sodium benzoate may increase jaundice in new-born infants (up to 4 weeks old). Not recommended: in children less than 6 months of age who at birth had <37 weeks of gestation, a body weight of <2.6 kg, or had <10 days of oral feeding; 2.5mg: not studied and therefore not recommended in combination with other antiplatelets e.g prasugrel or ticagrelor. In patients after recent revascularisation procedures of the lower limb due to symptomatic PAD with a previous stroke or TIA were not studied. Treatment with Xarelto 2.5 mg should be avoided in these patients receiving dual antiplatelet therapy. Use with caution: in patients treated concomitantly with medicines affecting haemostasis; when neuraxial anaesthesia or spinal/epidural puncture is employed; in patients at risk of ulcerative gastrointestinal disease (prophylactic treatment may be
considered); in children with cerebral vein & sinus thrombosis who have a CNS infection. 2.5mg treatment in combination with antiplatelet agents other than ASA & clopidogrel/ ticlopidine; in patients ≥75 years of age or with lower body weight (<60kg); in CAD patients with severe symptomatic heart failure. Patients on treatment with Xarelto & ASA should only receive concomitant treatment with NSAIDs if the benefit outweighs the bleeding risk. If required, e.g. after recent revascularisation procedure of the lower limb in PAD, dual antiplatelet therapy with clopidogrel should be short-term; concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations. 2.5mg/10mg in patients with moderate renal impairment concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations. 10mg/15mg/20mg in haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy; 15mg/20mg in patients with renal impairment concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations. Interactions: Not recommended: In patients receiving concomitant systemic treatment with strong concurrent CYP3A4- & P-gp-inhibitors, i.e. azole antimycotics such as ketoconazole, itraconazole, voriconazole & posaconazole or HIV protease inhibitors like ritonavir; in patients treated concomitantly on dronedarone as clinically relevant increased rivaroxaban plasma concentrations are observed. Use with caution: In patients concomitantly receiving NSAIDs, ASA or platelet aggregation inhibitors due to the increased bleeding risk; patients concomitantly receiving SSRIs/SNRIs due to a possible increased bleeding risk. Concomitant use of strong CYP3A4 inducers should be avoided unless patient is closely observed for signs & symptoms of thrombosis. Fertility, Pregnancy and Lactation: Pregnancy: Xarelto is contraindicated during pregnancy. Breast-feeding: Xarelto is contraindicated during breastfeeding; a decision must be made to discontinue breast-feeding or discontinue/abstain from therapy. Fertility: No specific studies with rivaroxaban in humans have been conducted to evaluate effects on fertility. In a study on male and female fertility in rats, no effects were seen. Effects on ability to drive & use machines: syncope (uncommon) & dizziness (common) were reported. Patients experiencing these effects should not drive or use machines. Undesirable effects: Common: anaemia, dizziness, headache (in children: very common), eye haemorrhage, hypotension, haematoma, epistaxis (in children: very common),haemoptysis, gingival bleeding, gastrointestinal tract haemorrhage, gastrointestinal and abdominal pains, dyspepsia, nausea, constipation, diarrhoea, vomiting (in children: very common),increase in transaminases, pruritus, rash, ecchymosis, cutaneous and subcutaneous haemorrhage, pain in extremity, urogenital tract haemorrhage (menorrhagia very common in women < 55 years treated for DVT, PE or prevention of recurrence, common in female adolescents after menarche), renal impairment, fever (in children: very common),peripheral oedema, decreased general strength and energy, post-procedural haemorrhage, contusion, wound secretion. Uncommon: thrombocytosis, thrombocytopenia (in children: Common), allergic reaction, dermatitis allergic, angioedema, allergic oedema, cerebral and intracranial haemorrhage, syncope, tachycardia (in children: Common), dry mouth, hepatic impairment, urticaria, hemarthrosis, feeling unwell, increases in: bilirubin (in children: Common), blood alkaline phosphate, GGT, LDH, lipase, amylase. Rare: jaundice, bilirubin conjugated increased (in children: uncommon), cholestasis, hepatitis (including hepatocellular injury), muscle haemorrhage, localised oedema, vascular pseudoaneurysm (uncommon in prevention therapy in ACS following percutaneous coronary intervention). Very Rare: Anaphylactic reactions including anaphylactic shock, Stevens-Johnson syndrome/ toxic epidermal necrolysis, DRESS syndrome. Frequency not known: compartment syndrome secondary to a bleeding, renal failure/ acute renal failure secondary to a bleeding. Classification of supply: Prescription only Medicine. Marketing Authorisation Holder: Bayer AG, 51368 Leverkusen, Germany.
PP-XAR-IE-0878-1
Irish Cardiac Society 72nd Annual Scientific Meeting and AGM, virtual, 7-9 October 2021
The ICS 72nd Annual Scientific Meeting
and AGM heard the much-anticipated Stokes Lecture 2021, which was delivered by Prof Ken McDonald and was titled ‘The transformation of heart failure: From nobody’s child to driving healthcare change’. The lecture was chaired by Prof Vincent Maher, who provided a brief outline of how Prof McDonald has “transformed heart failure in this country” in terms of treatment and prevention.
Prof McDonald provided an overview of the development of heart failure studies, diagnosis and treatment over the past 35 years and the current challenges. He also addressed the prospects for heart failure prevention and treatment in the near future and the varied opportunities heart failure presents for cardiology graduates.
He briefly discussed how the first heart transplant was performed in 1985 by Mr Maurice Neligan and how at that time, “heart failure patients didn’t have any access to cardiology care, but there was relatively little we could have done at that stage anyway. So it truly was a terminal illness then, if you were not that lucky one who ‘hit the jackpot’ and could get a heart transplant.” However, following that, a number of studies emerged that advanced
the understanding of heart failure and how it is possible to alter the natural history of the condition.
Regarding what he described as the “clinical trial era” in heart failure, Prof McDonald commented: “It can be rightly said that the clinical trial era in heart failure is probably one of the most impressive clinical trial programmes, not just in cardiology, but in medicine. It powers ahead even now and it has brought such a tangible improvement in outcomes for patients, predominantly with HFrEF [heart failure with reduced ejection fraction].”
He provided an overview of current therapies and discussed the need to better personalise treatments for heart failure more effectively, as well as the importance of disease management programmes. Prof McDonald also emphasised the importance of a multidisciplinary team led by a cardiologist with access to other specialists, including specialist nurses and allied health professionals.
He described the transition of heart failure from being a terminal illness to a chronic disease, and told the attendees: “It behooved us to develop strategies of care delivery which could be delivered more and more with specialist influence within the community, and not necessarily with hospital-dominated care,” said Prof McDonald. “We understood that heart failure was the exemplar chronic illness and anything we developed for heart failure would have ripple effects in other chronic diseases, because there is a generic aspect to managing chronic illnesses.”
Prof McDonald concluded: “I think we need a focused,
The ICS 72nd Annual Scientific Meeting and AGM hosted a wide range of poster presentations for assessment by a panel of adjudicators, as well as the prestigious Brian Maurer Young Investigator Award (YIA). The YIA was supported by Servier Laboratories Ireland Ltd.
The YIA candidates were Dr Jatinda Kumar, who spoke on ‘Incidence and prevalence of MINOCA (myocardial infarction with non-obstructive coronary arteries) in STEMI patients: Experience from Irish tertiary care’. The second presentation was delivered by Dr James Mannion, who addressed the meeting on the topic, ‘Arrythmogenic substrate stratification of posterior left atrial wall in atrial fibrillation versus sinus rhythm in persistent atrial fibrillation using automated voltage analysis’.
Next to speak was Dr Munza Hussain, on the theme of ‘Atrial uptake on technetium pyrophosphate scintigraphy: Clinical implications of this new phenomenon’. The final entrant was Dr Jane Murphy, who addressed the topic ‘Predictive genetic testing in inherited cardiac conditions: Findings from a large Irish cohort’.
The judging panel acknowledged the high quality of the entries and it was announced at the end of the meeting that the winner was Dr Hussain. “This is the biggest study looking not only at cardiac amyloid, but it also included patients without cardiac amyloid,” said Dr Hussain during her
presentation. “This study also emphasises the link between atrial uptake and atrial fibrillation, given the fact that if you have atrial uptake on your PYP scan, you are more likely to develop atrial fibrillation within the first year, and this leads to so many clinical questions.”
In the poster presentations section of the meeting, the winner of the Prof David Foley Intervention Case Competition was announced as Dr Lisa Brandon for her presentation on ‘What do cardiology and orthopaedics have in common? How to deal with an emergency fracture’.
Winner of the Best Oral Abstract presentation was Dr Daniel O’Hare, for ‘Clinical associations and pathological mechanisms of reduced atrial conduction velocity’.
Dr Habitha Sulaiman won the Best Moderated Poster prize for her poster titled ‘Influence of routine cardiac rhythm assessment in the long-term management of channelopathy patients’.
The Best General Poster winner was Dr Claire Tonry for ‘Identification of novel protein biomarkers for atrial fibrillation’.
The Brian McGovern Scholarship Recipient 2021, which was supported by Daiichi Sankyo Ireland, was announced as Dr Heather Cronin. Dr Cronin recently commenced a fellowship in inherited cardiac conditions in St Bart's Hospital in London under the supervision of Prof Perry Elliot.
risk-defined heart failure prevention strategy. We also need diagnostic pathways to minimise delays, and heart failure expertise needs to be given to everyone.
“We also need a policy,” he added. “We can see how things are moving at a pace. When we see a heart failure patient today, we need to have the capacity to be able to re-engage with that patient to ensure their therapies are being continually updated as care evolves.
“For cardiology, I think these are exciting times and for our trainees, and I think heart failure or related areas are particularly exciting,” he added. “As we train cardiologists, we need to consider that we are presenting this as a real sub-specialism, although that term might engender some debate. But there is great potential in this area and within the integrated care programme within the HSE, this has been a staggering development. We have only heard the negatives about Sláintecare recently because of people resigning, but behind that engine there have been very real developments for cardiac opportunities for our graduates, with 16 new positions now coming online in this country in the south of Ireland. These will be hospital appointments, but they will also be looking outwards to try to integrate the care for patients.”
Prof McDonald recalled: “I remember back in the 1980s when Brian Maurer arrived into the lab with the VHef study under his arm. He subsequently said, ‘The time is now for heart failure, not just in St Vincent’s and not just on this island, but internationally’. Not for the first time, he was right on the money.”
he ICS 72nd Annual Scientific Meeting and AGM heard from keynote speaker Prof Kausik K Ray of Imperial College London, who addressed the meeting on the topic, ‘ASCVD [atherosclerotic cardiovascular disease] Prevention: Unmet needs and the promise of population health through siRNA-based therapies’.
“I think we are at a really exciting time, because you can only start to fix problems when you look at the issues. Some of these may be clinical in terms of how we find patients, healthcare systems, and also in terms of patients’ behaviours and their health literacy,” said Prof Ray. “It doesn’t matter where you are in the world, we have a more or less global approach in terms of lipid-lowering and prevention. We don’t want to over-treat low-risk people, but we don’t want to under-treat high-risk individuals,” said Prof Ray. Many guidelines suggest what to do at a population level, but when it comes to data from cholesterol treatment trials, “the third iteration is really my favourite because it really shows you the two basic determinants of absolute benefits from lipid-lowering,” he told the attendees. Prof Ray presented data from guidelines and told the meeting: “The first thing to point out is, there is no such thing as a ‘normal’ LDL. The more you lower LDL cholesterol, the more benefit you get, and the amount of benefit you get really depends on the baseline risk.”
He explained that if there is an annualised risk of less than one per cent, “lower is clearly better. But if I am trying to implement a really aggressive approach in everybody who is at low risk, the more you lower LDL cholesterol, the more benefit you get, and the amount of benefit you get really depends on the baseline risk.” Prof Ray presented an overview of the European Society of Cardiology/European Atherosclerosis Society risk-based LDL-C goals and broke patients down according to their risk categories and rec-
ommended LDL-C goals. “What we can see is that as the risk increases, the cholesterol goals become lower and lower,” he pointed out.
As the LDL-C goals have become lower in recent years, the challenge for physicians is how to achieve those goals with existing therapies, he said. Prof Ray outlined data from the DA VINCI study and noted that “the aim is to get patients to control [cholesterol levels], irrespective of whether you are using one, two or three drugs”. He emphasised the importance of the study in changing thinking about cholesterol and said, “the message is simple – in Europe, between those two sets of guidelines, what we were practising was essentially statin-based monotherapy… the key thing to note about combination therapies is that it [level] was really low.
“With a statin-based monotherapy approach to our patients, in primary or secondary prevention, the risk-based goal attainment would only be effective in about 50 per cent of patients. As soon as we reset those goals to reflect the data and what we now have available, that’s going to fall to one-in-three. So we have to get it into our heads that we will have to use more combination therapy.”
SUSPECT ATTR-CM
(TRANSTHYRETIN AMYLOID CARDIOMYOPATHY)
A LIFE-THREATENING DISEASE THAT CAN GO UNDETECTED
Life-threatening, underrecognized, and underdiagnosed, ATTR-CM is a rare condition found in mostly older patients in which misfolded transthyretin proteins deposit in the heart.1-7 It is vital to recognize the diagnostic clues so you can identify this disease.
CONSIDER THE FOLLOWING CLINICAL CLUES, ESPECIALLY IN COMBINATION, TO RAISE SUSPICION FOR ATTR-CM AND THE NEED FOR FURTHER TESTING
heart failure with preserved ejection fraction in patients typically over 60 years old5-7
to standard heart failure therapies (ACEi, ARBs, and beta blockers)8-10
between QRS voltage and left ventricular (LV) wall thickness11-13
of carpal tunnel syndrome or lumbar spinal stenosis3,8,14-20
showing increased LV wall thickness6,13,16,21,22
LEARN HOW TO RECOGNIZE THE CLUES OF ATTR-CM AT:
—autonomic nervous system dysfunction-including gastrointestinal complaints or unexplained weight loss6,16,23,24
Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209-213.
MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135(14):1357-1377.
3. Connors LH, Sam F, Skinner M, et al. Heart failure due to age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290.
4. Pinney JH, Whelan CJ, Petrie A, et al. Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc. 2013;2(2):e000098.
5. Mohammed SF, Mirzoyev SA, Edwards WD, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2(2):113-122. 6. Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172.
7. González-López E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36(38):2585-2594. 8. Narotsky DL, Castano A, Weinsaft JW, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016;32(9):1166.e1-1166.e10. 9. Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS. Transthyretin cardiac amyloidosis in older Americans. J Card Fail. 2016;22(12):996-1003. 10. Castaño A, Drach BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163-178. 11. Carroll JD, Gaasch WH, McAdam KP. Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation. Am J Cardiol. 1982;49:9-13. 12. Cyrille NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol. 2014;114(7):1089-1093. 13. Quarta CC, Solomon D, Uraizee I, et al. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation. 2014;129(18):1840-1849. 14. Connors LH, Prokaeva T, Lim A, et al. Cardiac amyloidosis in African Americans: Comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. Am Heart J. 2009;158(4):607-614. 15. Nakagawa M, Sekijima Y, Yazaki M, et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23(1):58-63. 16. Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203-1212. 17. Sperry BW, Reyes BA, Ikram A, et al. Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol. 2018;72(17): 2040-2050. 18. Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223-228. 19. Yanagisawa A, Ueda M, Sueyoshi T, et al. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol. 2015;28(2):201-207. 20. Sueyoshi T, Ueda M, Jono H, et al. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011;42(9):1259-1264. 21. Phelan D, Collier P, Thavendiranathan P, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart. 2012;98(19):1442-1448. 22. Ternacle J, Bodez D, Guellich A, et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging 2016;9(2):126-138. 23. Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63-76. 24. Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22(2):123-131.
The health information contained in this ad is provided for educational purposes only.
Date of Preparation: February 2021 GCMA code: PP-RDP-IRL-0105
References
1.
2. Maurer
Attendees at the ICS 72nd Annual Scientific Meeting and AGM heard a round-up of the ‘Update on Irish cardiology training programme’ by Prof Brian McNeill and Dr Ross Murphy, National Specialty Directors in the Cardiology HST Programme, as well as an ‘Irish young cardiologists of tomorrow update’ from Dr Brian Traynor, and an ‘Irish Cardiac Society women in cardiology update’ from Dr Bethany Wong.
Attendees also heard the yearly ‘Brian McGovern Scholarship Update’ from Dr Sean Fitzgerald.
Prof McNeill noted that “2021 saw a record intake of SpRs. Thirteen candidates were selected for the programme and this is the highest intake we have had, and I think that reflects the high standard of applicants that we have had. Additional places also became available through a Covid response from the HSE.”
He also acknowledged BMS and Daiichi Sankyo for their
Authors: Dr Rehman Faryal, Prof Fionnuala Ní Áinle, Dr Barry Kevane, Department of Haematology, Mater Misericordiae University Hospital
sponsorship of travelling scholarships, “which form a very important part of the international experience for our trainees”.
He also noted that the ICS website has been thoroughly revamped, with a dedicated area containing information and resources for trainees.
Prof McNeill also paid tribute to Ms Barbra Dalton, Executive Director at the ICS and Irish Board for Training in Cardiovascular Medicine, and organiser of the conference.
“On behalf of Ross and I and all the trainers and trainees, I’d like to acknowledge Barbra’s great work. I cannot overstate her dedication and commitment to ensuring high-standard training and the resultant world-class graduates that it produces.”
Dr Traynor commented: “Over the past year, particularly through Dr Diarmuid Hughes and Barbra Dalton, we have developed a core curriculum in Covid times. This has been mainly webinar-based but it has gone down very well.”
Career coaching and resilience training were among the initiatives introduced, as well as fellowship planning.
On social events, Dr Traynor said: “The last couple of years have seen social events take a back seat, and these can be very helpful for building relationships between trainees. We do appreciate the effect this has had, particularly among the new trainees, and we are hoping in the near future to arrange a social event.”
Dr Wong reported results from a survey on Irish women in cardiology, titled ‘Perceptions of equality, flexible working and mentorship amongst Irish cardiology trainees and consultants’.
She told the attendees: “We found the prevalence of bullying, discrimination and lack of support is high,” she said.
“More than half of respondents would like to work parttime, but two-thirds reported that their colleagues would not be supportive.
“Both male and female trainees and consultants are interested in a mentorship programme, as well as increasing females in leadership positions.”
Closing the conference, Prof Vincent Maher, ICS President, thanked the attendees and presenters.
“Although we have seen the great merits of the virtual platform, I think we all relish the idea of a face-to-face meeting next year, and I am looking forward to that,” said Prof Maher.
The last couple of years have seen social events take a back seat, and these can be very helpful for building relationships between trainees. We do appreciate the effect this has had, particularly among the new trainees, and we are hoping in the near future to arrange a social event
Abbreviated Prescribing Information: Ranexa (ranolazine). Please consult the Summary of Product Characteristics (SPC) for full prescribing information. Presentation: Prolonged-release tablets containing 375 mg, 500 mg or 750 mg of ranolazine. 750 mg tablet contains E102 and lactose. Use: Ranexa is indicated as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies (such as beta-blockers and/or calcium antagonists). Dosage and administration: Oral administration. Patients should be instructed to list their medication to their health care professional at each visit. Adults: Initial dose is 375 mg twice daily. After 2-4 weeks, dose should be titrated to 500 mg twice daily and, according to patient’s response, further titrated to 750 mg twice daily. Concomitant treatment with moderate CYP3A4 and P-glycoprotein (P-gp) inhibitors: Careful dose titration is recommended. Renal impairment: Careful dose titration is recommended in mild to moderate renal impairment, and contraindicated in severe renal impairment. Hepatic impairment: Careful dose titration is recommended in mild hepatic impairment, and contraindicated in moderate to severe hepatic impairment. Elderly: Dose titration in the elderly should be exercised with caution. Low weight: Dose titration in patients with low weight should be exercised with caution. Congestive Heart Failure (CHF): Dose titration in moderate to severe CHF should be exercised with caution. Paediatric patients: No data in children below the age of 18 years. Ranexa tablets should be swallowed whole and not crushed, broken or chewed. They may be taken with or without food. Contra-indications: Hypersensitivity to the active substance or to any of the excipients. Severe renal impairment. Moderate or severe hepatic impairment. Concomitant administration of potent CYP3A4 inhibitors. Concomitant administration of Class Ia or Class III antiarrhythmics other than amiodarone. Warnings and Precautions: Caution should be exercised when prescribing or up titrating ranolazine to patients in whom an increased exposure is expected. QT prolongation: Caution should be observed when treating patients with a history of congenital or a family history of long QT syndrome, in patients with known acquired QT interval prolongation, and in patients treated with drugs affecting the QTc interval. Interactions: Co-administration with CYP3A4 inducers is expected to lead to lack of efficacy.
Renal impairment: Check renal function at regular intervals during treatment. Interactions: CYP3A4 inhibitors: Increase plasma concentrations of ranolazine. Combining ranolazine with potent CYP3A4 inhibitors is contraindicated. CYP3A4 inducers: Avoid initiation with Ranexa during administration of CYP3A4 inducers. CYP2D6 inhibitors: May increase plasma concentrations of ranolazine. Effect of ranolazine on other medicinal products: Dosage adjustment of sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range may be required. Lower doses of CYP2D6 substrates may be required. Caution with CYP2B6 substrates. Monitor digoxin levels following initiation and termination of Ranexa. Limit dose of simvastatin to 20mg once daily in patients taking Ranexa. Limit dose of atorvastatin and consider clinical monitoring in patients taking Ranexa. Monitor blood levels of tacrolimus when coadministering with Ranexa and adjust tacrolimus dose accordingly. Also recommended for other CYP3A4 substrates with a narrow therapeutic range. Drugs transported by the Organic Cation Transporter-2 (OCT2): Plasma exposure of metformin increased in subjects with type 2 diabetes mellitus when co-administered with Ranexa. The exposure of other OCT2 substrates may also be affected. Theoretical risk that concomitant treatment with drugs known to prolong the QTc interval may increase the possible risk of ventricular arrhythmias. Pregnancy and lactation: Ranexa should not be used during pregnancy unless clearly necessary. Ranexa should not be used during breast-feeding. Effect on fertility unknown. Side-effects: Generally mild to moderate in severity and often develop within the first 2 weeks of treatment. Common (1-10%): dizziness, headache, constipation, vomiting, nausea, asthenia. Uncommon (0.1–1%): anorexia, decreased appetite, dehydration, anxiety, insomnia, confusional state, hallucination, lethargy, syncope, hypoaesthesia, somnolence, tremor, postural dizziness, paraesthesia, blurred vision, visual disturbance, diplopia, vertigo, tinnitus, hot flush, hypotension, dyspnoea, cough, epistaxis, abdominal pain, dry mouth, dyspepsia, flatulence, stomach discomfort, pruritus, hyperhydrosis, pain in extremity, muscle cramp, joint swelling, muscular weakness, dysuria, haematuria, chromaturia, fatigue, peripheral oedema, increased blood creatinine, increased blood urea, prolonged QT corrected interval, increased platelet or white blood cell count, decreased weight. In a long term study, acute renal failure was also reported with an incidence less than 1% in placebo and ranolazine patients. Rare (0.1-0.01%): hyponatremia, disorientation, amnesia, depressed level of consciousness, loss of consciousness, coordination abnormal, gait disturbance, parosmia, impaired hearing, peripheral coldness, orthostatic hypotension, throat tightness, pancreatitis, erosive duodenitis, oral hypoaesthesia, angioedema, allergic dermatitis, urticaria, cold sweat, rash, acute renal failure, urinary retention, erectile dysfunction, elevated levels of hepatic enzyme. Not known: myoclonus. Increased incidence of congestive heart failure and transient ischaemic attacks seen in patients with history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention and treated within 2 weeks with ranolazine (1000 mg twice daily [dose not approved in Europe]) in a placebo-controlled post-PCI trial. Elderly, renal impairment and low weight: In general, adverse events occurred more frequently among elderly patients and patients with renal impairment. Adverse events in patients with low body weight were similar to those of patients with higher weight. Please consult the SPC for further information.Pack size: 60 tablets. Legal category: POM. Marketing authorisation numbers: EU/1/08/462/001, 003, 005 Marketing Authorisation holder: Menarini International Operations Luxembourg S.A. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd. Further information is available on request from A. Menarini Pharmaceuticals Ireland Ltd, 2nd Floor, Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924 or may be found in the SPC. Last updated: October 2020
Date of item: November 2020. IR-RAN-12-2020
References: 1. Chaitman, B.R., et al. JAMA, 2004; 291(3): p. 309-16.
Q1 The 2022 Winter Olympics will be held in Beijing in early 2022. What year did this city last host an Olympics?
Q2 Which baseball team won the 2021 World Series?
Q3 Shamrock Rovers have won the League of Ireland title for the second year in a row. Name their manager?
Q4 Who captained Ireland in their opening autumn rugby international against Japan last weekend?
Q5 Who won the 2021 MotoGP world title and in doing so claimed his first title?
Q6 Name the Swedish footballer who recently scored his 400th career league goal?
The winner of the 18 October 2021 Sporting Quiz Competition is Dr Karl Finnerty, Co Dublin
The winner of the 18 October 2021 Crossword is Dr Josephine Heward, Co Donegal
Q1 Who has become the new manager of Premier League strugglers Watford?
A: Claudio Ranieri
Q2 Who is the WBC world heavyweight boxing champion? A: Tyson Fury
Quiz
Q3 Name the quarterback who eclipsed the all-time passing yards mark last week in the NFL? A: Tom Brady
Q4 Which nation won the 2021 UEFA Nations League? A: France
Q5 Name the Irish cyclist who announced his retirement from professional competition earlier this month? A: Nicolas Roche
Q6 Which racing driver won the F1 Turkish Grand Prix? A: Valtteri Bottas
ACROSS
1 Early version of a document (5)
4 Next after sixth (7)
7 Twenty (5)
8 Very large animal (8)
9 Apart from (5)
11 Abruptly (8)
15 Free from error (8)
17 Produce as a fruit (5)
19 Most influential or important (8)
20 Only just able to be seen (5)
21 Use again (7)
22 Increase in size (5)
DOWN
1 Variety (9)
2 Before or by now (7)
3 Become tense (7)
4 Gesture (6)
5 Forgive for a fault (6)
6 Weary (5)
10 Indispensable (9)
12 Inquisitive (7)
13 Emotional stability (7)
14 Lots of (6)
16 Selection (6)
18 Picture (5)
TITLE: What is Life?: Understand Biology in Five Steps
AUTHOR: Sir Paul Nurse
PUBLISHER: Fickling Books 2020
REVIEWER: Prof Denis Gill
This is a curiously old-fashioned book in its presentation about up-to-date basic science. Hard-covered; small in size (pages of 8 x11 centimetres); containing no tables; no diagrams; no illustrations; no scientific bibliography; or no index – it is nonetheless a class book, in every sense of that adjective, with concise, incisive writing, and explanations.
I attended UCD medical school in the early 1960s, where anatomy, pathology, and microbiology were very well taught, but physiology was woefully explained, and, of biology, I have no memory.
Sir Paul Nurses’ book, What is Life?: Understand Biology in Five Steps , has filled gaps in my knowledge of basic science. Nurse is very perspicacious, a good teacher and communicator, and has written a profoundly simple book, an amalgam of science and history. Nurse is a geneticist and cell biologist, a Nobel Prize-winner, has a knighthood, and the Legion d’Honneur from France. Nurse is an apposite name to have, for nurses are surely doctors’ best friends and allies.
Nurse admits to plagiarising his title
What is Life? from a previous text written in 1944. First a few basic questions:
(1) The yolk of an egg you ate for breakfast is single cell. True or false? (2) A nerve that goes from your spine to the tip of your great toe – about one metre long – is a single cell. True or false? (3) E-coli cells can line up 3,000 abreast across a one millimetre gap. True or false? All are true.
The five kernel chapters are called:
(a) The cell (b) The gene (c) Evolution as natural selection (d) Life as chemistry
(e) Life as information. Cells are the basic unit of life. Cell theory is about 150 years old. The word cell derives from the Latin word cella , meaning a small room or cubicle. All cells are stacked in orderly columns. Bacteria, for example, can live as single cells – the most numerous life forms on earth. For ev-
ery one of 30 trillion human cells, we have at least one microbial cell. Every cell is a life form in its own right. All cells come from cells by division of existing cells. Cell division explains the apparently miraculous ways the body heals itself. Cancer is caused by uncontrolled growth and division of cells. Cells have an imperative to persist, to stay alive, and to reproduce.
The second kernel chapter concerns genes. Genes are the key sources of information life uses to build, maintain, and reproduce cells and, by extension, organisms made from cells. Every
cell in one’s body contains a copy of your entire complement of genes. All three billion DNA letters of the human genome were first sequenced in 2003.
The third kernel chapter covers natural selection. Did you know that there are more than one million species of beetle (including the lovely ladybird) throughout the world. JBS Haldane said that “God had an inordinate fondness for beetles”. Nurse refers to “creationist myths”, which exist in most cultures.
Nurse is an avid follower of Darwin’s survival of the fittest theory. Thus began, Nurse writes, his gradual descent from religious belief to sceptical agnosticism.
The fourth kernel chapter is complicated and covers the compartmentation of life. Life seems to have first appeared about 3.5 billion years ago. The keynote is that “chemical reactions are an expression of the life of a cell”. There are more than 40 million protein molecules in a tiny yeast cell, Nurse’s main source of investigation.
Throughout history most human lives have been ended, not by old age, but by infectious diseases. Witness the bubonic plague, which killed half of Europe’s population in the 14th Century, and the ‘Spanish’ flu, which killed an estimated 50 million people in the early 20th Century. We will never wholly win the battle with infectious diseases, particularly viruses, which we all now know – thanks to Covid-19 – mutate often and rapidly.
Viruses are not truly alive as they cannot reproduce themselves. The only way viruses can multiply is by infecting the cells of a living organism and hijacking the metabolism of the living cell. To evolve, living organisms must reproduce, must have a hereditary system, and must exhibit variability.
We live in an unimaginably vast universe and our earth is the only place in our universe where we know for certain that life exists.
I think that belief in a Godly creation is at least as plausible as the ‘Big Bang’ theory. Creation is compatible with evolution. There is a lot of speculation out there.
This is a fascinating book by a serious scientist. I would recommend it to all medics who want to know about our precious life.
According to Nurse, live entities are chemical, physical, and ‘infomational’ machines. It certainly opened my eyes to basic biology, where before there existed an abyss.
Nurse is very perspicacious, a good teacher and communicator, and has written a profoundly simple book, an amalgam of science and history
RCPI St Luke’s Symposium 2021, ‘Focus on Global Vaccination’, 14-15 October
The results of an Asthma Society survey have revealed that 77 per cent of respondents availed of the flu vaccine in 2020, with 12 per cent of those receiving the vaccine for the first time. The high uptake of the flu vaccine in 2020, due to the threat of Covid-19, looks likely to be replicated this year, with 83 per cent of respondents saying they intend to get the flu vaccine this winter.
The survey by the Society, conducted in October among 1,602 people with asthma and their carers, was supported by Sanofi and aims to highlight the importance of protecting people with asthma from flu this year.
The HSE advises that all people with moderate to severe asthma should ensure that they get their vaccine.
Of those surveyed, 9 per cent have been diagnosed with severe asthma with 29 per cent and 28 per cent with moderate and mild asthma respectively. A large majority said they would get a flu vaccine as they are very concerned about protecting themselves (74 per cent) and family members (35 per cent) against contracting flu this winter. Some 40 per cent of respondents said they would vaccinate to avoid prompting an asthma attack.
Ms Sarah O’Connor, CEO of the Asthma Society, is encouraging those with asthma or with family members with asthma to get the flu vaccine.
“It’s great to see such a positive response to vaccine uptake. It is so important to take extra precautions this time of year, and we know that colds and flu, along with respirato-
ry infections, can be triggers for many people with asthma. While it’s impossible to completely rule out the possibility of catching a virus, there are a few things you can do to protect yourself from the flu and reduce your risk of getting sick.
“Make sure your asthma is well under control before the flu season begins. It is heartening that 50 per cent of those surveyed intend to speak with their GP or respiratory specialist this year. We would encourage all asthma patients to speak to your doctor or asthma nurse specialist about getting the flu vaccine. You can also contact our free Asthma Adviceline on 1800 44 54 64 and WhatsApp messaging services on 086 059 0132 where our nurses are available to answer any questions that you may have.”
Dr Dermot Nolan, GP, former ICGP National Clinical Lead on Asthma and member of the Asthma Society medical advisory group, commented: “As we enter into flu season there are several things you can do to help minimise your chances of being infected with the flu virus or, if you do catch the virus, stop it spreading to others around you.
“The same precautions to prevent the spread of Covid-19 can be applied with flu. Cover your nose and mouth with a tissue when you cough or sneeze, throw away the tissue and thoroughly wash your hands afterwards. Try to avoid touching your mouth, eyes and nose, especially after coming into contact with an ill person.”
A drug used to treat agitation in people with dementia is no more effective than a placebo, and might even increase mortality, according to a new study published in The Lancet
The research has shown that antidepressant mirtazapine offered no improvement in agitation for people with dementia – and was possibly more likely to be associated with mortality than no intervention at all. The study was led by the University of Plymouth with Prof Iracema Leroi from the
poor outcomes, and so mirtazapine has been routinely prescribed. This study was designed to add to the evidence base around its effectiveness.
Funded by the UK National Institute for Health Research (NIHR), the study recruited 204 people with probable or possible Alzheimer’s disease from 20 sites around the UK, allocating half to mirtazapine and half to placebo. The trial was double-blind; meaning that neither the researcher nor the study participants knew what they were taking.
The results showed that there was no less agitation after 12 weeks in the mirtazapine group than in the control group. There were also more deaths in the mirtazapine group (seven) by week 16 than in the control group (only one), with analysis suggesting this was of marginal statistical significance.
The study is an example of the importance of clinical trials for dementia. Currently, less than 0.5 per cent of people with dementia participate in research in Ireland, despite the need for evidence to address the rapidly increasing impact of dementia on our aging society.
The study’s publication coincides with the launch of Dementia Trials Ireland (DTI), a five-year initiative funded by the Irish Health Research Board (HRB) and led by Prof Leroi and Prof Sean Kennelly, both faculty of GBHI at Trinity College. The aim of DTI is to significantly increase the
opportunities for people with dementia to participate in clinical trials in Ireland.
Prof Leroi said: “It is only through conducting robust and high-quality clinical trials for Alzheimer’s disease and other forms of dementia that we can hope to combat this condition, which affects so many families in Ireland. It is every patient’s right to participate in research and we therefore have to ensure that they have the opportunity to do so.”
Lead researcher Prof Sube Banerjee, Executive Dean of the Faculty of Health and Professor in Dementia at the University of Plymouth, explained why the results of the study were so surprising, but important.
“Dementia affects 46 million people worldwide – a figure set to double over the next 20 years. Poor life quality is driven by problems like agitation, and we need to find ways to help those affected. This study shows that a common way of managing symptoms is not helpful – and could even be detrimental. It’s really important that these results are taken into account and mirtazapine is no longer used to treat agitation in people with dementia. This study has added important information to the evidence-base, and we look forward to investigating further treatments that may help to improve people’s quality-of-life.”
The full study is available to view here: https://bit. ly/3nAeKGC
Some €3 million funding has been announced for the Clinical Research Facility Galway (CRFG) – a Health Research Board (HRB) centre supporting clinical trials to improve health and care. The investment is part of a €22 million fund from the HRB for clinical research facilities located at hospital sites and supported by universities.
The Clinical Research Facility Galway is a joint initiative of NUI Galway and Saolta University Health Care Group for the promotion of clinical research and conduct of clinical trials, bringing together clinicians, researchers, and academics to focus on studies aimed at understanding diseases and translating the knowledge gained into advances in patient care.
Prof Andrew Smyth, Director of the HRB Clinical Research Facility Galway and Consultant Nephrologist at Galway University Hospitals, said: “The HRBCFRG aims to improve patient care and population health through the delivery of clinical trials by providing the necessary infrastructure,
physical space, facilities, expertise, specialist training, and culture.
“This infrastructure funding support from the HRB puts us on the map globally in terms of the ability to manage and execute all stages of clinical trials from conception to conclusion.
“At the HRB Clinical Research Facility Galway we have the end-to-end services to guide breakthrough research including first-inhuman trials, medical technology/devices, pharmaceuticals, cancer trials and much more. Our portfolio is one of the most diverse nationally, and we have both the clinical expertise and clinical trial experience to grow our own trials from the ground up.
“The HRB infrastructure funding makes this possible and is essential for growth and expansion of our clinical trials.”
The overall HRB funding package will keep Ireland at the forefront of clinical research and trials internationally, while also increasing opportunities for patient participation and benefit.
NUI Galway researcher and academic Dr Karen Doyle has been appointed President of Neuroscience Ireland (NSI).
Global Brain Health Institute (GBHI), Trinity College Dublin, as co-investigator.
Agitation is a common symptom of dementia, characterised by inappropriate verbal, vocal or motor activity, and often involves physical and verbal aggression. Nondrug patient-centred care is the first intervention that should be offered, but when this doesn’t work, clinicians may move to a drug-based alternative. Antipsychotics have proven to increase death rates in those with dementia, along with other
Mater Private Network has appointed Garry McCabe as Group Chief People Officer. According to the organisation, Mr McCabe has over 20 years’ experience in strategic human resources (HR) and industrial relations and holds a business studies degree from University College Dublin, with a specialisation in HR management.
Mr McCabe began his industrial relations/HR career in Tayto before moving within the C&C Group to the Soft Drinks Division. Since 2007 he has worked with Kuehne+Nagel, the world’s leading freight and logistics company, and has experience in both human resources and commercial leadership roles.
Speaking about his appointment, Mr John Hurley, CEO, Mater Private
Network, said: “We are delighted to welcome Garry to our senior leadership team. He brings a wealth of experience to our organisation, having led the HR function in a number of leading Irish and global companies. We look forward to having the benefit of his expertise as we work to consolidate our position as the leading private hospital group and one of the top 10 most trusted companies in Ireland.”
Dr Doyle, a Senior Lecturer at the university and principal investigator at CÚRAM, the Science Foundation Ireland Research Centre for Medical Devices, is a former Vice-President of Neuroscience Ireland (2007–2009). She also led the foundation of Galway Neuroscience Centre in 2004 and was the leader of the centre from 2004 to 2009.
“I am delighted to accept the role of President of Neuroscience Ireland and look forward to promoting and supporting the important work of the society over the next two years. I want to thank Professor Áine Kelly for her outstanding leadership and contribution to NSI over the last two years,” commented Dr Doyle.
Prof Abhay Pandit, Scientific Director at CÚRAM, said: “We congratulate Dr Karen Doyle on this prestig-
ious appointment. Neuroscience Ireland plays a vital role in the promotion of research and education in the neurosciences. We look forward to seeing the society’s impact grow under her leadership in the coming years.”
Dr Doyle specialises in neurovascular stress and neuroprotection, focused on ischemic stroke, which occurs when a blood clot blocks or narrows an artery leading to the brain. Her research is investigating the characteristics of human blood clots that cause occlusive strokes, to inform medical device design and discover new biomarkers to advance stroke diagnosis and treatment.
NURSE REQUIRED
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
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
GP REQUIRED
(Full-time/sessions also available)
Riverwest Medical, Foynes, Co Limerick are looking for a GP to join our practice.
We are a two GP practice and we are supported by an excellent nursing and administration team.
We are fully computerised and our appointments are 15 minutes.
We have an excellent package, paid professional indemnity, and there is no out-of-hours commitment. Starting date is negotiable and we can accommodate a future start date for those in a current role.
Please contact us at dreileen@riverwest.ie or call Eileen on 087 296 6970 to arrange a meeting. See our website on www.riverwest.ie
GP POSITION AVAILABLE
GP opportunity to take over a thriving rural practice in West Limerick. Full rural practice allowance, purpose-built premises, computerised, full ancillary staff, appointment only, no on-call commitment, 30 minute drive to nearest university. This is a two-doctor practice. We are prepared to work part-time, to ease transfer. Very favourable terms for suitable candidate/s.
Contact 087 253 2584 or email catgercorrigan@yahoo.com
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
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.
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A round-up of news and oddities from left field by Dr Doug
WitherspoonAs we bid farewell to the more clement weather and it becomes more challenging to get a round of golf in, perhaps the more accident-prone among us are better off – even for the most skilled and coordinated pro, the strangest in-
30%
juries can befall them. For the trauma medicine aficionados, here's a brief round-up of how some of our favourite golfers seem to be so prone to bizarre injuries.
For instance, in 2017 Louis Oosthuizen returned to his home country to compete in the Joburg Open, but the elite sportsman
of infants experience symptoms of regurgitation1
For bottle-fed infants with frequent regurgitation
a stepped-care approach...
REVIEW the feeding history.
the feed volumes by trialling smaller, more frequent feeds (while maintaining an appropriate daily total).
TRIAL
was forced to pull out after jamming his fingers in between some trolleys at the airport.
"This morning is even worse than it was yesterday, so I tried to grip a golf club, but there's no way I can go to my grip position," reported lucky Louis.
Even less lucky was our own Padraig Harrington, who took one for the team at the FedEx St Jude’s Classic. An amateur hit Harrington on the shoulder with his club, leaving him with six stitches and a temporary panic over whether he would be able to play as a professional again. Padraig's take on it was thus: "There's no truth in the rumour that it was the amateur's best strike of the day. Ironic that a potential injury caused coaching an am[ateur] could have resulted in me becoming a full-time coach."
Just a couple of months before that, Dustin Johnson fell down the stairs at his Augusta home, putting him out of the Masters – rotten timing, as he had won the previous three tournaments in which he played. The tumble, and the resultant tricky low-back pain, put him out of action for a month.
Perhaps some of golf's finest are also not best suited to using dangerous machinery. It's a different type of swing. Both Greg Norman and Jamie Donaldson had chainsaw-related accidents; Donaldson almost lost his left-hand little finger, but was stitched-up and back in action after only three weeks. Norman went one better and almost lost his left hand after a chainsaw mishap. His account of the event is precise: "I was about four branches from being done, and there was one branch about chest high, and I cut through and took my finger off the trigger. The branch was just about ready, was falling straight down, and I went to grab it with my left hand, but it was a little heavier than I anticipated."
"The weight took my arm, right above where you wear your watch on your left wrist, and took it right into the chains as it was spooling down. I was very lucky in a lot of ways. If the chainsaw was going at full speed, my hand would have been cut off and it missed my ulna nerve and muscles, so I was extremely, extremely lucky in that regard, by fractions of millimetres."
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IMPORTANT NOTICE: Aptamil Anti Reflux is a food for special medical purposes for the dietary management of frequent reflux and regurgitation. It should only be used under medical supervision, after full consideration of the feeding options available including breastfeeding. This product should not be used in combination with antacids or other thickeners and is not suitable for premature infants. Suitable for use as the sole source of nutrition for infants from birth and as part of a balanced diet from 6 months.
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a thickened formula. July 2020
Keeping Ireland on the map is Rory McIlroy, who missed most of 2015 after a total rupture of his anterior talo-fibular ligament and associated joint capsule damage, whilst having a kickabout with his friends.
Even when they go to bed, it's not guaranteed that pro golfers are safe. Tour veterans Graeme McDowell and Sam Torrance took freak accidents to a new level when they both incurred midnight injuries. Late one night during the WGC-HSBC Champions tournament, McDowell went sleepwalking and woke up in his boxers in searing pain – him, not the boxer shorts – with his hand somehow caught in a door. No broken bones, luckily, but swelling and bruising meant he had to use a 10-finger 'baseball grip'. He was able to finish the tournament nonetheless.
An even stranger event saw Torrance miss his 1993 Ryder Cup singles match. In the wee hours, Torrance tackled what he thought was an intruder in his dimly-lit apartment, which turned out to be a yucca plant. The yucca plant won the tussle and Torrance was left with a broken toe. As you can imagine, the ribbing he got from fellow golfers was merciless – legend has it that every time Torrance hit a ball near a tree from then on, a cry would go up of 'Watch out Sam, it's a jungle out there!'
Northern Ireland: www.eln.nutricia.co.uk
But the last word goes to legend Lee Trevino, who was struck by lightning whilst playing the – you guessed it – 13th hole. That famous Father Ted episode springs to mind, but incredibly, even at odds of 300,000/1 of being struck by lightning, Trevino has been hit three times during his career.
There's a lot to be said for sticking to the 19th hole.
Aptamil Anti-Reflux is a thickened formula for the dietary management of reflux and regurgitation in bottlefed infants
Clinically proven to reduce infant regurgitation episodes by 78%2