The Medical Independent 28th November 2022

The next level of cancer care

Tight rotas and poor infrastructure cited by model 3 consultants

Tight rotas, poor communication, and inadequate training facilities, were among the challenges citied by consultants in model 3 hospitals during site visits this year by the HSE National Doctors Training and Planning (NDTP) unit.

In June, the Medical Independent reported on the the model 3 hospital network project, which is co-sponsored by NDTP and the RCSI and aims to provide methods to improve consultant recruitment to such sites.

Dr Consilia Walsh, Clinical Lead, NDTP, delivered an update on the project at a conference on 11 November, which marked the launch of the NDTP Strategic Plan 2022-2027.

During the site visits, model 3 hospital consultants raised the issues of tight rotas as well as communication problems.

“Since the disbandment of the medical boards and with the current governance structures, there isn't, in many hospitals, a

forum for consultants to meet,” according to Dr Walsh. She said some consultants reported issues with communication “between senior hospital management teams and the consultants on the ground”.

She added that some consultants “feel disconnected and disenfranchised from decisions” on service development.

Infrastructure deficits were also raised, with a reliance on cabins, insufficient office space, and “no reliable access to theatre” for elective work.

Consultants said the presence of trainees and medical students was very important to the model 3 hospitals and a “boost to morale”. However, some hospitals did not have any facilities for training, while facilities in other sites were inadequate.

Dr Walsh said the model 3 hospital network project report and recommendations should be completed towards the end of the year. The NDTP will then fund a project manager to progress implementation of the recommendations.

How to talk about death

Parents of critically ill children often want clarity from physicians over and above language choice, writes Dr Muiris Houston

PAGE 18

Staff retention to be 'significant focus' of 2023 HSE service plan

Staff retention and the impact of the Covid-19 pandemic on the workforce will be a “significant focus” in the 2023 HSE national service plan, according to Dr Philip Crowley, National Director for Strategy and Research.

Dr Crowley, speaking in Dublin at the Environment, Health and Wellbeing Conference 2022 on 9 November, said there would also be funding for actions on climate change and the HSE’s new climate action strategy.

He told the Medical Independent (MI) that work on the climate action strategy would begin immediately upon publication and “there will be reviews of it [the strategy] ... annually certainly”.

Speaking to conference attendees, Dr Crowley praised health

staff during the pandemic who had displayed “amazing use of improvement skills to really improve care overnight, [to]change care overnight, we put in new models of care overnight”.

“Obviously this has impacted on our staff as well... and it's a significant focus in our national service plan [2023], which we are finalising.... There will be focus there on staff retention, looking after our staff and trying to help them recover from the experience of managing the pandemic.”

In the question-and-answer session, he said that there will be “money put aside in that [national service plan] for climate action”.

The national service plan for 2023 will be submitted to the Minister for Health “for detailed consideration soon”, a HSE spokesperson told MI See news feature, p4-5.

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

The first and only treatment indicated to reduce:

• all-cause mortality

• frequency of CV-related hospitalisations in patients with wild-type or hereditary ATTR-CM.1

ATTR-CM=transthyretin amyloid cardiomyopathy; CV=cardiovascular.

References: 1. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.

2. VYNDAQEL Summary of Product Characteristics. Vyndaqelq 61 mg soft capsules (tafamidis) Prescribing Information: Before prescribing Vyndaqel please refer to the full Summary of Product Characteristics. Presentation: Vyndaqel 61 mg soft capsules. Each soft capsule contains 61 mg tafamidis. Uses: Vyndaqel is indicated for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM). Dosage: Treatment should be initiated under the supervision of a physician knowledgeable in the management of patients with amyloidosis or cardiomyopathy. When there is a suspicion in patients presenting with specific medical history or signs of heart failure or cardiomyopathy, etiologic diagnosis must be done by a physician knowledgeable in the management of amyloidosis or cardiomyopathy to confirm ATTR-CM and exclude AL amyloidosis before starting Vyndaqel, using appropriate assessment tools such as: bone scintigraphy and blood/urine assessment, and/or histological assessment by biopsy, and transthyretin (TTR) genotyping to characterise as wild-type or hereditary. The recommended dose is one capsule of Vyndaqel 61 mg (tafamidis) orally once daily. Vyndaqel 61 mg (tafamidis) corresponds to 80 mg tafamidis meglumine, tafamidis and tafamidis meglumine are not interchangeable on a per mg basis. Vyndaqel should be started as early as possible in the disease course when the clinical benefit on disease progression could be more evident. Conversely, when amyoid-related cardiac damage is more advanced, such as in NYHA Class III, the decision to start or maintain treatment should be taken at the discretion of a physician knowledgeable in the management of patients with amyloidosis or cardiomyopathy. There are limited clinical data in patients with NYHA Class IV. If vomiting occurs after dosing, and the intact Vyndaqel capsule is identified, then an additional dose of Vyndaqel should be administered if possible. If no capsule is identified, then no additional dose is necessary, with resumption of dosing the next day as usual. There are no recommended dosage adjustments for elderly patients or patients with renal or mild and moderate hepatic impairment. Limited data are available in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/min). Tafamidis has not been studied in patients with severe hepatic impairment and caution is recommended. There is no relevant use of tafamidis in the paediatric population. Method of Administration: The soft capsules should be swallowed whole and not crushed or cut. Vyndaqel may be taken with or without food. Contra-indications: Hypersensitivity to the active substance or to any of the excipients as listed in section 6.1 of SPC. Warnings and Precautions: Contraceptive measures should be used by women of childbearing potential during treatment with tafamidis and for one month after stopping treatment. Tafamidis should be added to the standard of care for the treatment of patients with transthyretin amyloidosis. Physicians should monitor patients and continue to assess the need for other therapy, including the need for organ transplantation, as part of this standard of care. As there are no data available regarding the use of tafamidis in organ transplantation, tafamidis should be discontinued in patients who undergo organ transplantation. Increase in liver function tests and decrease in thyroxine may occur. This medicinal product contains no more than 44 mg sorbitol in each capsule. Sorbitol is a source of fructose. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of

sorbitol (or fructose) should be taken into account. The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly. Pregnancy and Lactation: Tafamidis is not recommended during pregnancy and in women of childbearing potential not using contraception.Available data in animals have shown excretion of tafamidis in milk.A risk to the newborns/infants cannot be excluded. Vyndaqel should not be used during breastfeeding. Interactions: In a clinical study in healthy volunteers, 20 mg tafamidis meglumine did not induce or inhibit the cytochrome P450 enzyme CYP3A4. In vitro tafamidis inhibits the efflux transporter BCRP (breast cancer resistant protein) at the 61 mg/day tafamidis dose with IC50=1.16 μM and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter (e.g. methotrexate, rosuvastatin, imatinib). In a clinical study in healthy participants, the exposure of the BCRP substrate rosuvastatin increased approximately 2-fold following multiple doses of Page 2 of 2 2020-0065522 61 mg tafamidis daily dosing. Likewise, tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) with IC50=2.9 μM and IC50=2.36 μM,respectively,and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters (e.g. non-steroidal anti-inflammatory drugs, bumetanide, furosemide, lamivudine, methotrexate, oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, zidovudine, zalcitabine). Based on in vitro data, the maximal predicted changes in AUC of OAT1 and OAT3 substrates were determined to be less than 1.25 for the tafamidis 61 mg dose, therefore, inhibition of OAT1 or OAT3 transporters by tafamidis is not expected to result in clinically significant interactions. No interaction studies have been performed evaluating the effect of other medicinal products on tafamidis. Undesirable Effects: The following adverse events were reported more often in 176 ATTR-CM patients treated with tafamidis meglumine 80 mg compared to placebo: flatulence [8 patients (4.5%) versus 3 patients (1.7%)] and liver function test increased [6 patients (3.4%) versus 2 patients (1.1%)]. A causal relationship has not been established. Safety data for tafamidis 61 mg are not available as this formulation was not evaluated in the double-blind, placebo-controlled, randomised phase 3 study. Legal category: S1A. Marketing Authorisation Numbers: EU/1/11/717/003– 61mg (30 capsules). Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500. Last revised: 04/2021 q This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Ref: VY 61MG 2_0

Indicated for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM). 2

Sharp drop in debt collection expenditure at CHI

NIAMH QUINLAN

Expenditure on debt collection agencies to pursue unpaid fees and charges at Children’s Health Ireland (CHI) has decreased markedly between 2018 and 2021.

Figures released in response to a parliamentary question by Sinn Féin Deputy Johnny Guirke showed that €7,015 was spent in 2021, compared to €32,272 in 2020, €42,332 in 2019, and €50,508 in 2018.

Figures for 2022 were not included in the response to the parliamentary question. In September, inpa -

Growing anger among area medical officers

Ongoing delays to the payment of long sought wage increases is causing growing anger among area medical officers (AMOs), the Medical Independent (MI) has learned.

AMOs were due to receive pay bill rises last February, but are still awaiting payment due to a dispute with the HSE and Department of Health.

According to the IMO, a fund of 1 per cent of the pay bill for their members was placed in a fund under the Building Momentum public service pay agreement.

The fund was to be used to address individual disputes or for the provision of a 1 per cent increase for the entire group.

The IMO sought to use this fund to address a number of issues, including those affecting AMOs.

“This was due to be effective from 1 February 2022, but there have been ongoing delays and the IMO are in dispute with the HSE and Department about this process,” according to a spokesperson for the union.

AMOs have been seeking improved pay and conditions on a par with that of their senior medical officer colleagues for many years.

Conciliation talks aimed at resolving the dispute began at the Workplace Relations Commission (WRC) in 2020.

Dr Joe Quinn, AMO, told MI he believes the delays are because “the whole process has apparently been rejected by the Department of Public Expenditure and Reform (DPER)”.

Dr Quinn said he feels that he and his colleagues are being “played”.

“This can has been kicked down the road for almost 20 years now, and we have been continuously played for all of that time. I have always maintained that the plan is to just play down the clock, as in another year or so there will be no more AMOs left to fight the case.”

A HSE spokesperson said the matter had been referred to the WRC. Both the Department of Health and DPER confirmed that engagement was continuing and further comment would be “inappropriate”.

Approximately 12 AMOs work in community health services nationally, some on a part-time basis.

New structures were introduced in 2004 resulting in no further AMO recruitment.

tient public hospital charges for children under 16 were abolished under reforms announced by the Department of Health. This measure has removed the charges of €80 per night, up to a maximum of €800 per year, that were previously applied.

Speaking to the Medical Independent, Irish Cancer Society Advocacy Lead Ms Rachel Morrogh said the Society “is concerned that the use of debt collectors over many years has added to the worry and distress experienced by families who have to take a child to hospital".

“Each payment made by a family to a debt collector

will have been preceded by a spike in fear caused by the arrival of a letter or phone call from the debt collection agency.”

Describing the use of debt collectors as “a moral stain on the health service”, she said the Society was looking forward to the abolishment of all inpatient hospital charges in April 2023. The policy was announced as part of Budget 2023.

This would lead to the end of the practice of engaging debt collectors to “chase families at their most vulnerable point”.

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How to stop healthcare worsening a global health emergency

“Climate change is already killing us,” the World Health Organisation (WHO) Regional Director for Europe, Dr Hans Henri P Kluge, warned earlier this month. One example he cited was the WHO’s estimate that at least 15,000 people died in Europe, specifically due to the heat, in 2022.

However, Dr Kluge added that “strong action now” on climate change could prevent more deaths.

This month world leaders gathered in Sharm el-Sheikh, Egypt, at the 2022 United Nations Climate Change Conference (COP27). Concerns over the environment are rarely absent from national and international headlines and a growing sense of urgency is reflected in healthcare.

Neutral

The HSE’s Climate Action Plan 2022-2050 launch date “will be confirmed in the coming weeks”, a spokesperson told this newspaper.

It is the first plan of its kind and will commit the HSE to being climate neutral by 2050.

“We will be starting with this immediately,”

Dr Philip Crowley, HSE National Director for Strategy and Research, told the Medical Independent (MI). Asked about the significant length of time covered by the plan (28 years),

Dr Crowley said “there will be reviews of it [the plan] during it, annually certainly”.

He spoke about the upcoming strategy at the recent Environment, Health, and Wellbeing Conference 2022, which was held on 9 November in Dublin. It was jointly organised by the HSE, Environmental Protection Agency and the Economic and Social Research Institute.

Dr Crowley told attendees that climate change endangers health in a variety of ways. These include extreme heat leading to heat-related illness and death, and poor air quality leading to respiratory and cardiovascular disease. Extreme weather also could lead to droughts, which would have knock-on health effects. Dr Crowley also referred to the mental health impact of climate change.

This was highlighted recently by the Turn2Me charity, who reported “a huge increase” in the number of people with climate-related anxieties in Ireland.

“I think we have to strike some sort of sweet point between urgency and pessimism,” Dr Crowley told the conference.

“We need urgency, but we need some optimism as well.”

Dr Crowley added that healthcare had a significant environmental impact through the use high energy intensive buildings, waste from clinical procedures, and transportation due to the supply chain for pharmaceuticals and other goods.

Other examples included the use of anaesthetic gases and inhalers for asthma.

Dr Crowley said a procurement system that

reflected these environmental will form part of the new strategy (see panel).

The HSE has identified 170 “significant energy users” within the health service that account for 75 per cent of the energy use and carbon emissions. There are currently 111 local energy teams in place across the health service and in hospitals.

These will be reshaped into green teams, “so broadening their remit”.

Dr Crowley, who has a public health background and practises as a GP, said that different specialties have become increasingly aware of environmental health.

“Certainly, you could see that specialties like general practice and anaesthesiologists have really become aware of the particular impacts of their practice in their area,” he told MI

“Overall, I think, we [the HSE] need to continually raise awareness. That’s part of this communications programme that we are going to try and start. It is to get all of our staff… to come together. I really think we could achieve a lot.”

Mobilise

Dr Crowley said the experience of the health service and the Covid-19 pandemic could act as a blueprint with action taken at a local and national level.

“People pulled together around a common purpose,” he said.

“Climate change is the next thing. Obviously, it has been around a long time. But I think if we can mobilise our staff and all of their good ideas, if we can manage to enable people locally to institute changes around how they get to work, the environment they work in, waste, etc, we could change a lot without having to tell everybody what to do.”

There are concerns internally within the HSE over the possibility of achieving emission targets. In October, MI reported that the risk the HSE may not achieve a 51 per cent reduction in overall greenhouse emissions by 2030 has been included in its corporate risk register. However, the HSE said that where “challenges have been identified in meeting these targets, appropriate mitigation and control measures are in place”.

The Irish Doctors for the Environment (IDE) group has highlighted that the HSE need to first establish the current emission levels from its national building stock and from the cost of transportation and disposal

of items used in the health system.

Separately, the Department of Health told this newspaper that its climate change oversight group, which was formed in September 2021, met in plenary twice over the following 12 months. The meetings were held in September 2021 and February this year. The group, which is chaired at principal officer level, aims to “meet two to three times a year” depending on issues of relevance to its whole membership, a Department spokesperson told MI “The main value of the climate change oversight group is as a forum for regular bilateral engagement and sharing of climate related information and developments. Representation on the group covers a wide range of stakeholders from across the Department of Health and the HSE.”

COP

Speaking to MI when the COP27 conference was still ongoing, Dr Rachel MacCann, Infectious Diseases SpR and Operations Officer for the IDE, said that her main hope for the event in Egypt would be to bring some of the “focus towards healthcare”.

“Particularly focus on green healthcare procurement and also preventative strategies,” she said.

“If you have prevention as a sort of driver of healthcare you reduce the burden on the hospital system and you are making people more resilient to the challenges of climate change.”

Dr MacCann said that if the international healthcare sector was a country, it would be the fifth largest emitter in the world. Within this country, Irish healthcare accounts for 4.4 per cent of national carbon emissions.

She said procurement was also an “op-

portunity and it should be [used] to promote green businesses”.

Dr MacCann added the HSE and others “could have a dual impact [by procurement] both from a health point of view and even a national economic point of view”.

In January, MI reported on the growing trend of climate change activism and advocacy among doctors. After almost three years of a pandemic, are there signs of flagging energy?

Dr MacCann warned “burnout is important to recognise because the workforce is just so fraught with a lot of stress from Covid, but also [due to the general] restrictions that we sometimes face in the working environment and not being able to do our jobs properly in terms of resources and time”.

She told MI that doctors often “feel those same frustrations about climate change”.

“I have met so many staff who are so exasperated with how healthcare waste is carried out in hospitals. You know, people try to make a big effort [in their hospitals], which is to be applauded. But really, you need a whole system change, the whole hospital needs to be on board.

“If that sort of change is not brought about soon, staff will start getting fatigued and they will stop caring about, say, using the right bins in hospitals. So I think the appetite among healthcare workers is certainly there. But they also need buy-in from their employers to actually do the things they want to see done.”

Public health

In August, the HSE’s public health medicine environment and health group (PHMEHG) published its annual report. The group noted that its work was conducted over the

While the COP27 conference in Egypt attracted the world’s attention, David Lynch attended a meeting in Dublin on climate change and health. He speaks to doctors about how to limit the impact healthcare has on the environment

We need urgency, but we need some optimism as well

Taking action on... inhalers, anaesthetic gases, and procurement

Tackling the use of asthma inhalers, anaesthetic gases and procurement choices by the HSE are among the most high-profile actions that health campaigners in Ireland are currently highlighting.

On procurement, Dr Rachel MacCann, Operations Officer, Irish Doctors for the Environment (IDE), told the Medical Independent (MI) she would like to see a “particular focus” on green healthcare procurement.

Procurement

Speaking at the recent Environment, Health, and Wellbeing Conference, she said that individual actions at hospitals and at local level “were great achievements”.

“But when you look at the breakdown of emissions, about 78 per cent of healthcare emission can be attributed to procurement. So making one big change in one central area, I think, can have a more overarching and longer impact than a lot of the individual efforts.”

Speaking at the same conference, Dr Philip Crowley, HSE National Director for Strategy and Research, described “sustainable procurement” as a “complex” area.

“On the one level you would say the HSE has massive leverage,” he said.

“It is a very big buyer of pharmaceuticals and of all types of materials, etc, but actually you would be surprised in a way, particularly with global products like pharmaceuticals, how we have to use our leverage carefully because

last 12 months in the context of the “public health reform process in line with the Crowe Horwath Report”.

According to the report, PHMEHG “has advocated for [environment and health] to be included as a key component of health protection reform and as such, resourced adequately”.

The group also called for a national environment and health surveillance system and to “prioritise protecting health from serious environmental issues”.

“There are a number of clinical priorities for public health medicine related to the environment including the health impacts of air pollution, issues with water quality and quantity, climate change and the need for strong advocacy on preventing environmental issues that impact on health,” according to the PHMEHG report.

Public health doctors’ “important” role in environmental health could be developed and expanded as part of the current reform programme, Dr Ina Kelly, Consultant in Public Health Medicine and member of PHMEHG, told MI

The reform programme includes the appointment of 84 public health consultants by December 2023.

Dr Kelly said that public health consultants and specialist in public health medicine currently operate under statutory functions “and part of that is all influences on health... in-

we are a small market.”

“At the same time, we have leverage and we will use it to ensure we have a green procurement approach.”

Inhalers

On the issue of asthma inhalers, Dr Crowley noted a recent ICGP audit of inhaler use. He said the HSE had been working with the College to “explore” asthma care that protects the environment.

The ICGP sustainability working group would like the Executive to make moves in this area.

“One policy action the HSE could take...would be to suspend PCRS reimbursement for Ventolin [asthma inhalers],” Dr Sean Owens, who is a working group member, told MI

“With the urgency of the climate crisis, we really need to decarbonise the carbon hot spots first and foremost. In healthcare, these are undoubtedly anaesthetic gases and multi-dose inhalers (MDIs). For example, the seemingly innocuous blue reliever MDI is responsible for a significant proportion of the carbon footprint of the entire health service.”

Dr Owens said switching to “dual preventer and reliever inhalers for asthma has already been shown to be clinically effective, as per evidence base...”.

He noted that moving away from MDIs, in general, “will take time and need buy-in from all stakeholders including patients.” More importantly, he added, “such a move would send a strong signal externally that the HSE means to decarbonise.”

cluding the environmental aspect”.

“Definitely we will have a role in it, in terms of what’s happening and influencing peoples’ health and then also on doing something about it... and [the current legislation] tells us to advise local and the relevant authorities.”

Dr Kelly, who spoke on health risks and hazards from health waves and air quality at the recent Environment, Health, and Wellbeing Conference, believes changes may be coming as to how public health doctors engage with climate change.

“How will this be impacted by the reform programme? I think that as we build up our multidisciplinary teams … public health specialists or consultants in public health will have a farther reach and be able to do more,” the former IMO President told MI

“We have had so few resources up until now, that really we have been only touching the edges of what we can do. We need obviously to be working a lot more with all our colleagues, with all the different agencies that all have a different role in this, and we all need to be working together.”

She noted that the staff on the multidisciplinary teams “haven’t been working on the environmental side before”.

“It’s more on the infectious disease side,” Dr Kelly added. “So we are going to have to train them up in all of that. But I think, yes, we potentially will have a much better opportunity in the future to start impacting and providing

Anaesthetic gases

The IDE has an anaesthetic gases working group. Its primary aim is to make “anaesthesia more sustainable” and to reduce greenhouse gas emissions among anaesthesiologists through safe use of low-flow anaesthesia, “and sparing use of N2O and desflurane.”

“Anaesthetic gases are a huge area of emission in Ireland and our working group only recently published an incredible audit,” said Dr MacCann.

Speaking at the environmental conference, Dr Crowley noted one of the “arms of our [HSE] climate strategy are clinical impacts on climate, anaesthetic gases is a significant one”.

He highlighted the use of desflurane, in particular.

“The College of Anaesthesiologists of Ireland have, thankfully, been great partners in our initial work on creating a climate strategy along with the Irish Doctors for the Environment,” said Dr Crowley.

“They have been doing quite a significant amount of work on anaesthetic gases and we are going to build on that. But they are looking to reduce the use of inhalation anaesthetic agents, particularly those with a high environmental impact and they are going to promote environmentally friendly techniques.”

He said that recent work had meant that, at a national level, 20 per cent of anaesthetic departments have ceased using desflurane.

our experience into the [environmental] health of the public.”

Dr Kelly said the reform programme will mean “environmental health is going to have a higher profile that it did before” with a more national focus.

She said up until now public health had been providing “quiet leadership” at a more regional and local level.

GPs

In general practice, the ICGP’s sustainability working group is finalising a tool-kit to rollout next year to provide detail on where the carbon footprint is created in general practice.

It will offer “GPs, trainees, practice nurses, and practice staff practical steps they can take to work towards a more sustainable future,” Dr Sean Owens, who is a member of the working group, told MI. He added it is aimed to show “busy and time poor” GPs where the carbon footprint “is within our daily working lives”.

“We believe primary care can be leaders in planetary health by lowering our own carbon, plastic, water, antibiotic, and waste footprint and also by lessening the pressure on tertiary care, where much of healthcare emissions are to be found,” Dr Owens told this newspaper.

“Furthermore, with healthcare’s trusted role, we hope healthcare can affect change at political level by showing how the climate crisis is simultaneously a health crisis.”

MINDO NUMBERS

758

clients accessed abortion care through the Irish Family Planning Association (IFPA) in 2020 and 2021, according to the IFPA’s Activity Report for 2020 and 2021.

89

per cent of women who attended the IFPA service were less than nine weeks pregnant at the time of their abortion.

92 per cent self-managed their early medical abortion at home, which is in line with HSE guidance.

8

per cent of IFPA clients whose pregnancies were between 10 and 12 weeks, or who had other additional medical needs, were referred to hospitals for their abortion care.

537 million adults were living with diabetes in 2021. The number is expected to rise to 643 million by 2030 and 783 million by 2045, according to the International Diabetes Federation.

44 per cent of adults with diabetes remain undiagnosed (240 million), the majority of whom have type 2 diabetes, highlighted the Federation.

General register doctors need ‘equal training opportunities’ – Council President

Doctors on the general division of the Medical Council register need “equal training opportunities” and legislative support, Medical Council President Dr Suzanne Crowe told the recent HSE National Doctors Training and Planning (NDTP) conference in Dublin.

The conference on 11 November marked the launch of the NDTP Strategic Plan 2022-2027 (full coverage in the next issue).

The new plan includes a commitment to “work with the clinical educator network to enhance mentorship for doctors” on the general division of the register.

Speaking to the Medical Independent at the conference, Prof Brian Kinirons, NDTP Medical Director, said that these

measures are about “recognising the fact that there are doctors who need support in terms of training.... So it’s about trying to find measures to support them and recognising the fact that we have too many [doctors] on that [general] register and we need to reduce that number.”

More than one-third of all clinically active doctors in Ireland are on the general division of the register, according to the Medical Workforce Intelligence Report 2021, which was published by the Medical

Limited GP capacity contributing to D-Doc pressures

NIAMH QUINLAN

The north Dublin out-of-hours (OOH) GP service D-Doc is reaching capacity “more often than we should be”, according to Medical Director Dr Mel Bates.

Dr Bates told the Medical Independent (MI) that this is “probably the biggest issue” facing the service and the increase in attendance is “partly” due to the decreased capacity in daytime GP services.

He said: “It’s mainly at weekends…. More and more people can’t get doctors, or they are finding it difficult to get their own doctor in a timely manner and so they’re turning to D-Doc more and more.”

The daytime GP service has been facing workforce and workload crises and “everybody is feeling the pinch at the moment in terms of capacity”.

Dr Bates added: “There are those practices who are making a point of trying to deal with the urgent cases on a sameday basis, and that’s terribly helpful to out-of-hours.”

Although capacity is not being reached

every day, it is recorded when it happens and “we’re acutely aware of it and we try and avoid it”.

Dr Bates also told MI that the number of doctors working at D-Doc is higher at this time of year to deal with the extra winter attendances, but he expects the service to “get busier”.

“Even if there is no great Covid surge this winter, and that is a complete unknown, I expect it to be extremely busy,” he commented.

Council in September.

Speaking from the stage during the conference, Dr Crowe said that the Medical Council “can’t exist as a separate ivory tower” in regard to a workforce development strategy.

“Many doctors are on the general register and they work in relatively unaccredited posts and that has to be addressed and they have to receive accreditation for the experience that they have gained along with equal training opportunities.

“We [Medical Council] are going to focus much more on the upstream part of regulation so that doctors can be accredited [and] receive verification of their training. But this also needs to be supported by some legislative changes.” She said some doctors needed to be supported in terms of their visa and “making their home, and residency, in Ireland. So there are many pieces that need to come together.”

Control measures for gabapentinoids under examination

CATHERINE REILLY

Possible control measures in relation to pregabalin and gabapentin prescribing are being examined by a subcommittee chaired by the Department of Health.

The early warning and emerging trends (EWET) subcommittee, which is part of the national advisory committee on drugs and alcohol, is looking at potential control measures and how these may be introduced.

Pregabalin and gabapentin are indicated for the treatment of epilepsy, peripheral and central neuropathic pain, and generalised anxiety disorder, in adults.

The Department released no substantive details about the current process. In January, the Department had stated that the EWET was considering a consultation on the matter. At the time, the spokesperson said that controlling substances under the Misuse of Drugs Acts 1977-2016 required a “clear evidence base” and an

analysis of the benefits and risks. “If evidence exists to suggest that the scheduling of a substance would reduce its misuse or abuse, a multiple stakeholder approach is required, to include a referral to the European Commission.”

According to correspondence to GPs from the HSE Medicines Management Programme in 2020, there was a high level of pregabalin prescribing. The correspondence reiterated the “need for vigilance when prescribing pregabalin due to the risk of addiction, and potential for illegal diversion and medicinal misuse”.

Drug-related death figures compiled by the Health Research Board have shown an increase in deaths where pregabalin was implicated, from 14 in 2013 to 45 in 2017.

In 2019, the UK government reclassified pregabalin and gabapentin as class C controlled substances after experts highlighted rising fatalities linked to the drugs.

VOX BOX

We owe her a debt of gratitude that we must work tirelessly to repay by ensuring that women’s health is prioritised and promoted. Vicky’s legacy demands nothing less.

Ms Averil Power, CEO of the Irish Cancer Society, commenting on the passing of patient advocate Ms Vicky Phelan on 14 November.

Taking up the role of Confidential Recipient goes to the very heart of my belief that the most vulnerable in our society should receive the services they require, be valued, and treated with respect and dignity to make choices that are autonomous and emancipatory.

Antibiotic resistance will present a major issue for both Irish and global healthcare systems if we continue to overuse antibiotics for ailments of which it is not appropriate to do so. We can already see the negative effects of antibiotic overuse in play today.

For patients not adequately controlled on dual therapy with moderate to severe COPD

UNLEASH THE PROTECTION OF TRIXEO1,2

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 2022.

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.

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 and Hepatic Impairment: Use at recommended dose in patients with mild to moderate renal impairment, and patients with mild to moderate hepatic impairment. Can also be used at the recommended dose in patients with severe hepatic impairment, severe renal impairment or endstage renal disease requiring dialysis, only if expected benefit outweighs the potential risk. Patients with severe hepatic impairment should be monitored for potential adverse reactions. Paediatric Population: No relevant use in children and adolescents (<18 years of age). Method of administration: For inhalation use. Patient’s inhaler technique should be regularly reviewed by physician or other healthcare professional. Patients who find it difficult to coordinate actuation with inhalation may use Trixeo Aerosphere with a spacer.

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. 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, 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. Caution should also be exercised when treating patients with known or suspected prolongation of the QTc interval. 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. 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. 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. Clinical features of such infections can 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 ß2-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 of ß2adrenergic 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: 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 with other anticholinergic containing medicinal products is not recommended. 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 and 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: Coadministration with other anticholinergic and/or long-acting ß2-adrenergic agonist containing medicinal products is not recommended as it may potentiate known inhaled muscarinic antagonist or ß2-adrenergic agonist adverse reactions. Concomitant use of other beta-adrenergic medicinal products can have potentially additive effects, therefore caution is 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. ß-adrenergic blockers: ß-adrenergic blockers (including eye drops) can weaken or inhibit the effect of formoterol. Concurrent use should be avoided unless the expected benefit outweighs the potential risk. If required, cardio-selective ß-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 beta2-sympathomimetics. 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, College Business and Technology Park, Blanchardstown Road North, Dublin 15 Tel: +353 1 609 7100.

TRIXEO and AEROSPHERE are trademarks of the AstraZeneca group of companies.

Date of API preparation: 05/2022

Veeva ID: IE-3823

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

CHI tendering for external agency to recruit staff for EHR programme

Children’s Health Ireland (CHI) is looking for a company to recruit staff for its electronic health record (EHR) programme, the Medical Independent (MI) can report.

The requirement is one of two ‘lots’ in a tender that CHI is conducting for external recruitment services.

The successful company is expected to support the management of the recruitment process from pre-campaign to pre-employment.

The resulting contract will be valid for future ‘recruitment process outsourcing’ (RPO) requirements that CHI may have outside of the EHR programme in other business areas.

The tender states that the EHR is required for the New Children’s Hospital, which is now due to open in 2024.

“CHI need to undergo a bulk recruitment exercise to hire up to 82 members for the application team over a period of time to be commenced within a small timeframe,” the tender states.

It stipulates that this process needs to be completed by June 2023.

“In order to ensure that CHI can achieve this goal, the RPO team need to manage any/all recruitment functions,” according to the tender.

“It is in CHI’s best interest that an experienced recruit-

ment firm will run this recruitment campaign in partnership with the EHR team, supported by the CHI recruitment team, ie, a dedicated team which works as an extension to the overall process.”

In March, MI reported that the selection process for the provision of EHR system for the New Children’s Hospital was “still underway” more than two years after the process commenced.

There will be a fixed monthly management fee for the successful recruitment agency.

For candidates that are sourced separately to the recruitment process used by CHI and are ‘headhunted’ by the agency, CHI will pay a flat rate fee depending on the salary band for each post.

Search for senior HSE IT posts to begin next year

DAVID LYNCH

The search for people to permanently fill two key information technology (IT) positions in the HSE will commence early next year following the completion of a final review of the job descriptions, the Medical Independent (MI) has been informed.

The creation of the positions of Chief Information Security Officer (CISO) and Chief Technology and Transformation Officer (CTTO) was recommended by the post-incident review published in wake of the May 2021 cyberattack on the HSE.

In March this year, the HSE told this newspaper it intended to fill both these positions by the end of 2022. However, it has now emerged that the recruitment search will not begin until next year.

Currently the interim CISO is Mr

Puneet Kukreja and the interim CTTO is Mr John Ward.

“The permanent positions job specifications were approved after review and will be advertised in [the first quarter] of 2023 through the Public Appointments Service,” a HSE spokesperson told MI

Both positions were discussed at the June meeting of the HSE performance and delivery committee. According to minutes, “a final review of the job descriptions should be undertaken by the interim CTTO and CISO.”

Earlier this month, MI reported on the establishment of a new technology and transformation committee within the HSE.

“The new committee will provide board level oversight of the post-incident review implementation programme, together with oversight of key strategic transformation programmes,” according to the HSE.

The other ‘lot’, which forms part of the tender, is for a multi-supplier framework agreement for the provision of short-term/temporary management and administration agency placements.

According to tender documents, the framework will consist of up to five members.

“During the lifetime of the contract, CHI will inform the agencies of vacant role requirements as they arise,” the tender states.

“The agency deemed to be proposing the best quality candidate within the timeframe specified will be successful in filling the role.”

CHI will use its own resources to fill any temporary, short-term vacant roles as they arise prior to engaging with agency services “where possible”.

“The requirements listed here is what would be expected of a recruitment agency when engaging staff for CHI.

“The general specifications relate to all grades; however, it is important to note that some roles may have specific needs (qualifications, experience) depending on the job description criteria. Service providers should only submit a tender if they are confident they have capacity and suitably qualified staff with experience and expertise to meet CHI requirements.”

The deadline for both lots is 6 December.

Timeline for alcohol guideline review ‘not finalised’

DAVID LYNCH

The timeline for the next review of the HSE’s weekly low-risk alcohol guidelines has “not been finalised”, this newspaper has been told.

In January, the Medical Independent (MI) reported that the upcoming review of the guidelines would include the impact of the Covid-19 pandemic on population drinking patterns.

The weekly low-risk alcohol guidelines were last assessed in 2015 following a review commissioned by the HSE. The HSE alcohol programme has since been established and now oversees the guidelines.

The implementation plan for the HSE alcohol programme “is currently being finalised and will be available later this year”, a HSE spokesperson told MI

The alcohol programme plan will be released following the publication of a new implementation plan for Healthy Ireland.

“Timelines for the review and publication of the low-risk weekly drinking guidelines have not yet been finalised,” according to the spokesperson.

“A review of the up-to-date evidence base will be a key first step and any changes to the guidelines will be made in line with the best available evidence.”

In January, a Department of Health spokesperson told this newspaper that the “pandemic has resulted in a significant shift towards home drinking”.

“The next review and update of the weekly low-risk alcohol guidelines will need to take cognisance of these

changed drinking patterns and national and international literature.”

The current recommended weekly lowrisk alcohol guidelines are less than 11 standard drinks for women and 17 standard drinks for men. A standard drink in Ireland includes a pub measure of spirits (35.5ml), a small glass of wine (12.5 per cent volume), and a half pint of ‘normal beer’. A bottle of 12.5 per cent alcohol wine has about seven standard drinks.

According to the Healthy Ireland Survey 2021, published last December, 42 per cent of drinkers stated they were drinking less since the onset of the pandemic. Minimum unit pricing for alcohol was introduced in January this year.

Taking cancer care and research to the next level

Paul Mulholland speaks to Scientific Director at the Beaumont RCSI Cancer Centre, Prof Leonie Young , about how the Centre attained OECI accreditation and why the process is improving standards

Earlier this year, the Beaumont RCSI Cancer Centre (BRCC) reached a significant milestone.

It was announced in May that the Centre had achieved accreditation by the Organisation of European Cancer Institutes (OECI). It became only the second cancer centre in the country to receive the accolade, with the Trinity St James’s Cancer Institute (TSJCI) having been accredited in November 2020.

The assessment is based on standards across several domains, such as: Governance; research; multidisciplinary working; patient involvement and empowerment; organisational quality; prevention, diagnosis, and treatment of cancer.

The Centre is a collaboration between Beaumont Hospital, Dublin, the RCSI and St Luke’s Radiation Oncology Network (SLRON) and was established in 2019.

Scientific Director at the BRCC, Prof Leonie Young, told the Medical Independent (MI) that accreditation was a goal for the Centre since its establishment.

“We were enthusiastic from the beginning that we get outside accreditation for our centre because we knew it would enhance standards,” Prof Young said.

“It would also help give us a focus on the journey of bringing together the necessary elements of clinical care, research, and education. So we looked around at all the standards that could be achieved. We knew that our colleagues in the Trinity St James’s [Cancer] Institute had gotten OECI accreditation and we decided to go down the same route they did.”

Accreditation process

In the second quarter of 2020, the Centre reached agreement with the OECI that it would be evaluated for accreditation. The process begins with what the OECI terms “self-reflection”.

“This was a little bit more involved than we had first anticipated,” said Prof Young.

“It involved a really deep, evidenced-based reflection on your practice, on your research, and education offerings.”

Preparing for accreditation required “a huge body of work”.

“In terms of research, their bar is extremely high and that is something in Ireland that we would be well used to,” Prof Young said.

“And in terms of basic and translational research, for example, all biobanking activity had to be accredited by an outside organisation and publications had to be numerous and of a high standard.”

The OECI also required a broad interpretation of education offerings.

“It was really about the idea of offering education for all and not just those like clinical oncologists that you would associate with cancer education,” she said.

“That it would be for everybody involved in the delivery of cancer care and in cancer research. That everybody would have an open opportunity to education in cancer and that it would be relevant and forward looking.”

The self-assessment was submitted to the OECI in June 2021.

Prof Young admitted this was an “anxious” time.

“We really were anxious that we would meet a European standard. But once we passed the go/no go we knew we were in relatively good shape.”

The OECI conducted a site visit in October 2021. The inspectors visited both Beaumont Hospital and the SLRON centre at the site, as well as the RCSI.

“They talked to everybody from the porters to the nurses to the consultants to the CEOs,” according to Prof Young.

“Everybody was involved in-depth. But it was very good. And we came out of that with very good recommendations. They were very pleased with us – they were very pleased with the care that we provided, the level of patient partnership that we had, and the organisation of our research was also mentioned as particularly strong.”

The OECI prepared a final report, a draft of which was “amended a little” by the BRCC. It formed the basis of a five-year action plan for the Centre.

“The action plan is really a contract with them about how you are committing to maintaining and improving standards in care, research and education,” Prof Young said.

“It gives you a tight roadmap to follow. It is a really helpful piece of documentation, though onerous.”

Clinical trials

One of the targets in the action plan is to increase participation in clinical trials. Currently, 5 per cent of patients at the Centre are on clinical trials. Under the action plan, the aim is to increase participation to 10 per cent.

Prof Young said this is perhaps the “biggest challenge” contained in the document, but that the BRCC had to be “ambitious”.

I know [the current 5 per cent participation] sounds tiny, but when you think about the number of patients that are suitable for trials, and the amount of trials we can get open, it is not that bad,” she told MI

“And the National Cancer Control Programme (NCCP) standard is 6 per cent. So, though it is a big job, we are committed to doing it.”

She added that increasing the diversification of trials is another target to which the Centre is committed.

“That means not just thinking about the traditional pharmacological intervention trials, but maybe looking at surgical trials, more radiation trials, other intervention trials, and bringing up our translational trial portfolio, which will help feed into more investigator-initiated trials,” according to Prof Young.

“All of those things are hugely important to us.”

Research

Prof Young said Ireland is operating at a high level internationally in the cancer research arena. Her own re -

They were very pleased with the care that we provided, the level of patient partnership that we had, and the organisation of our research was also mentioned as particularly strong

search team has been making significant strides in the area of secondary breast cancer that has spread to the brain (see panel).

“We are operating at an international level,” Prof Young said.

“I don’t think there is any dispute about that. I think if you look at the publications from Irish cancer scientists, they stack up very, very well against their international counter-parts.”

However, she admitted that there is room for improvement, particularly regarding regulation.

“We can be a little bit mired with the pressure in terms of regulation.... It needs to be easier to open up a clinical trial, or it needs to be facilitated better. That is a national conversation… Ireland needs to be seen as an attractive place, and right now I’m not sure it is seen as a super attractive place.”

Data

A key part of the OECI accreditation process and subsequent action plan is standardising and improving data collection. While the Irish healthcare system is hindered by the lack of an electronic health record, Prof Young pointed out that progress is being made.

“That conversation is happening all the time. That is the important thing. We are moving towards the point where systems can communicate with each other, even if it is not the same system everywhere.”

She added that the manner in which data is collected and collated is important, not only the IT infrastructure.

“It is about making sure that everybody is collecting the same data so that the data can be analysed in a national format. That is part of the OECI journey – that everything will become standardised, and that we will be doing something in a standardised mechanism. Whatever system you have is only as good as the information that you are giving it.”

Prof Young said deciding upon which metrics are most important is key and can still be a matter of contention. She added that even if it were possible to capture every metric, these would quickly become meaningless.

“You have to make sure it is the most important metric that you are recording and that everybody is recording the same metric in the same way so you can analyse it across systems. That is a job of work to be done. And then also having an electronic system that is compatible across the centres will also be of huge importance. But at least it is recognised now.”

Conference

The BRCC held its first conference in Dublin on 22 September 2022. The event brought together healthcare professionals, academics and key stakeholders to mark the accreditation and present the Centre’s vision for comprehensive cancer care in Ireland.

“It was really a celebration, I suppose, for everybody who worked so hard to get the accreditation,” Prof Young said.

International keynote speakers included Prof Alastair Thompson, Breast Cancer Surgeon and Professor and Chief, Section of Breast Surgery, Baylor College of Medicine, US, and Dr Jean-Benoît Burrion, Chair of the OECI Accreditation and Designation Programme.

Prof Young described the networking event on accreditation held in the morning as particularly “fruitful”. It involved not only the BRCC and TSJCI, but also hospitals hoping to achieve accreditation, such as the Mater Private in Dublin, and sites based in Saolta University Health Care Group and the South/South West Hospital Group. The session was chaired by Dr Jerome Coffey, the former NCCP National Director.

“We had a really broad representation of people involved in cancer and cancer research and education, all looking to raise standards within the country,” Prof Young said.

“What we tried to do was to identify the challenges that were ahead of us in terms of getting accreditation, getting

New way to target secondary breast cancer that has spread to the brain

Prof Leonie Young was the Principal Investigator of a recent study which revealed a potential new way to treat secondary breast cancer that has spread to the brain, through the use of existing drugs.

The study, published in Nature Communications at the beginning of 2022, was funded by Breast Cancer Ireland with support from Breast Cancer Now and Science Foundation Ireland.

The research, led by Beaumont RCSI Cancer Centre investigators Prof Young, Dr Nicola Cosgrove, Dr Damir Varešlija and Prof Arnold Hill, was carried out in collaboration with the Mayo Clinic and University of Pittsburgh, US.

The research team genetically tracked the tumour evolution from diagnosis of primary breast cancer to its metastatic spread in the brain.

“We are really lucky that we have such a fabulous neurosurgery centre in Beaumont,”

Prof Young told the Medical Independent

“This enables us to research breast cancer patients where the cancer has metastasised to the brain. It is a really dreadful disease because life-expectancy is less than 12 months after diagnosis and there are currently no targeted therapies for these patients.”

The researchers found that almost half of the

organised and moving towards comprehensive standards.”

Prof Young said the discussion was “really collegiate”.

“It is really difficult to break down the barriers and the tribalism that often happens within different organisations. This was really an attempt to break that down and have a conversation with our colleagues about how to make things better.”

Support

Prof Young stressed how both the CEOs involved in the BRCC project – Mr Ian Carter, Beaumont Hospital and Prof Cathal Kelly, RCSI – have been very supportive of the OECI accreditation process.

“We have complete buy-in from our CEOs, which is phenomenal,” Prof Young said.

“They are supporting it with the resources that they have. Unless you have support throughout the organisation, at least from the top down, doing these types of things can be frustrating and very unrewarding. But this hasn’t been our experience. You are getting a commitment from the highest level of the organisation that this plan needs to be supported.”

While Prof Young said Government investment was essential to raise standards, other funding models needed to be pursued. This would include partnership models with industry and the charity sector.

“I don’t think we can just sit back and ask for investment and expect to get it. We need to identify key areas to make

tumours had changes in the way they repair their DNA.

“What we discovered was there were large deficiencies in the DNA repair mechanisms in the tumours that had gone to the brain,” she said.

“Before, these had been associated only with patients who had germline mutations – those who had a family history with either BRCA1 or BRCA2 genes. What we found was that it was much more prevalent than that.”

This discovery meant the tumours were vulnerable to PARP inhibitors, which work by preventing cancer cells to repair their DNA.

“It opened up the possibility of treating patients that didn’t necessarily have germline mutations with PARP inhibitors,” according to Prof Young.

“It has given us a new therapeutic strategy to treat patients with breast cancer brain metastasis.”

The research team is continuing to examine the area. They recently completed a study that shows aberrations in RNA methylation on brain metastasis, which could hopefully lead to “an actionable target”.

“We have just finished writing up those observations and we are looking now to see in terms of pre-clinical models if this new target will pan out,” according to Prof Young.

us stronger and then we need to go and see how we are going to raise that money to do the job that is necessary.”

Overall, Prof Young said applying for and attaining OECI accreditation has already led to improvements in patient care.

“There is a feeling that this is a team,” Prof Young concluded. “There is a feeling that we can be a centre of excellence. It has just raised everybody’s game.”

Biography

Prof Leonie Young graduated from Trinity College Dublin and completed her PhD training at University College Dublin in 1997. She leads the endocrine oncology research group at the RCSI. Her research is focused on uncovering networks involved in SRC-mediated resistance in breast cancer to both tamoxifen and aromatase inhibitors. In doing so, these investigations will identify markers that predict these outcomes and importantly develop new therapeutic targets. The research focuses on SRC-1 and takes a high-level view to harness data from high throughput experimental methods, molecular studies, functional models, and translational studies. Prof Young’s group capitalises on established strengths in translational research, in particular making use of primary breast cell cultures derived from patient tumours and large clinical datasets. By modelling the mechanism(s) of resistance associated with SRC-1, this research has defined new predictive markers and therapeutic targets suitable for commercial development and clinical trial interventions that could improve patient outcomes.

It needs to be easier to open up a clinical trial, or it needs to be facilitated better. That is a national conversation

Genuair®-has it ‘clicked’ yet?

The ONLY prefilled inhaler with visual and audible feedback for confirmed dose delivery1-4

Genuair - a simple to use inhaler for patients with COPD4

Abbreviated Prescribing Information

Eklira® Genuair® 322 micrograms inhalation powder. Please consult the Summary of Product Characteristics (SPC) for the full prescribing information. Presentation: Inhalation powder in a white inhaler with an integral dose indicator and a green dosage button. Each delivered dose contains 375 µg aclidinium bromide equivalent to 322 µg of aclidinium. Also, contains lactose. Use: Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).

Dosage: For inhalation use. Recommended dose is one inhalation of 322 micrograms aclidinium twice daily. Patients should be instructed on how to administer the product correctly as the Genuair inhaler may work differently from inhalers used previously. It is important to instruct the patients to read the Instructions for Use in the pack. No dose adjustments are required for elderly patients, or those with renal or hepatic impairment. No relevant use in children and adolescents. Contraindications: Hypersensitivity to aclidinium bromide or to any of the excipients. Warnings and Precautions: Stop use if paradoxical bronchospasm occurs and consider other treatments. Do not use for the relief of acute episodes of bronchospasm. Use with caution in patients with myocardial infarction in the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, or hospitalisation within the previous 12 months for heart failure functional classes III and IV. Dry mouth, observed with anticholinergic treatment, may be associated with dental caries in the long term. Use with caution in patients with symptomatic prostatic hyperplasia or bladder-neck obstruction or with narrow-angle glaucoma. Do not use in patients with rare hereditary problems of galactose intolerance, total lactose deficiency or glucose-galactose malabsorption. Interactions: Do not administer with other anticholinergic-containing medicinal products. No other interactions expected. Please consult the SPC for more details. Fertility, pregnancy and lactation: No data on use in pregnancy. Risk to newborns/infants cannot be excluded. Consider risk-benefit before using during lactation. Unlikely to affect fertility at the recommended dose. Side-effects: Common (1-10%): Sinusitis, nasopharyngitis, headache, cough, diarrhoea, nausea. Uncommon (0.1-1%): Dizziness, blurred vision, tachycardia, palpitations, dysphonia, dry mouth, stomatitis, rash, pruritus, urinary retention. Rare (0.01-0.1%): hypersensitivity. Not known: angioedema, anaphylactic reaction. Pack sizes: Carton containing 1 inhaler with 60 unit doses. Legal category: POM Marketing Authorisation Number: EU/1/12/778/002

Marketing Authorisation holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd., Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924. Further information is available on request to A. Menarini Pharmaceuticals Ireland Ltd. or may be found in the SPC. Last updated: February 2020

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions to: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, e-mail: medsafety@ hpra.ie. Adverse events should also be reported to A. Menarini Pharmaceuticals Ireland Ltd. Phone no: 01 284 6744.

Date of item: November 2020. IR-BRI-09-2020

Abbreviated Prescribing Information Brimica® Genuair® 340 micrograms/12 micrograms inhalation powder. Please consult the Summary of Product Characteristics (SPC) for the full prescribing information. Presentation: Inhalation powder in a white inhaler with an integral dose indicator and an orange dosage button. Each delivered dose contains 396 µg aclidinium bromide (equivalent to 340 µg of aclidinium) and 11.8 micrograms of formoterol fumarate dihydrate. Also, contains lactose. Use: Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Dosage: For inhalation use. Recommended dose is one inhalation of 340 µg/12 µg twice daily. Patients should be instructed on how to administer the product correctly as the Genuair inhaler may work differently from inhalers used previously. It is important to instruct the patients to read the Instructions for Use in the pack. No dose adjustments are required for elderly patients, or those with renal or hepatic impairment. No relevant use in children and adolescents. Contraindications: Hypersensitivity to the active substances or to any of the excipients. Warnings and Precautions: Do not use in asthma. Stop use if paradoxical bronchospasm occurs and consider other treatments. Do not use for the relief of acute episodes of bronchospasm. Use with caution in patients with myocardial infarction in the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, or hospitalisation within the previous 12 months for heart failure functional classes III and IV. Discontinue if increases in pulse rate, blood pressure or changes in ECG occur. Use with caution in patients with a history of or known prolongation of the QTc interval or treated with products affecting the QTc interval. Use with caution in patients with severe cardiovascular disorders, convulsive disorders, thyrotoxicosis and phaeochromocytoma. Hypokalaemia may occur, is usually transient and supplementation not needed. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment. Use with caution in patients with symptomatic prostatic hyperplasia, urinary retention or with narrow-angle glaucoma. Dry mouth, observed with anticholinergic treatment, may be associated with dental caries in the long term. Do not use in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Interactions: Do not administer with other anticholinergic and/or long-acting β2-adrenergic agonist containing medicinal products. Caution in use with methylxanthine derivatives, steroids, non-potassium-sparing diuretics, β-adrenergic blockers or medicinal products known to prolong the QTc interval. Please consult the SPC for more details. Fertility, pregnancy and lactation: No data on use in pregnancy. Consider risk-benefit before using during lactation. Unlikely to affect fertility at the recommended dose. Side-effects: Common (1-10%): Nasopharyngitis, urinary tract infection, sinusitis tooth abscess, insomnia, anxiety, headache, dizziness, tremor, cough, diarrhoea, nausea, dry mouth, myalgia, muscle spasms, peripheral oedema, increased blood creatine phosphokinase. Uncommon (0.1- 1%): Hypokalaemia, hyperglycaemia, agitation, dysgeusia, blurred vision, tachycardia, electrocardiogram QTc prolonged, palpitations, angina pectoris, dysphonia, throat irritation, stomatitis, rash, pruritus, urinary retention, increased blood pressure. Rare (0.01-0.1%): Hypersensitivity, bronchospasm, including paradoxical. Not known: anaphylactic reaction, angioedema. Pack sizes: Carton containing 1 inhaler with 60 unit doses. Legal category: POM Marketing

Authorisation Number: EU/1/14/963/001 Marketing Authorisation holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd., Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924. Further information is available on request to A. Menarini Pharmaceuticals Ireland Ltd. or may be found in the SPC. Last updated: October 2019

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

A call to action: Occupational health in Ireland

Our recently launched strategy sets out the value of occupational health for workers, employers, businesses, and wider society in Ireland

The way we work has changed dramatically and occupational health (OH) will play a vital role in addressing the new, complex, and evolving challenges of the future of work. We are uniquely positioned to empower safe and equitable workplaces, which benefit individuals, businesses, and society more widely. However, the profession must be supported to do so.

On Friday 11 November, the Faculty of Occupational Medicine at the RCPI launched its strategy entitled: Advocating for the Value of Occupational Health in Ireland – A call to action to our members and stakeholders. The strategy was supported by a range of groups including Ibec, the Irish Congress of Trade Unions and the HSE. Tánaiste Leo Varadkar welcomed the strategy with a video message of support. He said: “I want to congratulate the Faculty of Occupational Medicine for its work in producing this excellent strategy; thank you all for your work in raising awareness of occupational health.”

The strategy sets out the value of occupational health for workers, employers, businesses, and wider society in Ireland. The many benefits are identified and inform an action plan for occupational health professionals to engage with a range of work and health stakeholders to achieve the goal of providing universal access to good quality occupational health services.

An ageing workforce, and evolving models of work, rapid technological advancements, emerging novel public health risks and the climate crisis, all require advanced occupational health approaches and re-evaluation of statutory and organisational support for workers.

The Covid-19 pandemic brought this

into sharp focus. Occupational health professionals provided specialist advice to employers, workers and governments, assisting with the effective management of the crisis. We are uniquely qualified to navigate the future of work and we must be prepared to rise to the challenge, as it continues to evolve.

What is the value of occupational health?

Evidence of the wide-ranging value of occupational health is acknowledged. Trained and accredited OH professionals deliver quality evidence-based medical and psychosocial support for employee health and wellbeing and organisational effectiveness.

Occupational health supports individual health and ability to work, contributing to earning capacity, dignity, self-esteem, and lifespan. Occupational health improves business productivity, decreases medical and associated costs, and can enhance a company’s corporate image, as well as talent retention and recruitment. Occupational health contributes to wider society by improving local competitiveness and public health and reducing inequality.

Work-related ill health in Ireland remains a significant burden for individuals, employers, the State and society, which will be further exacerbated by the rising cost of living. Some 7.1 million DALY (disability-adjusted life years) are lost in the EU as a result of work-related injury and illness. And this individual disadvantage also has economic ramifications. For example, in most European countries, work-related cancer accounts for €119.5 billion or 0.8 per cent of the EU’s GDP.

Multiple studies show that access to paid sick leave, which can be vital to recovery and ability to undertake treatment, gives

rise to significant inequalities. Part-time workers, particularly those in small organisations and those with less than five years’ service, took less paid sick leave than equivalent full-time staff in 2021, according to a Central Statistics Office survey. Also, full-time employees in smaller organisations took less paid sick leave than those in larger organisations. It showed 20.6 per cent of workers took paid sick leave and 6.3 per cent took sick leave without pay over a 12-month period.

According to the most recent European Working Conditions Survey (2015), 52 per cent of workers reported continuing to work while they were sick, and 19 per cent said they did not feel they would be able to do their current job or a similar role up until the age of 60 and beyond.

A striking 21 per cent of Irish employees who completed the same survey felt that their health or safety was at risk because of their work.

Why now?

Informed, evidence-based occupational health solutions are vital to addressing these issues. Good work and good health are interchangeable and the state of work in Irish society is changing dramatically and constantly evolving. So too are the challenges such as: Multigenerational and ageing workforce; digital systems and remote working; evolving contracting models, increasing transient and precar-

ious employment; increasing workplace stress; a volatile employment market; and an emerging culture of working to enjoy a more wholesome life.

Looking to the future

Future proofing requires widescale recognition of the timely need to evaluate current provision and future needs for occupational health in Ireland and a commitment to support evidence-based, accredited quality OH practitioners and services. Now is the time to engender a sense of urgency around occupational health.

Aligned to this we must work to increase awareness of the full OH offering and value to individuals, organisations and society.

We are committed to increasing the representation of our membership across occupational health advocacy through key groups and initiatives. Longer term, our action plan is driving us towards universal OH access.

We will create a Faculty of Occupational Medicine infrastructure to support our advocacy, initiate engagement with key stakeholders, and work with them to build on and implement our strategy over time.

Right now, we are calling on others who value safe and equitable workplaces to:

 Generate evidence, drive awareness, and advocate for the value of OH in Ireland.

 Encourage accreditation of practitioners, and assimilation of evidence-based practices.

 Advocate for policy and legislative enhancements towards universal access to occupational health.

This call to action extends to the occupational health community, medical and education communities more widely, Government and allied organisations, the legal community, employers, and employer and employee representative groups and associations to support this recharging of occupational health in Ireland. Let’s take advocacy for occupational health seriously and let’s take it forward together.

We each have a role to play and everyone will reap the rewards.

The full strategy can be accessed on the RCPI website.

Selenium and Q10: Live long and prosper

Attendees heard a presentation by Professor in Cardiology Prof Urban Alehagen on the evidencebased approach to improving health and longevity with selenium and coenzyme Q10

The exclusive event, which was facilitated by Pharma Nord, saw a packed auditorium hear a presentation by Professor in Cardiology, Prof Urban Alehagen, who delivered a talk titled ‘Can supplements delay ageing?’ Prof Alehagen, from the Linköping University in Sweden, discussed compelling evidence for the efficacy of selenium and bio-quinone Q10 (Q10) as nutrients to increase longevity, as well as combating inflammation and oxidative stress and improving overall quality-of-life.

Among many other career distinctions, Prof Alehagen is a specialist in internal medicine, cardiology, and odontology and was the lead researcher in the seminal Kisel-10 study. He explained that in the first phase of the study and in the follow-up analysis at years 10 and 12, some 50,000 blood samples were collected. These provided valuable data on the impact of selenium and Q10 at a cellular level – one of the top-line findings was a significant difference in the microRNA and telomere length in older adults who take these nutrients. So compelling and clinically comprehensive were the results that the initial Kisel-10 study inspired a further 20 sub-studies on the topic, Prof Alehagen explained.

One of these studies, published in the journal Nutrients, showed that selenium and Q10 supplementation considerably reduced telomere shortening (telomere attrition) after 42 months in the active treatment group, compared to the placebo group. This preserved leukocyte telomere length due to selenium and Q10 was also shown to reduce cardiovascular mortality, decrease inflammation, and oxidative stress, and slow down the biological ageing process.

Kisel-10 study

The Kisel-10 study itself was published in 2012 in the International Journal of Cardiology and was a five-year, prospective, randomised, double-blind, placebo-controlled trial among elderly Swedish citizens. The findings were compelling and the researchers – among whom Prof Alehagen was lead author – found that participants taking these supplements showed that their biomarkers of cardiomyocyte wall tension, NT-proBNP, were significantly lowered.

Prof Alehagen gave the attendees an overview of data from the Kisel-10 study and its subsequent sub-studies, and emphasised the importance of selenium as it naturally occurs in the human body. “We get selenium from bread, meat, and fish,” he told the meeting. “The situation is that there is not one single country in Europe where we have enough selenium in the soil – this means we have selenium deficiency in every country in Europe, so we have a widespread problem.”

Discussing his research methodology, Prof Alehagen told the delegates: “We wanted to stress-test our results, so we applied them to a multivariate model,” he said. “Even if we took into consideration being a male, being a smoker, having ischaemic heart disease, diabetes – still we found a more than 50 per cent increased risk of cardiovascular death, just because these people were low on selenium, so obviously it [selenium deficiency] matters.”

Q10

He provided a brief overview of coenzyme Q10, which he described as “one of the most powerful antioxidants we have, and we all have it in all of our living cells”. Our level of Q10 decreases as we age, with the highest production of Q10 achieved when we are approximately 20 years old. When a person reaches 80 years old, they retain only approximately half of those levels in the body and because of age, the probability of disease increases in tandem. Citing previous research, Prof Alehagen told the attendees that “in order to get coenzyme Q10 activated, the cell needs the presence of selenium”, he said. “And in order to get optimal production of selenium protease, the cell needs the presence of coenzyme Q10, meaning that the cell requires both of these substances in order to build an optimal defence reaction if attacked, and also a normal antigen transfer process.” This was the rationalisation behind the Kisel-10 study, he explained.

The early findings of Prof Alehagen’s team, which were initially focused on cardiovascular mortality, suggested that selenium and Q10 supplementation also have an influence on the overall ageing process. Specific areas of the cardiovascular system were analysed and Prof Alehagen summarised the subsequent findings, which showed a

slowing-down of the biological ageing process. One of the biomarkers for this research was endothelial dysfunction, and changes in each individual were closely monitored by the researchers.

“We saw signs of better endothelial function via supplementation by giving selenium and Q10,” he explained. “That is startling information.”

A telomere is an important region of repetitive DNA sequences that caps chromosome ends and protects them from becoming tangled or frayed; each time a cell divides, telomeres become gradually shorter, Prof Alehagen explained. In time, these telomeres become so short that they are no longer capable of protecting the chromosome, and the cell perishes. Previous research has shown that telomere shortening is implicated in oxidative stress, inflammation, cardiovascular mortality, and the overall ageing process itself.

“By giving selenium and Q10 to the participants, we could demonstrate that there was no shortening of telomeres,” Prof Alehagen told the meeting. He also explained that there was a demonstrated shortening of telomere length in the placebo group and these surprising results were stress-tested and stringently validated, said Prof Alehagen. “We could see that by giving selenium, there was a reduced biological age,” he told the attendees. “We could see that in our group, the biological age was reduced from 88 years to 72 years.

“We know one thing for certain,” Prof Alehagen concluded. “If we can reduce inflammation, we can influence and improve quality-of-life…. I regard us all [medical professionals] as being part of the same team. I am convinced that we are all trying to give our patients the best possible care, and I am highlighting the chance to increase the potential to provide that best care – if we have that

chance, should we not reach out and grab that opportunity?”

‘Wonderful information’

Speaking with the Medical Independent (MI) following his presentation, Prof Alehagen discussed how new areas of research are opening up in terms of the broader benefits of selenium and Q10. He was asked if it is possible that research into these benefits may still be in its early stages. “I am absolutely convinced of that,” said Prof Alehagen. “In the past decade, the interest in research regarding selenium has increased – we had a lack of interest in this research in the decades before that, but now we have been using more sophisticated methods to analyse the mechanisms [of action], and this has given us even more wonderful information, such as the data on telomere length.”

Whilst his lecture was mainly focused on anti-ageing, Prof Alehagen and his team have also been researching the quality-of-life impact of supplementation with selenium and Q10. “If, by giving selenium and Q10 to a patient, we could prolong their life and the patient says to me, ‘okay, I’m living longer, but my life is hell,’ did we do any good? So we asked the patients what they thought [about using selenium and Q10], and what we found is that it improves quality-of-life, and there is published data on this. So we observed reduced mortality, the patients have a better quality-of-life, and the cost to society decreases. This is all positive.”

Following-up from Prof Alehagen’s observations on the potential public health benefits, he was asked if the benefits of selenium and Q10 have the potential to prevent hospital admissions and so take pressure off hospital services. “This is certainly true,” he said. “We have analysed the length of time we could keep the two groups in our studies out of hospital. We have published results that show we could keep those who received selenium and coenzyme Q10 out of hospital for a significantly longer time, compared to those who received placebo. This indicates that the cost to society is lower when we administer selenium and Q10… we know that healthcare systems are very expensive and we need to find means of making these systems as efficient as possible, and this is one positive way to do that.”

Prof Alehagen summed-up his takeaway message from the presentation: “Why not let the patient use a supplement that is evidenced to be positive, in order to reduce the imbalance in the body?” he told MI. “One way to do this is by adding selenium and coenzyme Q10 and there is hard evidence to show this improves public health.”

References available on request

The Chair of the regional health area (RHA) advisory group Mr Leo Kearns recently spoke before the joint Oireachtas committee on health about the RHA project.

The six proposed RHAs are in line with recommendations made in the Sláintecare Report published in 2017. The report stated that regional bodies should be responsible for the planning and delivery of integrated health and social care services.

The core vision driving RHA implementation is to improve care to patients through enabling a joined-up, integrated approach to service planning and delivery. It should be designed to empower those delivering care, according to Mr Kearns.

“There is still a significant risk RHAs are being viewed primarily as an organisational, back-office type exercise,” Mr Kearns told the committee at the end of last month.

“If this perception remains, then this reform programme will be undermined.”

Mr Kearns said it is not possible to define a clear role for RHAs without also doing the same for the HSE and for the Department of Health.

He stated there needed to be a guarantee of independence and authority for RHAs in line with the responsibility they are being given. There should be “absolute clarity” as to how an accountability framework will work and the same should apply to HSE central management in relation to the Department of Health.

“As a natural consequence of that principle, the plan to implement RHAs must also include an aligned change plan for HSE centre and for the Department of Health,” Mr Kearns said.

“In determining the levels of authority that should be delegated, the bias should be towards providing maximum devolved authority sufficient to allow the RHA to exercise effective de-

cision-making to deliver on its responsibilities while working within relevant national frameworks.”

Mr Kearns admitted there is the risk that RHAs could become centralised, “top-down” organisations, and just introduce another bureaucratic layer to the health service.

He said an RHA, which doesn’t organise itself in a way that is as close to the patient pathway as possible, would “not be fit-for-purpose”.

Regarding staffing, Mr Kearns said it is important to acknowledge RHA implementation is taking place at a time when “we are experiencing a workforce crisis at many levels”.

“Therefore, it is necessary to establish a credible, sustained, cross-system approach to a multi-layered workforce strategy,” he argued.

“Failure to make parallel progress on this will fatally undermine efforts to implement RHAs, as it will indicate to people that the implementation of RHAs is not serious about the delivery of better care.”

There needed to be meaningful engagement with stakeholders, so RHAs are not presented as a fait accompli.

“Implementing RHAs is an extremely challenging and large-scale change,” Mr Keans said in summary.

“It is not credible that change of this magnitude can be managed without a significant investment in an implementation support infrastructure.”

As previously reported in the Medical Independent, the project has already suffered from numerous delays. Reform of this scale was unlikely to be straightforward. The risks outlined by Mr Kearns are very real. The RHA project is central to the implementation of Sláintecare. It will go a long way to determining whether the troubled strategy will ultimately be viewed as a success or not.

MINDO CARTOON

READER COMMENTS

REACTION TO DR MUIRIS HOUSTON'S COLUMN, 'A MACHIAVELLIAN APPROACH TO CAPACITY DEFICITS?', 17 NOVEMBER

“You can’t solve capacity problems with flow solutions. You just get bad care and harassed staff. Worse it’s a cop out as it gives an opportunity to blame staff for capacity planning and funding failures @HSELive @DonnellyStephen."

Vida Hamilton, Anaesthesiology and Intensive Care, @vidamthamilton, 16 November

REACTION TO OUR NEWS INTERVIEW, 'SCANNING THE PRESENT AND FUTURE OF RADIOLOGY', 17 NOVEMBER

“This interview with Prof Dr Adrian Brady covers his role at #ECR2023, the state of #radiology in Ireland, the ethics of #ArtificialIntelligence, and more!" ESR Journals, @ESR_Journals, 17 November

REACTION TO OUR NEWS STORY, 'DIRECT ACCESS TO CONTRACEPTIVES IN PHARMACIES UNDER CONSIDERATION', 17 NOVEMBER

“Welcome news: Pharmacist access is supported by WHO guidelines and has been safely introduced in Canada and the US. Contraception should be provided through pharmacies and maternity hospitals, as well as GPs."

Womenscouncilireland, @NWCI, 15 November

REACTION TO OUR BREAKING NEWS STORY, 'DEFENCE FORCES CONTINGENT DEPLOYED TO GOLAN WITHOUT OWN MEDICAL OFFICER', 14 NOVEMBER

“If you are a parent or partner or child of a soldier you should be seriously concerned about this. This is disgraceful." South East Military Veterans, @EastVeterans, 15 November

“@simoncoveney. Deployed with no medical officer!!!! Shows how bad our defence forces have got. How long is it going to take for something to be done about the dwindling numbers, is it going to take an incident to occur before action is taken! Where's the duty of care?" Frances-Anne, @francesanne29, 14 November

“All time new low here!! Can't provide a doctor on overseas missions anymore!!" Johnny Walker, @johnnywalker373, 14 November

“@defenceforces contingent deployed to Golan without own medical officer. Unless we can agree attractive conditions of service for @DF_Medics we will lose this critical capability. We have been raising this with DF & DOD management for years." RACO, @RACO_DF, 14 November

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Establishing fit-for-purpose RHAs will be an immense challenge

Preventing patients from falling through the cracks

Ms Suzanne Creed provides advice on ensuring your test result tracking system is safe

In any busy healthcare department, the number of medical investigations, such as laboratory and radiology tests requested, can be staggering. Clinicians require robust and efficient systems for the management and follow-up of test results in order to make timely and informed decisions about patient care. From a risk management perspective, it is crucial that the clinician requesting the test has an effective system in place to ensure all tests requested are returned as results and that they are reviewed and acted upon in a timely manner. Inadequate or poor communication of test results to referrers and inadequate arrangements to follow-up patients are globally acknowledged as a significant source of errors in healthcare settings worldwide.

Poor test result management can have major consequences for the quality of care of patients and their relatives, leading to delayed or missed diagnoses, prolonged hospitalisations, and suboptimal patient outcomes. Similarly, poor test result management can adversely impact healthcare staff leading to time wasted on chasing up test results, additional time spent on repeating tests, the financial burden of additional appointments, reputational damage, and the potential increase in complaints and litigation.

Although the practice of medicine cannot always be perfect, accuracy is imperative when it comes to tracking patients’ test results. Accurate and timely tracking of results is generally achievable only if the tracking process is straightforward and comprehensive to capture all necessary information for each test requested. Then, the process must be consistently and completely performed on every single occasion. Policies that detail how the tracking system is operationalised should aim for zero tolerance in variation.

Designing the ‘tracking’ process

Process mapping is a technique that can be used when designing or implementing a quality improvement project in healthcare. This approach can help to map the whole patient journey or steps in a work process with the help of people who represent all the different roles involved. When devising or evaluating a tracking system, identifying the various steps in the process is helpful. Consider which steps of the patient’s test result journey are most prone to failures and the steps in which failures potentially could occur, such as:

 What could prevent a clinician from reviewing an important report? A possible reason is that the clinic or practice never received the report in the first place.

 Why might this occur? Perhaps the test was not requested in the first instance, or the patient failed to attend to have the testing done.

 Perhaps the specimens were lost in transit or misplaced once they arrived at the lab.

 Another possibility is that the test was completed, but the pathologist or radiologist failed to generate a report – or the report, once generated, was lost in transit.

 In hospital, what happens when a test result is returned, but the patient has been discharged? Who reviews these results, communicates them to the patient, and ensures appropriate follow-up of a result that is deemed to be significant?

A key element of a successful test result tracking system is to engage all key personnel involved in the process from the design to the implementation phase and to obtain regular feedback on what worked well and any perceived problems.

One strategy that healthcare organisations may decide to employ is assigning a staff member with the responsibility of ensuring that all reports have been reviewed (with acknowledgment by means of the clinicians’ signature or initials and date). The responsible individual could monitor the process to ensure no reports are filed prior to review and sign-off. Although this might be a labour-intensive activity, it could

prove vital to the organisation’s patient safety efforts. However, it is important to be aware that overall clinical governance lies with the clinician who orders the test to ensure that the results are reviewed and communicated to the patient and the patient is appropriately followed up in a timely manner.

Professional obligations

All doctors have an ethical obligation to provide safe patient care. The Medical Council’s Guide to Professional Conduct and Ethics states at paragraph 64.1: “You should make sure, as far as possible, that the services and treatment you provide are safe and comply with the standards of the profession.”

Healthcare providers have a duty to recognise when they do not receive requested test result reports and that is what a patient test result tracking system is intended to help them accomplish. No single approach is necessarily “the best” patient-tracking method. Many healthcare practices prefer to use electronic systems, while others still rely on paper-based methods. What is crucial is that the method used is intuitive, capable of capturing all of the necessary data and that clinicians and staff members can adhere to it without exception.

Documentation

As with all patient interactions, it is important that all relevant details of the test result process are documented in the patient’s clinical file. Documentation should include:

 Details of the test(s) requested;

 The results of the test;

 Patient notification of the results;

 Clinical decisions based on the results.

Clinicians should document their rationale for ordering or not ordering further clinical tests and patient reviews based on the test results. These details outline the clinicians’ thought processes and efforts made to provide high-quality safe patient care. Such information may be crucial in the event of a malpractice claim or complaint.

IT systems

Healthcare organisations that are using electronic health record systems or other technology to facilitate patient tracking should engage their IT providers to identify whether their systems can automate the process to improve timeliness and consistency. It may be feasible to have the system generate a daily task list that flags certain situations that could lead to risk exposure. Circumstances that should be flagged include:

 Tests ordered, but no results received within a reasonable timeframe;

 Test results received, but not viewed by a clinician;

 Test results viewed by a clinician, but not communicated to the patient in a timely fashion or the patient not followed up appropriately.

Routinely running reports to identify overlooked test results is also critical, even if test results are included on daily task lists.

Healthcare organisations should also consider working with their IT experts and reporting sources to devise a process in which critical test results are flagged for immediate attention. This might involve a colour-coding scheme, or other visual identifiers; the use of secure texting or email; or, preferably, calling the referring clinician.

In general practice settings, there should be arrangements in place in the event of the laboratory having a critically abnormal result requiring patient communication during out-of-hours.

Engaging patients

Finally, all clinicians should encourage patients to follow up with their healthcare organisation if they do not receive their results within a specified timeframe. The mantra ‘no news is good news’ should be changed to ‘no news is no news’. Engaging patients in the diagnostic process can provide an additional safeguard to prevent critical results from being overlooked.

In summary

With a large volume of medical investigations requested both in primary and secondary care, patient safety is dependent on healthcare organisations ensuring they have designed and implemented a robust test result tracking system. This requires ongoing input and feedback from all key personnel involved in the process. An effective test result tracking system should ensure that all tests requested are returned as results, reviewed by a clinician in a timely manner, and communicated to patients with appropriate follow-up measures in place. This can prevent your patients from falling through the cracks.

Medisec has a suite of educational resources to facilitate the safe management of test results in healthcare settings. For further information please visit the Medisec website or contact a member of the Medisec team.

References available on request

This article has been adapted with the kind permission of our business partner Medpro.

Accurate and timely tracking of results is generally achievable only if the tracking process is straightforward and comprehensive to capture all necessary information for each test requested

More tips on ‘gathering planning’

For my last column, I wrote about the preparations for the WiMIN conference and asked for people’s thoughts about what makes a useful and enjoyable professional gathering. Since then, I have received feedback from a number of people, most importantly those who attended the conference, and a few themes have emerged. I’ve decided to be very helpful to others who are planning conferences, now that we are fully back in the swing of face-to-face meetings and offer you some tips and advice. (You’re welcome).

We have made the decision to have free childcare available at all WiMIN conferences. This is becoming more commonplace in UK medical meetings, but is still a bit of a rarity here in Ireland, and many organisers feel that it would be very complicated and costly to run. However, like most things, it is actually really quite simple and does not require a huge amount of effort or resources. It allows attendees with young children to attend the meeting in person without having to arrange childcare at home and is especially useful for those last-minute childcare hiccups with which all parents are so familiar. Occasionally, I see tweets from conferences (mostly in the US, it seems) where mothers have been asked to leave

conference halls because they have a sleeping baby strapped to their chest. This is mind-blowingly dumb and offensive behaviour from conference planners and very bad publicity for the organisation concerned. So, why not introduce a more welcoming attitude to babies, children, and their cashand cachet-wielding parents, by hiring an extra room for the day and recruiting some garda-vetted, qualified, childcare professionals to provide onsite care for delegates’ children. The extra cost will be small and we were delighted to receive sponsorship from Challenge medical indemnity, which covered all the expenses. (For those who really want to know, the cost was less than €1,000). We were also able to provide a private room for breastfeeding, which was another €165 for the day and allowed mums to slip off into a quiet space for feeding while still being in touch with the conference proceedings (our plan to have a screen in there with a livestream from the main room didn’t quite come to pass, but we’ll do better next time!)

Many conferences have become more aware of the need to reduce waste and minimise their carbon footprint. We tried to limit the amount of unwanted merchandising and plastic waste that people would accumulate through the day, by using a pick-and-mix style layout for our goodie bags, and avoiding laminated name tags and glossy programmes. These might be small considerations in the greater scheme of the World-Is-About-To-End times we are currently experiencing, but I think we probably all have enough branded tote bags and USB drives and pop-sockets (whatever they are), and can manage to attend a conference without being responsible for another quarter acre of

How to talk about death

ice cap falling into the sea.

Of course, the very nature of in-person conferences means that a huge amount of energy is expended that could have been saved by hosting an online event. Yet we know, instinctively and through research, that it is a totally different kind of learning experience when you share a physical space with someone. There is a value to person-to-person contact that cannot be replicated in a virtual setting. At the same time, I think it is vital that people should have the choice. There are many reasons why someone might choose to stay at home and tune in to an event online rather than being there in person, but I believe that everyone needs to have both options open to them. This was WiMIN’s first hybrid event, and there is no doubt that there were some dodgy technical moments from which we will need to learn for our next meeting, but many of our delegates mentioned how useful it was to be able to join us from home or work because they could not travel to attend. Some organisations are put off by the extra work and resources involved with a hybrid set-up, but I think they owe it to their attendees to make their event as accessible as possible. Fair enough, it cost over €6,000 for us to provide this, but again we were so grateful to our sponsors for making this possible. (You’ll note I am being very open about costs here, which I realise can make people squirm in their chair, but there is nothing worse than people talking about the price of things, without talking about the price of things).

So those are a few unsolicited pieces of advice for anyone reading this who might be involved in planning a conference over the next few months.

As I said, you’re very welcome!

Parents of critically ill children often want clarity from physicians over and above language choice

Read more by Dr Muiris Houston at www.mindo.ie

@muirishouston

Doctors are aware of the need to avoid clinical jargon when speaking with patients. By and large, most of us manage to speak in the patient’s voice rather than our medical one. But euphemisms can trip us up.

While I like the language theory of euphemisms, some of them drive me mad: I can’t stand the expression ‘falling pregnant’ – it sounds like a woman trips up and lo and behold nine months later a baby pops out! And more recently the euphemism of ‘passing away’ for death has irritated me.

According to a recent article in Medscape, current consensus guidelines recommend against the use of euphemisms when discussing death with patients and families.

In a study published in JAMA Network Open , researchers reviewed conversations between clinicians and parents of critically ill children. The study participants included 20 parents of 13 infants with neurological conditions who were hospitalised in a paediatric ICU in a hospital in the south-eastern United States. Family meetings were scheduled to discuss prognosis and whether to start, not start, or discontinue life-sustaining treatment. The discussions were recorded, transcribed, and anonymised.

Twelve infants required mechanical ventilation, six required chest compressions, and five had a do-not-attempt resuscitation order placed. Two infants died during the hospital admission process.

The primary outcome of the study was language used to reference death during family meetings between doctors and families. In the family conversations, death was referenced 406 times (275 times by doctors and 131 times by family members). Families were more likely to use the words die, death, dying, or stillborn.

In addition to a category for use of words, such as ‘die’, ‘death’, ‘dying’, or ‘stillborn’, the researchers identified four types of euphemisms used in place of these terms. They characterised the types of euphemisms as survival framing (for example, ‘not live’); colloquialisms (for example, ‘pass away’); medical jargon or use of physiologic terms (for example, ‘irrecoverable heart rate drop’); and the use of pronouns without an antecedent (for example, ‘it might happen soon’).

Over 90 per cent of references to death in the conversations were euphemistic. Medical jargon was the most common type of euphemism used by clinicians (118 of 275 references), while colloquialism was the most common type used by family members (44 of 131 references).

The results show the high rates of euphemistic lan-

guage used in discussions of death, the authors noted. They also proposed that their classification of euphemistic language could provide a framework for the use of language in discussions of death. And more research is needed to assess the effect of language on understanding, decision-making, and doctor-patient relationships, the researchers concluded.

An accompanying editorial noted that using a euphemism, such as ‘pass on’ instead of ‘die’, may be an intentional choice by physicians to use less harsh language, but it may still cause confusion. However, if a family consistently uses softer terminology in these discussions it may be more empathetic for doctors to mirror that usage rather than persisting with direct references to death and dying.

While there is evidence of euphemistic language use in the adult setting, until now, there has been limited information about this in children. A striking aspect of the study is that parents used terms, such as ‘death’ or ‘die’ more often than clinicians, and they sometimes used these terms as a way to clarify what the doctor was saying. It suggests that parents often want clarity over and above language choice.

It should be possible to be both clear and compassionate, while supporting families and helping them make the best decisions for their children. And probably the next important piece of research is to learn more about what families experience as supportive during conversations with clinicians about death and dying.

Do you have strong views about the use of euphemisms in medical practice? Are there particular expressions that irritate you? If so, please drop us a line with your thoughts.

And if not, I may have to accept that I’m just a grumpy old bugger that needs to let these things pass on!

Following my recent column on preparing for meetings, here is what I learned from feedback after the WiMIN conference

DR SARAH FITZGIBBON

The results show the high rates of euphemistic language used in discussions of death, the authors noted

MULTIPLE CHOICE QUESTIONS

Question 1

Slipped capital femoral epiphysis

A. Must be suspected in any 10-to-15-year-old child presenting with a limp.

B. Patients characteristically have obesity.

C. Is nearly always caused by trauma.

D. Delayed diagnosis can lead to permanent disability.

E. Is best treated with a plaster spica.

Question 2

Impetigo

A. Incidence is greater in summer than in winter.

B. Recognised features include a burning sensation in the skin before the eruption appears.

C. Of the bullous variety, is caused by streptococcal infection.

D. Lesions heal without scarring.

E. Should always be treated with oral, not topical, antibiotics.

Question 3

In proliferative diabetic retinopathy

A. Cotton wool spots are seen on the retina.

B. Smoking is a risk factor.

C. Vitreous haemorrhage may occur.

D. Laser treatment significantly reduces the incidence of blindness.

E. Improved glycaemic control has no effect on the progression of the retinopathy.

Question 4

Enlarged glands in the groin

A. May be secondaries from carcinoma bowel.

B. Can occur during acute attacks of genital herpes.

C. Are a recognised response to an infection in the feet.

D. Are naturally solitary.

E. Are typically the only sign in Hodgkin’s disease.

Question 5

In a patient with headaches, the following features would tend to support a diagnosis of tension type headache rather than migraine

A. Bilateral location.

B. Pulsating/throbbing quality.

C. Aggravated by routine activity, eg, walking.

D. No nausea or vomiting.

E. Visual aura.

E. FALSE. Rarely affected alone. Other glands may be found to be smoothly and softly enlarged and spleen likely to be palpable.

D. FALSE. Multiple and subcutaneous.

C. FALSE. People with migraine may avoid routine activity

B. FALSE. If tension has pressing/ tightening quality.

A. TRUE. Migraine usually unilateral, though may spread to affect both sides.

ANSWER 5

C. TRUE. Or infection in legs or genitalia.

B. TRUE. Associated with genital ulceration.

A. TRUE. Or ovary in which case glands tend to be hard and tender.

ANSWER 4

E. FALSE. A reduction of HbA1C is associated with a reduction in laser therapy in the long-term.

D. TRUE. By at least 50 per cent at two years.

C. TRUE. Abnormal blood vessels (neovascularisation) are fragile and prone to bleed and are a major cause of catastrophic visual loss in diabetics.

B. TRUE. Can contribute to more extensive retinopathy and increase the risk of visual loss.

A. TRUE. Soft exudates indicating stagnation of axoplasmic flow.

ANSWER 3

E. FALSE. If mild, topical antiseptic may well be effective, if widespread need a penicillin or erythromycin.

D. TRUE . Will eventually clear, even without treatment.

C. FALSE. Quickly rupturing bullae are feature of staphylococcal infection.

B. FALSE. Suggests herpes simplex infection.

A. TRUE. And greater in warmer countries.

ANSWER 2

E. FALSE. Requires pinning of epiphysis to diaphysis, but until then must avoid weight bearing.

D. TRUE. With early onset of osteoarthritis.

C. FALSE. Most have no history of trauma and symptoms may be present for months before diagnosis is suspected.

B. TRUE. In 65 per cent of cases, person is over 95th centile for weight.

A. TRUE. Or with pain in the groin hip, knee or thigh.

ANSWER 1

Antimicrobial resistance: The silent pandemic

Healthcare professionals (HCPs) from the Republic of Ireland joined Prof Edmond Smyth of the Beacon Hospital in Dublin, Prof John Moore of Belfast City Hospital, and Dr Eavan Muldoon of the Mater Hospital in Dublin, for a webinar on antimicrobial resistance (AMR) and the opportunities and challenges of antimicrobial stewardship

Experts recommend redoubling efforts to tackle AMR, which is predicted to be a major threat to public health by 2050. An educational medical webinar, sponsored and organised by A.Menarini Pharmaceuticals on the 16th of November 2021, titled ‘Antimicrobial Resistance: The Silent Pandemic’, aimed to provide new insights into the consequences of AMR and empower healthcare professionals to implement safe and effective antimicrobial use.

The meeting was chaired by Prof Edmond Smyth, Consultant Medical Microbiologist in the Beacon Hospital, Dublin, and featured two other medical experts, Prof John Moore, Clinical Microbiologist in Belfast City Hospital, Belfast, and Dr Eavan Muldoon, Consultant in Infectious Diseases in the Mater Hospital, Dublin.

In 2001 Prof Smyth chaired the Strategy for control of Antimicrobial Resistance in Ireland (SARI) Committee, following which the concept of antimicrobial stewardship was formally introduced into Ireland for the first time.

Prof Moore has authored and co-authored over 500 peer-reviewed papers in several national and international journals on the clinical microbiology of cystic fibrosis and previously spearheaded an initiative, between Japan and the UK, examining AMR.

Dr Muldoon was the inaugural recipient of the Frank P Tally Fellowship in Infectious Diseases at Tufts Medical Center (Boston, Massachusetts, US) and received the Kass Award for Clinical Excellence from the Massachusetts Infectious Diseases Society.

Prof Smyth introduced the meeting by touching briefly on the importance of discussing AMR and stewardship, especially in the context of the ongoing Covid-19 pandemic.

‘Antimicrobial resistance: New insights’

Prof Moore began the webinar by briefly introducing the problem of AMR during his presentation titled ‘Antimicrobial resistance: New Insights’. He gave an overview of antibiotic resistance patterns emerging across the world, and highlighted the challenge of treating CF patients infected with highly resistant organisms, especially pan-resistant strains of Pseudomonas aeruginosa

Prof Moore gave a summary of the history of antibiotic discovery and remarked on its slow-down in recent years. He then discussed the escalating threat to public health caused by the global emergence of carbapenem resistance in Enterobacteriaceae, explaining that: “Carbapenem-resistant Enterobacteriaceae are usually resistant to all β-lactam agents, as well as most other classes of antimicrobials. This can lead to severe infections among residents of long-

term care facilities and care homes.”

He went on to share several real-world patient questions that require consideration by healthcare professionals in the context of AMR.

The role of laboratories

Prof Moore also discussed the importance of having adequate laboratory susceptibility testing capacity and turnaround-times. “As we see more and more resistance develop, we have to be able to counter that by having effective laboratory antimicrobial susceptibility testing assays in place,” he said. “That will allow antibiotic combinations to be decided upon and communicated to the physician.” He also suggested utilising local laboratories for microbiological testing, as they often meet quicker turnaround times than reference laboratories.

Looking to the future

Prof Moore provided some new insights by introducing several novel strategies currently being developed to treat infections that do not compromise antimicrobial susceptibility. He gave the example of utilising biocontrol with predatory bacteria, such as Bdellovibrio bacteriovorus, on pathogens, including Burkholderia cepacia complex, in cystic fibrosis. Prof Moore also showcased the work of doctors at University Hospital Southampton, who pioneered a nose drop containing Neisseria lactamica, a commensal bacterium that competes with Neisseria meningitidis, thus protecting against meningitis. In addition to these strategies, harnessing the potential of bacterial and other vaccines to help reduce the need for antimicrobials is vital, he said.

‘Antimicrobial stewardship:

Challenges and opportunities’

Dr Muldoon discussed the importance of

antimicrobial stewardship and how it can be implemented within a clinical setting. She said that stewardship can be defined as: “The right antibiotic, for the right patient, at the right time, with the right route, causing the least harm to patients and future patients.” She also noted that while the perception is often that stewardship focuses solely on policing and stopping antimicrobial use, it is more about optimising the antimicrobial prescription for each individual patient.

Challenges and barriers

Dr Muldoon outlined the challenges of antimicrobial stewardship, which include influencing behavioural changes in prescribing practice, inadequate medical education, limited resources, and the lack of rapid diagnostics.

Antimicrobial guidelines are not always followed due to a number of issues, including lack of awareness and concerns over applicability based on patient populations observed in clinical trials. Additionally, many clinicians are unable to perform the type of diagnostics outlined in guideline recommendations due to limited knowledge, lack of training or slow laboratory turnaround times.

Dr Muldoon also discussed the impact of Covid-19 on prescribing antimicrobials. She described how over the course of the pandemic, there has been an increase in antimicrobials used in hospitalised patients with Covid-19; however, the data show that there is no advantage in using antibiotics due to low levels of true bacterial coinfection in these patients.

Opportunities to improve antimicrobial stewardship

Dr Muldoon recommended using other methods of infection control, such as source

control, which can be used without the need for antibiotics. “Source control can be very important in controlling some infections, not only to ensure the best patient outcome, but also to prevent further development of antimicrobial resistance.”

Dr Muldoon stressed the importance of medical education in stewardship and elaborated that different approaches should be taken for medical students and continuing medical education programmes. For medical students in particular, infection is often difficult to fit into a systems-based learning programme. Dr Muldoon posited that: “Infection can become a bit of a no-man’s land, because it touches upon every system. In some cases it is no longer taught by infection specialists and can perhaps lose some of its emphasis.”

Other healthcare professionals play a vital role in preventing the spread of AMR; for example, pharmacists distribute antimicrobials and, therefore, have access to data on prescribing patterns, including departments that prescribe antimicrobials more frequently. Nurses, due to their frontline role, can identify important information and concerns, such as transitions from intravenous to oral antimicrobials. This information can be relayed to members of other teams to better inform their decisions. Furthermore, she highlighted the role of biomedical scientists who perform checks and balances on the reporting of antimicrobials.

Does one size fit all?

Dr Muldoon discussed how taking a customised approach when implementing an antimicrobial stewardship programme is important. Programmes need to be adapted according to specific problems that arise in a specific hospital, specific patient groups, and complications commonly seen. Also, it should be considered whether prescribers respond better to a restrictive or a collaborative approach.

Q&A

During an interactive Q&A-style discussion, Prof Smyth queried the effects of Covid-19 on AMR. Dr Muldoon responded that patients with Covid-19 have been receiving inappropriate antimicrobials which are not impacting their outcomes. When in isolation, patients are checked on less frequently by healthcare staff; thus there are fewer prompts to discontinue antimicrobials. In addition, lack of face-to-face interactions with patients and within teams have made it more difficult to change behavioural norms. Sharing the impact the Covid-19 pandemic has had on his patients with cystic fibrosis, Prof Moore explained that because of Covid-19, there has been a growth in telemedicine, which has made acquiring sputum samples from patients more difficult due to regulatory reasons. Sputum samples are an important part of monitoring patients with cystic fibrosis.

In their concluding remarks, Dr Muldoon reiterated the importance of culture data and diagnostics in clinical decision-making, while Prof Moore emphasised prescribing sufficient antimicrobial concentrations to prevent the development of further resistance while optimising clinical outcomes in patients.

In the treatment of advanced Parkinson’s disease

People in this piece are models, not actual patients.

Because ON TIME is their time1

You can offer your patients continuous dopaminergic stimulation with Duodopa®1,2

PRESCRIBING INFORMATION:

Duodopa 20 mg/ml + 5 mg/ml intestinal gel (levodopa/carbidopa)

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

Presentation: Intestinal gel containing 20mg/ml levodopa and 5mg/ml carbidopa monohydrate.

Indication: Advanced levodopa-responsive Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results. Dosage and Administration: Adults/Elderly: Administration by portable pump directly into the duodenum or upper jejeunum via a percutaneous endoscopic gastrostomy (PEG) or radiological gastrojejunostomy tube. Initially a nasoduodenal/nasojejunal tube should be considered to determine patient’s response before a PEG-J tube is placed. Where the physician considers this assessment is not necessary, the nasojejunal test phase may be waived and treatment initiated directly with placement of PEG-J. Duodopa is given initially as monotherapy and dose adjusted to optimal response for the individual patient. Total dose/day is composed of three individually adjusted doses: morning bolus, continuous maintenance and extra bolus doses administered over approximately 16 hours. Total morning dose usually 5-10ml (100-200mg levodopa) but not exceeding 15ml (300mg levodopa). Continuous maintenance dose should be between 1-10ml/hr (20200mg levodopa/hr) but usually 2-6ml/hr (40-120mg levodopa/hr). Maximum recommended daily dose is 200ml. Extra bolus doses (if patient becomes hypokinetic during the day) are normally 0.5-2.0ml. Increase maintenance dose if more than 5 extra bolus doses/day are needed. Fine adjustments to the morning bolus, maintenance and extra bolus doses should be made over a few weeks after the initial dose setting. Sudden deterioration in response with recurring motor fluctuations indicates tube may have moved from duodenum/ jejunum into stomach and needs repositioning. Medicine cassettes are for single use only and should not be used for longer than 24 hours, even if some medicinal product remains. Treatment is usually administered during the patient’s awake period. If medically justified, Duodopa may be administered for up to 24 hours. Opened cassettes should not be reused. Children: No relevant use in the paediatric population. Renal/hepatic impairment: No studies on the pharmacokinetics of carbidopa and levodopa in patients with hepatic or renal impairment. Dose titration should be conducted with caution in patients with severe renal and hepatic impairment. Contraindications, Warnings, Precautions etc: Contraindications: Hypersensitivity to ingredients, narrow-angle glaucoma, severe heart failure or cardiac arrhythmia, acute stroke. Conditions where adrenergics are contraindicated (e.g. pheochromocytoma, hyperthyroidism, Cushing’s syndrome). Nonselective MAO-inhibitors and selective MAO type A inhibitors are contraindicated and should be withdrawn at least two weeks before starting Duodopa. Duodopa should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma. Warnings/Precautions: Not recommended for drug-induced extrapyramidal reactions. Caution in severe pulmonary or cardiovascular disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or of convulsions, past or current psychosis, chronic wide-angle glaucoma, co-administration with antipsychotics with dopamine receptor blocking properties or with medicines which may cause orthostatic hypotension. In patients with a history of myocardial infarction who have residual nodal or ventricular arrhythmias, cardiac function should be monitored with care during initial dose adjustments. Monitor all patients for development of mental changes, depression with suicidal tendencies and other serious mental changes. Neuroleptic Malignant like Syndrome with secondary rhabdomyolysis has not been reported with Duodopa but may occur on abrupt dose reduction/withdrawal. Periodically evaluate hepatic, haematopoietic, cardiovascular and renal function during extended therapy. Increases in impulse control disorders have been reported and patients should be monitored and reviewed.

Patients and providers are advised to monitor for melanomas on a regular basis when using Duodopa. Ideally, periodic skin examinations should be performed by dermatologists. Dose may need to be adjusted downwards to avoid levodopa induced dyskinesia. Sudden or gradual worsening of bradykinesia may indicate an obstruction in the device and should be investigated. Duodopa contains hydrazine, a degradation product of carbidopa that can be genotoxic and possibly carcinogenic, clinical significance of exposure unknown. Reported complications in clinical studies include abscess, bezoar, ileus, implant site erosion/ulcer, intestinal haemorrhage, intestinal ischaemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumonia (including aspiration pneumonia), pneumoperitoneum, post-operative wound infection and sepsis. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing Dopamine Dysregulation Syndrome (DDS). Polyneuropathy has been reported in patients treated with levodopa/carbidopa intestinal gel. Before starting therapy evaluate patients for history or signs of polyneuropathy and known risk factors, and periodically thereafter. Drug Interactions: Antihypertensives, tricyclic antidepressants, anticholinergics, dopamine receptor antagonists, benzodiazepines, isoniazide, phenytoin, papaverine, sympathicomimetics, iron, protein-rich diet, COMT inhibitors (e.g. tolcapone, entacapone) amantadine. Duodopa dose adjustment may be needed when used with these drugs. Duodopa can be taken with MAO type B inhibitors (e.g. selegiline) although serious orthostatic hypotension may occur and the dose of levodopa may need to be reduced. Fertility, Pregnancy and Lactation: Limited data relating to the use of levodopa/carbidopa in pregnant women. Duodopa is not recommended during pregnancy. Breast-feeding should be discontinued during treatment with Duodopa. No adverse reactions on fertility have been observed in preclinical studies with carbidopa or levodopa alone. Ability to Drive and Operate Machinery: Caution; Duodopa can have a major influence on the ability to drive and use machines. Refrain from driving/operating machinery if somnolence and/or sudden sleep episodes occur. Side Effects: Very common: Weight decreased, Anxiety, Depression, Insomnia, Dyskinesia, Parkinson’s disease, Orthostatic hypotension, Nausea, Constipation, Fall, Common: Anaemia, Increased weight, Amino acid level increased (Metylmalonic acid increased), Blood homocysteine increased, Decreased appetite, Vitamin B6 & B12 deficiency, Abnormal dreams, Agitation, Confusional state, Hallucination, Impulsive behaviour, Psychotic disorder, Sleep attacks, Sleep disorder, Dizziness, Dystonia, Headache, Hypoaesthesia, On and off phenomenon, Paraesthesia, Polyneuropathy, Somnolence, Syncope, Tremor, Heart rate irregular, Hypertension, Hypotension, Dyspnoea, Oropharyngeal pain, Abdominal distension, Diarrhoea, Dry mouth, Dysgeusia, Dyspepsia, Dysphagia, Flatulence, Vomiting, Dermatitis contact, Hyperhidrosis, Oedema peripheral, Pruritus, Rash, Muscle spasms, Neck pain, Urinary incontinence, Urinary retention, Fatigue, Pain, Asthenia. Device and Procedure Related Adverse Reactions: Very common: Postoperative wound infection, Abdominal pain, Excessive granulation tissue, Complications of device insertion, Incision site erythema, Post procedural discharge, Procedural pain, Procedural site reaction. Common: Incision site cellulitis, Post procedural infection, Abdominal discomfort, Abdominal pain upper, Peritonitis, Pneumoperitoneum, Pneumonia/Aspiration pneumonia, Device dislocation, Device occlusion, Gastrointestinal stoma complication, Incision site pain, Postoperative Ileus, Post procedural complication, Post procedural discomfort, Post procedural haemorrhage. Laboratory values: May change. Prescribers should consult the SmPC for the complete list of reported side effects. HCPs are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; website: www.hpra.ie. Marketing Authorisation Number: PA 1824/2/1. Legal Category: POM (S1B). Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. Date of Revision: January 2021. PI/2/005

1. Duodopa® Summary of Product Characteristics, available on www.medicines.ie 2. Nyholm D. The rationale for continuous dopaminergic stimulation in advanced Parkinson’s disease. Parkinsonism Relat Disord. 2007;13(suppl):S13-S17. doi:10.1016/j.parkreldis.2007.06.005.

References:

IE-DUOD-210040. Date of Preparation: September 2021.

Duodopa® is indicated for the treatment of advanced levodoparesponsive Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results1

Parkinson’s disease: Diagnostic and therapeutic strategies

Case study: Part 1

A 55-year old man presented with a tremor which affected his right arm at rest. He had also noticed that his jogging had become slower and dancing, which he had previously enjoyed, was more difficult as he had “lost his rhythm”. He reported episodes over the preceding 10 years where he would seem to re-enact his dreams, often crying out or thrashing about in his sleep as if fighting or running. There was no family history of neurodegenerative disease or tremor. He had never been treated with antipsychotic or anti-emetic therapies. His examination revealed reduced facial expression, a coarse resting tremor of his right arm, mild rigidity of the right upper

Idiopathic Parkinson's disease (IPD) is a progressive, neurodegenerative disease characterised by cardinal motor features: rest tremor, rigidity, bradykinesia, postural instability, flexed posture, and freezing. A wide range of non-motor symptoms are described in IPD including fatigue, sleep disturbance, drooling of saliva, urinary dysfunction, skin changes, postural hypotension, and neuropsychiatric problems including cognitive impairment, anxiety, depression, apathy, and psychosis. IPD is highly heterogenous, with clinical manifestations varying widely between patients and over the time course of the disease. As a result of this, a range of therapeutic options must be considered to optimise function and quality-of-life for people with IPD.

Epidemiology

Diagnosis of IPD is based on clinical assessment and therefore estimates of incidence and prevalence vary depending on the diagnostic criteria and epidemiologic methods used. IPD is the second most-common neurodegenerative disease of ageing (Alzheimer’s disease is the most common) with a prevalence of 0.3 per cent in the general population, rising to 1 per cent in people over 60 years of age. Prevalence and incidence of IPD is 1.5-to-two times higher in men than women, which may be related to the effect of oestrogen on striatal dopamine levels.

Diagnostic criteria for IPD

Despite increasing interest in biochem-

limb, and slowness of rapidly alternating movement on the right, with a progressive reduction in the amplitude of movements.

An MRI of brain with susceptibility-weighted sequences was normal.

The patient was given a diagnosis of IPD based on the MDS Diagnostic Criteria for Parkinson's Disease 2015. Following a discussion regarding the risks and benefits of treatment options including deferring medical treatment, monoamine oxidase inhibitors, dopamine agonists, and levodopa, he was treated with extended-release ropinirole; starting at a dose of 1mg once per day, titrating up to 8mg per day.

ical and imaging biomarkers, IPD remains a clinically-defined entity. Due to the heterogeneity of IPD, presentations and clinical overlap between IPD and other neurodegenerative parkinsonisms (eg, DLB, MSA, CBS, and PSP) it is impossible to make a diagnosis of IPD with certainty during life. Therefore several diagnostic criteria have been proposed to aid the clinical diagnosis of IPD; the most recent guidelines from the Movement Disorders Society Clinical Diagnostic Criteria were published in 2015. These guidelines allow for a diagnosis of ‘clinically established PD’ based on the presence of parkinsonism (defined as the presence of bradykinesia with either rest tremor, rigidity, or both), the absence of exclusion criteria or red flags, and the presence of two supportive criteria, while ‘probable PD’ can be diagnosed in the presence of red flags which are counterbalanced by supportive criteria (Table 1). One notable alteration made by these criteria is the removal of early cognitive impairment as an exclusionary criterion and the inclusion of the category of ‘PD (Lewy body dementia subtype)’ to accommodate DLB.

The correlation between clinical diagnostic criteria and pathological diagnosis at autopsy remains imperfect, and it is hoped that in future biochemical biomarkers may provide insight into pathological processes while patients are living.

Treatment of early- to moderate-stage IPD

Treatment of IPD is complicated. Some patients will have a tremor-predominant

phenotype, some prominent postural and gait abnormalities, and some will have a mixed phenotype with additional non-motor features. The individual response to dopaminergic therapy varies, as does the tolerability of medications.

All patients with PD require an individualised approach to management with multidisciplinary input including physiotherapy, occupational therapy, speech and language therapy, general practice, and neurology/medicine for the elderly expertise. Patients may also require support from psychology, psychiatry, gastroenterology, and neurosurgical services.

Exercise plays an important role in maintaining strength and mobility in PD. Regular, consistent exercise is likely to be more effective than targeted, intense bursts. Speech and language therapy, in particular Lee Silverman Voice Treatment (LSVT), may help with hypophonia.

Pharmacological options in early-to-moderate stage disease include anticholinergics, monoamine oxidase B inhibitors (MAOB–I), dopamine agonists and levodopa treatment.

Where tremor is the predominant or only troublesome symptom, anticholinergic treatment may be helpful, but this has limited impact on non-tremor symptoms and its attendant side-effects of dry mouth, constipation, sexual dysfunction, and confusion can be difficult to tolerate, particularly in older patients or those with early cognitive involvement.

Case study: Part 2

The patient was initially treated with ropinirole with a significant improvement in his mobility. He continued to attend the neurology clinic over the following 10 years. After three years, increasing bradykinesia led to the decision to begin levodopa treatment and over the following several years his levodopa dose was increased until he was taking two tablets of carbidopa/ levodopa five times per day. When he attended clinic he complained that symptoms of uncomfortable stiffness and slowness recurred 45 minutes prior to his next scheduled dose. He also complained of troublesome dyskinesias, which occurred 30 minutes after each dose and lasted up to an hour.

MAOB–I such as selegiline and rasagiline give a minor symptomatic benefit and may be sufficient in very early disease. There is some evidence to support neuroprotective effect of MAOB inhibition, but interpretation of these trials is complicated by the long-lasting symptomatic effect of the medications.

Dopamine agonists are the second-most symptomatically effective treatment and offer the advantage, especially in younger patients, of postponing use of levodopa and the complications of prolonged levodopa use, such as dyskinesia and motor fluctuations. The use of dopamine agonists is complicated by side-effects including hypersomnolence, orthostatic hypotension, and impulse control disorders. Dopamine agonists are available in modified-release preparations that allow them to be take once per day or via a topical patch.

Exogenous levodopa, the immediate precursor to dopamine, is the most powerful drug available to counter the motor symptoms of PD. Levodopa has a short half-life, of approximately 90 minutes, and is usually given three-to-four times per day. Common early side-effects include nausea and light-headedness, while prolonged use is associated with the development of dyskinesias and motor fluctuations.

The case study patient in this article also describes symptoms consistent with REM sleep behaviour disorder (RBD), which is a common finding in IPD. RBD can precede the motor symptoms in IPD by many years (so-called prodromal PD). Treatment is indicated when symptoms are disruptive of sleep or if there is a risk of the patient injuring themselves or their bed partner. Melatonin starting at 2mg od and increasing in 2mg increments or clonazepam 0.5mg nocte may be helpful.

Treatment-related complications

Prolonged use of levodopa to treat the symptoms of parkinsonism results in treatment-associated complications such as motor fluctuations and dyskinesias. Risk factors for the development of these complications include younger age at onset, high levodopa dose, low bodyweight, use of entacapone in addition of levodopa, female gender, and more severe UPDRS score.

‘Wearing off’ describes the gradual return of parkinsonism with falling plasma concentration of levodopa. Problematic variations include ‘sudden offs’ (rapid onset of ‘off’ symptoms), ‘random offs’ (return of symptoms is unpredictable), ‘super offs’ (severe ‘off’ symptoms

Idiopathic Parkinson's disease (IPD) is a common, progressive, neurodegenerative disease, which affects 1 per cent of the population aged over 60 years

▸ Continued from p23

occurring at the start of the day). Motor symptoms during ‘off’ periods are also associated with non-motor symptoms which may include pain, depression, anxiety, drenching sweats, abdominal bloating, and dyspnoea. Dyskinesia in IPD typically refers to choreiform movements associated with higher levodopa levels. Although patients complain of dyskinesia less than they do of ‘offs’ (indeed, movements may be entirely unnoticed by the patient), it can be uncomfortable, exhausting, and socially embarrassing. Diphasic dyskinesia, or dyskinesia-improvement-dyskinesia (D-I-D) syndrome, refers to dyskinesias, which develop as the patient enters the ‘on’ phase, then abate as the levodopa levels increase and recur as the patients enters the ‘off’ phase. Diphasic dyskinesias may respond to higher doses of levodopa.

In treating worsening motor symptoms, it is worthwhile first to consider complicating factors, which may be exacerbating symptoms. Food, especially protein, can interfere with the absorption of levodopa so it is important to check that medication is being taken on an empty stomach (usually 30 minutes before or 60 minutes after a meal). Constipation may reduce the efficacy of dopaminergic treatment and should be treated. Pain, depression, poor or disturbed sleep, and concomitant illness or infection can exacerbate symptoms of PD.

Various strategies may be tried to achieve more consistent levels of plasma levodopa and reduce wearing-off. Increasing frequency of dosing may be tried, but this frequently leads to more rapid fluctuations and is unlikely to yield sustained benefits. The addition of a COMT (catechol-o-methyl transferase) inhibitor such as entacapone inhibits the peripheral breakdown of levodopa and prolongs its effects, however, this may increase the likelihood of peak dose complications such as confusion and dyskinesia. The addition of a MAOB–I or a dopamine agonist (already in place in the case study patient) may be considered, but their utility may be limited by associated side-effects.

Amantadine may be useful in treating peak dose dyskinesia, although its utility may be limited by side-effects including confusion and hallucinations.

Continuous administration of dopaminergic medications may help to ameliorate fluctuations in response. Apomorphine is a potent dopamine agonist, which may be given via a continuous subcutaneous pump. This treatment can reduce the number of ‘off’ periods, but potential complications include nausea, vomiting, and hypotension, as well as hallucinations, delusions, and impulsive behaviours.

Continuous infusion of carbidopa/ levodopa gel via a PEG tube with a jejunal extension (PEG-J) is an additional strategy, which may help to ameliorate motor fluctuations.

For selected patients with troublesome motor fluctuations, dyskinesia, and/

Essential criterion

Parkinsonism defined as bradykinesia in combination with at least one or rest tremor or rigidity

Clinically established PD

1. Absence of exclusion criteria

2. At least two supportive criteria

3. No red flags

Absolute exclusion criteria

Clinically probable PD

1. Absence of absolute exclusion criteria

2 No more than two red flags

3. Presence of red flags counterbalanced by supportive criteria:

a. If one red flag at least one supportive criterion present

b. If two red flags at least two supportive criteria present

1. Unequivocal cerebellar abnormalities (eg, cerebellar gait or oculomotor findings)

2. Downward vertical supranuclear gaze palsy or slowed downward saccades

3. Diagnosis of a probable behavioural variant frontotemporal dementia or primary progressive aphasia

4. Parkinsonian features restricted to the lower limbs for more than three years

5. Treatment with a dopamine receptor blocker or a dopamine depleting agent and a time course consistent with drug-induced parkinsonism

6. Absence of observable response to levodopa, despite at least moderate severity of disease

7. Cortical sensory loss, limb ideomotor apraxia, or progressive aphasia

8. Normal functional neuroimaging of presynaptic dopaminergic system (DaTSCAN)

9. Documentation of an alternative condition known to cause parkinsonism which is more likely than IPD

Supportive criteria

1. Clear and dramatic response to dopaminergic therapy (>30 per cent improvement in UPDRS III)

2. Presence of levodopa-induced dyskinesia

3. Rest tremor of a limb

4. Presence of either olfactory loss or cardiac sympathetic denervation on MIBG scintigraphy

Red flags

1. Rapid progression of gait impairment with regular use of wheelchair within five years of onset

2. A complete absence of progression of motor symptoms or signs over five or more years (unless stability is treatment-related)

3. Early bulbar dysfunction: Severe dysphonia, dysarthria, or dysphagia within the first five years

4. Inspiratory respiratory dysfunction: Inspiratory stridor or frequent inspiratory sighs

5. Severe autonomic failure within the first five years including:

a. Orthostatic hypotension (30mmHg drop in SBP or 15mmHg drop in DBP on standing)

b. Severe urinary retention or urinary incontinence in the first five years of disease

6. Recurrent falls within three years of onset

7. Anterocollis (dystonic) or contracture of the hands or feet within the first 10 years

8. Absence of any non-motor features despite five years disease duration

9. Unexplained pyramidal signs

10. Bilateral, symmetric parkinsonism from symptom onset

or treatment-resistant tremor and good cognitive function, deep brain stimulation (DBS), typically targeting the subthalamic nucleus or globus pallidus pars interna , is a potentially useful therapeutic strategy. Patient selection is key to delivering good outcomes. Criteria include five years of duration of PD (to allow time for features of atypical parkinsonism to emerge and assess response to dopaminergic medications), dopamine responsiveness (>30 per cent improvement in UPDRS), absence of dementia and depression, good cognitive function, and few comorbidities. Recently, there has been interest in using DBS earlier in the disease course, hoping to achieve improved quality-of-life and motor symptom control with lower doses of levodopa. Potential complications include dysarthria, worsening gait, cognitive dysfunction, and intracranial haemorrhage. Since January 2022, this procedure is available in Ireland and is accessed

through the National DBS Service at the Mater Misericordiae University Hospital, Dublin, with surgeries taking place in Beaumont Hospital, Dublin.

Key learning points

 IPD is a common, progressive, neurodegenerative disease which affects 1 per cent of the population over 60.

 Key clinical symptoms of IPD include parkinsonism (tremor, bradykinesia, and rigidity) as well as a broad range of nonmotor symptoms.

 IPD is a complex disease, which manifests in different ways over the course of disease.

 Treatment strategies must evolve with the predominant problem at each stage of the disease.

 In advanced disease, a range of therapeutic options including continuous administration of dopamine agonists and levodopa may be considered.

 DBS treatment for symptoms such as motor fluctuations, refractory tremor, and

disabling dyskinesias is now available in Ireland through the National DBS service.

References

1. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015;30(12):1591-1601

2. Defer GL, Widner H, Marie RM, Rem P, Levivier, M. Core assessment program for surgical interventional therapies in Parkinson’s disease (CAPSIT-PD). Mov Disord. 1999;14:572-584

3. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003;24(2):197-211

4. Hely MA, Reid WGJ, Adena MA, Halliday GM, Morris JGL. The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837–844

Q1 Some symptoms of PD may be present for many years before parkinsonism develops.

True or False?

Q2 MRI imaging of the brain can help to differentiate between atypical parkinsonian syndromes and IPD.

True or False?

Q3 Cognitive impairment is common at all stages of PD.

True or False?

Q4 Physical exercise and

Pre-assessment questions

physiotherapy should be encouraged in the early stages of PD.

True or False?

Q5 People with PD should inform their car insurance company of the diagnosis is they are to continue driving.

True or False?

Q6 Psychotic symptoms such as visual and auditory hallucinations and delusions are rare in PD and should prompt consideration of an alternative cause of parkinsonism.

True or False?

Q7 Impulse control disorders can occur in patients treated exclusively with levodopa preparations.

True or False?

Q8 Levodopa-induced dyskinesia is generally a benign complication which does not significantly impair quality-of-life.

True or False?

Q9 Deep brain stimulation (DBS) is especially useful in patients whose symptoms do not respond to levodopa.

True or False?

Epilepsy: An overview

The overall prognosis for people with newly-diagnosed epilepsy is good, with 60−70 per cent becoming seizure-free, many of whom do so in the early course of the condition

Epilepsy is a chronic neurological condition and the collective term for a large group of anatomical and functional disorders of the brain, characterised by repeated seizures; brief episodes of involuntary movement that may involve a part of or the entire body. By definition, epilepsy is a condition of recurrent unprovoked seizures. It occurs because of a predisposition to seizures from genetic susceptibility or a chronic pathologic process.

In Ireland, over 40,000 people are affected with epilepsy. Globally, over 50 million people are affected, and an estimated 2.4 million people are diagnosed with epilepsy each year.

The risk of premature death in people with epilepsy is up to three times higher than the general population, with highest rates found in low- and middle-income countries and rural versus urban areas.1,2,6 About 25-to-30 per cent of new-onset seizures are thought to be provoked or secondary to another cause. Epilepsy incidence is highest in younger and older age groups and increases steadily after 50 years of age. The most common cause of seizures and epilepsy in older people is cerebrovascular disease.4

Seizures can vary from the briefest lapse of attention or muscle jerks to se -

vere and prolonged convulsions accompanied by loss of consciousness and control of bladder and bowel function. They can also vary in frequency, from less than one per year to several per day. Up to 10 per cent of people worldwide have one seizure during their lifetime. One seizure does not signify epilepsy, which is defined as having two or more unprovoked seizures. Characteristics of seizures vary, depending on where in the brain the disturbance occurs, and how far it spreads. Temporary symptoms occur, such as loss of awareness or consciousness, disturbances of movement and sensation (including vision, hearing and taste), mood, or other cognitive functions. Triggers which make seizures more likely include missed medication, increased alcohol intake, sleep deprivation, stress, illnesses, and fevers. 2

Idiopathic epilepsy is the most common type, and in over half of cases there is no known cause. Epilepsy with a known cause is called secondary or symptomatic epilepsy. The causes of secondary epilepsy include: Brain damage from prenatal or perinatal injuries; congenital abnormalities or genetic conditions with associated brain malformations; severe head injury; stroke (CVA) that restricts the amount of oxygen to the brain; infections of the brain such as meningitis,

encephalitis, and neurocysticercosis; genetic syndromes; and brain tumours.1,2

Social and economic implications

Epilepsy has significant social and economic implications in terms of healthcare needs, premature death and workplace productivity. Nearly 80 per cent of people with epilepsy live in low- and middle-income countries. It accounts for 0.6 per cent, of the global burden of disease. Diagnosis and treatment of most people with epilepsy occurs in primary care without the use of sophisticated equipment. In low- and middle-income countries, however, 75 per cent of people with epilepsy may not receive the treatment they need.

Although social effects vary from country to country, people living with epilepsy can be targets of prejudice. Discrimination and social stigma surrounding epilepsy worldwide are often more difficult to overcome than the seizures themselves. The stigma of the disorder can discourage people from seeking treatment for symptoms, so as to avoid becoming identified with the disorder.

Diagnosis

To make a diagnosis of epilepsy, it is necessary to establish a tendency of recurrent, spontaneous epileptic seizures.

Q10 Lesioning procedures may be an option in PD patients who are not otherwise suitable for surgery.

True or False?

To complete this module and earn free CPD points, go to www.doctorCPD.ie and answer the 10 true or false questions and complete the five MCQs based on this article.

Many people have a single, isolated epileptic seizure at some point in their lives, but if a person has more than one, then a diagnosis of epilepsy may well be considered. One-in-20 people will have a single seizure and most never have another, while one-in-115 people will have more seizures and may then be diagnosed with epilepsy. Sometimes a person can be diagnosed after a first seizure if their tests confirm epilepsy, and the clinician feels it is likely they will have more seizures.1

History is key in assessment and will guide further evaluation. One of the first questions posed to the patient or caregiver is whether the event was a witnessed seizure or other type of transient event. A sudden alteration in consciousness with associated motor movements is a common description of a convulsive seizure. For generalised seizures with associated motor movements, the convulsion typically has a stiffening or tonic phase followed by clonic, rhythmic phased motor movements. There may be a noise or cry at the onset of the seizure. Some patients may describe a prodrome or aura before the event, and urinary incontinence may or may not be present. Tongue biting, if present, is most frequently lateral. Fol-

lowing a generalised tonic-clonic seizure, patients will have some transient alteration consciousness, referred to as the postictal state. There are many types of seizures other than generalised convulsions, and any transient alteration of consciousness or unusual behaviour or individualised perception might conceivably represent a type of seizure.4

Key points include history with attention to the history of seizures, medication use, past medical history, and social history, especially any history of alcohol or illicit drug use. A history of immunosuppression or malignancy is very important. Frequently there will be a history of unresponsive spells that might be seizures. Events leading up to the seizure are important, and friends, family, or co-workers may have important information. For the patient with known epilepsy, it is important to establish if there has been any irregularity with their medication use.1,4 Physical examination should include a general physical and a neurologic examination with attention to the detection of any focal deficits.4

A diagnosis of epilepsy is made by a consultant taking into account eye witness descriptions of seizures and test results. Results of tests can help support the diagnosis and pinpoint the seizure type. Tests include the routine awake EEG, sleep and sleep deprived EEG, and CT brain scan or MRI. Routine blood tests may be ordered.1

Treatment and management

The main treatment for epilepsy is anti-epileptic-drugs (AEDs), although surgery may be required for severe cases. Over the past few decades new drugs for epilepsy have become available, which allow many people with epilepsy to live virtually seizure-free lives. With AED treatment, up to 70 per cent of people with epilepsy will not have seizures while taking medication. A small number benefit from epilepsy surgery, which in some cases can manage the condition completely. However, for up to 30 per cent of people with epilepsy, seizures are difficult to control despite treatment.1 The potential for drug-drug interactions should always be considered when prescribing concomitant medication to a patient on AEDs and the National Medicines Information Centre (NMIC) provides up-to-date information on AED-related enquiries. 6

Drug-drug interactions occurring in patients with epilepsy can have substantial effects on clinical outcome and may often be predicted by the pharmacokinetic and pharmacodynamic profiles of the AEDs. Many patients with epilepsy have co-morbid conditions which require non-AED concomitant medications. Drug interactions between AEDs and contraceptive hormones are clinically important and need to be considered due to risks including contraceptive failure, potential teratogenicity of AEDs, and reduced seizure control.

There are widespread concerns about the teratogenic risks posed by AEDs, and

the utmost care must be taken with use in pregnancy. When used during pregnancy, sodium valproate-containing medicines are associated with a risk of major congenital malformations and developmental disorders. In February 2018, the European Medicines Agency (EMA) put in place measures to reduce the risk of exposure of babies to valproate in the womb.

These measures have been implemented in Ireland and include:

 For women with epilepsy, valproate must not be used in pregnancy unless there is no suitable alternative treatment.

 In female patients from the time they become able to have children, valproate must not be used unless the conditions of a pregnancy prevention programme are met.

the area of the brain that is causing seizures. Resections may be temporal or extratemporal, involving one of the other lobes of the brain. Lesionectomy is another type of resection and involves removing lesions such as tumours, scar tissue, haematomas, or abnormal blood vessels.

Disconnection includes hemispherectomy, the removal or disconnection of the side of the brain causing seizures, and hemispherotomy disconnecting the cortex of one side of the brain without removing it.

Corpus callosotomy involves cutting the corpus callosum, which connects the two sides of the brain, to prevent the seizure activity spreading. No brain tissue is removed.

Multiple subpial transection is only carried out when it is not possible to remove

much better quality-of-life and outcomes than in the past. The ability to accurately diagnose the disorder and provide safe and effective therapy has substantially improved. The overall prognosis for people with newly-diagnosed epilepsy is good, with 60-to-70 per cent becoming seizure-free, many of whom do so in the early course of the condition. The probability of obtaining freedom from seizures is particularly high in those with idiopathic generalised epilepsy and normal neurological examination. 8,10

In view of the increased risk of neural tube defects and other major congenital malformations associated with exposure to AEDs (particularly valproate and carbamazepine), current guidelines also recommend that a daily dose of 5mg folic acid is prescribed prior to conception and until at least the end of the first trimester for all women taking AEDs.

Some medications prescribed for other medical conditions can affect epilepsy or interact with epilepsy medication. These include certain antibiotics, anti-malaria drugs, pain medications, steroids, broncho-dilators, antihistamines, antidepressants, anti-psychotics, and benzodiazepines. Some cold and flu medicines, decongestants and antihistamines have been reported to increase the risk of seizures. Grapefruit and grapefruit juice can interact with many medicines, including some epilepsy medications such as carbamazepine and oxcarbazepine and emergency medications such as midazolam and Valium. Energy drinks with high levels of caffeine can provoke seizures too. Alcohol is also a trigger for seizures, and should be kept to moderate levels.1

A full list of current AEDs and their various indications and potential side-effects are available at: www.epilepsy.ie/content/ types-anti-epileptic-drugs-aeds

Refractory epilepsy

Surgery may be considered in epilepsy when seizures are not responding to medication. People with resistant partial seizures are more likely candidates for surgery than those with generalised seizures. If seizures are found to arise from only a single small area of the brain then this part may be removed to control the epilepsy.

Main types of epilepsy surgery1 Resection procedures involve removing

the area of the brain causing the seizures. Shallow cuts are made to the cortex to control the spread of seizure activity.

Success rates for epilepsy surgery depend on the type of surgery involved and differs with each individual. However, up to 70 per cent of people having temporal lobe epilepsy surgery are seizure-free two years after surgery.1

Research and outlook

The prognosis for patients with seizures depends mainly on the underlying cause. Patients with neoplastic causes of seizures or hypoxic brain injury fare worse than those with metabolic causes. There is little question, however, that many people living with epilepsy today have a

References

1. Epilepsy Ireland (2022). Epilepsy Information. Available at: www.epilepsy.ie

1. World Health Organisation.(2018). Epilepsy. WHO. Geneva. Available at www.who.int/news-room/ fact-sheets/detail/epilepsy

2. Epilepsy Ireland (2022). Anti-epileptic drugs (AEDs). Available at: www.epilepsy. ie/content/types-anti-epileptic-drugs-aeds

3. Huff J, Murr N (2022). Seizure. In StatPearls Publishing. Available at: www. ncbi.nlm.nih.gov/books/NBK430765/

4. Megiddo I, Colson A, Chisholm D, Dua T, Nandi A, Laxminarayan R. Health and economic benefits of public financing of epilepsy treatment: An agent-based simulation model.  Epilepsia. 2016 Mar;57(3):46474. doi: 10.1111/epi.13294

5. National Medicines Information Centre (2014). Pharmacological Management of Adults with Epilepsy (Vol 20, No 5). NMIC, St James’s Hospital.

Ongoing neuroimaging, neuropathology and genomics research is advancing our understanding of epilepsy. Advances in brain imaging are helping to identify the structural and functional causes and consequences of the epilepsies. Progress in genomic technology is driving a paradigm shift. Genomic medicine has the potential to transform the way we care for people with epilepsy, and it is believed that whole genome sequencing will help unravel the genetic architecture underlying the different types of epilepsy. With improved understanding of the gradual development of epilepsy, epigenetic determinants, and pharmacogenomics, comes the hope for better, disease-modifying, or even curative, pharmacological, and non-pharmacological treatment strategies. Other developments are clinical implementation of seizure detection devices and new neuromodulation techniques, including responsive neural stimulation.8,9

In April 2022, scientists at Trinity College Dublin announced a significant advance in our understanding of epilepsy, as they identified a potential method of preventing damaging seizure activity. Brain cells are nourished by an intricate network of capillaries that forms the blood-brain barrier (BBB), and the group of Trinity scientists believe that disruption to the integrity of these capillaries and the BBB is a key driver of seizure activity in humans. The new research shows that restoring the integrity can prevent seizures, and it is this finding that holds real potential in moving the discoveries closer to a real and meaningful therapy.6

Dublin. Available at: www.stjames. ie/GPsHealthcareProfessionals/ Newsletters/NMICBulletins/ NMICBulletins2014/2nd%20Bulletin%20 NMIC%20Pharmacological%20 Management%20of%20Epilepsy.pdf

6. Science Daily (2022). Scientists identify novel approach to preventing seizures. Available at: www.sciencedaily.com/ releases/2022/04/220414110816.htm

7. Epilepsy Society UK (2022). Unlocking the code through genomics. Available at: https://epilepsysociety. org.uk/research/genomics

8. Thijs R, Surges R, O'Brien T, Sander J. Epilepsy in adults. Lancet. 2019 Feb 16; 393(10172):689-701. doi: 10.1016/S0140-6736(18)32596-0

9. Holmes G, Noebels JL. The epilepsy spectrum: Targeting future research challenges. Cold Spring Harb Perspect Med. 2016 Jul 1; 6(7):a028043.doi: 10.1101/cshperspect.a028043

...for up to 30 per cent of people with epilepsy, seizures are difficult to control despite treatment

BOTOX® is indicated for symptom relief in adults fulfilling criteria for chronic migraine (headaches on ≥15 days per month of which at least 8 days with migraine) in patients who have responded inadequately or are intolerant of prophylactic migraine medications1

Legal category POM (S1A). Marketing Authorisation Numbers: PA 1824/017/1-3.

Further information is available on request from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, D24 XN32 or at www.medicines.ie

References:

1. BOTOX® Summary of Product Characteristics available on www.medicines.ie

A new paradigm for Parkinson’s treatment in Ireland

Despite decades of advances in the treatment of Parkinson’s disease, there remains a high unmet need among patients. It is thought that there are around 12,000 people living with Parkinson’s disease in Ireland, with this figure projected to reach 20,000 over the next 15-to-20 years.

The RCPI on Kildare Street was the venue for the eagerly-awaited launch of the first triple fixed combination therapy gel for the treatment of Parkinson’s disease, Lecigon. Incorporating levodopa, entacapone, and carbidopa in the form of an intestinal gel, Lecigon is indicated for the treatment of advanced Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia when available oral combinations of Parkinson’s medicinal products have not given satisfactory results.

The launch event was chaired by Prof Tim Lynch, Clinical Director of the Dublin Neurological Institute at the

Mater Misericordiae University Hospital in Dublin. Prof Lynch told the audience of clinicians, nurses, and other healthcare professionals that levodopa therapy is a mainstay of Parkinson’s management and is “phenomenal”, but there are problems with its absorption for some patients. Complex therapies are increasingly being used, as are dual therapies, he noted. Meanwhile, the cutting edge treatment of deep brain stimulation (DBS) is now available in Ireland, but not everyone will be suitable for this treatment.

“A new intestinal gel in the form of levo-carbidopa with entacapone is very welcome,” commented the Professor. “I can certainly see a role for it and it will be important to see how it fits into the treatment paradigm.”

Mr Robert Wood, General Manager of Britannia Pharmaceuticals Ltd, offered an introduction to the therapy. There are currently a total of 659 patients on the treat-

ment worldwide, 337 of which were added during 2022. As this number increases, real world data is being gathered in the form of a large pan-European non-interventional study (ELEGANCE); this is currently in the recruitment phase and enrolment will commence in Ireland in November 2022. “The key message is not to delay when it comes to advanced therapies,” Wood stated.

Developments in levodopa infusion therapies were covered by Prof Dag Nyholm, Department of Medical Sciences/Neurology Uppsala University, Uppsala University Hospital, Sweden.

The Dutch experience of treatment transition to Lecigon was outlined by Prof Teus van Laar, Medical Director of the Parkinson Expertise Centre at the University of Groningen in the Netherlands.

Lecigon is now available in Ireland and reimbursed on the high-tech scheme.

... a reduced levodopa dose can be given

The same effective and stable plasma levodopa levels are achieved

*Levodopa-Carbidopa Intestinal Gel 1. Lecigon Summary of Product Characteristics, 2021. ABBREVIATED PRESCRIBING INFORMATION. Lecigon 20 mg/ml + 5 mg/ml + 20 mg/ml intestinal gel. 1 ml contains 20 mg levodopa, 5 mg carbidopa monohydrate and 20 mg entacapone. Presentation: Yellow or yellowish-red opaque viscous gel. Indications: Treatment of advanced Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia when available oral combinations of Parkinson medicinal products have not given satisfactory results. Dosage and administration: Adults/Elderly: Administration by a portable infusion pump directly into the duodenum or upper jejunum via a percutaneous endoscopic gastrostomy(PEG) tube or radiological gastrojejunostony tube. Please consult Summary of Product Characteristics (SmPC) for further information. Only pump Crono LECIG (CE 0476) may be used for the administration of Lecigon. The dose should be titrated to achieve the optimal clinical response in the individual patient, which involves maximising the functional ON-time during the day by minimising the number and duration of OFF episodes (bradykinesia) and minimising ON-time with disabling dyskinesia. Total dose/day of Lecigon is composed of three individually adjusted doses: the morning bolus dose, the continuous maintenance dose, and extra bolus doses. Treatment is usually limited to the patient’s awake period. If medically justified, Lecigon can be administered up to 24 hours/day. The maximum recommended daily dose is 100 ml (2000 mg levodopa, 500 mg carbidopa monohydrate and 2000 mg entacapone. Please consult SmPC for further information. Total morning dose is usually 5–10 ml (100–200 mg levodopa) but not exceeding 15 ml (300 mg levodopa). Continuous maintenance dose is usually 0.7–5.0 ml/hour (15–100 mg levodopa/hour). Extra bolus doses are given if the patient becomes hypokinetic and are normally less than 3ml. An increase in the continuous maintenance dose should be considered if the need for extra doses exceeds 5 doses per day. Please consult SmPC for further information. After initial titration, the morning dose and maintenance dose are fine-tuned over the course of a few weeks. Lecigon is initially given as monotherapy. If needed, other anti-Parkinsonian medicinal products can be taken concurrently. If treatment with other anti-Parkinsonian medicinal products is discontinued or changed, it may be necessary to adjust the doses of Lecigon. Sudden deterioration in response with recurring motor fluctuations may indicate that the tube has dislocated to the stomach. This needs confirmation by X-ray and may require repositioning. Please consult SmPC for further information. The cartridge is for single use only and should not be used for more than 24 hours. Children: There is no relevant indication for use in children and adolescents. Contraindications: Hypersensitivity to the active substances or any of the excipients, narrow-angle glaucoma, severe heart failure, severe cardiac arrhythmia, acute stroke, severe hepatic impairment. Non-selective MAO-inhibitors and selective MAO type A inhibitors are contraindicated and should be discontinued at least two weeks prior to initiating therapy with Lecigon. Conditions in which adrenergics are contraindicated. Previous neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis. Suspected undiagnosed skin lesions or a history of melanoma. Please consult SmPC for further information. Warnings and precautions: Not recommended for the treatment of drug-induced extrapyramidal reactions. Caution in ischaemic heart disease, severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or of convulsions, past or current psychosis, chronic wide-angle glaucoma, concomitant administration of antipsychotics with dopamine receptor blocking properties or with medicines which may cause orthostatic hypotension. In patients with a history of myocardial infarction who have residual atrial nodal or ventricular arrhythmias, cardiac function should be monitored with particular care during the period of initial dosage adjustments. Monitor all patients for mental changes, depression with suicidal tendencies, and other serious mental changes. Neuroleptic malignant like syndrome with secondary rhabdomyolysis may occur on abrupt dose reduction/discontinuation of Lecigon. Patients should be monitored for the development of impulse control disorders and review of treatment is recommended if such symptoms develop. Patients and caregivers are advised to monitor for melanomas on a regular basis when using Lecigon. Dose may need to be adjusted downwards to avoid levodopa-induced dyskinesia. Periodically evaluate hepatic, haematopoietic, cardiovascular and renal function during extended therapy. Lecigon contains hydrazine, a degradation product of carbidopa that can be genotoxic and possibly carcinogenic. Reported complications for levodopa/carbidopa in clinical studies include bezoar, ileus, implant site erosion/ulcer, intestinal haemorrhage, intestinal ischaemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumoperitoneum and post-operative wound infection. Sudden or gradual worsening of bradykinesia may indicate an obstruction in the tubing system and should be investigated. Weight loss has been associated with the active substances contained in Lecigon, and caregivers should therefore be aware of weight loss. Monitoring of weight is recommended to avoid severe weight loss. Prolonged or persistent diarrhoea that appears during use of entacapone could be a sign of colitis. In case of prolonged or persistent diarrhoea, treatment with the medicinal product should be discontinued and other appropriate medical treatment and investigation considered. Replacement of Lecigon with either levodopa and a DDC inhibitor without entacapone or other dopaminergic therapy may be necessary and should be done slowly. For patients who experience progressive anorexia, asthenia and weight loss within a relatively short period of time, a general medical evaluation including liver function assessment should be considered. Please consult SmPC for further information. Interactions: Antihypertensives, antidepressants, anticholinergics, dopamine receptor antagonists, benzodiazepines, isoniazide, phenytoin, papaverine, sympathicomimetrics iron, protein-rich diet, amantadine and dopamine agonists (e.g. piribedil) may increase levodopa-related adverse events. Lecigon dose adjustment may be needed when used with these medicines. Lecigon can be taken with MAO type B inhibitors (e.g. selegiline) although serious orthostatic hypotension may occur and the dose of levodopa may need to be reduced. Lecigon may affect metabolism of medicinal products such as S-warfarin and patients should be monitored during initiation with Lecigon therapy when used with this medicine. Please consult SmPC for further information. Pregnancy and lactation: Lecigon is not recommended during pregnancy or in women of childbearing potential not using contraception unless the benefits for the mother outweigh the possible risks to the foetus. It is unknown whether carbidopa and entacapone or their metabolites are excreted in human milk. Breastfeeding should be avoided during treatment with Lecigon. Driving and operation of machinery: Caution; Lecigon can have a major influence on the ability to drive and use machines. Refrain if somnolence and/or sudden sleep episodes occur. Undesirable effects: Weight loss, anxiety, depression, insomnia, dyskinesia, Parkinson’s disease /exacerbation of parkinsonism (e.g. bradykinesia), orthostatic hypotension, nausea, constipation, diarrhoea, pain in muscles and tissues, musculoskeletal pain, chromaturia, fall. Complications of the device and surgery: Postoperative wound infection, abdominal pain, excessive granulation tissue, complication of device insertion, incision site erythema, post-procedural discharge, procedural pain, procedural site reaction. Refer to SmPC for other undesirable effects. Adverse events should be reported via HPRA Pharmacovigilance, website: www.hpra.ie. Special precautions for storage: Store in a refrigerator 2°C - 8°C. Do not freeze. Store in the original package in order to protect from light. For storage instructions after first opening of the medicinal product, refer to the summary of product characteristics. Pack size: 7 x 47 ml cartridges. Marketing authorisation holder: LobSor Pharmaceuticals AB, Kålsängsgränd 10 D, SE-753 19 Uppsala, Sweden.

Distributed by Clonmel Healthcare Ltd, Clonmel, Co. Tipperary. Marketing authorisation number: PA23144/001/001. Medicinal product subject to medical prescription. A copy of the summary of product characteristics is available upon request or alternatively please go to: www.clonmelhealthcare.ie Last revision date: March 2022. Date of Preparation: October 2022. 2022/ADV/LEC/268H

A combination of three effective Parkinson’s therapies in one convenient gel formulation for intestinal infusion1

The mind-body connection in skin diseases

Attendees at UCD’s Charles Institute Seminar Series heard an introduction by Dr Jillian Doyle to the discipline of psychodermatology and how its application can potentially improve outcomes

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 many 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 seminars are held using a hybrid model, combining in-person attendance with interactive online access.

The attendees heard a presentation by Dr Jillian Doyle, Senior Clinical Psychologist in the Specialist Perinatal Mental Health Team in the Rotunda Hospital, Dublin. Dr Doyle also works with the Department of Psychological Medicine at the Mater Misericordiae Hospital in Dublin, where she provides a service for patients attending the Dermatology and Cardiac Rehabilitation teams.

Dr Doyle addressed the seminar on the role of psychology in patients with dermatological issues and outlined how the fields of dermatology and psychology overlap, and how psychology can help to enhance patients’ quality-of-life and improve outcomes. She presented a number of case studies and told the attendees: “Psychodermatology is all about connecting the dots between the skin, stress, emotional wellbeing, and providing supports to people with pre-existing skin conditions,” she said.

“The discipline focuses on the overlap between dermatology and psychology; it holds that by only treating the skin, you may not be getting to the root of the issue. Psychologists and psychiatrists who work in this area research the role that stress plays in different skin disorders, or how skin disorders can lead to psychological consequences – for example, difficulties with self-esteem or problems with people’s views of themselves.” The types of issues commonly seen by psychodermatologists include anxiety (including social anxiety) and depression.

Interventions

Typically, interventions include helping dermatology patients to deal with psychological issues or, in the field of health psychology, helping patients to avoid developing certain conditions, such as melanomas. “Research shows that psychological interventions and the promotion of self-care may be a key factor in the treatment of some long-term chronic conditions,” Dr Doyle told the seminar. “It’s really important to think about how the brain and the central nervous system develop at the same time in utero; there is a lot of interaction between the skin and the mind. Psychodermatology complements the other line of treatments but there are little or no services in Ireland in this area, although Northern Ireland has a dedicated psychodermatology clinic.”

Approximately 90 per cent of people with skin diseases report that their condition affects their emotional and psychological wellbeing, and in the UK, some 18 per cent of these people receive some kind of psychological support, Dr Doyle pointed out.

Dr Doyle gave the attendees an overview of the therapy process for people with skin diseases and presented case

studies of psychodermatology patients of different ages and with different skin conditions. One of these included a patient suffering with hidradenitis suppurativa (HS), a potentially devastating and stigmatising condition that is notoriously difficult to treat and manage due to its abscesses and scarring characteristics. She also invited the attendees to participate in an interactive ‘selfie’ exercise to illustrate the power of a person’s perception of self, in comparison to what other people see. This relates to the lack of self-worth and self-esteem people with skin conditions suffer with and is a useful awareness exercise, Dr Doyle explained.

“The impact of clinically-significant skin disease may not be life-threatening, but it can be life-ruining,” said Dr Doyle. “A lot of people report symptoms of anxiety and depression and a considerable minority have suicidal thoughts… some of the other impacts are that people don’t stick to their medication regimens, or they use maladaptive coping mechanisms. These people can lose work days or have to withdraw from work, or be unable to get work, or experience discrimination in the workplace.” The relationships of these patients also suffer, and even those with skin conditions who are in a relationship may feel isolated from those closest to them, she added.

Infections

It is recognised that a person’s mental state can influence their response to infection and in parallel with this, a person’s physical illness affects their emotional well-

being, she pointed out. “Some psychiatric disorders are expressed in the body and often, people will see a dermatologist first because they see the physical manifestations first,” she continued. “Secondary psychiatric disorders are when the chronicity of the skin condition, or the stress caused by the condition, lead to psychological consequences. Something that is fairly visible can lead to consequences such as poor body image or low self-esteem, and subsequent depression and anxiety.”

Expanding on the relationship between emotional stress and exacerbation of skin conditions, Dr Doyle commented: “This response is through the hypothalamic-pituitary-adrenal axis, which ultimately leads to either a dysregulation of cortisol or too much cortisol, which can have a major impact on the immune system,” she told the seminar. “It also releases the ‘fight or flight’ hormones, which can have an impact on the skin barrier and inflammation and impact wound-healing. If this happens again and again, we often see chronic activation of the stress hormones on the skin, and this increases the reactivity to stimuli.”

Stress not only influences skin conditions, but also has an effect on the ageing process, she added, and therefore it is vitally important to help people to manage their stress levels, particularly if that stress is exacerbating a pre-existing medical condition. This is where an intervention with a psychodermatologist can yield results, said Dr Doyle.

The new clinical programme for dermatology in Ireland recognises the need for psychodermatology and suggests that psychodermatologists be linked to different teams in a hub-and-spoke model, and that the appointment of psychologists will assist people living with chronic skin conditions. This could help these patients to build resilience and develop coping strategies, reducing the impact of a skin disease on their lives, she concluded.

Standards and stigma

Dr Doyle’s presentation generated a lot of audience interest and during an interactive Q&A session, Prof Tobin commented on the general perception among some members of the public of people with a visible skin condition. Unrealistic portrayals of impossible-to-achieve beauty standards in advertisements, etc, are combined with a society that has supposedly become more tolerant to individuals’ appearance. “What is it about society that we almost seem to be going in the opposite direction,” he said, pointing out that in an apparently more tolerant society, stigma around skin conditions still exists. “That isolation and disconnect that is experienced by people with skin disease seems almost enhanced compared to what it was 15 or 20 years ago… what do you feel needs to be done now to push back that tide?”

Dr Doyle commented: “This is a huge thing and it’s in every realm [of society]. We are all told that we can be the ‘star in our own life’, and that is really hard to step out of… for good or bad, people have stepped away from things that they used to believe in, such as belief value systems, particularly in Ireland. Now we have a vacuum that has been filled by celebrities, beauty and so on. So I think [we need] a macro view on what society does, and also on an individual level in terms of what we can do. We need to think about how we can move towards people who are suffering, rather than away from them.”

RELIFE has had no input into the content of this article or series of seminars

The impact of clinicallysignificant skin disease may not be life-threatening, but it can be life-ruining

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Spotlight on aplastic anaemia

The Haematology Association of Ireland (HAI) Annual Meeting 2022 spanned two days and featured more than 20 presentations and lectures. It took place on 14-15 October in the Radisson Blu Hotel, Little Island, Cork. Speakers from Ireland and abroad, including the US and UK, delivered a range of talks on topics of special interest to haematologists.

The State-of-the-Art lecture on day one was chaired by Dr Su Maung, HAI Secretary/Treasurer. Dr Maung introduced Dr Emma Groarke, Haematologist and Assistant Research Physician at the Haematology Branch of the National Heart, Lung and Blood Institute, National Institutes of Health, US, who delivered a talk titled ‘Immune aplastic anaemia: Current considerations for diagnosis and management’.

Dr Groarke focused her talk on the management of aplastic anaemia and provided a synopsis of the condition, as well as a brief overview of what drives aplastic anaemia and its causes. She explained that aplastic anaemia is a bone marrow failure syndrome characterised by cytopaenias. Among the primary causes of aplastic anaemia, immune-acquired aplastic anaemia is by far the most common and accounts for over 70 per cent of cases, she said.

“Typically, in our approach to treatment, we look at the patient’s age and whether or not they have a fully matched sibling donor,” Dr Groarke told the conference. “In paediatric patients, we tend to go for transplant if possible – if these patients have a fully matched sibling donor then this is going to be the therapy of

choice. However, increasingly, if patients have an unrelated matched donor, we will also proceed to using a matched unrelated donor in the frontline setting.”

She described the typical transplant criteria for child and adult patients and provided an overview of trial data. “In adults and older adults, we still favour immunosuppressive therapy; in children, we lean towards transplant if possible,” said Dr Groarke. “If you look at transplant in comparison to immunosuppression, you

see [from data] that there isn’t a difference in overall survival, but there is a significant difference in eventfree survival. It can be a little challenging to measure event-free survival in aplastic anaemia because most of the events are actually driven by the relapse risks that we see in the condition. However, it still stands that the event-free survival is significantly different and for this reason, we are considering upfront [transplant] more frequently.”

She also briefly described second-line treatment options for relapsed/refractory aplastic anaemia and explained that it is currently not possible to provide therapy to prevent risk of relapse. “In refractory patients, we really try to push the transplant option if possible,” she told the conference.

“Haploidentical transplant is definitely something that’s emerging in aplastic anaemia,” said Dr Groarke. “The main advantage is that it opens up the donor pool. You can get grafts quickly and give stem cell boosts if necessary, and compared to the other alternate donor transplant [umbilical cord], it’s much cheaper and there are better cell doses. The issue with haploidentical transplant is the high graft vs host disease risk, and also the risk of graft failure,” she explained.

“Initially, aplastic anaemia is quite a severe disease and patients are quite sick,” she concluded. “Most patients will respond to therapy upfront; however, there can be a long course where patients are likely to relapse and further therapies may be required. There is still a lot of work to be done, particularly in the areas of relapse and clonal evolution.”

The US perspective on bleeding disorders and novel therapies

The Haematology Association of Ireland Annual Meeting 2022 also heard from Prof Robert Sidonio of the Emory University School of Medicine, US, who delivered a State-of-the-Art lecture titled ‘Novel therapies in bleeding disorders’ in a session introduced by Dr Kathryn Clarke of Queen’s University Belfast and the Belfast Health and Social Care Trust.

Prof Sidonio discussed novel therapies that are being used in the US to treat bleeding disorders and what he described as a “forgotten disorder”, namely Glanzmann’s thrombasthenia, which is a rare bleeding disorder characterised by prolonged or spontaneous bleeding starting from birth.

Prof Sidonio said: “The manifestations of bleeding are pretty significant – these are probably the worst nosebleeds you will ever see,” he told the attendees. “These patients have six- or seven-hour nosebleeds that you just can’t get to stop, and you can imagine the parents coming in with them [children] covered with blood. These children are often chronically anaemic and sometimes require a transplant because the bleeding is so severe.” The mainstay of treatment is to administer platelets from a donor, if the patient’s own platelets are dysfunctional, he explained, or recombinant 7 on demand (which is on-label in the US). He and his colleagues have been investigating prophylactic recombinant 7 therapy, and the published data showed some “dramatic results,” he said. A proof of principle trial is due to begin in early 2023 focused on prophylactic recombinant 7 on demand, and “you

can tell that a disorder is really rare when you have three sites with six patients, and you are super excited when you can get those six patients on the trial,” said Prof Sidonio.

He also briefly discussed drug treatments for a range of other disorders in the area of monoclonal antibodies and synopsised some of the trial data to support these treatments for bleeding events, and conditions such as von Willebrand disease. “Haemophilia often gets a lot of the new products and that’s where a lot of the investment goes,” said Prof Sidonio. “But there are ways that we can take what we have learned in haemophilia and apply it to the treatment of von Willebrand disease.”

Prof Sidonio also briefly discussed novel therapies in the pipeline for haemophilia, which he explained may have applications for other conditions. “I think this is going to be the trend,” he told the conference. “People are creating products that can actually be useful in multiple different disorders.”

Discussing various haemophilia treatments, specifically aptamer BT200, Prof Sidonio commented: “These products are actually very easy to manufac -

ture,” he said. “They have high affinity and specificity and are pretty inexpensive to produce… this one was almost a serendipitous discussion. They were looking at targeting VWF [von Willebrand factor] more as an antiplatelet anticoagulant, and more for patients with heart disease. What they found was that in certain concentrations, it actually blocks the binding site on the A1 domain and that overlaps with the clearance site, so it actually [aids] clearance in circulation, so it accumulates the patient’s VWF… data show that if you do PEGylate that region, you can actually attenuate the effect of clearance of VWF.

“The most exciting thing here is that we have been trying to encourage the company to look at women and girls with haemophilia and also target this population that is much more difficult to target because of all the regulations around reproduction,” he added. “In some countries, you can’t even do that without the animal studies being completed. We are hoping that we can target some non-severe haemophilia and von Willebrand’s. We can see that if we give this as a subcutaneous injection, the antigen levels get quite high… what’s really interesting is that this does not affect the pro-peptide level, but only affects the clearance, so you can also still give something like DDAVP [synthetic peptide desmopressin] to these patients. This is actually a benefit for those with mild haemophilia – not so much with moderate haemophilia, although there are still some patients who could benefit from it,” said Prof Sidonio. “This could potentially occupy the space where DDAVP is, with potentially less side-effects.”

ENCLYXTO® REGIMENS: DEEP RESPONSE** AND LONGER PFS WITH FIXED TREATMENT DURATION1,2

VENCLYXTO®▼ (venetoclax) 10 mg/50 mg/100 mg film-coated tablets. PRESCRIBING INFORMATION. Each film-coated tablet contains 10mg, 50mg or 100mg of venetoclax. Please refer to the Summary of Product Characteristics (SmPC) before prescribing. INDICATION: Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (see section 5.1) * . Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy*. Venclyxto monotherapy is indicated for the treatment of CLL in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B cell receptor pathway inhibitor or in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B cell receptor pathway inhibitor*. Venclyxto in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.† DOSAGE AND ADMINISTRATION: Oral. Treatment to be initiated and monitored by a physician experienced in the use of anticancer medicinal products. Patients treated with venetoclax may develop tumour lysis syndrome (TLS). Refer to SmPC for specific details on TLS management by disease indication. See SmPC for full posology. Posology (CLL): Dose-titration schedule: the starting dose is 20 mg of venetoclax, once daily for 7 days. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400 mg. Post-titration dose for venetoclax in combination with rituximab: The recommended dose of venetoclax in combination with rituximab is 400 mg once daily. Administer Rituximab after the patient has completed the dose-titration schedule and has received the recommended daily dose of 400 mg venetoclax for 7 days. Venetoclax is taken for 24 months from Cycle 1 Day 1 of rituximab. Venetoclax in combination with obinutuzumab: Venetoclax is given for a total of 12 cycles, each cycle consisting of 28 days: 6 cycles in combination with obinutuzumab, followed by 6 cycles of venetoclax as a single agent. Administer obinutuzumab 100 mg on Cycle 1 Day 1, followed by 900 mg which may be administered on Day 1 or Day 2. Administer 1000 mg on Days 8 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle, for a total of 6 cycles. Start the 5-week venetoclax dose-titration schedule (see Table 1) on Cycle 1 Day 22 and continue through Cycle 2 Day 28. After completing the dose-titration schedule, the recommended dose of venetoclax is 400 mg once daily from Cycle 3 Day 1 of obinutuzumab to the last day of Cycle 12. Posttitration dose for venetoclax monotherapy: the recommended dose of venetoclax is 400 mg once daily. Treatment should be continued until disease progression or no longer tolerated by the patient. Posology (AML): Day 1: 100mg; Day 2: 200mg; Day 3 (and beyond): 400mg. Azacitidine should be administered at 75 mg/m2 either intravenously or subcutaneously on Days 1-7 of each 28-day cycle beginning on Cycle 1 Day 1. Decitabine should be administered at 20 mg/m2 intravenously on Days 1-5 of each 28-day cycle beginning on Cycle 1 Day 1. Venetoclax dosing may be interrupted as needed for management of hematologic toxicities and blood count recovery. Venetoclax, in combination with a hypomethylating agent, should be continued until disease progression or unacceptable toxicity is observed. Patients should swallow the tablets whole with water at approximately the same time each day. The tablets should be taken with a meal. Prevention of tumour lysis syndrome (TLS): Prior to initiating venetoclax, tumour burden assessment, including radiographic evaluation must be performed for all patients. The following prophylaxis measures should be followed to minimise the risk of TLS and more intensive measures should be employed as overall risk increases; adequate hydration, administration of anti-hyperuricaemic agents if necessary, blood chemistry monitoring and correction of abnormalities. Monitoring should be increased for patients at high risk of TLS. All patient comorbidities should be considered for risk-appropriate prophylaxis and monitoring, either outpatient or in hospital. Dosing interruption and/or dose reduction for toxicities may be required. Dose modifications for TLS or other toxicities may need to be considered during treatment. See SmPC for full details of prophylaxis measures. Special Populations: Elderly: No dose adjustment required. Renal impairment: No dose adjustment is needed for patients with mild, moderate or severe renal impairment (CrCl ≥15 ml/min and <90 ml/min). Venclyxto should be administered to patients with severe renal impairment (CrCl ≥15 ml/min and <30 ml/min) only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS. Patients with reduced renal function may require more intensive prophylaxis to reduce the risk of TLS and closer monitoring. Safety in patients with severe renal impairment or on dialysis has not been established, and a recommended dose for these patients has not been determined. Hepatic impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. Patients with moderate hepatic impairment should be monitored more closely for signs of toxicity. A dose reduction of at least 50% throughout treatment is recommended for patients with severe hepatic impairment. These patients should be monitored more closely for signs of toxicity. Paediatric Population: The safety and efficacy of Venclyxto in children aged less than 18 years has not been established.

CONTRAINDICATIONS: Hypersensitivity to any of the active substances or excipients. In patients with CLL, concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase. In all patients, concomitant use of preparations containing St. John’s wort. SPECIAL WARNINGS AND PRECAUTIONS: Tumour lysis syndrome (TLS): The risk of TLS is a continuum based on multiple factors, including comorbidities (particularly reduced renal function), tumour burden and splenomegaly. Reduced renal function (CrCL < 80mL/min) further increases the risk. Assess patient-specific factors for level of risk of TLS and provide prophylactic hydration and anti-hyperuricaemics to patients prior to first dose of venetoclax to reduce risk of TLS. . Blood chemistries should be monitored and abnormalities managed promptly. Dosing should be interrupted if needed; when restarting venetoclax, dose modification guidance should be followed. More intensive measures should be employed as overall risk increases. Neutropenia and infections:

In patients with CLL, grade 3 or 4 neutropenia has been reported. In patients with AML, grade 3 or 4 neutropenia are common before starting treatment. The neutrophil counts can worsen with venetoclax in combination with a hypomethylating agent. Neutropenia can recur with subsequent cycles of therapy. Complete blood counts should be monitored throughout the treatment period. Dose interruptions or reductions are recommended for patients with severe neutropenia. Serious infections, including sepsis with fatal outcome, have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections are to receive prompt treatment, including antimicrobials and dose interruption or reduction as appropriate and the use of growth factors (e.g., G-CSF) as appropriate. Immunisation: Live vaccines should not be administered during treatment and thereafter until B-cell recovery as the safety and efficacy has not yet been established. CYP3A inducers: Co-administration of CYP3A4 inducers may lead to decreased Venclyxto exposure and consequently a risk for lack of efficacy. Concomitant use of Venclyxto with strong or moderate CYP3A4 inducers should be avoided. Women of childbearing potential: Women of childbearing potential must use a highly effective method of contraception while taking Venclyxto. INTERACTIONS: See SmPC for full details. Venetoclax is predominantly metabolised by CYP3A. CYP3A inhibitors: In patients with CLL, concomitant use of venetoclax with strong CYP3A inhibitors is contraindicated at initiation and during the dose-titration phase due to increased risk for TLS. Alternative treatments should be considered. In all patients, if a CYP3A inhibitor must be used, follow the recommendations for managing drug-drug interactions. If a moderate CYP3A inhibitor must be used, the doses must be reduced and patients should be monitored more closely. Refer to SmPC for full details. Grapefruit, Seville oranges and starfruit should be avoided during treatment. P-gp and BCRP inhibitors: Concomitant use of Venclyxto with P-gp and BCRP inhibitors at initiation and during the dose titration phase should be avoided; if a P-gp and BCRP inhibitor must be used, patients should be monitored closely for signs of toxicities. CYP3A inducers: For patients requiring concomitant use of Venclyxto with strong or moderate CYP3A inducers should be avoided. Preparations containing St. John’s wort are contraindicated during treatment with venetoclax. Bile acid sequestrants: Co-administration of bile acid sequestrants with Venclyxto is not recommended as this may reduce the absorption of venetoclax. If a bile acid sequestrant is to be co-administered with Venclyxto, the SmPC for the bile acid sequestrant should be followed to reduce the risk for an interaction, and Venclyxto should be administered at least 4-6 hours after the sequestrant. Warfarin: It is recommended that the international normalised ratio be monitored closely in patients receiving warfarin. Substrates of P-gp, BCRP, and OATP1B1: Co-administration of narrow therapeutic index P-gp, or BCRP substrates with Venclyxto should be avoided. If a narrow therapeutic index P-gp or BCRP substrate must be used, it should be used with caution. For an orally administered P-gp or BCRP substrate sensitive to inhibition in the gastrointestinal tract its administration should be separated from Venclyxto administration as much as possible to minimise a potential interaction. If a statin is used concomitantly with Venclyxto, close monitoring of statin related toxicity is recommended. FERTILITY PREGNANCY AND LACTATION: Women of childbearing potential/ Contraception in females: Women should avoid becoming pregnant while taking Venclyxto and for at least 30 days after ending treatment. Pregnancy: Venclyxto is not recommended during pregnancy and in women of childbearing potential not using highly effective contraception. Breast-feeding: Breast-feeding should be discontinued during treatment with Venclyxto. Fertility: Before starting treatment, counselling on sperm storage may be considered in some male patients. SIDE EFFECTS: See SmPC for full details on side effects. In patients with CLL: Very common side effects (≥1/10): Pneumonia, upper respiratory tract infection, neutropenia, anaemia, lymphopenia, hyperphosphataemia, hyperkalaemia, hypocalcaemia, diarrhoea, vomiting, nausea, constipation and fatigue. Common side effects (≥1/100 to <1/10): Sepsis, urinary tract infection, febrile neutropenia, tumour lysis syndrome, hyperuricaemia, and blood creatinine increased. In patients with AML: Very common side effects (≥1/10): Pneumonia, sepsis, urinary tract infection, neutropenia, febrile neutropenia, anaemia, thrombocytopenia, hypokalaemia, decreased appetite, dizziness, headache, hypotension, haemorrhage, dyspnoea, nausea, diarrhoea, vomiting, stomatitis, abdominal pain, arthralgia, fatigue, asthenia, weight decreased and blood bilirubin increased. Common side effects (≥1/100 to <1/10): Tumour lysis syndrome and cholecystitis. Tumour lysis syndrome (TLS): TLS is an important identified risk when initiating Venclyxto.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; Website: www.hpra.ie. Suspected adverse events should also be reported to AbbVie Limited on 01-4287900.

LEGAL CATEGORY: POM (S1A) MARKETING AUTHORISATION NUMBERS/PRESENTATIONS: 10mg filmcoated tablet, 14 tablets, EU/1/16/1138/002; 50mg film-coated tablet, 7 tablets, EU/1/16/1138/004; 100mg film-coated tablet, 7 tablets, EU/1/16/1138/005;100mg film-coated tablet, 14 tablets, EU/1/16/1138/006; 100mg film-coated tablet, 112 tablets, EU/1/16/1138/007. MARKETING AUTHORISATION HOLDER: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany. Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.

Haematology Association of Ireland, Annual Meeting, Radisson Blu Hotel, Little Island, Cork, 14-15 October 2022

Progress and challenges in B-cell lymphoma

The Haematology Association of Ireland Annual Meeting 2022 heard a lecture delivered by Prof John Leonard, Senior Associate Dean for Innovation and Initiatives at Weill Cornell Medicine, New York Presbyterian Hospital in the US, who delivered a State-of-the-Art lecture titled ‘Progress and challenges in precision therapy for diffuse large B-cell lymphoma’.

In his talk, introduced by Dr Amjad Hayat, Prof Leonard gave an overview of lymphomas and the standard treatment algorithm for the condition. He also presented a round-up of clinical trial data and discussed some of the potential challenges in practising precision medicine. “Sub-setting groups of patients has been very exciting and has a very strong scientific rationale, but unfortunately that has not really translated to the clinic,” said Prof Leonard.

“Now, in parallel, we have returned to strategies that are independent of the cell of origin. One example of what has changed things for the better in diffuse large B-cell lymphoma is CAR T-cell therapy, and you are all familiar with this… this immune effect has great potential for patients with relapsed large B-cell lymphoma. We now have several different CD19-directed CAR T-cell products in diffuse large B-cell lymphoma; they have some differences, but I would argue that they are more similar than they are different. All of these have significant activity in patients with recurrent diffuse large B-cell lymphoma… the response rates are fairly high, and the durability seems to be in patients with recurrent diffuse large B-cell lymphoma. If you get a response, particularly if you get a complete response, you have a good chance of achieving a longer-term remission, and potentially a cure.”

Prof Leonard presented trial data on CAR T-cell therapies and gave the attendees his key takeaway message on precision medicine strategies. “This is an agnostic therapy for cell of origin,” he told the conference. “As far as we know right now, there is not really a subset of patients that does better or worse with CAR T-cells. There are hints, if you look at hun-

dreds of patients… to my mind, much of it, when we talk about the disease itself, it’s a case of ‘if you have better disease, you do better’.”

He briefly discussed other agnostic cell of origin therapies and offered his thoughts on how to make precision medicine strategies more effective. “Patient selection in clinical trials has resulted in, or contributed to, the fact that precision medicine strategies have failed,” said Prof Leonard. He also referenced a study by himself and colleagues published in 2017 to show the limitations of clinical trials in this area.

“So, are we ready for precision therapy in diffuse large B-cell lymphoma?” Prof Leonard concluded. “We have lots of biomarkers that seem to predict outcomes; we have lots of active drugs that seem to be appropriate for subsets. However, these subsets seem to be getting more and more sub-classified, so that’s making it harder. Patient selection – whether we are doing it on purpose or that’s just the way it’s working out – may be an issue in operationalising that, because if you are targeting a less favourable subset, and you are excluding all the less-favourable patients, how are you going to see if your drug makes a difference?

“In parallel, all of these impactful drugs are working, but they are agnostic of subset, and that just tells us that they are imparting immune-based therapies and the immune system may or may not be as related to these subsets of disease. So why is this challenging?” he continued. “It may be challenging because we don’t have the best drugs; it may be challenging because we don’t have an assay that works, and that assay has to be robust and put patients in different subsets, and it has to be fast enough that you can act on it, but patient selection is a big factor in all of this.

“So as we go forward, we need to continue to use control groups, because when we make these retrospective-prospective comparisons, it’s going to make it challenging to interpret. We need better drugs, better biomarker assays, and we need flexibility, particularly in the first cycle, so that we can get more patients on the study, and innovative study design could sort all of this out.”

Quality and variety combined

The Haematology Association of Ireland (HAI) Annual Meeting 2022 featured a packed lineup of topics relevant to haematology professionals and specialists and was notable for the variety of clinical areas covered by national and international experts. Dr Feargal McNicholl, HAI President, spoke with the Medical Independent (MI) at the conference and touched on the overall content and attendance. “We have been discussing this and one of our visiting speakers commented on how impressed he was with the variety and the quality of the topics and the international speakers here,” said Dr McNicholl.

“In haematology, as well as in a number of other specialties, things have become so sub-specialised now that people tend to go to meetings [for content on] their own specific area or their own specific specialty,” he continued. “Haematology is actually a very broad discipline – [it incorporates] coagulation, lymphoma, leukaemia, aplastic anaemia, bone marrow failure syndromes, and chronic

lymphocytic leukaemias, among others.

“What we have had at this conference is a spread of really top quality national and international speakers on stateof-the-art topics,” he continued. “That’s of great benefit to those of us working in those particular areas, but it’s also very informative and important to keep abreast of all these other disciplines that we may be in contact with peripherally, but not centrally, so there has been a lot of learning here for a lot of people.”

Dr McNicholl also commented on the quality and variety of the oral presentations and abstracts at the conference.

“I was extremely impressed with the range and diversity of the orals and abstracts submitted by the people here in Ireland, and the breadth of research that is going on across the whole island,” he told MI

This year was also the first year since 2019 that the Association was able to have its annual meeting face-to-face, and this is a significant factor, Dr McNicholl said. “It’s very important, and it gives us an opportunity to talk to our

The Haematology Association of Ireland Annual Meeting 2022 hosted a stellar array of national and international speakers, including during the President’s Symposium, which was chaired by Dr Feargal McNicholl and Dr Su Maung.

The attendees heard a presentation by Ms Margaret Twohig of NUI Galway, which was titled ‘Trial engineering enhances expanded cord blood NK cell anti-leukaemic activity’. This was followed by a presentation titled ‘Epigenetic dysregulation promotes chemoresistance in acute leukaemia through altered signalling pathway activity’, which was delivered by fellow PhD candidate Mr Thomas Lefeivre of University College Dublin’s Systems Biology Ireland.

In this session, attendees also heard another stimulating presentation by Dr Claire Comerford of Beaumont Hospital in Dublin, who spoke on the topic ‘Von Willebrand Factor in multiple myeloma: Its association with poorer survival and roles in the bone marrow microenvironment’. Dr Comerford was followed by Dr Helen Fogarty of St James’s Hospital in Dublin and RCSI, who delivered a talk on ‘Blood transfusion ameliorates free haem-induced loss of thrombomodulin and endothelial cell activation in paediatric sickle cell anaemia’.

The final part of the session hosted the prestigious Liam O’Connell lecture, which was delivered by Dr Austin Kulasekararaj of King’s College Hospital in London, who chose ‘MDS advances: From biology to therapeutics’ as his lecture subject.

Over the two days, the attendees also enjoyed a comprehensive range of 10-minute oral presentations from doctors in centres from all over Ireland, including from NUI Galway, the RCSI, Queen’s University Belfast, Children’s Health Ireland at Crumlin, St James’s Hospital in Dublin, Children’s University Hospital in Temple Street, and University College Dublin, among others. Each presentation was well attended and the delegates heard talks on a plethora of topics ranging from acute myeloid leukaemia (AML) in children; to bone marrow failure syndromes; AML drug resistance; and immune responses to Covid-19 vaccination in patients with chronic lymphocytic leukemia (CLL), as well as a wide range of other clinical topics.

The other State-of-the-Art lecture was delivered by Dr Othman Al-Sawaf, Haematologist and Medical Oncologist at University Hospital Cologne in Germany, who spoke on the topic ‘CLL: State-of-the-art and future trends’.

peers and discuss common issues… having it all in the one venue where we can attend all the talks together and eat together has been a marvelous facility for networking – it has been a tremendous success and there is a real buzz around the event,” he said.

In terms of his priorities for his Presidency, Dr McNicholl stated: “The real aim has been to try to consolidate the haematology community as we now come out of Covid,” he said. “The re-establishment of those relationships and opportunities for collaboration between departments on the island is important for the benefit of our patients.

“One of the things we have really noticed over the past two-and-a-half years is how important collegiality and contact are for our own ability to practise, and that also benefits our patients,” he concluded. “We are social creatures – what we achieve, we achieve working together, so we are delighted with this meeting. We are delighted with the enthusiasm, with the participation, and we see this as a launch pad for our meeting next year, which will be held in Galway.”

Extremely high standard of clinical presentations and speakers

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

REINFORCE YOUR AML TREATMENT

FOR LONGER REMISSION COMPARED WITH STANDARD OF CARE

MYLOTARG™ significantly extends EFS and RFS* for patients with previously untreated de novo AML compared with the standard of care, chemotherapy with DNR and AraC1,2

▼ MYLOTARG® (gemtuzumab ozogamicin)

PRESCRIBING INFORMATION

Please refer to the Summary of Product Characteristics (SmPC) before prescribing MYLOTARG 5 mg powder for concentrate for solution for infusion.

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

Indications: MYLOTARG is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients aged 15 years and above with previously untreated, de novo CD33positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia (APL). Dosage: Administer under the supervision of a physician experienced in the use of cancer therapy and in an environment where full resuscitation facilities are immediately available. MYLOTARG should be used only in patients eligible to receive intensive induction chemotherapy. The recommended induction dose of MYLOTARG is 3 mg/m 2/dose (up to a maximum of one 5 mg vial) infused over a 2 hour period on Days 1, 4, and 7 in combination with DNR 60 mg/m2/day infused over 30 minutes on Day 1 to Day 3, and AraC 200 mg/m2/day by continuous infusion on Day 1 to Day 7. If a second induction is required, DNR should be infused at a dose of 35 mg/m2/day on Day 1 to Day 2 and AraC at a dose of 1 g/m2/every 12 hours on Day 1 to Day 3. MYLOTARG should not be administered during a second induction. For patients experiencing a complete remission (CR) following induction, defined as fewer than 5% blasts in a normocellular marrow and an absolute neutrophil count (ANC) of more than 1.0 × 109 cells/L with a platelet count of 100 × 109/L or more in the peripheral blood in the absence of transfusion, up to 2 consolidation courses of intravenous DNR (60 mg/m2 for 1 day [first course] or 2 days [second course]) in combination with intravenous AraC (1 g/m2 every 12 hours, infused over 2 hours on Day 1 to Day 4) with intravenous MYLOTARG (3 mg/m2/dose infused over 2 hours up to a maximum dose of one 5 mg vial on Day 1) are recommended. Dose modification of MYLOTARG may be required based on individual safety and tolerability.

References

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

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

Appropriate measures to help prevent the development of tumour lysis-related hyperuricaemia, such as hydration, administration of antihyperuricemics (e.g., allopurinol) or other agents for treatment of hyperuricaemia (e.g., rasburicase) must be taken.

Hepatotoxicity: Hepatotoxicity, including severe, life-threatening, and sometimes fatal hepatic failure and VOD/SOS have been reported in patients treated with MYLOTARG.

Adult patients who received MYLOTARG as monotherapy, either before or after a haematopoietic stem cell transplant (HSCT), and patients with moderate or severe hepatic impairment are at increased risk for developing VOD. Signs and symptoms of VOD/SOS should be monitored closely in all patients. For patients who develop abnormal liver tests, more frequent monitoring of liver tests and clinical signs and symptoms of hepatotoxicity is recommended. For patients who

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

2. Pfizer Cytarabine Summary of Product Characteristics.

PP-MYL-IRL-0094

Date of preparation February 2022

proceed to HSCT, close monitoring of liver tests is recommended during the post-HSCT period, as appropriate. Management of signs or symptoms of hepatic toxicity may require a dose interruption, or discontinuation of MYLOTARG (see section 4.2). In patients who experience VOD/SOS, MYLOTARG should be discontinued and patients treated according to standard medical practice. Myelosuppression/cytopenias : Neutropenia, thrombocytopenia, anaemia, leukopenia, febrile neutropenia, lymphopenia, and pancytopenia, some life-threatening and some with complications, were reported. Blood counts should be monitored prior to dosing and signs of myelosuppression should be monitored during treatment. Infusion related reactions: Infusion should be interrupted immediately for patients who develop evidence of severe reactions, especially dyspnoea, bronchospasm, or clinically significant hypotension. Patients should be monitored until signs and symptoms completely resolve. Discontinuation of treatment should be strongly considered for patients who develop signs or symptoms of anaphylaxis, including severe respiratory symptoms or clinically significant hypotension. The efficacy of MYLOTARG has been shown in AML patients with favourable- and intermediate-risk cytogenetics, with uncertainty regarding the size of the effect in patients with adverse cytogenetics (see smPC section 5.1). For patients being treated with MYLOTARG in combination with daunorubicin and cytarabine for newly diagnosed de novo AML, when cytogenetics testing results become available it should be considered whether the potential benefit of continuing treatment with MYLOTARG outweighs the risks for the individual patient (see smPC section 5.1) Fertility, pregnancy and lactation: Women of childbearing potential receiving this medicinal product, or treated male partners should use effective contraception during therapy and for at least 7 months or 4 months after completing therapy for females and males, respectively. There are no or limited amount of data from the use of MYLOTARG in pregnant women. Non-clinical studies have shown reproductive toxicity.

MYLOTARG must not be used during pregnancy unless the potential benefit to the mother outweighs the potential risks. The potential hazard to the foetus of MYLOTARG treatment must be explained to pregnant women, patients becoming pregnant while receiving treatment, or treated male partners of pregnant women. Because of the potential for adverse reactions in breast-fed children, women must not breast-feed during treatment

with MYLOTARG and for at least 1 month after the final dose. Based on non-clinical findings, male and female fertility may be compromised by treatment with MYLOTARG. Driving and operating machinery: MYLOTARG may cause fatigue and patients should exercise caution when driving or using machines. Undesirable effects: The overall safety profile of MYLOTARG is based on data from patients with acute myeloid leukaemia from the combination therapy study ALFA-0701, monotherapy studies, and from post-marketing experience. In the combination therapy study, safety data consisting of selected treatment emergent adverse events (TEAEs) considered most important for understanding the safety profile of MYLOTARG consisted of all grades haemorrhages, all grades VOD, and severe infections. The most common adverse reactions (> 30%) in the combination therapy study were haemorrhage and infection. In patients who received MYLOTARG in the combination therapy study ALFA-0701, clinically relevant serious adverse reactions were hepatoxicity including VOD/ SOS (3.8%), haemorrhage (9.9%), severe infection (41.2%), and tumour lysis syndrome (1.5%). See relevant SmPC (Table 5) for full details on specific comprehensive list of AEs for combination therapy. Instructions for reconstitution and dilution: Use appropriate aseptic technique for the reconstitution and dilution procedures. Following reconstitution and dilution, the solution should be protected from light and should be used immediately. If the product cannot be used immediately, the diluted solution may be stored up to 18 hours in a refrigerator (2°C–8°C) from the time of initial vial puncture with not more than 6 hours at room temperature (below 25°C). Legal Category: S1A. Marketing

Authorisation Number: EU/1/18/1277/001 – 5mg 1 vial. The Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@ pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500.

▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Last revised: 11/2020

Ref: ML 4_0

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

Haematology Association of Ireland, Annual Meeting, Radisson Blu Hotel, Little Island, Cork, 14-15 October 2022

SHINGRIX demonstrated >90% efficacy against shingles in all age groups aged 50 years of age or older, based on pooled data from two large, phase 3, randomised, controlled, clinical trials.2,3

Shingrix powder and suspension for injection in vials

(Please refer to SmPC before prescribing) Composition: After reconstitution, one dose (0.5 mL) contains: Varicella Zoster Virus glycoprotein E antigen1,2 50 micrograms. (1 adjuvanted with AS01B containing: plant extract Quillaja saponaria Molina, fraction 21 (QS-21) 50 micrograms, 3-O-desacyl-4’-monophosphoryl lipid A (MPL) from Salmonella minnesota 50 micrograms, 2 glycoprotein E (gE) produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology). Therapeutic indications: Prevention of herpes zoster (HZ) and post-herpetic neuralgia (PHN) in adults 50 years of age or older and in adults 18 years of age or older at increased risk of HZ. The use of this vaccine should be in accordance with official recommendations. Posology and method of administration: For intramuscular injection only, preferably in the deltoid muscle. Primary Vaccination: Initial dose of 0.5 ml followed by a second 0.5 ml dose 2 months later. For flexibility the 2nd dose can be administered between 2 and 6 months after the first dose. For subjects who are or might become immunodeficient or immunosuppressed and whom would benefit from a shorter vaccination schedule, the 2nd dose can be given 1 to 2 months after the initial dose. Booster doses: need not established. Contraindications: Hypersensitivity to the active substances or any of the excipients. Special warnings and precautions for use: The name and the batch number of the administered product should be clearly recorded. Appropriate medical treatment and supervision should be readily available in case of an anaphylactic event. Administration of Shingrix should be postponed in subjects suffering from an acute severe febrile illness. However, the presence of a minor infection, such as cold, should not result in deferral. A protective immune response may not be elicited in all vaccinees. Never administer intravascularly or intradermally; subcutaneous administration not recommended as it may lead to an increase in transient local reactions. Caution in individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following intramuscular administration. Syncope can occur following, or before any vaccination as a psychogenic response. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints. There are no data to support replacing a dose of Shingrix with another HZ vaccine. There are limited data to support the use of Shingrix in individuals with a history of HZ and in frail individuals including those with multiple comorbidities. The benefits and risks of HZ vaccination should be weighed on an individual basis. Interactions: Shingrix can be given concomitantly with unadjuvanted inactivated seasonal influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPV23) or reduced antigen diphtheria-tetanusacellular pertussis vaccine (dTpa). The vaccines should be administered at different injection sites. Fertility, pregnancy and lactation: There were no effects on male or female fertility in animal studies. It is preferable to avoid the use of Shingrix during pregnancy. The effect on breast-fed infants of administration of Shingrix to their mothers has not been studied. It is unknown whether Shingrix is excreted in human milk. Effects on ability to drive and use machines: Shingrix may have a minor influence on the ability to drive and use machines in the 2-3 days following vaccination. Undesirable effects: Very common (≥1/10): Headache, GIT symptoms, myalgia, injection site reactions, fatigue, chills, fever. Common (≥1/100 to <1/10): injection site pruritus, malaise. Uncommon (≥1/1000 to <1/100): lymphadenopathy, arthralgia. Rare (≥1/1000 to <1/100): Hypersensitivity reactions. Legal Category: POM A. Marketing Authorisation Number: EU/1/18/1272/001. Marketing Authorisation Holder: GlaxoSmithKline Biologicals

S.A., Rue de l’institut 89, B-1330 Rixensart, Belgium. Further information is available from GlaxoSmithKline (Ireland) Ltd. 12 Riverwalk, Citywest Business Campus, Dublin 24. Telephone: 014955000. Code: PI-7757. Date of preparation: March 2021.

1800 244 255.

Update on EMERGE trial at the Irish Endocrine Society meeting

The Annual Meeting of the Irish Endocrine Society (IES) took place in the Pillar Centre at the Mater Misericordiae University Hospital on 1112 November.

At the meeting, President of the IES, Prof Fidelma Dunne, delivered an update on the EMERGE trial, which assesses metformin administered to pregnant women with gestational diabetes mellitus (GDM).

EMERGE’s full title is ‘a randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects’.

The current first-line treatment for GDM is medical nutritional therapy with exercise in all cases, and 40 per cent of women are prescribed insulin. However, insulin can cause gestational weight gain, less successful breastfeeding and increased delivery by Caesarean section.

While metformin is recommended by NICE [National Institute for Health and Care Excellence] guidelines as a first-line treatment, Prof Dunne said there are still some gaps in the research.

“Our question was very simple,” she said. “Among pregnant women with GDM, does the addition of metformin to usual care reduce the need for insulin or fasting glucose rate greater than 5.1 [mmol/L] at week 32 or 38 [primary outcomes]? Does it reduce excessive maternal weight gain, and neonatal and maternal morbidities [secondary outcomes]? And is the cost of care reduced?”

Prof Dunne told the Medical Independent that the trial

has now been completed.

“We hope to have the results of the trial in the first quarter of next year and we will send a letter to all the women telling them about the outcome of the study,” she said.

“We will also be doing a follow-up of the mothers and their babies and we'll be in contact with them for their participation again.”

In total, 45.5 per cent of the study population required insulin. 13 per cent reached the glucose fasting level at week 32 and 10 per cent at week 38, both not on insulin.

The combined primary outcome shows that 315 or 60 per cent of the women "required insulin or had a fasting glucose rate of greater than 5.1".

The study also collected neonatal outcomes, showing birthweight prematurity and the number requiring neonatal intensive care unit attendance. It experienced a low drop-out rate and “excellent” adherence to the medication (92 per cent). The results presented were based on a total combined group to maintain blinding before publication.

Prof Dunne concluded: “If EMERGE is positive, it will change global clinical practice by providing evidence to support early active management with metformin in a broader GDM population.”

To conclude the meeting, Prof Dunne presented the O’Donovan Award for the best oral presentation to Dr Cliona O’Donnell. Dr O’Donnell presented her and her team's findings on the effect of glucagon-like-peptide-1 analogues (a class of glucose-lowering drugs) on metabolic activity in adipose tissue. They found that the upregulation of thermogenesis by the drugs can contribute to weight loss.

The second prize for the best poster, the Montgomery medal, was given to Dr Robert Lyons, for what Prof Dunne called his “ingenious” use of the MiniMed 780G insulin pump containing the drug teriparatide to treat symptomatic hypoparathyroidism in a patient with Barakat syndrome.

Diagnosing diabetes beyond type 1 and type 2

Delegates at the Irish Endocrine Society Annual Meeting were updated on the importance of considering different types of diabetes when diagnosing and treating patients.

Professor of Molecular Medicine at the University of Exeter, UK, Prof Andrew Hattersley, delivered the Hadden Lecture at the meeting.

The keynote address was entitled ‘Precision diabetes: The next advance in patient care’.

He told the Medical Independent (MI): “Not all diabetes is the same, and it's not all type 1 [and] type 2. And so you need to find the unusual types because they need different treatments.”

“The reason for thinking about other different types of diabetes is: Does it make treatment better? Because if it doesn't, it doesn't really matter to the patient. And I think the patient and their treatment is what everything should hinge on.”

In his presentation, Prof Hattersley showed how, through using genetics and precision medicine, subtypes of diabetes can be correctly defined and diagnosed to improve clinical care.

Maturity-onset diabetes of the young (MODY), which is caused by a gene mutation, is one such subtype of diabetes.

The genetic subtypes of MODY present as different clinical features and lead to different clinical treatments.

Prof Hattersley said: “All of that work [to stratify the MODY subtypes] was finished in 2002. And it's taken since then to get it adopted clinically. But I think we're finally managing it.”

Terming it “a success story for precision medicine”, Prof Hattersley described four subtypes of MODY, each of which has a different aetiology and treatment.

The stratification of neonatal diabetes subtypes is similar, according to the professor. Neonatal diabetes occurs within the first six months of life due to a genetic mutation.

Currently, 31 genetic subtypes of neonatal diabetes can be identified.

Due to this testing, “every single case of neonatal diabetes is getting a genetic diagnosis”, according to the professor.

However, he said that there was the need to look beyond genetics for type 2 diabetes. “We know that there are 400 genetic SNPs [genetic variation in DNA] that predispose [patients] to type 2 diabetes, and even more than that predisposed to obesity,” Prof Hattersley told delegates. “And what that means is there's not a single disorder, there's not a single gene that causes type 2 diabetes.

“You've got to do something other than genetics.”

Prof Hattersley said it was vital to assess clinical features, such as BMI, in clusters of patients, and “working out on average” as to who does best on which drugs. He also stressed the importance of patient preference.

In a study due to be published in the Nature Medicine journal, Prof Hattersley and colleagues studied 458 diabetes patients receiving three different medications. Each patient took one medication for 16 weeks before changing to a new medication, in a double-blind test. Patients were asked their preference for each drug.

The study found that drug preference was associated with lower HbA1c (blood glucose levels) and fewer side-effects.

He told MI: “I think it works very well in type 2 diabetes, where the drugs are all about the same on average…. When there's one drug that's definitely better than the other, then we shouldn't be doing this. But when it is not certain which is the best one, then the best person to choose is the patient.”

Professor of Paediatrics and Child Health and Director at the Centre for Rare Disease Studies at the University of Birmingham, UK, Prof Timothy Barrett, also gave a lecture over live video feed.

The title of Prof Barrett’s talk at the meeting was, ‘The changing patterns of childhood diabetes: Beyond type 1.’ His paediatric keynote lecture covered emerging treatment and the changing diagnostic challenges of diabetes.

He said: “Childhood diabetes is not just a practical management issue, but it really is a significant diagnostic challenge…. [If there is] any doubt in diagnosis, always treat as type 1 diabetes first and give insulin and we can revise the diagnosis later.”

BRING PROTECTION TO LIFE

BY REDUCING THE RISK OF THE COMPOSITE OF DECLINING KIDNEY FUNCTION (BY ≥ 50%), ESKD, AND RENAL OR CV DEATH IN CONJUNCTION WITH OTHER CKD THERAPIES WHEN COMPARED TO PLACEBO*1

FORXIGA IS INDICATED IN ADULT PATIENTS FOR THE TREATMENT OF CKD.2

treatment

GFR mL/min/1.73m2

FORXIGA 10 mg

Once daily

No titration required except in patients with severe hepatic impairment

Applicable for CKD, HFrEF, or T2D.2

*The DAPA-CKD study was an international, multicentre, randomised, double-blind, placebo-controlled study. In DAPA-CKD, the primary endpoint showed that FORXIGA in conjunction with other CKD therapies reduced the relative risk of the composite endpoint of ≥50% sustained decline in eGFR, reaching ESKD, and renal or CV death by 39% (5.3% ARR) vs placebo with other CKD therapies in 4304 adult patients with CKD with an eGFR of 75 to 25 mL/ min/1.73m2 and albuminuria (UACR ≥ 200 and ≤ 5000 mg/g) (median follow-up of 2.4 years; 9.2% vs 14.5%; HR 0.61; 95% CI (0.51 - 0.72; p<0.001).1 ESKD defined as sustained eGFR < 15 mL/min/1.73m2, chronic dialysis treatment or receiving a renal transplant. DAPA-CKD was stopped early due to efficacy benefit, because of the unplanned early stop, the secondary endpoints are considered nominally significant; Secondary endpoints showed that FORXIGA in conjunction with other CKD therapies reduced the relative risk of the composite of CV death or hHF by 29% (1.8% ARR: HR 0.71; 95% CI, 0.55 to 0.92; nominal p=0.009) and also reduced the relative risk of all-cause mortality by 31% (2.1% ARR; HR 0.69; 95% CI, 0.53 to 0.88; nominal p=0.004) vs placebo with other CKD therapies. There were comparable rates of the individual component of CV death, FORXIGA vs placebo (3.0% vs 3.7%; HR 0.81; 95% CI, 0.58, 1.12)1

The overall safety profile of dapagliflozin in patients with chronic kidney disease was consistent with the known safety profile of dapagliflozin.2 ©AstraZeneca 2022. All Rights Reserved.

ABRIDGED PRESCRIBING INFORMATION

FORXIGA® (dapagliflozin) 5MG & 10MG FILMCOATED TABLETS.

Consult Summary of Product Characteristics (SmPC) before prescribing.

Indications: Adults and children aged 10 years and above: Type 2 diabetes mellitus: For the treatment of insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance, or in addition to other medicinal products for the treatment of type 2 diabetes.

Adults: Heart Failure: Indicated in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction. Chronic kidney disease: Indicated in adults for the treatment of chronic kidney disease.

Presentation: Film-coated tablets. 5mg or 10mg of dapagliflozin (as propanediol monohydrate). Each 5mg tablet contains 25mg of lactose. Each 10mg tablet contains 50mg of lactose.

Dosage and Administration: Adults: Type 2 diabetes mellitus: The recommended dose is 10mg once daily. Consider a lower dose of insulin or insulin secretagogue such as a sulphonylurea when used in combination with dapagliflozin to reduce the risk of hypoglycaemia.

Children and adolescents: No dose adjustment in children aged 10 years and above. No safety and efficacy data available for children below 10 years of age. Heart Failure: The recommended dose is 10mg once daily. Chronic kidney disease: The recommended dose is 10 mg once daily. Children and adolescents: <18 years: Safety and efficacy not yet established. Elderly: ≥65 years: No dose adjustment is recommended based on age. Renal impairment: No dose adjustment is required based on renal function. Due to limited experience, it is not recommended to initiate treatment with dapagliflozin in patients with GFR < 25 mL/min. If GFR falls below 45 mL/min, additional glucose lowering treatment should be considered in patients with diabetes mellitus if further glycaemic control is needed. Mild or moderate hepatic impairment: No dose adjustment. Severe hepatic impairment: Starting dose of 5mg is recommended, if well tolerated, dose may be increased to 10mg.

Method of administration: Forxiga can be taken orally at any time of day with or without food. Tablets should be swallowed whole.

Contraindications: Hypersensitivity to dapagliflozin, or excipients.

Warnings and Precautions: Renal impairment: Due to limited experience, it is not recommended to initiate treatment with dapagliflozin in patients with GFR < 25 mL/min. The glucose lowering efficacy of dapagliflozin is dependent on renal function, and is reduced in patients with GFR < 45 mL/min and is likely absent in patients with severe renal impairment. Hepatic impairment: Exposure is increased in patients with severe hepatic impairment. Use in patients at risk of volume depletion and/or hypotension: Dapagliflozin increases diuresis which may lead to a modest decrease in blood pressure, it may be more pronounced in patients with very high blood glucose concentrations. Exercise caution in patients for whom a dapagliflozin induced drop in blood pressure could pose a risk, such as patients on anti hypertensive therapy with a history of hypotension or elderly patients. Careful monitoring of volume status and electrolytes is recommended in conditions leading to volume depletion, such as acute gastrointestinal illness. In volume depleted patients temporary interruption of dapagliflozin is recommended until volume depletion is corrected. Diabetic ketoacidosis (DKA): Rare cases of DKA, including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including dapagliflozin. In a

number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14mmol/L (250mg/dL). The risk of DKA must be considered in the event of nonspecific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level. In patients where DKA is suspected or diagnosed, dapagliflozin treatment should be stopped immediately. Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of blood ketone levels is preferred to urine. Treatment with dapagliflozin may be restarted when the ketone values are normal and the patient’s condition has stabilised. Before initiating dapagliflozin, factors in patient history that may predispose to ketoacidosis should be considered. Patients who may be at higher risk of DKA include patients with a low beta cell function reserve (e.g. patients with low C peptide or latent autoimmune diabetes in adults (LADA) or patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin requirements due to acute medical illness, surgery or alcohol abuse. SGLT2 inhibitors should be used with caution in these patients. Restarting SGLT2 inhibitor treatment in patients experiencing a DKA while on SGLT2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved. Dapagliflozin should not be used for treatment of patients with type 1 diabetes. Necrotising fasciitis of the perineum (Fournier’s gangrene): Postmarketing cases have been reported in female and male patients taking SGLT2 inhibitors. Urgent surgical intervention and antibiotic treatment is required. Advise patients to seek medical attention if they experience a combination of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Either uro-genital infection or perineal abscess may precede necrotising fasciitis. If suspected, discontinue Forxiga and institute prompt treatment (including antibiotics and surgical debridement). Urinary tract infections: Temporary interruption of dapagliflozin should be considered when treating pyelonephritis or urosepsis. Elderly (≥65 years): Elderly patients are more likely to have impaired renal function, be treated with medicines such as anti-hypertensives or diuretics, and be at a greater risk of volume depletion. Cardiac failure: Experience with dapagliflozin in NYHA class IV is limited. Chronic kidney disease: There is no experience with dapagliflozin for the treatment of chronic kidney disease in patients without diabetes who do not have albuminuria. Patients with albuminuria may benefit more from treatment with dapagliflozin. Lower limb amputations: Counsel patients with diabetes on routine preventative foot care as an increase in cases of lower limb amputation (primarily of the toe) has been observed in long term, clinical studies in type 2 diabetes mellitus with SGLT2 inhibitors. Urine laboratory assessments: Patients will test positive for glucose in the urine due to mechanism of action. Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take Forxiga.

Drug Interactions: Diuretics: Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension. Insulin and insulin secretagogues: Consider a lower dose of insulin or insulin secretagogue when used in combination with dapagliflozin to reduce the risk of hypoglycaemia. Interference with 1,5 AG assay: Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5 AG are

unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors. Alternative methods should be used. Interference with lithium: Dapagliflozin may increase renal lithium excretion and the blood lithium levels may be decreased. Serum concentration of lithium should be monitored more frequently after dapagliflozin initiation and dose changes. Please refer the patient to the lithium prescribing doctor in order to monitor serum concentration of lithium. Pregnancy and Lactation: Not recommended during the second and third trimesters of pregnancy. Treatment should be discontinued when pregnancy is detected. Do not use whilst breast-feeding.

Ability to Drive and Use Machines: Alert patients on the risk of hypoglycaemia when dapagliflozin is used in combination with a sulphonylurea or insulin.

Undesirable Events: Consult SmPC for full list of side effects. Very common (≥1/10): Hypoglycaemia (when used with SU or insulin). Common (≥1/100 to <1/10): Vulvovaginitis, balanitis and related genital infections, urinary tract infection, dizziness, rash, back pain, dysuria, polyuria, haematocrit increased, creatinine renal clearance decreased during initial treatment, dyslipidaemia. Uncommon (≥1/1,000 to < 1/100): Fungal infection, volume depletion, thirst, constipation, dry mouth, nocturia, vulvovaginal pruritus, pruritus genital, blood creatinine increased during initial treatment, blood urea increased, weight decreased. Rare (≥ 1/10,000 to < 1/1,000): Diabetic ketoacidosis (when used in type 2 diabetes mellitus). Very Rare (< 1/10,000): Angioedema, necrotising fasciitis of the perineum (Fournier’s gangrene), Tubulointerstitial nephritis.

Legal Category: Product subject to prescription which may be renewed (B).

Marketing Authorisation Number: EU/1/12/795/002; EU/1/12/795/007.

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

Further product information available on request from: AstraZeneca Pharmaceuticals (Ireland) DAC, College Business and Technology Park, Blanchardstown Road North, Dublin 15. Tel: +353 1 609 71 00.

FORXIGA is a trademark of the AstraZeneca group of companies.

Date of API preparation: 07/2022 Veeva ID: IE-4049

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

References:

1. Heerspink HJL et al. N Engl J Med. 2020;383(15):1436–1446.

2. FORXIGA 10 mg film-coated tablets. Summary of product characteristics.

ARR = absolute risk reduction; CKD = chronic kidney disease; CV = cardiovascular; DAPA-CKD = Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease; eGFR = estimated glomerular filtration rate; ESKD = end-stage kidney disease; hHF = hospitalisation for heart failure; HR = hazard ratio. HFrEF = heart failure with reduced ejection fraction; T2D = type 2 diabetes

Irish Endocrine Society, Annual Meeting, Mater Hospital, Dublin, 11-12 November 2022

McKenna Lecture addresses need to fortify iodine in Irish food products

The title of this year’s Irish Endocrine Society (IES) Annual Meeting McKenna Lecture was ‘Iodine – a public health triumph going sour’.

It was delivered by Dr Karen Mullan, Consultant Endocrinologist at the Belfast Health and Social Care Trust in Northern Ireland.

In the keynote lecture, Dr Mullan covered the mild iodine deficiencies in Irish populations, the causes, the implications for mothers and their babies, and how to best address this issue.

She discussed several studies showing iodine levels in populations around Ireland to be within or just above a mild deficiency. Figures from the Iodine Global Network in 2021 show iodine levels to be much lower than the US, Switzerland, India, and Australia, among other countries.

“I think that there's enough evidence now to suggest that we are deficient,” Dr Mullan told the Medical Independent . “UK and Ireland are in the minority now of countries that do not fortify [food products with iodine]…. We’re really behind the curve.”

Dr Mullan said this is important for “our women and our babies” as iodine deficiency is a contributor to low IQ. A 2013 analysis of results from the Avon Longitudinal Study of Parents and Children showed a link between the low IQ of children and low iodine levels in their mothers’ first trimester, she said in her lecture. High levels of iodine are often linked to a good intake

Progress of TEAMed-5 project discussed

Diagnostic practices in treating thyroid eye disease (TED) in Northern Ireland are improving following the initial steps of a quality improvement programme.

Commencing in the UK in 2020, the Thyroid Eye Disease Amsterdam Declaration Implementation Group (TEAMed-5) has been in place in Northern Ireland since January 2022.

The aim of the group is to standardise care for patients with TED.

At the Irish Endocrine Society Annual Meeting, Dr Muhammad Aamir Shahzad, Endocrinology SpR, presented the early data of the first 100 patients evaluated in the first eight months of the programme in Northern Ireland.

With TEAMed-5, the antibody associated with TED (TSH receptor) was screened more often in hypothyroidism presentations than the previous 2019 audit in Belfast (92 per cent versus 81 per cent). Of those, 66 per cent of patients were positive for TSH receptor antibodies and documentation of screening for TED was recorded in 74 per cent of patients.

However, early warning score cards and patient information

sheets were provided to 32 per cent of patients positive for TSH receptor antibodies. Smoking status and counselling for prevention of TED were documented in 43 per cent.

Dr Shahzad said in his presentation: “This early QI data indicates good levels of diagnostic practice, but improvement in screening and prevention are required.”

The programme referred four patients with significant eye diseases to specialists and under TEAMed-5 a new multidisciplinary clinic is planned to open in Northern Ireland in January 2023.

The aim of TEAMed-5 is to switch from an expectant to a pre-emptive approach for treating TED. The sooner the patient is picked up, the easier it is for trajectory of disease severity to be reduced.

However, recent data shows that in the UK, a patent can be waiting up to 27 months to access specialist treatment.

“We are quite excited because this is a study of its own… to pick up the thyroid eye disease patient very early, and treat them accordingly,” Dr Shahzad told the Medical Independent The TEAMed-5 study is a Europe-wide study.

of milk, yoghurt, and white fish. However, changes in farming practices, the dissolution of the milk marketing board in 2002, and a rise in “alternative” plant-based milk add to the decrease in iodine levels, according to Dr Mullan.

Cow’s milk intake has declined in women and girls, and “young women don't drink any more than a quarter of a pint per day”. Plant-based milk alternatives are much lower in iodine than conventional and organic cow milk. There is also low availability of iodised salt in supermarkets on the island of Ireland, according to a 2019 study from the European Journal of Clinical Nutrition, which Dr Mullan was involved in.

She also contributed to a study, published in the British Medical Journal in 2019, on the education of 200 pregnant women from Northern Ireland on their iodine requirements. They found 80 per cent did not know their iodine requirement increased during pregnancy, and only 9 per cent identified dairy as a source of iodine in their diet.

“We can't blame them,” Dr Mullan told delegates at the IES Annual Meeting. “The Northern Ireland pregnancy book has no mention of it.”

Looking forward, Dr Mullan highlighted a recently commenced study that will look at the effect of giving milk and advice to pregnant women compared to just giving advice on iodine levels.

Dr Mullan was also involved in the TEAMed-5 study.

research

Patient-centred research is important to provide a better biopsychosocial understanding of patients’ experiences living with diabetes and hypoglycaemia, according to Clinical Research Fellow at King’s College London diabetes research group, Dr Patrick Divilly.

Speaking to the Medical Independent (MI) at the Irish Endocrine Society Annual Meeting, Dr Divilly said: “It is really important that our research is focused on the person living with diabetes, and that we better understand their experiences and what's going on in their lives in terms of hypoglycaemia.”

Dr Divilly presented the results to date from a 10-week Hypo-METRICS study, comprising 602 participants – those with type 1 diabetes and insulin-treated type 2 diabetes – across nine sites in five countries. The study aims to “provide an evidence-based definition of CGM [continuous glucose monitoring] hypoglycaemia and further understanding of the clinical, psychological, and health economic impacts of hypoglycaemia”.

Participants wore a blinded CGM device to record their hypoglycaemia by a sensor. They also self-recorded hypoglycaemia to the Hypo-METRICS smartphone app in real-time.

hear

Recruitment has finished, but the study is not fully complete, Dr Divilly told MI The results presented showed that the use of CGM reduces the proportion of ‘asymptomatic hypoglycaemia’. This was where hypoglycaemia was detected by the sensor with no associated person-reported hypoglycaemia. A high percentage of impaired (where participants are unaware of) hypoglycaemia events in insulin-treated type 2 diabetes participants were also asymptomatic.

Dr Divilly told MI: “This study has been really driven by our patient advisory committee. They were instrumental in designing the study and helping us implement the study. And the results are really designed more so for them.”

A greater understanding of the impact of hypoglycaemia on people’s lives also helps to apply for funding for further technologies and treatments, he said.

Dr Divilly said that he anticipates in the future that most people living with type 1 and insulin-treated type 2 diabetes “will be on some form of diabetes tech”.

Asked about older patients with diabetes, Dr Divilly said: “Our data completion by our over-65s population was better than our younger population…. I think the bigger issue is people who are from socially deprived backgrounds getting left behind.”

Patient-focused

important when treating diabetes, endocrinologists

Parkinson’s disease: Diagnostic and therapeutic strategies

Idiopathic Parkinson’s disease (IPD) is a common, progressive, neurodegenerative disease which affects 1 per cent of the population over 60

Successful completion of this module will earn you 2 CPD credits

SPORTS QUIZ WIN €50 28 November 2022

Q1 Who is the new snooker UK champion?

Q2 How many tournaments did Padraig Harrington win in this season’s Challenge Tour?

Q3 Which soccer team has recently been accepted into the League of Ireland First Division from next season?

Q4 Who are the 2022 baseball World Series champions?

Q5 Who will replace Mick Schumacher in Team Haas for next year’s Formula One championship?

Q6 Which GAA county play their home fixtures in the Gaelic Grounds?

CROSSWORD COMPETITION

28 November 2022

The winner of the 7 November 2022 Sporting Quiz Competition is Dr Muiris Fitzgerald, Co Dublin The winner of the 7 November 2022 Crossword is Margaret Malone, Co Tipperary

Q1 Who are the 2022 League of Ireland Premier Division champions? A: Shamrock Rovers

Q2 Who captained Ireland to a famous victory over England at the Cricket T20 World Cup? A: Andrew Balbirnie

Q3 Who was named men’s player of the year at the Guinness Rugby Writers awards? A: Josh Van der Flier

Q4 How many All-Star Football Team awards did All-Ireland champions Kerry win? A: 7

Q5 Name the golfer who returned to the world number one slot last month, for the first time since 2020? A: Rory McIlroy

Q6 Which nation will the Republic of Ireland women’s soccer team face in their opening fixture at next summer’s World Cup? A: Australia

DOWN

1 Opposite of fail (4)

2 Figure with four equal straight sides (6)

3 Have an effect on another (9)

4 Neither gas nor solid (6)

6 Complete (6)

7 Plan of action (8)

11 Cyclone (9)

12 Pertaining to the body (8)

13 Peak (6)

14 End a dispute (6)

15 Come into view (6)

17 Not at home (4)

THE RICH, STORIED HISTORY OF ANAESTHESIA IN IRELAND

TITLE: Safety As We Watch: Anaesthesia in Ireland 1847-1998

AUTHORS: Declan Warde, Joseph Tracey, and John Cahill

PUBLISHER: Eastwood Books

REVIEWER: Prof Brendan Kelly

On 1 January 1847, John MacDonnell, surgeon to the Richmond Hospital, Dublin, successfully amputated the arm of 18-year-old Mary Kane without her experiencing any pain. This was the first administration of a general anaesthetic in Ireland. The Pilot , a Dublin newspaper, reported that “the patient, on recovering, stated that she had not been sensible to the slightest pain and had no recollection whatever of the operation”.

MacDonnell had no doubt about the importance of this event. He conveyed his enthusiasm in a case report in The Dublin Medical Press :

“I regard this discovery as one of the most important of the century. It will rank with vaccination and other of the greatest benefits that medical science has bestowed upon man. It adds to the long list of those benefits, and establishes another claim, in favour of that science, upon the respect and gratitude of mankind.”

MacDonnell was right. Since 1847, anaesthesia has evolved from an apprentice-based craft into a highly technical specialty, essential not only in the operating theatre, but across a growing range of medical settings. Anaesthesia transformed the way surgery is practised, impacted on virtually all areas of clinical work, and continues to open new therapeutic doors. The growth of anaesthesia is one of the most remarkable achievements in the history of medicine, along with vaccination and penicillin.

Safety as we watch presents a history of anaesthesia in Ireland. The book’s title is an English translation of the Latin motto on the coat of arms of the College of Anaesthesiologists of Ireland (CAI): Salus dum Vigilamus . This is a fitting name for a beautiful book that describes the individuals and institutions that led the development of anaesthesia in this country from 1847 to the foundation of the CAI in 1998. The book recounts a rich, storied history, covering the original discovery of anaesthesia, the achievements of MacDonnell and his contemporaries, and the subsequent establishment of anaesthesia as a core branch of medicine in Ireland.

I was especially captivated by the early history of anaesthesia in Ireland. The authors have an encyclopaedic knowledge of 19th Century medical literature, which they use to good effect, with vivid portraits of people, places, and events in medical history. The chapter on women entering the field, by Declan Warde, is particularly interesting and a valuable resource for historians

across several disciplines, not just medicine.

Moving to the 20th Century, the book outlines the foundation of the Association of Anaesthetists of Great Britain and Ireland in 1932, the conjoint Diploma in Anaesthetics in 1942, and the establishment of the Faculty of Anaesthetists (RCSI) in 1960. This part of the book will be especially interesting to readers who are involved with training structures and professional organisation in any branch of medicine, not just anaesthesia. There are transferrable lessons here about managing professional groups and developing training programmes that are reliable, robust, and open to change.

The authors of Safety as we watch bring a wealth of knowledge and expertise to their task. Declan Warde was appointed Consultant Paediatric Anaesthetist at

Temple Street Children’s University Hospital in 1986. Joseph Tracey was Director of the National Poisons Information Centre at Jervis Street/Beaumont Hospital for 25 years. John Cahill was appointed Consultant Anaesthetist at the Mercy Hospital Cork in 1984, and was elected to council of the CAI. Together, they have produced a valuable, involving book that reflects an inspiring history, which has been largely neglected to date.

Safety as we watch tells the story as far as 1998, when the CAI was founded. Located at 22 Merrion Square, the College has thrived over the past quarter century. As a recognised training body, it is responsible for setting training standards and for the organisation, supervision, and counselling of doctors in training.

Consistent with the distinguished history of its discipline, the College fosters continuing medical education through workshops, a masters degree programme, various training courses, and a range of other educational activities. The Faculty of Pain Medicine was founded in 2008 and the College awards a diploma in this area. Along with the RCPI and the RCSI, the College of Anaesthesiologists of Ireland is a constituent college of the Joint Faculty of Intensive Care Medicine in Ireland, founded in 2009.

All told, the story of anaesthesia in Ireland is a remarkable one, reflecting both the global development of the discipline and its particular story in Ireland. Safety as we watch is a unique historical record of this story, an immaculately researched account of anaesthesia in Ireland, and an exquisitely produced volume, published by Eastwood Books, an imprint of the Wordwell Group.

Brendan Kelly is Professor of Psychiatry at Trinity College Dublin and author of In Search of Madness: A Psychiatrist’s Travels Through the History of Mental Illness (Gill Books)

The authors have an encyclopaedic knowledge of 19th Century medical literature, which they use to good effect, with vivid portraits of people, places, and events in medical history

St Luke’s Symposium, No 6 Kildare Street, RCPI, Dublin, 11-14 October 2022

ACCORD HEALTHCARE WINS AT THE GLOBAL GENERICS AND BIOSIMILARS AWARDS 2022

Accord Healthcare took home four awards including Company of the Year at the Global Generics and Biosimilars Awards held in Frankfurt, Germany, on 2 November.

The company also won the Biosimilar Initiative of the Year, Value Added Medicine Initiative of the Year, and Regulatory Achievement of the Year.

Speaking after the success, Mr Paul Tredwell, Executive Vice President, Europe, Middle East, and North Africa region, said: “Year after year we are continuously recognised at these prestigious awards and that is a testament to our people, our culture, and our drive to make it better and the innovations we invest in.

“To be named Company of the Year, take the award for Biosimilar Initiative of the Year, Value Added Medicine Initiative of the Year, and Regulatory Achievement of the Year is a real accomplishment for everyone here at Accord and a real achievement to be awarded four [awards] in a highly competitive ceremony.”

ACCORD HEALTHCARE IRELAND PARTICIPATES IN TEAM HOPE

CHRISTMAS

Pictured are members of the Accord Healthcare Ireland Team who have filled shoe boxes for the Team Hope Christmas Shoebox Appeal.

Team Hope’s Christmas Shoebox Appeal is an annual campaign that delivers gifts to children affected by poverty. Often these shoebox gifts are the only present that a child will receive at Christmas. Since 2010, Team Hope has delivered over 2.1 million shoebox gifts to children across the world.

CROÍ CALLS ON ‘INVISIBLE NATION’TO ACTIVELY MANAGE HIGH CHOLESTEROL LEVELS

Heart and stroke charity Croí is calling on people aged over 45 years to have their cholesterol level checked the next time they visit their GP as new research reveals that the majority of respondents (83 per cent) do not mention cholesterol when thinking about their heart health. Atherosclerotic cardiovascular disease (ASCVD) is a silent, invisible disease that creates a large health and economic burden on society. ASCVD is caused by a fatty build up in the lining of the artery walls and is a major driver of heart attacks, strokes, and death. It is often invisible or unnoticed as most people do not experience any significant symptoms until the atherosclerotic plaque unexpectedly ruptures, causing a heart attack or stroke.

Mr Neil Johnson, CEO, Croí, added: “ASCVD is the underlying cause of 85 per cent of heart and stroke-related deaths, so it is worrying that most over-45s in Ireland do not know about this risk factor. This means that there is a large ‘invisible’ cohort of the population who are not focused on reducing their chances of a heart attack or stroke, and I would encourage them to visit www.croi.ie/ ascvd to learn more about ASCVD and cholesterol. It is time we put atherosclerotic cardiovascular disease high-

er on the political and health agenda to have a positive impact on public health in Ireland and globally.”

Visit www.croi.ie/ascvd or www.invisiblenation.com or follow #InvisibleNation #ASCVD #Cholesterol for more information.

DIABETIC RETINASCREEN HIGHLIGHTS IMPORTANCE OF SCREENING TEST FOR PEOPLE WITH DIABETES

On World Diabetes Day (14 November) the national Diabetic Retinopathy Screening (DRS) Programme highlighted the importance of screening tests for people with diabetes.

The HSE’s DRS Programme offers free regular screening to people with diabetes aged 12 years and older. Screening involves taking a specialised image of the eyes at one of over 130 screening locations nationally.

The test looks for early warning signs of diabetic retinopathy, a complication of diabetes caused by high blood glucose levels damaging the retina. If left undiagnosed and untreated, diabetic retinopathy may lead to blindness. However, if diabetic eye disease is found early, treatment can reduce or prevent damage to a person’s sight.

Diabetic RetinaScreen Programme Manager Ms Helen Kavanagh said: “If left undiagnosed and untreated diabetic retinopathy can deprive people of their sight, but it usually takes many years to reach that stage. This free eye screening test offers people with diabetes an opportunity to detect problems early, which can lead to more successful treatment and better outcomes. The longer you have diabetes the higher the risk, that’s why we’re encouraging everyone aged 12 years and older to be registered with Diabetic RetinaScreen today.”

Prof David Keegan, Diabetic RetinaScreen Clinical Director, said: “As we celebrate this year’s World Diabetes Day, we acknowledge the work and efforts of all involved in eye care delivery. We encourage all people with diabetes to take up their free diabetic retina screening appointment to detect and treat any possible sight-threatening retinopathy. Our teams are here to look after you.”

People can register for Diabetic RetinaScreen through their GP, practice nurse, dietitian, or eye doctor. Visit hse.ie/diabeticretinascreen or Freephone 1800 45 45 55.

BOOTS RAISE OVER €100K FOR THE IRISH CANCER SOCIETY NIGHT NURSES

Boots customers and colleagues have raised over €100,000 for the Irish Cancer Society night nurse service through the 2022 Boots Night Walk. The annual sponsored 5km walk saw participants and Boots colleagues raise €103,516 through fundraising and dona-

tions. The Irish Cancer Society night nurses provide in-home care through the night for cancer patients requiring end-of-life care, whilst also providing rest and respite for the patients’ families. The service is provided free of charge and is an invaluable support to families and their loved ones.

Boots has been a proud supporter of the Irish Cancer Society since 2012 and through the generosity of customers, patients, and colleagues has raised over €2.6 million, equating to over 7,500 nights of care for the service.

Across Boots stores, 150 Boots Irish Cancer Society Information Pharmacists and over 50 Boots Cancer Beauty Advisors are specially trained and on hand to support cancer patients and their loved ones.

Mr Stephen Watkins, Managing Director of Boots Ireland, said: “We are extremely proud to have raised €103,516 this year for the Irish Cancer Society night nurse service. Since 2012, our customers, patients, and colleagues have supported this special service, providing care and comfort to cancer patients and their loved ones. This ongoing partnership helps further our commitment to care for our customers and patients in the communities we serve at all stages of their life.”

Ms Averil Power, CEO, Irish Cancer Society, said: “On behalf of everyone at the Irish Cancer Society, I would like to thank Boots Ireland colleagues and customers for their continued support and enthusiasm for the Boots Night Walk, an absolutely wonderful fundraising initiative for the Irish Cancer Society night nursing service.

“The service allows end-of-life care for cancer patients in the comfort of their own homes, surrounded by their loved ones. With each year, demand for this valuable service grows. Approximately 97 per cent of the Society’s funding comes from donations, so we simply could not provide this crucial service without your generosity. Thank you for enabling us to be there for cancer patients and their families across Ireland, when they need us most.”

GP SUPPORTS ‘KNOW PNEUMO’ CAMPAIGN

Killarney GP Dr Gary Stack is encouraging people over the age of 65, and those with a weakened immune system or underlying health condition, to ask their doctor about ‘pneumo’.

Invasive pneumococcal disease, more generally known as ‘pneumo’, is a major cause of illness and death in Ireland, particularly among the very young, older people and those with a weakened immune system. Of those who develop an invasive infection:

 One-in-four will get pneumonia;

 One-in-four will get meningitis;

 One-in-10 will die.

A pneumococcal infection is caused by pneumococcal bacteria which is spread from person to person by coughing, sneezing or close contact. The bacteria can be carried in the nose and throat without doing any harm, but sometimes they can invade the lungs and bloodstream. This can cause many types of illness that range from mild to very severe, including pneumonia, meningitis, sinus, ear, bone, and blood infections.

More than 750,000 people in Ireland aged 65 and older are at risk of contracting pneumococcal. The pneumococcal vaccine is free of charge as part of the National Immunisation Programme for the over-65s and at-risk groups.

Dr Stack said: “As we approach the winter months, when we will see a return to family gatherings and group settings at Christmas time, it is more important than ever to be up-to-date on your vaccinations. As we enter into a prime time for those with weakened immune systems to catch infection that can cause serious illness, winter represents a significant risk with the return to normal activities, the need to be protected while engaging with society is more important than ever.”

Dr Stack added: “Pneumo disease is actually a yearround disease, meaning people can be impacted at any time, but it’s usually associated with more wet and damp conditions.”

medilearning

Free, independent CPD for doctors, nurses, and pharmacists… all under one roof

GP practice nurse required in friendly practice in Rathfarnham. 12 hours per week over 3 sessions.

To work alongside other full-time practice nurse. Previous experience desirable, but not essential. Training provided.

Good location. Modern bright purpose-built premises. Free parking.

Duties to include, but not exclusive to:

Phlebotomy, ear syringing, childhood vaccines and other immunisations, smear taking, chronic disease management, ECG, 24hr ABPM, removal of sutures/wound dressings, diabetes, assist with minor procedures, telephone triage, Covid/flu vaccinations.

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PRACTICE MANAGERS!

A round-up of news and oddities from left field by Dr

A climate of fear: The mental health consequences of climate change coverage

While raising awareness of what people can do to ameliorate the effects of climate change is important, there are indications that coverage of the issue is harming some people's mental health. To these people, the existential threat is imminent and is impacting on their quality-of-life.

Close to home, the mental health charity Turn2Me has recently announced that it is of great concern that there has

been "a huge increase in number of people reporting 'climate anxiety’" in Ireland. These feelings of angst include despair, frustration, hopelessness, and disillusion. That's quite a mix of feelings and it does not help that this is being seen on foot of a tsunami of anxiety over Covid-19.

Young people in particular seem to be especially vulnerable and are fearing about their future. The charity recognises this, and is offering activities, such as tree-planting,

cycling, and avoiding 'fast fashion'. If nothing else, doing these things may help to alleviate the anxieties of these young people. (For those of you unfamiliar with the term 'fast fashion', Wikipedia describes it as "the clothing industry's business model of replicating recent catwalk trends and high-fashion designs, mass-producing them at a low cost, and bringing them to retail stores quickly, while demand is at its highest. The term 'fast fashion' is also used generically to describe the products of the fast fashion business model.")

Is there a way to report on climate change without scaring the living daylights out of people? Yes, there needs to be awareness about climate change and our personal responsibility for doing our own part. But sensationalist, over-dramatic reporting, and doomsday predictions are – for a certain cohort of people – doing damage.

It's a complex issue, but for some people, they can only take so many doom-laden prophecies: Yes, the climate is changing. Yes, most ordinary people are doing what they can to do their bit (including paying a 'carbon tax'. You may also note that your Medical Independent you are holding is compostable, as well as recyclable). And yes, we can do better in reporting the scientific facts without scaring the living daylights out of psychologically and emotionally vulnerable people.

Meanwhile at COP27, the recent United Nations Climate Change Conference, the hypocrisy by our politicians and policy-makers was notable. Egyptian authorities informed the news wire AFP that some 400 private jets flew in to the Red Sea resort city of Sharm El-Sheik from around the world for the global meeting. To discuss how to limit carbon emissions. Ever heard of Zoom, folks?

Just in case you were wondering, the European Transport and Environment group estimates that a private jet can emit two tons of carbon dioxide in one hour. This is five-to-14 times more pollution per passenger than a commercial airliner. This does not sit well when these same people recommend that ordinary folks wash their clothes in cold water, stop having hot baths, or eat mealworms for the sake of the environment.

It's a case of 'one rule for thee and not for me' and does not help the cause.

Here are just a couple of offbeat climate change quotes to clean the palette.

• “According to a new UN report, the global warming outlook is much worse than originally predicted. Which is pretty bad when they originally predicted it would destroy the planet.” Jay Leno

• “A small ATM room having two ACs and four tubelights, working 24 hours, is asking me not to print a receipt to save the environment.” Anon

Is there a way to report on climate change without scaring the living daylights out of people?