The Medical Independent 11th August 2022

Children waiting years for psychology

GPs no longer see primary care psychology for children as a viable service due to long wait times. Niamh Quinlan reports

Potential donor audit for Ireland

PAGE 8-10

Navan ED closure in line with model of care – Clinical Lead

NIAMH QUINLAN

The replacement of the emergency department (ED) at Our Lady’s Hospital, Navan, with a 24-hour medical assessment unit (MAU) is “completely coherent” with the model of care for the National Clinical Programme for Emergency Medicine, according to the programme’s Clinical Lead Dr Gerry McCarthy.

The plan to establish the MAU was announced by the HSE on 13 June. However, the following day, Minister for Health Stephen Donnelly said no decision on the future of the ED had been made.

The HSE said the MAU would see approximately 80 per cent of the 25-30 patients who currently attend the hospital’s ED each day. Where appropriate, patients

would be triaged to Our Lady of Lourdes (OLOL) Hospital, Drogheda, and Connolly Hospital, Blanchardstown.

Dr McCarthy acknowledged to the Medical Independent (MI) the reaction to the HSE’s plan had been “tumultuous”.

“People are very wedded to their emergency department. People feel reassured that it’s immediately available,” he said.

There were two broad themes to the model of care, Dr McCarthy told MI.

“One is the recommendation to optimise the quality internal patient flow within emergency departments…. And the other broad brush is how should emergency departments support each other… in the form of what we would call an emergency care network.”

Emergency care networks (ECNs) consist of several collaborating emergency units, closely aligned with local pre-hospital services and primary care services, according to the model of care.

The on-site elements of the ECNs comprise of emergency departments, local emergency care units (such as MAUs), and local injury units.

It is vital for emergency departments and lower triage units, such as MAUs and injury units, to form linkages, according to Dr McCarthy.

“Ensuring that we pick out the most seriously ill and the most seriously injured at the earliest stage in their care journey is really the holy grail for us. Trying to make sure that the right patient gets to the right place at the right time.”

As well as current risks associ-

Over-stretching the doctor-patient bond

Patients who want respect, kindness, and competence must understand that doctors have human limitations, writes Dr Lucia Gannon

PAGE 24

ated with the Navan ED, Dr McCarthy also acknowledged the capacity risk in the OLOL and Connolly Hospital EDs.

“There are two risks here: One is the wrong patient arriving in the wrong place, whose needs are clearly too complex and immediate to be dealt with in that

Number of ICT contracts ‘unknown’ – HSE audit

A recent internal audit into the HSE’s information and communications technology (ICT) contracts library has found the Executive’s system to be “unsatisfactory”.

The audit from February this year, seen by the Medical Independent (MI), stated that the exact number of ICT contracts between the HSE and service providers was “unknown”.

According to the audit report: “The audit findings indicate that the level of assurance that may be provided to management about the adequacy and effectiveness of the governance, risk management and internal control system in the area reviewed is unsatisfactory.”

The report noted that the recording of contract information on a national basis had improved in recent years. However, there were legacy contracts, and contracts agreed at regional and local HSE level, that were not consistently captured centrally.

“As a result, at present, the exact number of all ICT-related contracts with service providers which the HSE have in place is currently unknown.”

The audit noted that the HSE’s procurement project management system should be the “single source of truth” recording all ICT contracts for the entire HSE.

However, a “significant discovery exercise will need to be undertaken in order to establish the true number of ICT-related contracts” in place.

A HSE spokesperson told MI “work is progressing to create a library of legacy contracts”.

“A library is established for national contracts utilising our existing projects management toolset,” the spokesperson said.

place. That’s the concern in Navan,” he said. “The risk in Lourdes ED and Connolly ED is the risk of crowding.”

A working group has been established by the HSE to review the reconfiguration plans for Navan hospital. It is expected to issue its recommendations within weeks.

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

Surgical trainees practice techniques at the RCSI surgical bootcamp 2022, which was held at the National Surgical and Clinical Skills Centre, RCSI, Dublin. The intensive course was developed to immerse core surgical trainees in the technical and non-technical skills needed as a surgeon.

Photo: Ray Lohan/RCSI

DAVID LYNCH

Catherine Reilly reports on a seminar examining how Ireland can learn from the Australian potential donor audit

In the management of adult patients with type 2 diabetes 1

THE POWER TO ACCOMPLISH MORE

Multiple benefits 1,2

• Significant reduction in HbA1C vs placebo at 24 weeks

• Reduction in weight and blood pressure vs placebo 1*

Proven protection 3†

• Reduction in risk of CV death vs placebo in adult patients with T2D and CVD: 38% RRR, 2.2% ARR

Type 2 diabetes mellitus

For adult patients with type 2 diabetes and CV disease JARDIANCE 10mg LICENSED FOR USE down to an eGFR of mL/min/1.73m2 1 mL/min/1.73m 30

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Heart failure

JARDIANCE is indicated in adults for the treatment of symptomatic chronic heart failure.

3. Zinman B, Wanner C, Lachin JM et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-2128 (& Supplementary Appendix).

Prescribing Information (Ireland) JARDIANCE® (empagliflozin) Film-coated tablets containing 10 mg or 25 mg empagliflozin. Indication: Type 2 diabetes mellitus: Jardiance is indicated for the treatment of adults with insufficiently controlled Type 2 diabetes mellitus as an adjunct to diet and exercise: as monotherapy when metformin is considered inappropriate due to intolerance; in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, refer to the Summary of Product Characteristics. Heart failure: Jardiance is indicated in adults for the treatment of symptomatic chronic heart failure. Dose and Administration: Type 2 diabetes mellitus: The recommended starting dose is 10 mg once daily. In patients tolerating empagliflozin 10 mg once daily who have eGFR ≥60 ml/min/1.73 m2 and need tighter glycaemic control, the dose can be increased to 25 mg once daily. The maximum daily dose is 25 mg. Renal impairment: The glycaemic efficacy of empagliflozin is dependent on renal function; efficacy is reduced in patients with moderate renal impairment and likely absent in patients with severe renal impairment. If empagliflozin is used for cardiovascular risk reduction as add on to standard of care, a dose of 10 mg empagliflozin once daily should be used in patients with an eGFR between 30 and 60 ml/min/1.73 m2. If further glycaemic control is needed, the addition of other antihyperglycaemic agents should be considered. Dose adjustment recommendations according to eGFR or CrCL: In patients with type 2 diabetes mellitus and an eGFR 45 to <60 ml/min/1.73 m2 or CrCL 45 to <60 ml/min; do not initiate, but in patients already taking empagliflozin continue with 10 mg empagliflozin. In patients with type 2 diabetes mellitus with an eGFR below 45 ml/min/1.73 m2 or CrCL below 45 ml/min empagliflozin is not recommended. In patients with type 2 diabetes mellitus and established cardiovascular disease with an eGFR 30 to <60 ml/min/1.73 m2 or CrCL 30 to <60 ml/min; initiate or continue with 10 mg empagliflozin. Empagliflozin is not recommended in patients with an eGFR <30 ml/ min/1.73 m2 or CrCL <30 ml/min. Heart failure: The recommended dose is 10 mg empagliflozin once daily. Renal impairment: For treatment of heart failure in patients with or without Type 2 diabetes mellitus, empagliflozin 10 mg may be initiated or continued down to an eGFR of 20 ml/min/1.73 m2 or CrCl of 20 ml/min. For patients with an eGFR <20 ml/ min/1.73 m2 or CrCl <20 ml/min empagliflozin is not recommended. All indications: When used with sulphonylurea or insulin, a lower dose of these may be considered to reduce the risk of hypoglycaemia. If a dose is missed, it should be taken as soon as the patient remembers; however, a double dose should not be taken on the same day. Renal impairment: Empagliflozin should not be used in patients with end stage renal disease (ESRD) or on dialysis. Monitoring of renal function: Assessment of renal function is recommended prior to initiation and at least annually; prior to initiation of any concomitant medicinal product that may have a negative impact on renal function. Hepatic impairment: No dose adjustment is required for patients with hepatic impairment. Not recommended in severe hepatic impairment. Elderly patients: No dose adjustment is recommended based on age. In patients 75 years and older, an increased risk for volume depletion should be taken into account.

Paediatric population: No data are available. Method of administration: The tablets can be taken with or without food, swallowed whole with water. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and Precautions: Ketoacidosis: Rare cases of ketoacidosis, including life-threatening and fatal cases, have been reported in patients with diabetes mellitus treated with SGLT2 inhibitors, including empagliflozin. The risk of ketoacidosis must be considered in the event of non-specific symptoms such as

nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Assess patients for ketoacidosis immediately, regardless of blood glucose level. In patients where ketoacidosis is suspected or diagnosed, treatment with empagliflozin should be discontinued immediately. Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of blood ketone levels is preferred to urine. Treatment with empagliflozin may be restarted when the ketone values are normal and the patient’s condition has stabilised. Before initiating empagliflozin, factors in the patient history that may predispose to ketoacidosis should be considered. Use with caution in patients who may be at higher risk of ketoacidosis. Restarting SGLT2 inhibitor treatment in patients with previous ketoacidosis while on SGLT-2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved. Jardiance should not be used for treatment of patients with Type 1 diabetes. Renal impairment: See under ‘renal impairment’ of Dose and administration section. Monitoring of renal function: See under ‘monitoring of renal function’ of Dose and administration section. Risk for volume depletion: Osmotic diuresis accompanying glucosuria may lead to a modest decrease in blood pressure. Therefore, caution should be exercised in patients with known cardiovascular disease, patients on anti-hypertensive therapy with a history of hypotension or patients aged 75 years and older. In case of conditions that may lead to fluid loss (e.g. gastrointestinal illness), careful monitoring of volume status and electrolytes is recommended. Temporary interruption of treatment with empagliflozin should be considered until the fluid loss is corrected. Elderly: See under Dose and Administration; special attention should be given to volume intake of elderly patients in case of co-administered medicinal products which may lead to volume depletion (e.g. diuretics, ACE-inhibitors). Complicated urinary tract infections: Temporary interruption of empagliflozin should be considered in patients with complicated urinary tract infections. Necrotising fasciitis: Cases of necrotising fasciitis of the perineum (Fournier’s gangrene), have been reported in patients with diabetes mellitus taking SGLT2 inhibitors. This is a rare but serious and potentially life-threatening event that requires urgent surgical intervention and antibiotic treatment. Patients should be advised to seek medical attention if they experience a combination of symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be aware that either uro-genital infection or perineal abscess may precede necrotising fasciitis. If Fournier’s gangrene is suspected, Jardiance should be discontinued and prompt treatment should be instituted. Lower limb amputation: An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term clinical studies with another SGLT2 inhibitor, counsel patients on routine preventative footcare. Hepatic injury: Cases of hepatic injury have been reported with empagliflozin in clinical trials. A causal relationship between empagliflozin and hepatic injury has not been established. Elevated haematocrit: Haematocrit increase was observed with empagliflozin treatment. Chronic kidney disease: There is experience with empagliflozin for the treatment of diabetes in patients with chronic kidney disease (eGFR ≥30 mL/ min/1.73 m2) both with and without albuminuria. Patients with albuminuria may benefit more from treatment with empagliflozin. Infiltrative disease or Takotsubo cardiomyopathy: Patients with infiltrative disease or Takotsubo cardiomyopathy have not been specifically studied.

Therefore, efficacy in these patients has not been established. Urine laboratory assessments:

Due to its mechanism of action, patients taking Jardiance will test positive for glucose in their urine. Lactose: The tablets contain lactose. Patients with rare hereditary problems of

galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product. Sodium: Each tablet contains less than 1 mmol sodium (23 mg), essentially ‘sodium free’. Interactions: Use with diuretics may increase the risk of dehydration and hypotension. Insulin and insulin secretagogues may increase the risk of hypoglycaemia therefore, a lower dose of insulin or an insulin secretagogue may be required. Empagliflozin may increase renal lithium excretion and the blood lithium levels may be decreased. Serum concentration of lithium should be monitored more frequently after empagliflozin initiation and dose changes. The effect of UGT induction (e.g. induction by rifampicin or phenytoin) on empagliflozin has not been studied. Co-treatment with known inducers of UGT enzymes is not recommended due to a potential risk of decreased efficacy. If an inducer of these UGT enzymes must be co-administered, monitoring of glycaemic control to assess response to Jardiance is appropriate. Interaction studies suggest that the pharmacokinetics of empagliflozin were not influenced by coadministration with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, torasemide and hydrochlorothiazide. Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically relevant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, simvastatin, warfarin, ramipril, digoxin, diuretics and oral contraceptives. Fertility, pregnancy and lactation: There are no data from the use of empagliflozin in pregnant women. As a precautionary measure, it is preferable to avoid the use of Jardiance during pregnancy. No data in humans are available on excretion of empagliflozin into milk. Jardiance should not be used during breast-feeding. No studies on the effect on human fertility have been conducted for Jardiance. Undesirable effects: Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Very common: hypoglycaemia (when used with sulphonylurea or insulin), volume depletion. Common: vaginal moniliasis, vulvovaginitis, balanitis and other genital infections, urinary tract infection (including pyelonephritis and urosepsis), thirst, constipation, pruritus (generalised), rash, increased urination, serum lipids increased. Uncommon: diabetic ketoacidosis, urticaria, angioedema, dysuria, blood creatinine increased/glomerular filtration rate decreased, haematocrit increased. Rare: necrotising fasciitis of the perineum (Fournier’s gangrene). Very rare: tubulointerstitial nephritis. Prescribers should consult the Summary of Product Characteristics for further information on side effects. Pack sizes: 10 mg; 28 tablets, 25 mg: 28 tablets. Legal category: POM. MA numbers: 10 mg/28 tablets EU/1/14/930/013; 25 mg/28 tablets EU/1/14/930/004. Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, 55216 Ingelheim am Rhein, Germany. Prescribers should consult the Summary of Product Characteristics for full prescribing information. Additional information is available on request from Boehringer Ingelheim Ireland Ltd, The Crescent Building, Northwood, Santry, Dublin 9. Prepared in March 2022.

Adverse events should be reported. Reporting forms and information can be found at https://www.hpra.ie/homepage/about-us/report-an-issue.

Adverse events should also be reported to Boehringer-Ingelheim Drug Safety on 01 2913960, Fax: +44 1344 742661, or by e-mail: PV_local_ UK_Ireland@boehringer-ingelheim.com

Possibility of GEM supports to be discussed

DAVID LYNCH

The possibility of providing “additional supports” to graduate-entry medicine (GEM) students will form part of this year’s annual estimates process, this newspaper has been told.

As reported in the Medical Independent (MI) in May, there was widespread concern expressed by medical students and doctors following Bank of Ireland’s decision to discontinue its specialist loan for GEM students. The bank was the only financial institution providing this type of loan.

As GEM is considered a second degree, students are ineligible for Student Universal Support Ireland (SUSI) grants and do not have fees covered by the State. Fees for GEM programmes are approximately €16,000 per year.

A spokesperson for the Department of Further and Higher Education, Research, Innovation, and Science said the findings of a recent review of the general student grant scheme system were being considered.

“There are significant policy, legislative, and funding considerations, as well as wider implications, if the current treatment of graduate-entry medicine was amended,” the spokesperson told MI

“However, we now have this review and all elements

will be subject to consideration and prioritisation, alongside other costs of education measures, through the annual estimates process.

“This will include consideration of the potential for additional supports for students of graduate-entry medicine, but this is all dependent on competing priorities for supports and demands on the exchequer.”

The spokesperson added that “in advance of the estimates process, the Minister [Simon Harris] intends to publish a paper outlining potential options and impacts,

to be considered in the budgetary process, related to the student grant scheme and other programmes related to student supports and costs of higher education”.

Separately, at the end of July, Minister Harris announced an expansion of higher education scholarships. “We... must ensure we help diversify our professions too,” said the Minister.

“That is why I am particularly pleased that we are allowing certain scholarship holders continue their bursaries for graduate-entry medicine courses.”

Over

10,000 children waiting to access talking therapies

NIAMH QUINLAN

Some 10,180 children were on a waiting list to access primary care psychology services from their respective Community Healthcare Organisations (CHOs) in December 2021, according to figures obtained by the Medical Independent (MI) under Freedom of Information law.

Primary care psychology for children is a free referral-based service for under-18s experiencing mild-to-moderate psychological challenges. Patients can be referred by healthcare professionals, such as GPs, occupational therapists, and public health nurses.

Responses from CHOs showed that children may wait years to access the service. In the Galway and Roscommon areas of Community Healthcare West (CHO 2), some children were waiting up to seven years and seven months. This CHO also covers Mayo.

Overall, 4,465 children were waiting over a year as of December 2021. The highest number was in Dublin South, Kildare, West Wicklow (DSKWW) (CHO 7), where there were 1,130 children waiting over a year. This comprised more than half of the 2,006 children waiting to be seen in DSKWW.

Cork Kerry Community Healthcare (CHO 4) had the longest waiting list overall, with 2,192 children waiting to access primary care psychology. CHO Dublin North City and County (CHO 9) had the second-longest list at 2,104, followed by DSKWW.

A spokesperson for Cork Kerry Community Healthcare told MI it was “working to provide appointments for those waiting the longest”. A project in the CHO facilitated patients waiting longer than 130 weeks to receive appointments this year.

In December 2021, there were 975 children waiting in South East Community Healthcare (CHO 5); 953 in Community Healthcare West; 628 in Midlands Louth Meath (CHO 8); 604 in Community Healthcare Cavan, Donegal, Leitrim, Monaghan, Sligo (CHO 1); and 400 in Mid West Community Healthcare (CHO 3).

Community Healthcare East (CHO 6) had the shortest wait list with 318 children waiting for the service as of December 2021, and five waiting more than a year.

A spokesperson for Community Healthcare East told MI that a waitlist initiative was introduced in 2021 and has continued this year. It has focused on reducing the number waiting over 12 months in children’s services. See news feature, p4-5.

NIAMH QUINLAN niamh.quinlan@mindo.ie

Children waiting years for primary care psychology

Primary care psychology for children, which provides free interventions for under-18s with mild-to-moderate mental and emotional issues, is facing its own struggle in relation to waiting lists.

With many children waiting years to access support, GPs express doubts about referring to the service but have few alternative options.

Primary care psychology is available in the nine Community Health Organisations (CHOs). The service is mainly for under-18s, with some areas in CHOs offering services into adulthood. Figures released to the Medical Independent (MI) in response to a Freedom of Information request show that the longest waiting lists are for children.

Wait times

Children could be left waiting for over seven years for access to primary care psychology.

In Galway/Roscommon, two of the three counties in CHO 2, figures from May showed a seven-year and seven months maximum wait for access to primary care psychology for under-18s. CHO 2 had around 400 children waiting to access the service in December 2021. In Mayo, the other county in CHO 2, the maximum wait time was one year and nine months.

Figures from the end of March showed that the longest wait time in the Kildare/ west Wicklow area of CHO 7 was six years and 11 months. In CHO 7’s other areas, the maximum wait times for a first appointment was five years in Dublin south city; four years and a month in Dublin southwest; and

three years and six months in Dublin west.

In CHO 4, the Cork/Kerry area, the longest wait time was three years, according to figures from the beginning of June. By December 2021, some 2,192 children were on the waiting list to receive care.

CHO 9 (Dublin north city and county) had a maximum wait of four years and nine months, while CHO 1 (Donegal, Sligo, Leitrim, Cavan, Monaghan) had a maximum wait of two years and one month.

CHO 3 (Limerick, Clare, north Tipperary) had a maximum wait of two years, CHO 6

(southeast Dublin, east Wicklow, and Dun Laoghaire) a maximum of one year and three months, and CHO 8 (Laois, Offaly, Longford, Westmeath, Louth, Meath) had a maximum of one year and one month.

Of the nine CHOs in the country, only CHO 5 (south Tipperary, Carlow, Kilkenny, Waterford, Wexford) did not respond to MI’s query on the longest waiting times for primary care psychology in their area.

Asked if clients and their families are communicated with while they are on the waiting list, a spokesperson for the HSE re-

Psychological and psychiatric services for children

There are a number of State-supported and provided mental health services for children.

Primary care psychology for children is a free psychological service in all nine Community Health Organisations (CHOs) in the country. Some CHOs have a continuation of primary care psychology for children into adulthood; however, most services are directed towards under-18s.

The service is for those with mild-tomoderate mental health difficulties. They can access primary care psychology for children by referral from a GP, public health nurse, occupational therapist or another public health worker. Upon a successful referral, the patient is added to a waiting list. Their position on the list is proportional to the clinical need identified during the initial assessment.

A child can be refused services from

primary care psychology, for example, if their issues are deemed too serious to be managed at community level. When this happens, GPs may refer the child to the Child and Adolescent Mental Health Services (CAMHS).

CAMHS “provides assessment and treatment for young people and their families who are experiencing mental health difficulties”, according to the HSE website. It is a specialist clinical service that provides supports to children up to the age of 18 who may be struggling with mental health difficulties, such as moderate-to-severe depression, anxiety, eating disorders, and self-harm.

The service can also provide supports to families, such as key workers linking directly with parents, education for parents, and directing parents to community-based supports with others in similar situations.

Another option for mental and emotional issues in children is the National Education Psychological Service (NEPS), which provides educational psychological support to pupils in primary and post-primary schools through several means. These can include access to individual pupil casework where there is need via a NEPS psychologist or through the Scheme for the Commissioning of Psychological Assessments (SCPA).

A spokesperson from the Department of Health told the Medical Independent : “The individual casework service involves the NEPS psychologist working with the student, teachers and parents, and other professionals if appropriate, to identify need and plan for intervention and review to support the student in school. This service extends to approximately 8,500 students per annum.”

sponded: “The amount of communication varies locally depending on the availability of administrative support.”

“Communication with families may include acknowledgement of referral, confirmation of acceptance/non-acceptance to the waiting list, estimated waiting time, and pre-intake preparation. From time to time, wait list validation may occur in the form of opt-in/out processes or check-ins.”

As primary care psychology for children is a “needs-based service”, those on the waiting list could be deprioritised in favour of clients who are considered to require the service more urgently.

According to the HSE spokesperson, there are a “number of factors” which account for the long waiting lists nationally. These include a reconfiguration of the national access policy and a revision of the Child and Adolescent Mental Health Services (CAMHS) operational guidelines, which meant a “large new cohort of referrals were transferred to receive care in primary care”.

Other issues, such as the cyberattack, decreased face-to-face appointments, increased staff sick leave, staff redeployment and anticipated increases in referrals ‘post-pandemic’ have contributed to long waiting lists. Different population sizes can also add to the varying wait times between each area.

A spokesperson for CHO 2 said that, in the Galway region specifically, there were “multiple factors” for the waiting time length, including staff vacancies, recruitment delays, inadequate training places for postgraduate psychology, and the legal requirement for a child with a disability to be provided with an assessment of need within six months of referral.

The spokesperson added: “Every effort is being made within our existing resources to meet the needs of children and families. Nationally, workforce planning could be used to establish a sustainable ratio for child psychology services per head of population and to fund new development posts to meet the need.”

Separately, the HSE stated that it is working on reducing the wait times, with schemes, such as the “successfully piloted and rolled out” psychology assistant grade, which has funded 114 posts in all CHOs, predominantly within psychology services for children. At the official launch of the grade in January, Minister for Mental Health and Older People Mary Butler said: “Such measures will complement ongoing work on the development of a sustainable primary care psychology service in the longer term.”

According to the HSE’s spokesperson: “Work is focused on the validation and treatment of those who are waiting over 12 months. There has been an 11 per cent reduction overall on those waiting over 12 months to access services. Discussions are ongoing with the Department of Health to extend this short-term waiting list initiative as part of core funding.”

‘Not a service’

IMO GP committee Chair, Dr Denis McCauley, said that the criteria for who need access to psychology should be clearer and more refined. He told MI: “Psychological services, I must admit my experience with them is very poor. In that, anybody I would consider sending to a psychologist, I’ve never really been successful in actually getting

GPs no longer see primary care psychology for children as a viable service, as under-18s may be waiting years to access therapies. Niamh Quinlan reports

Going private – is it an option?

After failing to get on to a waiting list or potentially facing a wait of years, parents may turn to private counselling for mild-to-moderate mental and emotional issues affecting their children.

Galway GP Dr Sinead Feeney told the Medical Independent that due to the years-long wait for people to access primary care psychology for children in some areas: “Usually what happens is that the parents ultimately will go privately in some way.”

“If they can afford it,” she added. The long waiting lists can disproportionately affect low-income families, according to Dr Feeney.

Multiple studies have shown that children in lower-income households are much more likely to suffer from emotional and mental issues. A 2015 report by the London Centre for Mental Health showed that children in the lowest income quintile had a 17 per cent chance of experiencing mental health issues, versus 4 per cent of children in households in the

an appointment.”

“But in their defence, I suppose the question is, who should be accessing psychological services?”

He said it was “somewhat confusing” as to who should access the services for their specific emotional or psychological needs as each issue would require a different or specific type of counselling.

Dr McCauley acknowledged there were probably some inappropriate referrals. “But even if you have an appropriate referral, I don’t think there’s a service there.”

He continued: “I suppose we don’t refer to it because we’ve never probably seen a result from it and that probably is just because of the length of the waiting list and the absence of a practical service. If the waiting list is several years, then practically, it’s not really a relevant service.”

Galway GP and Director of the Mental Health Programme at the ICGP, Dr Brian Osborne, has successfully referred a patient to primary care psychology for children, with a wait time of a few months. However, regarding a potential wait time of years in some areas, he said: “If someone needs psychology, waiting years is not going to do them any good at all. You can’t classify that as a service really.”

There is also a chance that the client will not make it on to the waiting list. The service may recommend that the patient be instead referred to CAMHS. However, upon referral to CAMHS, they may then be told that primary care psychology for children is more suitable for the patient. Dr Osborne termed this situation “a merry-go-round”.

“It’s distressing for families and it’s frustrating for GPs. You’re literally on a merry-go-round, that is, sending letters here,

highest income quintile.

The same report showed the lower the level of the parents’ educational qualifications, the higher the prevalence of severe mental health problems in children. “A family where there’s a lower level of education, the parents will be less able to advocate for their kids,” Dr Feeney said.

She added that if private psychological help is not an option, the child is left in an “endless cycle” of being bounced around between CAMHS and primary care psychology, or else spend years on a waiting list.

Private psychology services may not be available in some areas, Galway GP Dr Brian Osborne pointed out. “If they have the means, they may try to go privately. But, if you’re in a rural area or a smaller town, you will have to travel long distances to try and see a private practitioner.”

The shortage of GPs in rural areas combined with lengthy wait times adds to the difficulty in accessing primary care psychology.

there, and everywhere and being met with obstacles.”

Galway GP Dr Sinead Feeney has had similar experiences with primary care psychology for children. “I can send a referral and then they maybe will write back and say this person sounds like they’d be more suitable for CAMHS. And then after the CAMHS referral, they’ll send back that they [the patient] sound more... suitable for psychology or Jigsaw or anything else. Then you kind of go round in circles a few times.”

“Sometimes, if you try to go both ways and refer to CAMHS and psychology, in order to get access for the child quicker, then they’ll say, ‘Oh, I see that you’ve referred to CAMHS, so we won’t see them’,” she added.

Dr Feeney said she was aware of the years-long wait and as a result, “there’s just no point in referring to them.” She said she had successfully referred a client to primary care psychology for children only once, and it was a child who had previously availed of the service.

“We’re banging our heads off the wall,” she added. “Kids need to have a proper assessment.”

Pressure on CAMHS

Although CAMHS is for children with moderate-to-severe mental health issues, GPs will sometimes refer children to CAMHS as they know of the long waiting list for the psychology service, according to Dublin GP Dr Edel McGinnity.

“Primary care psychology would be, if it was functioning, a critical component of managing less severe mental health problems in children. But the prob -

lem is that there’s essentially no access to it because the waiting times are so long.”

The CAMHS referral criteria in the operational guidelines also state that for a patient to access the service, “comprehensive treatment at primary care level has been unsuccessful or was not appropriate in the first instance.”

“What happens then is that children who could be managed in the community, if they don’t have the appropriate and timely intervention of a service like psychology, they would eventually end up requiring CAMHS,” Dr McGinnity said. “[For example] psychological counselling, family work – if those are not available, things often get much worse, and then the child does get to a point where they may start to self-harm or they feel genuinely suicidal or their behaviour becomes unmanageable. And then they do need CAMHS.”

This in turn increases pressure on the CAMHS service.

CAMHS faced additional controversy earlier this year. The Maskey report found “unreliable diagnoses, inappropriate prescriptions, and poor monitoring of treatment and potential adverse effects” had exposed children to the risk of significant harm in South Kerry CAMHS.

Figures released by the HSE in May showed there were over 4,000 children on the waiting list for CAMHS. At the end of July, it was reported by the Irish Examiner that more than 500 children were waiting over a year to access the service.

Recent reports also showed that the number of referrals accepted by CAMHS was falling.

“The national waiting list for CAMHS… doesn’t include all the people whose referrals have been rejected,” Dr McGinnity said. “So the waiting list for CAMHS is kind of meaningless because there’s a huge amount of unmet needs that CAMHS doesn’t get because they’re never allowed on to the waiting list. And that’s not documented or recorded anywhere, so nobody knows what the need really is.”

To counteract this disconnection between services, Dr McGinnity suggested a common referral pathway to mental health services for under-18s.

She said: “All of these different agencies are working in their own little separate silo. And they don’t co-ordinate and they don’t agree, and they just send the referrals back to us all the time. It creates the most enormous amount of work.”

There is precedent to create common referral pathways, Dr McGinnity told MI. In an article she wrote for the ICGP’s Forum journal, she said: “One of the most striking experiences during the pandemic was the way in which the HSE was able to introduce significant changes at speed (eg, e-prescribing), and create complex, brand new structures (contact tracing, testing, and vaccination centres) when given the resources and the political will.”

“We need to see that same political will and resourcing applied to children’s mental health and disability services. We are witnessing the wholescale neglect of children’s’ health at this time, which if not addressed will generate huge costs for the health service, society as a whole, and above all will have profound adverse consequences for the individuals involved.”

MINDO NUMBERS

2,575

is the minimum number of additional whole-timeequivalent (WTE) medical staff required by 2035 to keep pace with demographic changes, according to new research from the Economic and Social Care Institute (ESRI).

3,236 is the maximum number of additional WTE medical staff required by 2035, the ESRI research stated.

8,868 is the maximum number of WTE nursing staff required by that year.

19,000 inpatient bed days were avoided as a result of projects funded through the Sláintecare Integration Fund (SIF).

3,000 emergency attendances were avoided, according to a new report, which sets out the notable achievements of projects supported by the SIF.

1 -in-four children in Dublin are vitamin D deficient, according to a new Trinity College Dublin study, which was published in the Journal of Nutritional Science.

Dr Denis McCauley

Dr Edel McGinnity

‘Preparatory’ work underway on review of GP services

DAVID LYNCH

Work has begun on a “strategic review” of GP services that will “inform future contractual changes”, this newspaper has been told.

In 2019, the IMO and the Department of Health signed an agreement that included the introduction of a chronic disease management programme for a number of conditions.

The terms also included a commitment to “undertake a strategic review of GP services” within the life -

time of the agreement.

However, a Department spokesperson told the Medical Independent (MI) that “elements” of the agreement, which was meant to come to an end this year, will continue until 2023.

“The [2019] agreement requires that GPs cooperate with a wide-ranging set of modernisation measures in the areas of e-health, medicines management, and multidisciplinary working,” the spokesperson told MI

The Department noted “good progress” on implementation, but stated there had been delays in some areas

Hundreds of appeals outstanding at ‘Disabled Drivers Medical Board of Appeal’

CATHERINE REILLY

Hundreds of appeals remain outstanding at the suspended Disabled Drivers Medical Board of Appeal (DDMBA) with no indicative date for its resumption, the Medical Independent can report.

All members of the previous DDMBA resigned in late 2021 due to concerns about the scheme’s criteria and the need for reform.

As of 5 July, there were 575 requests awaiting an appeal hearing, of which 382 dated from 2021 and 193 from 2022.

A scheme for drivers/passengers with specific severe and permanent disability provides tax reliefs linked to the purchase and use of specially constructed or adapted vehicles.

People wishing to access the scheme are assessed by community doctors through the HSE and appeals are heard by the DDMBA. Members of the DDMBA are doctors appointed by the Minister for Finance on the recommendation of the Minister for Health.

In May Dr Cara McDonagh, former Chair of the DDMBA, told the joint Oireachtas committee on finance, public expenditure and reform and Taoiseach, that the medical criteria were “very restrictive and exclude many people with genuine, severe and permanent disability from accessing support”.

“Concerns about the restrictive and inequitable nature of the medical criteria were expressed by my predecessors. Within the first year of my appointment [in 2015], at interactions with the Department of Finance,

I expressed my strongly held view that the scheme needed to be changed.”

Dr McDonagh also referred to a Supreme Court judgement in 2020 which found against the DDMBA and the Minister for Finance in an appeal brought by two people who had not been granted a primary medical certificate at an appeal hearing.

She told the committee that in communications with the Department of Finance she “repeatedly expressed my opinion that the Supreme Court decision further vindicated our concerns about the medical criteria and emphasised the importance of progressing rapidly with a comprehensive review of the scheme and complete revision”.

According to the Department of Finance, two expression of interest campaigns have been held seeking suitable candidates for the DDMBA. The Department of Health leads on these campaigns and “processes to support the nomination of suitable candidates are ongoing”.

The spokesperson added: “The Minister for Finance [Paschal Donohoe] has given a commitment that a comprehensive review of the scheme, to include a broader review of mobility supports for persons with disabilities, would be undertaken. In this context the Minister has been working with Roderic O’Gorman, Minister for Children, Equality, Disability, Integration, and Youth.”

However, progress had been delayed as Minister O’Gorman’s department “has been tasked with looking after the needs of Ukrainian refugees” as part of overall Government efforts, indicated the spokesperson.

“due to the impact of Covid-19”.

“Given the significant nature of the change programmes involved and the level of IT development required, there are elements of the agreement that will continue into 2023 to bring the programme to completion.”

The spokesperson said that this extension has been “acknowledged by all the parties to the agreement”.

On the promised “strategic review” of GP services, the spokesperson said “preparatory work has commenced”.

“The review will examine the broad range of issues affecting general practice and will set out measures necessary to deliver a sustainable service into the future.

The outcome of this review will inform future contractual changes.”

It was anticipated that GP representative bodies would have an important contribution to make to the review, according to the spokesperson.

Need for ‘broader awareness’ of risks in nursing home sector

ing the introduction of regulation.

There is a need to create “broader awareness of trends and risks in the nursing home sector” and engagement at policy level on the configuration of nursing homes, according to the board of HIQA.

The observation was made at a meeting of the board on 18 May during a discussion on the CEO’s report.

“Using alternative methods, such as the Citizens Assembly” to raise this broader awareness was suggested, according to the minutes of the meeting.

The board stated that consideration should be given to assessing the strengths and weaknesses of various nursing homes “as part of research opportunities”.

In response to the board’s comments, HIQA’s CEO Ms Angela Fitzgerald and Chief Inspector Ms Carol Grogan said consideration would be given to “available mechanisms” to create awareness and discussion on developments in the nursing home sector and related policy.

Homecare standards would also need to be appropriate and aligned to the forthcoming homecare regulations, according to the board.

In December 2021, the Authority called for immediate reform of Ireland’s homecare services, includ-

At its meeting in May, the board stated that HIQA should examine the “implications of an incremental approach” to homecare regulation on “discrete groups”.

Ms Fitzgerald and Ms Grogan replied that it was anticipated HIQA’s homecare function would commence by focusing on homecare support for people aged 18 and above.

“Monitoring of more complex homecare needs is more likely to be introduced in the longer term,” outlined the minutes.

Last year, Government gave approval to draft a General Scheme and Heads of a Bill to establish a licensing framework for home support providers. However, the Heads of Bill introducing regulation to the sector had yet to be developed.

Meanwhile, Ms Fitzgerald, who was appointed as CEO in March, told the board she intended to refine the format of the CEO report as she “becomes more familiar with the board” and their requirements. She invited board members to provide feedback on the level of detail and content provided.

During the meeting, the development of increased support in the CEO’s office to allow for better delegation, and “allow more time and space for progressing strategic matters”, was also noted.

Upward trend in Suboxone prescription continues

DAVID LYNCH

The number of patients being administered buprenorphine/naloxone (Suboxone) reached 656 at the end of May, continuing the upward trend since 2017. In February, there were 606 patients in receipt of Suboxone.

These figures are “based on data supplied from the central treatment list and exclusive of prisons”, according to a HSE spokesperson.

The number of people in receipt of Suboxone at the end

of April 2021 was 492; however, this figure included patients in prison.

Regulations were introduced in November 2017 to provide access to certain buprenorphine-based medicinal products in the opioid substitution treatment system on the same statutory basis as methadone. The Suboxone programme had not been impacted by the pandemic, stated the HSE in 2021.

At the end of May this year, there were 15 level 1 GPs prescribing Suboxone and 41 level 2 GPs. A level 1 GP pre -

scriber can treat stabilised opiate-dependent patients in their own practice, while a level 2 GP can provide a comprehensive assessment, initiation of treatment where appropriate, stabilisation maintenance of treatment, and/or detox of opioid-dependent patients.

Some 10,138 patients were in receipt of methadone at the end of May. There are 749 community pharmacies involved in the methadone protocol scheme, while there are 288 community pharmacies participating in the Suboxone scheme. See news feature, p12.

PAUL MULHOLLAND

Think Once-Weekly Ozempic for People with Type 2 Diabetes who have Atherosclerotic Cardiovascular Disease1-3

Ozempic® provided a significant 26% risk reduction of MACE# in people with type 2 diabetes* and cardiovascular disease.1,2,§

This includes a 39% relative risk reduction in non-fatal stroke.1,2,‡

Ozempic® also has superior blood glucose and weight-loss efficacy across all head-to-head clinical trials in the SUSTAIN program.1-9,†,‡

* 26% CV risk reduction in patients with type 2 diabetes and high CV risk, compared to placebo, in addition to standard treatment.

# Major Adverse Cardiovascular Events

† Results apply to Ozempic® across SUSTAIN trials, which included placebo, sitagliptin, dulaglutide, canagliflozin, exenatide PR and glargine U100.1-9

§ p=0.02 for superiority

‡ p<0.05

Ozempic® is recommended by the ADA/EASD Consensus Report for people with type 2 diabetes who have established atherosclerotic cardiovascular disease10

PR = Prolonged Release; ADA = American Diabetes Association; EASD = European Association for the Study of Diabetes.

SUSTAIN = Semaglutide Unabated Sustainability in treatment of Type 2 Diabetes.

*SUSTAIN was the phase 3 clinical trial programme investigating the effects of once weekly semaglutide versus other anti-diabetic agents.

ABBREVIATED PRESCRIBING INFORMATION

Ozempic®t semaglutide

Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Ozempic® 0.25 mg solution for injection in pre-filled pen. Ozempic® 0.5 mg solution for injection in pre-filled pen. Ozempic® 1 mg solution for injection in pre-filled pen. One ml of solution contains 1.34 mg of semaglutide (human glucagon-like peptide-1 (GLP-1) analogue). Indication: Ozempic® is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise • as monotherapy when metformin is considered inappropriate due to intolerance or contraindications • in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1 of the Ozempic® SmPC. Posology and administration: Administered once weekly at any time of the day, with or without meals. Injected subcutaneously in the abdomen, thigh or upper arm. Starting dose: 0.25 mg once weekly. After 4 weeks the dose should be increased to 0.5 mg once weekly. After at least 4 weeks with a dose of 0.5 mg once weekly, the dose can be increased to 1 mg once weekly to further improve glycaemic control. When Ozempic® is added to existing metformin and/ or thiazolidinedione therapy or to an SGLT2 inhibitor, the current dose of metformin and/ or thiazolidinedione or SGLT2 inhibitor can be continued unchanged. When Ozempic® is added to a sulfonylurea or insulin, a reduction in dose of sulfonylurea or insulin should be considered to reduce the risk of hypoglycaemia. Blood glucose self-monitoring is necessary to adjust the dose of sulfonylurea and insulin, particularly when Ozempic® is started and insulin is reduced. A stepwise approach to insulin reduction is recommended. Children: No data available. Elderly: No dose adjustment required, therapeutic experience in patients age ≥75 is limited. Renal impairment: No dose adjustment is required for patients with mild, moderate

or severe renal impairment. Experience in patients with severe renal impairment is limited. Not recommended for use in patients with end-stage renal disease. Hepatic impairment: No dose adjustment is required for patients with hepatic impairment. Experience with severe hepatic impairment is limited. Caution should be exercised when treating these patients with semaglutide. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special warnings and precautions for use: Should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Not a substitute for insulin. Diabetic ketoacidosis has been reported in insulin-dependent patients whom had rapid discontinuation or dose reduction of insulin. There is no experience in patients with congestive heart failure NYHA class IV and is therefore not recommended in these patients. Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions. This should be considered when treating patients with impaired renal function as nausea, vomiting, and diarrhoea may cause dehydration which could cause a deterioration of renal function. Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, semaglutide should be discontinued; if confirmed, semaglutide should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Use of semaglutide in combination with a sulfonylurea or insulin may have an increased risk of hypoglycaemia, therefore consider reducing the dose of sulfonylurea or insulin when initiating treatment with Ozempic®. In patients with diabetic retinopathy treated with insulin and semaglutide, an increased risk of developing diabetic retinopathy complications has been observed. Caution should be exercised when using semaglutide in patients with diabetic retinopathy treated with insulin. These patients should be monitored closely and treated according to clinical guidelines. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy, but other mechanisms cannot be excluded. When semaglutide is used

in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines. Fertility, pregnancy and lactation: Women of childbearing potential are recommended to use contraception when treated with semaglutide. Should not be used during pregnancy or breast-feeding. Discontinue at least 2 months before a planned pregnancy. Effect on fertility unknown. Undesirable effects: Very common (≥1/10): Hypoglycaemia when used with insulin or sulfonylurea, nausea, diarrhoea. Common (≥1/100 to <1/10): Hypoglycaemia when used with other oral antidiabetic medications, decreased appetite, dizziness, diabetic retinopathy complications, vomiting, abdominal pain, abdominal distension, constipation, dyspepsia, gastritis, gastrooesophageal reflux disease, eructation, flatulence, cholelithiasis, fatigue, increased lipase, increased amylase, weight decreased. Uncommon (≥1/1,000 to <1/100): Hypersensitivity, dysgeusia, increased heart rate, acute pancreatitis, injection site reactions. Rare (≥1/10,000 to <1/1,000): Anaphylactic reaction. Not known (cannot be estimated from available data): Angioedema. The SmPC should be consulted for a full list of side effects. MA numbers: Ozempic® 0.25 mg pre-filled pen EU/1/17/1251/002. Ozempic® 0.5 mg pre-filled pen EU/1/17/1251/003. Ozempic® 1 mg pre-filled pen EU/1/17/1251/005. Each pre-filled pen delivers 4 doses and includes 4 disposable NovoFine® Plus needles. Legal Category: POM. For complete prescribing information, please refer to the SmPC which is available on www. medicines.ie or by email from infoireland@novonordisk.com or from the Clinical, Medical and Regulatory Department, Novo Nordisk Limited, 1st Floor, Block A, The Crescent Building, Northwood Business Park, Santry, Dublin 9. Date last revised: March 2021.

tAdverse events should be reported to the Health Products Regulatory Authority. Information about adverse event reporting is available at www.hpra.ie. Adverse events should also be reported to Novo Nordisk on Tel: 1850 665 665 or complaintireland@novonordisk.com

versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulinnaive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol 2017;5: 355–66. 7. Sorli C et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol 2017; 5: 251–60. 8. Ahrén B et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol 2017; 5: 341–54. 9. Pratley RE et al. Semaglutide versus dulaglutide once-weekly in patients with type 2 diabetes (SUSTAIN

a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6275-286. 10.Buse JB et al. 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020 Feb; 43(2):487-493.

Ozempic® is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise • as monotherapy when metformin is considered inappropriate due to intolerance or contraindications • in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1. of the SmPC.1 tThis medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.

Novo Nordisk Limited, First Floor, Block A, The Crescent Building, Northwood Business Park, Santry, Dublin 9, D09 X8W3, Ireland. Tel: 01 8629 700, Fax: 01 8629 725, Lo call: 1 850 665665. infoireland@novonordisk.com www.novonordisk.ie

Ozempic® and the Apis bull logo are registered trademarks owned by Novo Nordisk A/S.

Date of preparation: October 2021. IE21OZM00098

Two consultants for Mater trauma centre recruited

DAVID LYNCH

Two consultant appointments have been made for the new major trauma centre (MTC) at the Mater Misericordiae University Hospital, Dublin, and 12 are at an “advanced stage”, the Medical Independent (MI) has been told.

Last year, the Government approved the designation of the Mater as the MTC for the new central trauma network.

A spokesperson for the HSE told MI that major trauma services are expected to commence at the Mater by the end of September.

“Implementation planning and preparations are currently underway to ensure that the required resources and clinical pathways are in place to support the opening of the MTC,” said the spokesperson.

On the recruitment of consultant staff, the spokesperson said that annual funding to appoint 17 consultants for the MTC at the Mater has been provided.

“Recruitment of consultant and other key clinical and support staff required to commence major trauma services at the MTC in Dublin is underway.”

As reported in MI in August 2021, the decision to designate the Mater as the MTC for the central trauma network led to criticism regarding neurosurgery provision. At the time, neurosurgeons

in Beaumont Hospital, Dublin, where the national neurosurgical centre is located, said they believed the national neurosurgical centre needed to be co-located with the MTC.

The HSE informed MI that in recent months an advisory group on this issue had been established and recently reported to the Executive.

“A neuro-trauma clinical advisory group (CAG) has been established to work through detailed service considerations to enable an integrated model of care for neurotrauma/neurocritical care services for the MTC in Dublin as a collaboration between the Mater Hospital and Beaumont Hospital,” said the spokesperson. “The CAG has met a number of times and recently presented an update on its work to the HSE.”

Development of new clinical pathway for liver ultrasounds is ‘ongoing’

NIAMH QUINLAN

There is still no date for the roll-out of transient elastography for liver disease testing in community settings, according to the HSE National Clinical Programme for Gastroenterology and Hepatology.

The development of the clinical pathway for altered liver functioning tests (LFTs) is a “work in progress”, a spokesperson for the programme told the Medical Independent

It is over a year since the programme’s hepatology working group was established in May 2021 to commence the design of the LFT pathway.

The programme is currently securing funding for the project, which will be aligned with Sláintecare principles.

Transient elastography (FibroScan) is a non-invasive test for liver stiffness to determine the degree of fibrosis or scarring that may be present in the liver from various liver diseases or conditions.

The programme spokesperson highlighted that much of the burden placed on hospitals regarding liver disease could be eased through a hub-and-spoke model utilising FibroScan.

“The new hub-and-spoke approach will provide more appropriate nurse and doctor outreach, therefore many outpatients and lower acuity inpatients could be managed in [model] 3 hospitals.”

Similar to the model employed in the

Northern Ireland health service, regional hepatology hubs would be delivered by advanced nurse practitioners (ANPs). The ANPs would complete diagnosis and staging, FibroScanning, venesection and motivational interviewing for behavioural change.

According to the clinical programme: “A submission to support a national rollout of a hub-and-spoke model for hepatology was put forward as part of [the] national service plan 2022. This submission included nine [whole-time equivalent] ANPs, which would support the development of regional liver hubs.”

According to Consultant Hepatologist at the Royal Victoria Hospital in Belfast, Dr Conor Braniff, transient elastography has been used by specialist nurses in Northern Ireland to test for viral hepatitis in communities.

CATHERINE REILLY catherine@mindo.ie

Progressing a potential donor audit in Ireland

A potential organ donor audit for Ireland has entered its development phase. Catherine Reilly reports on a recent seminar where the Australian system was discussed

In 2008, the Australian government announced a major national reform programme for organ donation that involved several elements including establishing a national potential donor audit (the DonateLife audit).

“As a government-led initiative in healthcare, this is one of the most impressive I have ever seen,” Assoc Prof Michael O’Leary, State Medical Director of the New South Wales Organ and Tissue Donation Service, told the Medical Independent (MI)

Assoc Prof O’Leary spoke at a recent seminar in Dublin organised by the National Office of Clinical Audit (NOCA) and attended by organ donation personnel. In March, NOCA published the Potential Donor Audit Feasibility Study Report , which was commissioned by HSE Organ Donation and Transplant Ireland. It recommended the development of a potential donor audit starting with implementation in one hospital in each of the six Hospital Groups and expanding to all acute hospitals, including paediatric hospitals, as organ donation nurse manager resources increase.

According to the report, evidence from other countries indicated that a potential donor audit was a key driver of improvement in organ donation rates. It noted the rate of organ donation in Ireland was 18 per million population (PMP) compared to 25 PMP in the UK and over 45 PMP in Spain.

Increase

Assoc Prof O’Leary said the Australian potential donor audit was an important element of the national reform programme, which received significant financial investment from government. The programme involved appointment of specialist organ donation nurses and doctors covering 81 hospitals across Australia, development of a national authority for organ donation, and enhancements to organ donation retrieval services.

Between 2009 and 2019, the number of donors increased by 122 per cent. The number of donors PMP rose from 9.8 (which was “really poor on the world stage”, acknowledged Assoc Prof O’Leary) to just over 20 in 2019.

Assoc Prof O’Leary said it was difficult to specify the

impact of the audit as it was part of a larger programme. “But I don’t think any of that would have been possible without an audit,” he told MI

The audit was “a very important part of the approach within the hospitals”, he continued.

“The idea back then was that we needed a way of determining the potentiality for donation so we know how many potential donors we might be able to get with best practice, and then to look at missed opportunities. So it is a classical audit system where you measure and then you have some form of feedback to the people who are involved in the management of the patients, and through that, you hope processes will be put in place that lead to practice change; that leads to an increase in the number of donors.

“So that is what we did. The initial way the audit worked back then, in the early stages, was principally focused on donor identification, missed opportunities and how they

The Mater Hospital

PRESCRIBING INFORMATION (PI)

RINVOQ® (upadacitinib) 15 mg and 30mg prolonged-release tablets. Refer to Summary of Product Characteristics (SmPC) for full prescribing information. PRESENTATION: Each 15 mg prolonged-release tablet contains upadacitinib hemihydrate, equivalent to 15mg of upadacitinib. Each 30mg prolonged-release tablet contains upadacitinib hemihydrate, equivalent to 30 mg of upadacitinib. INDICATION:

Treatment of moderate to severe active rheumatoid arthritis (RA) and active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. Treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy. DOSAGE AND ADMINISTRATION: Intended for use under guidance and supervision of a physician experienced in diagnosis and treatment of conditions for which upadacitinib is indicated. Dosage: RA, PsA and AS: The recommended oral dose is 15mg once daily. Consideration should be given to discontinuing treatment in patients with AS who have shown no clinical response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. AD (adults): The recommended oral dose is 15 mg or 30 mg once daily based on individual patient presentation. 30 mg once daily dose may be appropriate for patients with high disease burden and for patients with an inadequate response to 15 mg once daily. The lowest effective dose for maintenance should be considered. For patients ≥ 65 years of age, the recommended dose is 15mg once daily. AD (adolescents from 12 to 17 years): The recommended oral dose is 15mg once daily for adolescents weighing at least 30 kg. Adults and adolescents 12 years and older: Upadacitinib can be used with or without topical corticosteroids. Topical calcineurin inhibitors may be used for sensitive areas such as the face, neck, and intertriginous and genital areas. Consideration should be given to discontinuing upadacitinib treatment in any patient who shows no evidence of therapeutic benefit after 12 weeks of treatment. Special Populations: Elderly: For AD, doses higher than 15mg once daily not recommended in patients aged 65 years and older. Limited data for patients aged 75 and older. Renal: No dose adjustment required in mild-moderate renal impairment. Upadacitinib 15mg once daily should be used with caution in patients with severe renal impairment. Upadacitinib 30 mg once daily is not recommended for patients with severe renal impairment. Upadacitinib has not been studied in subjects with end stage renal disease. Hepatic impairment: No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Should not be used in patients with severe (Child Pugh C) hepatic impairment. Paediatric Population: No data available in the following paediatric patient populations: children with AD below the age of 12 years; children and adolescents with RA, PsA and AS aged 0 to less than 18 years. CONTRAINDICATIONS: Hypersensitivity to active substance or excipients. Active tuberculosis (TB) or active serious infections. Severe hepatic impairment. Pregnancy. SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details. Immunosuppression: Combination use, with immunosuppressants e.g. azathioprine, ciclosporin, tacrolimus, and biologic DMARDs or other JAK inhibitors has not been evaluated in clinical studies and is not recommended as the risk of additive immunosuppression cannot be excluded. Serious infections: Serious and fatal infections have been reported. Caution when treating patients ≥65 years. Frequently reported – pneumonia and cellulitis. Bacterial meningitis has been reported. Opportunistic infections reported –TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis. Do not initiate treatment in patients with active, serious infection, including localised infections. Consider the risk/benefit of treatment in patients with: chronic or recurrent infection, history of serious or opportunistic infection, those exposed to TB, those who have resided or travelled in areas of endemic TB or endemic mycoses, those with underlying conditions that may pre-dispose patients to infection. Closely monitor patients and interrupt treatment if there are signs and symptoms of infection pre and post treatment. Tuberculosis: Pre-screen patients for active or latent TB. RINVOQ should not be given to patients with active TB. Consider anti-TB therapy in patients with previously untreated latent TB or in patients with risk factors for TB infection. Consult with a physician with experience in TB therapy to assess whether initiating anti-TB therapy is appropriate for an individual patient. Monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

Viral reactivation: Cases of herpes virus reactivation have been reported e.g. herpes zoster. If herpes zoster is reactivated, consider interruption of upadacitinib therapy until the episode resolves. Screen for viral hepatitis and monitor regularly for reactivation before starting and during therapy with upadacitinib. Patients, positive for hepatitis C antibody/hepatitis C virus RNA and hepatitis B surface antigen/hepatitis B virus DNA were excluded from clinical studies. If hepatitis B virus DNA is detected while receiving RINVOQ, a liver specialist should be consulted. Vaccination: Use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunisations, including

HELP YOUR PATIENTS

THE ITCH & RASH OF MODERATE TO SEVERE ATOPIC DERMATITIS 1

RINVOQ demonstrated in an integrated analysis of the MEASURE UP 1 & 2 monotherapy studies at Week 16:

• EASI 75 skin clearance rates of 76% and 65% for patients treated with RINVOQ 30 mg QD and 15 mg QD, respectively, vs 15% with placebo (p<0.001 for both comparisons)2

• Itch reduction (mean percent change from baseline in Worst Pruritus NRS) of –70% and –58% for RINVOQ 30 mg QD and 15 mg QD, respectively, vs –24% with placebo (p<0.001 for both comparisons)2

prophylactic zoster vaccinations prior to starting therapy, in agreement with current immunisation guidelines.

Malignancy: Immunomodulatory therapies may increase the risk of malignancies including lymphoma and nonmelanoma skin cancer in RA patients. Malignancies were observed in clinical studies. Periodic skin examination recommended for patients who are at increased risk for skin cancer. See SmPC for full details. Haematological abnormalities: Do not start therapy if Absolute Neutrophil Count <1 x 109 cells/L, Absolute Lymphocyte Count <0.5 x 109 cells/L and Hb <8 g/dL. Monitor patients and temporarily stop therapy if abnormal haematological parameters as specified are detected during routine patient management. Diverticulitis: Events of diverticulitis have been reported in clinical trials and post-marketing. Upadacitinib should be used with caution in patients with diverticular disease and especially in patients chronically treated with concomitant medications associated with an increased risk of diverticulitis. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis to prevent gastrointestinal perforation. Cardiovascular Risk: RA patients have an increased risk for cardiovascular disorders. Manage patient’s risk factors for e.g. hypertension, hyperlipidaemia as per usual standard of care. Lipids: Monitor total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) at 12 weeks and thereafter according to international guidelines. Elevated LDL in clinical trials decreased to pre-treatment levels in response to statin therapy, although evidence is limited. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Hepatic transaminase elevations: Monitor liver enzymes at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. In such cases therapy should be interrupted until this diagnosis is excluded. Venous thromboembolism: Deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAKi, including upadacitinib. Use therapy with caution in patients at high risk for DVT/PE. Risk factors should be determined by patients age, obesity and medical history of DVT/PE, patients undergoing major surgery and prolonged immobilisation. If clinical features of DVT/PE occur discontinue therapy, evaluate and treat promptly. INTERACTIONS: Upadacitinib is metabolised mainly by CYP3A4 and plasma exposures may be affected by CYP3A4 inhibitors or inducers. Upadacitinib 15 mg once daily should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors. Upadacitinib 30 mg once daily dose is not recommended for patients receiving chronic treatment with strong CYP3A4 inhibitors. See SmPC for full details. FERTILITY, PREGNANCY AND LACTATION: Upadacitinib is contraindicated during pregnancy. Women of childbearing potential should be advised to use effective contraception during treatment and for 4 weeks following the final dose of upadacitinib. Female paediatric patients and/or their parents/caregivers should be informed about the need to contact the treating physician once the patient experiences menarche while taking upadacitinib. Upadacitinib should not be used during breast-feeding. The effect of upadacitinib on human fertility has not been evaluated. ADVERSE REACTIONS: Refer to SmPC for full details on adverse reactions. Very common adverse reactions (≥1/10): upper respiratory tract infections, acne. Common adverse reactions (≥1/100 to <1/10): bronchitis, herpes zoster, herpes simplex, folliculitis, influenza, anaemia, neutropaenia, hypercholesterolaemia, cough, abdominal pain, nausea, urticaria, fatigue, pyrexia, increased blood CPK/ALT/AST, increased weight and headache. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; website: www.hpra.ie.

LEGAL CLASSIFICATION: POM (S1A). MARKETING AUTHORISATION NUMBER/ PRESENTATION: EU/1/19/1404/001 and EU/1/19/1404/006 – Calendar blister packs containing 28 prolonged-release tablets. MARKETING AUTHORISATION HOLDER: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany. Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.

DATE OF REVISION: December 2021. PI-1404-005

Abbreviations: EASI – eczema activity and severity index; NRS – numerical rating scale; QD – once daily; EU – European Union.

* The recommended dose of RINVOQ is 15mg once daily for adolescents weighing at least 30kg. The safety and efficacy of RINVOQ in children with atopic dermatitis below the age of 12 years have not been established. No data are available. No clinical exposure data are available in adolescents <40kg. The posology in adolescent patients 30kg to <40kg was determined using population pharmacokinetic modelling and simulation.2

Reference: 1. Langan S. et al. Atopic dermatitis. The Lancet. 2020;396(10247):345-360. DOI: https://doi.org/10.1016/ S0140-6736(20)31286-1.

2. RINVOQ Summary of Product Characteristics, available on www.medicines.ie

3. Baricitinib Summary of Product Characteristics, available on www.medicines.ie 4. Abrocitinib Summary of Product Characteristics, available on www.medicines.ie

RINVOQ, the first and only oral JAK inhibitor indicated for the treatment of both adults and adolescents ≥12 years* with moderate to severe Atopic Dermatitis in the EU

This is a paid advertisement sponsored by AbbVie, it is part of a 3-page advertisement. Prescribing information for RINVOQ can be found on page 1 and for SKYRIZI on page 3

could be identified and how processes could be put in place to change that.”

Originally there was some scepticism about the extent of missed donation opportunities.

Assoc Prof O’Leary told MI: “As an intensive care specialist I believed we had no problem with donor identification in Australia, especially in the brain-dead pool. I thought there is no way we are missing brain-dead donors and we are probably doing nearly as good as we can… and I was proven completely wrong, we weren’t, and the increase in donors in that period was pretty much equally made up of brain-dead donors as DCD [donation after circulatory death] donors…. There was a really significant increase in brain-dead donors.”

Doctors may be resistant to change without the presence of hard data, according to Assoc Prof O’Leary.

Australia also has an ‘opt-in’ system and 36 per cent of the eligible population have registered as donors, according to 2021 data. Consent rates are substantially higher where a person has registered as a donor and/or their family are aware of their wishes.

Irish audit

Dr Alan Gaffney, Clinical Lead for the NOCA Potential Donor Audit, told MI that the Irish audit has moved to the development phase, which involves it being deployed in one hospital in six of the Hospital Groups. It is anticipated that this phase will continue until May 2023. The findings from the Potential Donor Audit Development Study will then be presented to the September meeting of the NOCA governance board for endorsement and publication.

Dr Gaffney, who is also Clinical Lead in Organ Donation at RCSI Hospital Group, said the appointment of specialist organ donation staff in hospitals is proven to boost donation rates. Currently, there are six clinical leads in organ donation and nine organ donation nurse manager posts (five nurse manager posts are filled with four in the recruitment process, according to the HSE). There are four additional nurse manager posts planned under the HSE National Service Plan 2022 .

The ultimate aim is to have an organ donation nurse specialist in every acute hospital.

“Yes, that is the idea,” said Dr Gaffney. “Again, in principle, if you have organ donation personnel in the units, on the ground, working with those ICUs, and they are trained well and they have got an audit, that is the most likely [way] to increase organ donation rates – at least that is the evidence from around the world.”

The forward to NOCA’s Potential Donor Audit Feasibility Study Report was authored by Dr Beatriz DomínguezGil, Director General of Spain’s Organización Nacional de Trasplantes – a world leader in the area. She stated that the key to improving deceased organ donation rates was “the exquisite management of a multidisciplinary process of high complexity – the deceased donation pathway”. This entailed appointment of the “right professionals, providing them with appropriate guidance and continuous training, and assessing performance”.

Dr Domínguez-Gil cautioned of “magic bullets”, such as promotional campaigns or reforming the existing legislation towards an ‘opt-out’ system, noting that these measures had never been proven to result in “sustained improvements in organ donation”.

Asked if it was a concern that this message was being lost with the Government’s focus on opt-out legislation, Dr Gaffney said: “I think so, yes. There is good and bad [in regard to the proposed legislation]. From a political point of view, changing legislation is something that politicians can do, so that can increase the visibility of organ donation within a country and that itself can have the side-effect of hopefully improving the community attitude towards organ donation, although there is nothing to suggest that that is not really high in Ireland…. There is a huge community acceptance of organ donation within the country already, which is great.”

However, he said it is vital that the complex processes

relating to organ donation in hospitals and the interaction with families are carried out in a “meticulous fashion”.

“We feel that having the right people in the ICUs to make sure that that happens and to be able to then measure and complete that feedback loop and make sure that what should be happening is happening, is the key.”

Dr Gaffney indicated that no definitive statements can be made on the number of donation opportunities in Ireland that may be missed until the necessary data is collected and analysed.

“What we are doing at the moment is comparing our donation rate per million of population to the rest of the world, and we are making an assumption that it could be better. If we make that assumption that it could be better, then by definition there are missed opportunities unless we can prove that there aren’t – and the only way to prove that there aren’t is to go out and do an audit, so to find out how many people are dying in circumstances where organ donation could be a possibility and how many of those [families] are we actually approaching and how many are actually going through that process.”

While Ireland has a low rate of DCD donation, Dr Gaffney highlighted that such donations have now been facilitated in several hospitals nationally, whereas previously they only took place in Dublin centres. He confirmed that it is planned the Irish audit will include potential DCD donations. Most countries, he noted, focus on optimising donation after brain death in the first instance.

“If you get that right, that is a good measure of how well the system is working. Once you have a very well-functioning system for donation after brain death, then donation after circulatory death is something that can certainly add to that…. Our view in the country at the moment is we should optimise the number of donations after brain death and then once that is in place, then start expanding the donation after circulatory death numbers.”

Dr Gaffney acknowledged that ICU capacity impacts on organ donation rates. However, he was encouraged by Government commitments to enhance capacity following the onset of the pandemic.

PPI

After NOCA’s recent seminar, a steering committee was formed with key stakeholders including public and patient interest (PPI) representatives for the potential donor audit. PPI representative Ms Martina Goggin founded the Strange Boat Donor Foundation with her husband Denis after the death of their son, Éamonn, to help support other organ donor families (further details can be found at www.organdonation.ie).

She commented: “As the parent of an organ donor I feel it is most important that potential donors always be identified, and their families given the opportunity of considering organ donation by being spoken to by an appropriately trained organ donation specialist.”

“Although I was very aware of organ donation, at a time of such overwhelming anguish when our son was on life support, if we had not been approached and asked about donating our son’s organs, quite possibly we would not have thought of it. How disappointing and devastating that would be knowing the comfort organ donation gives and the ongoing benefit to a donor family.”

Assoc Prof Michael O’Leary, State Medical Director, New South Wales Organ and Tissue Donation Service; and Dr Alan Gaffney, Clinical Lead in Organ Donation, RCSI Hospital Group and Clinical Lead, Potential Donor Audit

Pictured L-R: Ms Marina Cronin, Head of Quality and Development, National Office of Clinical Audit (NOCA); Mr John Walsh, Chief Operations Officer, Organ Donation and Transplant Ireland (ODTI); Assoc Prof Michael O’Leary, State Medical Director, New South Wales Organ and Tissue Donation Service; Ms Eimear Shields, Donor Coordinator, ODTI; Ms Hilary Barry, Quality Manager, ODTI; Ms Breda Doyle, Organ Donation Nurse Manager, South/South West Hospital Group; Mr Dara Kelly, System Administration Manager, ODTI; Ms Nikki Philips, Organ Donation Nurse Manager, Dublin Midlands Hospital Group; Ms Karen Healy, Organ Donation Nurse Manager, RCSI Hospital Group; Ms Gillian Shanahan, Organ Donation Nurse Manager, Saolta University Health Care Group; Dr Alan Gaffney, Clinical Lead in Organ Donation, RCSI Hospital Group and Clinical Lead, Potential Donor Audit; Ms Collette Tully, Executive Director, NOCA; and Dr Maria Kehoe, Postdoctoral Researcher, NOCA

*Ryaltris™ is indicated in adults and adolescents 12 years of age and older for the treatment of moderate to severe nasal symptoms associated with allergic rhinitis1

Ryaltris™ 25 mcg/actuation + 600 mcg/actuation nasal spray, suspension.

Prescribing information

Please consult the Summary of Product Characteristics (SmPC) for full prescribing information.

Presentation: One delivered dose contains mometasone furoate monohydrate equivalent to 25 mcg mometasone furoate and olopatadine hydrochloride equivalent to 600 mcg olopatadine. White, homogeneous suspension.

Uses: In adults and adolescents 12 years of age and older for the treatment of moderate to severe nasal symptoms associated with allergic rhinitis.

Dosage: For nasal use only. Adults and adolescents (12 years of age and over) two actuations in each nostril twice daily (morning and evening). Elderly: no dose adjustment required. Children under 12 years: not recommended. Renal and hepatic impairment: no dose adjustment expected.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Presence of untreated localised infection involving the nasal mucosa, such as herpes simplex. Recent nasal surgery or trauma until wound healing has occurred.

Warnings and Precautions: Instances of nasal ulceration and nasal septal perforation have been reported. Not recommended in case of nasal septum perforation. Patients using Ryaltris™ over several months or longer should be examined periodically for possible changes in the nasal mucosa and for evidence of Candida infection. Instances of epistaxis have been reported. Visual disturbance may be reported with systemic and topical corticosteroid use. Consider referral to ophthalmologist with symptoms such as blurred vision or other visual disturbances as cataract, glaucoma or rare diseases such as central serous chorioretinopathy have been reported after use of systemic and topical corticosteroids. Hypersensitivity reactions, including wheezing, may occur - discontinue. Immunosuppression: use with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract, untreated local or systemic fungal or bacterial infections, systemic viral or parasitic infections, or ocular herpes simplex. Potential systemic effects of corticosteroids include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Hypercorticism and adrenal suppression may appear at higher than recommended dosages or in susceptible individuals at recommended dosages - discontinue slowly. Increased risk of signs or symptoms of hypercorticism and/or suppression of the HPA axis possible with concomitant use with other inhaled corticosteroids. Careful monitoring needed for acute adrenal insufficiency in response to stress in patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids. In patients with asthma or other conditions requiring long term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of symptoms. Somnolence has been reported following administration of Ryaltris™ in clinical studies. Caution in patients operating machinery or driving a motor vehicle. Avoid concurrent use with alcohol or other central nervous system (CNS) depressants. Increased risk of antihistamine adverse effects with concomitant use of olopatadine or other antihistaminic drugs administered via nasal, ocular or oral route. Paediatric population: It is recommended that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. Contains 0.02 mg benzalkonium chloride in each actuation. Benzalkonium chloride may cause irritation or swelling inside the nose, especially if used for a long time.

Interactions: No interaction studies have been performed with Ryaltris™. Any interactions

from the combination of olopatadine and mometasone furoate are expected to reflect those of the components taken individually, no pharmacokinetic interaction between olopatadine and mometasone furoate was observed when administered in combination. Olopatadine: No interactions with other drugs expected. Mometasone Furoate: Cotreatment with CYP3A inhibitors should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects and patients should be monitored.

Pregnancy and Lactation: Avoid use during pregnancy unless potential benefit to mother justifies potential risk to mother, foetus or infant. Assess before prescribing in lactating mothers.

Side Effects: Common: dysgeusia, epistaxis, nasal discomfort. Uncommon: dizziness, headaches, somnolence, nasal dryness, dry mouth, abdominal pain, nausea, fatigue. Rare: bacterial vaginosis, anxiety, depression, insomnia, lethargy, migraine, blurred vision, dry eye, eye discomfort, ear pain, nasal inflammation, nasal mucosal disorder, oropharyngeal pain, sneezing, throat irritation, constipation, sore tongue, laceration. Frequency not known: pharyngitis, upper respiratory tract infection, hypersensitivity (including anaphylactic reactions, angioedema, bronchospasm, dyspnoea), cataracts, glaucoma, increased intraocular pressure and nasal septum perforation.

Pack Sizes: One bottle containing 30ml suspension (240 actuations).

Legal Category: POM.

Product Authorisation Numbers: PA 1543/002/001

Product Authorisation Holder: Glenmark Pharmaceuticals s.r.o., Hvezdova 1716/2b, 140 78 Prague 4, Czech Republic.

Marketed by: A. Menarini Pharmaceuticals Ireland Ltd. Further information is available on request from A. Menarini Pharmaceuticals Ireland Ltd., 2nd Floor, Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924 or may be found in the SmPC.

Date of Preparation: June 2022.

IR-RYL-12-2022 May 2022

Ryaltris™ Summary

The next steps for the naloxone service

The HSE is to “target” urban areas outside of Dublin to ensure greater availability of naloxone, the Medical Independent (MI) has been informed.

Naloxone is a medication used to reverse the effects of opioid drugs, such as heroin, morphine, and methadone in the event of overdose.

It is recommended by the World Health Organisation (WHO) for the treatment of opioid overdose cases. According to the HSE, it reverses the effects of opioid overdose “within minutes”. In Ireland, opioids are the main drug group linked to drug overdose deaths.

In 2015, the HSE carried out a naloxone pilot project. After a year it was deemed a success and the Executive has since developed an expanded naloxone training programme for service providers. It has also extended the availability of naloxone beyond the reach of the original pilot. Training has been delivered to service providers that would encounter people who use drugs (PWUD). This has included a particular focus on homeless services.

In June, the first evaluation of the programme was published since the assessment of the original pilot was published in 2016.

The new report, Naloxone Administration by Addiction and Homeless Service Providers in Ireland: 2018-2020 , found that “at least” 22 lives had been saved by the programme during those three years.

Geography

One of a series of recommendations in the report is that the programme should continue to be resourced and “expanded to achieve a stronger geographical spread given the demonstrated lifesaving benefits”.

The HSE has told MI it is now considering the possible expansion of services to a number of specific cities outside the capital.

“The report noted that the majority of administrations were in the Dublin region, with a sizeable number in Limerick,” the HSE spokesperson said.

“Other areas had lower levels of administration. The HSE will be examining this to determine if this was due to under reporting or lack of availability. In the first instance there will be a concerted effort to target those areas, urban areas, such as Galway, Cork, and Waterford, where reported use is low to ensure more product is available. Follow-up will take place with services there to improve reporting.”

The spokesperson added that the HSE has received additional funding this year of €50,000 to “expand” the naloxone programme in terms of “training and product”.

According to the new report, almost three-quarters of cases where naloxone was administered were in Co Dublin (400 overdoses). Four areas of Dublin city

(Dublin 7, Dublin 1, Dublin 8, and Dublin 2) accounted for over two-thirds (67 per cent) of overdoses where naloxone was administered. After Co Dublin, Co Limerick was the next highest, with naloxone administered in 92 cases of overdose.

On the publication of the report, Dr David Evans, Research and Data Officer with HSE Addiction Services, said that naloxone was administered on 569 occasions “in overdose situations” over the three years (2018-20).

“Using international literature on survival outcomes, it is estimated that this has resulted in saving at least 22 lives. In reality, these 22 individuals and their families have been given another chance at life.”

Ms Yvonne O’Neill, National Director of HSE Community Operations, said the programme “fundamentally saves lives, while also producing savings for the State”. According to the conclusions of the report, “for every €1 spent on the programme there was a return of €2.36 in terms of gained productivity due to death prevention.”

Also speaking at the report launch, Prof Eamon Keenan, National Clinical Lead for HSE Addiction Services, said it is

progress has been made.

“The PCRS are now sitting on the quality assurance group overseeing the naloxone project and are working closely with the addictions services in relation to reimbursement of the nasal product,” said the spokesperson.

“In relation to the intramuscular product, the manufacturer would have to make a submission to the NCPE. This topic will remain on the agenda of the quality assurance group. No date is available for a decision.”

The report found that of the over 500 naloxone doses administered between 2018-20, the vast majority were intramuscular (92 per cent), with just 8 per cent intranasal.

According to the Executive, the continued development of the programme will be “focused on ensuring that all those individuals who have been administered naloxone are signposted to relevant treatment services to ensure that their ongoing health needs are addressed”.

The report said that between 2018-2020, the supply of naloxone units by the HSE’s national social inclusion office increased by 149 per cent. This amounts to 8,881 units over the three years.

oid agonist treatment.

Just over half of those that had received naloxone were reported to have taken more than one substance, with 35 per cent taking two substances. Some 62 per cent of people were reported to have overdosed by injection. Over two-thirds (68 per cent) of those that had taken heroin had injected.

Other people were reported to have been present for 64 per cent of overdoses. The average number of people present was 2.7.

Recommendation

As well as increasing the geographical distribution of the service and the PCRS recommendations, the report also said it must be ensured that all individuals who have been administered naloxone are ‘signposted’ to relevant treatment services “to ensure that their ongoing health needs are addressed”.

The report also recommends that “ambulance services should be called in all instances where naloxone is administered. This should be a target set for all service providers and should be reviewed annually and this recommendation should be incorporated into training.”

The report authors conclude that a training programme should be “reviewed yearly” to ensure that the course content is up to date with developments in drug trends, “in particular any emergence of synthetic opioids that may influence naloxone requirements.”

“In addition, a refresher training programme should be developed to facilitate skill retention. This should contain practical examples and utilise both face-to-face and remote options to expand the provision of training.”

recognised that the increased availability of training and the provision of naloxone in the community has the potential to reduce drug-related deaths among a population who use opioid drugs.

“This report has highlighted this fact and continued investment will benefit individuals and their families,” said Prof Keenan.

“We have identified a need to improve research, expand provision and engage with stakeholders in relation to naloxone.... This is particularly relevant if we observe what is happening in relation to the emergence of synthetic opioids, which carry additional overdose risks, in parts of Europe and North America.”

Reimbursement

The new report also recommends reimbursement of intramuscular naloxone by the Primary Care Reimbursement Service (PCRS) “in line with the National Centre for Pharmacoeconomics (NCPE)” would merit consideration.

Asked whether this recommendation for reimbursement has been sent to the PCRS, the HSE stated that some recent

During the three years, 569 people were administered naloxone with 98 per cent surviving and nine deaths (2 per cent).

Gender

Of the 569 people who were administered naloxone, the majority were male. This proportion increased from 51 per cent in 2018 to 75 per cent in 2020.

Of all the people administered, 71 per cent were aged between 25 and 44 years. The average age over the three years was 37.6 years. This average increased on an annual basis from 36.2 years in 2018 to 40.3 years in 2020.

A larger proportion of females were 2534 years (41 per cent compared to 23 per cent for males), while a larger proportion of men were aged 45-54 years (28 per cent compared to 11 per cent for females).

According to the report, there was a need for “gender specific initiatives” in terms of overdose prevention and treatment and this issue “needs further recognition and wider implementation”.

Some 60 per cent of those that had received naloxone were also receiving opi-

Naloxone training and distribution to PWUD should include other potential bystanders, such as family members, close friends, and members of An Garda Síochána.

The report authors stated that a specific drug education programme for PWUD on overdose risks, in particular polydrug use, should be developed.

“The process of recording naloxone administrations should be streamlined to facilitate data analysis and to ensure that all naloxone administrations are recorded. Consideration should be given to redesigning the form and developing a secure mobile ‘app’ or online submission system, in line with GDPR.”

However, the overall conclusion of the report was positive.

“The study has demonstrated the value of distributing naloxone to addiction services and services providing care for homeless people and training staff and peers in the administration of this life-saving product,” according to the report.

“This initiative has saved and is continuing to save lives and the overall utility of the approach has been clearly demonstrated.”

This initiative has saved and is continuing to save lives and the overall utility of the approach has been clearly demonstrated

David Lynch examines a recent report on the naloxone service, which has saved more than 20 lives in three years

Whether your patients’ moderate-to-severe AD is FIERCE or TAMER,

CIBINQO is a convenient once-daily oral JAK1 inhibitor for moderate-to-severe atopic dermatitis (AD) that o ers1-4

Significant skin clearance at week 12, with sustained control at week 481,5

Rapid itch relief, superior to dupilumab + TCS at week 2 for CIBINQO 200 mg + TCS, with significant results as early as day 41,6

A once-daily pill available in multiple doses that can be used with or without medicated topical therapies so you can tailor treatment to meet the individual needs of your patients1-3,7,8

CONSISTENT SAFETY PROFILE: Rigorously studied in >3100 patients across 7 clinical trials, including one ongoing LTE 9

PRESCRIBING INFORMATION CIBINQO® ▼ (ABROCITINIB)

Please refer to full Summary of Product Characteristics (SmPC) before prescribing Cibinqo®.

Presentation: Film-coated tablets containing 50 mg, 100 mg, or 200 mg abrocitinib. Each tablet contains 1.37 mg, 2.73 mg, and 5.46 mg of lactose monohydrate, respectively.

Indications: For the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. Dosage: Treatment should be initiated and supervised by a healthcare professional experienced in the diagnosis and treatment of atopic dermatitis. Posology: The recommended starting dose is 200 mg once daily. A starting dose of 100 mg once daily is recommended for patients ≥ 65 years of age. For other patients who may benefit from a starting dose of 100 mg, see sections 4.4 and 4.8 of the SmPC. During treatment, the dose may be decreased or increased based on tolerability and e cacy. The lowest e ective dose for maintenance should be considered. The maximum daily dose is 200 mg. Can be used with or without medicated topical therapies for atopic dermatitis. Discontinuation of treatment should be considered in patients who show no evidence of therapeutic benefit after 24 weeks. Treatment initiation: Treatment should not be initiated in patients with a platelet count < 150 × 10 /mm , an absolute lymphocyte count (ALC) < 0.5 × 103/mm3, an absolute neutrophil count (ANC) < 1.2 × 10 /mm or who have a haemoglobin value < 10 g/dL. Dose interruption: If a patient develops a serious infection, sepsis or opportunistic infection, dose interruption should be considered until the infection is controlled. Interruption of dosing may be needed for management of laboratory abnormalities. Missed doses: If a dose is missed, patients should be advised to take the dose as soon as possible unless it is less than 12 hours before the next dose, in which case the patient should not take the missed dose. Thereafter, dosing should be resumed at the regular scheduled time. Interactions: In patients receiving dual strong inhibitors of cytochrome CYP2C19 and moderate inhibitors of CYP2C9, or strong inhibitors of CYP2C19 alone (e.g., fluvoxamine, fluconazole, fluoxetine and ticlopidine), the recommended starting dose of Cibinqo should be reduced by half to 100 mg or 50 mg once daily. Treatment is not recommended concomitantly with moderate or strong inducers of CYP2C19/CYP2C9 enzymes (e.g., rifampicin, apalutamide, efavirenz, enzalutamide, phenytoin). Renal impairment: No dose adjustment is required in patients with mild renal impairment, i.e., estimated glomerular filtration rate (eGFR) of 60 to < 90 mL/min. In patients with moderate (eGFR 30 to < 60 mL/min) renal impairment, the recommended dose of Cibinqo should be reduced by half to 100 mg or 50 mg once daily. In patients with severe (eGFR < 30 mL/min) renal impairment, 50 mg once daily is the recommended starting dose. The maximum daily dose is 100 mg. Cibinqo has not been studied in patients with end-stage renal disease (ESRD) on renal replacement therapy. Hepatic impairment: No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Cibinqo must not be used in patients with severe (Child Pugh C) hepatic impairment. Elderly: The recommended starting dose for patients aged 65 years or more 100 mg once daily. Paediatric population: The safety and e cacy of Cibinqo in children under 12 years of age have not yet been established. No data are available. Cibinqo has been studied in adolescents 12 to < 18 years of age. However, because of bone findings in juvenile rats (comparable to a 3 month old human), additional long-term data in growing adolescents is needed to conclude that the benefits outweigh the risks. Method of administration: This medicinal product is to be taken orally once daily with or without food at approximately the same time each day. In patients who experience nausea, taking Cibinqo with food may improve nausea. Tablets should be swallowed whole with water and should not be split, crushed, or chewed because these methods have not been studied in clinical trials. Contra-indications: Hypersensitivity to the active substance or to any of the excipients. Active serious systemic infections, including tuberculosis (TB), severe hepatic impairment, pregnancy, and breast-feeding. Warnings and Precautions: Serious infections: Serious infections have been reported in patients receiving Cibinqo. The most frequent serious infections in clinical studies were herpes simplex, herpes zoster and pneumonia. Treatment must not be initiated in patients with an active, serious systemic infection. Risks and benefits of treatment prior to initiating Cibinqo should be considered. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with abrocitinib. A patient who develops a new infection during treatment should undergo prompt and complete diagnostic testing and appropriate antimicrobial therapy should be initiated. The patient should be closely monitored, and therapy should be temporarily interrupted if the patient is not responding to standard therapy. Tuberculosis: Patients should be screened for TB before starting treatment and yearly screening for patients in highly endemic areas for TB should be considered. Abrocitinib must not be given to patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, preventive therapy for latent TB should be started prior to initiation of treatment. Viral reactivation: Viral reactivation, including herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical studies. The rate of herpes zoster infections was higher in patients 65 years of age and older and patients with severe atopic dermatitis at baseline. If a patient develops herpes zoster, temporary interruption of treatment should be considered until the episode resolves. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy and during therapy. Patients with evidence of active hepatitis B or hepatitis C (positive hepatitis C PCR) infection were excluded from clinical studies. Patients who were hepatitis B surface antigen negative, hepatitis B core antibody positive, and hepatitis B surface antibody positive had testing for hepatitis B virus (HBV) DNA. Patients who had HBV DNA above the lower limit of quantification (LLQ) were excluded. Patients who had HBV DNA negative or below LLQ could initiate treatment; such patients had HBV DNA monitored. If HBV DNA is detected, a liver specialist should be consulted. Vaccination: No data are available on the response to vaccination in patients receiving Cibinqo. Use of live, attenuated vaccines should be avoided during or immediately prior to treatment. Prior to initiating treatment with this medicinal product, it is recommended that patients be brought up to date with all immunisations, including prophylactic herpes zoster vaccinations, in agreement with current immunisation guidelines. Thrombotic events including pulmonary embolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving abrocitinib. Cibinqo should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient’s risk for DVT/PE include older age, obesity, a medical history of DVT/PE, prothrombotic disorder, use of combined hormonal contraceptives or hormone replacement therapy, patients undergoing major surgery or prolonged immobilisation. If clinical features of DVT/PE occur, treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment. Malignancy (including non-melanoma skin cancers): Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical

References:

studies with abrocitinib. Clinical data are insu cient to assess the potential relationship of exposure to abrocitinib and the development of malignancies. Long-term safety evaluations are ongoing. The risks and benefits of Cibinqo treatment should be considered prior to initiating in patients with a known malignancy other than a successfully treated NMSC or cervical cancer in situ or when considering continuing Cibinqo therapy in patients who develop a malignancy. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Haematologic abnormalities: Confirmed ALC < 0.5 × 10 /mm3 and platelet count < 50 × 103/mm3 were observed in less than 0.5% of patients in clinical studies. Treatment with abrocitinib should not be initiated in patients with a platelet count < 150 × 103/mm3 an ALC < 0.5 × 103/mm3, an ANC < 1.2 × 10 /mm or who have a haemoglobin value < 10 g/dL. Complete blood count should be monitored 4 weeks after initiation of therapy and thereafter according to routine patient management. Lipids: Dose dependent increases in blood lipid parameters were reported in patients treated with abrocitinib compared to placebo. Lipid parameters should be assessed approximately 4 weeks following initiation of therapy and thereafter according to the patient’s risk for cardiovascular disease. The e ect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Patients with abnormal lipid parameters should be further monitored and managed according to clinical guidelines, due to the known cardiovascular risks associated with hyperlipidaemia. In patients with a high burden of cardiovascular risk factors, the risks, and benefits of abrocitinib compared to that of other available therapies for atopic dermatitis should be considered. If abrocitinib is chosen, interventions to manage lipid concentrations should be implemented according to clinical guidelines. Elderly: The safety profile observed in elderly patients was similar to that of the adult population with the following exceptions: a higher proportion of patients 65 years of age and older discontinued from clinical studies and were more likely to have serious adverse reactions compared to younger patients; patients 65 years and older were more likely to develop low platelet and ALC values; the incidence rate of herpes zoster in patients 65 years of age and older was higher than that of younger patients. There are limited data in patients above 75 years of age. Immunosuppressive conditions or medicinal products: Patients with immunodeficiency disorders or a first-degree relative with a hereditary immunodeficiency were excluded from clinical studies and no information on these patients is available. Combination with biologic immunomodulators, potent immunosuppressants such as ciclosporin or other Janus kinase (JAK) inhibitors has not been studied. Their concomitant use with abrocitinib is not recommended as a risk of additive immunosuppression cannot be excluded. Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Drug Interactions: Potential for other medicines to a ect pharmacokinetics of abrocitinib: Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9 enzymes, and to a lesser extent by CYP3A4 and CYP2B6 enzymes, and its active metabolites are renally excreted and are substrates of the organic anion transporter 3 (OAT3). Therefore, exposures of abrocitinib and/or its active metabolites may be a ected by medicinal products that strongly inhibit or induce theses enzymes and transporter. Dose adjustments, as appropriate, may be required. Co-administration with products which increase gastric pH: The e ect of elevating gastric pH with antacids, H2-receptor antagonists (famotidine), or proton pump inhibitors (omeprazole) on the pharmacokinetics of abrocitinib has not been studied and may reduce the absorption of abrocitinib due to the low solubility of abrocitinib at pH above 4. Potential for Cibinqo to a ect pharmacokinetics of other medicinal products: No clinically significant e ects of Cibinqo were observed in drug interaction studies with oral contraceptives. Caution should be exercised for concomitant use of abrocitinib with dabigatran. Caution should be exercised as the levels of P-gp substrates with a narrow therapeutic index, such as digoxin, may increase. The exposures of medicinal products metabolised by CYP2B6 (e.g., bupropion, efavirenz) and CYP1A2 (e.g., alosetron, duloxetine, ramelteon, tizanidine) may be decreased and of those metabolised by CYP2C19 (e.g., S mephenytoin) may be increased initially and then decreased, when used concomitantly with abrocitinib. Fertility, pregnancy, and lactation:

Women of childbearing potential: Women of reproductive potential should be advised to use e ective contraception during treatment and for 1 month following the final dose of Cibinqo. Pregnancy planning and prevention for females of reproductive potential should be encouraged. Pregnancy: There are no or limited amount of data on the use of abrocitinib in pregnant women. Studies in animals have shown reproductive toxicity. Abrocitinib has been shown to cause embryo-foetal lethality in pregnant rats and rabbits, skeletal variations in the foetuses of pregnant rats and rabbits and to a ect parturition and peri/postnatal development in rats. Cibinqo is contraindicated during pregnancy. Breast-feeding: There are no data on the presence of abrocitinib in human milk, the e ects on the breast fed infant, or the e ects on milk production. Abrocitinib was secreted in milk of lactating rats. A risk to newborns/infants cannot be excluded and Cibinqo is contraindicated during breast feeding. Fertility: Based on the findings in rats, oral administration of Cibinqo may result in temporary reduced fertility in females of reproductive potential. The e ects on female rat fertility were reversible 1 month after cessation of abrocitinib oral administration. Driving and operating machinery: Cibinqo has no e ect on the ability to drive or use machines. Side E ects: The most commonly reported adverse reactions are nausea (15.1%), headache (7.9%), acne (4.8%), herpes simplex (4.2%), blood creatine phosphokinase increased (3.8%), vomiting (3.5%), dizziness (3.4%) and abdominal pain upper (2.2%). The most frequent serious adverse reactions are infections (0.3%) including herpes simplex, herpes zoster, and pneumonia. Refer to SmPC for further information on side e ects. Legal Category: S1A. Marketing Authorisation Numbers: EU/1/21/1593/002 - Cibinqo 50 mg (28 film-coated tablets), EU/1/21/1593/007 - Cibinqo 100 mg (28 film-coated tablets); EU/1/21/1593/012 - Cibinqo 200 mg (28 film-coated tablets). Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

For further information on this medicine please contact Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 467 6500.

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

Last revised: December 2021.

Ref: CQ 1_0 IE.

1. Bieber T, Simpson EL, Silverberg JI, et al. N Engl J Med. 2021;384(12):1101-1112.

2. Simpson EL, Sinclair R, Forman S, et al. Lancet. 2020;396(10246):255-266.

3. Silverberg JI, Simpson EL, Thyssen JP, et al. JAMA Dermatol 2020;156(8):863-873.

4. Boeri M, Sutphin J, Hauber B, et al. J Dermatolog Treat. 2020 Nov 2:1-10. doi:10.1080/09546634.1832185. 5. Reich K, Silverberg JI, Papp K, et al. Presented at the Revolutionizing Atopic Dermatitis Virtual Conference; 13 June 2021. 6. Ständer S, Yosipovitch G, Simpson EL, et al. Presented at the American Academy of Dermatology Virtual Meeting Experience 2021; 23-25 April 2021. 7. Cibinqo Summary of Product Characteristics. 8. Blauvelt A, Silverberg JI, Lynde CW, et al. J Am Acad Dermatol. Published online 17 August 2021. doi: 10.1016/j.jaad.2021.05.075. 9. Cork MJ, Deleuran MS, Geng B, et al. Presented at the European Academy of Dermatology and Venereology Virtual Congress 2021; 29 September-2 October 2021.

Although some clinical trials included adolescents, please note that CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy.

TCS includes low- to medium-potency topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase 4 inhibitors, per protocol guidance in JADE COMPARE. Nonmedicated topicals were also required.1

AD=atopic dermatitis; JAK=Janus kinase; LTE=long-term extension.

© 2022 Pfizer Inc. All rights reserved. June 2022. PP-CIB-IRL-0020

US walks dangerous path in the wake of abortion ruling

Bette Browne examines the healthcare impact of the US Supreme Court’s decision to reverse Roe v Wade

When the US Supreme Court struck down the constitutional right to abortion, it was hailed by some as protecting life.

However, many doctors say the decision will have a severely negative effect on healthcare and imperil their ability to safeguard the health and lives of their patients.

With the constitutional right ended, nearly half of America’s 50 states are now restricting or banning abortions outright, without exceptions for rape or incest. Some doctors are concerned that such bans could see them potentially facing a choice between upholding their oath or breaking the law.

The Supreme Court’s decision paved the way for 13 states – Arkansas, Idaho, Kentucky, Louisiana, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, Utah, and Wyoming – to immediately enact abortion bans that include provisions that would make performing an abortion a crime punishable by prison time. About a dozen other states are also planning to allow bans or other limits on the procedure to take effect.

Some doctors fear that such legal strictures could make it impossible for them to fulfil their professional and ethical obligations to provide the best care to their patients.

Dr DeShawn Taylor, an Obstetrician and Gynaecologist who provides abortion services in Arizona, put it this way on NPR radio: “I have no interest in going to jail – I did not go to medical school to go to jail.”

Dr Lisa Harris, Associate Chair of Obstetrics and Gynaecology at the University of Michigan, has explored some of the choices now facing many doctors across the country.

“In Michigan a 1931 law criminalising abortion will come into effect,” she wrote in the New England Journal of Medicine (NEJM)

“It’s among the strictest laws in the country, permitting abortion only to ‘preserve the life’ of a pregnant person (but) it’s unclear what, precisely, ‘lifesaving’ means. What does the risk of death have to be and how imminent must it be? Might abortion be permissible in a patient with pulmonary hypertension, for whom we cite a 30-to-50 per cent chance of dying with ongoing pregnancy? Or must it be 100 per cent?

“When we diagnose a new cancer during pregnancy, some patients decide to end their pregnancy to permit immediate surgery, radiation or chemotherapy; treatments that can cause significant foetal injury. Will abortion be permissible in these cases, or will patients have to delay treatment until after delivery? These patients’ increased risk of death may not manifest for years when they have a recurrence that would have been averted by immediate cancer treatment. We’ve identified countless similar questions.”

It is not that long ago since these types of questions arose in Ireland before the repeal of the Eight Amendment in 2018. Indeed, Ireland’s experience was cited in the NEJM on 13 July by Prof Zita Lazzarini, who teaches health law and bioethics at the University of Connecticut Health Centre and Harvard School of Public Health.

“State abortion restrictions will immediately endanger anyone who has a health- or life-threatening pregnancy complication, such as miscarriage, premature labour or ectopic pregnancy. Deaths reported in Ireland, Poland and elsewhere painfully illustrate the risks to

women’s lives from such laws’ chilling effect on physicians who fear that even managing a miscarriage could expose them to legal or criminal liability.”

Reversal

The US Supreme Court’s ruling on 24 June reversed a right that had been guaranteed under the 1973 landmark decision in Roe v Wade. The dissenting judges in the ruling stated: “After today, young women will come of age with fewer rights than their mothers and grandmothers had.”

They pointed out that Americans have relied on the availability of safe and legal abortion for nearly 50 years. Women have abortions for a variety of reasons, including where contraception failed or was unavailable, sex was non-consensual, or a planned pregnancy involved a serious foetal abnormality or maternal health complications, for example. Some procedures and medications used in abortions are also used when treating women who miscarry, but now there are concerns that such treatment may be denied or delayed, owing to the chilling effect of potential prosecution.

The dissenters were especially critical of the reliance of their fellow justices on “originalism”, the theory that the US Constitution should be interpreted as it would have been understood at its adoption in 1789.

“Those responsible for the original Constitution, including the 14th Amendment (in 1868), did not perceive

women as equals and did not recognise women’s rights. When the majority says that we must read our foundational charter as viewed at the time of ratification, it consigns women to second-class citizenship.

“Today’s decision, taken on its own, is catastrophic enough. As a matter of constitutional method, the majority’s commitment to replicate in 2022 every view about the meaning of liberty held in 1868 has precious little to recommend it.”

Women living in poverty will suffer most, they emphasised, and may even die employing an unsafe method of abortion.

“In states that bar abortion, women of means will still be able to travel to obtain the services they need. It is women who cannot afford to do so who will suffer most.

“These are the women most likely to seek abortion care in the first place. Women living below the federal poverty line experience unintended pregnancies at rates five times higher than higher income women do, and nearly half of women who seek abortion care live in households below the poverty line. Others – those without money or childcare or the ability to take time off from work – will not be so fortunate. Maybe they will try an unsafe method of abortion, and come to physical harm, or even die.”

A poll in the weeks before the 24 June ruling showed that three-quarters of Americans wanted to keep the right to abortion in place. On 27 June, three days after the decision, a majority of Americans said they disagreed with the ruling and believed it was politically motivated.

“With this decision,” President Joe Biden said, “the conservative majority of the Supreme Court shows how extreme it is, how far removed they are from the majority of this country. The court has taken away a constitutional right that is so fundamental to so many Americans. They didn’t limit it. They simply took it away. That’s never been done to a right so important to so many Americans.”

“Let’s be very clear: The health and life of women in this nation are now at risk. Women could be punished for protecting their health. Doctors will be criminalised for fulfilling their duty to care.” He added that the decision makes the United States “an outlier among developed nations on protecting reproductive rights”.

In some ways, the decision was not surprising and its likelihood had been leaked some weeks earlier. The make-up of the Supreme Court with the appointment of three conservative judges during the presidency of Donald Trump, made the decision almost inevitable.

This was a point also referred to by the dissenting justices: “Mississippi – and other states too – knew exactly what they were doing in ginning up new legal challenges to Roe. Other states quickly followed: Between 2019 and 2021, eight states banned abortion procedures after six to eight weeks of pregnancy, and three states enacted all-out bans. Mississippi itself decided in 2019 that it had not gone far enough. The year after enacting the law under review, the state passed a six-week restriction. A state senator who championed both Mississippi laws said the obvious out loud. ‘[A] lot of people thought finally we have (a conservative court) and so now would be a good time to start testing the limits of Roe.’”

Individual states had indeed been restricting abortion rights for some time. In Texas, for example, a state law that is set to go into effect bans almost all abortions from the moment of fertilisation and many other states are considering or implementing similar laws.

Medical organisations’ reaction

Many doctors have expressed concern about the impact

State abortion restrictions will immediately endanger anyone who has a health- or life-threatening pregnancy complication, such as miscarriage, premature labour, or ectopic pregnancy

Dr Lisa Harris

Continued from p14 ▸

on miscarriage and in vitro fertilisation. The practice of medicine will be reshaped or even contradicted “by laws not founded in science or based on evidence”, the American College of Obstetricians and Gynaecologists stated.

Abortion was a “safe, essential part of comprehensive healthcare and must be available equitably to people, no matter their race, socio-economic status or where they reside”, it outlined. “The restrictions put forth are not based on science or medicine. They allow unrelated third parties to make decisions that rightfully and ethically should be made only by individuals and their physicians.”

It added: “This is a dark and dangerous time for the women and doctors of America.”

The American Medical Association said it was “deeply disturbed” by the decision, which it called an “egregious allowance of government intrusion into the medical examination room and a direct attack on the practice of medicine and the patient-physician relationship, and a brazen violation of patients’ rights to evidence-based reproductive health services. States that end legal abortion will not end abortion – they will end safe abortion, risking devastating consequences, including patients’ lives.”

It added: “State restrictions that intrude on the practice of medicine and interfere with the patient-physician relationship leave millions with little or no access to reproductive health services while criminalising medical care.”

Physicians for Reproductive Health called the decision devastating. “Today’s decision is devastating for communities across the country,” Dr Jamila Perritt, the organisation’s President and CEO, said in a statement. “This decision allows the evisceration of abortion access in 26 states, more than half of our country. The real world impacts of these bans are devastating. People are forced to either leave their communities to seek care or forced to remain pregnant and give birth. Healthcare providers who have made an oath to do no harm are threatened by the government to deny patients the compassionate care they need. This moment is one our community of physicians worked to never be affronted with.”

Dr Perritt elaborated on this point in an interview on PBS TV: “We know that when doctors and other health-

care providers are turned into agents of the state, we’ve been asked to interrogate people about what they’ve done prior to seeking care, it keeps people out of care. So these laws suggesting that doctors should be acting as the police interrogating the patients when they’re seeking care is misaligned with public health and community health principles.”

The American Academy of Paediatrics warned about what it called the “grave consequences” of the ruling for teenagers “who already face increased barriers to the procedure, with evidence-based care (becoming) difficult or impossible to access”.

According to the Academy’s statement: “This decision carries grave consequences for our adolescent patients who already face many more barriers than adults in accessing comprehensive reproductive healthcare services and abortion care. (The) ruling means that in many places in the United States, this evidence-based care will be difficult or impossible to access, threatening the health and safety of our patients, and jeopardising the patient-physician relationship.”

As anti-abortion supporters celebrated the ruling, abortion-rights advocates called for protection for those seeking abortions. They cited data from the Centres for Disease Control and Prevention showing that childbirth in the US was 14 times more deadly than having an abortion.

The ruling could also have a major impact on areas of medical training, according to a study published in the journal Obstetrics & Gynecology. It found that roughly half of medical residencies would be in states that have or are predicted to restrict or ban abortion, so residents would no longer have access to such training (despite the fact that it is a requirement by the graduate medical accreditation council).

Medical organisations in other countries also expressed alarm at the impact the ruling would have on women’s health. In Ireland, the Institute of Obstetricians and Gynaecologists expressed its “deep concerns” about

“Public health accomplishments threatened”

By making abortion legal nationwide in 1973, Roe v Wade had a dramatic impact on the health and wellbeing of American women. Deaths from abortion have plummeted since then and are now a rarity.

In addition, women have been able to have abortions earlier in pregnancy when the procedure is safest. The proportion of abortions obtained early in the first trimester has risen from 20 per cent in 1970 to 56 per cent in 1998. “These public health accomplishments may now be seriously threatened,” according to the Guttmacher Institute, a research and policy organisation focusing on reproductive health.

Estimates of the number of illegal abortions in the 1950s and 1960s ranged from 200,000 to 1.2 million per year, the Institute said. By 1965, the number of deaths due to illegal abortion had fallen to just under 200, but illegal abortion still accounted for 17 per cent of all deaths attributed to pregnancy and childbirth that year.

Even in the early 1970s, when abortion was legal in some states, a legal abortion was simply out of reach for many. Minority women suffered the most: The Centres for Disease Control and Prevention estimates that in 1972 alone, 130,000 women obtained illegal or self-induced procedures, 39 of whom died. From 1972 to 1974, the mortality rate due to illegal abortion for non-white women was 12-times that for white women.

The year before the Supreme Court’s 1973 decision in Roe v Wade, just over 100,000 women left their own state to obtain a legal abortion in New York City.

Data from the New York City Department of Health confirm that, in practice, this option was only available to the small proportion of women who were able to pay for the procedure plus the expense of travel and accommodation.

In most states, until just before 1973, a woman had to demonstrate that her life would be endangered if she carried

her pregnancy to term. In some states, especially between 1967 and 1973, a woman also could receive approval for an abortion if it were deemed necessary to protect her physical or mental health, or if the pregnancy had resulted from rape or incest.

“It is by no means a given that the precise dimensions of the public health situation that existed before 1973 would reappear. However, it must be considered extremely likely that such an overhaul of US abortion jurisprudence would lead to the reestablishment of a two-tiered system in which options available to a woman confronting an unintended pregnancy would be largely determined by her socioeconomic status,” according to the Guttmacher Institute.

“Such a system has proved to be deleterious to the health of women, especially those who are disadvantaged, and is something that many had hoped would have been long consigned to the history books.”

the ruling. “The international evidence is clear that the rate of termination of pregnancy in countries where abortion is legally available is similar to those where it is restricted. Restricting access does not decrease the number of abortions, but instead increases the proportion of unsafe abortions,” the Institute said in a statement.

“This regressive action is out of step with the global community’s commitment to advance human rights and fails to take into account the overwhelming global medical evidence that supports abortion as essential healthcare. The result of the US Supreme Court’s action means that some of the most vulnerable members of society in the US will lose their right to access essential healthcare, their right to choose, and threatens to dismantle the progress made in provision of healthcare for women. We wish to reaffirm our commitment to recognise abortion care as essential healthcare and our belief that provision of termination services should be decriminalised.”

Within weeks of the ruling, news emerged that a 10-year-old girl who had been raped was blocked from having an abortion in her native Ohio and then travelled more than 270km to neighbouring Indiana to have a termination.

At least 10 states have already passed anti-abortion laws with no exception for rape or incest. California and states like New York have said they would welcome people travelling to their states for legal abortions. However, bans on such inter-state travel are also being considered in some states, although such moves would face strong challenges.

New York Governor Kathy Hochul told a meeting of US state governors that “just a handful of states” were going to have to take care of the health of women across the country.

“It is a matter of life and death for American women.”

Presidential action

President Biden also emphasised that the US Attorney General made clear that women “must remain free to travel safely to another state to seek the care they need. And my administration will defend that bedrock right.”

Many of his fellow Democrats and some medical organisations have urged the President to declare a public health emergency to protect those seeking abortion. “The administration must take the first step toward restoring national protections (and) declare a public health emergency now (to) ensure that medication abortion is available across the nation,” said Ms Nancy Northup, President and CEO of the Centre for Reproductive Rights.

On 8 July, two weeks after the ruling, the President signed an executive order directing his health department to expand access to abortion pills and to organise lawyers to help defend anyone criminally charged for seeking or providing the procedure.

The administration took further action three days later, telling hospitals that they must provide abortion services if the life of the mother was at risk. It said federal law on emergency treatment guidelines pre-empts state laws in jurisdictions that ban the procedure without any exceptions.

Democrats in Congress have also sought to codify the right to abortion in law, but they lack the required votes in Congress. Thus, it may well end up becoming an issue in congressional and state elections in November.

The wider consequences of the Supreme Court ruling also disturbed many Americans because one of the justices, Clarence Thomas, in a written opinion on 24 June, suggested that moves to restrict contraception and gay marriage could be next. He called the landmark cases protecting those rights “erroneous” and said the court could reconsider them in future decisions.

“Justice Thomas explicitly called to reconsider the right of marriage equality, the right of couples to make their choices on contraception,” President Biden said. “This is an extreme and dangerous path the court is now taking us on.”

Dr Jamila Perritt

Governor Kathy Hochul

Toujeo

Shared features with Toujeo ® SoloStar

• Pen size

• 5-second hold time5,6

• 42-day shelf life after first use1

• Same technical platform

*Toujeo ® DoubleStar™ is recommended for patients requiring at least 20 units of basal insulin per day1

®

Prescribing Information:

Toujeo (insulin glargine 300 units/ml)

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

Presentation: Toujeo SoloStar and DoubleStar pre-filled pens. Each ml contains 300 units of insulin glargine. SoloStar pen contains 1.5ml (450 units) of solution for injection. DoubleStar pen contains 3ml (900 units) of solution for injection.

Indication: Treatment of diabetes mellitus in adults, adolescents and children from the age of 6 years. Dosage and Administration: Toujeo is administered subcutaneously, by injection into the abdominal wall, the deltoid or the thigh, once daily, at any time of the day, preferably at the same time every day. Injection sites must be rotated within a given injection area from one injection to the next in order to reduce the risk of lipodystrophy and cutaneous amyloidosis. The dose regimen (dose and timing) should be adjusted according to individual response. Do not administer intravenously. In type 1 diabetes mellitus, Toujeo must be combined with short-/rapid-acting insulin to cover mealtime insulin requirements. In patients with type 2 diabetes mellitus, recommended daily starting dose is 0.2 units/kg followed by individual dose adjustments. Toujeo can also be given together with other anti-hyperglycaemic medicinal products. Switch between insulin glargine 100 units/ml and Toujeo: Insulin glargine 100 units/ml and Toujeo are not bioequivalent and are not directly interchangeable. When switching from insulin glargine 100 units/ml to Toujeo, this can be done on a unit to unit basis, but a higher Toujeo dose (approximately 10-18%) may be needed to achieve target ranges for plasma glucose levels. When switching from Toujeo to insulin glargine 100 units/ml, the dose should be reduced (approximately by 20%). Switching from other basal insulins to Toujeo: A change of dose and/or timing of the basal insulin and concomitant anti hyperglycaemic treatment may be required. Dose adjustments may also be required if the patient’s weight or lifestyle changes, the timing of insulin dose is changed or other circumstances arise that increase susceptibility to hypo- or hyperglycaemia. Toujeo must not be mixed or diluted with any other insulin or other medicinal products. Close metabolic monitoring is recommended during a switch and in the initial weeks thereafter. SoloStar 1-80 units per single injection in steps of 1 unit and DoubleStar 2-160 units in steps of 2 units. When changing from Toujeo SoloStar to Toujeo DoubleStar, if the patient’s previous dose was an odd number then the dose must be increased or decreased by 1 unit. Toujeo DoubleStar prefilled pen is recommended for patients requiring at least 20 units per day. Special Populations: Insulin requirements may be diminished in the elderly or patients with renal or hepatic impairment. Paediatric: When switching basal insulin to Toujeo, dose reduction of basal and bolus insulin needs to be considered on an individual basis, in order to minimise the risk of hypoglycaemia. The safety and efficacy of Toujeo in children and adolescents below 6 years of age have not been established. Contraindications: Hypersensitivity to insulin glargine or any excipients. Precautions and Warnings: Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Toujeo is not the insulin of choice for treatment of diabetic ketoacidosis. Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection

References:

1. Toujeo® Summary of Product Characteristics.

Date of preparation: November 2021 | MAT-IE-2101574 (v1.0)

site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may be considered. Hypoglycaemia: In case of insufficient glucose control or a tendency to hyper/hypoglycaemic episodes, the patient’s adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered. Particular caution should be exercised, and intensified blood glucose monitoring is advisable for patients in whom hypoglycaemic episodes might be of clinical relevance and in those where dose adjustments may be required. Warning signs of hypoglycaemia may be changed, less pronounced or absent in certain risk groups, potentially resulting in severe hypoglycaemia and loss of consciousness. Risk groups include patients in whom glycaemic control is markedly improved, hypoglycaemia develops gradually, an autonomic neuropathy is present, or who are elderly. The prolonged effect of subcutaneous insulin glargine may delay recovery from hypoglycaemia. Intercurrent illness: Requires intensified metabolic monitoring and often it is necessary to adjust the insulin dose. Insulin antibodies: administration may cause insulin antibodies to form. Use with pioglitazone: Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs. Medication errors: Insulin labels must always be checked before each injection to avoid errors between Toujeo and other insulins. Patients must be instructed to never use a syringe to remove Toujeo from the SoloStar or DoubleStar pre-filled pen, A new sterile needle must be attached before each injection. Needles must not be re-used. Pregnancy and lactation: There is no data from exposed pregnancies in controlled clinical trials. However, there is a large amount of data on use of insulin glargine 100 units/ml in pregnant women indicating no specific adverse effects on pregnancy and no specific malformative nor feto/neonatal toxicity. The use of Toujeo may be considered during pregnancy, if clinically needed. Careful monitoring of glucose control is essential. It is unknown if insulin glargine is excreted in breast milk. Interactions: Substances that affect glucose metabolism may require adjustment of insulin glargine. Adverse Reactions: Very common: Hypoglycaemia. Prolonged or severe hypoglycaemia may be life-threatening. Common: Lipohypertrophy, injection site reactions, including redness, pain, itching, hives, swelling, or inflammation. Legal Category: POM. Marketing Authorisation Number: SoloStar 3 Pen pack: EU/1/00/133/034, DoubleStar EU/1/00/133/038. Marketing Authorisation Holder: Sanofi Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany. Further information is available from: Medical Information, Sanofi 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact IEmedinfo@sanofi.com. Date of preparation: July 2020.

Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie; email: medsafety@hpra.ie Adverse events should also be reported to Sanofi Ireland Ltd. Tel: 01 403 5600. Alternatively, send via email to IEPharmacovigilance@sanofi.com

® DoubleStar™ holds more units per pen than any other basal insulin pen on the market1-4

Toujeo ® is available in two pre-filled insulin devices allowing you to choose the most suitable device for your patients

PAUL MULHOLLAND

The Irish health service’s shortage of key staff has been a problem for some time. Regarding the medical workforce, the difficulty in filling vacant consultant posts has resulted in what is commonly referred to as a “recruitment and retention crisis”.

So, the scale of the staffing requirements in public hospitals between 2019 and 2035 outlined by the Economic and Social Research Institute (ESRI) in its new report on the area is concerning.

Nationally, the population is projected to be 5.4 million by 2035, which means an increase of close to 500,000 between 2019 and 2035. The number aged 85 years and older is projected to more than double.

Driven by projected demographic change, particularly population ageing, workforce requirements for all staff categories examined are projected to increase substantially by 2035.

By that year the ESRI projects additional workforce requirements for medical staff of between 2,575 and 3,236 whole-time equivalents (WTEs) nationally. This represents an increase of between 1.7 and 2.1 per cent on average per annum.

“Across scenarios the highest projected regional increase per annum was 2.2 per cent, recorded in the east of the country,” according to the Institute.

There would also be a requirement for an increase in nursing and midwifery staff of between 5,726 and 8,868 WTEs nationally, with a rise of between 1.4 and 2.1 per cent on average per annum.

The largest increases in workforce are projected for health and social care professionals, who

are particularly required by older people in hospital. The highest per annum growth is projected for occupational therapists (2.7-3.3 per cent) and speech and language therapists (2.3-3.3 per cent).

Commenting on the report, Ms Anne Marie Hoey, HSE National Director of Human Resources, said the workforce projections will better inform decisions and resource planning for the new regional health areas.

Ms Hoey added they will be “a critical enabler for our joint discussions on workforce planning both with our funders and stakeholders”.

“Furthermore, this will facilitate the medium- and longer-term planning necessary in areas such as training and education to ensure the availability of graduates to fulfil the workforce requirements within the domestic market.”

Another report focusing on the community sector will also be published.

As Ms Hoey said, the research is important to facilitate a strategic approach to the running of the health service. The report’s findings are of great relevance in terms of the implementation of Sláintecare.

However, if the existing recruitment problems are anything to go by, hiring new healthcare staff on the scale outlined in the report will be difficult. Regarding consultants, the Medical Independent recently reported there were 297 more vacant posts at the end of June compared to the end of 2020. Talks on a new consultant contract have proven protracted and difficult.

Younger doctors are continuing to emigrate. Australia has issued 402 work visas to Irish doctors in 2022 so far, compared to 272 in 2019, heard the IMO AGM in May. Research conducted by Dr Niamh Humphries (PhD) has found emigration is being driven by a variety of factors, including poor working conditions and also “an absence of hope”.

The recent ballot for strike action among NCHDs was further evidence of the disillusionment among the group, even if current negotiations with health management avoid the need for industrial action.

These are just some of the immediate issues that will have to be resolved if the Irish acute service is to be able to meet the huge challenges of caring for a growing and aging population.

READER COMMENTS

REACTION TO OUR ONLINE NEWS FEATURE, 'AUDITS IDENTIFY SHORTFALLS IN SAFEGUARDING PRACTICE AT HSE COMMUNITY NURSING UNITS', 2 AUGUST

“Audits identify shortfalls in safeguarding practice at HSE community nursing units – Medical Independent. ‘.... under-reporting of elder abuse one of the challenges for adult safeguarding'." Care Champions #SafeguardingLawsNow, @CareChampions2, 30 July

“@Safeguarding_ie ‘emphasised the importance' of auditing HSE community nursing units given trends in annual reporting and concerns raised by the Community Healthcare Organisation (CHO) SPTs regarding ‘low reporting and the understanding of abuse in this sector'." Celine O'Connor, @CelineOConnor12, 30 July

REACTION TO OUR NEWS ARTICLE, 'STAFF HOURS DECISION WILL IMPACT RECRUITMENT TARGETS – HSE', 21 JULY

“Time to totally reconfigure the smaller half of our acute hospitals. Time to have every aspect of public health system online. Sláintecare – even more appropriate now than at its launch date. Time for root and branch reform of HR in the HSE/DOH." Dr Brendan O'Shea, @drbosheaGP, 2 August

REACTION TO OUR NEWS ARTICLE, 'LARGE INCREASE IN VACANT CONSULTANT POSTS SINCE NOVEMBER 2020', 21 JULY

“Not sure how this is even news anymore. Inequitable contracts. Toxic work environments. Poor support. Poor facilities. Job descriptions that couldn’t be less competitive or enticing. Rather than fix it though, let’s keep recycling the facts every 4-6 months…." Dr Fardod O'Kelly, @FardodOKelly, 25 July

REACTION TO DR SARAH FITZGIBBON'S COLUMN, 'THE MAGIC OF THE MEDICAL CONFERENCE WITH A DIFFERENCE', 21 JULY

“‘I spent the weekend finding out what was wrong with me. I discovered I am not entirely likeable, I am occasionally an asshole, I don’t enjoy myself enough and I should write more, draw more, sing more, dance more.' Great @DotMDConf summary! @SarahFitzWiMIN." Dr Nóirín Russell, @russellnoirin, 25 July

REACTION TO DR PAT HARROLD'S COLUMN, 'THE WONDERFUL WONCA WORLD OF RURAL PRACTICE', 21 JULY

“You all hosted an unforgettable @RuralWONCA conference. Thanks for such a special time, the music, the great plenaries, workshops, and opportunities to meet amazing people." Dr Vivi MartinezBianchi, @vivimbmd, 25 July

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ESRI projections on the health service’s workforce needs are concerning

However, if the existing problems in recruiting healthcare staff are anything to go by, recruiting on the scale outlined in the report will be difficult

50mgs once daily

50mgs once daily

Her 10th shopping trip since the day she started BETMIGA1

Prescribing Information: Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation: Prolonged-release tablet, containing mirabegron 25mg/50mg. Indication: Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. Posology and method of administration: The recommended dose is 50 mg once daily. A lower dose of 25mg is recommended for specific patient populations (renal and hepatic impairment) as well as in specific patient populations in combination with strong CYP3A inhibitors such as itraconazole, ketoconazole, ritonavir and clarithromycin.

Renal impairment: End stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis): Not recommended. Severe renal impairment (GFR 15 to 29 mL/min/1.73 m2): Reduce dose to 25 mg. Severe renal impairment and concomitant strong CYP3A inhibitors: Not recommended. Moderate renal impairment (GFR 30 to 59 mL/min/1.73 m2): 50 mg. Moderate renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Mild renal impairment (GFR 60 to 89 mL/min/1.73 m2): 50 mg. Mild renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Hepatic impairment: Severe hepatic impairment (Child-Pugh Class C): Not recommended. Moderate hepatic impairment

(Child-Pugh B): Reduce dose to 25 mg. Moderate hepatic impairment and concomitant strong CYP3A inhibitors: Not recommended. Mild hepatic impairment (Child-Pugh A): 50 mg. Mild hepatic impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. The tablet is to be taken once daily, with liquids, swallowed whole and is not to be chewed, divided, or crushed. It may be taken with or without food Contraindications: Hypersensitivity to the active substance or to any of the excipients (see the SPC for a list of excipients). Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg. Special warnings and precautions for use: Renal impairment: Betmiga has not been studied in patients with end stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis) and, therefore, it is not recommended for use in this patient population. Data are limited in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2); based on a pharmacokinetic study a dose reduction to 25 mg is recommended in this population. This medicinal product is not recommended for use in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) concomitantly receiving strong CYP3A inhibitors. Hepatic impairment: Betmiga has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and, therefore, it is not recommended for use in this patient population. This medicinal product is not recommended for use in patients with moderate hepatic impairment (Child-Pugh B) concomitantly receiving

strong CYP3A inhibitors. Hypertension: Mirabegron can increase blood pressure. Blood pressure should be measured at baseline and periodically during treatment with mirabegron, especially in hypertensive patients. Data are limited in patients with stage 2 hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg). Patients with congenital or acquired QT prolongation: Betmiga, at therapeutic doses, has not demonstrated clinically relevant QT prolongation in clinical studies. However, since patients with a known history of QT prolongation or patients who are taking medicinal products known to prolong the QT interval were not included in these studies, the effects of mirabegron in these patients is unknown. Caution should be exercised when administering mirabegron in these patients. Patients with bladder outlet obstruction and patients taking antimuscarinic medicinal products for OAB: Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medicinal products for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with Betmiga; however, Betmiga should be administered with caution to patients with clinically significant BOO. Betmiga should also be administered with caution to patients taking antimuscarinic medicinal products for the treatment of OAB. Interactions: Pharmacokinetic interactions: Mirabegron is a substrate for CYP3A4, CYP2D6, butyrylcholinesterase, uridine diphosphoglucuronosyltransferases (UGT), the efflux transporter P-glycoprotein (P-gp) and the influx organic cation transporters (OCT) OCT1, OCT2, and OCT3. Pharmacokinetic interactions involving the potential for other medicinal products to affect mirabegron exposures: Increases in mirabegron exposure due to drug-drug interactions may be associated with increases in pulse rate. Strong CYP3A inhibitors See Posology and administration above for dose adjustments recommended during concomitant use of strong CYP3A inhibitors in patients with renal or hepatic impairment. Mirabegron exposure (AUC) was increased 1.8-fold in the presence of the strong inhibitor of CYP3A/P-gp ketoconazole. CYP2D6 inhibitors: No dose adjustment is needed for mirabegron when administered with CYP2D6 inhibitors (or in patients who are CYP2D6 poor metabolisers). Inducers: Inducers of CYP3A (such as rifampicin) or P-gp may decrease the plasma concentrations of mirabegron. No dose adjustment of mirabegron is required as this effect is not expected to be clinically relevant. Pharmacokinetic interactions involving the potential for mirabegron to affect exposures to other medicinal products: Inhibition of CYP2D6: Moderate and time dependent inhibition of CYP2D6 by mirabegron may result in clinically relevant drug interactions. CYP2D6 activity recovers within 15 days after discontinuation of mirabegron. Caution is advised if mirabegron is co-administered with medicinal

products metabolized by CYP2D6 with a narrow therapeutic index such as thioridazine, Type 1C antiarrhythmics (e.g.flecainide, propafenone) and tricyclic antidepressants (e.g., imipramine, desipramine). Caution is also advised if mirabegron is co-administered with CYP2D6 substrates that are individually dose titrated. Inhibition of P-gp: Mirabegron is a weak inhibitor of P-gp. For patients who are initiating a combination of Betmiga and digoxin, the lowest dose for digoxin should be prescribed initially. Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect. The potential for inhibition of P-gp by mirabegron should be considered when Betmiga is combined with sensitive P-gp substrates e.g. dabigatran. Fertility, pregnancy and lactation: The effect of mirabegron on human fertility has not been established. Betmiga is not recommended during pregnancy and in women of child-bearing potential not using contraception. Mirabegron should not be administered during breast feeding. Refer to SPC for full guidance. Driving and use of machines: Betmiga has no or negligible influence on the ability to drive and use machines.

Undesirable effects: Summary of the Safety Profile: the safety of Betmiga was evaluated in 8433 patients with OAB, of which 5648 received at least one dose of mirabegron in the phase 2/3 clinical program, and 622 patients received Betmiga for at least 1 year (365 days). In the three 12-week phase 3 double blind, placebo controlled studies, 88% of the patients completed treatment with this medicinal product, and 4% of the patients discontinued due to adverse events. Most adverse reactions were mild to moderate in severity. The most common adverse reactions reported for patients treated with Betmiga 50 mg during the three 12-week phase 3 double blind, placebo controlled studies are tachycardia and urinary tract infections.

The frequency of tachycardia was 1.2% in patients receiving Betmiga 50 mg.

Tachycardia led to discontinuation in 0.1% patients receiving Betmiga 50 mg. The frequency of urinary tract infections was 2.9% in patients receiving Betmiga 50 mg.

Urinary tract infections led to discontinuation in none of the patients receiving Betmiga 50 mg. Serious adverse reactions included atrial fibrillation (0.2%). Adverse reactions observed during the 1-year (long term) active controlled (muscarinic antagonist) study were similar in type and severity to those observed in the three 12-week phase 3 double blind, placebo controlled studies. The following adverse reactions were observed with mirabegron in the three 12-week phase 3 double blind, placebo controlled studies. The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be established from the available data) Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse events

are grouped by MedDRA system organ class. Infections and infestations: Common: urinary tract infection Uncommon: vaginal infection, cystitis Psychiatric disorders: Not known: Insomnia*, confusional state* Nervous system disorders: Common: headache* dizziness* Eye disorders: Rare: eyelid oedema Cardiac disorders:

Common: tachycardia Uncommon: palpitation, atrial fibrillation Vascular disorders:

Very rare: Hypertensive crisis* Gastrointestinal disorders: Common: nausea*, constipation*, diarrhoea* Uncommon: dyspepsia, gastritis Rare: lip oedema Skin and subcutaneous tissue disorders: Uncommon: urticaria, rash, rash macular, rash papular, pruritus Rare: leukocytoclastic vasculitis, purpura, angioedema* Musculoskeletal and connective tissue disorders: Uncommon: joint swelling Renal and urinary disorders:

Rare: urinary retention* Reproductive system and breast disorders: Uncommon: vulvovaginal pruritus Investigations Uncommon: blood pressure increased, GGT increased, AST increased, ALT increased (*observed during post-marketing experience) Reporting of suspected adverse reactions: see below. Legal category: POM (S1B) Marketing Authorisation number: EU/1/12/809/003 - 25mg EU/1/12/809/010 50mg. Marketing

Authorisation holder: Astellas Pharma Europe B.V. Sylviusweg 62, 2333 BE Leiden, The Netherlands. Further information is available from: Astellas Pharma Co., Ltd, 5 Waterside, Citywest Business Campus, Dublin 24. Phone: +3531 467 1555. Summary of Product Characteristics with full prescribing information available upon request. Job number: BET_2019_0002_IE Date of preparation of API: 27 May 2019.

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

HPRA Pharmacovigilance Astellas Pharma Co. Ltd

Earlsfort Terrace, IRL - Dublin 2 Tel: + 353 1 467 1555

Tel: +353 1 6764971 E-mail: Irishdrugsafety@astellas.com

Fax: +353 1 6762517

Website: www.hpra.ie E-mail: medsafety@hpra.ie.

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,

LAMA + LABA

LAMA

The challenges presented by high-profile patients

Dr Rachel Birch , Medico-legal Consultant at Medical Protection, discusses the complexities in treating high-profile patients and provides some advice

When a high-profile patient dies, the circumstances around their death and sometimes their relationship with their doctor can be thrown into the media spotlight. This may be a daunting prospect for doctors. Although very few doctors will face such an extreme situation, it is useful to be aware of some of the potential medico-legal challenges that can arise when treating someone in the public eye.

Imagine you have a patient presenting with a viral sore throat and insisting on a course of antibiotics. As well as considering whether the symptoms could be Covid-related, we know that the right thing to do usually is to advise on symptomatic treatment, and not to prescribe antibiotics without clear evidence of bacterial infection. But what would you do in a situation involving a high-profile patient – perhaps a well-known politician or sportsperson? Would you feel it safer to prescribe the antibiotics when your patient is in a position of power and used to getting what they want?

From a medico-legal point of view, of course, your medical judgement should not be swayed depending on the social status, wealth or other influence of the patient you are treating. As a doctor, you have a duty of care to all your patients regardless of whom they are. Your prime consideration should be regarding their medical condition, and what you can do in your capacity as a doctor to help.

Confidentiality

Open up any gossip magazine and you may well find examples of celebrities’ personal health and mental health battles. For doctors, who treat these patients, dealing with issues around confidentiality is essential, although the patients may have concerns regarding their privacy. As a result, celebrities may request for details of their medical condition to be omitted from their records, or for no records to be made, in fear of it being leaked into the public domain.

The first step is to instil trust between yourself and the patient. Everyone has a right to confidentiality and high-profile patients may need extra reassurance that this right will be respected. However, it is never appropriate to intentionally leave relevant clinical information out of a medical record and this must be explained to the patient. Your duty to your patient includes ensuring that there is continuity of care, and omitting information from the record could mean other healthcare professions are misinformed about their condition and the patient is therefore put at risk.

The Medical Council’s Guide to Profes -

sional Conduct and Ethics for Registered Medical Professionals (the ‘Guide’) is clear and states:

“Medical records consist of relevant information learned from or about patients…. You must keep accurate and up-to-date patient records either on paper or in electronic form…. Patients benefit when all those treating them are fully informed about their condition and medical history.”

Remember that, under the General Data Protection Regulation (GDPR), patients have the right to ensure their information is accurate and are able to request that factual inaccuracies within their record are rectified. They do not, however, have the right for a medical opinion made by you as a professional to be changed. If you need to make a correction in a medical record, make sure you enter the date of the amendment and include your name. You should only comply with a request if you are satisfied that the entry is indeed factually inaccurate, but if you decide that a correction is not warranted, you should annotate the disputed entry with the patient’s view. The Data Protection Commission provides helpful guidance on GDPR, including further detail regarding the rights of data subjects.

Even the most demanding of patients should understand that it is your professional obligation to keep a record of their care, for their wellbeing and yours. Reassure them that they can take comfort in the fact that there are laws to protect against disclosure against their

wishes, and ensure their need for confidentiality is respected.

Pressure

Sometimes, despite building up a trusting doctor-patient relationship, outside influences, such as celebrities’ managers or other individuals involved in their dayto-day lives, may take it upon themselves to make decisions on behalf of their client. This can pose problems when the decisions they make are in conflict with what you believe to be in the patient’s best medical interests.

If you feel you are being pressured into a decision by a patient or third party, take time to consider your position. Ultimately, the right thing to do is to outline your concerns, the options, and tell them what the worst-case scenario would be if the patient were to refuse the advice. Except in emergency situations, you cannot enforce any treatment without the patient’s consent; equally, you shouldn’t proceed with treatment that you think is wrong merely because the patient has requested it. As with any patient, ensure you include details of all these discussions, including any refusal to treatment, in the medical notes.

You may wish to obtain the patient’s consent to discuss potential treatment options with other clinical colleagues as you might do with other patients. You can reassure the patient of confidentiality in any discussion and explain that this would be considered to be good practice.

It is important to remember that you

have been tasked with providing medical advice and treatment. No amount of pressure should deter you from maintaining the professional boundaries of the doctor-patient relationship to the best of your ability.

When treating high profile patients, we also need to take particular care in discussing and considering the patient’s individual needs and circumstances. For example, would a possible treatment impact on their career or talent?

The Medical Council’s Guide states that doctors must give patients enough information, in a way that they can understand, to enable them to exercise their right to make informed decisions about their care.

It emphasises, in particular:

“Patients will always need basic information about their condition, its investigation and treatment, and any serious or frequently-occurring risks. Patients will usually need more detailed information about procedures that carry a high risk of failure or adverse side-effects. They will also need more detailed information about an investigation for a condition that, if found to be present, could have serious consequences for the patient’s employment, social or personal life.”

A cautious approach is, therefore, required if the patient is presenting with problems relating to their particular talent. For example, if a famous concert pianist presents with bilateral carpal tunnel syndrome and a specialist hand surgeon recommends surgery, should they fail to warn the patient about the possible complications, or discuss the options available, they leave themselves open to criticism if something goes wrong during the procedure. Although adverse complications would be distressing for any patient, the potential loss of earnings of a talented pianist could mean that a claim brought against the surgeon would be of a much higher value than a patient who doesn’t rely on their finger dexterity and strength to make a living. Such a claim may also be high profile with the risk of reputational damage.

Starstruck

When faced with treating a high-profile patient, many doctors react in different ways. Some will be nervous, worried the patient could ask them to go outside the boundaries of what they consider to be best practice, while others may feel intimidated or even flattered that they have been chosen to consult for medical treatment or advice.

Despite these feelings, as a professional, you must maintain the same high professional standards as to any other patient. Remember that the usual rules apply: Communicate openly; keep detailed medical records; manage professional boundaries; seek informed consent; and maintain their confidentiality.

You may feel extra pressure when dealing with those in the public eye, but as long as you act in their best interests and can justify any decisions you make, your integrity and professionalism should remain intact.

If in doubt, or if you require advice, always contact your medical defence organisation.

Reflective practice in medicine

Medical writers have recently questioned our blind faith in diagnosis

DR MUIRIS HOUSTON

Read

more by Dr Muiris Houston at www.mindo.ie

@muirishouston

dotMD22 is over – long live dotMD. It was great to be back in Galway post-Covid. What a blast we had. A big thank you to those who attended, both virtually and in person.

Sarah Fitzgibbon has already graced these pages with an insightful look at the highlights of this year’s event. So I won’t bore with you with a repeat from me.

What I would like to do is to focus on John Launer, whom I was privileged to interview in Galway. We had fun discussing “Why are doctors so difficult?”, and were treated gently by the audience when we moved it up a notch to look at “why are doctors assholes?”. But I would like to examine John’s role in the development of narrative-based medicine.

He writes about narrative-based practice rather than narrative medicine. Are the terms the same or are they deliberately unrelated? He doesn’t see a huge difference, except to note that narrative-based medicine was the title of the seminal book by Trisha Greenhalgh and Brian Hurwitz, published in the 1990s. The term narrative-medicine was emphasised by Rita Charon, the US champion of the area, and I get a sense of a not unhealthy European vs US divergence in the nomenclature. I’m probably biased, but I sense a greater practicality about the direction of travel of the European movement.

John Launer is a GP, family therapist, educator, and writer. He has written or edited a number of books on interactional skills and medical humanities, including How Not to Be A Doctor. His latest publication, Reflective Practice in Medicine and Multi-Professional Healthcare, continues his exploration of narrative in a post-Covid-19 world.

One question I had for John was why the habit of recording patients’ actual words in clinical notes had fallen away? It seems to have been a casualty of early and overly rigid computer software programmes. John lamented the decline in recording of patient quotes. However, I was heartened by colleagues, whom I met after the interview, who told me the facility to record free text is now easily accessed in the latest software.

In his latest book, there are a couple of what could be labelled contrarian chapters – Launer labels the section ‘Provocations’. One is named ‘Against Diagnosis’, in which the author sets out some arguments against diagnosis. I love his rule-of-thumb conclusion: Avoid them when you can; be humbler about them when you cannot; and seek permission from their rightful owners whenever possible. He is not the only writer to recently question our blind faith in diagnosis.

In her latest book, The Imaginary Patient – How Diagnosis Gets Us Wrong, Consultant Neurologist Jules Montague takes aim at some of the hitherto unshakeable certainties associated with clinical diagnosis. She looks at ways to improve diagnostic accuracy, asking who gets to construct our diagnoses. She also makes the case for the need to report conflict of interests by those making a diagnosis, and the interesting concept of de-diagnosis, an annual appointment with a pa-

tient where a diagnosis is routinely challenged.

Launer has run training courses in interactional skills for over two decades. He bases them on the ideas and skills of therapists who see families and children. He labels the technique ‘conversations inviting change’ (CIC). Much of the training is based on narrative-based medicine, which teaches that everyone – doctors and patients – has a need to tell stories in order to make sense of their experience.

“Sometimes these stories can become stuck, but if we question people sensitively they will generally find a way of telling the story in a different way, and then see the problem in a different way too. Encouraging patients to develop a new and more hopeful story about themselves can be as much a part of healing as any physical treatment,” he writes.

John has run a CIC course here in Ireland and is open to running more. There is the genesis of an interest group here, which will hopefully develop and grow. He concludes the chapter on CIC, as follows:

“All conversations, whether with patients or colleagues, can be therapeutic. Collectively, good conversations can transform a working culture from one that is technocratic, impersonal, and potentially dangerous, to one that is kinder and safer. We need to persuade doctors everywhere that the lifelong development of interactional skills is a core professional need.”

John Launer, a very wise doctor, whom it was a real pleasure to spend time with.

Reflective Practice in Medicine and Multi-Professional Healthcare is published by CRC Press (Taylor and Francis)

The last of the clinician-aristocrats

Andrew Lees is from that generation of neurologists for whom the history and the physical exam are the most vital investigations

PROF SEAMUS O’MAHONY

Read more by Prof Seamus

O’Mahony at www.mindo.ie

Book reviews, I believe, should begin with a conflict-of-interest statement. Here’s mine: Andrew Lees, distinguished doctor and author, is a friend of mine. He is Professor of Neurology at the National Hospital for Nervous Diseases, Queen Square, one of the most highly-cited Parkinson’s disease researchers in the world, and the author of books on such diverse topics as the footballer Ray Kennedy, the explorer Percy Fawcett, and the writer William Burroughs. Lees’s latest book Brainspotting: Adventures in Neurology is a love letter to the speciality to which he devoted his long and garlanded career. Unusually for a London-based teaching hospital brahmin, Lees is a northerner, and a devotee of football and soul music. He studied medicine in the 1960s at the Royal London Hospital in Whitechapel and trained in neurology in the 1970s at University College Hospital and Queen Square, where he was appointed consultant in 1982 at the then very early age of 33. He is the last of that generation of neurologists for whom the history and the physical examination are the most important investigations; he laments the capture of neurology – and medicine in general – by technological innovations, particularly MRI, quoting his fellow-neurologist the late Bryan Matthews, who presciently wrote in 1963: “If investigations can be carried out by the signing of a form requesting someone else to do them, there is a temptation to obtain as much information as possible by this simple method.”

As a boy, Lees – despite his colour blindness – was an avid birdwatcher, a hobby that honed his skills of observation.

In 1972-3, he spent a year training at Charcot’s hospital, the Salpêtrière in Paris, where his “powers of inspection improved greatly”. He describes a bizarre and amusing anecdote involving the chef de service, François Lhermitte, who, at a meeting of the French Neurological Society showed a film illustrating the behaviour of patients with frontal lobe lesions. The film was shot in his own apartment, and the patient was a former nurse; shown into a chamber laid out like a consulting room, she proceeded to auscultate Lhermitte’s chest and then inject him in the bottom with a needle and syringe. Lhermitte later published this episode as a case report: “It was the first and only time in the history of neurology that an author’s buttocks had been displayed for posterity in a published illustration.”

Lees reckons that it took about a decade for him to become fully competent at the neurological examination; as a registrar he would often spend up to two hours examining a single patient. The classical “full” examination as we now know it was perfected by the great Irish neurologist Gordon Holmes (1876-1965), who was in his pomp at Queen Square in the years between the wars. “If the neurological examination was to be of value,” writes Lees, “it needed to be conducted with the discipline of a laboratory experiment.” Holmes, who came from Protestant farming stock in County Louth, and graduated from Trinity College Dublin, is always described as Anglo-Irish. (Holmes-Adie pupil, by the way, has been scandalously shortened to ‘Adie syndrome’.) Holmes’s ward rounds, conducted behind closed doors, went on for hours; can you imagine a round being granted so much hushed reverence now? In a neurological apostolic succession, Holmes taught MacDonald Critchley (father of the witty and worldly Tory MP Julian); and Critchley taught Lees.

Lees is just as devoted to another Holmes – Sherlock. The

inspiration for Conan Doyle’s detective was one of his teachers at the Edinburgh medical school, the surgeon Joseph Bell. Holmes led Lees to William Gowers, “arguably the greatest neurologist who ever lived,” whose 1905 clinical lecture “A Metastatic Mystery” could have been written by Conan Doyle. This passion for observation prompted Lees to take his students and trainees for tutorials on the Circle Line of the London Underground, where they would spot neurological signs in random strangers as they alighted the train.

Lees describes the prelapsarian Eden of medicine’s golden age, when ward rounds were accorded the same respect as a religious ceremony, when clinical doctors visited the mortuary to observe “the ultimate audit” – the post-mortem examination of their patient. (Lees, who stresses the importance of “braincutting” for clinical neurologists, co-founded the Queen Square Brain Bank in 1987.) It was an era when eccentric doctors were still tolerated, even celebrated; Lees’s affection and reverence for his teachers (Critchley, Gerald Stern, Robin Osler Barnard) is touching. He laments the capture of academic medicine by a new cadre, “divorced almost entirely from clinical practice,” whose time is spent sitting on committees and writing grant applications.

As the years went by, Lees gradually realised that while the Holmesian (Gordon that is, not Sherlock) neurological examination was a foundation of his practice, the history – or what he prefers to call “listening” – was even more important: “Listening carefully is the single most effective method of making a neurological diagnosis and being heard is a transformative ritual that facilitates healing.” Andrew Lees, although officially retired, still sees patients once a week, practising what he calls “soulful neurology”. I wonder if they know that he is one of the last of his kind.

Brainspotting: Adventures in Neurology is published by Notting Hill editions

Complaints and the over-stretching of the doctor-patient bond

Patients who want respect, kindness, and competence must understand that the doctor has human limitations

DR LUCIA GANNON

Read more by Dr Lucia Gannon at

www.mindo.ie

@LuciaGannon

On the hottest and sunniest weekend of the year, I spent over five hours writing a summary of my interactions with a patient over the past 18 months. These five hours resulted in a 7,500word report; the equivalent of two or three short stories or one-tenth of a novel. Only it was not immersive writing, not the type where you lose yourself, enter that flow state described by Csikszentmihalyi (pronounced Cheeks-sent-mehigh), where you lose all sense of time and self. When hours feel like seconds and you emerge from the creative project feeling refreshed, energised, and serene. No, this was the antithesis of a creative process, as I painfully hammered out every word while chewing my way through innumerable bags of jellies, (a childhood comfort food), stopping only to get rid of the evidence by throwing the empty packets in the bin. My creation gradually took the shape of a prosaic chronological report of repeated consultations detailing what I said, what they said, what I prescribed, how much, and why. There was no flow or literary merit and my conscious brain remained alert, screaming throughout that there was no point.

A non-specific written complaint suggesting poor med-

MULTIPLE CHOICE QUESTIONS

Question 1

ical performance left me with no choice but to revert to my practice complaints procedure. I followed the protocol and requested medico-legal advice before responding to the complainant. The advice I received cost me one of the warmest, sunniest days of the year. But the alternatives – to ignore the complaint or respond in haste – were not options. I am a professional trained in communication skills. I have spent years teaching communication skills. Our business has had a complaints procedure for years with little cause to put it into action despite thousands of consultations and patient interactions. Like most GP practices, patient grievances are dealt with calmly and swiftly, to the satisfaction of both doctor and patient, without the need to seek medico-legal advice.

Sometimes these actions have led to improvements in the service. More often, they have facilitated reconciling expectations of patients and doctors or staff members and strengthening the inter-personal relationships. Occasionally, patients have decided that the practice did not meet their expectations and have moved elsewhere.

The use of email has improved doctor-patient communication, but it has also made written complaints easier. In five or 10 minutes a patient can write and send an email asserting poor medical care with no regard for the consequences for the doctor. Verbal complaints are relatively easy to deal with. The patient can be taken to a quiet part of the building and have the benefit of face-to-face communication. Follow-up can be arranged if necessary. An email complaint cannot. Written in a moment of anger or frustration the sender will

In children, blocked nasolacrimal ducts

A. Blockage is normally at the lower nasal junction.

B. Cause persistent sticky eyes that are infected more often than not.

C. Discharge should be swabbed for microbiology.

D. If still blocked at six months of age, should be opened by probing.

E. Affect 30 per cent of children at birth.

Question 2

In acne rosacea

A. Peak age of onset is 50-to-60 years.

B. Areas around the eyes and mouth are spared.

C. Earliest sign is flushing of the cheeks in response to hot drinks.

D. Typical lesion is a comedone.

E. Eye involvement includes episcleritis.

Question 3

Recognised causes of a persistent cough (in adults) include

A. Rheumatoid arthritis.

B. ACE inhibitors.

C. Gastro-oesophageal reflux.

D. Hypothyroidism.

E. Allergic rhinitis.

Question 4

In cervical spondylosis

A. Patients may present with alteration of their gait pattern.

B. Neck pain may disturb sleep.

C. Patients should be reassured that, for the most part, the condition is self-limiting.

D. Collars should be avoided if at all possible.

E. The use of tricyclic antidepressants is contraindicated.

Question 5

Characteristic features of Cushing’s syndrome include

A. Moon face.

B. Tiredness and weakness.

C. Bruising.

D. Buccal and palmar crease pigmentation.

E. Hirsutism (in women).

never witness the effect of this action on the recipient. A patient may perceive that they were dismissed, short-changed, or disrespected. They may have other stressful events in their lives. The doctor may have triggered a negative emotion by evoking a memory of a didactic father, a dismissive mother, or an abusive sibling.

Sitting at the kitchen table with the sun glaring through the window, my husband happily engrossed in the Sunday matches, I had my own share of negative emotions that I tried to ignore, but could not. I felt no empathy for this person who was stealing precious hours of my weekend. This person who was unaware of the consequences of their action. Why did I have to justify myself when I had done nothing wrong? Was I not allowed to express irritation and simply tell this person where to go?

Even as I thought it, I knew I would never behave in such a way. But the price of always being professional and not speaking one’s mind is high. People can expect only so much empathy and tolerance from one person. Patients who want to be treated with respect, kindness, and competence must understand that the doctor has human limitations. Professionalism and all that it constitutes takes effort and energy. Abusive and passive-aggressive written communication may be convenient for the complainant, but there are inevitable negative consequences. The doctor-patient relationship is not immutable. Like an over-stretched elastic band, it can become fatigued, break, and outlive its usefulness to the doctor and patient.

It is desirable that patients consider how they treat their doctor if they want to receive the best possible medical care. Doctors do not have special powers and once a patient presses the send button, a doctor has no choice but to treat this seriously and engage with their complaints procedure, regardless of how trivial or inconsequential the doctor thinks it is. Self-restraint, willpower, and the continued effort to understand the perspective of another, are limited resources and like time, we need to be allowed to spend these wisely.

E. TRUE. And menstrual disturbance.

D. FALSE. Can occur in Cushing’s, but not characteristic.

C. TRUE. And striae.

B. FALSE. With anorexia and weight loss features of Addison’s disease.

A. TRUE. And truncal obesity, hypertension.

ANSWER 5

E. FALSE. May be of use in patients with more chronic pain.

D. TRUE. Reduce muscle tone and increase stiffness.

C. TRUE. General tendency towards deterioration is very gradual and there are likely to be long periods when the disease remains static.

B. TRUE. Radiates to shoulder and upper arms, and tends to be postural.

A. TRUE. Can present with neck pain, cervical radiculopathy, or cervical myelopathy. In myelopathy presents with clumsiness of the hands or gait problems.

ANSWER 4

E. TRUE. Or chronic sinusitis.

D. FALSE. There is no connection.

C. TRUE. If suspected, try a proton pump inhibitor.

B. TRUE. In 20 per cent of patients can cause an irritating, dry, throaty cough.

A. TRUE. A chronic cough in a patient with connective tissue disorder raises the possibility of pulmonary fibrosis.

ANSWER 3

E. TRUE. More usually blepharitis or conjunctivitis.

D. FALSE. Absent in rosacea, where one gets papules, pustules, and telangiectasia.

C. TRUE. Or spicy food.

B. TRUE. Cheeks, forehead, nose, and chin most frequently involved.

A. FALSE. 30s and 40s, especially in women.

ANSWER 2

E. FALSE. 15 per cent and great majority will open spontaneously during the first year of life.

D. FALSE. Probe if not opened by one year of age.

C. FALSE. Will yield a combination of normal bacterial flora.

B. FALSE. Not usually infected, as the discharge consists mainly of mucous and debris.

A. TRUE. So debris builds up in the lacrimal sac and is regurgitated onto the eye.

ANSWER 1

ATTR-CM IS LIFE-THREATENING

ORAL VYNDAQEL (TAFAMIDIS)

CAN HELP PATIENTS LIVE LONGER

WITH FEWER HOSPITALISATIONS

Vyndaqel 61 mg is indicated for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM)2

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

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.

Further information available upon request.

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

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.

AMGEVITA® AND ME

HOW AND WHEN IS IT GIVEN?

AMGEVITA® is injected under the skin (a subcutaneous injection) a specially designed pen called SureClick® or using a pre-filled

AMGEVITA® AND ME WHEN IS IT GIVEN?

is injected under the skin (a subcutaneous injection) with designed pen called SureClick® or using a pre-filled syringe.

AMGEVITA® 40mg SureClick® Pre-filled pen

You should inject in the tummy, or the tops of your legs (thighs), see diagram below.

The medicine travels into your bloodstream to work on the that are inflamed and causing your symptoms.

inject in the tummy, or the tops of your legs (thighs), below.

travels into your bloodstream to work on the areas inflamed and causing your symptoms.

Your doctor, pharmacist or nurse will show you or your parent/carer how to give the injection. It’s important the injection is given correctly for it to work.

pharmacist or nurse will show parent/carer how to give the important the injection is given it to work.

Further information is available on request or in the Summary of Product Characteristics (SmPC) at www.medicines.ie.

You may have the injection in hospital or doctor may change this to best suit what works for you.

©2022 Amgen Inc. All rights reserved.

IE-AMB-0122-00002. Date of preparation: January 2022.

Legal Category: POM. Marketing Authorisation Numbers:

EU/1/16/1164/001

have the injection in hospital or can give it to yourself or your can do this for you. Usually, the given every 2 weeks, but your change this to best suit what you.

Adverse reactions /events should be reported to the Health Products Regulatory Authority (HPRA) using the available methods via www.hpra.ie. Adverse reactions/events should also be reported to Amgen Limited on +44 (0) 1223 436441 or Freephone 1800 535 160.

Further information is available on request or in the Summary of Product Characteristics (SmPC) at www.medicines.ie.

References:

Adult

• Rheumatoid arthritis

• Ankylosing spondylitis (AS)

• Axial spondyloarthritis without radiographic evidence of AS

• Psoriatic arthritis

follow the advice of your team and ask to speak to them feeling well.

Paediatric

You need to follow the advice of your healthcare team and ask to speak to them if you are not feeling well.

• Polyarticular juvenile idiopathic arthritis (JIA) (from 2 years of age)

• Enthesitis-related arthritis (from 6 years of age)

1. BVBM Amgevita Product Information Sheet. https://www.hse.ie/eng/about/who/cspd/ncps/ medicines-management/best-value-medicines/best-value-biological-medicines/bvb-medicineamgevita-product-information-sheet.pdf. Accessed January 2022.

2. Medicines Management Programme Best-Value Biological Medicines: Adalimumab 20 mg solution for injection. https://www.hse.ie/eng/about/who/cspd/ncps/medicines-management/best-valuemedicines/best-value-biological-medicines/mmp-report-bvb-medicine-adalimumab-20mgmarch-2021.pdf. January 2022.

detailed instructions on how to your AMGEVITA®, please read the

• Crohn’s disease

• Ulcerative colitis

• Psoriasis

For full and detailed instructions on how to administer your AMGEVITA®, please read the instructions provided in the product carton.

• Hidradenitis suppurativa

• Uveitis

• Crohn’s disease (from 6 years of age)

• Ulcerative Colitis (from 6 years of age)

• Plaque psoriasis (from 4 years of age)

• Adolescent hidradenitis suppurativa (acne inversa) (from 12 years of age)

• Uveitis (from 2 years of age)

AMGEVITA® 20mg Pre-filled syringe

THERESA LOWRY-LEHNEN , RGN, GPN, RNP, BSc, MSc, M. Ed, PhD, Clinical Nurse Specialist and Associate Lecturer, South East Technological University

Coeliac disease

There are an estimated 50,000 people in Ireland living with Coeliac disease, which leads to chronic ill health and complications if untreated formis (DH), a skin condition caused by gluten intolerance. Dermatitis herpetiformis is an intensely pruritic papulovesicular rash that is distributed symmetrically over the extensor areas of the elbows, knees, buttocks, shoulders, and scalp. It usually responds to the exclusion of gluten from the diet, but can take a long time for a gluten-free diet to clear the rash. For individuals with dermatitis herpetiformis, a skin biopsy is usually sufficient for diagnosis of both DH and Coeliac disease. It is not necessary to perform an endoscopic biopsy, as the skin biopsy is definitive.14 Dapsone, a sulfone, is an oral antibacterial medication prescribed for DH, which is taken twice daily. Dapsone can cause side-effects such as headache and depression and may need to be prescribed for up to two years. The lowest effective dose should be prescribed. 3,4,13

Coeliac disease is an autoimmune disorder triggered by gluten ingestion in genetically-predisposed individuals, resulting in mucosal inflammation and villous atrophy in the small intestine leading to malabsorption. It is a chronic disease and is not an allergy or food intolerance. Coeliac disease is one of the most common autoimmune conditions, with a prevalence of 0.5-to-1 per cent of the general population, with a female-to-male ratio ranging from 2:1 to 3:1.1,2 Prevalence estimates based on serologic screens indicate the disorder may be present in 1/150 in Europe, and 1/250 in some parts of the US. Current prevalence estimates in some regions including Ireland are as high as 1/100.4 There are an estimated 50,000 people in Ireland living with Coeliac disease, and a further 400,000 who are gluten intolerant. Many cases of Coeliac disease go undiagnosed. 5,13

Onset of Coeliac disease can occur at any age, although symptoms are most likely to develop in early childhood after weaning with gluten, and the introduction of cereals into the diet in the first year of life. Coeliac disease can also occur in later adulthood, and is often diagnosed in people aged 40-to-60 years. Coeliac disease is higher in first-degree Coeliac disease relatives (10-to-20 per cent) and in other at-risk groups, particularly patients with Down syndrome, type 1 diabetes, or IgA deficiency.1,2 The condition is more common in people with type 1 diabetes and autoimmune thyroid disease. Between 4 and 9 per cent of people with type 1 diabetes also have Coeliac disease, compared with 1 per cent in the general population. People with autoimmune thyroid disease are at a higher risk (1-to-4 per cent) of having Coeliac disease compared with 1 per cent in the general population.12 Coeliac disease is a chronic condition, and currently, the only treatment consists of permanent exclusion of gluten from the diet. 3

Aetiology and pathophysiology

Coeliac disease is a hereditary disorder caused by sensitivity to the gliadin fraction of gluten, a protein found in wheat. Similar proteins are present in rye and barley. In a genetically susceptible person, gluten-sensitive T-cells are activated when gluten-derived peptide epitopes are presented. The inflammatory response causes characteristic mucosal villous atrophy in the small intestine. This destruction, in turn, leads to the decreased functionality of the intestinal surface and malabsorption. The lack of nutrient absorption impacts directly on the digestive system, but also indirectly on all the systems of the body. This results in generally poor health, and is why Coeliac disease can have signs and symptoms arising from almost any body system, and not just the gastrointestinal system.4

Presentation

Coeliac disease is more commonly detected in infants and children younger than three years of age, and is characterised by diarrhoea, anorexia, pallor, abdominal distention, muscle wasting, and failure to thrive. Stools are often soft, bulky, clay-coloured, and offensive. Older children may present with anaemia, weight loss or failure to grow normally. Adults may present with diarrhoea, bloating, constipation and abdominal pain. 3 Lassitude, weakness, and anorexia are common. Mild and intermittent diarrhoea is sometimes the presenting symptom and steatorrhoea ranging from mild to severe. Some patients have weight loss, although rarely enough to become underweight. Anaemia, glossitis, angular stomatitis, and aphthous ulcers are often seen in these patients. Manifestations of vitamin D and calcium deficiencies such as osteomalacia, osteopaenia, and osteoporosis are common. Both males and females may have reduced fertility and women may have amonorrhoea. 3,4

About 10 per cent of patients with Coeliac disease develop dermatitis herpeti-

Untreated Coeliac disease leads to chronic ill health and complications. Complications which may or may not be present at diagnosis include osteoporosis, ulcerative jejunitis, malignancy-intestinal lymphoma, functional hyposplenism, vitamin D deficiency, and iron deficiency.11

Serological testing for Coeliac disease should be offered to people with persistent unexplained abdominal or gastrointestinal symptoms; faltering growth; prolonged fatigue; unexpected weight loss; severe or persistent mouth ulcers; unexplained iron, vitamin B12 or folate deficiency; type 1 diabetes at diagnosis; autoimmune thyroid disease at diagnosis; irritable bowel syndrome in adults; and first-degree relatives of people with Coeliac disease.11

Diagnosis

A diagnosis of Coeliac disease is suspected clinically, based on history and laboratory abnormalities suggestive of malabsorption. Family incidence is an indicator and Coeliac disease should also be strongly considered in patients with iron deficiency without obvious

gastrointestinal bleeding. A confirmed diagnosis depends on serologic markers and a small-bowel biopsy. Anti-tissue transglutaminase antibody (tTG) and anti-endomysial antibody (EMA) have sensitivity and specificity 90 per cent. These antibodies decrease in titre in patients on a gluten-free diet and are useful in monitoring dietary adherence.4 Diagnostic serologic testing is done with patients following a gluten-containing diet. To obtain a reliable result the patient must have been consuming gluten for more than one meal a day for six weeks. It is important to advise the patient not to start a gluten-free diet until diagnosis is confirmed by a specialist, even if the results of a serological test are positive.11

Coeliac disease is strongly associated with variations of the human leukocyte antigen (HLA) DQ gene. Research has shown that the HLA DQ2 and HLA DQ8 variants are almost always present in people with Coeliac disease of white, Northern European background. Although less clear, these variants probably play a similar role in other ethnic groups. Testing for the HLA DQ2 and HLA DQ8 variants alone cannot be used to diagnose Coeliac disease, as these genes are present in a large proportion of the population, including people who do not have coeliac disease. In the UK, NICE recommends to only consider using HLA DQ2 (DQ2.2 and DQ2.5) and HLA DQ8 testing in diagnosis of Coeliac disease in specialist settings; eg, children who are not having a biopsy or people who have already limited gluten from the diet and choose not to have a gluten challenge.6,11

Serological tests to investigate suspected Coeliac disease in young people and adults should test for total immunoglobulin A (IgA) and IgA tissue transglutaminase (tTG) as the first choice; IgA endomysial antibodies (EMA) if IgA tTG is weakly positive and consider using IgG EMA, IgG deamidated gliadin peptide (DGP) or IgG tTG if IgA is deficient. Serological tests to investigate suspected Coeliac disease in children should test for total IgA and IgA tTG as the first choice, and consider using IgG EMA, IgG DGP or IgG tTG if IgA is deficient.11

If either serological test is negative, Coeliac disease is unlikely. However, it is possible to have a negative test and still have Coeliac disease; for example, patients already on a gluten-free diet and therefore the antibodies are negative. A minority of Coeliac patients may have IgA deficiency and the screening test results can be misleading so, the total serum IgA should be checked to detect IgA deficiency. 3,8

If either serological test is positive, the patient should have a diagnostic small-bowel biopsy. The gold standard for the diagnosis of Coeliac disease is a duodenal mucosal biopsy which shows villous atrophy.4 Biopsy remains essential for the diagnosis of adult Coeliac disease and cannot be replaced by serology alone. Exceptions are patients with coagulation disorders and pregnant women, in whom biopsy may not be feasible or

Table 1: Classification of histologic findings in celiac disease. Available at: https://celiac.org/about-celiac-disease/screening -and-diagnosis/diagnosis/

Continued from p27 ▸

should be postponed until postpartum. 8

In Coeliac disease, the damage to the lining of the intestine is classified according to the Marsh classification scale:7 Marsh 0: lining of the intestine is normal and unlikely that the person has coeliac disease.

Marsh 1: Increased number of lymphocytes seen, but there are normal villi.

Marsh 2: Increased number of lymphocytes, the depressions in the lining of the intestine are deeper than normal, but normal villi length.

Marsh 3: The villi are becoming flattened.

Marsh 4: The villi are completely flattened.

Originally the Marsh scale ranged from 0 to 4, with type 3 indicating Coeliac disease. The scale has since been simplified to allow for more consistency and reproducibility between pathologists.14

There are situations when the diagnosis is not clear. Some patients experience symptoms despite no identified changes on the small bowel biopsy. There is also seronegative Coeliac disease where despite typical symptoms and significant villous atrophy of the duodenal biopsy, there is no serological evidence of the disease. 3

Treatment and management

The main treatment of Coeliac disease is a lifelong, strict, gluten-free diet. These include wheat protein, gliadin, rye protein, secalin, and barley protein, hordein. The goal of treatment is to relieve symptoms, achieve mucosal healing, avoid complications of Coeliac disease , and have a good quality-of-life with a nutritionally-complete gluten-free diet. This is best achieved when patients are motivated, receive expert information and are involved in their own care and treatment. Follow-up and annual review are necessary to ensure adequate response to treatment, prevention of complications, and maintenance of motivation to remain gluten free. 8

As a gluten-free diet is the primary treatment option for people with Coeliac disease, it is important that a dietitian or healthcare professional with a specialist interest in Coeliac disease plays a significant role in the patient’s care and follow-up. Many of the common problems associated with the long-term management of Coeliac disease happen because of non-adherence to a gluten-free diet.11 Patient education is important and a healthcare professional with a specialist knowledge of Coeliac disease should explain to the patient, and their family members or carers the importance of a gluten-free diet, and provide detailed information to help the patient follow it. This should include: information on which types of food contain gluten and suitable alternatives, including gluten-free substitutes, explanations of food labelling information sources about gluten-free diets, recipe ideas and cookbooks, how to manage social situations, eating out and travelling away from home, including travel abroad, avoiding cross-contamination with gluten in the home, minimising the

risk of accidental gluten intake when eating out, and the role of national and local coeliac support groups.11

Many everyday foods are gluten free including meat, vegetables, cheese, potatoes and rice. Foods containing gluten include, bread, pasta, cereals, biscuits, crackers, cakes, pastries, pies, gravies and sauces. However, gluten free varieties of these and other products exist. It is important to check the labels on food, as many products, particularly processed food contain gluten additives. Gluten may also be found in non-food products such as some medications, postage stamps, and lipstick.13

Oats contain a protein called avenin which is like gluten, but most people with Coeliac disease can safely eat avenin. Before including oats in the diet, the Coeliac disease patient should talk to a dietician or clinician, and check the oats are pure with no possibility of contamination from other grains. Coeliac friendly versions of oats are widely available. Oats should be avoided until the gluten-free diet is working well. They can be re-introduced into the diet, when the patient is symptom free, but should be stopped if symptoms re-occur.13

Symptoms usually improve over the course of several weeks once a gluten-free diet is initiated. Patients who do not respond need further review, and also an assessment of compliance with the gluten free diet. Serology testing can assess compliance. Non-compliance can be unintentional, and an individual may be still ingesting gluten without realising it. 3

Treatment and management involve assessing the impact of malabsorption on the body. Nutritional deficiencies are common in Coeliac disease and should be identified and treated. Full blood count, iron stores, folate, ferritin, vitamin B12, levels of vitamin D and other fat-soluble vitamins, and bone mineral density should be monitored. 3 A DEXA scan may be required for those with bone thinning or osteoporosis. A gluten-free diet itself can also be associated with lower levels of certain micronutrients. Fibre, iron, calcium, vitamin D, vitamin B6, vitamin B12 and folate deficiencies have all been noted in people following a gluten-free diet. Gluten-free foods themselves have been shown to be lower in thiamine, riboflavin, niacin, folate, iron, and dietary fibre. This may primarily be because gluten-free foods tend not to be fortified, and be refined.

Coeliac patients should be encouraged to consume foods high in iron and folate to combat these deficiencies, and supplements should be considered if recommended intakes cannot be achieved through diet alone. Calcium and vitamin D deficiencies may also be present and supplements are necessary if intake is insufficient. Other nutritional deficiencies may include magnesium, zinc, niacin, and riboflavin. Most nutritional deficiencies will resolve due to mucosal healing and increased absorption, once a gluten-free diet is established. 9

The key elements of managing coeliac disease through diet are to choose and eat foods that are gluten-free; consume a well-balanced diet; including good

sources of calcium, iron, vitamin D and B vitamins; eat foods that are rich in fibre; always check foods and fluids in the coeliac society list of gluten-free foods, and check food labels. The emphasis of dietary management in Coeliac disease should focus on the nutritional quality of the diet, and not just simply ‘foods allowed or foods to avoid’. 9

Prognosis, outlook, and support

Prognosis for individuals diagnosed early and who remain compliant with a gluten-free diet is good, however, a lifelong diet completely free of gluten can be costly and challenging. Strict compliance with a gluten-free diet is difficult, and relapses are common. Many patients continue to experience symptoms, often due to imperfect adherence to a gluten-free diet.

People with Coeliac disease face a lifelong condition that can be emotionally and physically debilitating, and which left untreated can lead to a significant reduction in quality-of-life. While a large selection of gluten-free products are available in major supermarkets and food outlets with more supports available now than in the past, increased awareness of Coeliac disease as a worldwide health problem is necessary, to help patients cope with the illness and its treatment. Patient support and information is an integral part of the management of Coeliac disease. Clinicians play a lead role by providing ongoing assessment, management, support and education.

Future drug therapies are currently in development with the hope of reducing the burden of living with Coeliac disease, and improving long-term health outcomes. Clinical trials are in progress, but only a few have reached later clinical trial phases. Other scientific challenges include obtaining a better understanding of phenotypes and seronegative coeliac disease. There is ongoing work on developing possible non-dietary therapies that would enable people with Coeliac disease to tolerate gluten. One of the main focuses of the research in this area is immune modulators. Ongoing research and therapeutic strategies aimed at developing a vaccine and desensitising those with Coeliac disease to gliadin peptides, could provide a preventative and definitive cure for Coeliac disease. Identification of future cure and/or alternative treatments to a gluten-free diet brings hope for Coeliac disease patients, who are unavoidably burdened by dietary restrictions.

The Coeliac Society of Ireland https:// coeliac.ie/ is a registered charity that provides information and support to people diagnosed with Coeliac disease throughout Ireland. The Society is part of the European Association of Coeliac Societies (AOECS) involved in setting standards for gluten-free foods both within the European Union and internationally. The society empower the coeliac and gluten intolerant community by providing them with information, food lists, advice and practical solutions as they navigate a gluten-free lifestyle. They represent patient interests by advocating to government health agencies for improved resources and services, so that patients and their families can access the care they need.

References

1. Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A. (2019). Coeliac disease: A comprehensive current review. BMC medicine, 17(1), 142. doi: 10.1186/s12916-019-1380-z

2. Fasano A, Catassi C. Coeliac disease. N Engl J Med. 2012; 367:2419–2426. doi: 10.1056/NEJMcp1113994

3. Posner E, Haseeb M. (2022). Coeliac disease. Stat Pearls Publishing. Available from: www.ncbi.nlm. nih.gov/books/NBK441900/

4. Ruiz A. (2021). Coeliac disease. MSD Manual Professional Version. Available at: www.msdmanuals.com/ professional/gastrointestinal-disorders/ malabsorption-syndromes/celiac-disease

5. Coeliac Society of Ireland. (2021). Getting diagnosed. Available online at: https://coeliac.ie/getting-diagnosed/

6. Coeliac UK (2022). Advice before testing and recommended tests. Available at: www.coeliac.org.uk/healthcareprofessionals/diagnosis/recommendedtests/#:~:text=Testing%20for%20 the%20HLA%20DQ2,consider%20 using%20HLA%20DQ2%20(DQ2

7. Coeliac UK (2022). Classification of biopsy results. Available at: www. coeliac.org.uk/information-andsupport/coeliac-disease/gettingdiagnosed/blood-tests-and-biospy/

8. Ludvigsson J, Bai J, Biagi F, et al. Diagnosis and management of adult coeliac disease: Guidelines from the British Society of Gastroenterology. Gut 2014; 63: 1210-1228

9. Coeliac Society of Ireland. (2021). Nutritional Deficiencies. Available online at: https://coeliac.ie/healthcareprofessionals/nutritional-deficiencies/

10. Coeliac Society of Ireland. (2021). Healthcare professionals. Available at: https://coeliac.ie/ healthcare-professionals/

11. NICE (2015). Coeliac disease: recognition, assessment and management. NICE guideline. National Institute for Health and Care Excellence. Available at: https:// coeliac.ie/wp-content/uploads/2020/06/ coeliac-disease-recognition-assessmentand-management-1837325178565.pdf

12. Coeliac UK (2022). Conditions linked to coeliac disease. Available at: www. coeliac.org.uk/information-andsupport/coeliac-disease/conditionslinked-to-coeliac-disease/

13. HSE (2021). Coeliac disease. Treatment. Health Service Executive. Available at: www2.hse.ie/conditions/ coeliac-disease/treatment/

14. Coeliac Disease Foundation. (2021). Coeliac disease diagnosis. Available at: https://celiac.org/about-celiac-disease/ screening-and-diagnosis/diagnosis/

Prolonged-release tablets containing tofacitinib citrate, equivalent to 11 mg tofacitinib. Oral solution containing tofacitinib citrate, equivalent to 1 mg/mL tofacitinib. Indications: Please note not all presentations are licensed for all indications, please see dosage section for details: In combination with methotrexate (MTX) for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs. Can be given as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate. In combination with MTX for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease modifying antirheumatic drug (DMARD) therapy. For the treatment of adult patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy. For the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent. For the treatment of active polyarticular juvenile idiopathic arthritis (rheumatoid factor positive [RF+] or negative [RF-] polyarthritis, and extended oligoarthritis), and juvenile psoriatic arthritis in patients 2 years of age and older, who have responded inadequately to previous therapy with DMARDs. Can be given in combination with MTX or as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate. Dosage: Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of the condition for which tofacitinib is indicated. Tofacitinib is given orally, with or without food. RA and PsA: The recommended dose is 5 mg twice daily or 11 mg once daily which should not be exceeded. Treatment with tofacitinib 5 mg film coated tablets twice daily and tofacitinib 11 mg prolonged release tablet once daily may be switched between each other on the day following the last dose of either tablet. AS:

The recommended dose is 5 mg twice daily. Available data suggest that clinical improvement in AS is observed within 16 weeks of initiation of treatment. Continued therapy should be carefully reconsidered in AS patients exhibiting no clinical improvement within this timeframe. UC: The recommended dose is 10 mg twice daily for induction for 8 weeks. For patients who do not achieve adequate therapeutic benefit by week 8, the induction dose of 10 mg twice daily can be extended for an additional 8 weeks (16 weeks total), followed by 5 mg twice daily for maintenance. Tofacitinib induction therapy should be discontinued in any patient who shows no evidence of therapeutic benefit by week 16. The recommended dose for maintenance treatment is tofacitinib 5 mg twice daily.

Tofacitinib 10 mg twice daily for maintenance treatment is not recommended in patients with UC who have known venous thromboembolism (VTE) risk factors, unless there is no suitable alternative treatment available. For patients with UC who are not at increased risk for VTE, tofacitinib 10 mg twice daily may be considered if the patient experiences a decrease in response on tofacitinib 5 mg twice daily and failed to respond to alternative treatment options for UC such as tumour necrosis factor inhibitor treatment. Tofacitinib 10 mg twice daily for maintenance treatment should be used for the shortest duration possible. The lowest effective dose needed to maintain response should be used. Polyarticular JIA and juvenile PsA: The recommended dose in patients 2 years of age and older: 10 kg - < 20 kg: 3.2 mg (3.2 mL oral solution) twice daily, 20 kg - < 40 kg: 4 mg (4 mL oral solution) twice daily, and ≥ 40 kg 5 mg (5 mL oral solution or 5 mg tablet) twice daily. Patients ≥ 40 kg treated with tofacitinib 5 mL oral solution twice daily may be switched to tofacitinib 5 mg tablets twice daily. Available data suggest that clinical improvement is observed in paediatric patients within 18 weeks of initiation. Continued therapy should be carefully reconsidered in a paediatric patient exhibiting no clinical improvement within this timeframe. Dose interruption and adjustment:

Tofacitinib treatment should be interrupted if a patient develops a serious infection until the infection is controlled. Interruption of dosing may be needed for management of dose-related laboratory abnormalities including lymphopenia, neutropenia, and anaemia. It is recommended not to initiate dosing in patients with an absolute lymphocyte count (ALC) less than 0.75 x 10 9/L, an absolute neutrophil count (ANC) less than 1x10 9 /L or with haemoglobin less than 9 g/dL. It is recommended not to initiate dosing in paediatric patients with an absolute neutrophil count (ANC) less than 1.2 x 10 /L or with haemoglobin less than 10 g/dL. Renal impairment: No dose adjustment is required in patients with mild or moderate renal impairment. Patients with severe renal impairment the dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal renal function is 5 mg twice daily or 11 mg prolonged-release tablet once daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal renal function is 10 mg twice daily. Patients with severe renal impairment should remain on a reduced dose even after haemodialysis. Hepatic impairment: No dose adjustment is required in patients with mild hepatic impairment. Patients with moderate hepatic impairment dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal hepatic function is 5 mg twice daily or 11 mg prolonged-release tablet once daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal hepatic function is 10 mg twice daily. Tofacitinib should not be used in patients with severe hepatic impairment. Elderly: No dose adjustment is required in patients aged 65 years and older. Use with caution as increased risk and severity of adverse events. See also Warnings & Precautions for use in patients over 65 years of age. Paediatric population: The safety and efficacy of tofacitinib in children less than 2 years of age with polyarticular JIA and juvenile PsA has not been established. The safety and efficacy of tofacitinib in children less than 18 years of age with other indications (e.g. ulcerative colitis) has not been established. The safety and efficacy of tofacitinib prolonged-release formulation in children aged less than 18 years have not been established. Interactions: TTofacitinib total daily dose should be reduced by half in patients receiving potent inhibitors of cytochrome P450 (CYP) 3A4 (e.g. ketoconazole) and in patients receiving 1 or more products that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g. fluconazole). Coadministration with potent CYP inducers (e.g. rifampicin) may result in a loss of or reduced clinical response. Coadministration with potent inducers of CYP3A4 is not recommended. Contraindications: Hypersensitivity to any of the ingredients, active tuberculosis (TB), serious infections such as sepsis, or opportunistic infections, severe hepatic impairment, pregnancy and lactation. Warnings and Precautions: Patients treated with tofacitinib should be given a patient alert card. Use in patients over 65 years of age: Considering the increased risk of serious infections, myocardial infarction, and malignancies with tofacitinib in patients over 65 years of age, tofacitinib should only be used in patients over 65 years of age if no suitable treatment alternatives are available. Combination with other therapies: There was a higher incidence of adverse events for the combination of tofacitinib with MTX versus tofacitinib as monotherapy in RA clinical studies. Tofacitinib should be avoided in combination with biologics and potent immunosuppressants such as azathioprine, 6-mercaptopurine, ciclosporin and tacrolimus. Venous thromboembolism (VTE): Serious VTE events including pulmonary embolism (PE), some of which were fatal, and deep vein thrombosis (DVT), have been observed in patients taking tofacitinib. In a randomised post authorisation safety

MAKE FROM THE START1,2,a

If D-dimer test result is ≥ 2× ULN, confirm that clinical benefits outweigh risks prior to a decision on treatment continuation with tofacitinib. Tofacitinib should be used with caution in patients with known risk factors for VTE, regardless of indication and dose. Tofacitinib 10 mg twice daily for maintenance treatment is not recommended in patients with UC who have known VTE risk factors, unless there is no suitable alternative treatment available. Promptly evaluate patients with signs and symptoms of VTE and discontinue tofacitinib in patients with suspected VTE, regardless of dose or indication.

Infections: Serious and sometimes fatal infections have been reported in patients administered tofacitinib. Rheumatoid arthritis patients taking corticosteroids may be predisposed to infection. Patients should be closely monitored for infections, with prompt diagnosis and treatment. Treatment should be interrupted if a serious infection develops. As there is a higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used when treating the elderly and patients with diabetes.

Tuberculosis: Patients should be evaluated for both active and latent TB prior to being treated with tofacitinib. Patients who test positive for latent TB should be treated with standard antimycobacterial therapy before administering tofacitinib. Viral Reactivation: In clinical studies viral reactivation and cases of herpes zoster have been observed. Screening for viral hepatitis should be performed in accordance with clinical guidelines prior to starting therapy with tofacitinib. The impact on chronic viral hepatitis is not known. Major adverse cardiovascular events (MACE): MACE have been observed in patients taking tofacitinib. In a randomised post authorisation safety study in patients with RA who were 50 years of age or older with at least one additional cardiovascular risk factor, an increased incidence of myocardial infarctions was observed with tofacitinib compared to TNF inhibitors. In patients over 65 years of age, patients who are current or past smokers, and patients with other cardiovascular risk factors, tofacitinib should only be used if no suitable treatment alternatives are available. Vaccinations: Prior to initiating tofacitinib, it is recommended that all patients, particularly pJIA and jPsA patients, be brought up to date with all immunisations in agreement with current immunisation guidelines. Live vaccines should not be given concurrently with tofacitinib. Malignancy and lymphoproliferative disorder: Tofacitinib may affect host defences against malignancies. In a randomised post authorisation safety study in patients with RA who were 50 years of age or older with at least one additional cardiovascular risk factor, an increased incidence of malignancies excluding non-melanoma skin cancer (NMSC), particularly lung cancer and lymphoma, was observed with tofacitinib compared to TNF inhibitors. Lung cancers and lymphoma in patients treated with tofacitinib have also been observed in other clinical studies and in the post marketing setting. Other malignancies in patients treated with tofacitinib were observed in clinical studies and the post marketing setting, including, but not limited to, breast cancer, melanoma, prostate cancer, and pancreatic

cancer. In patients over 65 years of age, patients who are current or past smokers, and patients with other malignancy risk factors tofacitinib should only be used if no suitable treatment alternatives are available. NMSCs have been reported in patients treated with tofacitinib; the risk of NMSC may be higher in patients treated with tofacitinib 10 mg twice daily than in patients treated with 5 mg twice daily. Periodic skin examination is recommended in patients at increased risk for skin cancer. Interstitial lung disease: Caution is recommended in patients with a history of chronic lung disease as they may be more prone to infection. Asian patients are known to be at higher risk of ILD, caution should be exercised with these patients. Gastrointestinal perforations: Tofacitinib should be used with caution in patients who may be at increased risk, e.g. history of diverticulitis or concomitant use of corticosteroids or NSAIDs. Hypersensitivity: Cases of hypersensitivity associated with tofacitinib administration have been reported. Allergic reactions included angioedema and urticaria; serious reactions have occurred. If any serious allergic or anaphylactic reaction occurs, tofacitinib should be discontinued immediately. Laboratory Parameters: : Increased incidence of lymphopenia and neutropenia have been reported, and decreases in haemoglobin, which should be monitored in accordance with the SmPC. Monitor ANC and haemoglobin at baseline, 4-8 weeks and 3 monthly, ALC at baseline and 3 monthly. Tofacitinib has been associated with increases in lipid parameters, maximal effects were observed within 6 weeks. Monitoring should be performed 8 weeks after initiation and managed according to hyperlipidaemia guidelines. Increases in liver enzymes greater than 3x ULN were uncommonly reported; use caution when initiating with potential hepatotoxic medicinal products. Gastrointestinal obstruction with a non-deformable prolonged-release formulation: Caution should be used when administering tofacitinib 11 mg prolonged release tablets to patients with pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic). Pregnancy & Lactation: Use of tofacitinib during pregnancy and breast-feeding is contraindicated. Side Effects: RA: The most common serious adverse reactions were serious infections; pneumonia, cellulitis, herpes zoster, UTIs, diverticulitis, appendicitis and opportunistic infections. The most commonly reported adverse reactions during the first 3 months in controlled clinical studies were headache, upper respiratory tract infections, nasopharyngitis, diarrhoea, nausea and hypertension. UC: The most commonly reported adverse reactions in patients receiving tofacitinib 10 mg twice daily were headache, nasopharyngitis, nausea, and arthralgia. Commonly reported adverse reactions (>1/100 to <1/10) across all indications were pneumonia, influenza, herpes zoster, urinary tract infection, sinusitis, bronchitis, viral upper respiratory tract infection, pharyngitis, anaemia, headache, hypertension, cough, abdominal pain, vomiting, diarrhoea, nausea, gastritis, dyspepsia, rash, arthralgia, pyrexia, peripheral oedema, fatigue, increased creatine phosphokinase. Refer to section 4.8 of the SmPC for further information on side effects, including description of selected adverse reactions. Legal Category: S1A. Marketing Authorisation Number: EU/1/17/1178/003 – 5 mg (56 film-coated tablets); EU/1/17/1178/007 –10 mg (56 film-coated tablets); EU/1/17/1178/012 – 11 mg (28 prolonged-release tablets); EU/1/17/1178/015 1mg/mL oral solution. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com For queries regarding product availability please contact: Pfizer Healthcare Ireland, 9 Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24, + 353 1 467 6500. Last revised: 03/2022. Ref: XJ 15_0.

Clinical Gastroenterology

PRISCILLA LYNCH priscilla@mindo.ie

lcerative colitis [UC] is a chronic inflammatory bowel disease [IBD] characterised by colonic inflammation extending to a variable extent from the rectum. Key updates to the European Crohn’s and Colitis Organisation (ECCO) Guidelines on the Medical and Surgical Treatment of Ulcerative Colitis in Adults have recently been published, which summarise the current evidence.

Changes to medical management in new guidelines

Key areas of importance for the medical treatment of UC include clinical response and remission for maintenance and induction therapies, as well as steroid-free clinical remission. However, a key area of debate is when to escalate treatment. There is less evidence in UC than in Crohn’s disease on the importance of early treatment escalation. At the same time, the experience of recurrent symptom flares can lead to physical and psychological harm, as can repeated exposure to corticosteroids, notes ECCO. “Although the cost of an intervention is a factor reflected in the GRADE [Grading of Recommendations Assessment, Development and Evaluation] process when forming the strength of recommendation, as international guidelines there will be local health economic considerations that this document cannot address. Nevertheless, it is clear that appropriate and timely selection of patients for higher-cost interventions is critical to achieve optimal health economic outcomes,” the new updated guidelines state.

A notable shift from the 2017 ECCO guidelines is the recommendation on considering treatment options based on patient disease severity. Previously, guidelines advised treatment according to the site of the disease and its activity, whereas revised guidelines recommend treatment under sections labelled ‘Medical management of mildly-to-moderately active UC’ and ‘Medical management of moderately-to-severely active UC’. The decision to change this particular section aims to ensure that patients with limited disease who are displaying active symptoms have access to appropriate treatment options.

Another notable change is in regard to new data and treatments. Following the recent MERIT-UC trial conducted by Herfarth et al, which took place in 2018 and concluded that methotrexate was not superior to a placebo in maintaining steroid-free response or remission in UC, it has been removed from the guidelines. New data for vedolizumab, ustekinumab, and tofacitinib have been included in the updated ECCO Therapeutic Guidelines on UC, which have been written in a way that allows for new updates to therapeutics to be included.

The following is a summary of the key recommendations in the 2022 ECCO Guidelines on the Medical Treatment of Ulcerative Colitis in Adults

Medical management of mildly-to-moderately active UC

▶ Induction of remission in mild-

ly-to-moderately UC

Recommendation 1

ECCO recommends 5-aminosalicylates at a dose of ≥2g/day [d] to induce remission in patients with mildly-to-moderately active UC [strong recommendation; quality of evidence low].

Recommendation 2

ECCO recommends topical [rectal] 5-ASA at a dose of ≥1g/d for the induction of remission in active distal colitis [strong recommendation, low-quality evidence].

Recommendation 3

ECCO suggests the use of oral 5-ASA [≥2g/d] combined with topical [rectal] 5-ASA over oral 5-ASA monotherapy for induction of remission in adult patients with active UC of at least rectosigmoid extent [weak recommendation; very low-quality evidence].

Recommendation 4

ECCO recommends using topical [rectal] steroids for the induction of remission in patients with active distal colitis [strong recommendation, very low-quality evidence].

Recommendation 5

ECCO suggests treatment with topical [rectal] 5-ASAs over topical [rectal] steroids for induction of remission in patients with active distal UC [weak recommendation, very low-quality evidence].

Recommendation 6

ECCO suggests the use of colonic-release corticosteroids for induction of remission in patients with active mild-to-moderate UC [weak recommendation, low quality of evidence].

Recommendation 7

ECCO suggests against the use of thiopurines as monotherapy for the induction of remission in patients with active UC [weak recommendation, very low quality of evidence].

Recommendation 8

ECCO recommends the use of oral 5-ASA at a dose ≥2g/d for maintenance of remission in UC patients [strong recommendation; very low quality of evidence].

Recommendation 9

ECCO suggests the use of topical [rectal] 5-ASA for the maintenance of remission in patients with distal UC [weak recommendation, very low-quality evidence].

Recommendation 10

ECCO recommends monotherapy with thiopurines for the maintenance of remission in patients with steroid-dependent UC or who are intolerant to 5-ASA [strong recommendation, moderate quality of evidence].

Medical management of moderately-to-severely active UC

▶ Induction of remission in moderately-to-severely active UC

Recommendation 11

ECCO recommends oral prednisolone for induction of remission in non-hospitalised patients with moderately-to-severely active UC [strong recommendation; very low quality of evidence].

Recommendation 12

ECCO recommends treatment with anti-tumour necrosis factor [TNF] agents [infliximab, adalimumab, and golimumab] to induce remission in patients with moderate-to-severe

UC who have inadequate response or intolerance to conventional therapy [strong recommendation, moderate-quality evidence].

Recommendation 13

Updated ECCO guidelines on management of UC in adults U

ECCO recommends treatment with vedolizumab for the induction of remission in patients with moderately-to-severely active UC who have inadequate response or intolerance to conventional therapy [strong recommendation, low quality of evidence].

Recommendation 14

ECCO recommends treatment with tofacitinib to induce remission in patients with moderate-to-severe UC who have inadequate response or intolerance to conventional therapy [strong recommendation, moderate quality of evidence].

Recommendation 15

ECCO recommends treatment with ustekinumab for the induction of remission in patients with moderately-to-severely active UC with inadequate response or intolerance to conventional therapy. [strong recommendation, moderate quality of evidence].

▶ Maintenance of remission of moderately-to-severely active UC

Recommendation 16

ECCO recommends anti-TNF agents [infliximab, adalimumab, or golimumab] for the maintenance of remission in patients with UC who responded to induction therapy with the same drug [strong recommendation, high-quality evidence].

Recommendation 17

In UC patients who have lost response to an anti-TNF agent, there is currently insufficient evidence to recommend for or against the use of therapeutic drug monitoring to improve clinical outcomes.

Recommendation 18

ECCO recommends vedolizumab for maintenance of remission in patients with UC who responded to induction therapy with vedolizumab [strong recommendation, moderate-quality evidence].

Recommendation 19

We suggest the use of vedolizumab rather than adalimumab for the induction and maintenance of remission in patients with moderately-to-severely active ulcerative colitis [weak recommendation, low level of evidence].

Recommendation 20

ECCO recommends tofacitinib for maintaining remission in patients with UC who responded to induction therapy with tofacitinib [strong recommendation, moderate quality of evidence].

Recommendation 21

ECCO recommends ustekinumab for the maintenance of remission in patients with UC who responded to induction therapy with ustekinumab [strong recommendation, moderate quality of evidence].

Changes to surgical management of UC in new guidelines

While UC presents as a mild condition, it often leads to life-threatening and systemic complications that require urgent interventions. Up to 25 per cent of UC patients require a surgical intervention in their lifetime.

Key updates regarding surgery in cases of moderate-to-severe UC in the new ECCO guidelines include that reconstructive ileal pouch-anal anastomosis surgery can be offered to refractory and corticosteroid-dependent patients following evidence that this improves patient quality-of-life. The importance of pre-operative optimisation in patients with moderate-to-severe UC is also stressed. Another key update focuses on the use of steroids pre-operatively, which should be avoided or weaned off before restorative surgery, and where weaning is not possible, surgery should be postponed. Prophylactic anticoagulation therapy is also advised in adult patients with active UC to reduce the risk of venous thromboembolism, and systemic nutrition is advised despite a lack of evidence.

The updated guidelines state that the modified two-stage colectomy procedure may be associated with fewer complications, as patients are subjected to less surgery, but more evidence is needed to confirm this.

For patients with medically refractory UC, laparoscopic ileal pouch-anal anastomosis surgery is the advised choice. This technique is also an ideal option for young females, as it is associated with improved fecundity compared to open surgery. Ileo-rectal anastomosis (IRA) remains an option for patients with UC who have a minimally affected rectum.

Guideline summary Acute severe UC [ASUC] and medically-refractory UC represent the main indications for surgery in UC patients, the new ECCO guidelines note. ASUC may be the onset feature in up of one-third of UC patients, and is associated with a 30-to-40 per cent risk of colectomy after one or more severe exacerbations, and 10-to-20 per cent of patients with ASUC need a surgical intervention at their first admission.

Patients with ASUC require immediate hospitalisation, and the first-line treatment of ASUC consists of intravenous corticosteroid treatment. However, up to 30 per cent of patients fail to respond to conservative treatments and require a colectomy. In case of failure, after seven days without significant improvements, a surgical intervention is highly recommended to avoid the perioperative complications usually associated with emergent procedures, ECCO states.

Refractory UC includes steroid dependency and immunomodulator- or biologic-refractory disease, and is often accompanied by a deteriorated patient condition and is a recognised risk factor of poor postoperative outcomes; thus a staged procedure is often preferred, to improve patient status and minimise postoperative complications.

Despite the increasing availability of new pharmacological treatments, multiple attempts at conservative management and consequent therapeutic failures may affect

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the condition of patients with ASUC and refractory UC and considerably influence postoperative outcomes. Accordingly, multidisciplinary management of UC patients is of crucial importance to identify the best therapeutic pathway, says ECCO.

In recent decades, the surgical options for the treatment of refractory UC have evolved, combining technical advancements with a more comprehensive management of perioperative pathways.

The ECCO UC surgical guideline recommendations are as follows:

▶ Medical management of ASUC

Statement 1.1.

Intravenous corticosteroids as the initial standard treatment for adult patients with ASUC are recommended, as this treatment induces clinical remission and reduces mortality [EL3].

Statement 1.2.

Either infliximab or cyclosporine should be used in adult patients with steroid-refractory ASUC. When choosing between these strategies, centre experience and a plan for mainte-

The only licensed treatment for the reduction in recurrence of episodes of overt hepatic encephalopathy ≥

nance therapy after cyclosporine should be considered [EL3].

Statement 1.3.

There is currently insufficient evidence to determine the optimal regimen of infliximab rescue therapy in patients with ASUC refractory to corticosteroid therapy [EL4].

Statement 1.4.

Third-line sequential rescue therapies with calcineurin inhibitors [cyclosporine or tacrolimus] in ASUC refractory to corticosteroid therapy may delay the need for colectomy, but are associated with high rates of adverse events and should only be administered in specialised centres [EL2a].

▶ Medical versus surgical management of refractory moderate-to-severe UC

Statement 2.1.

Reconstructive surgery may be offered to refractory and corticosteroid-dependent patients and improves quality-of-life despite the risk of early and late complications [EL2b]. Proctocolectomy with end-ileostomy is an alternative for some patients and has lower morbidity and comparable quality-of-life [EL3a].

▶ Preoperative optimisation of refractory moderate-to-severe UC Statement 3.1.

Correction of altered body composition and nutrition imbalances is advised preoperatively, despite limited evidence [EL5]. There is no evidence to support routine enteral or parenteral nutrition to improve the surgical outcomes of patients with UC [EL5]. Iron supplementation is recommended when iron-deficiency anaemia is present [EL1].

Statement 3.2.

Patients taking >20mg prednisolone for >six weeks are at increased risk of early complications and pouch-specific complications. Steroids should be weaned before restorative proctectomy or proctocolectomy, and if this is not possible, surgery should be postponed [EL4]. Preoperative thiopurines or cyclosporine do not increase the risk of postoperative complications [EL3]. Patients on biologics might be at increased risk of developing early and late pouch-specific complications; three-stage or two-stage modified approaches with deferred pouch construction could be considered under these circumstances [EL4]. Single-stage restorative proctocolectomy should be avoided in patients receiving biologics [EL5]. Statement 3.3.

IE Prescribing Information: Targaxan 550mg (rifaximin-α)

REFER TO FULL SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) BEFORE PRESCRIBING

Presentation: Film-coated tablet containing rifaximin 550 mg. Uses: Targaxan is indicated for the reduction in recurrence of episodes of overt hepatic encephalopathy in patients ≥ 18 years of age. Dosage and administration:

Recommended dose: 550mg twice daily as long term treatment for the reduction in recurrence of overt episodes of overt hepatic encephalopathy. In the pivotal study, 91% of patients were using concomitant lactulose. TARGAXAN can be administered with a glass of water, with or without food. No dosage changes are necessary in the elderly or those with hepatic insufficiency. Use with caution in patients with renal impairment

The safety and efficacy in paediatric patients (aged less than 18 years) have not been established. Contraindications: Contraindicated in hypersensitivity to rifaximin, rifamycin-derivatives or to any of the excipients and in cases of intestinal obstruction. Warnings and precautions for use: The potential association of rifaximin treatment with Clostridium difficile associated diarrhoea and pseudomembranous colitis cannot be ruled out. The administration of rifaximin with other rifamycins is not recommended. Rifaximin may cause a reddish discolouration of the urine. Use with caution in patients with severe (Child-Pugh C) hepatic impairment and in patients with MELD (Model for End-Stage Liver Disease) score > 25. In hepatic impaired patients, rifaximin may decrease the exposure of concomitantly administered CYP3A4 substrates (e.g. warfarin, antiepileptics, antiarrhythmics, oral contraceptives). Both decreases and increases in international normalized ratio (in some cases

with bleeding events) have been reported in patients maintained on warfarin and prescribed rifaximin. If co-administration is necessary, the international normalized ratio should be carefully monitored with the addition or withdrawal of treatment with rifaximin. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

Ciclosporin may increase the rifaximin Cmax. This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodiumfree’. Pregnancy and lactation: Rifaximin is not recommended during pregnancy. The benefits of rifaximin treatment should be assessed against the need to continue breastfeeding. Side effects: Common effects reported in clinical trials are dizziness, headache, depression, dyspnoea, upper abdominal pain, abdominal distension, diarrhoea, nausea, vomiting, ascites, rashes, pruritus, muscle spasms, arthralgia and peripheral oedema. Other effects that have been reported include: Clostridial infections, urinary tract infections, candidiasis, pneumonia cellulitis, upper respiratory tract infection and rhinitis. Blood disorders (e.g. anaemia, thrombocytopenia).

Anaphylactic reactions, angioedemas, hypersensitivity. Anorexia, hyperkalaemia and dehydration. Confusion, sleep disorders, balance disorders, convulsions, hypoesthesia, memory impairment and attention disorders. Hypotension, hypertension and fainting. Hot flushes. Breathing difficulty, pleural effusion, COPD. Gastrointestinal disorders and skin reactions. Liver function test abnormalities. Dysuria, pollakiuria and proteinuria. Oedema. Pyrexia. INR abnormalities. Prescribers should consult the SmPC in relation to all adverse reactions.

IRELAND

Norgine B.V. Antonio Vivaldistraat 150, 1083 HP, Amsterdam, Netherlands Marketing Authorisation number: PA 1336/009/001 For further information contact: Norgine Pharmaceuticals Limited Norgine House Widewater Place, Moorhall Road, Harefield, Uxbridge, UB9 6NS, UK Telephone: +44 (0)1895 826 606 E-mail: Medinfo@norgine.com Ref: IE-HEP-XIF-2100010

Date of preparation: April 2021

Ireland

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance. Website: www.hpra.ie. Adverse events should also be reported to Medical Information at Norgine Pharmaceuticals Ltd on: Tel. +44 (0)1895 826 606 Email. Medinfo@norgine.com

References:

1. National Institute for Health and Care Excellence. Rifaximin for preventing episodes of overt hepatic encephalopathy: appraisal guidance TA337 for rifaximin. Available from: http://www.nice.org.uk/guidance/ta337

2. TARGAXAN® 550 Summary of Product Characteristics. Available for Ireland from: www.medicines.ie

Product under licence from Alfasigma S.p.A. TARGAXAN is a registered trademark of the Alfasigma group of companies, licensed to the Norgine group of companies. NORGINE and the sail logo are registered trademarks of the Norgine group of companies.

Prophylactic anticoagulation therapy in adult patients with active UC during hospitalisation is recommended, considering the high risk of venous thromboembolism [VTE] during UC flares [EL4].

▶ Surgical strategy of refractory moderate-to-severe UC Statement 4.1.

After total proctocolectomy for medically refractory UC, IPAA is the procedure of choice, but permanent end-ileostomy is also a reasonable option for some patients. A shared decision-making approach should be used to tailor procedure selection to the patient’s preference [EL3].

Statement 4.2.

IPAA may be performed as a two or three stage procedure. Modified two-stage IPAA may be associated with fewer complications and shorter length of stay than three-stage or twostage IPAA in patients with medically refractory UC operated in expert centres, but more evidence is needed [EL3].

▶ Technical aspects of surgical approaches for refractory moderate-to-severe UC Statement 5.1.

IPAA may be constructed using either a stapled or a handsewn technique, with comparable functional outcomes. Thus, the type of anastomosis should be left to the surgeon’s discretion [EL2].

Statement 5.2.

Laparoscopic surgery is the preferred approach to patients with medically refractory UC, as it is associated with lower intra- and postoperative morbidity, faster recovery, fewer adhesions and incisional hernias, shorter hospital length of stay, improved female fecundity, and better cosmesis [EL2].

Statement 5.3.

Legal category: Prescription only

Cost: €262.41 for 56 tablets Marketing Authorisation holder:

IE-HEP-XIF-2100002

Date of preparation: May 2021

Although associated with an increased risk of rectal dysplasia, cancer, and dysplasia or cancer recurrence, patients with UC and a minimally affected rectum can be offered the option of an ileo-rectal anastomosis [IRA] [EL4].

References on request

18 years1

At home they are still at risk; …TARGAXAN® rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy.2

25mg/ml

KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum containing chemotherapy1

• After at least 5 years of follow up KEYTRUDA monotherapy continued to show improved OS, ORR, and DOR compared with investigators choice of chemotherapy for patients with advanced platinum-resistant or platinum-refractory urothelial carcinoma.2

Results from KEYNOTE-045: A multicentre, open-label, randomised, phase 3 trial comparing KEYTRUDA with investigators choice of chemotherapy for patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy.1,2

There was no statistically significant difference between KEYTRUDA and Chemotherapy with respect to Progression Free

Median

KEYTRUDA 2.1 months vs Chemotherapy 3.3 months (HR, 0.95 [95%CI, 0.79-1.14]

After 5 years of follow up safety was consistent with that of previous reports.2 In the as-treated population, any grade treatment related adverse events of any cause occurred in 62% of participants in the pembrolizumab group and 90.6% of participants in the chemotherapy group. Grade 3 or worse adverse events of any cause occurred in 16.9% in the pembrolizumab group and 50.2% in the chemotherapy group.3

KEYTRUDA® (pembrolizumab)

ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION KEYTRUDA 25 mg/mL: One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. INDICATIONS KEYTRUDA as monotherapy is indicated for the treatment of adults and adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults and adolescents aged 12 years and older with Stage IIB, IIC or III melanoma and who have undergone complete resection. KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 with a ≥1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD L1 with a combined positive score (CPS) ≥ 10. KEYTRUDA as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 1. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic HNSCC in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy. KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma (RCC) in adults. KEYTRUDA, in combination with lenvatinib, is indicated for the first line treatment of advanced renal cell carcinoma in adults. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers Colorectal cancer (CRC) KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings: - first line treatment of metastatic colorectal cancer - treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine based combination therapy. Non-colorectal cancers KEYTRUDA as monotherapy is indicated for the treatment of the following MSI H or dMMR tumours in adults with (a) advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation, (b) unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy.

KEYTRUDA, in combination with platinum and fluoropyrimidine based chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10.

KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early stage triple negative breast cancer at high risk of recurrence. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple negative breast cancer in adults whose tumours express PD L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease.

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

the last dose of pembrolizumab. Immune-related adverse reactions affecting more than one body system can occur simultaneously. Immune-related adverse reactions are immune-related pneumonitis, immune-related colitis, immune-related hepatitis, immune-related nephritis, immune-related endocrinopathies (including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism), Immune-related skin adverse reactions (also including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)), Refer to SmPC for more information and management of immune-related adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with classical Hodgkin lymphoma undergoing allogeneic HSCT after previous exposure to pembrolizumab. Infusion-related reactions: Grades 1, 2, 3 or 4 infusion reactions including hypersensitivity and anaphylaxis, could be seen with pembrolizumab treatment. Refer to SmPC for more information and management of infusion-related reactions. Overdose: There is no information on overdose with pembrolizumab. In case of overdose, monitor closely for signs or symptoms of adverse reactions and treat appropriately. INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. No metabolic drug drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. Corticosteroids can be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. FERTILITY, PREGNANCY AND LACTATION Women of childbearing potential Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. No data on use in pregnant women. Do not use during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Breast-feeding It is unknown whether pembrolizumab is secreted in human milk. A risk to newborns/ infants cannot be excluded. Fertility No clinical data available. SIDE EFFECTS Refer to SmPC for complete information on side effects. Pembrolizumab is most commonly associated with immune-related adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-and infusion-related adverse reactions. When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment. For additional lenvatinib safety information related to advanced RCC see the SmPC for Kisplyx and for advanced EC see the SmPC for Lenvima. Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, pruritus, rash, fatigue. Common: pneumonia, thrombocytopenia, neutropenia, lymphopenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, insomnia, dizziness, dysgeusia, pneumonitis, colitis, dry mouth, hepatitis, severe skin reactions, vitiligo, dry skin, eczema, alopecia, dermatitis acneiform, erythema, dermatitis, myositis, pain in extremity, arthritis, influenza like illness, chills, AST and ALT increases, increase in blood alkaline phosphatase, hypercalcaemia, blood bilirubin increased, blood creatinine increased, infusion related reaction. In combination with chemotherapy: Very Common: neutropenia, anaemia, thrombocytopenia, leukopenia, hypothyroidism, hypokalaemia, decreased appetite, insomnia, neuropathy peripheral, headache, dizziness, dysgeusia, dyspnoea, cough, nausea, diarrhoea, vomiting, abdominal pain, constipation, alopecia, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pyrexia, fatigue, asthenia, oedema, ALT increase, AST increased. Common: pneumonia, febrile neutropenia, lymphopenia, infusion related reaction, adrenal insufficiency, thyroiditis, hyperthyroidism, hyponatraemia, hypocalcaemia, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, pneumonitis, colitis, gastritis, dry mouth, hepatitis, severe skin reactions, erythema, dermatitis acneiform, dermatitis, dry skin, eczema, pain in extremity, arthritis, acute kidney injury, influenza-like illness, chills, blood creatinine increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased. In combination with axitinib or lenvatinib: Very Common: urinary tract infection, anaemia, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, diarrhoea, abdominal pain, nausea, vomiting, constipation, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pain in extremity, fatigue, asthenia, oedema, pyrexia, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, infusion-related reaction, adrenal insufficiency, hyperthyroidism, thyroiditis, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, dizziness, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, pancreatitis, gastritis, dry mouth, hepatitis, severe skin reactions, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, arthritis,

CAOP syndrome – a ‘new kid on the block’

Attendees at UCD’s Charles Institute Seminar Series heard a presentation by Prof Ming Li on the relationship between genetics and a new disease, CAOP syndrome

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.

Attendees heard a presentation by Prof Ming Li, Chief Physician and Professor at Xinhua Hospital, Shanghai, China. Prof Ming’s chief research interests are focused on clinical and basic research into hereditary and allergic skin diseases, respectively, and he has helped to identify six new pathogenic genes for genodermatoses and has published more than 130 clinical papers.

In his Charles Seminar, Prof Ming discussed a new disease entity that he has co-discovered and named – Cataract, Alopecia, Oral mucosal disorder, and Psoriasis-like (CAOP) syndrome, which he researched in two unrelated and ethnically-diverse patients, one Chinese and one Hispanic. “We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease, or MBTPS1, S1P,” said Prof Ming. “Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability.”

S1P variants destabilise ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid b-oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) towards glycolysis, he added.

“Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored ETFA/ ETFB stability,” he commented. “This discovery of mutations in MBTPS1 has resulted in a new entity – CAOP syndrome –and helps to elucidate the mechanism of the mutations in this new disease.”

Case studies

Prof Ming went into more detail on study data and case studies involving two of his patients, one Chinese, and one Hispanic, and also outlined work using animal models that included mice and zebrafish. He briefly described the whole-exome sequencing process and defective cholesterol metabolism in these patients: “Cytoplasmic lipid droplets were observed in the patient’s skin lesions and abnormal lysosomes were consistently found in patients,” he said. “There was a significant increase in cholesterol esters and triglycerides, but no significant change in free fatty acids and glycerides in MBTPS1-gene knockout (KO) HaCaT keratinocytes by liquid metabolomics.”

Prof Ming discussed the first case study and told the seminar it was found that there was a 161.5 per cent increase in the number of mitochondria and morphological abnormalities in the mitochondria in the skin lesions of this individual. Furthermore, the mitochondrial lamellar cristae structure was disorganised, indicating severe damage to the mitochondria.

He outlined the function of the novel mitochondrial protein SP1, and the putative mechanism through which S1P

bility. “Decreased protein levels of ETFA and ETFB were observed in the skin biopsy of patient 1 compared with the control levels, but no significant changes in the mRNA expression of ETFA and ETFB were detected,” he said. “MBTPS1 gene knockout induced the rapid degeneration of ETF in HaCaT keratinocytes, which indicated that S1P may maintain the protein stability of ETF….

“MBTSP1 knockout did not affect the

respiration can be significantly reversed by riboflavin supplementation and ETFA/B overexpression in HaCaT cells,” he said. Prof Ming applied this principle in real-world treatment of one of his patients, and he explained that the patient was followed-up for three years after starting treatment and presented with a marked alleviation of severe inflammatory lesions, including oral stomatitis, psoriasis-like lesions, paronychia, and cheilitis, “with a slight improvement in photophobia and tongue fissures,” he told the attendees. “There was no change in nail dystrophy, alopecia, follicular keratosis or ichthyosis-like skin lesions.”

On ETA stability, he commented: “Riboflavin therapy rescues the ETF stability… the decreased global ATP production could be significantly reversed by riboflavin supplementation and ETFA/B overexpression in HaCaT keratinocytes.”

Lesions

During a lively Q&A interactive session and clinical discussion following the presentation, Prof Tobin commented: “This was a fascinating presentation of such a strong phenotype, but with a remarkable improvement with a relatively straightforward supplementation of riboflavin. It was very interesting to see very significant changes in some of the lesions. I would suspect that the alopecia-associated changes, because it is a scarring alopecia, are probably not possible to reverse. This is probably because you have lost the stem cells from the hair follicles as part of the original alopecia. But it is interesting to note the significant reversal of some of the other phenotypes,” he said.

regulates cellular respiration. “S1P acts as a novel mitochondria-localised electron transfer flavoprotein (ETF)-binding partner and is involved in the mitochondrial respiration chain reaction,” he said. “S1P dysfunction disrupts its translocation to mitochondria, impairs the flavination and stability of ETF, and shifts mitochondrial oxidative phosphorylation to glycolysis.”

He continued: “S1P was enriched in mitochondria, as demonstrated by a cellular component separation assay,” said Prof Ming. “Confocal immunofluorescence indicated that S1P protein expression co-localised with the mitochondrial tracer….” On the topic of S1P-ETFA-ETFB proteins, “the protein-protein interaction network suggested that ETF might play a central role in S1P-associated mitochondrial signalling,” he said.

Prof Ming went on to discuss the function of MBTPS1 variants and how MBTPS1 dysfunction impairs ETF sta -

mRNA level of ETF, but induced the rapid degradation of ETF in mice models, which indicated that S1P may maintain the protein stability of ETF…. So, loss of S1P impairs mitochondrial respiration and increases the glycolytic capacity. Loss of S1P initiates a metabolic switch characterised by a reduction in mitochondrial respiration, an increase in the glycolysis, and the derivation of pyruvate from fuelling the TCA cycle in glycolysis, with more conversion to lactic acid.” Loss of S1P impairs the mitochondrial respiratory chain, resulting in a 79.2 per cent increase in the generation of mitochondrial superoxide in MBTPS1-KO HaCaT cells, he explained.

Riboflavin

However, Prof Ming went on to discuss the potential value of riboflavin therapy in this syndrome and told the seminar that it effectively rescues mitochondrial respiration. “The S1P deficiency-induced abnormalities in mitochondrial

“Is there significant pain associated with these lesions?” he asked Prof Ming. “If there is pain involved, do patients report that it is high or medium-to-low pain, neuropathic or otherwise?”

Prof Ming responded: “The PPK (palmoplantar keratoderma) on the foot is not painful, but the nail dystrophy is quite painful,” he explained. “There is no pain associated with the psoriasis-like lesions.” On the subject of age of initial onset of disease in the Chinese and Hispanic patients, respectively, Prof Ming commented: “For the psoriasis-like lesions, the age of onset is around four or five years,” he said. “At around five years old, we can see the psoriasis-like lesions… we saw these patients at 11 years old and all their hair was gone, including alopecia of the eyebrows and eyelashes,” but the onset of alopecia can occur as early as one year old, he added.

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

Prof Ming Li

The decreased global ATP production could be significantly reversed by riboflavin supplementation and ETFA/B overexpression in HaCaT keratinocytes

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A CONSOLING BOOK FOR THE DARK TIMES WE LIVE IN

Title: On Consolation: Finding solace in dark times

Author: Michael Ignatieff

Publisher: Picador

Reviewer: Prof Brendan Kelly

Book sales rose during Covid-19, reaching record highs. In the midst of waves of infection, public health restrictions and endless trauma, people reached to the written word for solace, sustenance, and strength. Victor Hugo said that “it is from books that wise people derive consolation in the troubles of life”. The Covid-19 pandemic proved that this is still true.

Against this background, Michael Ignatieff’s new book, On Consolation: Finding solace in dark times , could scarcely be more timely. Ignatieff’s elegant book examines how people in extreme situations have connected with each other to find hope and resilience, sustenance and strength, and the simple power to survive. As Rory Stewart, author of The Places in Between , points out, On Consolation is “an extraordinary meditation on loss and mortality, drawing on all of Michael Ignatieff’s powers as a philosopher, a historian, a politician, and a man. His portraits of figures, such as Hume and Montaigne, are sharp and dignified, troubling and consoling, thoughtful and deeply humane.”

I will admit to a long-standing admiration for Michael Ignatieff. I recall watching him present the BBC arts programme The Late Show in the 1990s. He seemed impossibly intelligent and urbane. Since then, he has been active in both academia and politics, and his books include Isaiah Berlin: A Life , The Warrior’s Honor, and The Russian Album (a memoir). Scar Tissue , Ignatieff’s second novel, published in 1993 and shortlisted for the Man Booker Prize, made a lasting impression on me. The book is centred on a woman with Alzheimer’s or dementia and how this impacts on

people around her, especially her son. Today, Ignatieff is a professor at Central European University in Vienna, as well as former head of Canada’s Liberal Party, and Director of the Carr Centre for Human Rights at Harvard’s Kennedy School. He writes for the New York Times , New York Review of Books, and London Review of Books . He sounds busy. In the midst of this activity, and in the context of the pandemic, Ignatieff found time to write On Consolation , exploring the idea of solace through history, touching on The Bible, Cicero, Marcus Aurelius, Boethius, Dante, El Greco, de Montaigne, Hume, Condorcet, Karl Marx, and even Abraham Lincoln. He also explores the lives, work and coping mechanisms of Mahler, Max Weber, Anna Akhmatova, Primo Levi, and a host of other people who faced difficulties and somehow found a way through them. As Hermione Lee notes in The New York Review of Books : “Michael Ignatieff’s remarkable and moving new book, written out of the dark times of a

world pandemic… suggests what we might learn from individual examples of ‘the human experience’.” The examples he provides are full of possibility and hope. He even quotes Camus with optimism: “On the whole, men are more good than bad.”

Ignatieff’s chapter on Czech playwright and statesman, Václav Havel, who spent considerable time in prison, is very moving. Havel had a passion for truth and justice, but “his humour and self-deprecation carried him through the later years”. Ignatieff paints a picture of a complex, brilliant man whose sources of solace shifted, but whose ability to find them did not.

Religion features significantly in Ignatieff’s account. As the New York Times Book Review notes: “Ignatieff believes that holy texts of all denominations can be mined for comfort and insight even by the faithless, in their depiction of common human experience.” The idea of reverence pervades the book, not least through Ignatieff’s choice of stories to explore.

The penultimate chapter is titled ‘The Good Death: Cicely Saunders and the Hospice’. Ignatieff writes that Saunders’s “ideas about consolation” depended on the belief “that we are not masters of our bodies and that the task facing us is to make peace with the large portion of our life that is not in our power”.

This interplay of power and powerlessness is profound at many points in our lives, but especially towards the end. As humans, we have a great deal of influence and resource, but we do not have infinite control. Covid-19 has demonstrated this vividly. The world is less predictable than we thought, but we are more resilient than we imagined. Like Ignatieff, we find solace in many places, sometimes unexpected ones, even in dark times.

Michael Ignatieff

He also explores the lives, work and coping mechanisms of Mahler, Max Weber, Anna Akhmatova, Primo Levi, and a host of other people who faced difficulties and somehow found a way through them

Brendan Kelly is Professor of Psychiatry at Trinity College Dublin and author of The Science of Happiness: The Six Principles of a Happy Life and the Seven Strategies For Achieving It (Gill Books).

TIGUAN ALLSPACE IS STILL A PERFECT SOLUTION FOR MANY, IF NOT ALL, YOUR NEEDS

Getting into a large, diesel SUV has a slightly retro feel to it. My daily drive is a Škoda Enyaq, a fully ‘electric’ electric vehicle (EV). It is a car I have had for just about a year and have now become accustomed to. It is silent, potent and, of course, limited in some ways, and every drive involves that (increasingly less frequent) frisson of anxiety about range.

So, jumping into the latest Tiguan Allspace, a car that has been around in its current guise since 2017; albeit here with a raft of new upgrades, it does feel a little bit like a ‘Farewell Tour’ for this model as a diesel.

The Tiguan has been a huge success for Volkswagen, both internationally and domestically. For the environmentally conscious of you, concerned at the thought of a large, diesel SUV, here is a sobering fact: None of the ID.3 or ID.4 electric models would have come about if it wasn’t for the money made from selling these, very profitable, SUVs.

Here in Ireland the Tiguan quickly overtook the beloved Golf as the brand’s top-selling model. And now the Tiguan has been overtaken by the fully-electric ID.4. So what now for the Tiguan?

Well, whatever about the regular Tiguan, the Allspace still has an ace up its sleeve at the back, because, for now at least, you can’t get a seven-seater EV from Volkswagen (The ID.Buzz will eventually see to that, but expect both the price tag and availability to be equally depressing). Yes, of course, some of you aren’t yet quite ready to become EV owners. Either way, for now, a large seven-seater SUV that is capable of north of 800km on a full ‘tank’ means you are going to be buying a diesel. So what do we make of this one?

Well, let’s deal with the latest upgrades to the model and they are apparent as soon as you blip the key, where a large LED strip of light glows across the handsome radiator grille, which now gets the new Volkswagen logo. It wasn’t fitted to our test car, but you can also have the IQ.LIGHT LED matrix headlights (basically super-duper headlights). But even the regular ones look great and bring the Tiguan in line with the rest of the range. In some markets, you can have the Allspace as a five- or seven-seater, but here in Ireland it only (and thankfully) comes with the extra seats, which fold flat when you don’t need them, leaving an enormous luggage capacity of 700 litres with the seats folded away. Due to a slightly redesigned front, the Tiguan Allspace has grown by 22mm, but overall the dimensions are pretty much unchanged.

The most significant changes to the Tiguan Allspace have taken place inside the car. There are new infotain-

ment systems, a new ‘digital cockpit’ and some of the most comfortable seats you will find around. If you want to treat your back with love, order up the ergoActive seats with electric four-way lumbar support adjustment and massage function.

As mentioned, our Allspace came with the tried and trusted 150hp 2.0-litre TDI, which has been given some subtle tweaks to try and keep emissions in check. CO 2 emissions are 155g/km, putting it in VRT Band 17 with an annual motor tax of €280. That is quite decent considering the car’s considerable bulk.

This doesn’t feel like a rapid vehicle anymore in the era of neck-snapping electric car acceleration, but it never feels slow. 0-100km/h takes just under 10 seconds,

sports suspension, and shocks, and inside some ‘Art Velour’ upholstery and R-Line carpet mats.

Should you still be buying a Diesel Tiguan Allspace in 2022 or for 2023? It depends on your needs. If you don’t need the extra space and seats then the ID.4 will be a better buy long-term. But, as we have said, EVs still aren’t for everyone. Buy on a PCP (personal contract purchase) and the residual value risk is with Volkswagen, rather than you and you have a comfortable, handsome seven-seater that has never heard of range anxiety and will be a loyal and faithful family vehicle.

VOLKSWAGEN TIGUAN ALLSPACE ‘R-LINE’

which is fine for a vehicle that weighs in at 1,735kg. But this weight is significantly less than the equivalent ID.4, which can be around 2,200kg, but will get to 100km/h in around three seconds less in GTX form.

The addition of new items such as ‘travel assist’ (which will stop you and move off again in heavy traffic) and adaptive cruise control makes commuting and long journeys especially easy in the Allspace. And, of course, if you have kids and are driving them and their friends quite frequently, then the versatility the extra seats provided is always welcome.

There are a total of four grades of Tiguan. An entry-level manual model just named ‘Tiguan Allspace’ that costs €39,595. Then there is the Life model from €46,225; the Elegance from €58,280 (only available as a DSG auto); and then the model we were in, the R-Line, from €59,075. This gains 20” Suzuka alloy wheels, lots of R-Line logos throughout, a Sports Pack, with progressive steering,

Engine: 1,988cc four-cylinder turbocharged diesel engine, seven-speed DSG

Power: 150hp

Torque: 360Nm

0-100km/h: 9.8 seconds

Fuel economy: 5.7 l/100km

Top speed: 199km/h

Colour: Pyrite Silver Metallic (€1,000)

Transmission: Seven-speed DSG, front-wheel drive

Drive: Front C02 (WLTP): 155g/km

Price as tested: €60,075

Starting price: €39,595

Due to a slightly redesigned front, the Tiguan Allspace has grown by 22mm, but overall the dimensions are pretty much unchanged

Royal Victoria Eye and Ear Hospital Research Foundation –New Frontiers in Ophthalmology meeting, 16 June 2022

Mr Tim Carpenter; Ms Caroline Gardiner; and Dr Ursula Behan

Photos: David Coleman – Bobby Studio

Dr Denise Curtin; Dr Agnes Janovics; and Prof Louis Collum

Dr Brian Woods; Dr Emily Greenan; Dr Aoife Smyth; and Dr Aisling McGlacken-Byrne

Ms Jenny Hepschke and Ms Áine Ní Mhéalóid

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Ms Rizwana Khan; Ms Caroline Gardiner; and Dr Ursula Behan

Ms Diana Malata and Prof Louis Collum

Dr Moji Oshodi; Dr Amy Coman; Dr Maha El Sayed; and Dr Ngozi Soribe

Mr Michael Burdon and Ms Jenny Hepschke

Dr Tayseer Mohammed; Dr Hanan Wayel; and Dr Rana Al-Senawi

Dr Denise Curtin; Mr Barry Power; and Mr Shane Whitlow

Launch of Practitioner Health Matters Programme 2021 annual report, 19 May 2022

Pictured third from left is Dr Íde Delargy, Medical Director, Practitioner Health Matters Programme (PHMP), with Ms Eimear Bourke; Mr Colm Gerard McDermott; and Dr Sarah Fitzgibbon, winners of the Dr Aiden Meade Award 2021

Photos: David Coleman – Bobby Studio

Pictured L to R: Ms Niamh Muldoon; Prof Freddie Wood, Trustee, PHMP; Ms Noeleen Harvey, Trustee, PHMP; and Dr Íde Delargy

Dr Hugh Gallagher; and Dr Frank Murray, Chair, PHMP Dr Íde Delargy

Ms Romy Meade Moloney; Dr Íde Delargy; and Ms Siobhan Kelly

Mr Julian Smith, Trustee, PHMP; Mr Hugh Kane, Trustee, PHMP; and Prof Freddie Wood

Dr Noel Kavanagh, Trustee, PHMP; Ms Siobhan Kelly, Honorary Secretary/Trustee, PHMP; Mr Julian Smith; and Mr John O'Connor, Honorary Treasurer/Trustee, PHMP

Dr Paul Gannon; Dr Brian Kinirons; and Dr Justin Brophy

Prof Freddie Wood; Prof Frank Murray; Ms Noeleen Harvey; Mr John O’Connor; Dr Íde Delargy; Mr Hugh Kane; Ms Siobhan Kelly; and Dr Barney Murphy, Trustee, PHMP

STUDY SUPPORTS LINK BETWEEN VITAMIN D DEFICIENCY AND RISK OF DEMENTIA

A recent study published in the American Journal of Clinical Nutrition supports the role of vitamin D deficiency on brain health, notably for the risk of dementia.

Low vitamin D status was associated with neuroimaging outcomes and the risks of dementia and stroke even after extensive covariate adjustment, found the study.

Mendelian randomisation (MR) analyses supported a causal effect of vitamin D deficiency on dementia, but not on stroke risk.

The study, titled ‘Vitamin D and brain health: An observational and Mendelian randomisation study’, investigated the association between 25-hydroxyvitamin D [25(OH)D], neuroimaging features, and the risk of dementia and stroke.

The authors from the University of South Australia used prospective data from the UK Biobank (37–73 y at baseline) to examine the association between 25(OH)D concentrations with neuroimaging outcomes (N = 33,523) and the risk of dementia and stroke (N = 427,690; 3,414 and 5,339 incident cases, respectively). Observational analyses were adjusted for age, sex, ethnicity, month, centre, and socioeconomic, lifestyle, sun behaviour, and illness-related factors. Nonlinear MR analyses were used to test for underlying causality for neuroimaging outcomes (N = 23,901) and dementia and stroke (N = 294,514; 2,399 and 3,760 cases, respectively).

Associations between 25(OH)D and total, grey matter, white matter, and hippocampal volumes were nonlinear, with lower volumes both for low and high concentrations (adjusted P-nonlinear ≤0.04). 25(OH)D had an inverse association with white matter hyperintensity volume [per 10nmol/L 25(OH)D; adjusted β: –6.1; 95 per cent CI: –11.5, –7.0]. Vitamin D deficiency was associated with an increased risk of dementia and stroke, with the strongest associations for those with 25(OH) D <25nmol/L (compared with 50–75.9nmol/L; adjusted HR: 1.79; 95 per cent CI: 1.57, 2.04 and HR: 1.40; 95 per cent CI: 1.26, 1.56, respectively).

Nonlinear MR analyses confirmed the threshold effect of 25(OH)D on dementia, with the risk predicted to be 54 per cent (95 per cent CI: 1.21, 1.96) higher for participants at 25nmol/L compared with 50 nmol/L. 25(OH)D was not associated with neuroimaging outcomes or the risk of stroke in MR analyses. Potential impact fraction suggests 17 per cent (95 per cent CI: 7.22, 30.58) of dementia could be prevented by increasing 25(OH)D to 50nmol/L.

“Low vitamin D status was associated with neuroimaging outcomes and the risks of dementia and stroke even after extensive covariate adjustment. MR analyses support a causal effect of vitamin D deficiency on dementia, but not on stroke risk,” outlined the authors.

Larger MR studies were needed to confirm causality for the proposed associations between 25(OH)D concentrations and brain morphometry. The study’s MR results suggested no clear association with stroke, whereas “a causal relation with dementia risk provides an important opportunity for prevention”.

NEW HEART MODEL TO HELP TREAT PATIENTS WITH HEART FAILURE

Researchers from the RCSI University of Medicine and Health Sciences have developed a new lab-based model of a heart and circulatory system that will help test devices to treat patients with one of the most common forms of heart failure.

The study, which used two different types of circulatory models including a silicone heart model, was carried out by the RCSI in collaboration with the National College of Art and Design (NCAD). The research is published in the current edition of Frontiers in Cardiovascular Medicine

There are two common types of heart failure: Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Ejection fraction is the measurement used to determine the heart’s ability to pump oxygen-rich blood through the body.

In recent years, the number of patients presenting with heart failure with normal or preserved ejection fraction measurement is increasing, most likely due to the increase in prevalence of common risk factors, including old age, high blood pressure and obesity. Women are at greater risk than men.

In this research from RCSI, a model called a ‘mock circulatory loop’ was developed to mimic both a healthy heart and a heart in failure with preserved ejection fraction. The model enables potential heart failure treatment devices to be examined in terms of their effect on both chambers in the left side of the heart.

This model can test devices to examine the left atrium, the top chamber responsible for receiving oxygen-rich blood from the lungs, as well as the left ventricle, the lower chamber responsible for pumping the oxygen-rich blood around the body.

Senior author on the study, Dr Aamir Hameed, Lecturer in the Department of Anatomy and Regenerative Medicine and a Principal Investigator with the tissue engineering research group at RCSI, said: “Half of the patients presenting with heart failure have heart failure with preserved ejection fraction and the numbers are increasing in the developed world in particular due to the increase in the prevalence of risk factors. The condition can be difficult to treat with medicines and is causing a considerable burden to health services throughout the world.

“The development of this lab-based model is a milestone in heart failure research as it enables devices to be tested that have the potential to treat a condition that affects millions of people around the world, improving their quality of life and reducing the burden on health services.”

The first author on the study, Dr Andrew Malone, Postdoctoral Researcher at the RCSI, said: “Until now, no lab model had been developed that could both mimic the cardiac cycle and features two independently controlled cardiac chambers to fully simulate the blood flow of the left atrium and the left ventricle during the resting phase of the cardiac cycle. This is a key step forward in the development of a robust means of testing heart failure device treatments.”

The research was funded by Enterprise Ireland which is supporting the development of the RCSI pipeline spin-out company, Pumpinheart Ltd, which will be commercialising a novel medical device for the treatment of heart failure with preserved ejection fraction.

“We are looking forward to utilising this exciting new model through our spin-out Pumpinheart, which has the potential to develop our research into a real-world treatment for patients who otherwise may have limited treatment options,” Dr Hameed said.

Drs Hameed and Malone worked with RCSI colleagues Mr Jemil Saidi and Ms Gina Rizq, and collaborators Mr Sean Gallagher, Mr Enda O’Dowd, and Mr Derek Vallence in NCAD.

INTERNATIONAL CANCER EXPERTS JOIN WITH BEAUMONT RCSI CANCER CENTRE TO SHARE VISION FOR COMPREHENSIVE CANCER CARE

Ireland’s newly accredited European cancer centre, the Beaumont RCSI Cancer Centre, will hold its first conference on Thursday 22 September in Dublin.

The conference is the first of its kind to be held by the centre, which is a collaboration between Beaumont Hospital, RCSI University of Medicine and Health Sciences and St Luke’s Radiation Oncology Network.

The Beaumont RCSI Cancer Centre has recently been accredited by the OECI, Europe’s accreditation body for standards in cancer research, education and clinical care.

The inaugural cancer conference will bring together healthcare professionals, academics, and key stakeholders to cel-

ebrate the accreditation and present the centre’s vision for comprehensive cancer care in Ireland.

International keynote speakers include Prof Alastair Thompson, Breast Cancer Surgeon and Professor and Chief of the Section of Breast Surgery, Baylor College of Medicine, US, and Dr Jean-Benoît Burrion, Chair of the OECI accreditation and designation programme.

The Beaumont RCSI Cancer Centre is a partnership between Ireland’s leading healthcare professionals, academics, biologists, epidemiologists and statisticians across the disciplines of medicine, radiation, surgery and palliative care. The centre specialises in the treatment of a wide range of cancers including breast, colorectal, lung, endocrine, head and neck, neuro-oncology, urology, skin, haematology and upper gastro-intestinal.

UP TO ONE-IN-FOUR CHILDREN IN DUBLIN ARE VITAMIN D DEFICIENT – TCD STUDY

Scientists at Trinity College Dublin have found that up to one-in-four children in Dublin are vitamin D deficient and this number increases to one-in-three in socio-economically disadvantaged areas. Deficiency is most prevalent in females, older children (aged over 12) and during winter months. The study is the largest of its kind in Ireland to date and was published in the Journal of Nutritional Science on 27 July. It is the only study to explore vitamin D deficiency by an accurate measure of socio-economic status.

Vitamin D is vital for the rapid bone growth which occurs in childhood and adolescence, but studies on the vitamin D status of children in Ireland are limited.

The body creates vitamin D from direct sunlight on the skin outdoors. From October to March, people in Ireland do not make enough vitamin D from sunlight. Additionally, food sources of naturally occurring vitamin D are limited. Vitamin D is also important for the adequate absorption of dietary calcium which is equally vital for bone health.

Failure to maintain adequate vitamin D and calcium intake in childhood puts children at risk of osteoporosis in later life. Severe deficiency of vitamin D can also cause osteomalacia and lead to rickets in young children.

The children in this study had been referred to their GP for vitamin D tests in the Dublin area and variation was identified by sex, season, and socio-economic status in a sample size of 1,226 children.

The study found one-in-four children were vitamin D deficient, rising to one-in-three in low socio-economic areas. There were higher levels of deficiency in girls and teens (children over 12 years). The study highlighted the need to promote awareness of deficiency and to improve vitamin D intake. It also advised that targeted and tailored guidelines on vitamin D intake may be required for Irish children.

Lead researcher Ms Helena Scully, Mercers Glanbia Ireland Bone Research Fellow, MISA Institute, St James’s Hospital/ School of Medicine, Trinity College, said: “Our research findings indicate that low vitamin D status is common affecting more than one-in-four Irish children. This is concerning as it may have long-term implications for bone health. In particular girls, teens (over 12 years) and those living in low socio-economic areas were most vulnerable. Choosing foods, such as milk and cereal products with added vitamin D, and taking a supplement (10 micrograms or 400units per day), particularly in the winter, can help prevent low vitamin D levels.”

Dr Kevin McCarroll, Consultant Physician, St James’s Hospital and Clinical Senior Lecturer, Trinity College, said: “The study shows that vitamin D deficiency is just as prevalent in children as in adults, particularly during the teenage years when new bone mass is acquired. Reduced sun exposure, such as more sedentary behaviour or screen time and lower dietary vitamin D intakes are likely to be important factors.”

This research identifies the need to focus on strategies to improve vitamin D status in Irish children, especially in those found to be most at risk. The Food Safety Authority of Ireland recommends that everyone aged between 5-65 years get 10 micrograms (400 units) of vitamin D – through diet and supplements – per day. The research team believes the recommended daily allowance may need to include specific targets for children of between 10-15micrograms (400-600iu).

The paper can be read at the following link: www.doi. org/10.1017/jns.2022.57

Dr Aamir Hameed

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A round-up of news and oddities from left field by Dr Doug

Witherspoon

Neanderthal genes may affect how

The ‘poison is in the

There are people who, on first impressions, would seem to be carrying more than their fair share of Neanderthal genes. We have all encountered one or two in our time. But a recent study suggests that carrying certain Neanderthal genes may mean that some common medicines that would normally be beneficial become useless – or worse – to that patient.

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As is well known, certain enzymes in the body eliminate some medications, and the extent of these enzymes' influence varies between individuals. In a recent study, researchers looked at two enzymatic variants that seem to eliminate medications less efficiently and are in fact inherited from Neanderthals.

The teams from the Max Planck Institute for Evolutionary

Anthropology in Germany and Karolinska Institutet in Sweden found that two of the most important genetic variants involved in the body’s ability to eliminate drugs are inherited from Neanderthals, and are in fact carried by approximately 20 per cent of individuals in Europe today.

In the study, published in The Pharmacogenomics Journal, the authors noted that the genetic variants in the genes encoding enzymes in the cytochrome P450 family affect how efficiently these enzymes perform. Thanks to inbreeding tens of thousands of years ago, all of this adds-up to an important impact on how efficiently we absorb medicines.

They identified a DNA segment inherited from Neanderthals, carrying two cytochrome P450 enzymes, and concluded that these enzymes eliminate several common drugs, such as warfarin. They could also affect how the antiepileptic drugs phenytoin, statins, and common painkillers such as ibuprofen take effect in our systems. Put simply, the Neanderthal variants of the enzymes seem to be generally less efficient at eliminating drugs.

Suvezen is indicated for substitution therapy in adult patients who are adequately controlled with rosuvastatin and ezetimibe given concurrently at the same dose level as in the fixed combination, but as separate products, as adjunct to diet for treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or homozygous familial hypercholesterolaemia1

transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive

“Over the decade since the first Neanderthal genome was sequenced, gene flow from Neanderthals has been shown to influence many traits, such as skin pigmentation and neurological and psychiatric phenotypes,” wrote the authors in their discussion. For the genetics buffs among you, the allele frequencies of CYP2C9*2 and CYP2C8*3 across the ‘1,000 Genomes Project’ were studied.

and after setting the appropriate doses the switch to the fixed dose combination of the appropriate strength is possible. Patient should use the strength corresponding to their previous treatment. The recommended dose is one Suvezen tablet daily. To be administered at any time of the day, with or without food. The tablet should be swallowed whole with a drink of water. If co-administered with bile acid sequestrant (BAS), administration of Suvezen should occur either ≥2 hours before or ≥4 hours after administration of a BAS.

Elderly (>70 years): Starting dose of 5 mg rosuvastatin is recommended. The combination is not suitable for initial therapy. Hepatic impairment: Mild: No dosage adjustment is required. Moderate/Severe: Treatment with Suvezen is not recommended. Renal impairment: Mild: No dose adjustment is necessary. Moderate (creatinine clearance <60 ml/min): The recommended start dose is rosuvastatin 5mg. Race: The recommended start dose is rosuvastatin 5 mg for patients of Asian ancestry due to increased systemic exposure. The fixed dose combination is not suitable for initial therapy. Monocomponent preparations should be used to start the treatment or to modify the dose. Suvezen 40 mg/10 mg tablets are contraindicated in these patients. Genetic polymorphisms: In patients who are known to have specific types of genetic polymorphisms that can lead to increased rosuvastatin exposure, a lower daily dose of Suvezen is recommended. Dosage in patients with predisposing factors to myopathy: The recommended start dose is rosuvastatin 5mg in patients with pre-disposing factors to myopathy. Suvezen 40 mg/10 mg tablets are contraindicated in some of these patients. Concomitant therapy: The risk of myopathy (including rhabdomyolysis) is increased when Suvezen is administered concomitantly with certain medicinal products that may increase the plasma concentration of rosuvastatin (e.g. ciclosporin and certain protease inhibitors including combinations of ritonavir with atazanavir, lopinavir, and/or tipranavir).

Whenever possible, alternative medications should be considered, and, if necessary, consider temporarily discontinuing Suvezen therapy. In situations where co-administration of these medicinal products with Suvezen is unavoidable, the benefit and the risk of concurrent treatment and rosuvastatin dosing adjustments should be carefully considered. Contraindications: Hypersensitivity to the active substances or excipients. Pregnancy, breast-feeding and in women of childbearing potential not using appropriate contraceptive measures. Active liver disease or any serum transaminase elevations which are unexplained, persistent or exceeding 3x the upper limit of normal (ULN). Severe renal impairment (creatinine clearance <30ml/min); myopathy or receiving concomitant ciclosporin. 40mg/10mg dose contraindicated in patients with predisposing factors for myopathy/rhabdomyolysis; such factors include: Moderate renal impairment (creatinine clearance <60ml/min), hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate, alcohol abuse, situations where an increase in plasma levels of rosuvastatin may occur, Asian patients, concomitant use of fibrates. Precautions and Warnings: Skeletal muscle effects: have been reported in rosuvastatin-treated patients with all doses and in particular with doses >20mg. As with other HMGCoA reductase inhibitors, reporting rate for rhabdomyolysis is associated with use at doses >40mg. Postmarketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. If myopathy is suspected based on muscle symptoms or is confirmed by a creatine phosphokinase (CPK) level, Suvezen and any of these other agents that the patient is taking concomitantly should be immediately discontinued. All patients starting therapy with Suvezen should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness, particularly if associated with malaise or fever. Creatine kinase (CK) measurement: CK should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase. If CK levels are significantly elevated at baseline (>5x ULN) a confirmatory test should be carried out within 5 – 7 days. If the repeat test confirms a baseline CK >5x ULN, treatment should not be started. Patients with pre-disposing factors for myopathy/rhabdomyolysis: Caution should be exercised in these patients. Risk: benefit of treatment should be considered and clinical monitoring is recommended. CK levels should be measured in these patients. Therapy should be discontinued if CK levels are markedly elevated (>5x ULN) or if muscular symptoms are severe and cause daily discomfort. If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing treatment at the lowest dose. Immune-mediated necrotising myopathy (IMNM): Clinically characterised by proximal muscle weakness and elevated serum CK, has been reported very rarely during or after treatment with statins, including rosuvastatin, despite discontinuation of statin treatment. In clinical trials an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives. Suvezen should not be used in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures). Liver effects: In controlled coadministration trials in patients receiving ezetimibe with statin, consecutive transaminase elevations ≥3x ULN have been observed. It is recommended that liver function tests be carried out prior to, and 3 months following, the initiation of treatment. Rosuvastatin should be discontinued or the dose reduced if the level of serum transaminases is >3x ULN. The reporting rate for serious events is higher at the 40mg dose. In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with rosuvastatin. Liver disease and alcohol: As with other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease. Renal effects: Proteinuria has been observed in patients treated with higher doses of rosuvastatin and was

renal disease. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40mg. Diabetes mellitus: Some evidence suggests that statins raise blood glucose and in some patients, at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5.6 – 6.9mmol/l, BMI >30kg/m raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines. Interstitial lung disease: Exceptional cases have been reported with some statins, especially with long term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected, statin therapy should be discontinued. Severe cutaneous adverse reactions: Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which could be life-threatening or fatal, have been reported with rosuvastatin. If signs and symptoms suggestive of this reaction appears, Suvezen must be discontinued immediately and an alternative treatment should be considered. Treatment with Suvezen must not be restarted at any time. Protease inhibitors: Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. Consideration should be given both to the benefit of lipid lowering by use of Suvezen in HIV patients receiving protease inhibitors and the potential for increased rosuvastatin plasma concentrations when initiating and up titrating rosuvastatin doses in patients treated with protease inhibitors. The concomitant use with certain protease inhibitors is not recommended unless the dose of rosuvastatin is adjusted. Fibrates: The safety and efficacy of ezetimibe administered with fibrates have not been established. If cholelithiasis is suspected in a patient receiving Suvezen and fenofibrate, gallbladder investigations are indicated and therapy should be discontinued. Anticoagulants: If Suvezen is added to warfarin, another coumarin anticoagulant, or fluindione, the International Normalised Ratio (INR) should be appropriately monitored. Fusidic acid: Suvezen must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination. The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness. Statin therapy may be reintroduced seven days after the last dose of fusidic acid. In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of Suvezen and fusidic acid should only be considered on a case by case basis and under close medical supervision. Suvezen contains lactose monohydrate and sodium: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodiumfree’.

Interactions: Contraindicated combinations: Ciclosporin. Not-recommended combinations: Fibrates and other lipidlowering products, protease inhibitors, transporter protein inhibitors and fusidic acid. Other possible interactions: Cytochrome P450 enzymes, antacids, colestyramine, anticoagulants, Vitamin K antagonists, erythromycin, oral contraceptive/hormone replacement therapy. When co-administering rosuvastatin with other medicinal products known to increase exposure to rosuvastatin, doses should be adjusted (see SmPC for full details). The maximum daily dose should be adjusted so that the expected rosuvastatin exposure would not likely exceed that of a 40mg daily dose of rosuvastatin taken without interacting medicinal products. Fertility, Pregnancy and Breastfeeding:

No clinical data are available on the use of ezetimibe during pregnancy. Potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy. If a patient becomes pregnant during use of Suvezen, treatment should be discontinued immediately. Animal studies have shown excretion of medicinal product through breast milk. However, there are no data in humans. No clinical trial data on the effects of fertility in humans. Adverse Reactions: Adverse drug reactions previously reported with one of the individual components (ezetimibe or rosuvastatin) may be potential undesirable effects with Suvezen. Common (≥1/100 to <1/10): diabetes mellitus, headache, dizziness, constipation, nausea, abdominal pain, diarrhoea, flatulence, myalgia, ALT and/or AST increased, asthenia and fatigue. Uncommon (≥1/1,000 to <1/100): decreased appetite, paraesthesia, hot flush, hypertension, cough, dyspepsia, gastroesophageal reflux disease, nausea, dry mouth, gastritis, pruritus, rash, urticaria, arthralgia, muscle spasms, neck pain, back pain, muscular weakness, pain in extremity, ALT and/or AST increased, blood CPK increased, gamma-glutamyltransferase increased, liver function test abnormal, chest pain, pain, asthenia, oedema peripheral. Rare (≥1/10,000 to <1/1,000): thrombocytopenia, hypersensitivity reactions including angioedema, pancreatitis, increased hepatic transaminases, myopathy (including myositis), rhabdomyolysis, lupus-like syndrome and muscle rupture. Very rare (<1/10,000): polyneuropathy, memory loss, jaundice, hepatitis, arthralgia, haematuria, gynaecomastia. Not known: thrombocytopenia, hypersensitivity (including rash, urticaria, anaphylaxis and angioedema), depression, peripheral neuropathy, sleep disturbances (including insomnia and nightmares), dizziness, paraesthesia, cough, dyspnoea, diarrhoea, pancreatitis, constipation, hepatitis, cholelithiasis, cholecystitis, Stevens Johnson syndrome, erythema multiforme, drug reaction with eosinophilia and systemic symptoms, immune-mediated necrotising myopathy, tendon disorders (sometimes complicated by rupture), myalgia, myopathy/rhabdomyolysis, oedema, asthenia. Prescribers should consult the SmPC in relation to other adverse

“... The clinical impact of Neanderthal genetic variants is less well elucidated, especially in terms of genetic variants with strong effect sizes that need to be taken into account in clinical practice,” they continued. “Recently, the major genetic risk factor for a severe outcome of Covid-19 infection as well as a protective variant have been shown to be of Neanderthal origin....

“Here, we show that two of the most important alleles in pharmacogenetics are inherited from Neanderthals. Although this knowledge itself does not change clinical practice, it explains differences observed across ancestries seen in clinical practice.”

Study lead Dr Hugo Zeberg put it more succinctly: “This is one case where the admixture with Neanderthals has a direct impact in the clinic. Otherwise therapeutic doses can be toxic for carriers of the Neanderthal gene variant.”

It’s a small twist in the road towards precision medicine. At the very least, if the findings stand up to further scrutiny, it could help clinicians to sculpt more accurate and effective drug delivery to the right patient at the right dose.

One problem Neanderthals did not have to deal with was toxic weedkiller finding its way into the food chain through genetically-modified crops.

Another recent research project in the US showed that the weedkiller glyphosate, sold as Round-Up, was found in the urine of more than 80 per cent of study participants, with almost one-third of these between the ages of six-to-18 years. Bucking the general trend towards concerns about the environment and effects on public health, the use of glyphosate has increased at least 15-fold since the 1990s.

During Covid, health authorities hung on the words of the US Centres for Disease Control and Prevention, which produced this study using data from the 2013–2014 National Health and Nutrition Examination Survey involving 2,310 people.

Perhaps those with an interest in public health and environmental campaigners in the US should also be exercised by this data.