The Medical Independent 17th November 2022

A new era for pharmacists?

Community pharmacists continue to seek an enhanced role in Irish healthcare, including in contraception provision.

Catherine Reilly reports

Scanning the future of radiology

The President of the European Society of Radiology, Prof Adrian Brady,

PAGE 10-12

‘Composite’ Human Tissue Bill could undermine organ donation – clinicians

CATHERINE REILLY

The inclusion of organ donation and transplant provisions in the same Bill that addresses the separate area of post-mortem practice could undermine public sentiment on donation, senior clinicians have warned the Department of Health.

“Conflating the organ donation and transplant section of the [Human Tissue] Bill with post-mortem, particularly organ retention, poses a risk of undermining the ethos of organ donation, as it exposes organ donation to being adversely affected should there be shortcomings in handling of human tissue in the future,” a spokesperson for HSE Organ Donation and Transplant Ireland (ODTI) told the Medical Independent (MI)

The Bill, which has not yet been published, will regulate post-mortem practice, including retention and disposal of human tissue from deceased persons. It will also provide general conditions for the donation and use of organs and tissues from deceased and living persons for transplantation; and provide for an opt-out system of consent for organ donation and for an associated register.

The Government is under increasing pressure to publish the Bill in light of scandals relating to the retention and disposal of infants’ organs without consent following post-mortem.

At a meeting of the national organ donation and transplantation advi-

Improving mental healthcare

Mental health attracts a great deal of discussion, but more work is required to improve services, writes Prof Brendan Kelly

PAGE 22

DPER raised concerns over HSE Covid costs reporting

DAVID LYNCH

The Department of Public Expenditure and Reform (DPER) raised concerns over the "lack of weekly Covid flash reporting" from the HSE during the first three months of this year, the Medical Independent (MI) can report.

According to minutes of the April meeting of the health budget oversight group, DPER queried the level of expenditure on Covid-19 measures to date in 2022, when compared with the opening months of 2021.

"Concern was raised about the lack of weekly Covid flash reporting in Q1 [quarter one of 2022]. Concern was also raised about the approach taken to planning for Covid expenditure to end 2022, with little evidence of the exploration of options for mitigation."

The flash report is a HSE financial report provided to the Department of Health and DPER. It was introduced dur-

ing the Covid pandemic and provides an early indication/estimation of Covid-19 costs incurred on a weekly basis.

"The weekly flash report has been in operation in quarters two and three," a DPER spokesperson told MI.

"This effectively addresses DPER’s concerns regarding this reporting.”

DPER is "continuing to engage with the Department of Health on the overall 2022 position for health sector expenditure, including all the key components of health expenditure,” said the spokesperson. "The Department of Health is responsible in the first instance for managing expenditure appropriately."

In March, DPER also raised issues about bed numbers at the health budget oversight group. "DPER noted that different bed numbers were being provided in different reports and highlighted the need for consistency going forward," noted minutes of the meeting.

XELJANZ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent.

XELJANZ in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs.

XELJANZ in combination with MTX is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy.

XELJANZ is indicated for the treatment of adult patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy.

XELJANZ is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (rheumatoid factor positive [RF+] or negative [RF-] polyarthritis and extended oligoarthritis), and juvenile psoriatic arthritis (PsA) in patients 2 years of age and older, who have responded inadequately to previous therapy with DMARDs.

Photo credit: Fintan Clarke, Coalesce Ltd

Pictured at the Fighting Blindness Retina Conference, which took place in the Radisson Blu Royal Hotel in Dublin on 3-4 November, are (L-R): Prof Catherine Bowes Rickman, Duke University, Durham, North Carolina, US; Mr Finbarr Roche, CEO, Fighting Blindness; and Dr Sarah Doyle, Associate Professor in Immunology, Trinity Institute of Neurosciences, Trinity College Dublin.

talks to David Lynch about his new position

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

Fax: +353 1 6762517

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

E-mail: Irishdrugsafety@astellas.com

sory group (NODTAG) in May, the Director of ODTI Prof Jim Egan “reiterated the need to ‘divorce’ organ donation from retention and post-mortem aspects of the Bill”, according to minutes obtained by MI following a Freedom of Information request. Mr Andrew Conlon, a Principal Officer at the Department of Health, responded that this would potentially cause a delay in publishing the Bill.

Dr Colm Henry, HSE Chief Clinical Officer, suggested that NODTAG “formally document all these concerns” to the Department, and Prof Egan confirmed this had already occurred.

At NODTAG’s next meeting in June, Mr Conlon gave an update on the status of the Bill, “noting the Minis -

Direct access to contraceptives in pharmacies under consideration

CATHERINE REILLY

The potential for oral contraceptives becoming available from pharmacists, without a doctor’s prescription, is being considered by an expert group in the HSE. It is due to report to the Department of Health by the end of the year.

A Department spokesperson said this issue was considered as part of the work of the contraception implementation group and was deemed to require consideration by an expert group.

“Accordingly, the matter has been referred to clinical experts in the HSE, requesting a formal recommendation,” the spokesperson told the Medical Independent “The clinical expert group includes pharmacists, nurses and midwives, obstetricians, and general practitioners; the group are currently examining clinical considerations and the national and international guidance in order to underpin a formal response. The advice is expected to be received by the Department of Health before the end of the year. Needless to say, any subsequent regulatory actions will depend on the nature of clinical recommendations.”

The Irish Pharmacy Union had been informed by Government that potential direct access to oral contraceptives from pharmacists will be considered under plans to expand age eligibility for the free contraception scheme in 2023.

To date, the Health Products Regulatory Authority (HPRA) has not received an application from a pharmaceutical company to reclassify an oral contraceptive medicine to permit sale and supply without a prescription.

However, the Authority was “open” to reviewing such applications. “This is in line with the HPRA's policy to make medicines and health products available at the most convenient point of access for people, where it is safe and appropriate to do so,” said a HPRA spokesperson. See news feature, p4-5.

ter’s wishes to include post-mortem and transplantation legislation in a single piece of legislation, despite NODTAG advising otherwise.”

The HSE informed MI the concerns were first raised during initial consultation on draft legislation and subsequently formally communicated in April 2022.

The Department of Health had acknowledged the concerns raised.

A Department spokesperson said “concerns around the composite nature” of the Bill had been discussed at meetings of NODTAG, of which the Department is a member.

“The concerns centre on the possibility of public confusion around the legislation and the risk that this inadvertently creates a negative response to measures to

Mater Private Network | Cork

increase organ donation rates. However, it is important to highlight that the Government has committed to the roll-out of a public information campaign focused solely on organ donation and transplantation.

“This campaign will raise awareness of the changes to the law and the introduction of a ‘soft opt-out’ regime, and will encourage people to make their wishes known to their family so that these can be followed should the opportunity to donate arise. As such, it will bring clarity and a focus on the importance of organ donation in saving lives.”

The proposed approach “has been agreed by Government and will bring Ireland in line with other countries with regards to human tissue legislation more generally”.

Women’s Health Study Evening

Date & Time Thursday 24th November | 7.00pm - 8.30pm

Location Centre for Women’s Health, Citygate, Mahon, Cork

Agenda

Overview of Urinary Incontinence

Prof. Barry O’Reilly Consultant Obstetrician & Gynaecologist

Matters of Menopause

Dr. Alex O’Brien General Practitioner with special interest in Women’s Health

Endometriosis: The Past, Present & Future

Dr. Aoife McSweeney Consultant Obstetrician & Gynaecologist Transvaginal Laser & Magnetic Stimulation of the Pelvic Floor

Dr. Susan Wilson Gynaecology Fellow (SPR Obs & Gynae)

The Practical Pessary Elaine Dilloughery CNMII

Q&A

Presentations will be followed by a Panel Discussion / Q&A. Questions can be submitted in advance to events@materprivate.ie or online during the live webinar.

For in-person attendees: Hot buffet served/ facility tour from 6.30-7.00pm. CPD applied for.

Registration

To attend online, via QR code or www.MedCafe.ie

To attend in-person, via email to: events@materprivate.ie www.materprivate.ie

Does a new era beckon for community pharmacists?

The availability of oral contraceptives in pharmacies, without a doctor’s prescription, is being considered by Government, according to President of the Irish Pharmacy Union (IPU) Mr Dermot Twomey.

The IPU had been informed that this measure will be considered under plans to expand age eligibility for the free contraception scheme in 2023. The scheme was launched in September for 17-to-25-yearold women and is due to extend to 16-to-30year-olds next year.

The union has long argued that expanding the remit of community pharmacists will improve healthcare accessibility. Community pharmacy could also be better utilised to alleviate pressures on GPs, it has said.

“In terms of expansion of services, we would see areas such as contraception without a prescription, and an expanded minor ailments scheme, as being beneficial from the perspective of the patient, in terms of accessibility,” Mr Twomey told the Medical Independent (MI)

In 2016, the Pharmaceutical Society of Ireland (PSI), the regulator of pharmacy practice, published a research paper that also envisaged an enhanced role for the profession in the context of patient needs and alleviating some of the challenges to the health system.

This document, Future Pharmacy Practice in Ireland, made several recommendations pertaining to community pharmacists, including expanding their role in supporting patients to treat minor and self-limiting conditions; and exploration of mechanisms to enable pharmacists and GPs to work more closely together in chronic disease management (ie, supplementary prescribing activities, such as dosage adjustment or therapy continuation by the pharmacist in line with agreed protocols).

A PSI spokesperson told MI: “The PSI’s intention is to continue to work with the relevant stakeholders – Department of Health, the HSE and the pharmacy sector – and to be ready to respond to policy developments driven by the Department of Health, and to be prepared from a regulatory perspective to support pharmacy policy direction and its implementation.

The PSI is an active participant in the HSEled Community Pharmacy Planning Forum chaired by Pat Healy of the HSE. The intended purpose of this Forum is that its participants will work together to progress the Sláintecare agenda in respect of community pharmacy. The work of this Forum is at the initial stage.”

The spokesperson added: “Ongoing projects intended to position pharmacy to best meet future demands include review of the CPD [continuing professional development] model for pharmacists; consideration of the emerging risks to the future pharmacy workforce; and revision of the core competency framework for pharmacists. Our proposal to expand our approach to the regulation of retail pharmacies by the addition of a standards-based approach is also something in early development.”

The PSI will be available to engage “on any evolution of service provision that may be considered as part of the revision of the HSE community pharmacy contract as and when requested to do so”.

The Programme for Government in 2020 committed to commencing talks with pharmacists on a new contract and “enhancement of their role”, including via e-prescribing and issuance of repeat prescriptions.

A Department of Health spokesperson told MI: “The work of the Community Pharmacy Planning Forum, established during the Covid-19 pandemic, has now transitioned to discussing the strategic direction of the community pharmacy profession. This will prove invaluable in the context of future contractual reform. Of course, any publicly funded pharmacy service expansion should address unmet public healthcare needs, improve ac-

“The clinical expert group includes pharmacists, nurses and midwives, obstetricians, and general practitioners; the group are currently examining clinical considerations and the national and international guidance in order to underpin a formal response.” The advice is expected to be received by the Department before the end of the year.

To date, the Health Products Regulatory Authority (HPRA) has not received an application from a pharmaceutical company to reclassify an oral contraceptive medicine to permit sale and supply without a prescription.

However, the Authority was “open” to reviewing such applications. “This is in line with the HPRA’s policy to make medicines and health products available at the most convenient point of access for people, where it is safe and appropriate to do so,” said a HPRA spokesperson.

healthcare”. It has cited a number of drivers, including limitations on scope of practice, under-funding, and excessive form-filling and paperwork requirements.

Community pharmacists are under significant workload pressures and any expansion of services would need to be implemented gradually, Mr Twomey agreed.

Contraception

Mr Twomey noted that direct access to oral contraceptives from community pharmacists has been implemented in several jurisdictions. In July 2021, the UK government announced that women would be able to buy progestogen-only oral contraceptives in pharmacies without a prescription. The Royal College of Obstetricians and Gynaecologists, UK, supported this policy change.

“There is plenty of evidence there for pharmacists working under a protocol to expand their scope,” commented Mr Twomey.

Nevertheless, some physician organisations have opposed such moves. Last year, the Australian Medical Association opposed reclassification proposals on the grounds that “pharmacists are not trained to properly assess patients for key risk factors or provide advice on other, potentially more effective forms of contraception”.

Australia’s Therapeutic Goods Administration (TGA) subsequently issued an interim decision against the reclassification of certain oral contraceptives (the proposals had included mitigations, such as prior prescription by a doctor).

The TGA interim decision considered that “the adverse effects of oral contraceptive substances, and the potential for evolving risks over time, are significant and require management by a medical practitioner”. The TGA interim decision noted that the use of oral contraceptive pills could cause significant adverse effects that were not consistent with over-the-counter (OTC) medicines. These effects included weight gain, anxiety, heavy bleeding, and thromboembolism, particularly with increasing age.

The final decision, released in December 2021, also noted that regular reassessment by a medical practitioner allowed routine preventive health screening as well as regular review of the suitability of continued oral contraception compared to other forms of long-acting reversible contraceptives (LARCs), which were not available without a prescription.

cess to existing public health services, and provide better value for money.”

The value of care provided by community pharmacists was recognised by the Minister, the spokesperson said.

The potential to make some forms of prescription contraception available through pharmacies without a doctor’s prescription “is a wider issue than the free contraception scheme”, added the Department’s spokesperson. However, this was considered as part of the work of the Department’s contraception implementation group and was deemed to require consideration by an expert group.

“Accordingly, the matter has been referred to clinical experts in the HSE, requesting a formal recommendation,” said the spokesperson.

Scope of practice

The permitted scope of practice “has not moved on a huge amount in the last 20 years”, according to Mr Twomey, Owner and Pharmacist at Cloyne Pharmacy, Co Cork. “There have been some wins in the areas of vaccination and emergency contraception, but there is far more that can happen.”

The development of pharmacists’ role is important for recruitment and retention, added Mr Twomey. “If we want to attract and retain our best and brightest, we have to make it possible for pharmacists to practise to the fullest of their scope.”

The IPU has highlighted a growing shortage of community pharmacists, which it said is becoming a “major threat to community

Conversely, in June, the American Medical Association expressed strong support for availability of oral contraception as an OTC medication in order to improve access.

According to Mr Twomey: “The reality is, we don’t see ourselves in competition with our medical colleagues. I have great relationships with the doctors we work with closely, I have huge respect for the work they do, I believe they have respect for the work I do as well… I think it is good to be flexible and look at what the needs are for the patient…”

Speaking to MI, IMO GP committee Chairperson Dr Denis McCauley said a key point on contraception was that general practice could offer patients all available options, including LARCs (not all GPs fit LARCs, but cross-refer to GP colleagues who provide this service). Dr

Community pharmacists continue to seek an enhanced role in Irish healthcare, including in the area of contraception provision. Catherine Reilly reports

If we want to attract and retain our best and brightest, we have to make it possible for pharmacists to practise to the fullest of their scope

Mr Dermot Twomey

McCauley said that with due respect to pharmacists, there may be unconscious bias where a service can only offer one type of option.

“I think it is better that a person goes to a ‘one-stop shop’ where that lady has full information about all the products and can choose one, rather than going into one environment where there is only one thing on offer.”

The medical assessments for the oral contraceptive pill were not always straightforward, he added. The consultation may require cross-reference with various information on the patient record, “because people don’t always remember all of their relevant health information there and then”. It was in the best interests of the patient to attend a healthcare professional who had “full information and possession” of their medical facts and the relevant skills to analyse this information.

Asked if he saw any role for community pharmacy in direct supply of oral contraceptives, Dr McCauley said: “I think in the initiation, no.”

Any additional role for pharmacists in the provision of contraception initiated by GPs could not be countenanced in the absence of appropriate clinical governance and health information transfer systems, he indicated.

Assurance of competency was also required.

On a minor ailments scheme, Dr McCauley said there was a substantial training requirement to become skilled in differentiating minor from non-minor ailments.

Without the required expertise and knowledge, the tendency to refer was greater. He acknowledged that pharmacists provided advice to patients every day and were “very sensible, practical people”.

“But to put it into an actual clinic… how far further from what they are doing now are you going…

“It all sounds good, but you have to look at what you are asking them to do and to what level are they trained, and you want somebody immediately reassured and not referred [where appropriate].”

In regard to the majority of consultations in general practice, “we analyse [the presentation] and we can reassure them on the spot, and they leave quite happy. Anything that prolongs that diagnostic journey inappropriately adds to extra pressure and stress.”

Notwithstanding the capacity issues in general practice, “it is better, if you are going to present yourself to a healthcare professional, that you get the best trained person there to give you the most succinct advice to hopefully reassure you and if necessary – if there is something up – to spot it competently so they refer appropriately.”

Dr McCauley emphasised that “pharmacists are very good at what they do” and acknowledged their important role in the ongoing Covid-19 vaccination programme.

Mr Twomey of the IPU said a protocol for consultations on contraception would need to be developed and should include information on LARCs. He said a protocol for pharmacist consultations on emergency hormonal contraception had incorporated information on methods of contraception and sexually-transmitted infections, for example. Emergency hormonal contraception has been available from community pharmacists in Ireland without a doctor’s pre-

scription since 2011.

On potential fragmentation of care and loss of opportunistic interventions by GPs, Mr Twomey maintained such matters could be addressed by appropriate protocols. He said pathways to share information with GPs would be vital.

“We would be happy to work within appropriate protocols and guidance. Let us be clear on this: There are a number of online consultations [by online doctor services] that happen for oral contraception that are not even a consultation at all, in fact many of the online doctors ask the pharmacy to check BMI or blood pressure as well…”

Minor ailments

Mr Twomey added that a minor ailments scheme was essentially in operation for private patients.

“Medical card patients are disadvantaged there in that, if they want to get products for hay fever, indigestion, thrush, head lice, a lot of those products, if they don’t have money in their pocket they go to their GP to get a prescription, whereas what we would like to see, working in a collaborative approach, is that there would be certain conditions that it would be possible for medical card patients to get [medications] without a prescription from their pharmacist through a protocol.”

This would also help free-up GPs to do more specialised work in the face of increasing pressures and patient multimorbidity, he said. “We see it at pharmacy level. A lot of patients have polypharmacy… there is a lot of complex stuff going on.”

Mr Twomey cited research led by the University of Aberdeen (Community Pharmacy Management of Minor Illness: MINA Study), which was published in 2014.

A systematic review, conducted under the MINA Study, derived evidence that suggested community pharmacy-based minor ailment schemes were “an effective and cost-effective strategy for managing patients”. Analysis of routine data showed that the prevalence of emergency department (ED) and general practice consultations deemed to involve minor ailments suitable for management in community pharmacy was 5.3 per cent and 13.2 per cent, respectively.

A cohort study as part of MINA research suggested equivalence of health-related outcomes for pharmacy-managed patients presenting with symptoms similar to those presenting to GPs and EDs (and at lower cost). The four target conditions in the cohort study were musculoskeletal pain (aches or pain in arms or legs or back or hands or feet); eye discomfort; upper respiratory tract-related (sore throat or cough or cold or sinus problems); and gastrointestinal disturbance (nausea or vomiting or diarrhoea or constipation).

Internationally, minor ailments services in pharmacy are operational in a number of health systems, including in the NHS.

Mr Twomey said there were ongoing training requirements for pharmacists and requirements set down by the regulator.

“It is important that there are appropriate protocols in place… and that appropriate questions are asked. We do that anyway… we do it for emergency hormonal contraception, where we have the consultation in a consultation room. We are trained in emergency medicine, such as adrenaline for anaphylaxis, and many pharmacists are trained in other areas [including] using salbutamol for emergency asthma.”

In 2016, the HSE conducted a three-month feasibility study, across four centres, on a pharmacy-delivered minor ailment service. The conditions included were dry eye; dry skin; scabies; threadworms; and vaginal thrush.

Later, the Department stated that while the pilot successfully tested operational and administrative procedures, the patient takeup was small and “no meaningful clinical or outcome data emerged”. It indicated in subsequent statements that more extensive trialling would be required to assess the proposal.

The ICGP, the professional body for GPs, has acknowledged that pharmacists already treat several minor ailments “such as minor coughs and respiratory infections and some skin infections, among other ailments”. This helped to reduce pressure on the hospital emergency services and on other parts of the health service.

“A community pharmacist-provided minor ailments scheme would require clear guidelines, protocols, and governance structures, as well as training of pharmacy support staff.”

Asked about the potential future introduction of independent pharmacist prescribers, as well as pharmacist supplementary prescribing as part of shared care with a GP, the College stated: “A highly trained pharmacist prescriber under the governance and supervision of the managing GP would be an additional valuable resource in the community. If care is shared with GPs and is guided and directed by the GP, then a pharmacist prescriber would add to the community support team for patients. Pharmacist prescribers would require extra training and thorough and comprehensive guidelines and protocols in order to ensure patient safety and wellbeing.”

Warfarin service

Mr Twomey is particularly well-placed to discuss extended practice in community pharmacy, having provided a warfarin (anticoagulant) service since 2010. It includes patient consultation, point-of-care blood testing, and dose adjustments as required.

He was the first community pharmacist in Ireland to embark on this practice, having undertaken a period of training under two consultant haematologists who supervised his work and deemed his level of expertise as appropriate. Mr Twomey has continued to work under the protocols set out by the consultants.

“Warfarin is not as popular a medicine as it once was, so I have much less patients. Having said that, every week we still manage our patients on warfarin. We have shown we can provide a high level of care in certain conditions when working under a protocol and our clinic has been independently reviewed by academic research, which showed we have done it to a higher standard than the local hospital.”

Patients were transferred either from their GP or local hospitals to access the warfarin service and Mr Twomey has regularly communicated with GPs where difficulties have arisen (ie, an excessively high INR level).

Mr Twomey said his practice always collaborates with the patient’s GP in such circumstances. “It is very important if we are managing that level of care that the communication is seamless.”

Currently, there is no joined-up electronic healthcare record capability between community pharmacists and GPs nationally. “But this is the future, where a person’s health data will be accessible across a spectrum of healthcare professionals to help with their healthcare needs.”

MINDO NUMBERS

8

was the median number of long Covid symptoms reported for each person in a new study conducted by APC Microbiome Ireland on the burden of disease in Irish patients.

6 out of every 10 people had missed work days (at some stage) due to their long Covid symptoms, reported the study.

1,600 healthcare service users contacted the Patient Advocacy Service in its first two years of service, according to the Department of Health.

10,679+ people were without a hospital bed in the month of October, according to the Irish Nurses and Midwives Organisation (INMO) Trolleywatch figures, making it the second-highest October figure on record.

393+ children under the age of 16 were on trolleys in the month of October, the worst month for paediatric overcrowding on record, outlined the INMO.

59

the predicted percentage increase in the total number of strokes by 2035, the HSE National Clinical Programme for Stroke highlighted as it launched its National Stroke Strategy 2022-2027.

Dr Denis McCauley

HSE progressing healthcare learning analytics unit

DAVID LYNCH

The new national learning analytics unit for healthcare professionals will be developed over “three overlapping phases” between now and 2028, this newspaper has been told.

The Medical Independent reported in January that the HSE was providing “initial seed funding” to develop the unit, which will be hosted in the College of Anaesthesiologists.

A presentation on the then proposed unit was made to the HSE safety and quality committee in October 2021.

According to minutes, the purpose of the unit would be “to analyse data from existing and novel sources to identify specific actionable targets, which will deliver personalised formative feedback for doctors in training, training programme quality improvement, and clinical risk mitigation at hospitals and other clinical sites”.

According to the HSE, since January “stakeholder engagement” had continued between “four core partners”, namely the HSE, State Claims Agency, Science Foundation Ireland Research Centres for Data Analytics and the Forum of Irish Postgraduate Medical Training Bodies.

“They have contributed to a proposal made by the

For the treatment of active rheumatoid arthritis, severe recalcitrant disabling psoriasis & severe psoriatic arthritis in adult patients. Induction of remission in moderate steroid-dependent Crohn’s disease in adult patients, in combination with corticosteroids and for maintenance of remission, as monotherapy, in patients who have responded to methotrexate

HSE to fund the establishment of the unit, commencing with the health estimates process for 2023,” said the spokesperson.

They added that the unit will be a HSE entity within the remit of the Chief Clinical Officer and headquartered in the College of Anaesthesiologists in Dublin. Prof Hendrik Drachsler (Leibniz Institute, Frankfurt) has been appointed as lead advisor on learning analytics to the project.

A steering group will be established before the end of this year.

“To that end, positive engagement has begun with other healthcare professional bodies, including the Pharmaceutical Society of Ireland and the Nursing and Midwifery Board of Ireland.”

THE METHOTREXATE AUTO-INJECTOR WITH THE PATIENT IN MIND

Indications: Active rheumatoid arthritis in adult patients. Polyarthritic forms of severe, active juvenile idiopathic arthritis, when the response to nonsteroidal anti-inflammatory drugs (NSAIDs) has been inadequate. Severe recalcitrant disabling psoriasis, which is not adequately responsive to other forms of therapy such as phototherapy, PUVA, and retinoids, and severe psoriatic arthritis in adult patients.

Induction of remission in moderate steroid-dependent Crohn’s disease in adult patients, in combination with corticosteroids and for maintenance of remission, as monotherapy, in patients who have responded to methotrexate. Dosage and administration: Nordimet should only be prescribed by physicians with expertise in the use of methotrexate and a full understanding of the risks of methotrexate therapy. Patients must be educated and trained in the proper injection technique when self-administering methotrexate. The first injection of Nordimet should be performed under direct medical supervision. Nordimet is injected once weekly, administered subcutaneously. Rheumatoid arthritis:

Recommended initial dose is 7.5 mg of methotrexate once weekly.

Depending on the individual activity of the disease & patient tolerability, the initial dose may be increased. A weekly dose of 25 mg should in general not be exceeded. Once the desired therapeutic result has been achieved, the dose should be reduced gradually to the lowest possible effective maintenance dose. Polyarthritic forms of severe, active juvenile idiopathic arthritis: The recommended dose is 10-15 mg/m² body surface area (BSA) per week. In therapy-refractory cases the weekly dose may be increased up to 20mg/m² BSA per week. Use in children < 3 years of age is not recommended. Psoriasis vulgaris and psoriatic arthritis: A test dose of 5 - 10 mg subcutaneously administered one week prior to

initiation of therapy is recommended. Recommended initial dose 7.5 mg methotrexate once weekly. The dose is to be increased gradually but should not, in general, exceed a weekly dose of 25 mg of methotrexate. Once the desired therapeutic result has been achieved, dose should be reduced gradually to the lowest possible effective maintenance dose.

In a few exceptional cases a higher dose than 25 mg might be clinically justified, but should not exceed a maximum weekly dose of 30 mg of methotrexate. Crohn’s disease (adult patients): 25 mg/week administered subcutaneously. Once patients have adequately responded to combination therapy, the corticosteroids should be tapered. Maintenance treatment: 15 mg/week administered subcutaneously, as monotherapy, if the patient has entered remission. Renal impairment, hepatic impairment or elderly patients: Please refer to SmPC. Note: When switching from oral to parenteral use, a reduction in the dose may be required, due to the variable bioavailability of methotrexate after oral administration.

Contraindications: Hypersensitivity to methotrexate or to any of the excipients. Severe hepatic impairment, if serum bilirubin is > 5 mg/dl (85.5 µmol/l). Alcohol abuse. Severe renal impairment (creatinine clearance < 30 ml/min). Pre-existing blood dyscrasias (e.g. bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anaemia). Immunodeficiency.

Serious, acute or chronic infections such as tuberculosis & HIV. Stomatitis. Ulcers of the oral cavity and known active gastrointestinal ulcer disease.

Pregnancy. Breast-feeding. Concurrent vaccination with live vaccines.

Special warnings and precautions: Patients must be clearly advised that the therapy is to be administered once a week, and not every day.

Patients receiving therapy should be appropriately monitored. Doses exceeding 20 mg/week can be associated with significant increase in toxicity, especially bone marrow suppression. The possible risks of effects on reproduction, pregnancy loss and congenital malformations should be discussed with male and female patients of childbearing potential. Methotrexate contact with skin and mucosal membranes is to be avoided; in cases of contamination rinse the area with plenty of water. Interactions: Consult SmPC for detailed information on interactions. Undesirable

effects: See SmPCs for full list of undesirable effects. Very common: Stomatitis. Dyspepsia. Appetite loss. Abdominal pain. Nausea. Abnormal liver function tests (increased Alanine aminotransferase (ALAT), Aspartate aminotransferase (ASAT), alkaline phosphatase and bilirubin). Common: Leukopenia. Anaemia. Thrombopenia. Headache. Tiredness. Drowsiness. Pneumonia. Interstitial alveolitis/pneumonitis. Oral ulcers. Diarrhoea. Exanthema. Erythema. Pruritus. Uncommon: Pharyngitis. Pancytopenia. Precipitation of diabetes mellitus. Depression. Confusion. Dizziness. Enteritis. Pancreatitis. Gastrointestinal ulceration and bleeding. Cirrhosis, Fibrosis and fatty degeneration of liver. Arthralgia, myalgia, osteoporosis. Inflammation and ulceration of bladder. Renal impairment. Rare: Infection. Conjunctivitis. Sepsis. Allergic reactions. Anaphylactic shock. Hypogammaglobulinaemia. Visual disturbances. Pericarditis. Pericardial effusion. Pericardial tamponade. Thromboembolic events. Pulmonary fibrosis. Pneumocystis carinii pneumonia. Shortness of breath and bronchial asthma. Pleural effusion. Acute hepatitis. Renal failure. Anuria. Very rare: Lymphoma. Agranulocytosis. Lymphoproliferative disorders. Severe courses of bone marrow depression. Acute aseptic meningitis. Convulsions. Paralysis. Impaired vision. Retinopathy. Haematemesis. Toxic megacolon. Hepatic failure. Stevens-Johnson syndrome. Toxic epidermal necrolysis. Not known: Eosinophilia. Encephalopathy/Leukoencephalopathy. Pulmonary alveolar haemorrhage. Jaw osteonecrosis (secondary to lymphoproliferative disorders). Legal classification: POM. MA numbers: EU/1/16/1124/001 – 008. Further information available from: Nordic Pharma Ltd, 4045 Kingswood Road, Citywest Business Park, Co Dublin. Date of Prescribing Information: July 2021. Item code: IE/21/NOR/008-00.

CATHERINE REILLY

The potential identification of a cohort of GPs prescribing moxifloxacin in order to issue them with correspondence from the HSE Medicines Management Programme (MMP) was discussed by the antimicrobial consumption subgroup, according to minutes of its meeting in May.

The meeting agreed that a letter would be drafted about moxifloxacin use and an alert was to be circulated to GPs pending information from the MMP. The issue was also discussed by the subgroup in February.

In 2019, the HSE’s antimicrobial resistance and infection control section issued a patient safety alert to GPs on use of moxifloxacin when appropriate alternative antibacterial agents were available and likely to be effective. According to this alert, data from the Primary Care Reimbursement Service showed that oral moxifloxacin continued to be used “in substantial quantities in primary care”. This was a concern because circumstances in which moxifloxacin was preferable to other fluoroquinolones with a lower potential for QT prolongation, were likely to be “exceptionally rare” in primary care.

The 2019 alert noted that all fluoroquinolones, including moxifloxacin, were associated with significant adverse effects and generally not appropriate for first-line use in primary care. Fluoroquinolones were valuable in specific settings where the benefit outweighed risk.

According to the HSE, the overall use of fluoroquinolones had decreased by 33 per cent from 2018 to mid-2022 (3 per cent of overall antibiotic prescriptions down to 2 per cent).

Following the subgroup meeting in May, the manufacturer of moxifloxacin issued notification that it would no longer be marketed in Ireland from July 2022. “Therefore, further individual analysis of moxifloxacin was not deemed necessary,” stated the HSE spokesperson.

The HSE noted a positive trend in the proportion of preferred (green) antibiotics prescribed by GPs in the GMS and a reduction in the proportion of non-preferred (red) antibiotics prescribed.

Concern about GP moxifloxacin prescribing raised at group

ICGP hopes to discuss curriculum changes with GP professors

NIAMH

QUINLAN

The ICGP intends to convene a meeting with professors of general practice and the deans of the medical schools to discuss increasing general practice placements in the medical school curriculum, this newspaper has been informed.

In October, the ICGP published 10 possible solutions to tackle the capacity crisis in general practice in the Shaping the Future of General Practice discussion paper. One of the proposals was increasing students’ exposure to general practice by ensuring a minimum 25 per cent of the medical school curriculum consisted of GP placements.

The ICGP confirmed to the Medical Independent (MI) that the College is hoping to have a meeting to discuss implementation of the recommendation at the end of November, although no exact date has been confirmed.

CEO of the ICGP, Mr Fintan Foy, told MI: “At the meeting we will discuss… how that might be achieved, what the barriers may be, and to work collaboratively to address any barriers. We hope by increasing exposure to general practice at an undergraduate level, this will increase the numbers wishing to enter the specialty.”

Professor of Urban General Practice at University College Dublin School of Medicine, Prof Walter Cullen, told MI that the school welcomed this meeting and looked forward to engaging with the ICGP on this “priority issue”.

He added: “While growing this footprint to 25 per cent of the clinical curriculum would indeed be welcome, a change of this scale… would be complex and would require the support of many stakeholders. It would be a challenge, but one that needs to be addressed if we are serious about shifting healthcare into the community to the

New national employment record app ‘will help NTSDs’

NIAMH QUINLAN

The new national employment record (NER) app aims to simplify the process by which non-training scheme doctors (NTSDs) can apply for training schemes, according to HSE National Lead NCHD, Dr Jennifer Finnegan.

The new app is an extension of the already established NER web-based portal and allows access to the NCHD e-portfolio. The NER e-portfolio, launched in 2021, was undertaken to help NCHDs, particularly those not on a training scheme, to record their career development and have their experience verified/validated.

Speaking to the Medical Independent (MI), Dr Finnegan said: “We hope that the uptake [among NTSDs] will improve with the app. When they are on call, when they’re having a break… they can upload their competencies and the skills they’ve just done, rather than having to

revisit it at home.”

Dr Finnegan also said “substantial” input from NTSDs was sought when developing the app.

NCHDs can also apply for funding under the training support scheme and the clinical course exam and refund scheme via the NER app.

The overall aim of the app is to help streamline the completion and uploading of pre-employment screening documentation for NCHDs. It will “enhance the user experience” and “it should make things a little bit quicker”, according to Dr Finnegan.

“One of the trainees had said to me that he once had two suitcases of paperwork when it came to trying to get his training recognised,” she told MI. “It removes the barrier to having to find a space, sit down with your USB keys, your email, and have all your receipts to hand.”

The app was launched on Apple and Android app stores on 7 November.

extent that is envisaged at a national policy level.”

Currently, University of Limerick School of Medicine is the only medical school that allocates 25 per cent of its curriculum to general practice.

Ireland ‘vastly underserved’ by number of radiologists

DAVID LYNCH

The Irish health service is “vastly underserved” in terms of the number of radiologists being trained and employed, the new President of the European Society of Radiology (ESR) has warned.

Prof Adrian Brady, who is a Consultant Radiologist at Mercy University Hospital, Cork, told the Medical Independent (MI): “There is a lot of talk in the press about expanding access to diagnostic tests in Ireland, which is a good idea. But there is very little talk about where those people who are going to interpret those diagnostics tests are going to come from.”

Prof Brady, who became ESR President in the summer, said there was an “inadequate number of people coming on stream” as fully trained radiologists.

“The need for central approval for

salaries for additional trainee posts, and the limits applied to those approvals, are the chief limiting factors on the numbers of future consultants being trained.”

Prof Brady said that “if you put this on top of the other recruitment difficulties that exist for recruiting consultants in Ireland [in general]…then yes, we do have a major problem in terms of the people who are training and the numbers of people we are employing”.

MI previously reported that a meeting of the HSE safety and quality committee in March discussed “risk in relation to the ability to recruit consultant radiologists for BreastCheck”.

A HSE spokesperson admitted to this paper that “recruiting breast radiologists in Ireland is challenging for many reasons”. See interview, p10-12.

Minister for Health Stephen Donnelly on the opening of the National Forensic Mental Health Service (NFMHS) in Portrane, Co Dublin, on 4 November. It is Ireland’s largest capital project and cost approximately €200 million.

VOX BOX

Today is a significant and historic day for the Irish health service. This fantastic new facility brings real and necessary change to the lives of some of the most vulnerable in our society.

Mr Fintan Foy

This is a welcome day for patients, family/carers, and our staff and this new facility provides us with opportunities to be a world leader in this specialist field.

Mr Patrick Bergin, Head of Service at the NFMHS, on the opening of the new facility.

The app provides selfcare and signposting information regarding adult ADHD [attention deficit hyperactivity disorder]. It is important to note that is not a treatment programme or a replacement for medical advice and care.

Dr Margo Wrigley, HSE National Clinical Lead for the ADHD in adults clinical programme, on a new app launched to support adults with ADHD.

Shingrix powder and suspension for injection in vials (Please refer to SmPC before prescribing) Composition: After reconstitution, one dose (0.5 mL) contains: Varicella Zoster Virus

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

E

Holder: GlaxoSmithKline Biologicals

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

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

should also be reported to GlaxoSmithKline on 1800 244 255.

antigen1,2 50 micrograms. (1 adjuvanted with

Scanning the present and future of radiology

The recently elected President of the European Society of Radiology, Prof Adrian Brady, talks to David Lynch about his new role, workforce challenges, and how artificial intelligence is affecting the specialty

Radiology is a diagnostic process which plays a vital role from the earliest moments of life until after it ends. This will be reflected in next year's European Congress of Radiology (ECR) in Vienna, Austria, in early March.

The official theme of ECR 2023 is 'The Cycle of Life', and it was chosen by the European Society of Radiology's (ESR) new President, Prof Adrian Brady (see panel on p12).

Prof Brady is Consultant Radiologist at the Mercy University Hospital, Cork, and a Clinical Professor of Radiology at University College Cork (UCC), with particular interests in interventional radiology and abdominal imaging.

The annual meeting is organised by the ESR and Prof Brady became President when ECR 2022 came to a close during the summer. The ECR is regarded as one of the biggest scientific meetings on the calendar in Europe.

Prof Brady already has his eyes on next year's event in Austria.

"The theme I have picked is the cycle of life," he told the Medical Independent (MI). "What I'm thinking about in that respect is that I want to reflect the fact that radiology has a major impact and input into every aspect of life... to after life."

He said that ECR 2023 will have many sessions "about conventional radiological issues that would happen at any conference" dealing with "children, adolescents, adults and older people, which will all be an essential part of the programme".

However, the upcoming March conference will also "take a broader view towards content to show just how broad our specialty is".

So next year's event will host sessions and lectures on antenatal radiology, for example, and will include lectures and

sessions on post-mortem imaging and forensic radiology.

"There will also be courses on radiology's application to other areas that would not automatically come to mind. For example, radiology's input into archaeology, palaeontology, and radiology's impact in other non-medical applications, such as studying artwork. These will be peripheral aspects of what we will be doing in the Congress – most of it will be very conventional. But we want to show the fact that radiology is a significant contributor to healthcare throughout life and beyond."

While organising the ECR is a significant part of the ESR's business, the Society has a wider remit. According to its website, the ESR’s "mission at all times is to serve the healthcare needs of the general public through the support of science, teaching and research, and the quality of service in the field of radiology".

With over 129,000 members across the globe, it has grown to become the largest radiological society in the world.

Therefore, the ESR reflects the challenges and current issues in the world of radiology, from workforce planning to the growing

influence of technological innovation.

Workforce

Everyone working in medicine in Ireland has grown familiar with the details of the 'recruitment and retention crisis' for consultants across many specialities. Radiology is no different, and it faces some particular workforce challenges.

In September 2021, this newspaper reported that the national clinical programme for radiology recommended the training of approximately 30 additional interventional radiologists to deliver 24/7 access to treatment for patients in Ireland. The authors of the recommendation said that Ireland needs at least an additional 150 radiologists over the next decade, including the 30 interventional radiologists.

Earlier this year, MI reported that the HSE safety and quality committee meeting in March discussed “risk in relation to the ability to recruit consultant radiologists for BreastCheck".

An Executive spokesperson admitted to this paper that “recruiting breast radiologists in Ireland is challenging

for many reasons".

"A joint working group with the National Cancer Control Programme has been established following sign-off by the Chief Clinical Officer [Dr Colm Henry] to consider medium- and long-term goals to support breast radiology," the spokesperson added.

Do the significant challenges of recruiting radiologists in Ireland make this country stand out from other developed nations?

"Yes, Ireland is an outlier," said Prof Brady. "Not to put too fine a point on it, if you look at OECD data for the number of radiologists per 100,000 of the population, the two countries that are right at the bottom in the developed world are the UK and Ireland." The ESR President said that he had just returned from a conference in the UK where this "very issue" was discussed.

With regard to Ireland, "we are both vastly underserved in terms of the number of radiologists who are being trained and the number of radiologists who are

Prof Adrian Brady

*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.

being employed.”

"There is a lot of talk in the press about expanding access to diagnostics in Ireland, which is a good idea. But there is very little talk about where those people who are going to interpret those diagnostic tests are going to come from."

Prof Brady said there is an "inadequate number of people coming on stream" as fully trained radiologists.

“The need for central approval for salaries for additional trainee posts, and the limits applied to those approvals, are the chief limiting factors on the numbers of future consultants being trained,” he explained.

Prof Brady said this all means "that you end up with a pretty underserved system, with a workforce in place which is being asked to deal with a workload about double what would be the norm in most equivalent countries…. Even within those parameters it is hard to find bodies to fill those slots.

"If you put this on top of the other recruitment difficulties that exist for recruiting consultants in Ireland [in general]... then yes, we do have a major problem in terms of the people who are training and the numbers of people we are employing."

Prof Brady is currently co-leading a Europe-wide project that is funded by the European Commission to look into issues of education, training, workload, and workforce availability for positions, such as radiologists, radiation oncologists, and radiographers.

"We are running this project for the next three years on behalf of the European Commission," said Prof Brady.

“The intention, at the end of it, is that I'm hoping we'll produce a set of recommendations that will include things like – if you have a population of x then you should have y number of radiologists or radiation oncologists and so on."

It is hoped that this will lead to European level guidance on how many people should be trained and employed in a given specialty to serve a set population.

"I've absolute confidence that if such guidance was available now, it would show that the numbers of radiologists in Ireland are vastly inadequate in comparison with other developed countries."

Artificial intelligence

Prof Brady has published and spoken widely in recent years on professional issues. These issues have included radiologists' workload, errors and discrepancies, reporting style and structure, value-based imaging, and artificial intelligence (AI) in radiology.

On the latter topic, prior to the Covid-19 pandemic, MI reported on an address Prof Brady gave to the Annual Health Informatics Society of Ireland (HISI) Conference and Scientific Symposium in November 2019. At that meeting in Croke Park, he tackled issues around ethics, liability and the impact of the technology on radiologists' working life.

Three years on, does AI still remain a major topic within the specialty?

"Very much so," he confirmed. "AI is actually opening whole new areas for radiology that we never thought about before. So yes, it is going to change things."

However, early predictions from some that the technology could eventually replace radiologists have proved far-fetched.

"Back around about 2015, some people were predicting that AI would do away with radiologists. It wasn't radiologists who were saying this," he said. "But it's not going to put us out of business. Like any other development what it does is that it opens up new opportunities."

He said that AI may take on "a lot of the mundane tasks" which are done on a predominantly manual basis.

It is in areas such as personalised medicine where its greatest impact may yet be made. For example, this would include the potential of the technology to help create targeted therapies for specific cancer cells in individual patients.

"In terms of the ethical issues, we are kind of learning about AI as we go on and by using it," said Prof Brady. "We are also learning about what are the potential pitfalls, what are the things that can go wrong; this is where my work on the

ethics behind AI comes in."

"We need to define the standard of how this is done before we start using this [AI technology] in a widespread manner. Because it would be unimaginable to find ourselves in a scenario where these new tools are being used but we haven't thought about whether it is ethical to do what we are doing."

Prof Brady, who has been involved in international work to produce published statements on the ethics of AI in radiology, noted the potential for abuse of patient data as an example of something that must be addressed.

"There is nothing intrinsically ethical or unethical about machine learning algorithms. What matters is how they are written and programmed and we need to think about all the sort of things that can happen with the data that are being used to develop the algorithms."

Discrepancies

Prof Brady has also recently written on the issue of 'errors' and 'discrepancies' in radiology. The ESR President thinks there is a lack of general understanding outside of the specialty on these matters.

The Cycle of Life – an Irish influence

The European Congress of Radiology (ECR) 2023 poster takes its inspiration from the Congress slogan, ‘The Cycle of Life’, and it is also influenced by Irish history and culture.

The theme of the ECR 2023 was chosen by European Society of Radiology (ESR) President, Prof Adrian Brady.

According to the ESR's website, "the foundation of the poster is based on the tri-spiral (triskelion), or ‘Spiral of Life’, an ancient motif carved in the Irish neolithic passage tomb at Newgrange, built around 3200 BC, and represented at the apex of the poster."

"It has been ascribed many different meanings in different usages; one suggestion is that the spiral of life represents the cycle of life, death, and rebirth."

The website notes that the various stages of life are depicted on the poster.

"The clock on which all these elements are mounted is shown at 20.23hrs, the year of our Congress.

"Finally, all of these elements are connected together through an

intricate array of cogs and wheels, powered by one man on a bicycle, keeping all the elements turning by the strength and capacity of his body. This acts as a reminder that each person’s cycle of life is unique, sustained as much as possible by their own abilities and efforts."

"A lot of people misunderstand the nature of what we do," he said.

Prof Brady gave the example of a CT scan where a patient may be disappointed if there is not a clear "confident" diagnosis.

"One thing I would like people to understand a little bit better is that medicine is, by its nature, an uncertain business most of the time," he said.

"We are asked quite often to rule out something following an x-ray or scan... but you can't rule out something that begins at the level of one cell. You can't take a CT scan and rule out cancer, because cancer may be there at a level that is undetectable."

The same applies to detecting an infection through a chest x-ray.

He said that if a radiologist does not make what is perceived to be a "confident diagnosis" people often think the radiologist has perhaps made an error.

"Of course, that is not what it is like at all... infection [in the case of a chest x-ray] may be at a level that is simply not visible."

Prof Brady said that when he describes the lack of understanding he does not mean just patients or some in medicine.

"I mean the general public, politicians, commentators in the press,” he stated. “They need to understand that medicine is riven with uncertainty."

"At all times we are trying to use the information that is available to us to get as close to certainty as we can, and most of the time we achieve that. But expecting certainty, expecting binary ‘yes’ or ‘no’ decisions, is misunderstanding the whole situation."

President

Founded in 2005, the ESR was created through the merger of two established radiological societies, the European Association of Radiology (EAR) and the European Congress of Radiology (ECR). Since its foundation 17 years ago, the ESR has not had an Irish President until now.

Prof Brady has been involved in ESR activities for many years and chaired the ESR quality safety and standards committee from 2017 to 2020.

After medical school and radiology training in Dublin, he moved to Canada for fellowship training in Hamilton, Ontario, before becoming a staff radiologist in Toronto. In 1995, he moved to his present post in Cork.

The presidential role is an elected one following the votes of eligible European countries and some beyond the continent. Prof Brady said that he is "very proud" to be elected considering he hails from a country of just five million people.

He added that he hopes that his time in office "raises the profile of Ireland on an international medical stage, and of the academic bodies we represent, the universities, such as my own university [UCC]".

"I hope it raises the profile of the skills that are available in the radiology workforce within Ireland, which are at a magnificent level. Ireland is a very highly skilled country in terms of the graduates we produce and the services we provide."

ESR website: https://www.myesr.org/

But expecting certainty, expecting binary ‘yes’ or ‘no’ decisions, is misunderstanding the whole situation

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The rocky road to reforming assisted decision-making

The Assisted Decision-Making Act is to come into effect following warnings about the lack of deprivation of liberty safeguards. Kieran Feely reports

The former HSE CEO Mr Paul Reid wrote to Secretary General of the Department of Health Mr Robert Watt highlighting concerns relating to the absence of deprivation of liberty safeguards in the Assisted Decision-Making (Capacity) Act 2015 (ADMA).

This was disclosed in minutes of the HSE board meeting held on 27 April 2022. The minutes stated that the HSE was concerned there was a lack of a clear legislative basis governing restraints on liberty of persons lacking capacity or persons with complex needs.

This followed HSE criticism of the ADMA and the Assisted Decision-Making (Capacity) (Amendment) Bill 2022 in its submission to the joint Oireachtas committee on children, equality, disability, integration, and youth (JOC) during pre-legislative scrutiny of the Bill in February this year.

In its submission, the HSE stated that the failure to provide for review mechanisms and rights to legal representation in relation to deprivation of liberty would be in breach of the Constitution and the European Convention on Human Rights. The HSE also said that the fact that a person might be deprived of their liberty under the enduring powers of attorney provisions were “unacceptable and indefensible”. This level of criticism of Government policy by a public body is unusual and indicates an acute level of unease on the part of the HSE in relation to the ADMA.

The Bar of Ireland, the representative body for barristers, told the Oireachtas committee that the absence of deprivation of liberty safeguards in the ADMA placed vulnerable people at significant risk of harm.

Minister for Children, Equality, Disability, Integration and Youth Roderic O’Gorman told the Seanad on 15 September that the 2015 Act needed to be amended. The Minister was speaking at the second stage of the Assisted Decision-Making (Capacity) (Amendment) Bill 2022.

“The Bill will, first and foremost, enable us to commence the 2015 Act. The need for amending legislation became clear over the course of intensive interdepartmental work that had been underway to prepare for the full operationalisation of the Act and the decision support service (DSS),” said Minister O’Gorman.

The ADMA was scheduled to come into full operation in June 2022, but was delayed. A revised date for the Act coming into operation was set for 21 November 2022. A spokesperson for the Minister told the Medical Independent (MI) that it has been delayed again because the 2022 Bill has not been passed into law.

“A new date is currently being sought and will be released as soon as it is available,” said the spokesperson.

Deprivation of liberty safeguards

Mr Paul Reid

Deprivation of liberty safeguards (DOLS) relate to the procedures by which a person may be deprived of their liberty. According to a press summary from the Supreme Court of the United Kingdom in the so-called ‘Cheshire Case’, their purpose is to secure independent professional assessment of (a) whether a person lacks the capacity to make their own

decision about whether to be accommodated in a hospital or care home, or for medical treatment, and (b) whether it is in their interests to be detained.

The press summary goes on to state that the key feature of deprivation of liberty is whether a person is under continuous supervision and control and is not free to leave.

Assisted Decision-Making (Capacity) Act 2015

The ADMA was passed by the Oireachtas and signed into law in late 2015. The main object of the Act is to abolish the wards of court system and replace it with a tiered system of assisted decision-making support for people whose capacity may be diminished.

The Act provides that all persons are presumed to have capacity and equal recognition under the law. A three-tier decision-making system was introduced.

Decision-making assistance is designed for people who need support with sourcing and interpreting information. A co-decision-making option is available for those who wish to make a joint decision with a family member or friend. Where serious capacity issues exist, the courts can appoint a decision-making representative to make decisions on a person’s behalf.

Advance healthcare directives are also provided for, whereby a person can decide in advance what medical treatments they wish to have in future in the event that they have lost capacity to make such decisions at the relevant time.

The existing position in Ireland

Persons who lack capacity may be deprived of their liberty and/or have medical treatment decided by others under the wards of court procedure or under the Mental Health Acts.

The Law Reform Commission (LRC), in its report titled Vulnerable Adults and the Law (2006), stated the legal effect of a person being made a ward of court is that the court is vested with jurisdiction over all matters relating to their person and estate.

Criticism of the wardship system

In compiling its report in 2006, the LRC found that the wardship system was unsatisfactory on numerous grounds.

The Commission found that the system was archaic and complex; the paternalistic concepts were at odds with social and human rights models, which emphasise ability over disability and the concept of capacity in functional terms; there are inadequate procedural safeguards to protect human rights; the focus is on the protection of assets; and proceedings are inquisitorial rather than adversarial where evidence presented is not challenged.

This means that the person who is the subject of a wardship application does not have the opportunity to cross examine those who give evidence to the court, including expert medical witnesses, according to the report.

The LRC identified groups of people affected by capacity issues. These include persons with an intellectual disability, dementia, mental illness, or an acquired brain injury. The Commission went on to state that affected persons do not necessarily lack all capacity to decide how to live their lives, but that the wardship system represents an ‘all-ornothing’ approach. The system changes a person’s status from a person with capacity to a person without capacity and takes no account of the variations in capacity that exist among vulnerable groups.

These criticisms were echoed in a judgment of the Supreme Court (AC v Cork University Hospital) given in 2019. The court stated that the “paternalistic” approach and its association with the making of decisions by others in the best interests of a person with impaired capacity, is increasingly under interrogation as failing to afford sufficient importance to the right of individuals to make their own decisions.

The Supreme Court stated that the healthcare system operated on the principles of voluntarism and duty of care and went on the discuss the doctrine of necessity.

The doctrine of necessity applies where there is a need to act, but it is not possible to communicate with the assisted person, and the action to be taken is such that a reasonable person would take in the best interests of the assisted person in the circumstances.

However, since it is in the nature of the doctrine of neces-

Minister Roderic O’Gorman

Four Courts building

Significantly improves exercise duration and reduces angina frequency1

Abbreviated Prescribing Information: Ranexa (ranolazine). Please consult the Summary of Product Characteristics (SPC) for full prescribing information. Presentation: Prolonged-release tablets containing 375 mg, 500 mg or 750 mg of ranolazine. 750 mg tablet contains E102 and lactose. Use: Ranexa is indicated as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies (such as beta-blockers and/or calcium antagonists). Dosage and administration: Oral administration. Patients should be instructed to list their medication to their health care professional at each visit. Adults: Initial dose is 375 mg twice daily. After 2-4 weeks, dose should be titrated to 500 mg twice daily and, according to patient’s response, further titrated to 750 mg twice daily. Concomitant treatment with moderate CYP3A4 and P-glycoprotein (P-gp) inhibitors: Careful dose titration is recommended. Renal impairment: Careful dose titration is recommended in mild to moderate renal impairment, and contraindicated in severe renal impairment. Hepatic impairment: Careful dose titration is recommended in mild hepatic impairment, and contraindicated in moderate to severe hepatic impairment. Elderly: Dose titration in the elderly should be exercised with caution. Low weight: Dose titration in patients with low weight should be exercised with caution. Congestive Heart Failure (CHF): Dose titration in moderate to severe CHF should be exercised with caution. Paediatric patients: No data in children below the age of 18 years. Ranexa tablets should be swallowed whole and not crushed, broken or chewed. They may be taken with or without food. Contra-indications: Hypersensitivity to the active substance or to any of the excipients. Severe renal impairment. Moderate or severe hepatic impairment. Concomitant administration of potent CYP3A4 inhibitors. Concomitant administration of Class Ia or Class III antiarrhythmics other than amiodarone. Warnings and Precautions: Caution should be exercised when prescribing or up titrating ranolazine to patients in whom an increased exposure is expected. QT prolongation: Caution should be observed when treating patients with a history of congenital or a family history of long QT syndrome, in patients with known acquired QT interval prolongation, and in patients treated with drugs affecting the QTc interval. Interactions: Co-administration with CYP3A4 inducers is expected to lead to lack of efficacy.

Renal impairment: Check renal function at regular intervals during treatment. Interactions: CYP3A4 inhibitors: Increase plasma concentrations of ranolazine. Combining ranolazine with potent CYP3A4 inhibitors is contraindicated. CYP3A4 inducers: Avoid initiation with Ranexa during administration of CYP3A4 inducers. CYP2D6 inhibitors: May increase plasma concentrations of ranolazine. Effect of ranolazine on other medicinal products: Dosage adjustment of sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range may be required. Lower doses of CYP2D6 substrates may be required. Caution with CYP2B6 substrates. Monitor digoxin levels following initiation and termination of Ranexa. Limit dose of simvastatin to 20mg once daily in patients taking Ranexa. Limit dose of atorvastatin and consider clinical monitoring in patients taking Ranexa. Monitor blood levels of tacrolimus when coadministering with Ranexa and adjust tacrolimus dose accordingly. Also recommended for other CYP3A4 substrates with a narrow therapeutic range. Drugs transported by the Organic Cation Transporter-2 (OCT2): Plasma exposure of metformin increased in subjects with type 2 diabetes mellitus when co-administered with Ranexa. The exposure of other OCT2 substrates may also be affected. Theoretical risk that concomitant treatment with drugs known to prolong the QTc interval may increase the possible risk of ventricular arrhythmias. Pregnancy and lactation: Ranexa should not be used during pregnancy unless clearly necessary. Ranexa should not be used during breast-feeding. Effect on fertility unknown. Side-effects: Generally mild to moderate in severity and often develop within the first 2 weeks of treatment. Common (1-10%): dizziness, headache, constipation, vomiting, nausea, asthenia. Uncommon (0.1–1%): anorexia, decreased appetite, dehydration, anxiety, insomnia, confusional state, hallucination, lethargy, syncope, hypoaesthesia, somnolence, tremor, postural dizziness, paraesthesia, blurred vision, visual disturbance, diplopia, vertigo, tinnitus, hot flush, hypotension, dyspnoea, cough, epistaxis, abdominal pain, dry mouth, dyspepsia, flatulence, stomach discomfort, pruritus, hyperhydrosis, pain in extremity, muscle cramp, joint swelling, muscular weakness, dysuria, haematuria, chromaturia, fatigue, peripheral oedema, increased blood creatinine, increased blood urea, prolonged QT corrected interval, increased platelet or white blood cell count, decreased weight. In a long term study, acute renal failure was also reported with an incidence less than 1% in placebo and ranolazine patients. Rare (0.1-0.01%): hyponatremia, disorientation, amnesia, depressed level of consciousness, loss of consciousness, coordination abnormal, gait disturbance, parosmia, impaired hearing, peripheral coldness, orthostatic hypotension, throat tightness, pancreatitis, erosive duodenitis, oral hypoaesthesia, angioedema, allergic dermatitis, urticaria, cold sweat, rash, acute renal failure, urinary retention, erectile dysfunction, elevated levels of hepatic enzyme. Not known: myoclonus. Increased incidence of congestive heart failure and transient ischaemic attacks seen in patients with history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention and treated within 2 weeks with ranolazine (1000 mg twice daily [dose not approved in Europe]) in a placebo-controlled post-PCI trial. Elderly, renal impairment and low weight: In general, adverse events occurred more frequently among elderly patients and patients with renal impairment. Adverse events in patients with low body weight were similar to those of patients with higher weight. Please consult the SPC for further information.Pack size: 60 tablets. Legal category: POM. Marketing authorisation numbers: EU/1/08/462/001, 003, 005 Marketing Authorisation holder: Menarini International Operations Luxembourg S.A. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd. Further information is available on request from A. Menarini Pharmaceuticals Ireland Ltd, 2nd Floor, Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924 or may be found in the SPC. Last updated: October 2020

Date of item: November 2020. IR-RAN-12-2020

References: 1. Chaitman, B.R., et al. JAMA, 2004; 291(3): p. 309-16.

Continued from p14 ▸

sity that it is designed only to deal with urgent situations, it lacks formal safeguards and procedures, and it cannot be relied upon for more than a temporary justification of such detention, the court said

Supreme Court case

The Supreme Court judgment dealt with a wide range of issues relating to deprivation of liberty and consent to medical treatment.

AC was an older woman who was admitted to Cork University Hospital (CUH) for medical treatment in 2016. AC was treated for her injury and was deemed fit for discharge, but was prevented from leaving CUH on two occasions in 2016. After her treatment, members of her family wanted to remove AC from the hospital, but members of staff were concerned that adequate arrangements had not been made for her care, post-discharge, and the hospital prevented her from leaving.

There followed lengthy, complex legal actions, which resulted in AC being made a ward of court on the application of CUH and eventually being accommodated permanently in a nursing home.

The Supreme Court identified two questions to be addressed in the treatment of AC. These were whether AC was deprived of her liberty and, if she was, whether it was in accordance with law.

The court concluded, in relation to the first question, that the measures taken by CUH involved restraint and she was kept in hospital for an indefinite period under the control of those caring for her.

It considered whether this finding was altered if AC did not have capacity. The court stated that the Constitutional right to liberty protects people with a mental impairment in the same manner as everyone else and that deprivation of liberty must in all cases be in accordance with law. The court went on to state that if benevolent intentions meant that there was no deprivation of liberty, and therefore no grounds for inquiry into the legality of deprivation of liberty, there would be no legal basis upon which the courts could ask whether the measures taken were justified and were in fact in the individual’s best interests. This would leave vulnerable people without legal protection against arbitrary or unnecessary detention. The persons or institution that takes charge of them would thereby appoint themselves as a substitute decision-maker without legal process. It concluded that neither the European Convention on Human Rights nor the Constitution permit this.

The court said that it must be clearly understood that the hospital has no overriding legal right to appoint itself as a substitute decision-maker for the patient, no legal power to decide how the right to liberty is to be balanced against the other rights and general welfare of the patient, and no general power to detain. It does, however, have the legal power to take such measures as can be justified under the doctrine of necessity.

Public consultation on deprivation of liberty

The need for legislative clarity on deprivation of liberty safeguards for people with capacity issues had been recognised with the publication of a consultation paper and draft Heads of a Bill by the Department of Health in 2017.

The consultation paper stated that deprivation of liberty safeguards were needed to meet the obligations of the United Nations Convention on the Rights of Persons with Disabilities. Ireland ratified the Convention in 2018.

According to the consultation paper, the central issue to be addressed is that existing legislation, including the ADMA, does not provide a procedure for admitting persons without capacity to relevant facilities and does not provide procedural safeguards to ensure that such persons are not unlawfully deprived of their liberty.

A report on the public consultation was published by the Department of Health in 2019.

The proposals in the consultation were intended to apply to residential centres for persons with disabilities, nursing homes, and some mental health facilities.

The case of AC v CUH raises questions about the position

of persons who lack capacity who may be detained in hospitals, along with consent to medical treatment.

A spokesperson for the Minister for Health told MI that work on legislation for deprivation of liberty safeguards was paused in 2020 due to the Covid-19 pandemic.

“This work resumed during 2022 and the development of policy and legislative proposals is under active consideration,” said the spokesperson.

Pre-legislative scrutiny of the 2022 Bill Pre-legislative scrutiny of the Assisted Decision-Making (Capacity) (Amendment) Bill 2022 by the JOC took place during the first quarter of 2022. The report of the committee was finalised on 5 April 2022.

The HSE assisted decision-making implementation steering group, with support from the HSE national office for human rights and equality, made the submission to the JOC on behalf of the Executive.

The submission stated that the absence of a statutory scheme on deprivation of liberty is a significant concern.

“In the absence of such a scheme we are very concerned that the provisions of s.38(2) will become a de-facto scheme on deprivation of liberty without the appropriate legal safeguards and protection mechanisms. We are concerned that there is a potential for use of s.38(2) to authorise – and, for many people currently in residential care facilities, to regularise – deprivation of liberty of individuals,” said the HSE.

DOLS created a legislative gap.

There are currently many persons with disabilities living in nursing homes, other residential facilities, and houses in the community who are subject to some form of deprivation of liberty. At present, the only way these arrangements can be lawfully authorised, reviewed, and scrutinised is through the wardship procedure.

In its submission, the Bar of Ireland said that when the sections of the ADMA dealing with deprivation of liberty are brought into operation, this will remove the legal basis for regulating restrictions on liberty of a large cohort of people.

The Bar of Ireland said it is concerned that this will bring about a legal vacuum where extremely vulnerable people will either be unlawfully deprived of their liberty or released from detention orders, which are a necessary element of their care and treatment.

The Bar of Ireland maintained that the absence of DOLS will place that cohort of people at significant risk of harm.

The Bar of Ireland pointed out that the Supreme Court and the European Court of Human Rights have made it clear that, in the absence of safeguards, many of the living arrangements for persons with disabilities who are detained or have restrictions placed on them are not lawful.

Government response

MI put these criticisms to Minister O’Gorman and sought his response.

A spokesperson for the Executive told MI that in relation to the concerns of the HSE in respect of section 38(2) of the 2015 Act, and to clarify the proper vehicle for applications to the courts where detention may be linked to treatment or care, the Minister moved an amendment to the 2022 Bill at report stage in the Dáil.

The amendment adds a new subsection (5) to section 4 stating that “nothing in this Act shall affect the inherent jurisdiction of the High Court to make orders for the care, treatment or detention of persons who lack capacity”.

“This was introduced to the Bill to ensure that the High Court, which has competence with regard to the protection and vindication of constitutional rights, would consider any need for detention linked to care or treatment,” said the spokesperson.

[The concerns that related to the jurisdiction of the High Court were raised by the Bar of Ireland. The HSE did not raise any concerns about the jurisdiction of the High Court].

The submission goes on to say that section 38(2) allows a court to make an order “making the decision or decisions concerned on behalf of the relevant person where it is satisfied that the matter is urgent or that it is otherwise expedient for it to do so”.

“As we understand it, it is possible that this authority may be used to authorise the deprivation of liberty of individuals in the same way as the wardship jurisdiction is currently used to authorise the deprivation of liberty by order of the court,” said the HSE.

The HSE also expressed concerns relating to enduring powers of attorney. Section 59 of the 2015 Act allows for the appointment by a person of an attorney on whom they confer authority in relation to the “personal welfare” of the person. Personal welfare is defined in the 2015 Act as including whether or not the person should live in a designated centre. A designated centre means a residential facility for persons with disabilities and other dependent persons and nursing homes.

“This is particularly troubling,” said the HSE, as it could result in a deprivation of liberty contrary to the wishes of the person. The Executive said there is a lack of oversight and the enduring power of attorney may take effect by simply notifying the Director of the DSS.

The HSE said that the fact that a person might be deprived of their liberty, despite there not necessarily being any contention or evidence that they lack capacity to make a specific decision regarding where they live, is “unacceptable and indefensible”.

The Bar of Ireland submission was also highly critical of the legislation. It said the abolition of the wardship procedure on commencement of the ADMA in the absence of

In relation to the criticisms by the Bar of Ireland, the Minister’s spokesperson told MI that he moved additional amendments to the Bill to strengthen the provisions regarding the review of detention arrangements in part 10 (sections 104-108) of the 2015 Act. The amendments add new subsections (3A) to sections 107 and 108 and provide for additional applications by a ward’s committee or legal representative where the ward is detained.

Speaking during committee stage in the Seanad on 6 October 2022, Minister O’Gorman said that the amendments ensure that appropriate detention review periods are in place. “This increased frequency of review proceedings will further protect the rights of relevant persons and bring provisions in line with those of the Mental Health Act 2001,” said the Minister.

The section of the 2015 Act complained of by the Bar of Ireland, section 108(2), has not been amended.

The HSE and the Bar of Ireland were asked for their views on these amendments.

A spokesperson for the HSE said that the HSE assisted decision-making implementation steering group is satisfied with the amendment made in respect of section 38(2).

The steering group was specifically concerned about the lack of clarity in the legislation regarding the limitations of the exercise of the authority of the Circuit Court under this section. The amendment clarifies that, following the abolition of wardship, the High Court will be the court that considers matters relating to deprivation of liberty.

A spokesperson for the Bar of Ireland told MI that the submission was prepared in response to draft legislation at a particular stage in the legislative process, which has now passed.

“We haven’t formed a view on the further proposed amendments, although it’s something we will keep under consideration,” said the spokesperson.

In the absence of such a scheme we are very concerned that the provisions of s.38(2) will become a de-facto scheme on deprivation of liberty without the appropriate legal safeguards…

Pippo: Transforming the future of GP-patient services

The new patient-focused app from Clanwilliam will support the digital transformation plans of general practices across Ireland

Over the last two years, we have witnessed the growing importance of digital technologies to our health services. During this time, it has become increasingly clear why we need to harness these technologies to make those same services more agile, flexible and responsive, for the benefit of both healthcare professionals and their patients.

While before the pandemic, digital maturity may have been considered a ‘nice to have’ for health services, its necessity for health service providers is now widely understood, with an expectation from patients around ease and efficiency of use that arguably did not exist before Covid-19.

Digital transformation journey

At Clanwilliam, we’ve been pioneering the use of technology in health for over a quarter of a century. Our founding objective, some 25 years ago, was to improve connectivity, efficiency and transparency in healthcare settings. From technology for nursing homes to revenue cycle management software for hospitals, technology has played a major role in helping us to achieve that goal ever since.

When Covid-19 emerged, thankfully we were able to pivot many of the functionalities and systems we’d been developing to adapt to the needs of this unprecedented health crisis. To support our healthcare frontline workers, we rose to this challenge by accelerating our development roadmap and prioritising new functionality that would help our users to fight the pandemic for us all.

From e-prescriptions to e-referrals and video consultations, we innovated at speed to ensure that our customers were equipped with the solutions they required to deliver to meet patient needs during those challenging times. The end result was that in a very short period, millions of people came to realise the true value of healthcare technology, and our software and services in particular.

The task now is to keep this momentum going by building sustainable, trusted services that facilitate doctor-patient interactions in a simple, effective, and reliable way.

Pippo – a patient-focused app

That’s why we’re delighted to launch the pilot of our latest innovation this month – Pippo. Our new patient portal app, Pippo will enable the digital transformation plans of GPs across Ireland, helping to make dayto-day interactions with their patients as seamless and straightforward as possible.

Free to use, the app will allow patients to book, cancel, reschedule and pay for their appointment online. Pippo will also enable them to meet their GP remotely via video consultation, helping to make health checkups more efficient and save valuable time. Meanwhile, for practices, the app will free up valuable resources by reducing the number of inbound calls, as well as the time it takes to receive payment directly from a patient.

The portal is also designed to fully integrate with GPs’ existing practice management systems (Socrates and Helix Practice Management) to eliminate double entry or double diary management and is fully GDPR compliant. And, built using security and privacy by design, Pippo will give patients and practitioners peace of mind at all times that their data is safe and secure.

Accelerating the pace of digital transformation

At Clanwilliam, we will continue to develop the range of functionalities offered by Pippo in the coming months. This will include the addition of repeat prescription ordering and patients’ electronic health records — all of which will be available directly within the app.

As noted by HIQA, patient summaries or electronic health records are vital for creating a truly joined-up healthcare service. From ensuring the safe and effective treatment of a patient receiving unscheduled care to supporting information sharing, the potential benefits are substantial. After 10 years of development, we’re excited that Clanwilliam will soon be in a place where it can provide this shift in service to healthcare practitioners and patients through the power of technology.

Game-changer

As the first app of its kind to be launched in Ireland, we believe that Pippo will be a game-changer when it comes to transforming the future of GP-patient services.

Ever wanted to make a GP appointment but haven’t had the time or privacy to make a phone call? Ever been put on hold or not been able to get through? Or maybe you’ve forgotten your wallet at the doctor’s office? Pippo will cover patients for all of these eventualities, helping to make GP appointments quicker, easier and more convenient.

Critically, Pippo will also support wider efforts by Government to accelerate digital transformation across our health services. As a long-standing partner to the HSE in the implementation of its Stay Left, Shift Left – 10X strategy, we want to empower the type of innovations and improvements that will allow us all to benefit from doing healthcare 10X better, faster, cheaper and at increased capacity.

With its focus on seamless, secure and efficient patient-GP interactions, as well as the promise of future exciting innovations, through the launch of Pippo, we want to help to make this ambition a reality, while moving one step closer to realising our own vision of a fully connected healthcare system for all.

Pippo can only be used currently by registered patients of practices using the app. Pippo will be made freely available to all Socrates and Helix Practice Manager users in Ireland in early 2023.

To learn more about Pippo, visit: www.pippo.ie

Free to use, the app will allow patients to book, cancel, reschedule and pay for their appointment online

PAUL MULHOLLAND

The HSE finally opened the National Forensic Mental Health Service (NFMHS) in Portrane, Co Dublin at the beginning of the month. It is the only centre in the Republic to provide specialist forensic psychiatric treatment for acute and medium-to-longer-term psychiatric care.

The relocation of the Central Mental Hospital (CMH) in Dundrum to this new state-of-the art, purpose-built facility is a significant step in the development of mental health services in this country.

However, the opening of the new facility has been a long time in coming, having suffered numerous delays, the most recent of which was due to an industrial relations dispute with the Psychiatric Nurses Association.

It is Ireland’s largest capital project and cost in the region of €200 million. This was higher than the original budget and it is another example of the difficulty in keeping the cost of healthcare infrastructural projects from spiralling.

The new facility will provide care for 130 patients and has the capacity to care for 170 patients on campus when fully operational, as well as providing community and prison in-reach services. The hospital also has a forensic child and adolescent mental health service and an intensive care rehabilitation unit (ICRU) on site.

The design concept for the new facility is to support the underlying roles of therapeutic care and security with dignity, embodying the best principles of high secure mental healthcare design. A total of 130 single-patient bedrooms are laid out in small wards around shared indoor and outdoor spaces, in which collective activities and therapies take place.

The final report of the high-level taskforce to consider the mental health and addiction challenges of those who come into contact with the criminal justice sector, which was published in September, welcomed the imminent opening of the new facility. The report stated that the Portrane facility “will greatly assist in alleviating the existing bed capacity pressures on the system”. It also stated the Portrane model of care is the appropriate clinical pathway to manage patients following their admission to the CMH.

However, the report noted there will continue to be capacity issues despite the new building.

“Under different scenarios, in males, bed capacity will be exceeded in 2023 if the current pattern of admissions from prison, approved centres, and as a result of NGRI [not guilty by reason of insanity] is maintained,” according to the report.

“This trend will continue up to 2026 and result in increasing waiting lists for CMH admission.”

It recommended the development of an additional facility for patients who require a long-term, medium secure setting. Planning for this facility should commence at the “earliest opportunity” in order to meet the male bed capacity requirements for the new NFMHS in Portrane.

The report also stated the need for “egress solutions” to ensure that the NFMHS bed capacity is optimised and “throughput of patients can be achieved”. In this regard, it was recommended that further ICRUs are planned.

The new facility is a positive step, but more work is required to improve specialist forensic psychiatric services, which have been allowed to languish for too long.

MINDO CARTOON

READER COMMENTS

REACTION TO DR LUCIA GANNON'S COLUMN, 'LESSONS FROM WIMIN', 7 NOVEMBER

“Thank you @LuciaGannon for this wonderful reflection on #WiMINLimerick22, a day filled with energy and positivity, as well as some uncomfortable truths. ‘Women are still facing significant challenges in the workplace. The first step towards changing this is awareness'." WiMIN, @WomenMedIreland, 5 November

“I was at this lovely event. Absolutely heartened by the amazing women there." Dr Marie Casey, @marietcasey, 5 November

“@LuciaGannon captures the uplifting atmosphere at @WomenMedIreland conference last month. Challenges remain, but the will to tackle them is now everywhere." Dr Lisa McNamee, @lisa_mcnamee, 5 November

REACTION TO OUR IES CONFERENCE PREVIEW, 'ENDOCRINOLOGISTS LOOK FORWARD TO MAJOR ANNUAL GATHERING', 7 NOVEMBER

“The Medical Independent speaks to local organiser of the Irish Endocrine Society’s upcoming annual meeting, Dr Matthew Murphy, about the event and the high quality of research in endocrinology being undertaken in #Ireland. #IES2022." Irish Endocrine Society, @IrishEndocrine, 5 November

REACTION TO OUR NEWS FEATURE, 'NEW CLINICAL EDUCATION AND TRAINING MODEL GETS ROLLING', 7 NOVEMBER

“Our director Prof Brian Kinirons in the latest @med_indonews." NDTP, @NDTP_HSE, 4 November

REACTION TO DR MICHAEL CONROY'S COLUMN, 'WHAT NEXT FOR NCHDS?', 27 OCTOBER

“Completely agree with this. Doctors going on strike or anyone else in the healthcare services is certainly morally dubious. However, with 48 per cent of doctors still working over the 24hr shift and 48hr/weeks, patients are going to suffer adverse incidents and doctors face litigation and censure."

Florence Horsman Hogan, @Florencehhogan2, 3 November

REACTION TO OUR RCPI ST LUKE'S SYMPOSIUM COVERAGE, 'THE TIME FOR INTEGRATED CARE HAS COME', 27 OCTOBER

“A major theme in #MentalHealth #integratedcare #nobarriers #accessible #ANP #NP #RANP." @MHANPI (Mental Health ANP Ireland), @MHANPIreland, 27 October

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Portrane facility should be beginning, not end, of forensic mental health reform

PRESCRIBING INFORMATION (PI)

SKYRIZI®▼ (risankizumab) 75 mg solution for injection in pre-filled syringe; Skyrizi 150 mg solution for injection in pre-filled pen and Skyrizi 150 mg solution for injection in prefilled syringe. Refer to Summary of Product Characteristics (SmPC) for full information before prescribing. PRESENTATION: Skyrizi 150 mg solution for injection in pre-filled pen/syringe: each prefilled pen/syringe contains 150 mg risankizumab in 1 mL solution. Skyrizi 75 mg solution for injection in pre-filled syringe: each pre-filled syringe contains 75 mg risankizumab in 0.83 ml mL solution. INDICATION: For treatment of moderate to severe plaque psoriasis in adults 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 psoriasis. Dosage: The recommended dose of Skyrizi is 150 mg by subcutaneous injection at weeks 0, 4, and every 12 weeks thereafter. Two 75mg pre-filled syringes should be injected for the full 150 mg dose. Consider discontinuation of treatment in patients showing no response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. Special Populations: Elderly: No dose adjustment required. Renal or hepatic impairment: No dose adjustment required. Paediatric Population: No data available. Overweight patients: No dose adjustment required. CONTRAINDICATIONS: Hypersensitivity to any of the active substances or excipients. Clinically important active infections (e.g. active tuberculosis). SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Skyrizi may increase the risk of infections. In patients with a chronic infection or history of recurrent infections, or known risk factors for infection, Skyrizi should be used with caution. Treatment with Skyrizi should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. Patients should be evaluated for tuberculosis infection prior to initiating treatment. Anti-TB therapy should be considered prior to initiating Skyrizi in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Completion of all appropriate immunisations should be considered prior to initiating therapy. If a patient has received live vaccination (viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment with Skyrizi. Patients treated with Skyrizi should not receive live vaccines during treatment and for at least 21 weeks after treatment. If a serious hypersensivity reaction occurs, administration of Skyrizi should be discontinued immediately and appropriate therapy initiated. Excipients with known effect (75 mg solution for injection only): Skyrizi contains 68.0 mg sorbitol and less than 1 mmol sodium (23 mg) per 150 mg dose. INTERACTIONS: The safety and efficacy of Skyrizi in combination with immunosuppressants, including

Defined as 75% achievement of PASI90 at Week 16 and ≥50% achievement of PASI 100 at Week 52 in UltIMMa-1 and UltIMMa-2.1

biologics or phototherapy have not been evaluated. PREGNANCY AND LACTATION: Women of Childbearing potential: An effective method of contraception during treatment and for at least 21 weeks after treatment should be used. Pregnancy: Limited data available. It is preferable to avoid the use of Skyrizi during pregnancy as a precautionary measure. Lactation: It is not known whether Skyrizi is excreted in breast milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A decision should be made whether to discontinue/abstain from Skyrizi therapy, taking into account the benefit of breastfeeding to the child and the benefit of Skyrizi therapy to the woman. Fertility: The effect of Skyrizi on human fertility has not been evaluated. ADVERSE REACTIONS: See SmPC for full details on adverse reactions. Very common adverse reactions (≥1/10): Upper respiratory infections. Common adverse reactions (≥1/100 to <1/10): Tinea infections, headache, pruritus, fatigue and injection site reactions.

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

LEGAL CLASSIFICATION: POM (S1A). MARKETING AUTHORISATION NUMBERS/PRESENTATIONS:

Skyrizi 75 mg solution for injection in pre-filled syringe (Pack of 2 pre-filled syringes): EU/1/19/1361/001; Skyrizi 150 mg solution for injection in pre-filled pen: EU/1/19/1361/002; Skyrizi 150 mg solution for injection in pre-filled syringe: EU/1/19/1361/003. Not all presentations may be marketed. Further information is available from: AbbVie Ltd., 14 Riverwalk, Citywest Business Campus, Dublin 24. DATE OF REVISION: May 2021 PI/1361/003

HRQoL, Health-Related Quality of Life; PASI, Psoriasis Area Severity Index.

REFERENCES: 1. Gordon KB, et al. Lancet 2018; 392: 650-661. 2. Ryan C et al. Poster presented at the 27th European Academy of Dermatology & Venerology (EADV) Congress 2018; September 12–16; Paris, France.

Skyrizi® Summary of Product Characteristics, available on www.medicines.ie.

Date of preparation: August 2021 | IE-RISN-210075

When it comes to your patients’ psoriasis treatment goals

Giving patients weight advice

Ms Sinead Lay, Case Manager at Medical Protection, offers advice on conversations around a patient’s weight and suggests why it is likely to become more commonplace in future

The World Health Organisation (WHO) reports that worldwide obesity has nearly tripled since 1975. According to an Irish Times article based on a new WHO report, Ireland ranks ninth of 53 European countries for obesity in adults and eleventh for overweight and obesity. Children between five and nine years old rank ninth for overweight and obesity, while 10-to-19 year-olds rank 10th. It may be alarming to know that most of the world’s population live in countries where being overweight and obesity kills more people than being underweight or malnourished.

At the forefront of the obesity epidemic, obesity bias and stigma (also known as ‘fat shaming’) is an under-recognised and widely prevalent barrier to optimal care of patients living with obesity.

What

is weight bias?

Internalised weight bias means holding negative beliefs about oneself due to weight or size. These internalised negative self-beliefs can be bolstered by external influences such as other people’s negative attitudes towards, and beliefs about, a person because of their weight. These negative attitudes may be manifested by stereotypes and/or prejudice towards people who are overweight. Medical professionals are not always an exception to this. Patients who are overweight or obese can find using the healthcare system daunting. Patients who feel they are experiencing obesity bias from healthcare professionals may cancel or delay appointments as well as avoid preventative healthcare and screenings. Sometimes doctors can be guilty of holding negative attitudes, both explicit and implicit, about patients with excess weight. This weight bias could potentially lead to delays in care and other downstream health consequences as seen in the following case study.

Case study

Mr Z, a patient living with obesity, twisted his right ankle whilst out for a walk one evening through a muddy field. Mr Z attended his GP, Dr F, who examined him and advised he had a soft tissue injury.

Mr Z’s symptoms worsened over the next two weeks and he returned to Dr F, who advised Mr Z that the strain he suffered whilst out walking and the pain associated with it were greatly exacerbated by his obesity. Dr F weighed Mr Z and advised that he needed to lose a significant amount of weight and this would alleviate the pain he was experiencing.

A month later, Mr Z’s worsening pain led him to, the emergency department in his local hospital. An x-ray of his ankle revealed a displaced posterior malleolus fracture, which required surgical treatment.

Mr Z and his wife filed a complaint against Dr F with the Medical Council. The preliminary proceedings committee (PPC)

looked into the complaint on the grounds of poor professional performance. Following the PPC’s investigation, it made the decision that no further action be taken. However, the months taken to investigate the complaint had been incredibly stressful for Dr F and the matter was not resolved.

The patient went on to pursue a medical negligence claim against Dr F, alleging that failure to diagnose the ankle fracture had led to a delay in surgical treatment and unnecessary pain and suffering. It was also alleged that Mr Z had experienced psychological distress as a result of Dr F attributing his symptoms solely to his weight.

An expert witness report, provided for Mr Z, concluded that Dr F had breached his duty to his patient by failing to refer him for an x-ray when his symptoms did not settle within a reasonable timeframe. Had the patient been referred for an x-ray sooner, the fracture would have been diagnosed and possibly would have been displaced, which may have meant that surgery could have been avoided. The case was settled for an undisclosed sum.

Avoiding weight bias

Approaching the subject of weight with someone can be challenging in everyday life, let alone in a healthcare setting. Asking for permission from a patient to discuss their weight is always a good start. Psychologically speaking, this makes patients feel more in control of the conversation and its direction from the offset. Questions such as “Could we talk about your weight today?” or “How do you feel about your weight?” are always good conversational starting points when discussing weight.

If the patient declines to discuss their weight, doctors should respect that decision. The conversation could end by letting the patient know that you are available to discuss the issue whenever they feel

the time is right for them.

When discussing the topic of weight with patients, it is important for doctors to choose their words wisely and steer away from any language that places blame. Stigmatising or blaming words, such as ‘fat’, ‘morbidly obese’, and ‘chubby’ should be replaced with words such as ‘weight’, ‘unhealthy weight’, and ‘high BMI’. Adopting a people-first language – by not labelling a patient by their health condition – can be beneficial, especially when it comes to weight concerns. It would be better to identify a patient as having obesity rather than an ‘obese patient’.

Practical strategies for healthcare professionals when managing patients with obesity:

▶ Recognise the complex causes of obesity and communicate this to colleagues and patients, thus dispelling the stereotype that obesity is solely attributable to personal willpower or lack thereof.

▶ Although weight may be contributing to a patient’s symptoms, do not rule out other causes. Ensure that when they are presenting with symptoms, they are afforded proper and adequate assessment and/ or specialist referral to rule-out all causes of presenting problems.

▶ Be mindful that patients may have had negative experiences with other health professionals regarding their weight, and approach patients with sensitivity.

▶ Recognise that many patients have unsuccessfully tried to lose weight repeatedly.

▶ Discuss holistic approaches to weight loss with the patient, including behavioural and lifestyle adjustments, ensuring to not focus solely on the number on the scale. Emphasise to patients that even small weight losses can result in significant health gains.

▶ Offer practical suggestions such as advising the patient to take up an exercise programme or eat at home, rather than

simply saying, “You need to lose weight.”

▶ Acknowledge the difficulty that patients living with obesity may have with adopting new lifestyle changes.

▶ First impressions count so consider creating a supportive healthcare environment from the offset. Implementing large, armless chairs in waiting rooms, appropriately-sized medical equipment and patient gowns, and friendly patient reading material in the waiting area may be helpful in reducing patient anxiety prior to a consultation.

▶ Researching reputable patient advocacy groups within your local community or nationwide, and encouraging patients to engage in such support groups is another way to ensure a patient leaves a consultation feeling informed and supported.

The European Coalition for People living with Obesity (ECPO) helps the European scientific and clinical community better understand the patient experience. The group regularly holds online workshops for patients and clinicians alike, encouraging open and frank conversations around the topic of obesity bias and stigma in healthcare settings.

A very useful online tool healthcare professionals may consider using to assist in overcoming obesity bias is The Rudd Centre’s eight-module toolkit self-assessment course. The toolkit offers easy-to-implement solutions and resources to improve delivery of care for patients who are overweight or obese. The resources include ways to improve doctor-patient communication, ways to make positive changes in the clinical environment, and self-examination of personal biases.

Fighting obesity bias as clinicians

Healthcare professionals can make a huge difference with the obesity epidemic by initially striving to overcome any personal obesity bias and discrimination they may hold within themselves. They can also lead the way by addressing obesity bias in their interactions with their patients. By becoming knowledgeable about evidence-based obesity care, they can make a big difference to the way patients manage their own health.

The education of current and future healthcare professionals should focus on raising awareness of attitudes and bias toward obesity as well as addressing the development of empathy for the struggle of patients who are living with obesity. Doctors should be mindful of the fact that most individuals with excess weight are very much aware of their weight and will have tried repeatedly to lose weight, and many of these individuals may have had previous negative experiences regarding their weight. Creating a supportive environment will help patients living with obesity feel comfortable when seeking medical care, and it could encourage patients to take on effective and tailored weight management.

When a DPP-4 inhibitor is needed

Simplicity. Reinforced .

for a BROAD RANGE of adults with type 2 diabetes (T2D)

UNIQUE CONVENIENCE through always one dose, once daily 1 5mg once daily

Demonstrated CV AND KIDNEY SAFETY PROFILE 2,3

PROVEN EFFICACY VS PLACEBO

for adults with T2D 1,4

References:

1. TRAJENTA® (linagliptin) Summary of Product Characteristics. SmPC available at: https://www.medicines.ie/

2. Rosenstock J, et al. JAMA. 2019;321:69–79

3. Rosenstock J, et al. Cardiovasc Diabetol. 2018;17:39

4. McGill JB, et al. Diabetes Care. 2013;36:237–44

Prescribing Information (Ireland) TRAJENTA® (Linagliptin)

Film-coated tablets containing 5 mg linagliptin. Indication: Trajenta is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control as: monotherapy when metformin is inappropriate due to intolerance, or contraindicated due to renal impairment; combination therapy in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. Dose and Administration: 5 mg once daily. If added to metformin, the dose of metformin should be maintained and linagliptin administered concomitantly. When used in combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin, may be considered to reduce the risk of hypoglycaemia. Renal impairment: no dose adjustment required. Hepatic impairment: pharmacokinetic studies suggest that no dose adjustment is required for patients with hepatic impairment but clinical experience in such patients is lacking.

Elderly: no dose adjustment is necessary based on age. Paediatric population: the safety and ef cacy of linagliptin in children and adolescents has not yet been established. No data are available. The tablets can be taken with or without a meal at any time of the day. If a dose is missed, it should be taken as soon as possible but a double dose should not be taken on the same day.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and Precautions: Linagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Hypoglycaemia: Caution is advised when linagliptin is used in combination with a sulphonylurea and/or insulin; a dose reduction of the sulphonylurea or insulin may be considered. Acute pancreatitis: Acute pancreatitis has been observed in patients taking linagliptin. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, Trajenta should be discontinued. If acute pancreatitis is con rmed, Trajenta should not be restarted. Caution

should be exercised in patients with a history of pancreatitis. Bullous pemphigoid: Bullous pemphigoid has been observed in patients taking Linagliptin. If bullous pemphigoid is suspected, Trajenta should be discontinued. Interactions: Linagliptin is a weak competitive and a weak to moderate mechanism-based inhibitor of CYP isozyme CYP3A4, but does not inhibit other CYP isozymes. It is not an inducer of CYP isozymes. Linagliptin is a P-glycoprotein substrate and inhibits P-glycoprotein mediated transport of digoxin with low potency. Based on these results and in vivo interaction studies, linagliptin is considered unlikely to cause interactions with other P-glycoprotein substrates. Effects of other medicinal products on linagliptin: The risk for clinically meaningful interactions by other medicinal products on linagliptin is low. Rifampicin: Multiple co-administration of 5 mg linagliptin with rifampicin, a potent inductor of P-glycoprotein and CYP3A4, decreased linagliptin steady state AUC and Cmax. Thus, full ef cacy of linagliptin in combination with strong P-glycoprotein inducers might not be achieved, particularly if administered long term. Coadministration with other potent inducers of P-glycoprotein and CYP3A4, such as carbamazepine, phenobarbital and phenytoin has not been studied. Effects of linagliptin on other medicinal products: In clinical studies linagliptin had no clinically relevant effect on the pharmacokinetics of metformin, glibenclamide, simvastatin, warfarin, digoxin or oral contraceptives (please refer to Summary of Product Characteristics for a full list of interactions and clinical data). Fertility, pregnancy and lactation: The use of linagliptin has not been studied in pregnant women. As a precautionary measure, avoid use during pregnancy. A risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from linagliptin therapy taking into account the bene t of breastfeeding for the child and the bene t of therapy for the woman.

No studies on the effect on human fertility have been conducted

for linagliptin. Undesirable effects: Adverse reactions reported in patients who received linagliptin 5 mg daily as monotherapy or as add-on therapies in clinical trials and from post-marketing experience. Frequencies are de ned as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) or very rare (<1/10,000). Adverse reactions with linagliptin 5 mg daily as monotherapy: Common: lipase increased. Uncommon: nasopharyngitis; hypersensitivity; cough; rash; amylase increased. Rare: pancreatitis; angioedema; urticaria; bullous pemphigoid. Adverse reaction with linagliptin in combination with metformin plus sulphonylurea: Very common: hypoglycaemia. Adverse reaction with linagliptin in combination with insulin: Uncommon: constipation. Prescribers should consult the Summary of Product Characteristics for further information on side effects. Pack sizes: 28 tablets. Legal category: POM. MA number: EU/1/11/707/003. Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, D-55216 Ingelheim am Rhein, Germany. Prescribers should consult the Summary of Product Characteristics for full prescribing information. Additional information is available on request from Boehringer Ingelheim Ireland Ltd, The Crescent Building, Northwood, Santry, Dublin 9. Prepared in September 2021.

Adverse events should be reported. Reporting forms and information can be found at https:// www.hpra.ie/homepage/about-us/report-an-issue. Adverse events should also be reported to Boehringer-Ingelheim Drug Safety on 01 2913960, Fax: +44 1344 742661, or by e-mail: PV_local_UK_Ireland@boehringer-ingelheim.com

Building a better mental health service

PROF BRENDAN KELLY

Read more by Prof Brendan Kelly at www.mindo.ie

October 10th was World Mental Health Day. One person in eight lives with a mental disorder, according to the World Health Organisation. Globally, anxiety and depression are the most common conditions, but only one-third of people with depression receive mental healthcare.

In Ireland, this year’s Budget increased funding for mental health by €58 million, but vastly more is needed – and not just more money. We need more trained mental health professionals, more reasons for them to stay and work in Ireland, and – yes – more resources for treatment: Expanded counselling in primary care, supported housing for people with acute crises and enduring illnesses, and enhanced specialist services for those who need them.

Mental health currently attracts a great deal of public discussion. Issues relating to psychological wellbeing, psychiatric diagnoses, and services are constantly in the public arena.

Covid-19 brought further focus and a serious reality-check. During the pandemic, one person in every five experienced symptoms of stress, anxiety, or depression that exceeded their usual coping mechanisms. This rose to two-in-five healthcare workers.

Today, many people struggle with long Covid and the losses of the pandemic: Loss of loved ones, loss of financial security, loss of a sense of safety in the world. A combination of informal support, counselling, and formal mental healthcare is needed.

While GPs, psychiatrists, and other mental health professionals do excellent work, our mental health service struggles with recruitment and retention. We have the third lowest number of inpatient psychiatry beds per 100,000 population in the EU. Public expectations are rightly high, but there is a mismatch between expectations and service provision.

In addition to enhancing resources over and above the additional €58 million in the Budget, four other issues require attention if we are to build a better mental health service.

First, we are all on a spectrum between mental health and mental illness, but we need to distinguish between problems of living and serious mental disorders, such as depression, bipolar disorder, and schizophrenia. Psychiatric services are at their best when we focus on treating mental illness rather than the emotional ups and downs of life. Conflating problems of living with mental disorders medicalises unhappiness, disempowers people, decreases understanding, and increases stigma. Everyone who suffers needs support, but not everyone who suffers is ill.

Second, we need to be more pragmatic about psychiatric treatments. Once they are used correctly, most common medications offer substantial benefits, although they are imperfect and never enough on their own. Psychological engagement and social support are vital. The keys lie in focusing on the individual person, being realistic about medication, emphasising community treatment, and ensuring that inpatient care is available when needed. A balance is required, delivered with humanity, holism, and hope. We are not just brains; we have souls, too.

Third, mental healthcare is a social endeavour. We suffer, heal, and help each other in families, communities, and societies. For people with problems of living, the best solutions are rooted in communities rather than psychiatric services. Formal psychological care is the next step for

services

more pressing issues. GPs and primary care teams are well positioned to assist, but require rapid access to low-threshold psychological programmes. The Counselling in Primary Care scheme needs to be expanded.

People with serious mental illness require specialist services in conjunction with social interventions. Homelessness and imprisonment make psychiatric care exceptionally difficult, although not impossible. Prison is toxic for people with mental illness. The opening of the new forensic hospital in Portrane is a step in the right direction.

Finally, we need to update our legislation. The Assisted Decision-Making (Capacity) Act 2015 is due to commence in the coming months. This development is around a century overdue, but better late than never. Last-minute amendments should ensure the legislation delivers benefits in practice and not just on paper. Further measures are needed to regulate deprivation of liberty in nursing homes. Revisions to the Mental Health Act 2001 should also be amended and expedited.

To make all of this happen, social and political activism is essential: To achieve better funding for services, more supported housing, a meaningful safety net for people who fall between the cracks, and reform of criminal law, court procedures, and prison policies.

To effect change, stakeholders can campaign for better services, advocate loudly, write to politicians, register to vote, and ensure that all public representatives and decision-makers promote the rights of people with mental illness and their families – the right to treatment as well as the right to liberty, with particular emphasis on social justice.

Prof Brendan Kelly is Professor of Psychiatry at Trinity College Dublin and author of In Search of Madness: A Psychiatrist’s Travels Through the History of Mental Illness (Gill Books).

A Machiavellian approach to capacity deficits?

The system, known as a continuous model of care or a proactive flow model, has undergone trials in the NHS

DR MUIRIS HOUSTON

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

@muirishouston

Over 10,679 people have been without a hospital bed in the month of October, according to the Irish Nurses and Midwives Organisation’s Trolleywatch figures. The union noted this was a more than 25 per cent increase on the same period last year and more than double the figures for October 2020.

More than 393 children under the age of 16 were on trolleys in the month of October, making it the worst month for paediatric overcrowding on record.

So what’s new, I hear you ask? In one sense, there is nothing new. After all, this year-on-year rise is inexorable and apparently beyond the ability of Department of Health and the HSE to resolve. Yes, the fact that children now face significant delays before securing a hospital bed is new for 2022. And there is now talk of introducing a new model of care, whereby patients are transferred from the emergency department into wards whether or not any empty beds are available.

The system, known as a continuous model of care or a proactive flow model, has undergone trials in some Trusts by NHS England. In Bristol, this sees one patient moved to acute admissions every hour and one to a frailty unit every two hours. It aims to reduce numbers of ambulances queu-

ing outside emergency departments (EDs) and to encourage wards to discharge and so reduce blockages in patient flow.

Prior to implementing the new model, the North Bristol NHS Trust had on average 14 ambulances queueing outside EDs for four hours each day, while its longest handover delays were nine hours – a situation that was causing the local ambulance provider to lose 139 hours a day. The Trust said that its average length of stay in EDs was 13 hours. However, after adopting the new model, the North Bristol Trust was able to reduce the number of ambulances queueing outside EDs, and reduce its longest delays to three hours, resulting in the average time patients spent in EDs dropping to 10 hours.

While there is no specific mention of a proactive flow programme in the HSE Winter Plan 2022/2023, it has been the subject of discussion at leadership level, and may well be rolled out as ED pressures rise to new heights in the months ahead.

Does it all sound a bit Machiavellian? I think so. It definitely sends a not-so-subtle message to inpatient ward staff that they are delaying patient discharges. And that if they don’t smarten up, they will be looking after a lot of additional patients.

My problem with this is that without additional physical beds on these wards and without a safe staff to patient ratio, what kind of care will people get? Will they be lying on blowup beds? Will they have to compete with other admitted patients for the attention of overstretched ward staff?

Proponents argue that spreading the risk across the patient pathway, rather than concentrating it in ED, reduces the risk. Unsurprisingly, some emergency medicine specialists are in

favour, saying that if you spread the risk across the whole patient pathway you dilute the risk.

But medical consultants aren’t so sure. UK Acute Medicine Consultant Nick Scriven, past President of the Society for Acute Medicine, told the British Medical Journal that better evidence was needed. “There is really no good evidence around any harm this could cause and no data beyond some presentations in the public domain on which to base decisions,” he said.

Both ED and acute medical consultants agree that a forced, blanket imposition of a continuous model of care would be a disaster. Robust evidence is needed before making a change of this scale.

The commentary from across the Irish Sea comes at a time when the hospital system there has reached 94 per cent occupancy levels, the highest ever recorded. Of course, we in the Republic have recorded occupancy levels of 100 per cent on a regular basis in recent years. Like us, the NHS struggles with ‘decanting’ patients from hospital. It has 12,000 patients ready for discharge, suggesting the crisis is as much about outgoing patients as it is about those trying to get in.

While some Dublin hospitals no longer appear in the league table of highest levels of overcrowding, three hospitals in the west and south feature regularly. In October, these were Cork University Hospital, University Hospital Limerick, and University Hospital Galway.

At this point it seems that a proposed continuous flow model would do little to solve the existential crisis facing the public health system in Ireland.

Mental health currently attracts a great deal of discussion, but more resources and work are required to improve

MULTIPLE CHOICE QUESTIONS

Question 1

With spirometry

A. During testing, the patient should stand up.

B. The patient should blow out as hard and as fast as possible, and keep blowing hard until he or she runs out of breath.

C. Beta2-agonist inhalers should not be used in the 12 hours prior to testing.

D. The forced expiratory ratio (FER) should normally be 50-to-70 per cent.

E. Reversibility in COPD can be assessed.

Question 2

Characteristic features of guttate psoriasis include

A. Affects children and young adults.

B. Gradual onset.

C. Lesions particularly affect the trunk and proximal parts of the limbs.

D. No scaling.

E. Spontaneous resolution within three-to-four weeks.

Question 3

After removing a foreign body from

A. You should use an antibiotic ointment.

B. Always pad the eye.

the eye

C. Send the patient to the emergency department for the eye to be checked with a slit lamp.

D. You should install fluorescein to check there is no corneal ulcer.

E. You should follow up all patients the next day.

Question 4

Characteristic features of childhood absence epilepsy ( petit mal ) include

A. Absences most likely to be in the evening.

B. Associated motor symptoms.

C. Child returns to completely normal awareness as soon as the episode ceases.

D. Blank spells each last about 30 seconds or so.

E. Less than 10 absences a day.

Question 5

The use of non-steroidal and anti-inflammatory drugs ( NSAID s) is relatively contraindicated in patients

A. With congestive cardiac failure.

B. With abnormal liver function.

C. Who are diabetic.

D. Who are older persons.

E. Who are on lithium therapy.

E. TRUE. NSAIDs can have serious interactions with lithium as well as anticoagulants and anticonvulsants.

D. TRUE. Or frail, as these patients have an increased risk of serious gastrointestinal sideeffects.

C. FALSE. This is not a contraindication.

B. TRUE. Or even mild renal insufficiency.

A. TRUE. NSAIDs can interact adversely with diuretics and hypertensive drugs.

ANSWER 5

E. FALSE. Parents usually report 10-to-20, but ECG monitoring shows most are missed and some children have over 100 in a day.

D. FALSE. Usually very brief, lasting only a few seconds (most no longer than 15 seconds).

C. TRUE. Unlike complex partial seizures, which are followed by a period of confusion.

B. TRUE. 90 per cent have some motor symptoms, such as small-range automatisms or low-amplitude rhythmic jerking.

ANSWER 4

E. FALSE. Not if there is minimal pain, the foreign body is small and easily removed, and vision is good.

D. FALSE. Do this as part of the examination if there is no obvious foreign body.

A. FALSE. Most likely soon after wakening.

A. TRUE. This should be used for the next 24 hours.

ANSWER 3

E. FALSE. Clears spontaneously within a few months.

D. FALSE. Lesions well defined with a silvery scale.

C. FALSE. You should refer the patient if you suspect an intraocular foreign body, but not if you have removed a nonpenetrating foreign body.

C. TRUE. Small, usually profuse lesions.

B. FALSE. Lesions appear suddenly.

A. TRUE. Often associated with a recent streptococcal URTI.

B. FALSE. Use a pad if near bedtime, if there was significant pain or if removal of the foreign body was difficult.

ANSWER 2

E. TRUE. By measuring response to bronchodilators.

D. FALSE. The FER, defined as the proportion of forced vital capacity (FVC) blown out in the first second of expiration, is normally 70 per cent or more.

C. FALSE. They should not be used within four hours prior to testing.

B. TRUE. With no pauses.

A. FALSE. The patient may sit or stand, but use the same approach each time with that patient.

ANSWER 1

Ireland and Northern Ireland Abbreviated Prescribing Information: XTANDITM (enzalutamide) 40 mg film-coated tablets. For full prescribing information, refer to the Summary of Product Characteristics (SPC). Presentation: 40 mg film-coated tablets each containing 40 mg of enzalutamide. Indications: The treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy. The treatment of adult men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC). The treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. The treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy. Posology and administration: Treatment with enzalutamide should be initiated and supervised by specialist physicians experienced in the medical treatment of prostate cancer. The recommended dose is 160 mg enzalutamide (four 40 mg film-coated tablets) as a single oral daily dose. The tablets should be swallowed whole with water, and can be taken with or without food. Medical castration with a luteinising hormone-releasing hormone (LHRH) analogue should be continued during treatment of patients not surgically castrated. If a patient experiences a ≥ Grade 3 toxicity or an intolerable adverse reaction, dosing should be withheld for one week or until symptoms improve to ≤ Grade 2, then resumed at the same or a reduced dose (120 mg or 80 mg) if warranted. Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SPC. Women who are or may become pregnant. Special warnings and precautions for use: Risk of seizure: Use of enzalutamide has been associated with seizure. The decision to continue treatment in patients who develop seizures should be taken case by case. Posterior reversible encephalopathy syndrome: There have been rare reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving XTANDI. PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of XTANDI in patients who develop PRES is recommended. Second Primary Malignancies: Cases of second primary malignancies have been reported in patients treated with enzalutamide in clinical studies. In phase 3 clinical studies, the most frequently reported events in enzalutamide treated patients, and greater than placebo, were bladder cancer (0.3%), adenocarcinoma of the colon (0.2%), transitional cell carcinoma (0.2%) and bladder transitional cell carcinoma (0.1%). Patients should be advised to promptly seek the attention of their physician if they notice signs of gastrointestinal bleeding, macroscopic haematuria, or other symptoms such as dysuria or urinary urgency develop during treatment with enzalutamide. Concomitant use with other medicinal products: Enzalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products. A review of concomitant medicinal products should therefore be conducted when initiating enzalutamide treatment.

Concomitant use of enzalutamide with medicinal products that are sensitive substrates of many metabolising enzymes or transporters should generally be avoided if their therapeutic effect is of large importance to the patient, and if dose adjustments cannot easily be performed based on monitoring of efficacy or plasma concentrations. Co-administration with warfarin and coumarin-like anticoagulants should be avoided. If XTANDI is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted. Renal impairment: Caution is required in patients with severe renal impairment as enzalutamide has not been studied in this patient population. Severe hepatic impairment: An increased half-life of enzalutamide has been observed in patients with severe hepatic impairment, possibly related to increased tissue distribution. The clinical relevance of this observation remains unknown. A prolonged time to reach steady state concentrations is however anticipated, and the time to maximum pharmacological effect as well as time for onset and decline of enzyme induction may be increased. Recent cardiovascular disease: The phase 3 studies excluded patients with recent myocardial infarction (in the past 6 months) or unstable angina (in the past 3 months), New York Heart Association Class (NYHA) III or IV heart failure except if Left Ventricular Ejection Fraction (LVEF) ≥ 45%, bradycardia or uncontrolled hypertension. This should be taken into account if XTANDI is prescribed in these patients. Androgen deprivation therapy may prolong the QT interval: In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating XTANDI. Use with chemotherapy: The safety and efficacy of concomitant use of XTANDI with cytotoxic chemotherapy has not been established. Co-administration of enzalutamide has no clinically relevant effect on the pharmacokinetics of intravenous docetaxel; however, an increase in the occurrence of docetaxel-induced neutropenia cannot be excluded. Hypersensitivity reactions: Hypersensitivity reactions manifested by symptoms including, but not limited to, rash, or face, tongue, lip, or pharyngeal oedema have been observed with enzalutamide. Severe cutaneous adverse reactions (SCARs) have been reported with enzalutamide. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions.

Excipients: This medicine contains less than 1 mmol sodium (less than 23 mg) per film-

References: 1. XTANDI Summary of Product Characteristics.

XTANDI™ is indicated for the treatment of adult men with metastatic castrationresistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgendeprivation therapy, in whom chemotherapy is not yet clinically indicated.1

XTANDI is also indicated for the treatment of adult men with metastatic castration – resistant prostate cancer whose disease has progressed on or after Docetaxel.1

coated tablet, that is to say essentially ‘sodium-free’. Interactions: Potential for other medicinal products to affect enzalutamide exposures: CYP2C8 plays an important role in the elimination of enzalutamide and in the formation of its active metabolite.

Strong inhibitors (e.g. gemfibrozil) of CYP2C8 are to be avoided or used with caution during enzalutamide treatment. If patients must be co-administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily. No dose adjustment is necessary when XTANDI is co-administered with inducers of CYP2C8. CYP3A4 plays a minor role in the metabolism of enzalutamide. No dose adjustment is necessary when XTANDI is co-administered with inhibitors or inducers of CYP3A4. Potential for enzalutamide to affect exposures to other medicinal products: Enzalutamide is a potent enzyme inducer and increases the synthesis of many enzymes and transporters; therefore, interaction with many common medicinal products that are substrates of enzymes or transporters is expected. Enzymes that may be induced include CYP3A in the liver and gut, CYP2B6, CYP2C9, CYP2C19, and uridine 5’-diphospho-glucuronosyltransferase (UGTs - glucuronide conjugating enzymes). Some transporters may also be induced, e.g. multidrug resistanceassociated protein 2 (MRP2) and the organic anion transporting polypeptide 1B1 (OATP1B1). In vivo studies have shown that enzalutamide is a strong inducer of CYP3A4 and a moderate inducer of CYP2C9 and CYP2C19. The full induction potential of enzalutamide may not occur until approximately 1 month after the start of treatment, when steady-state plasma concentrations of enzalutamide are reached, although some induction effects may be apparent earlier. Patients taking medicinal products that are substrates of CYP2B6, CYP3A4, CYP2C9, CYP2C19 or UGT1A1 should be evaluated for possible loss of pharmacological effects (or increase in effects in cases where active metabolites are formed) during the first month of enzalutamide treatment, and dose adjustment should be considered as appropriate. In consideration of the long half-life of enzalutamide (5.8 days), effects on enzymes may persist for one month or longer after stopping enzalutamide. A gradual dose reduction of the concomitant medicinal product may be necessary when stopping enzalutamide treatment. In vitro data indicate that enzalutamide may be an inhibitor of the efflux transporter P-gp. A mild inhibitory effect of enzalutamide, at steady-state, on P-gp was observed in a study in patients with prostate cancer that received a single oral dose of the probe P-gp substrate digoxin before and concomitantly with enzalutamide (concomitant administration followed at least 55 days of once daily dosing of 160 mg enzalutamide). The AUC and Cmax of digoxin increased by 33% and 17%, respectively. Medicinal products with a narrow therapeutic range that are substrates for P-gp (e.g. colchicine, dabigatran etexilate, digoxin) should be used with caution when administered concomitantly with XTANDI and may require dose adjustment to maintain optimal plasma concentrations. At steady state, enzalutamide did not cause a clinically meaningful change in exposure to the probe breast cancer resistance protein (BCRP) substrate rosuvastatin in patients with prostate cancer that received a single oral dose of rosuvastatin before and concomitantly with enzalutamide (concomitant administration followed at least 55 days of once daily dosing of 160 mg enzalutamide). The AUC of rosuvastatin decreased by 14% while Cmax increased by 6%. No dose adjustment is necessary when a BCRP substrate is co administered with XTANDI. Based on in vitro data, inhibition of MRP2 (in the intestine), as well as organic anion transporter 3 (OAT3) and organic cation transporter 1 (OCT1) (systemically) cannot be excluded. Theoretically, induction of these transporters is also possible, and the net effect is presently unknown. Since androgen deprivation treatment may prolong the QT interval, the concomitant use of XTANDI with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated. Fertility, pregnancy and lactation: There are no human data on the use of XTANDI in pregnancy and this medicinal product is not for use in women of childbearing potential. This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant. It is not known whether enzalutamide or its metabolites are present in semen. A condom is required during and for 3 months after treatment with enzalutamide if the patient is engaged in sexual activity with a pregnant woman. If the patient engages in sexual intercourse with a woman of childbearing potential a condom and another form of birth control must be used during and for 3 months after treatment. Enzalutamide is not for use in women. Enzalutamide is contraindicated in women who are, or who may become, pregnant. It is not known if enzalutamide is present in human milk. Enzalutamide and/or its metabolites are secreted in rat milk. Animal studies showed that enzalutamide affected the reproductive system in male rats and dogs. Effects on ability to drive and use machines: XTANDI may have a moderate influence on the ability to drive and use machines as psychiatric and neurologic events including seizure have been reported. Patients should be advised of the potential risk of experiencing a psychiatric or neurological event while driving or operating machines.

Undesirable effects: Summary of the safety profile: The most common adverse reactions are asthenia/fatigue, hot flush, hypertension, fractures, and fall. Other important adverse reactions include ischemic heart disease and seizure. Seizure occurred in 0.5% of enzalutamide-treated patients, 0.2% of placebo-treated patients, and 0.3% in bicalutamide-treated patients. Rare cases of posterior reversible encephalopathy syndrome have been reported in enzalutamide-treated patients. Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to <

1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Adverse reactions are presented according to Medical Dictionary for Regulatory Activities (MedDRA) system organ classification and within each frequency grouping they are presented in order of decreasing seriousness. Adverse reactions identified in controlled clinical trials and post-marketing: Blood and lymphatic system disorders:

Uncommon: leucopenia, neutropenia; Not known*: thrombocytopenia. Immune system disorders: Not known*: face oedema, tongue oedema, lip oedema, pharyngeal oedema Psychiatric disorders: Common: anxiety; Uncommon: visual hallucination. Nervous system disorders: Common: headache, memory impairment, amnesia, disturbance in attention, dysgeusia, restless legs syndrome; Uncommon: cognitive disorder, seizure ; Not known*: posterior reversible encephalopathy syndrome. Cardiac disorders: Common: ischemic heart disease†; Not known*: QT-prolongation. Vascular disorders: Very common: hot flush, hypertension. Gastrointestinal disorders: Not known*: nausea, vomiting, diarrhoea. Skin and subcutaneous tissue disorders: Common: dry skin, pruritus; Not known*: erythema multiforme, rash. Musculoskeletal and connective tissue disorders: Very common: fractures‡; Not known*: myalgia, muscle spasms, muscular weakness, back pain. Reproductive system and breast disorder: Common: gynaecomastia. General disorders and administration site conditions: Very common: asthenia, fatigue. Injury, poisoning and procedural complications: Very common: fall. * Spontaneous reports from post-marketing experience. As evaluated by narrow Standardised MedDRA Queries (SMQs) of ‘Convulsions’ including convulsion, grand mal convulsion, complex partial seizures, partial seizures and status epilepticus. This includes rare cases of seizure with complications leading to death. † As evaluated by narrow SMQs of ‘Myocardial Infarction’ and ‘Other Ischemic Heart Disease’ including the following preferred terms observed in at least two patients in randomized placebo-controlled phase 3 studies: angina pectoris, coronary artery disease, myocardial infarctions, acute myocardial infarction, acute coronary syndrome, angina unstable, myocardial ischaemia and arteriosclerosis coronary artery. ‡ Includes all preferred terms with the word ‘fracture’ in bones. Description of selected adverse reactions: Seizure: In controlled clinical studies, 24 patients (0.5%) experienced a seizure out of 4403 patients treated with a daily dose of 160 mg enzalutamide, whereas four patients (0.2%) receiving placebo and one patient (0.3%) receiving bicalutamide experienced a seizure. Dose appears to be an important predictor of the risk of seizure, as reflected by preclinical data, and data from a dose-escalation study. In the controlled clinical studies, patients with prior seizure or risk factors for seizure were excluded. In the 9785 CL 0403 (UPWARD) single-arm trial to assess incidence of seizure in patients with predisposing factors for seizure (whereof 1.6% had a history of seizures), 8 of 366 (2.2%) patients treated with enzalutamide experienced a seizure. The median duration of treatment was 9.3 months. The mechanism by which enzalutamide may lower the seizure threshold is not known but could be related to data from in vitro studies showing that enzalutamide and its active metabolite bind to and can inhibit the activity of the GABA-gated chloride channel. Ischemic Heart Disease: In randomized placebocontrolled clinical studies, ischemic heart disease occurred in 3.9% of patients treated with enzalutamide plus ADT compared to 1.5% patients treated with placebo plus ADT. Fifteen (0.4%) patients treated with enzalutamide and 2 (0.1%) patients treated with placebo had an ischemic heart disease event that led to death. Prescribers should consult the full SPC in relation to other adverse reactions. Overdose: There is no antidote for enzalutamide. In the event of an overdose, treatment with enzalutamide should be stopped and general supportive measures initiated taking into consideration the half-life of 5.8 days. Patients may be at increased risk of seizures following an overdose. Cost (excluding VAT): XTANDI 40 mg film-coated tablets x 112: Ireland: POA. Northern Ireland: £2,734.67. Legal classification: Ireland: POM/ S1A. Northern Ireland: POM. Marketing Authorisation number: XTANDI 40 mg filmcoated tablets: EU/1/13/846/002 Marketing Authorisation Holder: Astellas Pharma Europe B.V., Sylviusweg 62, 2333 BE Leiden, The Netherlands. Date of preparation of Prescribing Information: April 2022 Job number: XTD_2022_0079_IE Further information is available on request from: Ireland: Astellas Pharma Co. Ltd., 5 Waterside, Citywest Business Campus, Dublin 24. Tel.: +353 1 467 1555. Northern Ireland: Astellas Pharma Ltd, Medical Information 0800 783 5018. For full prescribing information, refer to the SPCs, which may be found at www.medicines.ie (Ireland) and https://www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

Adverse events should be reported. For Ireland, Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance, Website: www.hpra.ie or Astellas Pharma Co. Ltd. Tel: +353 1 467 1555, E-mail: irishdrugsafety@astellas.com

Adverse events should be reported. For Northern Ireland, reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Astellas Pharma Ltd on 0800 783 5018.

The hyperlinks on this page will take you to non-Astellas websites. Astellas does not endorse or accept liability for sites controlled by third-parties.

NCCP updates National Clinical Guideline for patients with prostate cancer

The National Cancer Control Programme (NCCP) recently launched an update to a module of the National Clinical Guideline – Diagnosis and Staging of Patients with Prostate Cancer, which was developed in collaboration with clinicians, patient representatives, and key stakeholders.

This evidence-based guideline replaces recommendations within the original guideline – Diagnosis, Staging and Treatment of Patients with Prostate Cancer (published in 2015).

The guideline is intended for all healthcare professionals involved in diagnosing, staging, and treating patients with prostate cancer. It is also relevant to those involved in clinical governance, in both primary and secondary care, to help ensure that arrangements are in place to deliver appropriate care for the population covered by this guideline. This guideline is also of interest to patients undergoing investigations for prostate cancer and their families and carers.

The guideline was co-chaired by Mr David Galvin, Consultant Urologist, Mater Hospital and St Vincent’s University Hospital, Dublin; and Dr Eve O’Toole, Head of the Evidence and Quality Hub, NCCP.

Speaking about the update, Dr O’Toole explains: “We have decided to take a phased approach to updating our National Clinical Guidelines to ensure they are based upon the latest evidence. This guideline integrates the best current research evidence with clinical expertise and patient values. It aims to reduce variation in practice and to improve the quality of care delivered to patients.”

According to Mr Galvin: “The updated guideline ensures a comprehensive review of current radiological and diagnostic strategies for patients with prostate cancer. It provides doctors and nurses with the necessary information to achieve excellence in care for these patients. The contributions from patients, nurses and a variety of medical specialists greatly enriched the process and the output from it. Over the last 10-to-15 years the diagnostic, staging and treatments in Ireland have evolved enormously and represent some of the latest advances in prostate cancer care.”  Clinical knowledge and judgment should be used in applying the principles and recommendations contained in this guideline.

The updated prostate cancer guideline, National Clinical Guideline – Diagnosis and Staging of Patients with Prostate Cancer, is available at: www.hse.ie/eng/services/list/5/ cancer/profinfo/guidelines/prostate/updated-diagnosis-and-staging-of-prostate-cancer-guideline.pdf

Burden of prostate cancer in Ireland

As shown by National Cancer Registry Ireland (NCRI) data, the average number of newly-diagnosed cases of prostate cancer in Ireland between 2017 and 2019 was 3,869 cases per year (NCRI, 2021). This represents 30 per cent

Staging

Biochemical recurrance:

• Following radical prostatectomy (two rising PSA levels above undetectable)

•Following radiotherapy (a PSA value of 2µg/L above the nadir after treatment)

of all invasive cancers for men (excluding non-melanoma skin cancer), making prostate cancer the most commonly-diagnosed invasive cancer in men in Ireland. Prostate cancer incidence in Ireland is currently the highest in Europe (GLOBOCAN, 2020).

The number of deaths from prostate cancer in Ireland was 554 per year, during the period 2016-2018. This represents 20.2 deaths per 100,000 population attributing to 12 per cent of male cancer deaths (NCRI, 2021). Prostate cancer is the joint second (with colorectal cancer) most common cause of cancer death among males.

Prostate cancer is, however, a very treatable disease, which is reflected in the increase in survival rates over the last number of decades. Five-year net survival has improved from 61 per cent from 1994-1999 to 94 per cent from 2014-2018 (NCRI, 2021), while 10-year survival is currently approximately 89 per cent. The increase in survival is most likely due to im-

provements in diagnosis and treatment.

Risk factors

Increasing age is the most important risk factor for prostate cancer. In Ireland, the majority of cases are detected in men aged 65to-74 years, with 41 per cent detected in men <65 years of age. Family history is associated with an increased risk of developing prostate cancer: Men with a father or a brother diagnosed with prostate cancer at age 50 years have an approximately two-fold increased risk of prostate cancer. Asian men are less likely to develop prostate cancer, whereas black men have the highest incidence of prostate cancer of any group (231.9 per 100,000). Obesity has been associated with higher-grade prostate cancers, possibly as a result of altered hormone levels

Treatment

Current management of prostate cancer in-

PSMA PET-CT or conventional imaging (isotope bone scan, CT

PSMA PET-CT if it will influence patient management or conventional imaging (isotope bone scan, CT and MRI)

volves a multidisciplinary approach, with input from primary care, radiology, pathology, urology, radiation oncology, and medical oncology. Management depends on the presentation of prostate cancer: Early/localised cancer, locally-advanced cancer, biochemical failure (rising PSA in the absence of metastatic disease), hormone-sensitive metastatic disease, and hormone-refractory metastatic disease.

Treatment options for patients with prostate cancer include active monitoring, radical prostatectomy, external beam radiotherapy and brachytherapy. Hormone therapy (androgen deprivation or anti-androgens) is the primary treatment for metastatic prostate cancer, but is also increasingly being used for patients with locally-advanced, non-metastatic disease. In patients with localised prostate cancer, the choice of treatment is guided by whether the disease is considered low-, intermediate-, or high-risk.

The National Cancer Control Programme recently published an updated version of the National Clinical Guideline (diagnosis and staging) for patients with prostate cancer

Figure 1: Diagnosis and staging algorithm for patients with suspected prostate cancer referred from a urologist (NCCP guideline)

PRISCILLA LYNCH priscilla@mindo.ie

Unsuitable candidate for mpMRI

PI-RADS 1 and 2 PI-RADS 3 PI-RADS 4 and 5

THERESA LOWRY-LEHNEN , RGN, PG Dip Coronary Care, RNP, BSc, MSc, PG Dip Ed (QTS), M Ed, PhD, Clinical Nurse Practitioner, and Associate Lecturer, South-East Technological University

Testicular cancer in focus

Testicular cancer is the most common cancer in men aged 15-to-45 years and represents one of the most curable malignancies

when identified promptly

Testicular cancer is a rare disease, representing 1 per cent of male cancers and 5 per cent of urological cancers worldwide.1 Its incidence has increased in the past few years, however, especially in Western and industrialised countries.

It is also the most common cancer found in young men aged between 15 and 34 years, and approximately 173 men are diagnosed with testicular cancer in Ireland each year.7

Mortality associated with testicular cancer is relatively low at approximately 0.1 per cent of all annual cancers, and cure rates are greater than 90 per cent for all stages, with over 95 per cent five-year survival rates.1,9

The rise of testicular cancer in Western and industrialised countries in recent years is possibly due to an increased exposure to aetiological factors. The highest incidence of testicular cancer is observed in Western and Northern Europe at 8.7 and 7.2 per 100,000 men, respectively.9

Testicular cancer includes several types of cancer such as germ cell tumours (GCT), sex cord-gonadal stromal tumours, and secondary testicular tumours. About 90-to-95 per cent of testicular tumours arise from germ cells to generate the GCT, followed by 5-to-10 per cent gonadal stromal tumours, mixed GCT and secondary tumours.2

Anatomy and physiology of the testes

The testes (male gonads) are located in a skin-covered, highly pigmented, muscular sack called the scrotum that extends from the body behind the penis. They produce both sperm and androgens such as testosterone and are active throughout the reproductive lifespan of the male. Paired ovals, the testes are approximately 4-to-5cm in length and are surrounded by two distinct layers of protective connective tissue. The outer tunica vaginalis is a serous membrane that has both a parietal and a thin visceral layer. Beneath the tunica vaginalis is the tunica albuginea, a tough, white, dense connective tissue layer covering the testis, which also inverts to form septa that divide the testis into 300-to-400 structures called lobules. Within the lobules, sperm develop in structures called seminiferous tubules.8

Risk factors

The main non-modifiable risk factors for testicular cancer are cryptorchidism (undescended testicle), family history, previous history of testicular cancer, genetic predisposition, ethnicity, congenital abnormalities, and infertility.2

In cryptorchidism, the undescended testicle remains in the abdomen or groin, and the risk of developing the disease does not change even after surgery to move the testicle into the scrotum. In patients with cryptorchidism, the relative risk of developing testicular cancer ranges from 2.9to-6.3. The risk is increased in both testes, although the risk is much higher in the ipsilateral testis (6.3 vs 1.7).5 Family history correlates to an increased risk, and testicular cancer risk is significant in men whose father or brother had the disease. Patients with a father or brother with testicular cancer have a 3.8- and 8.6-times greater risk, respectively.5

Those diagnosed with cancer in one testicle are also more likely to get cancer in the other testicle. Patients with a personal history of testicular cancer have a 12-times greater risk of developing a contralateral testicular cancer than the general population. However, the greatest risk is in the first five years after diagnosis and the 15-year cumulative risk is 1.9 per cent. 5

Genetic and environmental factors play an important role in the genesis and development of testicular cancer. Several genes are implicated in its pathogenesis and different environmental factors have been investigated.1 Klinefelter’s syndrome, caused by a chromosomal abnormality, has been associated with testicular cancer and other cancer types, and congenital abnormalities of the testicles, penis, or kidneys may also contribute to an increased

risk of testicular cancer.

Age wise, the highest incidence of GCT is found in men between 15 and 35 years of age.

Infertility is also strongly associated with testicular cancer. Caucasian men have a higher chance of getting the disease than Afro-Caribbean or Asian men.1,3

Symptoms

Testicular cancer may present as a painless scrotal mass, an incidental radiologic finding, post-traumatic symptom, or scrotal pain.5 An enlarged testicle or a small lump or area of hardness are usually the first signs of testicular cancer. Any lump, enlargement, hardness, pain, or tenderness in the testicle should be evaluated as soon as possible. Other symptoms of testicular cancer usually do not appear until after the cancer has spread to other parts of the body.

Symptoms of testicular cancer may include:4

 A painless lump or swelling on either testicle. Found early, a testicular tumour may be about the size of a pea or a marble, but it can grow much larger.

 Pain, discomfort, or numbness in a testicle or the scrotum, with or without swelling.

 Change in the way a testicle feels or a feeling of heaviness in the scrotum. For example, one testicle may become firmer than the other or testicular cancer may cause the testicle to grow bigger or to become smaller.

 Dull ache in the lower abdomen or groin.

 Sudden build-up of fluid in the scrotum.

 Although rare, some testicular tumours make hormones that cause gynaecomastia.

 Lower back pain, shortness of breath, chest pain, and bloody sputum or phlegm can be symptoms of later-stage testicular cancer.

 Swelling of one or both legs or shortness of breath from a blood clot can be symptoms of testicular cancer.

When cancer spreads to other sites such as the lungs, brain, abdomen, or neck, symptoms including nausea, vomiting, gastric upset, cough, shortness of breath, weakness, sensory disturbances, abdominal pain, lumps in the neck/groin areas, and back pain can occur. Prompt evaluation is important to ensure early diagnosis and treatment and decrease the burden of treatment in advanced disease.9

Testicular cancers are defined based on their cell type. The most common histology of testicular cancer is germinal-seminoma and non-seminoma. About 95 per cent of testicular cancers begin in germ cells, specialised cells in the testicles that make sperm. While these tumours typically start in the testicles they also occasionally arise in the abdomen, chest, or other areas of the body, even if there is no evidence of cancer in or near the testicles. Seminomas make up about half of all GCTs. They usually grow slowly and are less likely to metastasise to other parts of the body. Non-seminomas are often more aggressive than seminomas, and more likely to spread beyond the testicle. Approximately 5 per cent of testicular cancers start in stromal cells, which make testosterone. Testicular stromal tumours are often benign.3

Diagnosis

Evaluation by clinicians is guided by a complete history of the presenting symptoms, physical examination, and assessment for risk factors. Testicular examination should include the affected and unaffected testis for comparison. The normal testis is 3.5-5cm in length, smooth, homogenous, movable, and detached from the epididymis. Hard, firm, or fixed areas within or adjacent to the testes are abnormal and warrant further investigation. Physical examination should also include evaluation of the inguinal and supra-clavicular lymph nodes, the abdomen, and the chest for gynaecomastia.5 It is important to ask specifically about

the history of cryptorchidism, orchiopexy, or inguinal hernia repair as an infant. A family history of testicular cancer in the father or a brother should be elicited. Physical examination findings of any solid intra-testicular mass should be considered to be testicular cancer until proven otherwise.9

Many signs and symptoms of testicular cancer are similar to those caused by non-cancerous conditions such as a spermatocele, varicocele, hydrocele, inguinal hernia, lymphoma, epididymo-orchitis or epididymitis, and differential diagnosis is important.4

Blood tumour markers include Alpha-fetoprotein (AFP), beta human chorionic gonadotrophin (bHCG), and Lactate dehydrogenase (LDH).6

Scrotal ultrasonography can confirm the presence of a mass, and has a sensitivity of 92-to-98 per cent and specificity of 95-to-99.8 per cent.5

Once a solid intra-testicular tumour is identified, radical inguinal orchiectomy is performed both for diagnostic and therapeutic purposes.12 A biopsy of the suspect mass will be carried out and when suspicion for metastatic disease is present, additional imaging with CT of the chest and abdomen may be done for staging.5

Staging

Staging is determined by the size of the tumour, lymph node involvement, whether the cancer has spread and if tumour markers are present.10 Tumour staging guides further management with options including active surveillance, chemotherapy, retroperitoneal lymph node dissection, and radiation therapy.9

Stages are based on four categories:11,12

 T (Tumour): This describes whether the tumour has spread to tissues near the testicle.

 N (Node): Indicates whether the testicular cancer cells have spread to regional lymph nodes.

 M (Metastasis): This refers to whether the cancer has metastasised.

 S (Serum): This indicates the level of tumour marker proteins in the serum, or blood.

Once the individual T, N, M, and S components are scored, they are combined to determine the overall testicular cancer stage group.

The stages of testicular cancer are:

Stage 0:  The cancer cells have not spread beyond the testicle. At this stage, tumours are also referred to as carcinomas in situ.

Stage 1 testicular cancer:  The cancer has invaded tissues next to the testicle, but has not spread to lymph nodes, or more distant sites in the body. Levels of tumour marker proteins may be normal or elevated. The three subcategories of stage 1 testicular cancer are:

 Stage 1A: The tumour may have grown through the inner layer of tissue surrounding the testicle, but not the outer layer, and it has not spread to blood or lymph vessels. Serum levels of tumour markers are normal.

 Stage 1B: Tumours at this stage may have spread to blood or lymph vessels or may have invaded the outer layer surrounding the testicle, the spermatic cord, or the scrotum. Serum levels of tumour markers are normal.

 Stage 1C: These cancers can demonstrate any degree of invasion of nearby tissues, and levels of tumour markers measured after the tumour has been removed by surgery are elevated.

Stage 2 testicular cancer: Testicular cancers at this stage have invaded tissues next to the testicle and can now be found in at least one nearby lymph node. Tumour marker levels may be normal or slightly elevated. Stage 2 testicular

cancer has three subcategories:

 Stage 2A: Tumours at this stage have spread to one or more lymph nodes, but no node is larger than 2cm.

 Stage 2B: Tumours at this stage have spread to at least one lymph node, which is between 2-5cm in size.

 Stage 2C: These tumours have spread to at least one lymph node larger than 5cm.

Stage 3 testicular cancer: Testicular cancers at this stage have spread to distant lymph nodes or organs. Stage 3 testicular cancer has three subcategories:

 Stage 3A: These cancers have spread to a distant lymph node or the lungs. Tumour marker protein levels are normal or slightly elevated.

 Stage 3B: At this stage of testicular cancer, patients have

moderately elevated levels of tumour marker proteins, and the disease has either spread to nearby or distant lymph nodes or the lungs.

 Stage 3C: These cancers have high levels of tumour marker proteins and may have spread to nearby or distant lymph nodes, or the lungs. Alternatively, they may have spread to other distant organs such as the liver or the brain, but in this case serum tumour markers can be at any level.

Treatment and prognosis

Treatment options for testicular cancer include surgery, radiation therapy, chemotherapy and stem cell transplant. Sometimes more than one type of treatment might be used including chemotherapy and/or radiotherapy. 9

The management of seminomas depends on the extent of spread of the cancer. Surgery, radiotherapy, and chemotherapy are used to treat seminomas and the stage of cancer will decide treatment options. Non-seminomas are usually treated with surgery and chemotherapy.10

When a diagnosis of testicular cancer is suspected based on physical examination and ultrasound findings, radical inguinal orchiectomy is performed, which removes the testicle, epididymis, and spermatic cord up to the level of the internal inguinal ring. In this procedure, these structures are delivered through an inguinal incision made along Langer’s lines in the groin. If the mass is too large to pass through a standard 3-to5cm inguinal incision, the incision can be carried inferiorly to the anterior scrotum to allow for removal of the testis in its tunics along with the spermatic cord. Trans-scrotal orchiectomy or biopsy is contraindicated, as doing so alters the lymphatic drainage patterns and impacts further management. Further surgery or radiotherapy or chemotherapy will be based on the disease’s stage and response to the initial management. 9 Following radical inguinal orchiectomy, patients should avoid heavy lifting and high-impact activities for four weeks and should wear supportive underwear to prevent scrotal swelling or haematoma. Retroperitoneal lymph node dissection is major intra-abdominal surgery, after which dedicated post-operative rehabilitation should be undertaken. 9

Removing one testicle does not affect libido or the ability to have an erection providing the remaining testicle is normal. The removal of a testicle may be traumatic, especially for a young man, and a testicular prosthesis can be placed in the scrotum at the time of surgery. Fertility can be compromised by testicular cancer treatment. However, the potential to father children should not be greatly affected provided the other testicle is normal. Chemotherapy, however, does affect sperm production in this testicle and it is recommended that patients with testicular cancer arrange to freeze sperm in case there are problems with fertility later on.7 Adequate counselling should be given regarding the possibility of infertility, sperm-banking and also regarding the placement of a testicular prosthesis if required. 9

Prognosis is determined by the histology, extent of distant tumour spread, and extent of tumour marker elevations. For men with disseminated seminomas, the main adverse prognostic variable is the presence of metastases to visceral organs other than the lungs. A tumour that originated in the mediastinum has a worse prognosis when compared to a tumour that originated within the testicle. 9

Patient education and testicular self-examination

There is no national screening programme for detecting testicular cancer in Ireland.6 Testicular self-examination is one of the simplest and most effective ways to identify testicular cancer early, although there is controversy about its efficacy.7 Despite opportunities for an early diagnosis, most men seek medical help only after some time has passed, when symptoms have intensified, or after receiving information about the condition from someone else or the media. Despite the fact that knowledge about testicular cancer and testicular self-examination in developed counties is higher, testicular self-examination is still rarely performed. Most patients present with a testicular mass, which suggests that testicular self-examination could aid early detection.1

It is important to educate men of all ages about testicular cancer and testicular self-examination and that healthcare professionals, especially nurses, are well informed and able to discuss it with their patients. Healthcare professionals play a key role in providing information about testicular cancer risk factors and symptoms and in explaining the importance of testicular self-examination.7

Figures 1A and B: Testicle physiology

Testicular self-examination guidance for men

 Often the best place to check is in the bath or shower where the scrotum is relaxed and the testicles can be felt easily.

 Hold the scrotum in both hands.

 Use your fingers and a thumb to examine the testicles.

 It is common for one testicle to be slightly larger than the other.

 Gently feel each testicle, one at a time. You should be able to feel a soft tube at the top and back of both testi-

cles. This tube called the epididymis carries the sperm. It may be slightly tender, but do not confuse this with an abnormal lump in the testicles.

 If you notice a lump or anything unusual contact your GP immediately. The GP will be able to assess and if necessary, refer to a consultant for further investigations.

 Do not be embarrassed or nervous.

 Remember early detection of the disease is the best chance of a cure.

 Testicular self-examination should be performed every month.7

Men tend to seek help late for testicular problems for

many reasons such as anxiety and fear of receiving an undesired diagnosis. Others feel ashamed, deprived of their masculinity and are too embarrassed to talk about it with anyone, even a partner. Researchers have found that when men are properly educated about testicular self-examination they are more likely to carry it out and recognise symptoms of testicular cancer.1

Outlook

Testicular cancer is the most common cancer in men aged 15-to-45 years and represents one of the most curable malignancies when identified promptly and treated with a multimodal approach. 9 It has excellent survival rates and having awareness about the disease and seeking prompt healthcare attention is of the utmost importance. Since treatment is successful for most men with testicular cancer, one of the major future goals is to reduce the side-effects of treatment for those with early-stage cancer. In addition, treatments for poor-risk and recurrent cancers are being studied in clinical trials, along with research on the causes and genetics of testicular cancer. Stem cell transplant is most often used to treat testicular cancers that have re-occurred after treatment with chemotherapy. Current studies are looking at whether a stem cell transplant may be valuable as part of the first treatment for some patients with advanced germ cell cancers. Clinical trials are also underway to find better ways of reducing symptoms and side-effects of current testicular cancer treatments, so as to improve patients’ comfort and quality-of-life.13

References

1. Bresciani Boarin M, Facconi L, Manara F, Villa G. Awareness of testicular cancer among young men: A literature review. Int J Urol Nurs. 2020 Jul 17;15(1): 5-11. doi: 10.1111/ijun.12248

2. Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, et al. Testicular cancer from diagnosis to epigenetic factors. Oncotarget . 2017 Sep 18;8(61):104654104663. doi: 10.18632/oncotarget.20992

3. MSK. (2021). Testicular cancer: Germ cell tumours. Available at: www.mskcc.org/cancercare/types/testicular-germ-cell-tumors

4. CancerNet. (2020). Testicular cancer: Symptoms and signs. Available at: www.cancer.net/cancertypes/testicular-cancer/symptoms-and-signs

ABBREVIATED PRESCRIBING INFORMATION

Please refer to the Summary of Product Characteristics (SmPC) before prescribing Pelgraz▼(peg lgrastim) 6 mg solution for injection in pre- lled syringe or prelled injector. Presentation: Each pre- lled syringe or pre- lled injector contains 6 mg of peg lgrastim* in 0.6 mL solution for injection. The concentration is 10 mg/mL based on protein only**. *Produced in Escherichia coli cells by recombinant DNA technology followed by conjugation with polyethylene glycol (PEG). ** The concentration is 20 mg/mL if the PEG moiety is included. Indications: Reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes). Dosage and Administration Pelgraz therapy should be initiated and supervised by physicians experienced in oncology and/or haematology. Posology: One 6 mg dose (a single pre- lled syringe or pre- lled injector) of Pelgraz is recommended for each chemotherapy cycle, given at least 24 hours after cytotoxic chemotherapy. Safety and e cacy of Pelgraz in children and adolescents has not yet been established and no recommendation on a posology can be made. No dose change is recommended in patients with renal impairment, including those with end-stage renal disease. Method of administration: Pelgraz is for subcutaneous use. The injections should be given subcutaneously into the thigh, abdomen or upper arm. See SmPC for instructions on handling of the medicinal product before administration.

Contraindications: Hypersensitivity to peg lgrastim or any of the excipients in Pelgraz.

Warnings and precautions To improve the traceability of biological medicinal products, the trade name of the administered product should be clearly recorded. The long-term e ects of peg lgrastim have not been established in acute myeloid leukaemia (AML); therefore, it should be used with caution in this patient population. Granulocytecolony stimulating factor (G-CSF) can promote growth of myeloid cells in vitro and similar e ects may be seen on some non-myeloid cells in vitro The safety and e cacy of peg lgrastim have not been investigated in patients with myelodysplastic syndrome, chronic myelogenous leukaemia, and in patients with secondary AML; therefore, it should not be used in such patients. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from AML. The safety and e cacy of peg lgrastim administration in de novo AML patients aged < 55 years with cytogenetics t(15;17) have not been established. The safety and e cacy of peg lgrastim have not been investigated in patients receiving high dose chemotherapy. This medicinal product should not be used to increase the dose of cytotoxic chemotherapy beyond established dose regimens. Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported after G-CSF administration. Patients with a recent history of pulmonary in ltrates or pneumonia may be at higher risk. The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological signs of pulmonary in ltrates, and deterioration in pulmonary function along with increased neutrophil count may be preliminary signs of adult respiratory distress syndrome (ARDS). In such circumstances peg lgrastim should be discontinued at the discretion of the physician and the appropriate treatment given. Glomerulonephritis has been reported in patients receiving lgrastim and peg lgrastim. Generally, glomerulonephritis resolved after dose reduction

or withdrawal of lgrastim and peg lgrastim. Urinalysis monitoring is recommended. Capillary leak syndrome has been reported after G-CSF administration and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. Generally asymptomatic cases of splenomegaly and cases of splenic rupture, including some fatal cases, have been reported following administration of peg lgrastim. Spleen size should be carefully monitored (e.g. clinical examination, ultrasound). A diagnosis of splenic rupture should be considered in patients reporting left upper abdominal pain or shoulder tip pain. Treatment with peg lgrastim alone does not preclude thrombocytopenia and anaemia because full dose myelosuppressive chemotherapy is maintained on the prescribed schedule. Regular monitoring of platelet count and haematocrit is recommended. Special care should be taken when administering single or combination chemotherapeutic medicinal products which are known to cause severe thrombocytopenia. Peg lgrastim in conjunction with chemotherapy and/or radiotherapy has been associated with development of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) in breast and lung cancer patients. Patients treated in these settings should be monitored for signs and symptoms of MDS/AML. Sickle cell crises have been associated with the use of peg lgrastim in patients with sickle cell trait or sickle cell disease. Therefore, use caution when prescribing peg lgrastim in patients with sickle cell trait or sickle cell disease, monitor appropriate clinical parameters and laboratory status and be attentive to the possible association of this medicinal product with splenic enlargement and vasoocclusive crisis. White blood cell (WBC) counts of 100 × 109/L or greater have been observed in less than 1% of patients receiving peg lgrastim. No adverse reactions directly attributable to this degree of leukocytosis have been reported. Such elevation in WBCs is transient, typically seen 24 to 48 hours after administration and is consistent with the pharmacodynamic e ects of this medicinal product. Consistent with the clinical e ects and the potential for leukocytosis, a WBC count should be performed at regular intervals during therapy. If leukocyte counts exceed 50 × 109/L after the expected nadir, this medicinal product should be discontinued immediately. Hypersensitivity, including anaphylactic reactions, have been reported with peg lgrastim. Permanently discontinue peg lgrastim in patients with clinically signi cant hypersensitivity. Do not administer peg lgrastim to patients with a history of hypersensitivity to peg lgrastim or lgrastim. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. Stevens-Johnson syndrome (SJS), which can be life-threatening or fatal, has been reported rarely in association with peg lgrastim treatment. If the patient has developed SJS with the use of peg lgrastim, treatment must not be restarted at any time. As with all therapeutic proteins, there is a potential for immunogenicity. Rates of generation of antibodies against peg lgrastim is generally low. Binding antibodies do occur as expected with all biologics; however, they have not been associated with neutralising activity at present. Aortitis has been reported after lgrastim or peg lgrastim administration in healthy subjects and in cancer patients. The symptoms experienced included fever, abdominal pain, malaise, back pain and increased in ammatory markers (e.g.

C-reactive protein and WBC count). In most cases aortitis was

diagnosed by CT scan and generally resolved after withdrawal of lgrastim or peg lgrastim. The safety and e cacy of Pelgraz for the mobilisation of blood progenitor cells in patients or healthy donors has not been adequately evaluated. Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging ndings. This should be considered when interpreting bone-imaging results. The additive e ect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. Pelgraz contains less than 1 mmol sodium (23 mg) per 6 mg dose, that is to say essentially ‘sodium-free’. The needle cover contains dry natural rubber (a derivative of latex), which may cause allergic reactions. Pregnancy and Lactation: Peg lgrastim is not recommended during pregnancy and in women of childbearing potential not using contraception. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from peg lgrastim therapy taking into account the bene t of breastfeeding for the child and the bene t of therapy for the woman. Adverse Events include: Adverse events which could be considered serious include: Common: Thrombocytopenia. Uncommon: Myelodysplastic syndrome, acute myeloid leukaemia, sickle cell anaemia with crisis, capillary leak syndrome, glomerulonephritis, hypersensitivity reactions (including angioedema, dyspnoea, anaphylaxis), splenic rupture (including some fatal cases), Sweet’s syndrome (acute febrile neutrophilic dermatosis), pulmonary adverse reactions including interstitial pneumonia, pulmonary oedema and pulmonary brosis have been reported. Uncommonly cases have resulted in respiratory failure or ARDS which may be fatal. Rare: Aortitis, pulmonary haemorrhage, Stevens-Johnson syndrome. Other Very Common adverse events: Headache, nausea, bone pain. Other Common adverse events: Leukocytosis, musculoskeletal pain (myalgia, arthralgia, pain in extremity, back pain, musculoskeletal pain, neck pain), injection site pain, non-cardiac chest pain. See SmPC for details of other adverse events. Shelf Life: 3 years. Store in a refrigerator (2∞C – 8∞C). Pelgraz may be exposed to room temperature (not above 25°C ± 2°C) for a maximum single period of up to 72 hours. Pelgraz left at room temperature for more than 72 hours should be discarded. Do not freeze. Accidental exposure to freezing temperatures for a single period of less than 24 hours does not adversely a ect the stability of Pelgraz. Keep the container in the outer carton in order to protect from light. Pack Size: One pre lled syringe or pre lled syringe injector with one alcohol swab, in a blistered packaging.

5. Baird D, Myers, G, Darnall C, Hu J. Testicular cancer: Diagnosis and treatment. Am Fam Physician. 2018 Feb 15; 97(4):261-268. www. aafp.org/afp/2018/0215/p261.html

6. Irish Cancer Society. (2021). Symptoms and diagnosis of testicular cancer. Available at: www.cancer.ie/cancerinformation-and-support/cancer-types/testicularcancer/symptoms-and-diagnosis-of-testicular-cancer

7. Marie Keating Foundation (2021). Testicular cancer. Available at: www.mariekeating.ie/ cancer-information/testicular-cancer/

8. Anatomy and physiology of the male reproductive system. Available at: https://courses.lumenlearning. com/suny-ap2/chapter/anatomy-and-physiologyof-the-male-reproductive-system/

9. Gaddam S. (2021). Testicular cancer. StatPearls: Available at: www.statpearls.com/ArticleLibrary/viewarticle/29984

10. St James’s Hospital. (2021). Testicular cancer. Available at: www.stjames.ie/cancer/ typesofcancer/testicularcancer/

11. MacMillan Cancer support. (2021). Stages of testicular cancer. Available at: www.macmillan.org.uk/cancerinformation-and-support/testicular-cancer/stages

12. Markman M. (2021). Testicular cancer stages. Available at: www.cancercenter.com/ cancer-types/testicular-cancer/stages

13. CancerNet. (2020). Testicular cancer: Latest research. American Society of Clinical Oncology: ASCO. Available at: www.cancer.net/cancertypes/testicular-cancer/latest-research

A personalised approach now leads the way for lung cancer treatment

Our understanding of lung cancer and how to manage it is evolving with unprecedented speed and there is great cause for optimism

Despite rapid advances in the field, lung cancer remains the leading cause of cancer death worldwide and is projected to remain so in developed and developing countries for decades to come. In Ireland, it is the second and third most common cancer in women and men, respectively, and the leading cause of death in both with an average of 1,880 people dying each year between 2016 and 2018. The high mortality in lung cancer is largely attributed to late diagnosis, which is associated with the disease.

Broad trends in lung cancer incidence over the past 25 years have been downward in men but, of concern, upward in women. This likely reflects changes in smoking patterns over time. While smoking is still overwhelmingly the leading preventable cause of lung cancer death, a small, but appreciable number are due to exposure to asbestos and radon gas.

Up until roughly 20 years ago, treatment for lung cancer was based solely on surgery, radiation and chemotherapy. Among the 25-to-30 per cent of patients who present with early-stage lung cancer (stage I and II), their disease may be curable with surgery. Adjuvant (post-operative) chemotherapy is sometimes given to reduce chance of recurrence.

For patients with more locally advanced disease involving lymph nodes (stage III), a combination of chemotherapy and radiation is offered with intention of cure and now followed by one year of immunotherapy. However, the majority of these patients will ultimately relapse.

Finally, for those with advanced (stage IV) disease, treatment is palliative in nature. Treatments such as chemotherapy, immunotherapy or the combination of both are given to the majority of patients, with a view to improving quality-of-life and prolonging life expectancy. These approaches were based on a narrow pathological understanding of lung cancer as either small cell (SCLC) or nonsmall cell lung cancer (NSCLC) in nature, with little further distinction to guide treatment plans.

Fortunately, this ‘one-size-fits-all’ approach to lung cancer management is something of the past. The deeper understanding of the molecular basis of lung tumours has led to a much more tailored approach, termed ‘personalised medicine’. This involves molecular testing of tumour samples to identify potential causes of the cancer (‘driver mutations’) and to guide further treatment (targeted therapy and immunotherapy).

Targeted therapy

Targeted therapy in lung cancer first emerged as a concept in the early 2000s, and lung cancer has since become the ‘poster

child’ for targeted therapy (Figure 1).

When tyrosine kinase inhibitors (TKIs), which target epidermal growth factor receptor (EGFR), were approved in NSCLC patients in 2002, they were known to be more effective in patients that were female, non-smokers and of Asian ethnicity. It was only later that a test for activating mutations in EGFR was developed, and revealed that patients who benefitted most from EGFR-targeted agents were those who had an activating mutation in EGFR. This heralded an exciting era where treatment could be based on mutations rather than on tissue type. Those mutations that were considered to confer a growth advantage to the tumour and be causally implicated in the cancer are called ‘driver mutations’. By contrast, some genetic mutations may be present in a tumour, but not contribute to cancer growth. These are named ‘passenger mutations’.

We have since progressed through firstand second-generation EGFR TKIs to third-generation drugs. For patients who are diagnosed with stage IV EGFR-mutated lung cancers today, treatment with osimertinib can lead to a median survival of almost 39 months. By contrast, life expectancy with the best chemotherapy available in similar trials was 17 months.

Similar progress has been made in targeting other driver mutations such as ALK fusions, BRAF mutations, RET fusions, MET alterations, and the list goes on. All of these actionable mutations

represent a small proportion of NSCLC overall in Western populations – approximately 15 per cent of NSCLCs harbour an EGFR mutation, and 3-to-7 per cent have an ALK fusion. However, cumulatively, these amount to significant progress for the subset of patients whose cancers have these alterations.

The most common driver events in NSCLC, and among all cancers, are KRAS mutations. These occur in 25-to-30 per cent of NSCLC and, unlike EGFR and ALK, were considered for a long time to be ‘undruggable’. This is due to structural and biochemical obstacles, such as binding sites that are small and hard to target. Hence, an effective inhibitor for KRAS has long been considered a ‘Holy Grail’ of medical oncology. Excitingly, this hurdle was finally overcome in mid-2021 with the publication of data supporting the use of a KRAS-targeted drug called sotorasib in the management of NSCLC with a KRAS (G12C) mutation. Despite the majority of patients on trial having received both chemotherapy and immunotherapy before, 81 per cent maintained either stable disease or achieved a response to sotorasib. While this represents an early (phase 2) trial, it is promising news for this substantial minority of patients with a KRAS mutation.

Checkpoint inhibitor immunotherapy

Parallel to developments in targeted therapy, checkpoint inhibitor immunothera-

py was developed in the early 2010s. These drugs were developed on the knowledge that a major role of our immune systems is to prevent cancer development, but some tumours have a means of evading detection by our immune systems to proliferate regardless. Drugs initially targeting the CTLA-4 cell surface protein, and later targeting a different protein called PD1, are able to turn off immune inhibitory mechanisms and promote the desired immune response to tumours. Specifically in NSCLC, it has been found that tumour cells which express higher levels of PD-1 (in particular, if greater than 50 per cent of cells) are significantly more likely to respond to immunotherapy alone. A response is also observed in tumours which express lower levels of PD-1, if combined with chemotherapy. This can lead to five-year survival rates of 32 per cent, compared to an average of 6.9 per cent among patients treated before the advent of immunotherapy.

Liquid biopsy

A mounting challenge in the face of needing such a broad array of molecular tests is successfully obtaining the tissue for testing. Traditionally tissue is obtained via bronchoscopy or CT-guided lung biopsy. However, these procedures are time-consuming to perform, carry risk to the patient, and about 30 per cent of specimens are insufficient for testing. Hence, interest is growing in blood-based genotyping, also known as the ‘liquid biopsy’. This uses a simple blood test to measure circulating tumour DNA, shed by the tumour into circulation. While having a lower sensitivity for detecting driver mutations than traditional testing methods, it has a high concordance with biopsy results and median turnaround time of seven-to-10 days. At present in Ireland, this approach is only used to test for the development of resistance to EGFR mutations. In future, though, it is hoped that liquid biopsy will be used for routine diagnosis of NSCLC and also to assess for residual disease following tumour resection.

Conclusion

In conclusion, our understanding of lung cancer and how to manage it is evolving with unprecedented speed and there is great cause for optimism. While the changes of the past 20 years have been diverse, they share in common a more textured and nuanced understanding of lung cancer than before. This personalised approach allows us to consider each patient individually and find an approach that will bring them the greatest benefit with the least harm. As we emerge from two years of grief and, often, pessimism, this is at least something to be optimistic about.

References available on request

DR MICHAEL CONROY, 1 DR CATRÍONA DOWLING , 2 and PROF JARUSHKA NAIDOO, 1,3 1. Beaumont RCSI Cancer Centre, Dublin. 2. University of Limerick School of Medicine. 3. Sidney Kimmel Comprehensive Cancer Centre at Johns Hopkins University, Baltimore, MD, US

Figure 1: Pie chart displaying oncogenic drivers associated with NSCLC. Sections in yellow represent the mutations that currently have targeted therapies

S.aureus and eczema: The bacterio-therapy approach

Attendees at UCD’s Charles Institute Seminar Series heard a presentation by Prof Catherine O’Neill on translational research into the relationship between microbiota and common skin conditions

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 Catherine O’Neill, Professor of Translational Dermatology at the University of Manchester, UK, who spoke about the relationship between the skin and its microbiota, and how bacteria and bacteria-related products can be used for the treatment of skin conditions. Prof O’Neill has formed two spin-out companies, SkinBiotherapeutics PLC and Curapel, which use evidence-based medicine to develop products that help to manage skin conditions such as psoriasis and eczema.

In her talk titled ‘Bacterio-therapy for the Management of Staphylococcus aureus in Eczema’, Prof O‘Neill explained that in atopic dermatitis (AD), any area of the body can be affected but the most common areas for flare-ups include the elbows, face and scalp, backs of the knees and hands, and these are most prone to flare-ups of red, itchy and dry skin. One of the major culprits for these flare-ups is Staphylococcus aureus (S.aureus) infecting the skin, said Prof O’Neill, and this is usually treated with a course of antibiotics. However, with the ongoing proliferation of antimicrobial resistance, there is now an unmet need for new clinical solutions to treat S.aureus

Antimicrobial defences

She told the attendees that with her team, they are researching whether human microbiome bacteria could be an effective alternative to control S.aureus infection, and she presented evidence to show lysates from Lactobacillus rhamnosus (LGG) may be able to inhibit the adhesion of S.aureus to keratinocytes and human skin in organ culture. Prof O’Neill and colleagues have also discovered that LGG can boost the skin’s own natural antimicrobial defences and actually improve skin barrier function in vivo. These findings, she said, suggest that LGG, among others that are under investigation, hold promise as a novel clinical approach to the management of AD and potentially, other S.aureus infections.

Prof O’Neill gave the attendees an overview of a variety of research projects in her lab and explained that in AD, bacteria exacerbate flare-ups and S.aureus is present in 90 per cent of cases. Recurring infection is also common, she added. “What we think happens is that these bacteria, when they are internalised, act as a sort of reservoir for further infections, and we now need to understand the triggers and how they set up the next infection.”

She also gave an overview of the effects of different lactobacilli and the need to protect keratinocytes and maintain their viability. “If we add a neutralising antibody to the receptor, we can protect keratinocyte viability — so there is a link between the keratinocytes

staying alive, and the ability of staphylococci to adhere. So, if you stop them from adhering, the keratinocytes can stay alive.” Her research also led to the finding that lactobacilli are also preventing staphylococci from adhering, Prof O’Neill added. “If we add the lysate first, before the staphylococci, less of them adhere. And if we add the S.aureus first and then add the lysate, that seems to be able to knock-off any bound staphylococci — so it can stop them binding in the first place, and if they are bound, it can knock them off again.”

Lactobacilli protect keratinocytes from S.aureus-induced toxicity in a very species-dependent way, explained Prof O’Neill. “They are not equivalent,” she told the seminar. “Some S.aureus species can exclude the staphylococci… some can displace them, so they can knock them off their binding sites. Most of the lactobacilli that we have looked at, whatever assay we put them through, have very species-dependent effects. So, for people who buy cosmetics — and microbiome-based cosmetics are in vogue at the moment — don’t believe claims that suggest any old lactobacillus species will do. Some lactobacilli are actually quite toxic to keratinocytes.”

She outlined how different experimental models were developed in the laboratory as the researchers’ knowledge on the topic expanded, and this often involves obtaining human skin samples from cosmetic surgery procedures.

“We also showed that LGG can enhance the expression of human skin stratum corneum markers… filaggrin expression is up-regulated in the presence of lysates, so it’s having some really big effects on the host too. So basically, it could be a really good therapy for eczema, because it’s good at inhibiting S.aureus, which is a major inducer of eczema flares. It’s also really good at improving barrier properties, as we know the barrier is weak in eczema.” She went on to describe how this could be tested in humans and emphasised the importance of making the translational leap from investigations in the laboratory, to human applications, including funding issues. This ultimately led to the formation of her companies, she added.

Alternatives

Prof O’Neill described how different alternatives to S.aureus management, other than lactobacilli, were investigated in her lab. Two central aspects of the pathogenesis of AD are the release of cytokines IL33 and TSLP: “These cytokines are released very early, and we think that they sort of ‘prime’ the rest of the TH2 response and improve other type 2 cytokines that are important for AD pathogenesis,” she said. Prof O’Neill and her team looked at the release of these cytokines in response to different staphylococci, and it appears that only S.aureus promotes the release of IL33 and TSLP, “so this also fits in with the concept of S.aureus being the major instigator of eczema flares,” she said. This led to investigations on dampening IL33 and TSLP release in an effort to prevent this type 2 cascade from occurring. The team then looked for bacteria within the skin’s own microbiome that can inhibit S.aureus-induced IL33 and TSLP and this work is ongoing, she explained.

“But we are probably more interested in the metabolites from these bacteria, because we think most of the skin’s commensal bacteria reside in the top layers, so if they are doing anything lower down, it is probably through the secretion of metabolites and other products,” she told the seminar. “We now have a whole pipeline of interesting bacteria that we put through various assays.”

Prof O’Neill concluded: “Management of S.aureus is a mainstay of AD treatment, but alternatives to antibiotics are crucial, obviously because of antibiotic resistance,” she said. “Inhibition of adhesion may be an alternative to killing S.aureus, but another approach may be to modify the host response to S.aureus using the skin’s own microbiome for the dampening of cytokine release.”

Barrier defects

During a lively Q&A session and clinical discussion following the presentation, Prof Tobin spoke about the potential applications for LGG. “Has LGG been used for barrier defects that have no link with the disturbance of the microbiome — for example, a blistering condition that may have a genetic underpinning. Is it possible that keratinocytes in those conditions could also be responsive to LGG?”

Prof O’Neill responded: “Yes, potentially — we have had a look at this in models of wound-healing, because LGG promotes migration proliferation, and certainly, wounds heal a lot faster if you apply lysate rather than if you don’t. So yes, it is having some pretty profound effects on the host, which is why the regulators are insisting on caution, and so they should.”

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

Prof Catherine O’Neill

There is a link between the keratinocytes staying alive, and the ability of staphylococci to adhere

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Irish Osteoporosis Society, Annual Medical Conference, virtual, 22 October 2022

IOS Annual Medical Conference ‘a great success’

The Irish Osteoporosis Society (IOS) Annual Medical Conference for Health Professionals was held virtually on Saturday, 22 October. The well-attended conference featured a varied range of presentations from expert speakers on topical issues relating to osteoporosis.

President of the Society, Prof Moira O’Brien, told the Medical Independent she was delighted attendees could get updates in so many areas of bone health on the day.

“Osteoporosis is the commonest bone disease worldwide, but it is preventable, and it is treatable [for the majority],” stated Prof O’Brien.

“Dr Kevin McCarroll spoke about the importance of normal vitamin D levels and parathyroid hormone on bone and the different issues that can arise.

“Prof Bernard Walsh discussed the horrendous sec -

ondary impact Covid-19 has had on people’s bone health, including the increased risk of falls.

“I believe many people were shocked when they heard from [physiotherapist] Aoife Ni Eochaidh that 75 per cent of people with incontinence issues can reverse the problem [with pelvic floor training] and the other 25 per cent can improve the issue.

“Mr Derek Bennett spoke about the importance of not only fixing bone fractures, but increased diagnosis of osteoporosis by orthopaedic surgeons

Call for ‘health passports’ for children to reduce disease risk

Ireland should introduce a system of ‘health passports’ for children to support them in keeping physically active in an effort to stave off chronic disease and ill health later in life, according to Prof

he said needs to be addressed.

“The presentation on denosumab by Dr Rosie Lannon clarified that patients on this treatment should not be put on 'drug holidays' from it, as unfortunately some patients have been told to stop/put on hold their osteoporosis medications for dental work to be done, which is placing these patients at risk of fractures."

Prof O’Brien also praised the presentation given by Prof Niall Moyna on exercise and chronic diseases.

“I graduated medical school in 1956 and I have been involved in sports medicine since the 1960s, and at 89 I am still working as an osteoporosis consultant.

"In my opinion Prof Niall Moyna’s idea of health passports, for children, is by far the most ingenious yet simplest one that I have heard presented to date.”

More information and resources on osteoporosis are available on the IOS website, www.irishosteoporosis.ie

Niall Moyna, Professor of Clinical Exercise Physiology,

Dublin City University.

During a very well-received presentation at the IOS 2022 Annual Medical Conference, Prof Moyna highlighted the importance of physical activity and a healthy, active lifestyle in maintaining good health and preventing the development of chronic conditions. “There is compelling evidence for the benefits of physical activity in relation to health.”

Speaking during the questions and answers session, he said that physical activity levels in Irish children are inadequate and below the recommended levels in the majority, and their fitness levels are not monitored or supported (outside of competitive sports and PE).

However, Prof Moyna suggested that a ‘health passport’ system, where children would be assessed in school on their fitness over regular intervals, in a fun, 'child-centric way', using validated scores, would provide an ideal opportunity to intervene early on when needed and would educate children on the importance of physical activity for good health. This would encourage children to remain fit throughout their life and provide important data to help inform policy at a national level.

“The whole idea would be to identify kids early on who are at risk and, in a very sensitive way, to bring that to the attention of the public health nurse and let them intervene rather than wait until it’s too late,” he said.

He pointed out that one-third of people over the age of 18 years have a chronic condition, which rises to one-in-two aged over 50 years, “which is quite alarming.” These conditions, including chronic obstructive pulmonary disease, heart disease, and neurological conditions, accounted for 76 per cent of all deaths in Ireland in 2021, and lead to years of ill health, increased risk of hospitalisation, and premature death.

Prof Moyna quoted a number of studies showing that people with various levels of physical activity have much better health, and are less likely/slower to develop chronic health conditions.

He quoted supporting data, adding that modern medicine tends to focus far more on medication or surgery rather than lifestyle adjustments, despite the overwhelming evidence on the benefits, which

Prof Moyna discussed the findings of a recent major meta-analysis of studies involving over 115,000 people, which showed the positive health benefits of physical activity in reducing various negative health risks and outcomes.

“If you can increase your function capacity just by one MET [metabolic equivalent of task], you will get a 13 per cent reduction in all-cause mortality, a 15 per cent reduction in cardiovascular events, a 7 per cent decrease in waist circumference, a 5 per cent decrease in systolic blood pressure, and improvements in triglycerides and resting blood pressure…. So every one MET increase we can have between four and 10 METs is hugely important in relation to longevity and risk of death.”

Prof Moyna also looked at international physical activity guidelines, which advocate a mixture of daily moderate activity and more vigorous activity a couple of times a week. He said that daily walking, even for just 30 minutes, dramatically reduces the risk of developing chronic diseases, as well as aiding bone mineral density.

Speaking to the Medical Independent after the conference, Prof O’Brien praised Prof Moyna’s presentation and suggestions on improving child fitness.

“I agree with Prof Moyna where he states that prevention of diseases should begin in childhood.

“His idea of having health passports for children would make both logical and financial sense, [and] is something that the Government should look very seriously at investing in.

“Such an initiative would significantly decrease the long-term financial burden on our already creaking health system. It would also ensure that our younger generations would live healthier lifestyles than previous generations, and they would carry this through to their adulthood and old age.

“Physical activity should be compulsory in all schools from pre-school right through to when the student finishes school, by which stage physical activity has become a way of life.

“Personally, I cannot see why our Government would not initiate this type of programme. I am unsure that if we want a healthier Ireland, spending millions on bicycle lanes is the answer.

“I would also like to add at this point, that I believe we are extremely lucky to have the expertise of such a knowledgeable, health-focused individual working tirelessly for better lifestyles for the next generation and for generations to come in Ireland.”

Three-quarters of women with incontinence issues who have pelvic floor muscle training see improvement or resolution of their symptoms, the IOS 2022 Annual Medical Conference heard.

Pelvic floor training also leads to significant improvement in faecal incontinence, constipation, pelvic organ prolapse, and sexual dysfunction, and erectile dysfunction in men, Ms Aoife Ni Eochaidh, Chartered Physiotherapist, Clinical Specialist Physiotherapist, Women’s and Men’s Health and Continence, Bon Secour Consultant’s Clinic, Galway, reported during her presentation on women’s health.

She noted that bowel obstruction and constipation are a key cause of hospitalisation in older adults, with an over-dependence on laxatives and surgery despite conservative methods giving good results. “Training the pelvic floor will help the bowel fill, store, and empty.”

Ms Ni Eochaidh looked at issues caused by hormonal changes in menopause, which impact smooth muscle and affect the pelvic floor, “leading to atrophy, loss of bulk… and huge problems during menopause such as itchy vaginal skin… bacterial vaginitis, thrush, UTIs [urinary tract infections], etc.”

She stressed the importance of regular exercise, pelvic floor training, and hormone replacement therapy and probiotics, and other suitable supplements, where indicated, in helping address these issues.

She also noted the risk of osteoporosis in this cohort and the impact of osteoporosis on the pelvic floor, ie, incontinence issues, which can raise the risk of falls.

“The physical mechanical changes with osteoporosis affect the pelvic floor… the woman needs to be doing weight-bearing exercise, but you need a good pelvic floor so that it can be enjoyable. Start first with the pelvic floor in any training programme. Don’t forget the fluids and the fibre and then the weight bearing [exercise].”

Ms Ni Eochaidh said her clinic can also provide ‘blended’ pelvic floor training programmes, through online video sessions, which can be more convenient and cost-effective for some patients.

Concluding, she stressed that “no amount of urine leakage is normal” and “pelvic floor muscle training is for life, it is not a quick fix. I think it should be called ‘patience floor training’ because you need patience. It can take 12 months, but in general six months… it is essential for good bone health and in menopause, as well as during and after pregnancy.”

Incontinence issues can be successfully cured in most women by pelvic floor training

Ms Aoife Ni Eochaidh

Prof Moira O'Brien

These are the bones

Abbreviated Prescribing Information

Please refer to the Summary of Product Characteristics (SmPC) before prescribing Sondelbay® (teriparatide) 20 micrograms/80 microlitres solution for injection in pre- lled pen Presentation: One pre- lled pen of 2.4 ml contains 600 μg of teriparatide. Each dose contains 20 μg of teriparatide in 80 μL. Indications: Indicated in adults. Treatment of osteoporosis in postmenopausal women and in men at increased risk of fracture. In postmenopausal women, signi cant reduction in the incidence of vertebral and non-vertebral fractures but not hip fractures have been demonstrated; Treatment of osteoporosis associated with sustained systemic glucocorticoid therapy in women and men at increased risk for fracture. Dosage and Administration: Recommended dose of Sondelbay is 20 μg administered once daily. Maximum total duration of treatment should be 24 months. The course should not be repeated over a patient’s lifetime. Patients should receive supplemental calcium and vitamin D supplements if dietary intake is inadequate. Following cessation of Sondelbay therapy, patients may be continued on other osteoporosis therapies. Elderly: Dosage adjustment is not required. Renal impairment: Must not be used in patients with severe renal impairment but should be used with caution in patients with moderate renal impairment. No special caution is required for patients with mild renal impairment. Hepatic impairment: Should be used with caution as no data are available. Paediatric population and young adults with open epiphyses: Should not be used in paediatric patients (<18 years), or young adults (>18 to 29 years) with open epiphyses due to lack of safety and e cacy data. Method of administration: Sondelbay should be administered once daily by subcutaneous injection in the thigh or abdomen. Patients must be trained to use the proper injection techniques. Contraindications: Hypersensitivity to the active substance or to any of the excipients; Pregnancy and breast-feeding; Pre-existing hypercalcaemia; Severe renal impairment; Metabolic bone diseases other than primary osteoporosis or glucorticoidinduced osteoporosis; Unexplained elevations of alkaline phosphatase; Prior external beam or implant radiation therapy to the skeleton; Patients with skeletal malignancies or bone metastases. Warnings and

Precautions: Traceability: The name and batch number of the administered product should be clearly recorded. Serum and urine calcium: In normocalcaemic patients, slight and transient elevations of serum calcium concentrations have been observed following teriparatide injection. Serum calcium concentrations reach a maximum between 4 and 6 hours and return to baseline by 16 to 24 hours after each dose of teriparatide. Therefore, if blood samples for serum calcium measurements are taken, this should be done at least 16 hours after the most recent teriparatide injection.

strength for independence

Routine calcium monitoring during therapy is not required. Urolithiasis: Sondelbay should be used with caution in patients with active or recent urolithiasis because of the potential to exacerbate this condition. Orthostatic hypotension: In short-term clinical studies with teriparatide, isolated episodes of transient orthostatic hypotension were observed. Typically, an event began within 4 hours of dosing and spontaneously resolved within a few minutes to a few hours. Renal impairment: Caution should be exercised in patients with moderate renal impairment. Younger adult population (>18 to 29 years): Experience is limited (including premenopausal women). Treatment should only be initiated if the bene t clearly outweighs risks in this population. Excipient: Contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially “sodium-free”. E ects on ability to drive and use machines: No or negligible in uence on the ability to drive and use machines. Transient, orthostatic hypotension or dizziness was observed in some patients. These patients should refrain from driving or the use of machines until symptoms have subsided. Fertility, Pregnancy & Lactation: Women of childbearing potential: E ective methods of contraception should be used during use of teriparatide. If pregnancy occurs, Sondelbay should be discontinued. Pregnancy and breast-feeding: Contraindicated for use. It is not known whether teriparatide is excreted in human milk. Fertility: The e ect on human foetal development has not been studied. The potential risk for humans is unknown. Adverse Events include: Adverse events which could be considered serious: Common: Syncope, dyspnoea, hiatus hernia. Uncommon: tachycardia, nephrolithiasis. Rare: anaphylaxis, renal failure/impairment. Other Very Common adverse events: Pain in limb. Other Common adverse events: Anaemia, hypercholesterolaemia, depression, dizziness, headache, sciatica, vertigo, palpitations, hypotension, nausea, vomiting, gastro-oesophageal re ux disease, sweating increased, muscle cramps, fatigue, chest pain, asthenia, mild and transient injection site events. See SmPC for details of other adverse events. Shelf Life: Unopened vial – 2 years. Pack size: available in pack sizes of 1 pre- lled pen or 3 pre- lled pens. Each pre- lled pen contains 28 doses of 20 micrograms (per 80 microliters). Marketing Authorisation Numbers: EU/1/22/1628/001-002. Marketing Authorisation Holder: World Trade Centre, Moll de Barcelona s/n, Edi ci Est, 6ª Planta, 08039, Barcelona, Spain. Legal Category: POM. Full prescribing information including the SmPC is available on request from Accord Healthcare Ireland Ltd, Euro House, Little Island, Co. Cork, Tel: 021-4619040 or www.accord-healthcare.ie/products. Adverse reactions can be reported to Medical Information at Accord Healthcare Ltd. via email: medinfo@accord-healthcare.com or Tel: +44(0)1271385257. Date of Generation of API: June 2022. IE-01851.

that danced in the summer of love, that brought three children into the world, that worked hard until retirement, that will stand up to osteoporosis and dance some more.

SONDELBAY® is indicated in adults for treatment of osteoporosis in postmenopausal women and in men at increased risk of fracture.1

The SONDELBAY® pen, designed specifically for people with osteoporosis & is the only pen to have a visible dose counter2

More focus needed on prevention of fractures

There needs to be much more focus on the prevention of osteoporotic fractures in Ireland and globally, rather than simply trying to fix bones after they break, according to the President of the Irish American Orthopaedic Society.

Speaking at the IOS 2022 Annual Medical Conference, Mr Derek Bennett, Consultant Orthopaedic Surgeon in Galway and Mayo, noted that osteoporosis is a leading cause of fractures that necessitate orthopaedic surgery, with these patients also having the poorest outcomes.

Moreover, the projected incidence of hip fractures is expected to increase dramatically as people live longer, with greater complexity of fractures.

“And what impact does this have on our beds? We also know that osteoporosis already accounts for more bed days than breast cancer, diabetes or heart attacks combined. So

it really is a huge issue and can we reliably expect to refer all these problems to the local orthopaedic surgeon, and have them fix them? [No].”

He pointed out that Ireland has long had one of the lowest number of orthopaedic surgeons in Europe, “with no signs this is going to change any time soon” despite increased demand. In 2021, 20 per cent of all HSE outpatient attendances were to fracture clinics.

“We are facing a tsunami of patients with fractures, with a thin blue line of orthopaedic surgeons,” he said. “So, very clearly, we have to become more focused on prevention.”

Mr Bennett maintained that orthopaedic surgeons need to move away from just treating the consequences of osteoporosis, rather than the disease itself.

“We’re always very focused on how we fix the fracture, and advancing how we treat them, but perhaps we should

Guidance on use of denosumab in osteoporosis

Denosumab is a very effective treatment for severe osteoporosis/bone loss with high patient satisfaction and adherence rates; however, patient selection is important, the IOS 2022 Annual Medical Conference heard.

While the six-monthly subcutaneous injection is a very potent treatment, its effects can wear off very quickly if stopped suddenly (rebound), rapidly increasing fracture risks.

During her presentation on its usage, Dr Rosie Lannon, Consultant Physician in Geriatric Medicine, St James’s Hospital, Dublin, quoted data from the FREEDOM trial, highlighting the positive impact of denosumab on bone mineral density (BMD), and reduction in fracture risk.

When deciding if it is right for a patient, she advised taking an individualised approach.

A rare risk factor with denosumab, like bisphosphonates, is the development of osteonecrosis of the jaw (ONJ); however, the very few cases identified so far have largely been associated with dental/jaw surgery.

A key question with denosumab usage is when, or if, to stop, Dr Lannon acknowledged.

The optimal duration of denosumab is unknown, she noted, adding that while there is a lack of published evidence for its benefit beyond 10 years, the continued benefit and low risk of adverse events seen in the FREEDOM and Extension study at 10 years “are reassuring”.

However, while ONJ and atypical femoral fractures are rare, the number of cases thus far are too low to estimate the risk associated with prolonged (post-10 years) denosumab treatment. This means prescribers have been left uncertain regarding the risk:benefit of longerterm treatment.

“The optimal duration should be guided by clinical judgement and re-evaluation of fracture risk... when starting denosumab you do have to be prudent and pragmatic about how long the patient may be on it.”

If stopping denosumab, it must be done in a carefully planned, structured way, given the increased fracture risk once it wears off, she stressed, with administration of follow-on therapy (zoledronic acid by IV or oral bis-

phosphonates) and monitoring of BMD/bone turnover markers vital.

Dr Lannon also clarified that patients on denosumab should not be put on ‘drug holidays’ from the medication, as rapid rebound bone loss places such patients at high risk of fractures. The 2020 and 2021 IOS Annual Medical Conferences heard that denosumab stoppage/delays had been a particular issue during the Covid-19 pandemic, despite guidelines to continue scheduled injections as a priority.

Prof O’Brien echoed Dr Lannon’s comments, saying that the message needs to be very clear about the risks to patients if breaks are taken in denosumab. “There should absolutely not be any drug holidays with denosumab,” she said.

Concluding, Dr Lannon summarised her take home message as: “Pick your patients, make sure no doses are missed, and have a strategy for if or when stopping, and counsel on the risk of rebound.”

Meanwhile, in a separate presentation, Dr Eimear Mooney, Specialist Oral Surgeon Registrar, National Maxillofacial Unit, St James's Hospital, discussed the risks of ONJ when taking bisphosphonates and denosumab, and how to minimise them. “Medication-related ONJ is a severe debilitating disease with significant detrimental consequences on the quality-of-life for those affected.”

She stressed that “prevention is key”, and patients must be proactive with their dental health and address any issues before commencing bisphosphonates or denosumab, and have regular dental reviews while on treatment to ensure avoidance/early detection of dental issues.

When dental work is needed while on osteoporosis treatment, patients must be adequately advised on the risks involved, with an individualised risk assessment and shared decision-making approach with the physician treating the patient. In general, when a patient is on denosumab, dental work being done when a patient has been on it 5.5 months is the optimal time, as it is at its lowest level, prior to the follow-up injection. Regarding oral bisphosphonates they can still be in a patient’s system several years after stopping them.

be more focused on recognising and treating the underlying disease, osteoporosis…. And on prevention of osteoporotic fractures.”

He also noted that 20 per cent of hip fracture patients die within six months.

“Many of the rest of them suffer a permanent disability and are unable to live independently and lose [the ability to carry out] a lot of their activities of daily living, [eg washing themselves],” Mr Bennett told the conference.

“So the bottom line from all this is we certainly cannot resolve the problem of osteoporosis by throwing resources at fixing the fractures – we’ve got to come up with a new paradigm where we recognise that there is underlying disease and try to prevent it. The key to this is to have a team approach [to include fracture liaison nurses and physiotherapists].”

Covid-19 lockdowns negatively impacted bone heath

The Covid-19 pandemic had a detrimental impact on physical activity, muscle strength, and bone health, leading to increased falls and fracture risks in at-risk populations, the IOS 2022 Annual Medical Conference heard.

Prof Bernard Walsh, Consultant Physician and Geriatrician, Bone Health Unit, St James's Hospital, Dublin, and Trinity College Dublin, gave a detailed presentation on the subject. He quoted numerous national and international studies showing the negative impact prolonged pandemic-related lockdowns had not only in physical activity rates among the elderly, but across the population, from young to old.

Public Health England data showed that older people experienced a considerable reduction in strength and balance activity between March and May 2020, with the greatest change in the 70-to-74 years age group. Older people in the most deprived groups were more likely to be inactive than the least

deprived, and these socio-economic inequalities have persisted. Modelling data has projected a significant increased risk of falls due to this decline in physical activity and consequent decline in muscle and bone strength. “To rest is to rust, and if you don’t use it, you lose it,” Prof Walsh noted, calling for increased awareness and specific measures to address the situation.

Also speaking during this session was Dr Kevin McCarroll, Consultant Physician and Geriatrician, Bone Health Unit, St James's Hospital. Dr McCarroll gave an overview of hyperparathyroidism, which raises calcium levels in the bloodstream, and therefore can lead to decreased bone strength and increased osteoporosis risk. Hyperparathyroidism mainly occurs in patients over 60, and is more common in women, with other risk factors including genetic risk (10 per cent of cases), lithium use, and radiotherapy treatment to the neck in childhood. There is a strong association between vitamin D deficiency and hyperparathyroidism.

IOS 2022 Research Award Winners

Young Investigator Award

Dr Donal Fitzpatrick, St James’s Hospital, Dublin. (The effect of BMI on the risk of hip osteoporosis: Findings from the TUDA cohort)

Most Interesting Clinical Case Award

Dr Donal Fitzpatrick.

(Acute severe kidney injury after the first dose of zoledronic acid)

Best Poster Award

Dr Mina Aleman, St James’s Hospital, Dublin.

(Dual therapy with denosumab and teriparatide – experience from a bone health clinic)

Best Overall Scientific Abstract Award

Dr Donal Fitzpatrick.

(Seasonal variation in hyperparathyroidism in older patients)

Irish Thoracic Society, Annual Scientific Meeting, Killashee Hotel, Naas, 1-3 December 2022

A breath of fresh air for the respiratory medicine community

The Medical Independent speaks to Dr Ruairi Fahy about the Irish Thoracic Society’s upcoming Annual Scientific Meeting

The Irish Thoracic Society (ITS) will soon host its first in-person Annual Scientific Meeting since 2019. The meeting will take place in Killashee Hotel, Naas, Co Kildare, between 1-3 December.

For Dr Ruairi Fahy, a member of the meeting’s organising committee, the face-to-face nature of the event is significant.

“Interpersonal relationships are so important,” Dr Fahy, who is Consultant Respiratory Physician in St James’s Hospital, Dublin, told the Medical Independent (MI)

“You can do a lot of things by Zoom... It is easy to disperse general knowledge through the Internet, through computers, but it is not the same as attending in person because you fail to make the individual connections that I think are important.”

The first session of the meeting on Thursday, 1 December, will focus on specialist registrar training. This will be followed by two parallel sessions – a case study forum and a case study poster review. Case study oral presentations will round-off the evening, before the prize-giving ceremony and dinner.

On Friday, 2 December, a poster review session will commence proceedings. Parallel discussions on specific diseases will follow. These will focus on: Asthma; interstitial lung disease; lung cancer; patient care; tuberculosis; and pleural and sleep disorders. After a short break, a second poster review session will take place, and additional parallel discussions. These will be on: Cystic fibrosis; chronic pulmonary obstructive disease (COPD); Covid-19; general respiratory; and telehealth.

Lunch and the ITS AGM will take place from 1.00 to 2.30, followed by oral presentations and affiliate meetings, which will be held concurrently for the majority of the afternoon. These include the ITS paediatric forum and the ANÁIL forum. ANÁIL is a body that seeks to support specialist respiratory nurses and promote respiratory care in the wider nursing community nationally and internationally through creating opportunities for networking, education, and representation on regional and national fora. The forum of the Chartered Physiotherapists in Respiratory Care will also be held, as well as that of the Irish Institute of Clinical Measurement Physiology, Respiratory Faculty.

Dr Fahy stressed the importance of the affiliate meetings, stating the members of these groups “are an integral part of the services we offer and we really can’t work effectively without them”.

Sarcoidosis

Following the affiliate meetings, the first guest lecture of the Annual Scientific Meeting will be heard. It will be delivered by Dr Elliott Crouser, Associate Professor, Internal Medicine, Ohio State University, US. Dr Crouser will speak about developments in sarcoidosis pathogenesis and treatment.

Sarcoidosis is one of Dr Fahy’s areas of special interest and he is very much looking forward to the talk.

“He’s going to talk about developments in sarcoidosis pathogenesis and treatment,” according to Dr Fahy.

“So, he will be looking at new pathways of pathogenesis or disease progression that have been identified in the last five years and then new novel treatments that we have started to use over this period.”

After the lecture, there will another prize-giving ceremony and drinks reception, followed by the gala dinner.

E-cigarettes

The final day of the meeting, Saturday, 3 December, will commence with a debate entitled ‘E-cigarettes are more harm than good.’

Dr Fahy said the debate will be interesting as “there are strong opinions” both for and against e-cigarettes. Some see the benefit of using e-cigarettes to help 'wean' patients, with COPD for example, off cigarettes. However, others believe they lead to the normalisation of smoking and can act as a gateway for young people. Also, the long-term health impact of inhaling e-cigarettes is not yet known and will take years to be understood.

“I can see both sides of the argument,” Dr Fahy told MI

“I probably think that, if you want to use inhaled nicotine, it shouldn’t be available over the counter. It should on prescription for those patients, through their GP, or through their specialist, who want to quit but find it very difficult.”

Interstitial lung disease and physiology lectures

The debate will be followed by the second guest lecture. It will be delivered by Prof Aurelie Fabre, St Vincent’s University Hospital, Dublin (SVUH). The title of Prof Fabre’s talk is ‘The role of the pathologist in the diagnosis of interstitial lung disease’.

Dr Fahy pointed out that Prof Fabre is an international expert in the area. She is Consultant Histopathologist at SVUH and Full Clinical Professor at University College Dublin (UCD), School of Medicine, with a special interest in thoracic pathology. She is also a member of the heart and lung transplant team of the national transplant unit at the Mater Misericordiae University Hospital, Dublin. Prof Fabre graduated from Trinity College Dublin in 1996, then received a Masters in medical sciences in pathology at UCD in 1998. She went on to train in histopathology in Paris and in London, where she received her MRCPath in 2002. Prof Fabre then completed a PhD thesis in lung fibrosis in parallel to a Fellowship in thoracic pathology at Bichat Claude-Bernard Hospital, Paris, in 2007. Her main interests include interstitial lung diseases, heart and lung transplant pathology, lung cancer, and cardiac/cardiovascular pathology.

Interstitial lung disease is another of Dr Fahy’s special interests and he expects the lecture to be of great interest to attendees.

“Pathology is one of the most important areas that we use to try and differentiate the different types of interstitial lung disease,” he said.

“Some of it is relatively straightforward, but a huge amount of interstitial lung disease is idiopathic. As we develop genetic

tests, and as we come up with new diagnostic parameters, we probably will chip away at that. That’s what happened in the last 20 years, by subcategorising these interstitial lung diseases more and more, which helps us treat them better.”

The third guest lecture asks, ‘What physiology is essential to the respirologist in 2022?' It will be delivered by Prof Franco Laghi, Pulmonary and Critical Care Medicine, Loyola University Chicago, US.

Prof Laghi has a particular interest in pulmonary function studies and cardiopulmonary exercise stress testing. Dr Fahy pointed out that these were standardised in the 1960s and 1970s, when “the basic physiology was the dominant part of respiratory medicine”.

“The importance of this lecture will be getting an international expert to go over the pulmonary physiology in relation to cardiopulmonary stress testing, which we can make use of as respiratory physicians."

National programme

Dr Fahy also highlighted the final guest lecture, which will provide an update on the HSE national clinical programme for respiratory health. The update will be provided by the Clinical Lead for the area, Dr Stanley Miller, who is also Consultant Respiratory Physician at the Mater Hospital.

COPD is the most prevalent respiratory disease in Irish adults and is a major cause of morbidity and mortality. It is estimated that 380,000 people are living with COPD, yet only 110,000 are diagnosed. At least 1,500 patients die each year of this disease and over 15,000 patients are admitted to hospital in Ireland. The course of the disease involves ongoing medical care and in certain patients, results in frequent hospital admissions.

A major initiative that the clinical programme has been involved with has been the roll-out of 34 community-based dedicated pulmonary rehabilitation teams around the country. These are intended to empower people living with COPD to improve their symptom management and decrease hospitalisations.

The HSE and clinical programme continue to support people in community and hospital settings, with the establishment of specialist teams in the community, including respiratory integrated care teams. This will support the care of more patients in the community, and lessen the need for hospital-based care (hospital admissions for acute exacerbation of COPD can be significant events for patients). Some of the services that will be made available in the community include evidence-based interventions, such as pulmonary rehabilitation.

Workforce

Like many specialties in Ireland, respiratory medicine is under significant pressure due to insufficient consultant numbers. Dr Fahy said that even though respiratory medicine had a significant role to play in managing patients during the Covid-19 pandemic, the number of additional consultant appointments has been disappointing.

“It is unfortunate that despite the Covid-19 pandemic and all the hard work that respiratory physicians and their ICU colleagues did in managing Covid-19 patients, it resulted in very little of an increase in respiratory physicians within Ireland,” he said.

The Annual Scientific Meeting covers a vast range of topics, which Dr Fahy said is reflective of the subspecialisation that has taken place within the specialty over the last number of years.

“Respiratory medicine, like a lot of other areas, has subspecialised to improve quality of care,” he explained.

“That would be my take-home message in terms of the future of respiratory medicine. We are subspecialising, and because of subspecialising it is probably no longer tenable to have one or two respiratory physicians in any given centre. You really need about four or five to cover all the areas you need to be an expert in. That is where the future is.”

Respiratory medicine, like a lot of other areas, has subspecialised to improve quality of care

Dr Ruairi Fahy

* Relvar Ellipta is indicated for the regular treatment of asthma in adults and adolescents aged 12 years and older where use of a combination medicinal product (long-acting β 2-agonist and inhaled corticosteroid) is appropriate: patients not adequately controlled with inhaled corticosteroids and ‘as needed’ inhaled short acting β 2-agonists or patients already adequately controlled on both inhaled corticosteroid and long-acting β 2 - agonist 2

For Healthcare Professionals only. Images used are for illustrative purposes only. Relvar is well tolerated. Most common adverse events are nasopharyngitis and headache2 PM-IE-FFV-ADVT-210002 September 2021

Relvar Ellipta was developed in collaboration with

Relvar® Ellipta® (fluticasone furoate/ vilanterol [as trifenatate]) Prescribing information

(Please consult the full Summary of Product Characteristics (SmPC) before prescribing)

Relvar® Ellipta® (fluticasone furoate/vilanterol [as trifenatate]) inhalation powder. Each single inhalation of fluticasone furoate (FF) 100 micrograms (mcg) and vilanterol (VI) 25mcg provides a delivered dose of 92mcg FF and 22mcg VI. Each single inhalation of FF 200mcg and VI 25mcg provides a delivered dose of 184mcg of FF and 22mcg of VI. Indications: Asthma: Regular treatment of asthma in patients ≥12 years and older where a long-acting β2-agonist and inhaled corticosteroid combination is appropriate and where patients are not adequately controlled on inhaled corticosteroids and “as needed” short-acting inhaled β2-agonists, or where patients are already controlled on both inhaled corticosteroid and long-acting β2-agonist. COPD (Relvar 92/22mcg only): Symptomatic treatment of adults with COPD with a FEV1<70% predicted normal (post-bronchodilator) and an exacerbation history despite regular bronchodilator therapy). Dosage and administration: Inhalation only. Asthma: Patients with asthma should be given the strength of Relvar Ellipta containing the appropriate fluticasone furoate (FF) dosage for the severity of their disease. Prescribers should be aware that in patients with asthma, FF 100 mcg once daily is approximately equivalent to fluticasone propionate (FP) 250 mcg twice daily, while FF 200 mcg once daily is approximately equivalent to FP 500 mcg twice daily. Adults and adolescents ≥12 years: one inhalation once daily of: Relvar 92/22mcg for patients who require a low to mid dose of inhaled corticosteroid in combination with a long-acting β2-agonist. If patients are inadequately controlled then the dose can be increased to one inhalation once daily Relvar 184/22mcg. Relvar 184/22mcg can also be considered for patients who require a higher dose of inhaled corticosteroid in combination with a long-acting β2-agonist. Regularly review patients and reduce dose to lowest that maintains effective symptom control. COPD: one inhalation once daily of Relvar 92/22mcg. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose

KEEP ASTHMA TAMED

Proactive asthma control that lasts1,2

RELVAR ELLIPTA (fluticasone furoate/vilanterol)

monohydrate & magnesium stearate). Precautions: Pulmonary tuberculosis, severe cardiovascular disorders, heart rhythm abnormalities, thyrotoxicosis, uncorrected hypokalaemia or patients predisposed to low levels of serum potassium. chronic or untreated infections, diabetes mellitus. Paradoxical bronchospasm – substitute alternative therapy if necessary. In patients with hepatic with moderate to severe impairment 92/22mcg dose should be used. Acute symptoms: Not for acute symptoms, use short-acting inhaled bronchodilator. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases. Therapy should not be abruptly stopped without physician supervision due to risk of symptom recurrence. Asthma-related adverse events and exacerbations may occur during treatment. Patients should continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of Relvar. Systemic effects: Systemic effects of inhaled corticosteroids may occur, particularly at high doses for long periods, but much less likely than with oral corticosteroids. Possible Systemic effects include: Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract, glaucoma. More rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Increased incidence of pneumonia, including pneumonia requiring hospitalisation, has been observed in patients with COPD receiving inhaled corticosteroids. If a patient presents with visual disturbance they should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma, or rare diseases such as central serous chorioretinopathy. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations. Risk factors for pneumonia include: current smoking, older age, low body mass index and severe COPD. The incidence of pneumonia in patients with asthma was common at the higher dose of Relvar (184/22mcg). Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption

should not use Relvar. Interactions with other medicinal products: Interaction studies have only been performed in adults. Avoid β-blockers. Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir, cobicistat-containing products). Concomitant administration of other sympathomimetic medicinal products may potentiate the adverse reactions of FF/VI. Relvar should not be used in conjunction with other longacting β2-adrenergic agonists or medicinal products containing long-acting β2-adrenergic agonists. Pregnancy and breast-feeding: Experience limited. Balance risks against benefits. Side effects: Very Common (≥1/10): Headache, nasopharyngitis. Common (≥1/100 to <1/10): Candidiasis of the mouth and throat, pneumonia, bronchitis, upper respiratory tract infection, influenza, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, muscle spasms, fractures, pyrexia. Uncommon (≥1/1,000 to <1/100): Hyperglycaemia, vision blurred, extrasystoles. Rare (≥1/10,000 to <1/1,000): Hypersensitivity reactions including anaphylaxis, angioedema, rash and urticaria; palpitations, tachycardia, tremor, anxiety, paradoxical bronchospasm. Marketing authorisation (MA) Holder: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. MA Nrs: 92/22mcg 1x30 doses [EU/1/13/886/002]; 184/22mcg 1x30 doses [EU/1/13/886/005].

Legal category: POM B. Last date of revision: January 2021. Code: PI-2046. Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Campus, Dublin 24. Tel: 01-4955000.

Adverse events should be reported directly to the Health Products Regulatory Authority (HPRA) on their website: www.hpra.ie. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

Irish Thoracic Society, Annual Scientific Meeting, Killashee Hotel, Naas, 1-3 December 2022

AGENDA

16.30 – 17.00

–

Developments in sarcoidosis pathogenesis and treatment

Dr Elliott Crouser, Ohio State University

19.00 – 19.45 Prize-giving and Drinks Reception 20.00

Role of the pathologist in the diagnosis of interstitial lung diseases

Prof Aurelie Fabre, St Vincent’s University Hospital, Dublin

What physiology is essential to the respirologist in 2022? Prof Franco Laghi, Loyola University Chicago, Medical School 12.00 – 12.30 GUEST LECTURE IV

Update on the National Clinical Respiratory Programme

Dr Stanley Miller, HSE National Clinical Lead, Respiratory

AFFILIATE MEETINGS – FRIDAY 2 DECEMBER Killashee Hotel, Naas, Co Kildare

I’d smoked for years. I just thought I was get ting out of shape.

▼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. Anoro® ▼ Ellipta® (umeclidinium bromide/vilanterol [as trifenatate]) Prescribing information (Please consult the full Summary of Product Characteristics (SmPC) before prescribing)

Anoro® Ellipta® 55/22mcg (umeclidinium bromide/ vilanterol [as trifenatate]) inhalation powder. Each single inhalation of umeclidinium bromide (UMEC) 62.5 micrograms (mcg) and vilanterol (VI) 25mcg provides a delivered dose of UMEC 55mcg and VI 22mcg. Each delivered dose contains approx. 25 mg lactose. Indications: COPD: Maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. Dose and administration: Inhalation only. COPD: One inhalation once daily at the same time of the day.

Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate and magnesium stearate). Precautions: Anoro Ellipta should not be used in patients with asthma. Treatment with Anoro Ellipta should be discontinued in the event of paradoxical bronchospasm and alternative therapy initiated if necessary. Cardiovascular effects may be seen after the administration of muscarinic receptor antagonists and sympathomimetics therefore Anoro Ellipta should be used with caution in patients with severe cardiovascular disease. Anoro Ellipta should be used with caution in patients with urinary retention, narrow angle glaucoma, convulsive disorders, thyrotoxicosis, hypokalaemia, hyperglycaemia and severe hepatic

References:

impairment. No dose adjustment is required in renal or mild to moderate hepatic impairment. Patients with rare hereditary problems of galactose intolerance, the Lapp total lactase deficiency or glucose-galactose malabsorption should not use Anoro Ellipta. Acute symptoms: Anoro Ellipta is not indicated for acute episodes of bronchospasm. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases, a re-evaluation of the patient and of the COPD treatment regimen should be undertaken. Interactions with other medicinal products: Interaction studies have only been performed in adults. Avoid β-blockers. Caution is advised when co-administering with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, itraconazole, ritonavir, telithromycin). Anoro Ellipta should not be used in conjunction with other long-acting β2-adrenergic agonists or medicinal products containing long-acting muscarinic antagonists. Caution is advised with concomitant use with methylxanthine derivatives, steroids or non-potassium-sparing diuretics as it may potentiate possible hypokalaemic effect of β2-adrenergic agonists. Fertility, pregnancy, and breast-feeding: No available data. Balance risks against benefits. Side effects: Common: Urinary tract infection, sinusitis,

1. Feldman GJ et al. Adv Ther 2017;34(11):2518-2533.

2. Alcázar Navarrette B et al. Pulm Ther 208;4:171-183.

3. Maltais F et al. Adv Ther 2019;36:2434-2449.

4. ANORO Ellipta SmPC 2021.

ANORO ELLIPTA was developed in collaboration with ©2022 GSK group of companies. All rights reserved.

nasopharyngitis, pharyngitis, upper respiratory tract infection, headache, cough, oropharyngeal pain, constipation and dry mouth. Uncommon: Hypersenstivity reactions including rash, tremor, dysgeusia, dysphonia, atrial fibrillation, supraventricular tachycardia, rhythm idioventricular, tachycardia, supraventricular extrasystoles and palpitations. Rare: Anaphylaxis, angioedema, urticaria, vision blurred, glaucoma, intraocular pressure increased, paradoxical bronchospasm, urinary retention, dysuria and bladder outlet obstruction. Frequency not known: Dizziness. Marketing Authorisation (MA) Holder: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.

MA Nr: 55/22mcg 1x30 doses [EU/1/14/898/002]. Legal category: POM B. Last date of revision: January 2021.

Job Ref: PI-3826. Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Campus, Dublin 24, Tel: 01-4955000.

Adverse events should be reported directly to the Health Products Regulatory Authority (HPRA) on their website: www.hpra.ie. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

Anoro and Ellipta are registered trademarks of the GlaxoSmithKline group of companies

PM-IE-UCV-ADVT-210003

Date of Preparation: January 2022

ANORO▼Ellipta is the only LAMA/LABA to demonstrate superiority in lung function within the class.1-4 Learn more by visiting: www.anoro.ie/head-to-head

SPORTS QUIZ WIN €50 17 November 2022

Q1 Who are the Cricket T20 World Cup champions of 2022?

Q2 Who is the new manager of Aston Villa football club?

Q3 The FIFA World Cup kicks off this weekend. Who are the defending champions?

Q4 Which tennis player has finished the season as the men’s world number one?

Q5 Who do Ireland open their Rugby World Cup pool fixtures against next year?

Q6 Name the Irish gymnast who recently won gold at the World Championships on the pommel horse?

CROSSWORD COMPETITION

17 November 2022

The winner of the 27 October 2022 Sporting Quiz Competition is Dr Wafa Hussein The winner of the 27 October 2022 Crossword is Dr Shona Reid, Co Mayo

Q1 Who scored the winning goal for Ireland in the defeat of Scotland, thus sealing qualification to next year’s Women’s World Cup? A: Amber Barrett

Q2 Which former Heineken Cup winning Premiership team was forced into administration this month? A: London Wasps

Q3 Who will face off in this season’s FAI Cup Final next month?

A: Derry City and Shelbourne

Q4 Who defeated Ireland in their opening game of the Cricket T20 World Cup? A: Zimbabwe

Q5 Who won the Northern Ireland Snooker Open? A: Mark Allen

Q6 Which city will host the summer Olympic Games in 2024? A: Paris

ENYAQ SHOWS ITS TEETH WITH NEW POTENT 80X VERSION

The Škoda Enyaq has been on the market since mid-2021 and is one of the most coveted electric vehicles (EVs) around. However, in Ireland, supply has been limited compared to its Volkswagen ID.4 cousin. On the plus side for owners, it has meant residual values are pretty much peerless. Year-old Enyaqs are changing hands for similar prices to a new one, such is its rarity. Those jurors that voted for the Enyaq as their number one choice did so because the Enyaq hits the mark in a lot of areas. It looks good; it is spacious, has a high-quality finish and is ‘reasonably’ affordable compared to its rivals (yes, we know all EVs are expensive right now). The 80x that we are driving here is the all-wheel drive version of the Enyaq. Instead of one electric motor powering the rear wheels, there is a second powering the front wheels, too, so you get a little more power.

The Enyaq is regarded as one of the best-looking SUVs on the market, and we can see why. It has a handsome design, with some of the elements that have made cars like the Karoq and Kodiaq so hugely popular. Given that it is built on the Volkswagen Group’s MEB platform, it gives the model much more scope in terms of design, with greater use of interior space. There is, of course, no requirement for a standard grille as you will find in internal combustion engine cars. There is a covered grille of sorts, so the Enyaq does look like a conventional

SUV, yet it is anything but. It looks at its best shod in 21” wheels, which this test car has fitted as a €1,481 optional extra, but they look great. Overall, the proportions of the Enyaq are very good; it is a generously-sized car without ever feeling too bulky and sits quite a bit lower than a standard large SUV.

The Enyaq uses much of the wisdom Škoda has gained from making excellent family cars, such as the Superb and Kodiaq to good effect. Like many new cars, the centre console is dominated by a 13” infotainment system, which is genuinely one of the most intuitive you will come across. It responds quickly and connects to

your mobile phone wirelessly using Apple CarPlay or Android Auto, but there are also USB C-ports in the front, and they come in the rear as part of an options pack (‘clever pack’ for €3,662 in the 80x). If you choose the almost €9,000 ‘advanced pack’, you get the heads-up display, which is particularly impressive, if slightly unnecessary. The entry pack, the clever pack, is pretty essential as it adds the wireless charging pad, heated front seats and climatronic three-zone air conditioning – so it really is a must. Space for passengers, front and rear, is generous. There is plenty of capacity in the rear in terms of legroom thanks to a flat floor, and luggage space at 585 litres is very large and will be more than enough for most family needs.

The additional electric motor at the front wheels of the 80x adds another 210kg to the already hefty 2,540kg in a standard Enyaq with a larger battery. But the extra motor adds more power, making the 80x the most powerful Enyaq you can buy, for now, with 265hp and 425Nm of torque, which is 115Nm more than the standard version. The extra motor shaves just under two seconds 0-100km/h sprint. It also increases the towing capacity from 1,000kg to 1,200kg.

The iV 60 can charge up to 100kW DC as standard and up to 125kW on the 80 and 80x. The WLTP [Worldwide Harmonised Light Vehicle Test Procedure] range of the 80x we were driving is 521km, slightly less than the 544km of the standard single-motor rear-wheel drive

The 80x is hard to justify as a purchase unless you really need the extra grip or towing capacity

80 (77kWh) model. In real-world terms obviously, it depends on how you drive it, but you should expect to be getting north of 400km from a full charge in the 80x without trying too hard. If you aren’t, then perhaps you need to look at your driving style. For some, the extra grip provided by the extra electric motor will be helpful, especially if you live in an area prone to ice and frost, but remember the grip will only be as good as the tyres fitted to the car. If you expect this higher-powered version of the Enyaq to be quick and come with eye-watering acceleration, then you will be disappointed, as the car’s considerable bulk never really feels fast in the way a Tesla or Ford Mustang Mach-E does.

The Enyaq is a pricey vehicle and you can end up going down the rabbit hole when it comes to the options list. A few clicks of the options and you are suddenly in a €70,000-plus car. The 80x is hard to justify as a purchase unless you really need the extra grip or towing capacity. The best buy for us is the standard 80 model in Sportline trim, with the Sportline offering items, such as the pretty 20” ‘Vega’ alloy wheels, Sportline exterior pack, and Matrix LED lights.

The Enyaq was tested by Euro NCAP [New Car Assessment Programme] and scored one of the highest-ever results with five-stars and a number of positive comments from the testers. This is one of the safest cars you can drive, which gives it a huge appeal for family car buyers.

The Enyaq is one of the best cars on sale in Ireland today; the difficulty is that they are pretty hard to get. Supply should get better soon, but if you can get one, then you will have one of the best cars to own. It is a big, heavy car, so you should probably get the larger battery version. Do you need this 80x version? Well, that depends on your needs. You are paying for extra grip and power, but this adds more weight too. Stick with the standard single-motor 80 version in a Sportline trim, if your budget allows.

Engine: 77kWh battery/ 195kW electric motor

Power: 195kw/265hp

Torque: 425Nm

0-100km/h: 6.9 seconds

Battery Economy: 17.4kWh/

100km

Top Speed: 160km/h

Colour: Velvet Red

Transmission: Single speed auto

CO 2 : 0g/km

Annual Motor Tax: €120

Luggage Capacity: 585 litres

Price as tested: €64,180

Price: €51,286

Intern Network Executive, HSE National Doctors Training and Planning, National Academic Track for Internship Showcase Event, 29 September 2022

Pictured L-to-R: Prof Michael Gill; Prof Martina Hennessy; Dr Barry Lyons; and Prof Brian Kinirons

Dr Linda Doyle, Provost, Trinity College Dublin (TCD)

Ms Samantha Wakerlin, final year medical student, University College Cork (UCC); Ms Ciara Donoghue, final year medical student student, UCC; Dr Sadhbh O’Connor; and Dr Kieran Joyce Dr Annie Duffy; Dr Sian McGarel; Dr Ray Abbas; and Dr Rachael Power

Prof Colin Doherty, Head of School of Medicine, TCD

Dr Ronan Doherty; Dr Richard Farnan; Mr Richard Melotte; and Prof Colin Doherty

Photos: David Coleman - Bobby Studio

Prof Martina Hennessy; Dr Molly Godson Treacy; Dr Elaine Burke; Dr Cormac Kennedy; and Dr Dan O’Reilly

Prof Michael Gill and Dr Karen Misstear

Prof Liam Plant and Prof Finbarr O’Connell

Ms Sara Sotirakos; Ms Katharina Nagassima; Mr Stefan Elekes; Ms Rachel Cooney; Mr Damien Doherty; and Ms Imad Mirza – Final year medical students, TCD

Dr Caoimhe Leneghan; Ms Susanne Lalor; and Dr Chloe McDermott

Dr Emily Panteli and Dr Michael Keane

EVERY SIDE-EFFECT REPORTED TO THE HPRA HELPS TO IMPROVE THE SAFETY OF MEDICINES

Launched by the Health Products Regulatory Authority (HPRA), the seventh annual #MedSafetyWeek ran until 13 November and encouraged everyone to report suspected side-effects of medicines. This year’s global campaign involved medicines regulators from 82 countries and focused on the key role of every healthcare professional, patient, and carer who reports a suspected side-effect and contributes to using medicines safely.

All medicines may cause side-effects in some patients, so there are steps in place to continuously monitor their safety after they are placed on the market. The purpose of safety monitoring is to gain more information about known side-effects and find out about new ones. Regulators operate systems to detect and analyse those side-effects and prevent harm to future patients.

The HPRA collects, organises, and investigates reports of suspected side-effects. Reports of side-effects have helped identify several safety issues which were not previously recognised as being linked to a particular medicine until the HPRA received information from reports.

By reporting suspected side-effects to the HPRA, healthcare professionals and the general public are actively participating in identifying emerging safety issues so that the HPRA can take action when necessary and protect people from harm.

Ms Sinead Curran, Director of Human Products Monitoring at the HPRA, said: “Every report made by a patient, a healthcare professional, or a carer plays a key role in gaining more knowledge about the benefits and risks of medicines in clinical use and allows action to be taken to minimise risks.

“Reporting suspected side-effects to the HPRA helps to improve the safety of medicines for all patients and, in some cases, can result in better tailored prescribing advice, which can improve patient outcomes.

“If you, or a patient you are supporting, experience a side-effect with a medicine, make sure to report it to us promptly.”

Anyone can report suspected side-effects to the HPRA. You can submit a report in many ways:

 Completing the HPRA’s online reporting forms;

 Emailing a completed form;

 Printing and posting a completed form;

 Phoning the HPRA on (01) 676 4971.

Visit the HPRA’s reporting webpage to complete an online form, or to download or print a form: hpra.ie/report

RCSI RESEARCH DISCOVERS NEW ROLE FOR BLOOD CLOTTING PROTEIN IN TRIGGERING INFLAMMATION

Research by RCSI University of Medicine and Health Sciences has discovered a new role for the blood clotting protein, von Willebrand factor (VWF), that could lead to the development of new treatments for patients with inflammatory and blood clotting disorders.

Published in Nature Communications , the research finds that VWF plays an important role in regulating immune responses at sites of blood vessel injury. This means that the protein has a newly discovered role in repairing damaged blood vessels in addition to its role in blood clotting.

Deficiency in VWF is called von Willebrand disease and occurs in about 1-in-1,000 people in Ireland. People with this condition have increased risk of serious heavy bleeding. In contrast, people with high levels of the protein in their blood are at risk of developing serious blood clots. For example, very high VWF levels have been implicated in the unusual blood clots seen in the lungs of patients with severe Covid-19.

This research shows, for the first time, that VWF not only regulates blood clotting at the site of damage, but

also triggers local immune responses. Understanding this new biological role for VWF in regulating inflammatory responses may offer the opportunity to develop entirely new treatment options for patients with inflammatory and blood clotting disorders, such as von Willebrand disease, deep vein thrombosis and myocardial infarction.

Lead author of the research, Prof James O’Donnell, Director of the Irish Centre for Vascular Biology at RCSI School of Pharmacy and Biomolecular Sciences, said: “For more than 50 years, it has been known that VWF plays a key role in preventing bleeding by acting as a glue at the site of injury. This research now helps us to further understand the role that VWF plays in linking blood coagulation and inflammation and thereby paves the way for the development of new treatments.”

The research was conducted by RCSI in collaboration with Trinity College Dublin and the National Coagulation Centre in St James’s Hospital, Dublin.

The study was funded by Science Foundation Ireland and the US National Institutes of Health.

TRINITY TEAM IDENTIFY POTENTIAL CLUES TO VIRAL RESISTANCE

Scientists from Trinity College Dublin have identified factors that may help explain why some people are able to resist viral infections, having screened the immune systems of women exposed to hepatitis C virus (HCV) through contaminated anti-D transfusions given over 40 years ago in Ireland.

The research, recently published in leading journal Cell Reports Medicine , has implications from improving fundamental understanding of viral resistance to the potential design of therapies to treat infected people.

Between 1977 and 1979, several thousand women in Ireland were exposed to the hepatitis C virus through contaminated anti-D, which is a medication made using plasma from donated blood and given to Rhesus negative women who are pregnant with a Rhesus positive foetus. The medication prevents the development of antibodies that could be dangerous in subsequent pregnancies. Some of the anti-D used during the 19771979 period was contaminated with hepatitis C.

Arising from this outbreak, three groups of people were identifiable: Those who were chronically infected; those who cleared the infection with an antibody response; and those who appeared protected against infection without making antibodies against hepatitis C.

Prof Cliona O’Farrelly, Professor of Comparative Immunology in Trinity’s School of Biochemistry and Immunology, is the senior author of the research article.

Ms O’Farrelly, who is based in the Trinity Biomedical Sciences Institute, said: “We hypothesised that women who seemed to resist HCV infection must have an enhanced innate immune response, which is the ancient part of the immune system that acts as a first-line of defence.

“To test this we needed to make contact with women exposed to the virus over 40 years ago and ask them to help us by allowing us to study their immune systems to hunt for scientific clues that would explain their differing responses.

“After a nationwide campaign over 100 women came forward and we have gained some unique and important insights. That so many women – many of whom have lived with medical complications for a long time – were willing to help is testament to how much people want to engage with science and help pursue research with the potential to make genuine, positive impacts on society. We are deeply grateful to them.”

The scientists ultimately recruited almost 40 women from the resistant group, alongside 90 women who were previously infected.

In collaboration with the Institut Pasteur in Paris they then invited almost 20 women in each group to donate a blood sample that they stimulated with molecules that mimic viral infection and lead to activation of the innate immune system.

Mr Jamie Sugrue, PhD Candidate in Trinity’s School

of Biochemistry and Immunology, is first author of the research article. He said: “By comparing the response of the resistant women to those who became infected, we found that resistant donors had an enhanced type I interferon response after stimulation. Type I interferons are a key family of antiviral immune mediators that play an important role in defence against viruses including hepatitis C and SARS-CoV-2….”

“We think that the increased type I interferon production by our resistant donors, seen now almost 40 years after the original exposure to hepatitis C, is what protected them against infection.

“These findings are important as resistance to infection is very much an overlooked outcome following viral outbreak, primarily because identifying resistant individuals is very difficult – since they do not become sick after viral exposure, they wouldn’t necessarily know that they were exposed. That’s why cohorts like this, though tragic in nature, are so valuable – they provide a unique opportunity to study the response to viral infections in an otherwise healthy population.”

The lab’s efforts are now focused on leveraging these biological findings to unpick the genetics of viral resistance in the HCV donors. Their work on HCV resistance has already helped ignite international interest in resistance to other viral infections, including SARS-CoV-2.

The O’Farrelly lab has expanded its search for virus-resistant individuals by joining in the Covid human genetic effort (www.covidhge.com) and by recruiting members of the public who have been heavily exposed to SARS-CoV-2, but never developed an infection (www. viralresistanceproject.com).

This research was supported by Science Foundation Ireland, the Swedish Research Council and an Irish Research Council – Campus France Ulysses award. The journal paper is available at the following link: www.cell.com/ cell-reports-medicine/fulltext/S2666-3791(22)00363-9)

PROMISING RESULTS FROM PSILOCYBIN THERAPY TRIAL FOR TREATMENT-RESISTANT DEPRESSION

Researchers at Trinity College Dublin have participated in the largest and most rigorous clinical trial to date of psilocybin (a psychoactive ingredient in magic mushrooms), pointing to the possibility that COMP360 psilocybin with psychological support could be a beneficial therapeutic strategy for people with treatment-resistant depression (TRD).

The study has been published in the New England Journal of Medicine

Prompted by promising preliminary findings, this funded multi-centre, randomised, double-blind, phase 2b clinical trial was launched in 2018 to determine the safety and potential antidepressant effects of a single dose of COMP360 psilocybin (25mg or 10mg), compared to 1mg, with psychological support in people with TRD. The study was sponsored by COMPASS Pathways, a mental health company based in the UK, which also developed COMP360 – its proprietary formulation of synthetic psilocybin administered in conjunction with psychological support.

The trial, which included 233 people with TRD across 10 countries, including the Irish site at Tallaght University Hospital, showed that patients who received a single dose of 25mg COMP360 psilocybin experienced a highly statistically and clinically significant rapid reduction in symptoms of depression compared to 1mg at three weeks (p<0.001).

This offers hope that COMP360 psilocybin with psychological support could be an effective antidepressant treatment paradigm for some people with TRD, if proven effective and safe in larger studies. COMPASS Pathways will be running a larger phase 3 programme of COMP360 psilocybin therapy in TRD, which is on schedule to begin in 2022.

The paper, ‘Single-dose psilocybin for a treatment-resistant episode of major depression’, can be accessed at the following link: www.nejm.org/doi/full/10.1056/ NEJMoa2206443

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A round-up of news and oddities from left field by Dr Doug Witherspoon

Future medicine: A peek down the pipeline

Necessity is indeed the mother of all invention and this issue's Dorsal View is dedicated to a couple of the more unusual discoveries and innovations that might change the way some diseases are diagnosed and treated First stop is the Massachusetts Institute of Technology (MIT) in the US. Recent years have shown us how fruitful collaborations between physicians and engineers can be. The latest such partnership has seen these two disciplines work together in an effort to find alternatives to bulky, expensive and time-consuming ultrasound scans.

The result is so-called 'ultrasound adhesives', devices about the size of a postage stamp that provide a clear image of internal organs for up to 48 hours. The adhesives stick to the skin and provide continuous imaging, are safe, non-invasive, and provide physicians with clear images of whatever they need to see.

It works by having trained technicians use ultrasound wands and probes to channel sound waves through the body, which reflect back to the adhesives, providing high-resolution images of internal organs.

Volunteers participated in the testing of these devices –

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the adhesives successfully produced live, high-quality images that showed not only activity in blood vessels, but also in deeper organs such as the stomach, heart, and lungs. It was also possible to observe changes in organs whilst the volunteers were either at rest, or performing tasks, such as cycling and running. A liquid gel is applied to the patient's skin, which transmits the ultrasound waves, and a transducer is then pressed tight to the gel. This sends sound waves into the body, which 'echo' from internal organs and back to the probe and these are then translated into images.

The researchers point out that this has the potential to freeup considerable amounts of time for doctors. Even in its current form, the system is capable of being used in hospitals in a similar way to adhesive electrodes, they say. Work is now underway to make the adhesives even more accessible and completely wireless, with the ultimate goal of having them available from a doctor's clinic or even a pharmacy.

Prof Xuanhe Zhao, Professor of Mechanical Engineering and Civil and Environmental Engineering at MIT, is optimistic about the potential applications. "We believe we've opened a new era of wearable imaging: With a few patches on your body, you could see your internal organs," he said. "We envision a few patches adhered to different locations on the body and the patches would communicate with your cellphone, where AI algorithms would analyse the images on demand."

For the clinically curious, the paper was published recently in Science.

Meanwhile, a team comprised of researchers from Johns Hopkins University and Vanderbilt University, US, and the University of Toronto, Canada, have teamed-up to come to the novel conclusion that cells move more quickly through mucus than they do through blood. This, they say, could have implications for research into tumour progression, as well as lung scarring in cystic fibrosis, and the mechanisms of wound-healing.

Certain cells have 'ruffled' edges that 'sense' their environment and accordingly adapt to increase their speed, say the researchers. The findings indicate that the viscosity of a cell's environment could contribute to disease progression, among other factors. Co-author Prof Sergey Plotnikov, Assistant Professor at the University of Toronto, explained: "This link between cell viscosity and attachment has never been demonstrated before. We found that the thicker the surrounding environment, the stronger the cells adhere to the substrate and the faster they move – much like walking on an icy surface with shoes that have spikes, versus shoes with no grip at all."

He continued: "Targeting the spreading response in fibroblasts, on the other hand, may reduce tissue damage in the mucus-filled lungs affected by cystic fibrosis. Because ruffled fibroblasts move quickly, they are the first type of cells to move through the mucus to the wound, contributing to scarring rather than healing. These results also may imply that by changing the viscosity of the lung's mucus, one can control the cell movement."

The work is ongoing, specifically targeted at cystic fibrosis and cancer, but the initial findings were published recently in Nature Physics