An eye on AI
With a national artificial intelligence strategy imminent, David Lynch looks at recent trends in the area and what the future promises
Epilepsy and medical cannabis
Neurologists specialising in epilepsy are urging inclusion of a purified cannabidiol product in the State’s new access programme. Catherine Reilly reports
Keep Our Doctors
Dr Shubhangi Karmakar talks to doctors involved in the Keep Our Doctors campaign about why barriers faced by international graduates must be removed
Career breaks under consideration for staff due to Covid impact
The HSE has listed ‘career breaks’ as one of a range of potential supports for employees as a result of the significant strain of the Covid-19 pandemic. This is despite an acknowledgement that adequate staffing is the biggest challenge in the restoration of regular healthcare services this year.
In a recent document entitled, ‘A safe return to health services – Restoring health and social care services in a Covid environment’, the HSE outlines there is an acceptance of a likely increase in demand for a range of resources, such as ongoing psychological supports for staff, due to the impact of the pandemic.
“In response we have developed a psychosocial framework, to provide the supports required. In this context, attrition of existing staff may be a significant risk to a given speciality or
to the organisation, or both,” according to the document, which was completed in March 2021.
“This will require careful management with consideration being given to redeployment, retraining or career breaks, for example.”
However, the most critical challenge to restoring health and social care services in a Covid-19 environment is adequate staffing, according to the HSE.
The document also states that while it is expected absenteeism will decrease overall, in line with the reducing number of cases and the impact of vaccination, annual leave will be carried over into the latter half of the year and will impact on staffing.
It states the recruitment of additional whole-time-equivalent staff could mitigate the effect of annual leave being carried over.
The report noted how during the third surge of Covid-19,
staffing levels fell “considerably” in various sites.
The Medical Independent recently reported how 6,700 staff were on Covid-related absence during one week in January.
Despite the reduction in numbers of Covid-19 cases, all services will be required to protect Covid pathways of care through the “phased prioritised restoration of services” and a continued focus on hospital avoidance through the ongoing development of enhanced community services.
The document also acknowledges there will continue to be reduced capacity in the healthcare system, due to social distancing and infection prevention and control requirements.
“Decisions in relation to the type and volume of activity will be made at site level based on local case numbers, available capacity and guidance from national clinical leads,” according
is BTA Secretary and Consultant Endocrinologist, Dr Carla Moran, who runs a new rare thyroid disease clinic at St Vincent’s University Hospital, Dublin, and who presented Dr Tansey with his prize at the virtual event.
to the document.
“Ongoing vigilance with regard to infection prevention and control measures will be essential given the vulnerability
Low number of complaints about doctors from employers – Council
The Medical Council has told the Department of Health it intends addressing the proportionally low number of complaints about doctors received from their employers in comparison to other countries.
It advised the Department earlier this year that it planned to write to the Minister for Health and the HSE CEO to “re-establish” a memorandum of understanding on information exchange.
Representatives from the Council discussed the matter during a governance meeting with Department officials in January.
According to minutes of the meeting, obtained by the Medical Independent following a Freedom of Informa-
tion request to the Department, the Council “advised that the experience in other countries is that a higher proportion of complaints about medical practitioners are referred by employers (as opposed to members of the public) than in this jurisdiction”.
“The Department welcomed the Council’s review of these issues and advised that it would support the Council in any way possible,” reported the minutes.
According to the Council’s annual report for 2019, most complaints about doctors came from members of the public (357), followed by healthcare professionals (26).
The source of just three complaints was attributed to a healthcare institution and only four to the HSE.
of healthcare settings to Covid-19 transmission. The need to parallel Covid and non-Covid pathways will also impact on the pace of service restoration.”
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Pictured is Dr David Tansey, SpR in Endocrinology and Diabetes and ASPIRE MBA Scholar at the Michael Smurfit Graduate Business School, who was awarded the best overall presentation in the clinical case competition at the Annual Meeting of the British Thyroid Association (BTA) on 21 May. Also pictured
Emily Clarke Gifford speaks to the Clinical Lead of the HSE’s Sexual Health and Crisis Pregnancy Programme about the challenges Covid-19 has posed for people living with HIV
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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 efﬁcacy of linagliptin in children and adolescents has not yet been established. No data are available. Take the tablets 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. 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 has been observed in patients taking
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Failure to attract consultants to ‘peripheral’ hospitals
The failure to attract consultants to “peripheral” hospital locations remains a significant challenge to the health service, according to members of the Sláintecare Implementation Advisory Council (SIAC).
“We are in a perpetuating cycle where consultants are not attracted to peripheral hospital locations where rotas, facilities, and options in these locations are much less attractive to them,” according to minutes of the SIAC’s meeting in December.
“We should work on making positions in peripheral hospitals attractive to consultants through an appropriate package of incentives.”
As previously reported, Council members at this meeting also expressed strong disagreement with Minister for Health Stephen Donnelly’s view that progressing the new regional health areas should be postponed as a result of the Covid-19 pandemic.
On the specific issue of consultant recruitment in the regions, Council members agreed that “there must be suitable positions for them [consultants] in the community”.
At the meeting, SIAC Chair Dr Tom Keane raised “the huge injection of funds that the system is to receive in 2021” to recruit resources across acute and community areas.
“This is at a time when the health system is facing a deficiency in availability of human resources and this includes consultants, nursing and other clinical healthcare roles right across the health system.”
On staff recruitment and retention, Dr Keane noted “we will not solve this problem solely with money. We must understand the challenges and problems and work innovatively to address them. There is a real opportunity now, given the rapid changes shown in Covid-19 and the new funding to address recruitment and retention.”
In recent weeks, the IHCA and the IMO have raised significant concerns regarding the Government’s planned implementation of the new Sláintecare consultant contract.
DoH in ‘bilateral’ discussions on new AI strategy
The Department of Health has had bilateral discussions with the Department of Enterprise, Trade and Employment on the new National Irish Strategy on Artificial Intelligence (AI), this newspaper has learned.
The draft strategy is currently being finalised and is “expected to be published before the end of June,” a Department of Enterprise, Trade and Employment spokesperson told the Medical Independent (MI)
The public consultation process for the strategy took place at the end of 2019 with the submissions published on the Department’s website in recent weeks. There were 85 responses to an online questionnaire on the strategy.
There were a further seven separate written submissions, none of which came from medical organisations.
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“There has been extensive consultation with stakeholders from all relevant sectors during the development of the strategy, including repeated consultations with other Departments,” the spokesperson told MI
“The Department of Health has actively engaged in these consultations, and has also met with the Department of Enterprise, Trade, and Employment bilaterally.”
The new national policy is being readied for publication just as the HSE is under an unprecedented cyberattack.
Dr Maria Helen Murphy, Assistant Professor in Law at Maynooth University, told MI the cyberattack “illustrates the vulnerability of systems, including our most sensitive government systems”.
As AI relies on the processing of enormous amounts of information, “cybersecurity and data protection must be central considerations” in the development of AI policies, she noted. See news feature, p4-5.
y Depar tment
The Health Products Regulatory Authority (HPRA) has received 44 reports that potentially relate to the poorly-understood condition ‘breast implant illness’.
These reports may contain duplications and the HPRA understands they relate to 31 individuals overall.
The figures represent an increase from the 33 reports relating to 24 individuals provided to the Medical Independent in June 2020.
“Some individuals and health researchers have used the term ‘breast implant illness’ to refer to the experiencing of a range of symptoms in association with having breast implants,” stated the HPRA’s spokesperson.
“Symptoms such as joint pain, rashes, memory loss, ‘brain fog’ or other symptoms have been described. These symptoms and what causes them are not well understood at this time. The symptoms which have been reported to the HPRA are similar to those reported in the scientific literature and reported to regulatory agencies in other jurisdictions.
“There is ongoing research to try to understand these symptoms and their origin. The reports which the HPRA have received relate to a range of breast implant products and manufacturers.”
Breast implant illness is a separate phenomenon to breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).
The HPRA has received “less than five” reports of BIA-ALCL.
“It is very important that individuals with breast implants, and the healthcare professionals who look after them, are aware that ‘breast implant illness’ and BIA-ALCL are different conditions with different symptoms, treatment options, and outcomes,” outlined the Authority’s spokesperson.
“The HPRA advises anyone who has health concerns relating to breast implants to contact their GP or implanting surgeon.”
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31 individuals may be affected by ‘breast implant illness’
DAVID LYNCH email@example.com
An eye on AI
With a national artificial intelligence (AI) strategy imminent and an increasing number of AI health projects underway in Ireland, David Lynch looks at recent trends in the area and what the future promises
The era when artificial intelligence (AI) was confined to the plot lines of sci-fi novels and movies has long since passed. Its use is established and expanding in a number of areas of medicine and the Government is due to publish its first national AI strategy in the coming weeks.
However, the use of AI in health still provokes questions, particularly around ethics, law, effectiveness, and cost.
Dr Eric Topol, an American cardiologist and author of Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again told The New York Times in 2019 that the key areas where AI shows promise included “machine pattern recognition to promote the rapid and accurate reading of medical scans, slides, skin lesions, the pickup of small polyps during colonoscopy”.
However, when asked where it is most likely to fail, he warned that “there’s no shortage of deep liabilities” for AI in healthcare.
“The liabilities include breaches of privacy and security, hacking, the lack of
explainability of most AI algorithms, the potential to worsen inequities, the embedded bias and ethical quandaries.”
Development of the use of AI is a key digital goal, Prof Martin Curley (PhD), HSE Director of the Digital Transformation and Open Innovation, told the AI Summit 2021.
The HSE had lifted its digital “maturity” level during the pandemic, he told the online conference attended by the Medical Independent (MI). He was speaking before the recent cyberattack on the HSE.
“Our ambition is to move Ireland from being a digital health laggard, to a digital health leader,” Prof Curley told delegates.
“We have made some progress during the Covid-19 pandemic; we estimate that we have lifted maturity level in the last year, but our ambition is to be a European leader by 2026.
“In general, healthcare is about a decade
Law and learning
As AI in medicine develops in the coming years, it raises new ethical and legal issues.
In an Irish Medical Journal piece last year Dr Toni Anderson, Tallaght University Hospital, and other authors, raised a number of possible medico-legal challenges created by AI in radiology.
Is there a role for medical colleges or the Medical Council in highlighting and educating in this new area?
“I am not sure if the curriculum has changed in recent years,” Dr Anderson, who qualified in 2015, told MI. “But certainly, when I was a medical student, although we learned about medical law and ethics, the curriculum really focused on our duty of care towards the patient rather than learning about areas of possible medico-legal liability regarding our own practice.”
However, she added that as AI in medicine “becomes more and more topical, it is getting more airtime in [the] university curriculum, but I doubt there is much focus on medico-legal aspects of it because it is so new”.
“As you know in Ireland, we operate a common law-based legal system, with precedent set from previous cases,” she said. “AI in medicine is still in its infancy, meaning that there is a paucity of case-law surrounding it, making
the future uncertain.”
A paper published in The Lancet in April, titled ‘AI-facilitated healthcare requires education of clinicians’, emphasised the importance of education for doctors in the use of AI.
The authors noted that AI advances “begun to percolate into medicine, with deep learning systems capable of diagnosing skin cancer and fully autonomous AI approved for diabetic retinopathy screening”.
“Although AI-enabled healthcare has huge potential, we are still only in its early stages. As the field matures, a key concern is how should clinicians be educated in these advances and what roles they will assume in developing, validating, and implementing these technologies.”
‘The impact of the introduction of Artificial Intelligence to Ireland’ T Anderson, WC Torreggiani, Department of Radiology, Tallaght University Hospital https://imj.ie/ the-impact-of-the-introduction-ofartificial-intelligence-to-ireland/
‘AI-facilitated healthcare requires education of clinicians’ by Dr Pearse
A Keane and Dr Eric J Topol www. thelancet.com/journals/lancet/article/ PIIS0140-6736(21)00722-4/fulltext
behind [other industries when it comes to AI]. What we are starting to see is a catchup... we know we are a laggard in terms of technology, but we are hoping to accelerate. One of our key focus areas is the use of AI.”
Prof Curley admitted that Ireland is “quite a way behind some of the other OECD countries. But there is an opportunity for us to leapfrog, not just into the new digital health model, but to leapfrog into the application of AI.”
He said the HSE CEO and the Chair of the board are “increasingly” aware of the digital opportunities and “they see digital as an important tool in fighting Covid-19 and modernising” the broader health service.
Prof Curley outlined how the influence of AI had spread from the everyday use of FitBits to the “huge untapped” area of drug discovery.
“In Ireland, we have to first go from automating our transactions to then going onto the ‘S curve’ of growth, which is [about] applying AI to a lot of clinical data that we will capture in the coming years.”
Prof Curley noted there is a particular focus of AI in radiology. “We also know there is a global issue around the supply of radiologists. But this is something that can be addressed quite soon using technology,” he told the AI Summit.
Last year, Dr Toni Anderson, Radiology SpR in Tallaght University Hospital, co-authored a paper in the Irish Medical Journal titled ‘The impact of the introduction of AI to Ireland.’ The paper noted that “based on the literature... not many foresee the imminent replacement of radiologists by AI”. Radiologists will remain a central crucial cog in the diagnostic process of image-based medicine, with AI acting as a “cognitive companion”.
“There is no doubt that in medicine there is a huge reliance on imaging for making diagnoses, and as such, radiologists are getting busier and busier,” Dr Anderson told MI. “There is definitely a lot of scope for AI in radiology. However, from what I’ve seen to date in our specialty, AI is not foolproof and makes errors and misinterpretations.”
Dr Anderson said the technology “currently needs the eyes of a doctor to oversee it and either concur with its findings or disagree”.
“The human body is so complex, there are innumerable anatomic variations that make every person different and knowing the patient’s previous medical history hugely impacts on the interpretation of a medical image.
“Technology is, however, obviously getting exponentially better as we have seen in other industries.”
She said there is little doubt “that it will continue to grow and augment radiology interpretation in the future. It will undoubtedly make reporting more robust and help to reduce errors.”
“It could also help in speeding up time-consuming tasks, such as following up and measuring designated multi-focal metastases in malignancy, with the ability to make multiple measurements in the fraction of the time manual measurements may take.
“Radiologists would embrace such a helpful tool,” said Dr Anderson.
This summer marks a significant moment in the history of AI in Ireland.
During his presentation to the Summit, Prof Curley said the Irish health service has “come out of the AI winter”. He added that Ireland is in the very early stages of the deployment of AI, “but we think the opportunities are really immense” and
THE MEDICAL INDEPENDENT | 10 JUNE 2021 4
Prof Martin Curley (PhD)
the next decade will see “huge changes and benefits for patients in the use of AI in healthcare”.
These changes will at least in part be directed by a new Government policy that will be unveiled in the coming weeks.
The draft national AI strategy is currently being finalised and “is expected to be published before the end of June”, a spokesperson for the Department of Enterprise, Trade, and Employment told this newspaper.
The public consultation process for the National Irish Strategy on Artificial Intelligence took place at the end of 2019. The public submission period was only open for a month (6 October-7 November 2019).
The Department only published the submissions on its website in late May 2021. There were 85 responses to an online questionnaire on the strategy. How-
ever, personal identifying information contained in these submissions has been redacted and will not be published.
There were only seven separate written submissions, none of which came from medical organisations. The organisations that submitted included IBEC, the Law of Society of Ireland and Microsoft. AI use in medicine, the ethical and other challenges it faces, is not a significant focus of any of these submissions.
The IBEC submission provided an outline of some AI developments from the business sector in recent years, noting that “IBM has been exploring AI technologies and techniques for decades”.
“IBM Research-Ireland is currently collaborating with UCD/Mater Misericordiae Hospital, the Royal College of Surgeons Ireland (RCSI), and digital pathology software company Deciphex to use AI techniques in helping surgeons to better identify cancers and improve medical interventions for patients,” outlined the IBM submission.
“The research team is using bio-physical models, applied mathematics, video analytics and AI alongside novel dye technologies to assist surgeons with cancer tissue identification and comprehension for improved precision in surgery.”
The submission also notes that Dell EMC Ireland work with healthcare organisations to deliver technological solutions “that can create positive patient outcomes”.
“Researchers at the Irish Centre for Foetal and Neonatal Translational Research (INFANT) and University College Cork are harnessing AI techniques, enabled by Dell technology, to help healthcare professionals detect seizures in new-born babies as they occur so that prompt treatment can be provided, and long-term outcomes improved.”
Given that AI in health is such a significant area, does the lack of input from medical bodies during the public submission period concern the Department in its creation of the new national strategy?
“There has been extensive consultation with stakeholders from all relevant sectors during the development of the strategy, including repeated consultations with other Departments,” a spokesperson told MI
“The Department of Health has actively engaged in these consultations and has also met with the Department of Enterprise, Trade and Employment bilaterally.”
AI in practice
Experts will be awaiting the publication of the policy with some interest.
“From my perspective, a strategy for fostering further meaningful societal engagement and ongoing consultation on AI is crucial,” Dr Maria Helen Murphy, Assistant Professor in Law at Maynooth University, told MI
Dr Murphy is an Executive Board
Member of the Irish Council for Civil Liberties and a team member of the Centre for AI and Digital Policy. She has written on AI policy matters in Ireland.
On the upcoming national policy, she said it needs to be open to future development and input.
“National AI strategies tend to be broad by nature,” she said. “So continuous consultation on specific issues with relevant and diverse stakeholders would be particularly welcome as issues evolve.”
The new national policy is being readied for publication just as the HSE is under an unprecedented cyberattack. Does this attack or those on other institutions in Ireland and abroad have an impact on AI policy?
Dr Murphy said the cyberattack “illustrates the vulnerability of systems, including our most sensitive government systems”.
She noted that, as AI relies on the processing of enormous amounts of information, “cybersecurity and data protection must be central considerations” in the development of AI policies.
Two years ago, there was a commitment in the Sláintecare Action Plan 2019 to complete research on the potential impact of AI, robotics and other technologies on workforce planning, and on services for patients and service users.
MI enquired as to the progress of this research and was told this work was currently being assessed.
“Research on this topic was delayed due to the Covid-19 pandemic and response,” a Department of Health spokesperson told MI.
However, the Department did complete the research late last year.
“The findings, including actions arising, are under consideration as part of the Sláintecare reform programme.”
million people in Ireland have private health insurance, according to new figures from the Health Insurance Authority.
29 – the percentage drop in overall level of claims during the year since the beginning of the Covid-19 pandemic.
46.4 per cent of the Irish population have private health insurance.
6,000 people die in Ireland each year from the effects of smoking, according to the HSE. International World No Tobacco Day was on 31 May.
8 million deaths every year are caused by tobacco, states the World Health Organisation.
There are a number of AI programmes currently taking place across the Irish health service.
“One of our flagship programmes is focused on emergency general surgery in Letterkenny University Hospital (LUH),” Prof Martin Curley, HSE Director of the Digital Transformation and Open Innovation, told the recent AI summit.
“We hope to have the use of AI sometime later in the year in Letterkenny.
“We know that emergency general surgery accounts for 10 per cent of all hospital admissions and has
one of the highest mortality rates in medicine... we know there is high variability in patient outcomes.”
“Digital data has enormous potential in risk assessing emergency general surgery patients and surgical decision making.”
Prof Curley said the team in LUH is led by Consultant Surgeon Mr Michael Sugrue.
“We are making good progress towards creating a new digital registry that could be used nationally.”
He said that once data is in place it will host AI systems for data collection
and clinical decision support. Some of the AI modes to be used will be a supervised learning model for assessing patients’ mortality and morbidity risk.
“We’ll have decision trees to evaluate patient pathways”, he said.
Prof Curley said this was a “project of high promise”. He also mentioned a number of other AI-based projects underway including some in St James’s Hospital, Dublin, which have helped reduce waiting lists in dermatology and another project underway to examine how AI technology can be used in the processing of particular fracture scans.
50 per cent of adults – 1.9 million – had received a first dose of Covid-19 vaccination by the end of May, including 20 per cent fully vaccinated, according to Government figures.
45 – the percentage fall in number of patients recruited to clinical trials in the first quarter of 2021, compared to the same period last year, according to Cancer Trials Ireland.
THE MEDICAL INDEPENDENT | 10 JUNE 2021 5 Feature News
Dr Maria Helen Murphy
NCCP Director raises staff burnout and endoscopy access
Staff burnout and patient access to endoscopy services were among the “key areas of concern” arising from the Covid-19 pandemic’s impact on cancer services, the Director of the National Cancer Control Programme (NCCP) told a HSE meeting in March.
Prof Risteárd Ó Laoide made a presentation to the HSE safety and quality committee on the impact of Covid-19 on cancer services.
In Ireland, the key areas of concern were patients’ access to endoscopy and cancer services’ access to data. The latter was “hindered by difficulties extracting it from various unintegrated sources and from the private sector”.
Prof Ó’Laoide emphasised that the risk of staff burnout in
This material is for healthcare professionals only
all areas including cancer services was significant, which the committee “was particularly concerned by”, stated meeting minutes.
He also advised that access to diagnostics and IT infrastructure were “the two key areas” that must be addressed in cancer services and the wider health service.
Last month, the Medical Independent reported that clinicians at Cancer Trials Ireland had written to Minister for Health Stephen Donnelly urging him to take action to prepare for an unprecedented rise in cancer cases due to missed diagnoses and treatment gaps caused by Covid-19.
On 2 June, IMO consultant committee Chair Dr Clive Kilgallen told the Oireachtas Health Committee that in the first three months of this year, 450 people per month were not seen within the recommended four weeks for an urgent colonoscopy
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(compared to 15 per month pre-Covid).
In September 2020, just 60 per cent of new patients attending rapid access breast, lung, and prostate clinics were seen within the recommended timeframe.
HSE CIO noted ‘hugely challenging’ ICT implementation
The HSE’s Interim Chief Information Officer (CIO) highlighted the “hugely challenging environment” affecting implementation of the information and communications technology (ICT) capital plan, in the weeks preceding the cyberattack.
At a meeting in February of the HSE performance and delivery committee, Mr Fran Thompson provided an update on implementation of the ICT capital plan for the first six weeks of 2021.
“The CIO advised that ICT-enabled projects are critical to the success of the health service reform agenda, however, 2021 is remaining a hugely challenging environment as the Covid-19 response continues to absorb resources,” stated meeting minutes.
“In particular, workforce management and recruitment are proving problematic, which impacts on all other elements of the plan.”
Areas such as development costs of business proposals, immunisation systems and patient-centred design thinking for ICT projects were also discussed at the meeting.
“The committee discussed the importance of patient experience of ICT projects and emphasised that the development of new systems should be user-centric.”
In April, the Medical Independent (MI) reported that difficulties in filling key roles in ICT had been raised by Mr Thompson at a meeting of the HSE’s audit and risk committee in late 2020.
In March, MI reported that Minister for Health Stephen Donnelly had sought a “more formal assessment” and “appropriate levels of accountability” of HSE investment in ICT, in correspondence sent in February to HSE board Chair Mr Ciarán Devane.
“A closer coupling and more formal assessment of the outputs of capital investment in ICT at the end of each calendar year versus the capital plan, will be required,” outlined the Minister in a letter that approved the HSE National Service Plan.
Controlling gabapentinoids under examination
The Department of Health is engaged in a process to determine whether gabapentinoids should be scheduled as controlled drugs, the Medical Independent (MI) has been informed.
A Department spokesperson told MI: “The Health Products Regulatory Authority and the Department of Health are in ongoing discussions in relation to potential for misuse or abuse of gabapentinoids. Data is being gathered on the matter before considering whether to recommend the scheduling of gabapentinoids as controlled substances.”
In a recent interview with MI, the then Medical Council President Dr Rita Doyle said pregabalin and gabapentin should be made controlled drugs in Ireland. She said addiction to pregabalin is a “huge” issue in this country. Pregabalin, also known by the brand name Lyrica, is licenced for use in epilepsy, generalised anxiety disorder, and peripheral and central neuropathic pain. Gabapentin, also known by the brand name Neurontin, is licenced for epilepsy and peripheral neuropathic pain.
Dr Doyle noted that pregabalin and gabapentin had been made controlled drugs in the UK “and I certainly foresee that will happen here”.
An over-prescribing working group at the Medical Council is also discussing prescription of opioids in Ireland.
TOMORROW IN THE FUTURE
For the management of cow’s milk allergy
without LGG ®, rice, soy or amino acids (p<0.001)
During a period of 3 years vs.
without LGG ® (p<0.001)
48 hours 2–4 successfully accelerate return to cow’s milk after 12 months of use**5 reduce the risk of future allergic manifestations by ~50%†6
Nutramigen_Trade_ad_255x166_RB_Ireland_FINAL.indd 1 18/05/2020 12:03
OF BABIES WITH COW’S MILK ALLERGY
News THE MEDICAL INDEPENDENT | 10 JUNE 2021 6
5 ADDITIONAL INDICATIONS NOW PUBLICLY AVAILABLE* IN IRELAND
KEYTRUDA, now publicly available for 5 additional indications, bringing the total number of indications now publicly available in Ireland to 9.
• NEW In combination with pemetrexed and platinum chemotherapy for the firstline treatment of metastatic non-squamous non-small cell lung carcinoma in adults whose tumours have no EGFR or ALK positive mutations.
• NEW As monotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy.
• NEW In combination with carboplatin and paclitaxel for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC).
• NEW As monotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with a combined positive score (CPS) ≥10.
• NEW As monotherapy is indicated for the adjuvant treatment of adults with Stage III melanoma and lymph node involvement who have undergone complete resection.
ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION KEYTRUDA 25 mg/mL: One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. INDICATIONS KEYTRUDA as monotherapy is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with Stage III melanoma and lymph node involvement who have undergone complete resection. KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 with a ≥1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD L1 with a combined positive score (CPS) ≥ 10. KEYTRUDA as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 1. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic HNSCC in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy. KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma (RCC) in adults. KEYTRUDA as monotherapy is indicated for the first line treatment of metastatic microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in adults. DOSAGE AND ADMINISTRATION See SmPC for full details. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. The recommended dose of KEYTRUDA as monotherapy in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes. The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL is 2 mg/kg bodyweight (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes. The recommended dose of KEYTRUDA as part of combination therapy in adults is 200 mg every 3 weeks administered as an intravenous infusion over 30 minutes. KEYTRUDA must not be administered as an intravenous push or bolus injection. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Treat patients until disease progression or unacceptable toxicity. Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. Recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. For the adjuvant treatment of melanoma, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year. KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued (a) For Grade 4 toxicity except for: endocrinopathies that are controlled with replacement hormones; or haematological toxicity, only in patients with cHL in which KEYTRUDA should be withheld until adverse reactions recover to Grade 0-1; (b) If corticosteroid dosing cannot be reduced to ≤10 mg prednisone or equivalent per day within 12 weeks; (c) If a treatment-related toxicity does not resolve to Grade 0-1 within 12 weeks after last dose of KEYTRUDA; (d) If any event occurs a second time at Grade ≥ 3 severity. Patients must be given the Patient Alert Card and be informed about the risks of KEYTRUDA. Special populations Elderly: No dose adjustment necessary. Data from patients ≥ 65 years are too limited to draw conclusions on cHL population. Data are limited in patients ≥ 75 years for pembrolizumab monotherapy in patients with resected Stage III melanoma and MSI-H or dMMR CRC; for pembrolizumab in combination with axitinib in patients with advanced RCC; for chemotherapy combination in patients with metastatic NSCLC; for pembrolizumab (with or without chemotherapy) in patients receiving first line treatment for metastatic or unresectable recurrent HNSCC. Renal impairment: No dose adjustment needed for mild or moderate renal impairment. No studies in severe renal impairment. Hepatic impairment: No dose adjustment needed for mild hepatic impairment. No studies in moderate or severe hepatic impairment. Paediatric population: Safety and efficacy in children below 18 years of age not established except in paediatric patients with cHL. CONTRAINDICATIONS Hypersensitivity to the active substance or to any excipients. PRECAUTIONS AND WARNINGS Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations. Immune-related adverse reactions Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. Most immune-related adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Immune-related adverse reactions have also occurred after the last dose of pembrolizumab. Immune-related adverse reactions affecting more than one body system can occur simultaneously. See SmPC for full details. Immune-related pneumonitis: Patients should be monitored for signs and symptoms of pneumonitis. Suspected pneumonitis should be confirmed with radiographic imaging and other causes excluded. Refer to SmPC for information on management of immune-related pneumonitis. Immune-related colitis: Patients should be monitored for signs and symptoms of colitis, and other causes excluded. Consider the potential risk of gastrointestinal perforation. Refer to SmPC for information on management of immune-related colitis. Immune-related hepatitis: Patients should be monitored for changes in liver function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and symptoms of hepatitis, and other causes excluded. Refer to SmPC for information on management of Immune-related hepatitis. Immune-related nephritis: Patients should be monitored for changes in renal function, and other causes of renal dysfunction excluded. Refer to SmPC for information on management of immune-related nephritis. Immune-related endocrinopathies: Severe endocrinopathies, including adrenal insufficiency, hypophysitis, type 1 diabetes
mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism have been observed with pembrolizumab treatment and patients should be monitored for these endocrinopathies. Refer to SmPC for information on management of immune-related endocrinopathies. Immune-related skin adverse reactions: Patients should be monitored for suspected severe skin reactions and other causes should be excluded. Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving pembrolizumab. If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued. Other clinically significant immune-related adverse reactions: The following additional clinically significant, immune-related adverse reactions, have been reported in clinical studies or in post-marketing experience: uveitis, arthritis, myositis, myocarditis, pancreatitis, Guillain-Barré syndrome, myasthenic syndrome, haemolytic anaemia, sarcoidosis, encephalitis, myelitis and vasculitis. Refer to SmPC for information on management of significant immune-related adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Allogeneic HSCT after treatment with pembrolizumab: Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with classical Hodgkin lymphoma undergoing allogeneic HSCT after previous exposure to pembrolizumab. Allogeneic HSCT prior to treatment with pembrolizumab: In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with pembrolizumab. Infusion-related reactions: For Grades 3 or 4 infusion reactions including hypersensitivity and anaphylaxis, stop infusion and permanently discontinue pembrolizumab. With Grades 1 or 2 infusion reactions, infusion may continue with close monitoring. Premedication with antipyretic and antihistamine may be considered. Overdose: There is no information on overdose with pembrolizumab. In case of overdose, monitor closely for signs or symptoms of adverse reactions and treat appropriately. INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. No metabolic drug-drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. Corticosteroids can be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. FERTILITY, PREGNANCY AND LACTATION Women of childbearing potential Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Pregnancy No data on use in pregnant women. Do not use during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Breast-feeding It is unknown whether pembrolizumab is secreted in human milk. A risk to newborns/ infants cannot be excluded. Fertility No clinical data available. SIDE EFFECTS Refer to SmPC for complete information on side effects. Pembrolizumab is most commonly associated with immune-related adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-and infusion-related adverse reactions. Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, rash, pruritus, fatigue. Common: pneumonia, thrombocytopenia, lymphopenia, neutropenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, thyroiditis, insomnia, dizziness, dysgeusia, pneumonitis, colitis, dry mouth, severe skin reactions, vitiligo, dry skin, alopecia, eczema, dermatitis acneiform, dermatitis, erythema, myositis, pain in extremity, arthritis, influenza like illness, chills, AST and ALT increases, hypercalcaemia, increase in blood alkaline phosphatase, blood bilirubin increased, blood creatinine increased, infusion related reaction. Combination with chemotherapy: Very Common: anaemia, neutropenia, thrombocytopenia, hypokalaemia, decreased appetite, dizziness, neuropathy peripheral, dysgeusia, headache, dyspnoea, cough abdominal pain, alopecia, diarrhoea, nausea, vomiting, constipation, rash, pruritus, musculoskeletal pain, arthralgia, pyrexia, fatigue, asthenia, oedema, blood creatinine increased. Common: pneumonia, febrile neutropenia, leukopenia, lymphopenia, infusion related reaction, hypothyroidism, hyperthyroidism, hyponatraemia, hypocalcaemia, insomnia, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, pneumonitis, colitis, dry mouth, severe skin reactions, erythema, dry skin, myositis, pain in extremity, arthritis, nephritis, acute kidney injury, chills, influenza-like illness, hypercalcaemia, ALT increase, AST increased, blood alkaline phosphatase increased. Combination with axitinib: Very Common: hyperthyroidism, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, dysphonia, diarrhoea, abdominal pain, nausea, vomiting, constipation, palmar-plantar erythrodysaesthesia syndrome, rash, pruritus, musculoskeletal pain, arthralgia, pain in extremity, fatigue, asthenia, pyrexia, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, anaemia, neutropenia, leukopenia, thrombocytopenia, infusion related reaction, hypophysitis, thyroiditis, adrenal insufficiency, hypokalaemia, hyponatraemia, hypocalcaemia, insomnia, dizziness, lethargy, neuropathy peripheral, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, dry mouth, hepatitis, severe skin reactions, dermatitis acneiform, dermatitis, dry skin, alopecia, eczema, erythema, myositis, arthritis, tenosynovitis, acute kidney injury, nephritis, oedema, influenza like illness, chills, blood
alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased. PACKAGE QUANTITIES KEYTRUDA 25 mg/mL: 4 mL of concentrate in a 10 mL Type I clear glass vial. Legal Category POM. Marketing Authorisation numbers EU/1/15/1024/002. Marketing Authorisation holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: March 2021. © Merck Sharp & Dohme B.V. 2021. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 or from www.medicines.ie. Date of Preparation: May 2021. II/090. Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to MSD (Tel: 01-2998700) References 1. Keytruda Summary of Product Characteristics, May 2021, available at www.medicines.ie. IE-KEY-00382 Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 Ireland
* Reimbursed as of May 1st 2021 on the Oncology Drugs Management System
5057_KEYTRUDA_Reimbursement5_Ad_250_346_v.indd 1 17/05/2021 16:28
Concern over MHC’s dependence on agency staff
The Mental Health Commission’s (MHC) finance, audit and risk committee (FARC) expressed concern earlier this year about the Commission’s “high dependency” on agency staff.
At a meeting of the MHC’s board in February, Chair of the FARC Mr Patrick Lynch welcomed the budgetary allocation for 2021, which amounted to €21.2 million.
However, Mr Lynch noted the FARC had concerns in relation to the high dependency on agency staff in 2021.
The increase in agency staff levels was “due to identified staffing shortages needed to deliver statutory functions, additional reporting responsibilities required by NPHET [national public health emergency team] due to Covid-19, covering short-term vacancies due to maternity leave and
leavers”, according to meeting minutes.
“It was noted that the executive is actively reviewing its agency requirements and furthermore, there is an action in the 2021 business plan to review the staffing levels and activities of staff within the organisation.”
It was further noted there was no sanction from the Department of Health in 2020 to take on additional permanent staff, notwithstanding the additional work relating to Covid-19.
The MHC’s 2021 budget includes additional once-off projects, which had been included in the business plan for the year.
The FARC requested that a mid-year review of expenditure to date be completed by the executive. If there were significant savings mid-year, additional projects would then be proposed for the second half of the year.
Covid-19 presented challenges for HIV treatment access
EMILY CLARKE GIFFORD
People living with HIV faced notable challenges in accessing treatment during the Covid-19 pandemic, the Clinical Lead of the HSE’s Sexual Health and Crisis
Pregnancy Programme has told the Medical Independent (MI)
Due to Covid-19 restrictions, patients found it challenging travelling to HIV clinics, with some fearing the use of public transport.
Prof Fiona Lyons, Consultant in Genitourinary and HIV Medicine at St James’s Hospital, Dublin, said patients experienced “quite a lot of stress around having to travel and to collect their medication and having to go through checkpoints”.
She told MI “a lot of work had to be done” to ensure patients continued to receive their medications.
Some patients expressed concern about visiting the HIV clinics to receive medication or to get tested.
As a result of the pandemic, HIV clinics were reconfigured to allow for greater social distancing.
In addition, arrangements were made by HIV clinics to send patient files to those living abroad to ensure they could access their
Prof Lyons said a key priority early in the pandemic was to maintain treatment for people living with HIV and see those newly diagnosed.
While Prof Lyons said this “hasn’t been easy”, she hoped that access will improve as society emerges from the “worst” of the pandemic.
According to provisional data from the Health Protection Surveillance Centre, published last year, there were 539 diagnoses of HIV notified in 2019. The organisation HIV Ireland stated this was the highest level in Ireland since records began.
Dr Nicola O’Sullivan, an independent social care consultant, speaking before the ‘Reconnecting with the heart of frontline practice’ one-day virtual seminar. The seminar, which was held on 25 May, explored the roles of humility, vulnerability, and compassion in frontline practice.
Meanwhile, the Inspector of Mental Health Services has said the use of mechanical restraint in one of the country’s child and adolescent mental health centres is a concerning development.
Dr Susan Finnerty’s comments were made with regard to Linn Dara Child and Adolescent Mental Health Service in Dublin 10, one of three inspection reports recently published by the MHC.
In total, the reports identified four critical and 10 highrisk non-compliances.
“The use of mechanical restraint in the form of soft cuffs for a young person in Linn Dara is of significant concern,” according to Dr Finnerty. “Nationally, the use of mechanical restraint is confined to the adult forensic mental health services and then only in very limited circumstances, involving transport to and from the Central Mental Hospital.”
Rotunda presses ahead with critical care wing development
The Rotunda Hospital in Dublin has commenced the process of selecting a design team to lead the development of a new critical care wing for the hospital.
According to tender documents: “With the likelihood of the hospital remaining on campus for the next 15-to-20 years, the Rotunda needs to upgrade its ageing infrastructure in order to continue to provide services to women and babies in an appropriate environment.”
The documents outline the hospital’s requirements to address its most urgent critical care and clinical infrastructural deficiencies.
These include: A new intensive care unit together with other areas, such as outpatients, ward accommodation, “labour and delivery”, and various additional clinical and support accommodation.
“These requirements will be brought together as a project to form a new critical care wing for the hospital,” according to the document.
“In the normal way for a project of this scale and complexity, any future development at the Rotunda Hospital must be designed in an orderly manner, reflecting the requirement to protect the ongoing clinical activity on the wider hospital campus.
“Consideration will therefore be given to the most appropriate approach to deliver the project requirements, while protecting current activity and future development potential on the hospital campus. The critical care wing develop-
ment will be set out as part of an overall coherent and ordered plan for the campus, and the design team will be required to advise on the most appropriate approach in that context.”
The principal services sought in the tender include: Architectural services; quantity surveying; mechanical and electrical engineering; and civil and structural engineering.
Following the conclusion of this competition, the services of all design team disciplines will be provided together, led by the architectural consultant who will act as the design team leader. Interested parties were to issue their submissions by the end of May.
The Medical Independent recently reported that roof damage at the Rotunda’s colposcopy/ administration building represented a “major” infrastructural risk as it housed the main IT server room. In addition, a cap remained on admissions to the neonatal intensive care unit to mitigate infection risks associated with constrained infrastructure.
8 THE MEDICAL INDEPENDENT | 10 JUNE 2021 News
It is an essential task for frontline practitioners to contain the anxiety and vulnerability of those in their care and that can be hard to sustain. We know that many in frontline professional roles are often so busy responding to competing and complex service demands that they find it hard to get in touch with that fatigued part of themselves.”
Prof Fiona Lyons
The Rotunda Hospital, Dublin
This online system will help make Covid-19 testing more available and will mean that in these three locations those seeking a Covid-19 test – whether symptomatic or asymptomatic, can attend a walk-in centre or book their test online in advance.”
HSE National Lead Testing and Tracing Ms Niamh O’Beirne on the new online booking system for Covid-19 tests, which is being piloted for people living in the vicinity of three test centres: Citywest, and the National Show Centre Swords in Dublin, and Letterkenny in Co Donegal.
The information we have so far shows that the Covid-19 vaccines do not have any negative effect on babies in the womb. We would strongly encourage people to consider taking up their vaccine when offered, as it greatly reduces the chances of you becoming unwell from the Covid-19 virus.”
Dr Peter McKenna, National Clinical Director of the HSE National Women and Infants Health Programme, on pregnant women between 14 and 36 completed weeks gestation now being offered an mRNA vaccine.
treatment of HIV-1
Make Doravirine a Part of Every Day
DELSTRIGO® (100 mg doravirine/300 mg lamivudine/300 mg tenofovir disoproxil fumarate, equivalent to 245 mg of tenofovir disoproxil) is indicated for the treatment of adults infected with HIV-1 without past or present evidence of resistance to the NNRTI class, lamivudine, or tenofovir.1
PIFELTRO® (doravirine) is indicated, in combination with other antiretroviral medicinal products, for the treatment of adults infected with HIV-1 without past or present evidence of resistance to the NNRTI class.2
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
doravirine. Delstrigo: film-coated tablet containing 100 mg doravirine, 300 mg lamivudine and 300 mg tenofovir disoproxil fumarate, equivalent to 245 mg of tenofovir disoproxil. INDICATIONS Pifeltro: For use in combination with other antiretrovirals, for the treatment of HIV-1 without past or present evidence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). Delstrigo: For the treatment of HIV-1 without past or present evidence of resistance to NNRTIs, lamivudine or tenofovir. DOSAGE AND ADMINISTRATION Therapy should be initiated by a physician experienced in HIV infection management.
Pifeltro: One 100 mg tablet once daily. Delstrigo: One 100/300/245 mg tablet once daily. Pifeltro and Delstrigo: If co-administered with rifabutin or other moderate CYP3A inducers, increase doravirine dose to 100 mg twice daily (12 hours apart). Pifeltro: Elderly: No dose adjustment necessary. Renal impairment: No dose adjustment necessary. Hepatic impairment: mild to moderate: no dosage adjustment required; severe: use with caution. Delstrigo: Elderly: Special care advised. Renal impairment: estimated creatinine clearance (CrCl) ≥ 50 mL/min: no dose adjustment necessary; estimated CrCl <50 mL/min: not recommended. Hepatic impairment: mild to moderate: no adjustment required; severe hepatic: use with caution. CONTRAINDICATIONS Hypersensitivity to the active substance or excipients Co-administration with strong CYP3A inducers. PRECAUTIONS AND WARNINGS A residual risk of sexual transmission of HIV-1 cannot be excluded and precautions should be taken in accordance with national guidelines. Use with CYP3A inducers may reduce the exposure of doravirine. Autoimmune disorders (such as autoimmune hepatitis) and immune reactivation syndrome have been reported in patients treated with combination antiretroviral therapy which may require investigation and treatment. Contains lactose monohydrate. Delstrigo: Post-treatment exacerbation of HBV (including hepatic decompensation and liver failure) have been reported in patients co-infected with HIV-1 and HBV following discontinuation of lamivudine or tenofovir disproxil. Monitor patients co-infected with HIV-1 and HBV after discontinuation of Delstrigo and if appropriate initiate anti-HBV therapy. Renal impairment, including acute renal failure and Fanconi syndrome have been reported with tenofovir disoproxil. Assess estimated CrCl prior to initiation and during therapy. In patients at risk of renal dysfunction, serum phosphorus, urine glucose, and urine protein should also be assessed. Discontinue therapy if estimated CrCl declines below 50 mL/min. Avoid with concurrent or recent use of nephrotoxic medicinal products (e.g. high-dose or multiple NSAIDs). Evaluation of renal function is recommended for persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness. Assessment of bone mineral density should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms. Doravirine/lamivudine/tenofovir disoproxil must not be co-administered with other medicinal products containing lamivudine, tenofovir disoproxil, or tenofovir alafenamide or with adefovir dipivoxil. Doravirine/lamivudine/tenofovir disoproxil should not be administered with doravirine unless needed for dose adjustment (e.g. co-administered with rifabutin). Drug interactions: Refer to SmPC for full information on drug interactions. Pifeltro and Delstrigo: Doravirine is metabolized
primarily by CYP3A. Do not co-administer with strong CYP3A enzyme inducers. If co-administration with rifabutin or other moderate CYP3A inducers cannot be avoided, increase doravirine dose to 100 mg twice daily (taken 12 hours apart). Use with caution when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that have a narrow therapeutic window (e.g., midazolam, tacrolimus and sirolimus). Delstrigo: Do not administer with other antiretroviral medicinal products. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion may increase serum concentrations of lamivudine. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion via OAT1, OAT3 or MRP4 may increase serum concentrations of tenofovir. Avoid with concurrent or recent use of nephrotoxic medicinal products. Pregnancy and Lactation: Pifeltro and Delstrigo: Avoid use during pregnancy. An Antiretroviral Pregnancy Registry has been established. Breastfeeding is not recommended. SIDE EFFECTS Refer to SmPC for complete information on side-effects. Pifeltro and Delstrigo: Common: abnormal dreams, insomnia, headache, dizziness, somnolence, nausea, diarrhoea, abdominal pain, flatulence, vomiting, rash, fatigue alanine aminotransferase increased. Uncommon: hypophosphataemia, nightmare, depression, suicidal ideation, paraesthesia, asthenia. Rare: hypomagnesaemia, blood creatine phosphokinase increased. Delstrigo: Common: cough, nasal symptoms, alopecia, muscle disorders, fever. Uncommon: neutropenia, anaemia, thrombocytopenia, pancreatitis, rhabdomyolysis, proximal renal tubulopathy (including Fanconi syndrome), aspartate aminotransferase increased. Rare: lactic acidosis, hepatitis, angioedema, myopathy, acute renal failure, renal failure, acute tubular necrosis, nephritis (including acute interstitial) and nephrogenic diabetes insipidus. Very Rare: pure red cell aplasia, peripheral neuropathy (or paraesthesia). Lactic acidosis Cases of lactic acidosis have been reported with tenofovir disoproxil alone or in combination with other antiretrovirals. Patients with predisposing factors such as patients with decompensated liver disease, or patients receiving concomitant medications known to induce lactic acidosis are at increased risk of experiencing severe lactic acidosis during tenofovir disoproxil treatment,
PIFELTRO® ▼ (Doravirine) DELSTRIGO® ▼ (Doravirine/Lamivudine/Tenofovir disproxil fumarate) This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SPC for how to report adverse reactions. ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION Pifeltro: film-coated tablet containing 100 mg
PACKAGE QUANTITIES Bottle of 30 tablets. Legal Category: POM. Marketing Authorisation numbers: Pifeltro: EU/1/18/1332/001. Delstrigo: EU/1/18/1333/001. Marketing Authorisation Holder: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: June 2020. © Merck Sharp & Dohme B.V., 2020. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 or from www.medicines.ie. Date of Preparation: April 2021. IB/0019. References: 1. DELSTRIGO Summary of Product Characteristics, June 2020. 2. PIFELTRO Summary of Product Characteristics, November 2019. Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to MSD (Tel: 01-2998700) Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 Ireland 5002_Doravirine_250_346_Ad_April2021_v.indd 1 27/05/2021 20:22
Epileptologists seek inclusion of purified CBD product in State programme
Neurologists specialising in epilepsy are urging inclusion of a purified cannabidiol product in the State’s medical cannabis access programme. Catherine Reilly reports
Most Irish neurologists specialising in epilepsy will be highly reluctant to utilise the Government’s long-awaited medical cannabis access programme (MCAP) until a purified cannabidiol (CBD) product is included, the Medical Independent (MI) understands. The MCAP was due to launch this month.
A group of leading neurologists have advised Minister for Health Stephen Donnelly not to launch the scheme until a purified CBD product is made available in accordance with the Department of Health’s clinical guidance on medical cannabis. This situation could undermine a scheme that aims to facilitate better access to cannabis-based products of a standardised quality for three indications, where standard treatments have failed.
The three indications are spasticity associated with multiple sclerosis; intractable nausea and vomiting associated with chemotherapy; and severe refractory epilepsy.
As of late May 2021, four products had been accepted under the MCAP. Applications are submitted by suppliers on an ongoing basis and a “small number” were currently under review at the Health Products Regulatory Authority (HPRA), which assists the Department in the assessment of applications.
The products must meet the requirements of the Misuse of Drugs (Prescription and Control of Supply of Cannabis for Medical Use) Regulations 2019.
Letter to Minister
In correspondence sent in April to Minister Donnelly, nine neurologists and neurophysiologists representing the HSE National Clinical Programme in Epilepsy, Epilepsy Ireland and the Irish Epilepsy League, welcomed the MCAP as a means of providing “a safer, more controlled environment” whereby people with severe, treatment-resistant epilepsy can access cannabis-based products.
However, their understanding was the MCAP had no purified CBD product for severe refractory epilepsy that met the criteria in the Department’s clinical guidance document.
They said that “the evidence supporting use of purified (>98 per cent) CBD in epilepsy is far more encouraging than the published evidence supporting use of THC [tetrahydrocannabinol] both in terms of efficacy and safety”.
“Purified CBD has been shown in clinical trials to be effective for some patients with specific diseases associated with severe epilepsy such as Dravet syndrome, tuberous sclerosis and Lennox-Gastaut syndrome. In addition, CBD is proving to be relatively safe for patients, albeit under clinical supervision (as CBD can interact with conventional anti-seizure medications, and has some risk of side-effects).
“On the other hand, not only is there a lack of evidence to support the use of THC in epilepsy, but there are significant concerns regarding its psychiatric and cognitive effects, particularly when used in children.”
They said a number of “high potency” THC products had been accepted under the MCAP.
The correspondence pointed to “significant misunderstanding” among patients and the public regarding the role of cannabis-based products and a risk of “heightening” expectations.
“This is in contrast to the available data and the significant concerns among neurologists who will be tasked with supervising the administration of MCAP-supported products.”
Epidyolex, the only authorised CBD-only medicine for certain forms of epilepsy, had not yet been reimbursed by the HSE. The neurologists had hoped the MCAP would provide a means for accessing a purified CBD product for people with severe epilepsy pending availability of Epidyolex in Ireland.
Products containing only CBD and 0 per cent THC are not
included within the scope of the MCAP (typically CBD-only products have ‘trace’ THC).
Epilepsy Ireland has highlighted a lack of clarity as to whether CBD-only products that contain only trace elements of THC can be processed for inclusion in MCAP as per the existing legislation, as these products may or may not be considered as “controlled”. MI also understands that because the regulations only allow for products available in another EU country, potential UK options appear to be excluded.
According to the HPRA, an application submitted for a cannabis-based product with “any level of THC, including a product containing predominantly CBD”, could be considered for inclusion. This includes products with trace THC.
The HPRA’s spokesperson said the review process also involved establishing whether a product was aligned with the Department’s clinical guidance.
Consultant Neurologist at Beaumont Hospital in Dublin, Dr Peter Widdess-Walsh, who was a signatory of the letter to Minister Donnelly, said neurologists wanted to abide by “evidence-based medicine where an evidence-base is clinical trials”.
“And we have good clinical trial data for cannabidiol for initially Dravet syndrome, then Lennox-Gastaut syndrome and just recently tuberous sclerosis,” he told MI
“Our group consensus as neurologists and paediatric neurologists around the country is that we only favour using evidence-based products, which means cannabidiol and not these other products – that is not to say necessarily that we haven’t tried them from time to time.
“But in terms of a national programme that is going to be paid for by the Department of Health and made available around the country, we only want to use safe evidence-based products that we know how to use, and we know will be safe….
“The products currently in the access programme we don’t feel comfortable using and we may not actually use them at all.”
He confirmed patients with treatment-resistant and other epilepsies regularly enquire about medical cannabis – including those for whom “we wouldn’t prescribe it or think it would be appropriate”.
“We wish there was a better PR education set-up to inform practitioners, GPs, pharmacists, patients, about the relevant important points to know – for instance, the difference between cannabis-based products and cannabis-based medicines.”
In most cases patients accepted their consultant’s “advice and reassurance”.
“But I guess, yes, there are some who put a little bit more pressure on us to prescribe cannabis products or even THC-containing products. All we can do is try and talk to them, reassure them and advise them, and try to educate them about what is evidence-based, what we think is safe and what is not.”
Dr Widdess-Walsh expressed concern the MCAP will be launched with “fanfare” by politicians while not providing any products that the neurologists deemed appropriate for epilepsy.
The programme will also entail significant administrative work for “very stretched” neurology services.
“We have identified that we probably need about four fulltime equivalent support staff to do this around the country, with two centres, one in the east and south, that would be able to coordinate this and collect data.”
Dr Widdess-Walsh added that medical cannabis was not the only potential option for people with drug-resistant epi-
lepsy. Surgical and stimulation device options may be considered as well as the ketogenic diet, with a dietary centre established in St James’s Hospital, Dublin.
However, some other potential treatments are not available in Ireland.
“For example, there is a device we’d love to have that is available in the US called an RNS or responsive nerve stimulation Neuropace device, which can pick up and detect and stimulate seizure areas in the brain to stop them.”
Neurologists are exploring the introduction of deep brain stimulation for epilepsy, which is approved in Europe.
There was also a “promising” new drug called cenobamate. Some Irish patients were receiving this drug, which is approved in the US, through an early access programme.
Asked if outcomes were improving for syndromes such as Dravet and Lennox-Gastaut, Dr Widdess-Walsh said “they are probably better than they were 10 years ago”.
He stated that CBD “can make a big difference” to some of these patients. But “not everyone”, he underlined.
If a randomised controlled trial (RCT) demonstrated THC as safe and effective in epilepsy, it would be used. “But we don’t have that information at the moment.”
Many professional neurological associations in other countries have adopted this position.
However, some clinicians have suggested this reflects an orthodoxy and conservatism in the medical profession.
According to Prof Mike Barnes, a UK-based neurologist who specialised in neuro-rehabilitation and is now a consultant on medical cannabis: “High CBD with a little bit of THC… works remarkably well in the full spectrum products. The neurologists and paediatric neurologists, I am going to be blunt – they don’t understand or don’t want to understand.”
He noted that access issues often involved children with severe treatment-resistant epilepsies who had “come to the end of the road with licensed medicines”.
“They have tried all the licensed anticonvulsants. They have tried the ketogenic diet; [some] have even been referred for brain surgery. I am not saying at all that cannabis is the first-line medicine, not in the slightest. Try the licensed medicines.”
While RCTs may be conducted where a cannabis entity such as CBD is purified and compared to placebo, “you lose out on the entourage effect of the plant,” claimed Prof Barnes.
“You get a better effect for epilepsy, pain or anxiety if you take the whole plant because it has got a whole number of different cannabinoids and different terpenes that seem to work synergistically together to produce a better effect.”
Prof Barnes referred to a recent study of whole plant medical cannabis products by Project Twenty21, which aims to create the UK’s “largest body of evidence for the effectiveness and tolerability of medical cannabis”.
The retrospective open-label study was based on reports from carers and clinicians involved in the management of the children’s care. It reported, on average, a 84 per cent reduction in monthly seizure frequency across the cohort (21 children with treatment-resistant epilepsy) with “no significant adverse event”.
Prof Barnes also cited an observational data meta-analysis, published in Frontiers in Neurology in 2018 (Pamplona et al), which stated CBD-rich extracts seemed to present a better therapeutic profile than purified CBD in a population of patients with refractory epilepsy.
The authors (who were involved in commercial development of medical cannabis) said this was likely due to the synergistic effects of CBD with other phytocompounds (‘entourage effect’), but “this remains to be confirmed in controlled clinical studies”.
At press time, MI awaited responses from the HSE and Department in regard to the MCAP.
THE MEDICAL INDEPENDENT | 10 JUNE 2021 10
Dr Peter Widdess-Walsh
CATHERINE REILLY firstname.lastname@example.org
Skudexa ® 75 mg/25 mg ﬁlm-coated tablets (tramadol hydrochloride/dexketoprofen).
Abbreviated Prescribing Information
Please consult the Summary of Product Characteristics (SmPC) for full prescribing information.
Presentation: Film-coated tablets containing tramadol hydrochloride 75 mg and dexketoprofen 25 mg. Excipients with known effects: croscarmellose sodium and sodium stearyl fumarate
Use: Symptomatic short term treatment of moderate to severe acute pain in adult patients whose pain is considered to require a combination of tramadol and dexketoprofen. Dosage:
Adults: 1 tablet (75 mg tramadol hydrochloride/ 25 mg dexketoprofen), additional doses as needed with a minimum dosing interval of 8 hours. Maximum daily dose 3 tablets/day. Use lowest effective dose for the shortest duration necessary to control symptoms. Maximum duration of use is 5 days. Patients with mild-moderate hepatic dysfunction or mild renal dysfunction: maximum daily dose is 2 tablets/day. Elderly: initial dose is 2 tablets/day can be increased to a maximum of 3 tablets/day after good tolerance established. Use with caution in patients over 75 years. Contra-indications: Hypersensitivity to any component or other NSAID or excipients. NSAID induced attacks of asthma, bronchospasm, acute rhinitis, or nasal polyps, urticaria or angioneurotic oedema. Known photoallergic or phototoxic reactions during treatment with ketoprofen or ﬁbrates. History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Active peptic ulcer/gastrointestinal/ haemorrhage or any history of gastrointestinal bleeding, ulceration or perforation, chronic dyspepsia, other active bleeding or bleeding disorders, Crohn’s disease or ulcerative colitis, severe heart failure, moderate-severe renal dysfunction, severe hepatic dysfunction, haemorrhagic diathesis and other coagulation disorders, severe dehydration. Acute intoxication with alcohol, hypnotics, analgesics, opioids or psychotropic medicinal products. Concomitantly with MAO inhibitors or within 14 days of having taken them. Inadequately controlled epilepsy. Severe respiratory depression. Pregnancy and lactation. Warnings and precautions: Dexketoprofen: Caution in allergic conditions. Avoid use with concomitant other NSAIDs including COX-2 selective inhibitors. Gastrointestinal bleeding, ulceration or perforation which can be fatal, have been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. When gastrointestinal bleeding or ulceration occurs withdraw treatment. The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in older people. Ensure cure of oesophagitis, gastritis and/or peptic ulcer before starting treatment. Consider combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors), and in patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk. Monitor patients with a history of gastrointestinal toxicity, particularly when elderly, for unusual abdominal symptoms (especially gastrointestinal bleeding) particularly in the initial stages. Caution in patients receiving oral corticosteroids, anticoagulants, SSRIs or anti-platelet agents. Caution in patients with impairment of renal function, receiving diuretic therapy or those who could develop hypovolaemia. Ensure adequate ﬂuid intake. Caution in liver impairment. Appropriate monitoring and advice required with history of hypertension and/or mild to moderate heart failure. Special caution in patients with cardiac disease, especially episodes of previous heart failure. Only treat patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease after careful consideration. Similarly for risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking). Caution in haematopoietic disorders, systemic lupus erythematosus, connective tissue disorders, impairment of hepatic and/or renal functions, history of hypertension and/or heart failure, diuretic therapy, the elderly. Older people are more likely to be suffering from impaired renal, hepatic and cardiovascular function. Serious skin reactions (some of them fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis were reported very rarely. Particular caution is required in patients with congenital disorder of porphyrin metabolism, dehydration, directly after major surgery. Severe acute hypersensitivity reactions have been observed on very rare occasions. Discontinue treatment at the ﬁrst signs of severe hypersensitivity reactions. Can cause asthma attacks or bronchospasm, particularly in subjects allergic to acetylsalicylic acid or NSAIDs. Avoid use in case of varicella. Do not use with warfarin, other coumarins or heparin. Can mask the symptoms of infectious diseases. Tramadol: Use with particular caution in patients with an addiction, head injury, shock, reduced level of consciousness of uncertain origin, disorders of respiratory centre or function or increased intracranial pressure. Use with caution in patients sensitive to opiates. Care should be taken in treating patients with respiratory depression, with concomitant CNS depressant drug administration or signiﬁcant excess of the recommended dose as resulting respiratory depression cannot be excluded. Convulsions have been reported with recommended doses of tramadol, this risk may increase when exceeding the recommended upper daily dose limit (400mg). Seizure risk increases in patients taking other seizure threshold lowering medications. Only treat patients susceptible to seizures with tramadol if circumstances are compelling. Tolerance, psychic and physical addiction may develop. For patients with abuse/dependence potential only treat for short periods under strict medical supervision. Consider tapering dose gradually when discontinuing treatment to prevent withdrawal symptoms. CYP2D6 deﬁciency may reduce the analgesic effect, whereas ultra-rapid metabolisers of CYP2D6 incur risk of opioid toxicity even at commonly prescribed doses. Extreme caution and close monitoring for opioid toxicity required when administering tramadol to children for post-operative pain relief. Not recommended in children with compromised respiratory function. Skudexa: Not for use in children and adolescents. Concomitant use with sedative medicines such as benzodiazepines or related drugs should be reserved for patients with no alternative treatment options, using the lowest effective dose and an as short as possible treatment duration while following them closely for signs of respiratory depression and sedation. Interactions:
Dexketoprofen: Other NSAIDs, anti-coagulants, heparins, corticosteroids, lithium, methotrexate, hydantoines and sulphonamides, diuretics, ACE inhibitors, antibacterial aminoglycosides and angiotensin II receptor antagonists, pentoxyﬁlline, zidovudine, sulfonylureas, betablockers, cyclosporin and tacrolimus, thrombolytics, anti-platelet agents and SSRIs, probenecid, cardiac glycosides, mifepristone, quinolone antibiotics, tenofovir, deferasirox, pemetrexed.
Tramadol: MAOIs, coumarin derivatives (e.g. warfarin), mixed agonists/antagonists opioid receptors (e.g. buprenorphine, nalbuphine, pentacozine), SSRIs, SNRIs, tricyclic antidepressants, antipsychotics and other seizure threshold-lowering medication (e.g. bupropion, mirtazapine, tetrahydrocannabinol), sedative medicines such as benzodiazepines, centrally depressant medications or alcohol, cimetidine, carbamazepine, ondansetron (5-HT3 antagonist) and substances inhibiting CYP3A4 (e.g. ketoconazole, erythromycin). Pregnancy and lactation: Contra-indicated during pregnancy and lactation. Do not use in women attempting to conceive. Side-effects: Skudexa: Common (≥ 1/100, <1/10): dizziness, nausea, vomiting. Uncommon (≥ 1/1000, <1/100): thrombocytosis, laryngeal oedema, hypokalaemia, psychotic disorder, headache, somnolence, periorbital oedema, vertigo, tachycardia, hypertensive crisis, hypotension, abdominal distension, constipation, dyspepsia, raised LFTs, face oedema, hyperhidrosis,urticaria, haematuria, asthenia, chills, discomfort, feeling abnormal, BP increased, increased alk phos, increased LDH. For less frequent side effects and side effects associated with the individual constituentssee SmPC. Pack size: 15 tablets. Legal category:
POM A Marketing authorisation number: PA 865/20/1 Marketing authorisation holder:
Menarini International Operations Luxembourg S.A., 1 Avenue de la Gare, L-1611 Luxembourg.
Marketed by: A.Menarini Pharmaceuticals Ireland Ltd. Further information is available on request to A Menarini Pharmaceuticals Ireland Ltd, 2nd Floor, Castlecourt, Monkstown Farm, Monkstown, Co. Dublin Co. Dublin, Ireland A96 T924 or may be found in the SmPC. Date of preparation: January 2020
This medicinal product is subject to additional monitoring. This will allow quick identiﬁcation of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@ hpra.ie. Adverse events should also be reported to A. Menarini Pharmaceuticals Ireland Ltd. Phone no: 01 284 6744.
75mg/25mg ﬁlm coated tablets
Fixed Dose Combination for Moderate to Severe Acute Pain1
CENTRAL & PERIPHERAL ACTION2
LONG LASTING PAIN RELIEF3*
FAST ACTING EFFICACY 3
Multimodal analgesia with central and peripheral action.2,4
* In a model of acute pain (third molar extraction) Skudexa demonstrated a median duration of action of 8.1 hours post-dose3
References: 1. Skudexa Summary of Product Characteristics, October 2019 2. Moore RA et al. BMC Anaesthesiol. 2016; 16:9 3. Moore RA et al. The Journal of Headache and Pain. 2015; 16:60 4. McQuay HJ et al. Br J Anaesthesia. 2016; 116:269-276
of item: January 2020. IR-SKU-19-2019
Continued strides in HIV treatment
Emily Clarke Gifford speaks to Clinical Lead of the HSE's Sexual Health and Crisis Pregnancy Programme, Prof Fiona Lyons, about the challenges Covid-19 has posed for people living with HIV, new treatments, and the stigma still faced by this population
It is estimated that there are over 6,000 people living with human immunodeficiency virus (HIV) in Ireland.
According to provisional data from the Health Protection Surveillance Centre (HPSC), published last year, there were 539 diagnoses of HIV notified in 2019. The organisation HIV Ireland pointed out this was the highest level in Ireland since records began.
In 2018, there were 523 diagnoses of HIV notified, according to HPSC data for that year.
In addition to the existing issues such as ensuring diagnosis, and combatting ongoing societal stigma, people with HIV are facing new challenges due to the Covid-19 pandemic.
Speaking to the Medical Independent (MI), Consultant in Genitourinary Medicine at St James’s Hospital, Dublin, and Clinical Lead of the HSE’s Sexual Health and Crisis Pregnancy Programme, Prof Fiona Lyons, said that maintaining treatment regimens for people with HIV was prioritised during the pandemic.
“The bottom line very early on in the pandemic was certainly the key priority for services, and [that] was to maintain treatment for people who were living with HIV,” as well as seeing those who were newly diagnosed, Prof Lyons told MI
She explained that people’s access to testing has been “impacted at different stages in the last 15 months”. While Prof Lyons said this “hasn’t been easy”, she hoped that access will improve as society emerges from the “worst” of the pandemic.
Prof Lyons said that travelling to receive medications was a new challenge that people with HIV faced. This was due to the stress some patients felt when collecting medication and having to go to the clinics, while Covid-19 restrictions were in place.
She added that “some of our patients are stuck overseas; that was a really big challenge for patients and trying to make sure that they were maintained on treatment”.
In response to this, Irish HIV clinics had to arrange for medical files to be sent abroad so people had access to medication where they were based. “There's no onesize-fits-[solution]…. It had to be very bespoke to the individual circumstances,” said Prof Lyons.
A lot of work was done to ensure “everyone went for their treatments, including working with people on an individual basis to ensure they did not miss out on their medication”, she said
HIV treatments have always been free of charge in Ireland and Prof Lyons outlined that there was a “vast array” of treatments available to people.
In a 2018 audit, it was found that 90 per cent of people who were attending HIV services were on treatment and over 90 per cent had viral suppression, she explained.
In terms of new medication, injectable cabotegravir/rilpivirine has been approved by regulators in North America and Europe as an antiretroviral HIV
treatment. Rilpivirine is from a class of drugs known as non-nucleoside reverse transcriptase inhibitors. Cabotegravir is from a class of drugs known as integrase inhibitors. The two work together to reduce the viral load of HIV in a person’s body.
Recently, data released from the phase 3 ATLAS study on long-acting cabotegravir and rilpivirine for the treatment of HIV showed continued virologic suppression to 96 weeks.
The European Medicines Agency approved both a once-monthly and an every-other-month regimen. In the US and Canada, only the monthly regimen received approval.
Prof Lyons told MI that the treatment will go through the Irish approval process in due course.
In a panel discussion at the Conference on Retroviruses and Opportunistic Infections 2021, Prof Diane Havlir, Professor of Medicine and Chief of the HIV/AIDS Division at the University of California, San Francisco, US, said that the next decade promises to be an era of long-acting products.
Long-acting treatments give more options to patients who find it difficult to take medication on a daily basis.
The report also recommended that more information was needed to create an awareness of the rights of people living with HIV regarding employment, health, social services, education, and housing.
Just over half (56 per cent) of people living with HIV were aware that it is illegal to discriminate against a person with HIV.
Employers, unions, schools and other educational institutions, primary health care providers, and housing bodies, need to have a greater awareness that to discriminate on the basis of HIV status is illegal under the Employment Equality Act 1998 and the Equal Status Acts 2000 and 2004.
In response to stigma and misinformation, the HSE launched a campaign on the issue in January 2020. Campaign posters with the tagline, ‘Effective treatment means you can’t pass HIV onto partners’ appeared on public transport, social venues, and college locations across the country, as well as on digital platforms. The campaign also referenced the global U=U campaign (‘undetectable equals untransmittable’).
Prof Lyons explained that the campaign aimed to emphasise that “people who are on treatment cannot transmit HIV”.
“That is something that should serve to reduce the amount of stigma, because a lot of the stigma is around people's fear that they're going to acquire HIV,” she said.
While there is an abundance of material on HIV treatments available online, Prof Lyons emphasised the need for more information.
“We know that if we can get the information out there to people that effective treatment prevents transmission through sexual contact, then that's going to help with that stigma that people experience.”
While there is no cure for HIV, current treatments can offer people a “functional cure”, said Prof Lyons. When on treatment, people living with HIV have viral suppression and can live a full life.
Prof Lyons said the situation where people on treatment can enjoy a similar life expectancy to the general population represented “massive progress in medicine”.
Regarding her work in the area, Prof Lyons said that “it’s been an amazing journey for me as a doctor", going from a situation where patients had limited life expectancy to now, where patients can expect a normal life.
Although HIV treatments have been available since the 1980s, people living with HIV still face significant stigma.
According to HIV Ireland’s 2019 report 'HIV-related stigma and discrimination in Ireland today ', 84 per cent of those living with HIV agreed that they were viewed negatively by Irish society.
Among the general public, 54 per cent of people agreed that people with HIV were viewed negatively, ranking third to drug users and Travellers in terms of stigma.
Despite this, 77 per cent of the population expressed sympathy and understanding towards those living with HIV/ AIDS. However, 23 per cent said they would be worried about eating a meal that was prepared by someone with HIV and 37 per cent agreed that if a family member were to contract the virus, they would keep their HIV status a secret. The report said the more personal the experience of HIV, the greater the perceived stigma and discrimination.
Prof Lyons noted that “misinformation is always going to drive stigma”.
HIV Ireland recommended tracking the level of stigma and discrimination against people living with HIV as this information was “crucial to understand the phenomenon of stigma in Ireland”.
THE MEDICAL INDEPENDENT | 10 JUNE 2021 12 News Feature
We know that if we can get the information out there to people that effective treatment prevents transmission through sexual contact, then that's going to help with that stigma that people experience
Prof Fiona Lyons
Poster from the HSE's 2020 campaign to address HIV-related stigma
Time for a change – the fight to keep non-EU doctors in the health service
The Keep Our Doctors campaign is advocating for intern jobs for all graduating doctors in Ireland. Dr Shubhangi Karmakar speaks to some of the doctors involved about why the barriers faced by international graduates need to be removed
e have so many wonderful Irish and international students that are working on the campaign, but we realised very quickly that something about stats, or stories that didn’t have an emotionally compelling angle, just wasn’t working,” says recent RCSI graduate Dr Isadora Lamego.
“And it put me in a situation where I was like, ‘I’m about to get married. I’m heavily invested in staying in Ireland. I’m going to put my life out there, to try and convince people this is a good cause.’”
This process of advocating through personal stories has been long and drawn out for Dr Lamego, and for many of her peers in the Keep Our Doctors campaign. Coming to Dublin as an undergraduate of University of California, Berkeley, studying Irish Literature in University College Dublin, Dr Lamego fell in love with the RCSI on an impromptu student-led campus tour, during part-time research writing for the Irish Heart Foundation. Some of these students, she would later find out, were close friends of her “incredibly brilliant” fiancé, a Specialist Registrar and RCSI graduate.
Dr Lamego’s short trip to Ireland fundamentally changed her relationship not just to the country, but to medicine. She told her family and her RCSI interviewers about how Ireland has “creative, wonderful, and fascinating doctors”. When her interviewers asked her where else she applied, she replied: “Well, it’s just you guys.”
However, with up to 600 doctors set to leave Ireland after a gruelling year of pandemic management, and the HSE only reinstating 100 of its 300 additional intern posts from its 2020 intake after significant national campaigns, the prospects for non-EU Irish-trained interns, even those with credentials in medical research and the medical industry such as Dr Lamego, remain uncertain.
“One of the reasons the campaign is necessary for younger doctors, is because there are so few spots for interns, registrars, and SHOs; they constantly feel like they’re in competition with each other. Overall, our campaign was definitely successful in getting about a half and half mix of Irish and international students; but we definitely encountered some resistance from medical schools, because some of the students said they didn’t want to compete with other people.
“I kept thinking, ‘that is so sad, that you think we’re the enemy, or that international students who just want to stay and help are a problem for you.' But that isn’t really the issue; it’s that the HSE isn’t giving us enough spots for all the doctors who want to train and stay here, even when the country already has a retention problem.”
Even as the Department of Health has committed to review its stance “to ensure the number of intern places are in line with future medical workforce planning requirements”, over the coming months, members of the IMO and its NCHD committee are already reflecting on the ways that last year’s interns shaped the clinical response to Covid-19, as well as the recent cybersecurity compromise.
Despite teething pains, the rapid integration of all interested non-EU students as Irish interns in 2020 has been vital to service delivery. IMO NCHD committee member Dr Gabriel Beecham observes: “There were challenges, which took a few months to shake down, but these related more to the speed with which additional posts needed to be allocated with only a few weeks of lead-in time, in the context of the simultaneous first wave of the Covid-19 crisis.”
“In essence, training and experience is for the most part quite uniform across Irish medical schools and whether or not they hold an EU passport is completely irrelevant to how good they are at being doctors. In that regard, it made a significant difference to have an additional cadre of interns over the past year. They have been hard-working, enthusiastic colleagues.”
Mr Naveed Abbas, Surgical Registrar and proponent for access to citizenship and to training opportunities for non-EU Irish-trained and international medical graduates, adds: “I have always considered our interns a key component of our teams, whose enthusiasm and drive often dictates the pace of their teams. During the pandemic, many of our interns worked tirelessly long hours with lit-
cept if they were offered it. So that was also a strange thing, knowing I was inherently trying to pick rotations that might be difficult, that people wouldn’t want to do.”
Mr Abbas continues to highlight that these disparities are not new to non-EU NCHDs, but a chronic phenomenon accompanying them along the training ladder in the HSE.
“I have been fighting this system for 10 years, during which I have faced numerous incidents where my career was considered unimportant in HSE and NTDP [National Doctors Training and Planning ] plans,” he says.
“I had the constant feeling of being a second-class citizen. It remains both depressing and humiliating and strikes at the core of basic human dignity. During this decade of my life, the only real progress I have made is the very intentional decision to become part of a concerted stance and present a united front. To not expect or accept less.”
Dr Lamego notes that the dehumanisation of the current system removes some incoming joy and “romance” of being a doctor, because of the prevailing artificial ‘scarcity-necessity’ narrative.
“I love the Irish countryside and all of my Irish doctor friends all really want to be in Dublin. You know, I would be very happy being a rural GP, living in Sligo – and it’s very hard to hear in Ireland, ‘oh, we don’t have enough rural GPs' over and over again, when I’m sat here thinking, 'hello, guess who would be very willing and happy to be a rural GP, if you would give them a job.’”
Dr Beecham points out how the IMO can support non-EU doctors in self-advocacy.
“Numerous reports on hospital medical staffing over the past four decades have indicated the need to move to a consultant-delivered model of care. The long-term solution has to include guiding doctors currently in our system through to specialist-level training – it's the only model that addresses improved patient care, reformed postgraduate training, and continued care on a 24/7 basis.
tle support, amidst a rapidly changing healthcare system, which often did not do them justice.”
A lack of support for non-EU Irish graduates continues to concern Dr Lamego and the Keep Our Doctors campaign.
The announcement that one-third of last year’s additional posts constituted 100 ‘extra’ jobs this year left members feeling superfluous and unvalued.
“Knowing that you’re basically not going to get a job adds such a different level of stress to medical school. It became really hard for me to thrive, because I spent so long thinking, ‘well I don’t want to have to marry my partner to stay in Ireland.' But not applying to any other countries was a hard decision for us to come to,” according to Dr Lamego.
“I was a finalist for the Academic Track due to my research background and experience in a global health network in San Francisco. But when I and my fellow international students found out we didn’t really have a shot, we couldn’t justify spending three days preparing for that interview, rather than studying to get the best grade we could to get through.
“And it’s hard, because most people rank their jobs and go, ‘ok, these are my top 50 jobs.’ But what my fiancé and I actually did was, he listed out the jobs for me to pick – not the worst – but I actually had to pick the 50 least popular rotations. The ones that people would be the least likely to ac-
“The IMO is in the fairly unique position of explicitly seeking to represent all members of the medical profession in Ireland – local or international graduates, specialists or NCHDs, in hospitals or the community. That means all doctors can benefit from the backing and services of a registered trade union and shared professional association.
“It is difficult for NCHDs to organise locally for many reasons, such as the transient nature of our temporary contracts and the significant proportion of the medical workforce recruited from overseas who may be less familiar with local employment rights, or who may understandably feel more vulnerable about raising or escalating complaints on their own. Being part of a union mitigates much of this – we can achieve much more with a common voice than we can achieve alone.”
Mr Abbas outlines where he believes the Keep Our Doctors campaign can find its home in the ecosystem of Irish medicine.
“Keep Our Doctors is a perfect example of all non-EU and EU doctors coming together for a single purpose,” he says.
“It serves as a blueprint of the possibilities that can be achieved with collective action. Non-EU doctors need to amalgamate better and play their role actively in society; it is no good if you see the Irish passport and not Ireland as your identity. EU doctors will need a better understanding of issues that are faced by non-EU doctors. For that they have to sometimes think a little more broadly and consciously participate in movements of social responsibility.”
THE MEDICAL INDEPENDENT | 10 JUNE 2021 13 Feature News
I had the constant feeling of being a second-class citizen. It remains both depressing and humiliating and strikes at the core of basic human dignity
Dr Isadora Lamego
Mr Naveed Abbas
Dr Gabriel Beecham
How will the cyberattack influence health service’s use of AI?
The impact of the recent cyberattack on the HSE has highlighted the health service’s increasing dependence on technology. The ransomware strike had the effect of practically shutting down many services in hospitals and other healthcare settings. The effects of the incident continue to be felt weeks later by healthcare professionals and patients.
The answer to the cyberattack will not be a return to the days of pen and paper. In fact, dependence on technology will only grow in the coming years. In this issue of the Medical Independent, we publish a feature on artificial intelligence (AI) and what it means for healthcare. In April, the third national AI Summit was held. The Summit, which came as Ireland develops its first AI strategy, featured a presentation by Prof Martin Curley, HSE Director of the Digital Transformation and Open Innovation.
REACTION TO OUR NEWS INTERVIEW WITH OUTGOING MEDICAL COUNCIL PRESIDENT DR RITA DOYLE, 31 MAY
"Absolute legend @ritakj." Michelle-Herbert, @MichelleMPS, 29 May
REACTION TO OUR BREAKING NEWS STORY, 'DOCTOR WELLBEING A KEY PATIENT SAFETY CONCERN, WARNS COUNCIL', 27 MAY
"Well done @ritakj @MedCouncilIRL. It is so important for all of us to realise that we all share these exceptional challenges throughout the pandemic and now the cyberattack and it was no pancake before all of this."
Dr John Gillman, @Gillman0John, 27 May
REACTION TO OUR NEWS FEATURE, 'BUILDING A STRONGER BIOETHICAL INFRASTRUCTURE', 10 MAY
"David Lynch of the @med_indonews covered the recent @RIAdawson event on bioethics in Ireland. @DerickOMisteal chaired session on genomics highlighted. If you missed the session, you can view it here: https://ria.ie/ news/science." IPPOSI, @IPPOSI, 10 May
Prof Curley said the HSE’s “ambition is to move Ireland from being a digital health laggard, to a digital health leader”. This comment is more striking after the recent cyberattack, which made it clear just how far the Executive is from being a ‘digital leader’. While healthcare in general is behind other industries when it comes to AI, other OECD health services are much further along the road than Ireland in the utilisation of the technology.
The Sláintecare Action Plan 2019 committed to research on the potential impact of AI, robotics and other technologies on workforce planning and services. This research, however, was delayed due to Covid-19 and its findings remain under consideration.
While the forthcoming national strategy does not just apply to healthcare, it is likely to outline a path for how AI can be applied in the sector. Healthcare is constantly evolving, and AI will play its part in that evolution. Con-
cerns that the technology will herald the replacement of doctors are premature. Regarding radiology, where AI is already being innovatively applied in the diagnostic process, it is regarded as another tool. A cutting-edge tool, but a tool nonetheless. And one which is not foolproof and still relies on clinician intervention and judgement.
As our reliance on technology grows, so do the risks. For every problem solved, there is a potential danger, especially if proper safeguards are not put in place. The use of AI in healthcare poses a number of challenges, including those of an ethical nature. Quite how the recent cyberattack will factor into the new strategy and greater integration of AI into healthcare remains to be seen. We don’t need to watch 2001: A Space Odyssey or The Terminator for a lesson in the possible perils of technology, but only witness what has happened to our hospitals in the last number of weeks.
REACTION TO OUR TWEET FROM THE ICGP CONFERENCE, '#ICGPCONF21 VOTES THAT COLLEGE WILL INCREASE EDUCATIONAL MATERIAL FOR GPS RELATING TO #BREASTFEEDING AND WILL PROCEED TO CEASE TO ACCEPT SPONSORSHIP AND ADVERTISING REVENUE FROM FORMULA MILK COMPANIES', 22 MAY
"What level of revenue has #ICGPConf21 been receiving from formula milk companies? Why?"
Alice O'Donnell, @AliceODonnell10, 23 May
"Meeting women's needs… well done @ICGPnews #ICGPConf21 #onegoal #onehymnsheet."
Stephanie Murray, @stephlooney1, 22 May
"I attended my first @ICGPnews AGM two years ago and was dazzled by the process of democracy in bringing motions to the floor for discussion and decision. Delighted to see that process working again today to support my view that sponsorship by formula milk companies needs to stop."
Dr Sarah Fitzgibbon, @SarahFitzWiMIN, 22 May
"Amazing news!" DrNiamhKM, @Niamh22K, 22 May
"Very welcome news - well done @ICGPnews! Time for other professional bodies and interest groups to follow suit."
Marita Hennessy, @MaritaHennessy, 22 May
In the very first sentence of Prof Gill's review of 'The Inevitable: Dispatches on the Right to Die' in 20 May's Mindo, I took exception to his comment that "'dying with dignity' is no more than a euphemism for mercy killing".
The concept of dying with dignity is an absolutely key aspect of palliative care and is generally nothing to do with euthanasia. Otherwise I found the review, of a book I recently read myself, was very good and his comments about the lack of an index were very apposite.
Dr Michael Cushen, Consultant in Palliative Medicine, Laois/Offaly
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: RESPONSE TO PROF DENIS GILL’S REVIEW OF KATE ENGELHART’S BOOK, THE INEVITABLE
Caring for colleagues in the time of Covid-19
Dr Stephen Priestley, Senior Medical Educator for Medical Protection’s Risk Prevention and Cognitive Institute, suggests ways to support doctors to sustain their own physical and mental wellbeing and support their colleagues during the pandemic
While Ireland has begun to flatten the curve of Covid-19 transmission, the thought of another wave is probably looming at the back of your minds. Many healthcare professionals have ‘flat batteries’ and in any downtime you have, you are just surviving rather than positively recharging and recovering.
Doctors are humans first and clinicians second. During the pandemic, doctors have been exposed to the same feelings as others – feelings of anxiety, an acute sense of personal threat, and a loss of control as the uncertainty of the Covid-19 disease continued to manifest. Many have also worked on the frontline, resulting in an additional degree of risk, both individually and to their loved ones.
More than ever, your wellbeing and safety is critically dependent on the performance of those you work with. Caring for each other will keep all of us performing at our best, so that we can face these challenges together and maintain our performance for the long haul.
Prof Don Berwick, a leading authority in healthcare improvement and safety, states that “without a physically and psychologically safe and healthy workforce, excellent health care is not possible”.
Wellbeing through the lens of Maslow’s hierarchy of needs
In thinking about caring for others (and indeed self-care) as we face the pressure and stress from increasingly complex work throughout this pandemic, we can draw on a concept developed by Abraham Maslow in 1943. His hierarchy of needs is a simple model that illustrates the range of human needs and how needs at a lower level have to be met before higher needs and aspirations can be addressed.
Because Covid-19 stands to threaten all layers of Maslow’s hierarchy, deficits across each of these core needs can have negative consequences for our physical and mental health.
1. Meeting the basic needs and ‘saying no for safety’
It is extraordinary that so many doctors downplay the importance of all team members attending to their basic physiological needs on a regular basis. Great performers know that this is fundamental to resilience.
In healthcare, we have not necessarily made it easy or acceptable to take a break, for a meal or a trip to the bathroom, or a few minutes of rest. This is related less to individuals and more to the culture of our workplaces. But, if we want to be at our best, we have to pay attention to those needs and make it easier for our colleagues to attend to their own wellbeing. This can be as simple as noting the needs of others and giving permission to take a break.
There is evidence about the negative consequences of dehydration in doctors.
A study by Lemaire from Canada compared an intervention of providing free healthy nutrition choices and enforcing nutrition breaks. It found that the intervention group had greater nutrient intake and statistically significant reduction in dehydration. Furthermore, cognition score testing indicated that dehydration can impair attention, short-term memory, visual perceptual abilities, psychomotor skills, alertness, and increased fatigue.
Thus, at the basic needs level, we can think about simple things like providing access to things that we need at work, such as showers, meditation or quiet rooms, healthy beverages and snacks, and safe transport home for our colleagues and ourselves when fatigued. The best idea of all may be to simply ask your colleagues what they need.
Another principle that we firmly support at Medical Protection is the ability and responsibility of ‘saying no for safety’. By that we mean a clinician’s right to say no to some form of work activity, or extension of hours, or carrying out tasks beyond their scope of practice and training because they believe it
to be unsafe – for either their patients or themselves. Saying ‘no’ often creates enormous anxiety. This anxiety comes both from within ourselves and external expectations. This ties up with the rescue model of healthcare. When people ask for help, we often automatically rescue them. I know that most of us would miss a meal break or put our own needs aside to attend to a patient.
At the moment, a firm ‘no’ may require moral courage, but evidence suggests we promote safety more effectively by being clear and holding those boundaries. As colleagues, we need to validate to our colleagues that saying no for safety is ultimately a professional action.
Routines can also be powerful as they can act as a ‘psychological inoculation’, giving us a sense of confidence, security and safety.
As colleagues and healthcare leaders, it is worth considering if there are routines or rituals that have been disrupted during Covid-19 that need to be reinstated or reimagined.
3. Sense of belonging
Enjoying workplace camaraderie and a shared sense of purpose are powerful protectors of wellbeing at work. But this may have been much harder during the pandemic due to working in high pressure situations with changing guidelines, reduced availability of communal space and time to speak to colleagues. As colleagues, we need to look at how we can provide support to our co-workers who may be working in isolation or in unfamiliar environments. This will require deliberate and creative action to ensure that everybody is included and that all colleagues are treated appropriately when it comes to the sharing of tasks and resources and rewards and recognition.
Extensive literature supports that formal and informal peer support networks are important and effective in promoting wellbeing. If you have not already done so, now might be a time to try something new such as a peer support responder system, or another means of social support at work, which could continue beyond the pandemic.
4. Esteem and attaining self-actualisation
2. Physical and psychological safety and support for habits/routines
Physical safety might seem an obvious priority in a pandemic, where there has been an emphasis on infection control and the correct use of personal protective equipment. However, psychological safety is also vital to consider.
A working definition of psychological safety is: ‘If I make a mistake, or ask for information or help, others will not punish me or think less of me.’
A psychologically safe environment can be created by supporting our colleagues’ right to contribute, by genuinely listening to them and by refraining from being judgmental. It is important to invite others to speak up or ask for feedback from them.
Additionally, when we show appropriate vulnerability and admit when we are wrong, this also creates psychological safety for others.
Supporting your colleagues in maintaining resilience is worthwhile as habits and routines require very little cognitive effort; they can be protective in times of stress and overload. We can actively develop habits that support both our performance and wellbeing. While initially requiring deliberate planning and action, positive behaviours eventually become subconscious, thereby reducing cognitive load and assisting you to maintain your performance in times of lower willpower and motivational energy.
Civility at work is even more important during times of crisis. But courteous respectful communication in our workplace can be challenging because our emotional state can sometimes get in the way.
A useful phrase that is well supported by the literature is ‘civility creates safety’. A growing number of peer-reviewed papers in health and safety literature support the conclusion that a civil and respectful environment is safer for patients, promotes better communication and enhanced teamwork.
For those who are not working in frontline roles, directly engaging in the care of patients with Covid-19, it may seem there is less recognition and value when compared with staff working directly with patients. As colleagues, it is important that we recognise and celebrate the value and the contribution of all roles, regardless of their position or duties.
Psychologist Carol Dweck described in her book Mindset: The New Psychology of Success that showing appreciation encourages the development of a growth mindset, a valuable resilience factor. Her research found that our personal growth can be encouraged when we recognise staff – not simply with empty praise – but through articulation of not just the outcome, but the effort and the process that the staff went through to get that outcome.
Caring for others also leads us to the very top of Maslow’s pyramid: Self-actualisation. We have all been facing challenges in this area of professional fulfilment in the last year as we are pressured to work in a different way, or when we are taking on unfamiliar roles.
Many of our plans for professional development have been delayed and, in many cases, abandoned. Trainees have seen their training programmes halted or changed in such a way that they cannot get the experiences they need to successfully complete training.
So is there also an opportunity for creative or professional individual growth and to foster the potential of others? I urge you to consider how you might derive professional fulfillment during this time and equally how you might help colleagues in doing the same. Remaining engaged in meaningful work is such a powerful wellbeing factor and warrants personal investment.
Medical Protection members can view the full webinar on this topic at https://prism.medicalprotection.org/course/ view.php?id=1222. Wellbeing services are also available at http://medicalprotection.org/ireland/wellbeing
THE MEDICAL INDEPENDENT | 10 JUNE 2021 15 Medico-Legal Opinion
As colleagues, we need to look at how we can provide support to our co-workers who may be working in isolation or in unfamiliar environments
Figure 1: Maslow’s pyramid
File it under ‘maybe’
DR CHRISTINE O’MALLEY
Back in April, my brother told me the schools in Nenagh were closing, due to Covid. I responded “Is that a true story? Or merely a good one”? I’ve learned to be careful, after years living in Tipperary.
A friend once said to me “Did you hear that story about drugs wasn’t true”? I must have looked puzzled. She continued: “I forgot – you don’t do gossip.” Now I was definitely puzzled. It was news to me that I don’t do gossip. But it’s true I have a mental file called “maybe” where I store a lot of unconfirmed nuggets. On this occasion, the whole town of Nenagh knew that four young men from “good” families were in court in a nearby town, on drugs charges. Except now the whole town knew it wasn’t true. The priest, at Mass on the altar, told his flock that he had personally gone and looked at the court records and there was no such case.
Yes, that happened a long time ago. But I learned an important lesson. The “maybe” file is very useful. The stories are always relayed as absolute fact. To confuse matters, there’s often some truth mixed in there too.
There was great excitement recently when the helicopter was called to Dromineer. A young man had collapsed. The village turned out to organise the traffic and let the ambulance through. But it was very sad – he died. Everyone knew his name, where he worked. Except he didn’t die. The personal details were correct, but later it emerged he was well and recovering in hospital.
A year ago, I was told that a Dubliner, a regular visitor to Dromineer, had married. I was rather surprised. I know he’s already married and his wife has a difficult illness. Still, such things happen in life, so “maybe” it’s true. Later I learned that it was his son who got married. In pandemic times, there has simply been no news, just Covid stories.
At Easter weekend, I was stopped at a Garda checkpoint in Dromineer. I was legal, just a few hundred yards from my house, but most of the crowds of visitors that day were not. Dromineer was thronging, despite the five-kilometre restriction in place at the time. Later, I was upset to hear that one of the cars stopped by the gardaí that day belonged to an elderly gentleman and his wife, well known in the town. They regularly drive out to Dromineer and sit safely in their car looking out at the lake. The gardaí fined them €100 each for being outside the limit. Even worse, they were so distressed, they were staying home because of it.
Older people have had such a hard time during Covid. It seemed very unfair. I know very few people of any age
who didn’t break some public health rules. Over the Easter break, I met several families who had travelled down from Dublin. They were out and about, queueing up at the Lake Café and suffered no penalty.
A week later, I met a daughter of this unfortunate couple and said how sorry I was for her parents. She laughed out loud. It never happened. They don’t know where the story started, but it was all over the town.
In 2020, Nenagh was relatively spared by Covid. Unfortunately, that all changed at New Year. “Who has the virus” was a great topic of discussion, leading to a whole new world of gossip and rumour. Under the “maybe” rule, I mostly waited until people confirmed to me that they had a positive test. They’re usually happy to do so when recovered. After all, high community transmission means we don’t know the source.
Then my brother said the schools in Nenagh were closing due to Covid. I demanded evidence, but unfortunately it was true. A number of schools closed. This has been a tough time for teenagers and young adults.
“Be careful”, a neighbour said. “It’s here in Dromineer.” A toss of the head indicated where the cases were. And the blame started: A birthday party in the boys’ school and another in the girls’ school, actually there were three parties. Even worse, these same local people were seen shopping in the supermarket, despite having Covid. It was all very troubling.
Some time later, I stopped to commiserate with that family and ask how they all were following Covid. They laughed. Yes, a teenager in the extended family had tested positive, but the rest were negative. And by the way, there weren’t three birthday parties, or two. Was there one?
That file called “maybe” just got a lot bigger.
Lost in translation
A note of caution on dipping your toe in the waters of Australian-English
when Down Under
beginning of their presentations when visiting Ireland, wouldn’t it be just lovely to use a few well-chosen Australianisms to show my appreciation of the invitation.
In Canada, it’s possible to find a man lounging on a chesterfield in his rented bachelor wearing only his gotchies while fortifying his Molson muscle with a jambuster washed down with slugs from a stubby.
This fine sentence is full of Canadian-English. As readers may be aware I’m fond of Canada. No surprise really when you consider I’m married to a Canadian and my son, his fiancée and my granddaughter live there. I spent three months in Newfoundland as a medical student and have spent a number of lovely holidays in Western Canada.
Readers will also be aware of my love of words, accents and regional dialects of English. The most creative of these in my view is Australian-English. So you can imagine my (over) excitement, when, having completed a Masters in Medical Humanities by distance learning at the University of Sydney, I decided to head Down Under for the graduation. And the university kindly invited me to give a lecture on narrative medicine while I was there. As the Aussies would say: Fair dinkum.
I became quite obsessed with introducing my lecture with some Australianisms – the formal term for the lexicon of Australian-English. I reasoned that just as I have heard lecturers from abroad say a cúpla focail at the
It was possibly one of the most delightful pieces of research I have ever undertaken. Beyond ‘Sheela’ and ‘Bruce’ was an entire cornucopia of creative reworking of the English language. It soon became clear that I wouldn’t be short of a bon mot or two with which to treat the local audience.
So I made up a first slide that started with:
“Good Arvo everyone!”
“I come from a woop-woop in the west of Ireland. Just got here yesterday and I’m a bit carked from jet lag. So please excuse me if I come across as being a few roos short in the top paddock....”
(Translation: Good afternoon. I come from a small village in the west of Ireland. I’m feeling dead from jet lag so please excuse me if I come across as a little crazy.)
Now I was just getting into my stride at this point and I would happily have put together a few more slides of carefully chosen Australianisms. I was itching to fit in “dry as a dead dingo’s donga” as I asked for a glass of water, but there was a whole lecture to work through, so common sense prevailed and I left it at that.
Fast forward to the long flight to Sydney. At some point I fished out my iPad and began to go over my presentation. It was then that the doubts set in. The opening slide would be ok, wouldn’t it? I mean they would know I was reaching out to them with my Australianese, wouldn’t they?
A brief snooze later and I woke up even more full of doubt. We were flying on an Emirates aircraft, which as
many of you know are staffed by about 20 flight attendants from all over the world. They wear a national flag on their name badges so you can tell where they are from. I reckoned there had to be an Australian attendant on our flight. Sure enough, I found a pleasant young woman in the galley with the appropriate moniker. I explained my situation to her and she asked me to say exactly what I had placed on the first slide. To her credit, she didn’t laugh, she checked it was the University of Sydney I was planning to speak at and then she firmly advised that I scrub the entire slide. She announced that I might just get away with it if I was presenting at a small town hall in deepest rural Australia, but that the sophisticated citizens working in the oldest university in Australia would not be amused. An opening like that could even jeopardise the award of the masters degree, she reckoned, to drive her point home.
I was reminded of this close shave when I read the recent obituary of the editor of the Canadian Oxford Dictionary. The Oxford University Press hired Katherine Barber as the founding editor of its Canadian dictionary in 1991, in order to create an authoritative reference work to decode contemporary Canadian words and meanings. While not as colourful as its Commonwealth counterpart, the dictionary accumulated a good slice of Canadianese.
And for those of you still working out the opening paragraph in this column, it describes a man on a sofa in a studio apartment wearing only underwear while expanding his beer belly with a jelly doughnut and a squat brown beer bottle.
The Australian equivalent is unprintable.
Opinion THE MEDICAL INDEPENDENT | 10 JUNE 2021 16
There is a world of difference between a good story and a true one
Read more by Dr Christine O’Malley at www.mindo.ie
Read more by Dr Muiris Houston at www.mindo.ie @muirishouston
I know very few people of any age who didn’t break some public health rules
How much does industry influence how we prescribe?
There is an obligation on us as doctors to question why we are choosing a particular medication when we write a prescription
TV recommendations are still one of the greatest currencies we have as we gradually emerge from lockdown and I’m happy to share that I recently watched a brilliant documentary originally broadcast on HBO called Crime of the Century. It was a shocking exposé of how corrupt drug companies in the US have lied to and manipulated doctors in their marketing of oxycodone and fentanyl products since the 1990s, which has directly led to the deaths of more than 760,000 Americans in what is known as the opioid crisis.
In times long ago when we were still able to get on planes and travel to the United States, part of the fun was turning on the TV and marvelling at the ads for antipsychotics or anticoagulants on news channels. This could never happen back home, we would say. Drug companies are far more regulated. We could never be influenced in this way.
Although the documentary was about actual criminal acts, the bribing of doctors, and lying in Congress; it did lead me to think how the medical profession interacts with pharma companies here. The days of the free holiday or even the free pen are gone, but we’ve all been there and done the polite smile as the very nice rep gives their spiel about their latest hot new thing, which is 50 per cent more effective than its closest market rival, praying for it to end so we can go back to the free platter of sandwiches and
MULTIPLE CHOICE QUESTIONS
the paper cup of coffee.
I’m not for a second suggesting that drug reps here don’t act with the greatest integrity and standards, but it is naive at best to think that we wouldn’t be as subconsciously influenced by that advertising as we are by the ads we see on TV after a long day at work.
It can be very easy to think highly of ourselves and say I wouldn’t dream for a second of prescribing that opioid or that benzo or sleeper, sure everyone knows that they’re bad news. But we do find ourselves prescribing a hell of a lot of the newer heavily-marketed painkillers without really wondering how they can truly be different than anything else that acts upon an opioid receptor in the brain.
Previous opioids brought onto the market have ironically caused huge headaches for doctors as years later we’re still trying to wean patients off them. The plastic packets of the neuropathic analgesics that we were all told were brilliant for sciatic back pain litter the pavements of our towns and cities as they now hold a street value almost as great as heroin, which, let’s not forget, was originally a brand name for morphine brought onto the market by Bayer in 1895.
Patients are always going to need serious analgesia and there should be a role for it in our clinical practice. But we have to question why we are choosing a particular
In patients with palpitations, features supporting a diagnosis of supraventricular tachycardia ( SVT ) include
A. Sudden onset.
B. Abates with breath-holding.
C. Regular heart rate of 100-to-120 per minute.
D. A history of rheumatic heart disease.
E. Patient is well between episodes.
A. Most commonly affects eight-to-12-year-olds.
B. Patients present with locking of the knee.
C. Occurs at the lower end of the patella.
D. Diagnosis should be confirmed on x-ray.
E. Should be treated with a special exercise programme.
In adults with a suspected foreign body in the eye, it is good practice to
A. Take a careful history and always accept it at face value.
B. Always enquire about the use of power tools.
C. Assume that if there is no pain on blinking that the foreign body has gone.
D. View floaters as a sinister symptom.
E. Avoid the use of topical anaesthetics.
In the treatment of non-insulin-dependent diabetes mellitus, sulphonylureas
A. Are contraindicated in pregnancy.
B. Can be given with each other if control is poor.
C. Should be started at the maximum dose and reduced gradually as indicated by the results.
D. May result in weight gain.
E. Are recognised as a cause of pruritus.
Recognised presenting features of bone tumours in children include
A. Nocturnal pain.
B. Pathological fracture.
C. Pyrexia of unknown origin.
E. Deep swelling unrelated to trauma.
medication as we write a prescription or fill a kardex. Is it because it’s the most evidence-based for that indication or is it just the one drug in its class that you consistently know the dose of off the top of your head? (It can’t just be me.) Or perhaps it is because you have been more subconsciously influenced than you realise by the free croissant at grand rounds or the sponsorship at the annual conference.
Some hospitals and clinical sites have a policy of not allowing drug reps in at all and perhaps that is to be applauded. Conversely, it could be argued that there is a valid role for drug reps in the course of our daily clinical practice and that drug companies have the right as businesses in a capitalist society to market and profit from their drugs they develop.
There is a myriad of factors that lead us to choose a certain medication over another. However, it is important to remember that doctors are consistently named in surveys as one of the most trusted professions by the public and we have a responsibility to uphold that trust every time we sign a script with our name and Medical Council number.
When both suspicion of ‘big pharma’ is at an all-time high and drug companies like Pfizer and AstraZeneca are household names, it beholds us all to act with the greatest integrity, now more than ever.
E. TRUE. Presence of either bony or soft tissue swelling unrelated to trauma should prompt urgent orthopaedic referral.
D. TRUE. Antalgic limp in a weight-bearing limb.
C. TRUE. Also weight loss, malaise, and fatigue.
B. TRUE. As an x-ray would be available this diagnosis is unlikely to be missed.
A. TRUE. Tumour should be considered if muscular pain fails to resolve within two weeks, especially if nocturnal in nature.
E. TRUE. Other sideeffects include rashes, haemolytic anaemia, aplasia, and elevated liver enzymes.
D. TRUE. Tends to plateau after a gain of about 4kg.
C. FALSE . Start with minimum dose and increase depending on results.
B. FALSE. Can be given with metformin, but not with each other.
A. TRUE. And in patients with serious intercurrent illness.
E. FALSE. It may help with examination or removal of foreign body.
D. TRUE. This suggests vitreous haemorrhage secondary to ocular penetration.
C. FALSE. If it entered the eye at high speed there is often no pain except at the moment of impact.
B. TRUE. And always ask whether safety glasses were worn.
A. FALSE. Do not accept a history at face value as the patient may mislead you for a variety of reasons.
E. FALSE. Like most overuse injuries, treat by reducing physical activity until pain is at a manageable level.
D. FALSE. An obvious clinical diagnosis.
C. FALSE. Sinding-LarsenJohansson syndrome or patellar tendonitis (‘jumper’s knee’) does.
B. FALSE. Swelling, discomfort, and local tenderness in the region of the tibial tuberosity.
A. FALSE. 12-to-16-year-old footballers (ie, sports that require frequent running/jumping).
E. TRUE. SVT usually occurs in young, fit patients.
D. FALSE. Most likely to be associated with atrial fibrillation.
C. FALSE. A rate of over 160 per minute is typical of SVT.
B. TRUE. Or other vagal stimulating manoeuvres like stooping.
A. TRUE. Tends to come on suddenly and without warning.
THE MEDICAL INDEPENDENT | 10 JUNE 2021 17
DR NEASA CONNEALLY
Read more by Dr Neasa Conneally at www.mindo.ie @neasaconneally
C M CY CMY K
Society of Ireland)
Asthma and allergic rhinitis
Asthma is a heterogeneous disease, usually characterised by chronic airway inflammation defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation (GINA, 2020). Asthma affects over 380,000 people in Ireland; 7.1 per cent of Irish adults have asthma with 890,000 likely to experience it sometime in their lifetime. It is estimated that over 80 per cent of people with asthma have allergic rhinitis (AR).
AR is a risk factor for asthma – 10-to-40 per cent of people who have AR also have asthma. AR is more likely to develop initially with asthma developing later. Therefore, people with AR should be assessed for asthma due to the increased risk of developing asthma. Similarly, patients with persistent asthma should be assessed for AR.
Symptoms of AR
Typical symptoms of seasonal (hay fever) and perennial AR are:
Itchy, blocked, or runny nose;
Red, itchy, or watery eyes;
Itchy throat, inner ear, or mouth;
Postnasal drip (a drip of mucus from the back of the nose into the throat);
Loss of concentration and generally feeling unwell;
Reduced sensation of taste and smell. Patients may experience all or some of the above. Symptoms may be confused with symptoms of Covid-19. Figure 1 illustrates the differences between asthma, COPD, AR, Covid-19, the common cold, and flu.
Classification of AR
In 2019, the classification of ‘seasonal’ and ‘perennial’ rhinitis was changed to ‘intermittent’ and ‘perennial’ rhinitis by the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, which develops internationally applicable guidelines for allergic respiratory diseases. Intermittent rhinitis is classed as occuring less than four days per week or for less than four weeks. Persis-
tent rhinitis lasts more than four days and longer than four weeks. Both intermittent and persistent AR can be mild or moderate/ severe (see Figure 2).
Presentation of the patient with AR
The early response usually occurs within minutes of exposure to the allergen resulting in an inflammatory response. Mast call degranulation occurs resulting in nasal congestion, an increase in nasal secretions and nasal airway resistance. Several neural peptides, sympathetic and parasympathetic fibres are involved. The late response usually occurs hours later resulting in cellular inflammation. Symptoms recur at this this stage especially nasal congestion. T-cells and mast cells also produce cytokines during the late response. See Figure 3
Pharmacological interventions (ARIA 2019)
There are several treatment options available to the patient and a combination of these options may be required for optimal relief of symptoms. These are outlined in Table 1. Saline douching/nasal irrigation should also be encouraged and is available either as a saline rinse or saline spray. Saline rinsing involves high volume at a low pressure, whereas saline spray is a low volume delivered at high pressure. The advantages of saline douching include:
Removal of mucous and inflammatory mediators;
Reduces bacterial burden;
Reduces mucus thickness;
Improves mucociliary function by increasing ciliary beat frequency.
Smoking cessation should be encouraged at every opportunity. Smoking increases the likelihood of chronic nasal symptoms and may be associated with the development of nasal polyposis. Passive smoking, environmental exposure, e-cigarettes, and vaping also increase the likelihood of chronic nasal symptoms and nasal polyposis.
Mild intermittent AR treatment options include oral and nasal decongestants, which can be used as a rescue medication. These medications will reduce nasal congestion and should be used for no longer
DRUG THERAPY OPTIONS SYMPTOMS
Oral H1 antagonists Sneezing, rhinorrhoea, nasal itch, eye symptoms
Intranasal HI antagonist Sneezing, rhinorrhoea, nasal itch
Intraocular HI antagonist Eye symptoms
Intraocular cromones Eye symptoms
Intranasal decongestants Nasal blockage
Oral decongestants Nasal blockage
Leukotriene receptor antagonists (LTRA) Rhinorrhoea, nasal blockage, eye symptoms
Intranasal corticosteroids (INCS) All symptoms
Oral corticosteroids All symptoms
Table 1: Pharmacological treatment options for allergic rhinitis
than seven days and should be avoided in pregnancy and breastfeeding. Oral H1 antagonists block the physiological effects from mast cell derived histamine. Second generation antihistamines are preferred due to their less sedating effect and are available over the counter. Antihistamines are also available intranasally or intraocular. Intranasal corticosteroids (INCS) are the first-line treatment for moderate/severe intermittent and persistent AR. These medications are used once or twice daily to each nostril and good technique is essential. If the nasal cavity is very obstructed, a nasal spray may not be effective. Nasal drops may be more effective in this scenario. Nasal spray and nasal drop technique can be viewed on www.asthma.ie/about-asthma/resources/ inhaler-technique-videos
Efficacy of INCS is not improved when used with oral corticosteroids (OCS). Figure 4 provides a stepwise approach to the management of AR.
Sub-lingual immunotherapy (SLIT)/
allergen immunotherapy (AIT) is now recommended by GINA (2020) as a treatment option for patients with asthma who are sensitised and have AR. Immunotherapy is also recommended by ARIA (2019) for patients with AR who do not get an optimal response from oral H1 or INCS therapies. These medications are not available on the GMS and can be prescribed by GPs.
Keep windows closed at night-time or when the pollen count is high.
Monitor the pollen tracker on www.asthma.ie and minimise time spent outdoors when the pollen count is high.
Apply Vaseline around nostrils when outdoors to trap pollen.
Wear wraparound sunglasses to minimise levels of pollen irritating the eyes. Splash the eyes with cold water to
THE MEDICAL INDEPENDENT | 10 JUNE 2021 19 Respiratory Medicine Clinical
Allergic rhinitis is a risk factor for asthma, with 10-to-40 per cent of people who have allergic rhinitis also having asthma symptoms
RUTH MORROW, Registered Advanced Nurse Practitioner (Primary Care), Respiratory Nurse Specialist ( WhatsApp Messaging Service Asthma
Figure 2: Classification of allergic rhinitis (ARIA, 2019)
Continued on p20 ▸
help flush out pollen and soothe and cool the eyes.
Shower, wash hair and change clothes if you have been outdoors for an extended period of time.
Exercise in the morning rather than the evening when there are higher rates of pollen falling.
Avoid drying clothes outdoors and shake clothes outside before bringing them inside – particularly bedclothes.
Minimise contact with pets that have been outdoors and are likely to carry pollen.
Put an Asthma Action Plan in place (Figure 5).
An Asthma Action Plan contains all the information a person with asthma needs to keep their condition in control. Every person with asthma should be offered a plan. It should be reviewed frequently and any time medication is changed. These can be downloaded for free from www.asthma.ie and should be filled out with the person’s healthcare professional.
Exam time tips
Walker et al (2007) showed that students undertaking exams may drop a grade in their exam results because of AR as a result of symptoms, sedating medication, and poor sleep. Having AR under optimal control cannot be underestimated. Some tips to help with exam time are listed in Table 2.
Endonasal phototherapy has an immunosuppressive effect by inhibiting allergen induced histamine released from mast cells. It also induces apoptosis in the T-lymphocytes and eosinophils. The procedure directs a combination of UVB, UVA and visible light into the nasal cavity. Endonasal phototherapy is generally well-tolerated and effective and is a treatment option when pharmacological treatment is insufficient or contraindicated.
It is considered that AR is a medical condition which requires medical intervention. However, if symptoms are unilateral; septal deviation, nasal polyps or tumour should be considered. Patients will still need to have an AR plan in place post-surgical intervention.
Be prepared – around Easter, patients should have a review with their GP and have a plan in place to optimise control of AR symptoms
Students should be advised to avoid sitting near open windows, if possible
Bring antihistamine /nasal spray to exam
Have optimal technique in using nasal spray/nasal drops
Splash eyes with cold water before exam
Keep a supply of tissues to hand
Special considerations in AR
Children under four years
Figure 6 illustrates the typical age of onset of allergies in children. Outdoor allergens are unusual in children under two years of age. Type 2 sub-endotype IL4/ IL-13 are associated with AR in children. IL-5 is associated with asthma. Treatment of children under four years should focus on allergen avoidance and saline spray. Cetirizine is the oral H1 antagonist of choice. Cetirizine is licensed from two years, but good safety is reported from six months of age. For moderate/severe persistent AR, intranasal corticosteroids such as fluticasone or mometasone should be considered first-line treatment. Longterm follow-up studies suggest no growth retardation if used as a once-daily dose. Caution should be taken in children who are also using inhaled or topical corticosteroids for asthma or dermatitis. In children with resistant symptoms and those with co-existing asthma, leukotriene receptor antagonists should be considered. Parents should be educated in relation to possible side-effects of sleep disturbance and mood disorders.
AR affects 20 per cent of pregnancies and women with pre-existing AR can experi-
Persistent rhinitis: Intermittent rhinitis:
Consider referral to allergist and ENT
ence an increase in symptoms. Medications should be avoided where possible and should only be used if benefits to the mother are greater than risk to the foetus. Medication should be avoided in the first trimester if possible. Topical administration of medication should be first-line where possible.
This article has explored the relationship between asthma and AR. Pharmacological and non-pharmacological interventions for the management of AR have been discussed. Special considerations in children
and pregnancy have been addressed. The impact of AR on health and well-being is significant, with many people experiencing impairment of daily activities, learning and cognitive function, as well as reduced productivity at work and school. Optimal control of symptoms through pharmacological and non-pharmacological treatment regimes in combination with education, self-management, and empowerment are paramount to manage this distressing condition.
References available on request
Clinical Respiratory Medicine THE MEDICAL INDEPENDENT | 10 JUNE 2021 20
Figure 3: Patient presentation with allergic rhinitis
Table 2: Exam time tips for AR
Figure 4: Stepwise pharmacological treatment for allergic rhinitis
Figure 6: The allergic march in children
Figure 5: Asthma Action Plan
▸ Continued from p19
Allergic rhinitis relief
The incidence of epistaxis during long term treatment was higher than 10% but was generally mild to moderate in intensity 1
AVAMYS 27.5 micrograms/spray, nasal spray suspension
Abbeviated Prescribing Information (Refer to the full Summary of Product Characteristics before prescribing)
Composition: Each spray actuation delivers 27.5 micrograms of fluticasone furoate. One actuation delivers 8.25 micrograms of benzalkonium chloride. Uses: Treatment of symptoms of allergic rhinitis in adults and children aged 6 years and over. Dosage and Administration: For intranasal use only. Adults and adolescents (12 years and older): Two sprays per nostril once daily (total daily dose, 110 micrograms). Once symptoms controlled, use maintenance dose of one spray per nostril once daily (total daily dose, 55 micrograms). Reduce to lowest dose at which effective control of symptoms is maintained.
Children aged 6 to 11 years: One spray per nostril once daily (total daily dose, 55 micrograms). If patient is not adequately responding, increase daily dose to 110 micrograms (two sprays per nostril, once daily) and reduce back down to 55 micrograms daily dose once control is achieved. Contraindication: Hypersensitivity to active substance or excipients. Special warnings and precautions: Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. Consider additional systemic
corticosteroid cover during periods of stress or elective surgery. Caution when prescribing concurrently with other corticosteroids. A reduction in growth velocity has been observed in children treated with fluticasone furoate 110 micrograms daily for one year. Therefore, children should be maintained on the lowest possible efficacious dose which delivers adequate symptom control. It is recommended that growth of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. Consider referring to a paediatric specialist. May cause irritation of the nasal mucosa. If a patient presents with visual disturbance they should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma, central serous chorioretinopathy. Contains benzalkonium chloride; long-term use may cause oedema of the nasal mucosa. Drug interactions: Caution is recommended when co-administering fluticasone furoate with potent CYP3A inhibitors including cobicistat-containing products as an increase in the risk of systemic side effects is expected. Co-administration should be avoided unless the benefit outweighs the increased risk. Co-administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate. Pregnancy and Lactation: No adequate data available. Recommended nasal doses result in minimal systemic exposure. It is unknown if fluticasone furoate nasal spray is excreted in breast milk. Only use if the expected benefits to the mother outweigh the possible risks to the foetus or child. Side effects: Very common (≥1/10): epistaxis. Epistaxis was generally mild to moderate, with incidences in adults and adolescents higher in longer-term use (more than 6 weeks). Common (≥1/100 and <1/10): headache, dyspnoea, nasal ulceration. Uncommon (≥1/1000 and <1/100): rhinalgia, nasal discomfort (including nasal burning, nasal irritation, and nasal soreness), nasal dryness. Rare (≥1/10,000 and <1/1000): hypersensitivity
reactions including anaphylaxis, angioedema, rash, and urticaria. Very rare (<1/10,000): Nasal septum perforation. Not known: transient ocular changes, vision blurred, bronchospasm, growth retardation. Marketing Authorisation (MA) Holder: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. MA Number: EU/1/07/434/003. Legal category: POM B. Last date of revision: January 2021. Job Ref: PI-5555. Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Camp, 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.
1. Avamys Summary of Product Characteristics, available on www.medicines.ie, accessed April 2021
Date of preparation: April 2021
Document size: 250mm x 346mm (WxH)
Relieving the symptoms of allergic rhinitis in patients over 6 years1
Not actual size
LOC_IE_May 21_PM-IE-FLF-ADVT-200003_D1.indd 1 20-05-2021 17:25:07
Allergic rhinitis in focus
Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa induced by immunoglobulin E (IgE)-mediated reactions to inhaled allergens. It is one of the most common chronic conditions globally causing a major health burden and is associated with substantial economic costs. AR often co-occurs with asthma and conjunctivitis and is also associated with atopic dermatitis and nasal polyps. It is estimated that up to 50 per cent of people with asthma and up to 30 per cent of people with eczema also have AR. Classic symptoms of the disorder are nasal congestion, nasal itch, rhinorrhoea and sneezing. A less recognised symptom is post-nasal drip. AR is frequently associated with allergic conjunctivitis with redness, tearing, and itching of the eyes. Approximately 60 per cent of patients with AR have concomitant allergic rhino conjunctivitis. AR symptoms can be debilitating, resulting in sleep disturbance, fatigue, depressed mood and decreased function that impairs quality-of-life and productivity.
AR adversely affects the daily living activities of nearly 1.38 million Irish people and affects up to 30 per cent of adults and 40 per cent of children in industrialised countries. Approximately 80 per cent of individuals diagnosed with the condition develop symptoms before the age of 20 years. Older children have a higher prevalence than younger children with a peak occurring at ages 13-to14 years. During early childhood, boys are more likely to be affected by AR than girls, during puberty girls have a higher incidence and by age 20 and over the prevalence rates among men and women are equal.
AR has long been considered a disorder of the nose and nasal passages, however, evidence suggests that it may represent a component of a systemic airway disease involving the entire respiratory tract. Allergen provocation of the upper airways not only leads to a local inflammatory response, but may also lead to inflammatory processes in the lower airways, and this is supported by the fact that rhinitis and asthma frequently co-exist. AR affects 60-to-80 per cent of people with asthma. Some patients have AR alone, whereas others have AR and asthma with or without other allergic manifestations, although few patients have asthma alone. Although it is well established that rhinitis can lead to asthma, the exact phenotype of AR prone to developing asthma is still unclear. It is possible that poly-sensitised individuals can more commonly develop asthma.
Traditionally categorised as seasonal or perennial, AR is better classified according to symptom duration (intermittent or persistent) and severity (mild, moderate or severe). ARIA (Allergic rhinitis and its impact on asthma) guidelines classify AR as intermittent or persistent depending on the duration of symptoms, with persistent rhinitis occurring for more than four days a week for more than four weeks in a row and as mild, moderate or severe, depending on whether sleep and daily ac-
tivities are affected or whether symptoms are troublesome.
Risk factors for AR include antibiotic use, inhalant and occupational allergens, as well as genetic factors. Common triggers include dust mites, animal allergens, pollens, spores, and moulds.
AR is an autoimmune condition and symptoms occur when the immune system overreacts to a normally harmless substance such as pollen. When the body encounters an allergen, cells in the lining of the nose, mouth and eyes release histamine-triggering symptoms of an allergic reaction. Allergic reactions do not occur the first time a person comes into contact with an allergen. The allergic immune response begins with a sensitisation phase when the patient is first exposed to an allergen without experiencing clinical symptoms. In AR, numerous inflammatory cells, including mast cells, CD4-positive T-cells, B-cells, macrophages, and eosinophils, infiltrate the nasal lining upon exposure to an allergen. In allergic individuals, the T-cells infiltrating the nasal mucosa are predominantly Th2 and release cytokines, eg, interleukin [IL]-3, IL-4, IL-5, and IL-13 that promote immunoglobulin E (IgE) production by plasma cells. Crosslinking of IgE bound to mast cells by allergens, in turn, triggers the release of mediators, such as histamine and leukotrienes, which are responsible for
arteriolar dilation, increased vascular permeability, itching, rhinorrhoea, mucous secretion, and smooth muscle contraction in the lung. The mediators and cytokines released during the early phase of an immune response trigger a further cellular inflammatory response, which results in the recurrent symptoms that often persist.
A thorough history and physical examination are important for establishing a diagnosis of AR. History should include questions regarding a family background of atopic disease, the impact of symptoms on quality-of-life and the presence of comorbidities, such as asthma, mouth breathing, snoring, sleep apnoea, sinus involvement, otitis media, and nasal polyps. Clinical history should note when and where symptoms occur and any exacerbating and relieving factors. Chest, ears, throat, abdomen and skin should be examined for other symptoms and a review of any treatments and their efficacy carried out. Testing for allergen-specific IgE using skin prick or blood tests to identity the allergen can support the diagnosis. Other tests may include a nasal endoscopy, nasal inspiratory flow test, and CT scan. Rhinitis has important co-morbidities. Asthma should always be assessed for in patients with AR and if needed an objective measurement, such as spirometry, carried out owing to the frequent co-occurrence
of these disorders. Patients should also undergo ear inspection as otitis media with effusion may be a co-morbidity in children with rhinitis and in adults with severe forms of rhinosinusitis. The general examination should include skin examination for atopic dermatitis and assessment of thyroid function by checking for slow relaxation after the ankle jerk and for eye signs, such as puffiness, redness and/or bulging (hypothyroidism) in patients with obstructive rhinitis. Children’s growth should be assessed, as the combined use of INCS and inhaled corticosteroids can reduce height at high doses. The presence of features such as conjunctivitis, nasal allergic crease, allergic salute or double creases beneath the eyes all suggest an allergic diathesis. Nasal examination is required in patients with moderate to severe AR or in those with uncontrolled symptoms despite optimal treatment. Examination should include assessment of the external appearance followed by internal examination, preferably with a nasoendoscope although an otoscope may suffice in children. Position of the nasal septum, size and colour of the inferior turbinates together with the appearance of the mucosa and the presence and nature of any secretions, polyps, bleeding, tumours, crusting or foreign bodies should be noted.
Therapeutic options for AR include avoidance measures, nasal saline irrigation, oral antihistamines, intranasal corticosteroids, combination intranasal corticosteroid/antihistamine sprays, leukotriene receptor antagonists (LTRAs), and allergen immunotherapy. Other therapies that may be useful for some patients include decongestants and oral corticosteroids.
It is important to differentiate over-thecounter (OTC) and prescription therapies for AR. Nasal decongestant sprays are highly effective if used infrequently. Available options include Sudafed nasal spray (xylometazoline HCL), Otrivin (xylometazoline HCL), and Afrin (oxymetazoline HCL). Despite being available OTC, caution should be advised as incorrect use can lead to adverse effects. It is important that patients are aware that these decongestant sprays are not recommended for monotherapy in chronic AR.
First-line treatment of AR involves reduced exposure and avoidance of relevant allergens and irritants, such as house dust mites, moulds, pets and pollens, etc, that trigger the condition. Nasal saline irrigation is most effective when used for mild symptoms or before intranasal glucocorticoid (INGC) application. INGC options include Avamys, Nasonex, and Flixonase. If symptoms remain refractory to an intranasal glucocorticoid, a second generation oral antihistamine will be prescribed.
Second-generation oral anti-histamines such as loratadine and cetirizine are firstline pharmacological treatments recommended for all patients with AR. They re-
Clinical Respiratory Medicine THE MEDICAL INDEPENDENT | 10 JUNE 2021 22
One of the most common autoimmune conditions, allergic rhinitis can significantly impact quality-of-life, but a range of effective treatments are available
PhD, National PRO of the Irish General Practice Nurses Educational Association
THERESA LOWRY-LEHNEN, CNS, GPN,
Figure 1: Stepwise treatment approach to allergic rhinitis
Continued on p24 ▸
Vimovo® is indicated in adults for the symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, in patients who are at risk for developing non-steroidal anti-inflammatory drug (NSAID)-associated gastric and/or duodenal ulcers and where treatment with lower doses of naproxen or of other NSAIDs is not considered sufficient.1
In randomised controlled studies, Vimovo treatment provided significant improvement in WOMAC pain2, WOMAC function2, and PGA-scores2, compared to placebo3. The PGA questionnaire asked patients “Considering the way your arthritis affects you, how well are you doing today?„ and the WOMAC pain and function included items such as walking on a flat surface, climbing stairs and going shopping.
duodenal ulcers and where treatment with lower doses of naproxen or of other NSAIDs is not considered sufficient. Dosage and method of administration: Adults: Oral use. Swallowed whole (not split, chewed or crushed) with water. Recommended to take at least 30 minutes prior to food intake. One tablet twice daily. Use lowest effective dose for shortest duration possible. Patients not treated with NSAID previously, or when 1000mg/day of naproxen is not considered appropriate, alternative therapeutic treatment with lower strength of naproxen or of other NSAIDS as non-fixed combination should be utilised. Review at regular intervals and discontinue if no benefit or if worsening. Not intended for relief of acute pain conditions. Flares of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis may be treated. Renal / Hepatic impairment: Use cautiously in mild to moderate renal/hepatic impairment and monitor closely. Consider reduction in total daily naproxen dose. Elderly (>65 years): older people are at risk of serious consequences of adverse reactions. Paediatric population: Safety and efficacy not established in 0 to 18 years.
Contra-indications: Hypersensitivity to ingredients, history of asthma, urticaria or allergic-type reactions induced by administration of acetylsalicylic acid or other NSAIDs, third trimester of pregnancy, severe heart failure, severe renal impairment, active peptic ulceration, gastrointestinal (GI) bleeding, cerebrovascular bleeding or other bleeding disorders, must not be used concomitantly with atazanavir and nelfinavir. Special Warnings and precautions: Avoid concomitant NSAIDs use. Can be used with low dose acetylsalicylic acid. Undesirable effects may be minimized by using lowest effective dose for the shortest duration necessary. Assess at meaningful intervals to prevent over-treatment. Risk-factors to develop NSAID related GI complications include high age, concomitant use of anticoagulants, corticosteroids, other NSAIDs including low-dose acetylsalicylic acid, debilitating cardiovascular disease, Helicobacter pylori infection, and a history of gastric and/or duodenal ulcers and upper GI bleeding. In Inducible porphyries and systemic lupus erythematosus and mixed connective tissue disease use only after rigorous benefit-risk ratio. Patients on long-term treatment should be kept under regular surveillance. Contains very low levels of methyl and propyl parahydroxybenzoate. Elderly: Naproxen: Older people have an increased frequency of adverse reactions especially GI bleeding, and perforation, which may be fatal. Gastrointestinal effects: Naproxen: GI bleeding, ulceration or perforation, which can be fatal with or without warning symptoms or a previous history of serious GI events. Risk is higher with increasing NSAID doses, patients with history of ulcers and in older people. Start with low dose and consider combination therapy with protective agents. Caution in patients receiving NSAIDs with concomitant medications which could increase risk of ulceration or bleeding. Withdraw treatment if GI bleeding or ulceration. Caution in patients with a history of GI disease. Esomeprazole: In the presence of any alarm symptom and when gastric ulcer is suspected, malignancy should be excluded. Dyspepsia could still occur. May lead to increased risk of GI infections. May reduce absorption of vitamin B12 due to hypo- or achlorhydria. Cardivascular and cerebrovascular effects: Naproxen: Appropriate monitoring and advice for patients with history of hypertension and/or mild to moderate congestive heart failure. The use of coxibs and some NSAIDs may be associated with a small increased risk of arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with naproxen after careful consideration. Consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events. Renal effects: Naproxen: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. Patients at greatest risk of this are those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics, angiotensin converting enzyme (ACE) inhibitors, or angiotensin II receptor antagonists and older people. Use with great caution in patients with impaired renal function and monitoring of serum creatinine and/or creatinine clearance is advised. Contraindicated in patients with baseline creatinine clearance less than 30 ml/min. Assess renal function before and during therapy in patients with compromised renal blood flow. Hepatic effects: Borderline elevations of liver tests may occur, due to hypersensitivity rather than toxicity. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some with fatal outcomes have been reported. Hepatorenal syndrome: Use of NASAIDs may be associated with acute renal failure in patients with hepato-cirrhosis. These patients frequently also have concomitant coagulopathy related to inadequate synthesis of clotting factors. Antiplatelet effects associated with naproxen could further increase risk of severe bleeding. Haematological effects: Naproxen: Careful observation when administered to patients who have coagulation disorders or are receiving drug therapy that interferes with haemostasis. Increased risk of bleeding if given to patients with high risk of bleeding and those on full anti-coagulation therapy. Naproxen decreases platelet aggregation and prolongs bleeding time. If active and clinically significant bleeding from any source occurs, withdraw treatment. Eye effects: Naproxen: recommend ophthalmic examination if any change or disturbance in vision occurs. Dermatological effects: Naproxen: Discontinue at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Esomeprazole: associated with very infrequent cases of subacute cutaneous lupus erythematosus (SCLE). If lesions occurs and if accompanied by arthralgia, seek medical help promptly and consider stopping treatment. SCLE after previous treatment with a PPI may increase the risk of SCLE with other PPIs. Anaphylactic (anaphylactoid) reactions: Naproxen: anaphylactic (anaphylactoid) reactions may occur in patients with and without a history of hypersensitivity or exposure to acetylsalicylic acid, other NSAIDs or naproxen-containing products. They may also occur in individuals with a history of angio-oedema, bronchospastic reactivity, rhinitis and nasal polyps. Pre-existing asthma: Naproxen: Use with caution and should not be administered to patients with aspirin-sensitive asthma. Inflammation: Naproxen: may reduce fever and other signs of inflammation thereby diminishing their utility as diagnostic signs. Female fertility: not recommended in women attempting to conceive. Combination with other medicinal products: Must not be used with atazanavir. Esomeprazole is a CYP2C19 inhibitor. When starting or ending treatment, the potential for interactions with drugs metabolised through CYP2C19 should be considered. Concomitant use with clopidogrel should be discouraged. Hypomagnesaemia: Severe hypomagnesaemia has been reported in patients treated with Proton Pump Inhibitors (PPIs). Consider measuring magnesium levels before starting PPI treatment and periodically during treatment in patients expected to be on prolonged treatment or those on concomitant digoxin or drugs that may cause hypomagnesaemia. Bone fracture: PPIs, if used in high doses and over long durations (>1 year), may increase the risk of hip, wrist and spine fracture, predominantly in older people or in presence of other recognised risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and have an adequate intake of vitamin D and calcium. Interference with laboratory tests: Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, treatment should be stopped for at least 5 days before CgA measurements. Interactions: Antiretroviral agents: Concomitant use of atazanavir and nelfinavir with esomeprazole is not recommended and concomitant administration with Vimovo is contraindicated. Concomitant use with precaution: Other analgesics including cyclooxygenase-2 selective inhibitors: Concomitant use with other NSAIDs except for low-dose acetylsalicylic acid (≤ 325 mg/day), is not recommended. Acetylsalicylic acid: Can be administered with low dose acetylsalicylic acid (≤ 325 mg/day). In clinical trials, Vimovo in combination with low-dose acetylsalicylic acid did not have increased occurrence of gastric ulcers. However, concurrent use may still increase risk of serious adverse events. Clinical pharmacodynamic data suggests concomitant naproxen usage for more than one day consecutively may inhibit the effect of low-dose acetylsalicylic acid on platelet activity and this inhibition may persist for up to several days after stopping naproxen. Clinical relevance of this interaction is not known. Tacrolimus: A reinforced monitoring of tacrolimus concentrations as well as renal function should be performed and dose of tacrolimus adjusted if needed. Ciclosporin: caution when coadministered because of increased risk of nephrotoxicity. Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazides in some patients. Observe patient closely for signs of renal failure as well as to assure diuretic efficacy. SSRIs: Concomitant use of NSAIDs, including COX-2 selective inhibitors, and SSRIs increases the risk of GI bleeding. Corticosteroids: Increased risk of GI bleeding when combined with NSADIs including COX-2 selective inhibitors. Caution when NSAIDS are concomitantly administered with corticosteroids. ACE-inhibitors/Angiotensin II receptor antagonists: caution when combined with NSAIDs in patients who are older, volume-depleted, or with renal impaired renal function as NSAID may diminish antihypertensive effect and increase risk of renal impairment associated with ACE-inhibitor or angiotensin II receptor antagonists. Digoxin: NSAIDs may increase plasma cardiac glycoside levels when co-administered with cardiac glycosides such as digoxin. Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Observe carefully for lithium toxicity. Methotrexate: esomeprazole and naproxen could enhance the toxicity of methotrexate. Caution when administered concomitantly with methotrexate. In high-dose methotrexate administration a temporary withdrawal of Vimovo is recommended. Sulphonylureas, Hydantoins: Naproxen is highly bound to plasma albumin; thus a theoretical potential for interaction with other albumin-bound drugs (sulphonylureas, hydantoins). When coadministered patients should be observed for adjustment of dose. Clopidogrel: Concomitant use should be discouraged due to inconsistent data on clinical implications of a PK/PD interaction of esomeprazole in terms of major cardiovascular events reported from observational and clinical studies. Anti-coagulants and thrombocyte aggregation inhibitors: NSAIDs may enhance the effects of oral anti-coagulants, heparins and thrombocyte aggregation inhibitors. Close monitoring when initiating and ending treatment with warfarin or other coumarine derivatives. Beta receptor-blockers: Naproxen and other NSAIDs can reduce the antihypertensive effect of propranolol and other beta-blockers. Probenecid: Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly. Drugs with gastric pH-dependent absorption: gastric acid suppression during treatment with esomeprazole, and other PPIs might decrease or increase the absorption of drugs with a gastric pH dependent absorption. The absorption of drugs such as ketoconazole, itraconazole, posaconazole and erlotinib can decrease while the absorption of drugs such as digoxin can increase. Concomitant use with posaconazole and erlotinib should be avoided. Other Information Concerning Drug Interactions: Studies evaluating concomitant administration of esomeprazole and either naproxen or rofecoxib did not identify any clinically relevant interaction. Concomitant administration of cholestyramine can delay absorption of naproxen. In healthy volunteers, concomitant administration esomeprazole resulted in an increase in area under the plasma concentration-time curve and prolonged elimination half-life but no significant increase in peak plasma levels of cisapride. Esomeprazole has been shown to have no clinically relevant effects on the pharmacokinetics of amoxicillin and quinidine. Esomeprazole inhibits CYP2C19, the major esomeprazole metabolising enzyme. Esomeprazole is also metabolised by CYP3A4. Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John‘s Wort) may lead to decreased esomeprazole serum levels. Omeprazole and esomeprazole act as inhibitors of CYP2C19. Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking quinolones may have an increased risk of developing convulsions. Drug/Laboratory Test Interaction: Naproxen may decrease platelet aggregation and prolong bleeding time. Naproxen may result in increased urinary values for 17-ketogenic steroids. Suggested therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used. Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA). Pregnancy and lactation: In women attempting to conceive or in first and second trimester, do not give unless potential benefit to patient outweighs risk to foetus. Duration of treatment should be as short as possible. Contraindicated during third trimester. Should not be used during breastfeeding. Effects on driving and using machinery: minor influence on the ability to drive and use machines; based on that some of the adverse effects (e.g. dizziness) reported following the use may reduce the ability to react.
Undesirable effects: Reported fromVimovo clinicaltrials: Very common (≥1/10): dyspepsia. Common (≥1/100 to <1/10): dizziness, headache, taste disturbance, hypertension, abdominal pain, constipation, diarrhea, esophagitis, flatulence, gastric/duodenal ulcers, gastritis, nausea, vomiting, skin rashes, arthralgia, oedema. Other important undesirable effects: paraesthesia, syncope, arrhythmia, GI bleeding, stomatitis, urticaria, (Uncommon (≥ 1/1,000 to < 1/100), diverticulitis, hypersensitivity reactions, myocardial infarction, tachycardia, rectal bleeding, renal failure, (Rare (≥ 1/10,000 to < 1/1,000). Naproxen: adverse experiences reported during trial and through postmarketing reports: Common (≥1/100 to <1/10): diverticulitis, depression, insomnia, dizziness, drowsiness, headache, lightheadedness, vertigo, visual disturbances, tinnitus, hearing disturbances, palpitations, dyspnea, dyspepsia, abdominal pain, nausea, vomiting, diarrhea, constipation, heartburn, pepticulcers, stomatitis, pruritus, ecchymoses, purpura, skin rashes, fatigue, oedema, sweating, thirst. Other important undesirable effects: sepsis, agranulocytosis, eosinophilia, granulocytopenia, Pancytopenia, thrombocytopenia, anaphylactic reaction, anaphylactoid reactions, hypersensitivity reactions, coma, convulsions, optic neuritis, paresthesia, syncope, corneal opacity, papilloedema, arrhythmia, myocardial infarction, tachycardia, eosinophilic pneumonitis, pneumonia, respiratory depression, gastric/duodenal ulcers, gastrointestinal bleeding and/or perforation, pancreatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn‘s disease), rectal bleeding, cholestasis, hepatitis, jaundice, liver failure, exanthema, urticaria, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, erythema multiforme, systemic lupus erythematosus, pseudoporphyria, nephrotic syndrome, renal failure, renal papillary necrosis, tubular necrosis, Uncommon (≥ 1/1,000 to < 1/100), Rare (≥ 1/10,000 to < 1/1,000). Esomeprazole: adverse drug reactions identified or suspected in clinical trial for enteri-coated esomeprazole and/or post marketing. None were found to be dose-related: Common (≥1/100 to <1/10): headache, abdominal pain, diarrhea, flatulence, nausea/vomiting, constipation, fundic gland polyps (benign). Other important undesirable effects: paraesthesia, pruritus, urticaria, fracture of the hip, wrist or spine (Uncommon (≥ 1/1,000 to < 1/100). leukopenia, thrombocytopenia, hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock, depression, paraesthesia, syncope, arrhythmia, gastrointestinal bleeding, stomatitis, pruritus, urticaria, (Rare (≥ 1/10,000 to < 1/1,000)). agranulocytosis, pancytopenia agranulocytosis, pancytopenia, hepatic failure, hepatic encephalopathy in patients with pre-existing liver disease, erythema multiforme, Interstitial nephritis, (Very rare (< 1/10,000)). Overdose: Effects of overdose expected to reflect the effects of naproxen overdose. Significant naproxen overdosage may be characterized by lethargy, dizziness, drowsiness, epigastric pain, abdominal discomfort, heartburn, indigestion, nausea, transient alterations in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, disorientation or vomiting. GI bleeding can occur. Hypertension, acute renal failure, respiratory depression, and
VIMOVO 500mg/20mg modified-release tablets (naproxen and esomeprazole) Refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentation: Modified-release tablet (oval, biconvex, yellow, marked 500/20 in black ink) containing enteric-coated naproxen (500 mg) and film-coated esomeprazole (20 mg). Indication: In adults for the symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, in patients who are at risk for developing non-steroidal anti-inflammatory drug (NSAID)-associated gastric and/or
coma may occur, but rare. Anaphylactoid reactions have been reported. A few patients have experienced convulsions. It is not known what dose of the drug would be life-threatening. The symptoms in connection with esomeprazole overdose are transient. Patients should be managed by symptomatic and supportive care following a NSAID overdose, particularly with respect to GI effects and renal damage. Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of protein binding. Emesis and/or activated charcoal and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose. Forced diuresis, alkalinization of urine or hemoperfusion may not be useful. Esomeprazole is not readily dialyzable. There are no specific antidotes for naproxen or esomeprazole. Legal classification: POM. Marketing Authorisation number, pack sizes: PA 1019/024/001, 60 packs. Marketing Authorisation Holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden. Date of preparation: August 2020. M-VMO-IE-08-20-0001. References: 1. Vimovo Summary of Product Characteristics. 2. Bellamy N. WOMAC: a 20-year experiential review of a patient-centered self-reported health status questionnaire. The Journal of Rheumatology. 2002;29(12):2473-2476. 3. Hochberg MC, Fort JG, Svensson O et al. Fixed-dose combination of enteric-coated naproxen and immediate-release esomeprazole has comparable efficacy to celecoxib for knee osteoarthritis: two randomized trials. Curr Med Res Opin. 2011;27(6):1243-1253. M-VMO-IE-10-20-0004 – October 2020 Combined to reflect their potential
quire once-daily dosage, are non-drowsy and are available OTC without prescription. Second-generation antihistamines offer several advantages over classical H1 antihistamines, such as lack of sedation and impairment of performance, longer duration of action, and absence of anti-cholinergic side effects. However, loratadine is best avoided in elderly patients and patients with liver problems.
First-generation sedating antihistamines, such as diphenhydramine and chlorpheniramine, are also effective in relieving symptoms, however, they have been shown to negatively impact cognition and functioning, may affect the patient’s ability to drive and operate machinery and are not routinely recommended for the treatment of AR. They should not be used in patients with prostatic hypertrophy or narrow-angle glaucoma.
The advantages of oral antihistamines are once-a-day administration, rapid and effective action and low cost. However, they are less effective than intranasal corticosteroids (INCS), particularly for nasal congestion which is a common symptom of AR. Oral antihistamines are often sufficient for the treatment of mild AR, and many patients prefer oral medications to other formulations. Some oral antihistamines may, with caution, be used in pregnancy or in women who are breastfeeding for example, cetirizine.
Other first-line therapeutic options for patients with mild persistent or moderate/severe symptoms are INCS and they can be used alone or in combination with oral antihistamines. When used regularly and correctly, INCS effectively reduce inflammation of the nasal mucosa and improve mucosal pathology. Studies and meta-analyses have shown that INCS are superior to antihistamines and leukotriene receptor antagonists in controlling symptoms of AR, including nasal congestion and rhinorrhoea.
INCS are not systemically absorbed. The most common adverse effects are local, including nasal irritation, stinging and epistaxis, and can usually be prevented by aiming the spray slightly away from the nasal septum. Long-term use does not damage nasal mucosa or induce glaucoma, and growth effects in children seem to be minimal. Some INCS, such as budesonide, can be safely used during pregnancy at the recommended therapeutic dose after a thorough medical evaluation.
If INCS are not effective, a combination corticosteroid/antihistamine spray, such as Dymista, can be used. LTRAs should be considered when oral antihistamines, INCS, and/or combination corticosteroid/antihistamine sprays are not well tolerated or are ineffective in controlling the symptoms of AR. For patients with AR refractory to INGCs and concomitant asthma, a trial of an LTRA, such as montelukast, is advised. If combination pharmacological therapy with oral antihistamines, INCS, combination corticosteroid/ antihistamine sprays and LTRAs is not effective or is not tolerated, then allergen immunotherapy should be considered.
Allergen-specific immunotherapy (AIT) is
currently the only potential treatment for allergies including AR that can modify the underlying course of the diseases. AIT is indicated for AR, allergic rhino-conjunctivitis and/or asthma when symptoms remain uncontrolled with avoidance measures and appropriate pharmacotherapy in adherent patients. The aim of AIT is to induce tolerance to the allergens and therefore reduce the symptoms of allergic diseases.
By gradually increasing the patient’s exposure to the allergen that causes the allergy, the patient becomes tolerant to it. Immunotherapy is only used in patients with severe symptoms and must be done by a specialist. AIT for the management of allergic disease has entered a new phase. Safe, effective, oral sub-lingual immunotherapy (SLIT) preparations are becoming increasingly available for use in allergy de-sensitisation as opposed to allergy injections. The use of AIT by 'allergy shots/ injections' was severely curtailed in Ireland and the UK from 1986 when a number of deaths were reported with its use in general practice, particularly in those patients who had unstable underlying asthma. The situation has changed over the past decade however, with strong evidence that AIT can effectively treat AR , eradicate it and even prevent the development of asthma in allergic children if used early enough.
For a sustained effect, AIT should be applied for a minimum of three years, either continuously or pre-seasonally. Benefit may not appear until the end of the first year of treatment, but may persist for many years beyond the course of treatment. Prolonged desensitisation using increasing doses of the culprit allergen both by subcutaneous immunotherapy (SCIT) and SLIT reduces rhinitis symptoms which have been refractory to INGC and oral antihistamines.
Grazax and Oralair are two licenced SLIT preparations available for grass pollen AR in Ireland. If patients have co-existing asthma, it must be recognised and treated and their lung function test must be normal. Patients must be advised to place the tablet under the tongue for one-to-two minutes and then swallow it. Grazax should be commenced two-to-four months before the pollen season starts in late May/June and continued daily for a total of three years. Oralair is commenced at the same time for a period of six months per year for three successive years if there is an effect seen after the first season.
SLIT is now viewed as a significant advance in the treatment of allergic diseases. It is very effective in the treatment of rhinitis with long-lasting benefits seen after the treatment is discontinued. It is the only treatment that offers the possibility of reducing long-term costs and the burden of allergies by changing the natural course of the disease.
Other emerging therapies
Biological therapies represent a potential step forward in providing individualised care for patients with uncontrolled severe upper airway diseases. Biologics like omalizumab and dupilumab have demonstrated efficacy in patients with chronic AR and with nasal polyps. These monoclonal antibodies target type 2 inflammatory cytokines, including IL-4, IL-5, 1L-13 and IgE and have convincing evidence in proof of concept studies. The
immediate goals in biologic therapies for allergies and asthma are to develop biomarkers to identify patients most likely to respond to these therapies and to monitor disease severity. As experience with biological therapies continues to grow, they are expected to move from their current position as add-on therapies for severe allergic disease to play a more prominent role in treatment strategies for many more allergy patients.
House dust allergy tips
Allergy-proof covers for mattresses, duvets and pillows;
Choose wood or hard vinyl floor coverings instead of carpet;
Fit roller blinds that can be easily wiped clean;
Regularly clean cushions, soft toys, curtains and upholstered furniture, either by washing or vacuuming them;
Use synthetic pillows and acrylic duvets instead of woollen blankets or feather bedding;
Using a vacuum cleaner fitted with a high-efficiency particulate air (HEPA) filter can remove more dust than an ordinary vacuum cleaner;
Use a clean damp cloth to wipe surfaces – dry dusting can spread allergens further.
If a pet cannot permanently be removed from the house:
Keep pets outside as much as possible or limit them to one room, preferably without carpet;
Do not allow pets in bedrooms;
Wash pets at least once a fortnight;
Groom dogs regularly outside;
Regularly wash bedding and soft furnishings a pet has been on;
Taking an antihistamine one hour before entering a house with a pet can help reduce symptoms.
To avoid exposure to pollen:
Check weather reports for the pollen count and stay indoors when it is high;
Avoid line-drying clothes and bedding when the pollen count is high;
Wear wraparound sunglasses to protect eyes from pollen;
Keep doors and windows shut during mid-morning and early evening, when there's most pollen in the air;
Shower, wash hair and change clothes after being outside;
Avoid grassy areas, such as parks and fields, when possible;
If you have a lawn, consider asking someone else to cut the grass for you.
To help prevent mould spores:
Keep your home dry and well ventilated;
When showering or cooking, open windows, but keep internal doors closed to prevent damp air spreading through the house, and use extractor fans;
Avoid drying clothes indoors, storing clothes in damp cupboards and packing clothes too tightly in wardrobes;
Prevent damp and condensation in the home.
References on request
Clinical Respiratory Medicine THE MEDICAL INDEPENDENT | 10 JUNE 2021 24
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PC-IE-101115 370x255 10mm border ad Water Bottle Final.indd 1 2/9/21 4:20 PM
Fishing for answers on melanocytes and melanoma
Attendees at UCD’s Charles Institute Seminar Series recently heard a presentation from Prof Liz Patton of the University of Edinburgh on the latest research into melanocytes and melanoma in zebrafish models
The Charles Institute, Ireland’s national dermatology research and education centre, played host to a range of guest speakers who covered a variety of topics ranging from skin cancer to psoriasis, among others. The series, which was sponsored by RELIFE (part of the A.Menarini group), was designed to provide expert advice from a range of distinguished national and international experts in their respective fields and was 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 were broadcast to attendees with a special interest in dermatology in other locations, who accessed the talks remotely via an audio-visual link.
Attendees heard a presentation from Prof Liz Patton, MRC Human Genetics at the Institute of Genetics and Cancer, University of Edinburgh, UK, who delivered a talk to the attendees titled ‘Discovering and Targeting New Melanocytes and Melanoma Cell Populations in Zebrafish’. Prof Patton explained that dynamic cellular heterogeneity underlies melanoma progression and therapy resistance, and zebrafish are a powerful model system to identify new cell subpopulations and better understand how they contribute to disease progression, as well as helping to identify new drug targets. She provided an overview of how she and her team are applying chemical genetics, imaging and single-cell technologies to discover new cell states in melanoma with a view to improving future treatment options.
“One of the advantages of using zebrafish as models is their ability to move between the developmental stages and the adult stages,” Prof Patton told the seminar. “Even in an embryo, which is just a few millimetres long, already you can see the melanocytes and they already have a beating heart, circulating blood, an innate immune system, digestive system — so they are already, at that stage, little formed animals,” she said. “Using fluorescent reporter lines, we are able to visualise cell populations.”
Using fluorescent reporter lines allows Prof Patton and her colleagues to study undifferentiated cells, “or as we call them melanocyte stem cells, which are just tucked under the neural tube at the site of the future dorsal root ganglia,” she said.
Zebrafish melanomas appear quite similar to human melanomas, Prof Patton explained, as they share histopathology, genetics and transcriptional signatures and so are a good model to study, particularly for cutaneous melanomas in the context
of Prof Patton’s research.
She provided an outline of research objectives for her team, including identifying cell populations in melanoma models, in particular at a stage of residual disease in melanomas after bulk tumour collapse, but prior to regrowth. Prof Patton also outlined her work in trying to identify mechanisms of cell state transitions, among other areas of research focus.
“The cancer genome atlas identified many mutations in melanoma, with the most frequent ones being BRAF, RAS and NF1 mutant,” she told the attendees. “But they also identified transcriptional signatures in melanoma and what’s quite interesting is that although the genetic mutations didn’t correlate with patient outcomes, in fact the transcriptional signatures did.” Three groups of transcriptional clusters have been identified — immune signature, keratin signature, and MITF (melanocyte-inducing transcription factor)-low signature, said Prof Patton.
“MITF is the master melanocyte transcription factor and it is required for a neural crest cell to become a melanocyte,” she told the attendees. “What was found in the MITF-low signature is that the MITF targets were down, but other neuronal-type were up. These transcriptional signatures have been identified by other groups… it has been found that this MITF-low subgroup really predicts the poorest outcomes for patients.”
MITF protein, she explained.
Another objective was to establish how dependent tumours are on MITF activity for their survival, said Prof Patton. “We found that having lower levels of MITF, if we cross it to p53 mutant zebrafish, we get melanomas,” she told the seminar. “These are primarily superficial spreading melanomas and if we add in BRAF mutation, this accelerates the onset of melanoma; we see superficial growth patterns, but we also see large, nodular, very proliferative tumours.”
The next step was to see how the MITFlow zebrafish model compare to the human MITF-low state, she explained. “We compared our zebrafish MITF-low to zebrafish MITF-high tumours and we compared the genes and pathways between them,” she said. “We also compared the lowest levels of MITF and highest and did the same sort of analysis, and we could really see a strong overlap between our zebrafish MITF-low melanomas and human MITF-low melanomas.”
These MITF-low melanomas are enriched with neural crest signatures, which appear to be highly invasive mesenchymal-like cells, Prof Patton explained. “We wonder if this is one of the reasons why patients in this MITF-low type transcriptional state have such poor outcomes — possibly because they have this very high expression of these invasive signatures.”
tant as we move forward and think about the next generation of therapies.”
Prof Patton summarised: “Using zebrafish is a powerful model for studying both melanocyte development and melanoma. What we are learning is that melanocyte development becomes dysregulated and is important in our melanoma models,” she told the seminar. “We were able to generate a MITF-low melanoma models that resemble the transcriptional signatures of MITF-low patient melanomas. We were able to discover cells that were independent of MITF, so they had lost their melanocyte identity,” continued Prof Patton. “We were also able to identify two new mechanisms in these lineages that affects cell states.”
During an interactive discussion and Q&A session, Prof Tobin commented on the search for the melanocyte stem cell in zebrafish and the issue of residual disease regrowth. Prof Patton added: “We had been thinking of these cells as a little bit more like the hair follicle stem cell, but now we are looking at their transcriptomes, we are wondering if they are a little more like the Schwann cell precursor-like cells that perhaps have the potential to even become other cell types. Because of the transcriptional analysis, we have recently started to change our thinking.”
Prof Tobin also commented on extracellular vesicles in the context of where regrowth and residual disease come from, and asked: “One way you have of chasing these cells down is through regional or body-map location, but do you ever see residual disease regrowth happening at a site that is distant from the primary tumour?”
This prompted Prof Patton and her colleagues to try to model a transcriptional state in melanoma, rather than just looking at genetic mutations, and this was achieved by identifying a temperature-sensitive allele. “When we increased the water temperature, we decreased the amount of wild-type MITF transcripts that are created, so we reduced MITF activity as we increased the water temperature,” she said. This does not change the transcription from the MITF promoter, but rather changes the amount of active
One of the advantages of having a temperature-sensitive allele that can be turned off is that it allows the researchers to address the dependency of the tumours on MITF for survival, explained Prof Patton.
Prof Patton touched on the importance of residual disease in melanoma and told the seminar: “Patients who are given BRAF and MEK inhibitors often have a similar trajectory, in that they respond quickly to the therapy and the tumour can decrease in bulk, but the tumour often comes back,” she said. “So understanding residual disease is very impor-
Prof Patton commented: “In most of our models, we don’t see that,” she said. “In most of our models, in the way we are conducting the experiments, they are really coming from the same site. Having said that, of course there will be metastases; when we first started working with zebrafish melanoma, we didn’t think they would be so good as a model for studying metastases, because the tumours can become quite bulky and then we have to put the animal down.
“However, there has been some really good work… studying metastases in zebrafish and I think we have an opportunity to follow this now,” she continued.
“So the question is very relevant — so far, we have focused on the same site, but when we do our lineage-tracing analysis, it would be great to investigate where those cells start to come back up.”
RELIFE has had no input into the content of this article or series of seminars
Clinical Dermatology THE MEDICAL INDEPENDENT | 10 JUNE 2021 26
Article and series in association with UCD CHARLES INSTITUTE SEMINAR SERIES
Prof Liz Patton
The cancer genome atlas identified many mutations in melanoma, with the most frequent ones being BRAF, RAS and NF1 mutant
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Irish Society for Rheumatology Spring Meeting, virtual, 13 May 2021
Diabetes screening necessary in patients with GCA and polymyalgia rheumatica
Dr Sarah Mackie, Consultant Rheumatologist and Associate Professor at the University of Leeds, presented to delegates at the Irish Society for Rheumatology (ISR) Spring Meeting, which was held virtually on 13 May, on the subject of polymyalgia rheumatica and giant cell arteritis (GCA).
Dr Mackie provided an overview of a systematic review and meta-analysis of 68 studies, including 14,037 patients who had suspected GCA. Findings of the meta-analysis revealed that where the likelihood ratio of a symptom was greater than one, it was likely that
GCA was present, whereas when the likelihood ratio was less than one, it was unlikely that GCA was present. While each of the four existing methods of assessing pre-test probability in GCA has its benefits and limitations, Dr Mackie highlighted the necessity of addressing diagnostic uncertainty
while utilising and tweaking the chosen method to fit specific settings.
Dr Mackie referenced the British Society of Rheumatology (BSR) guidelines on the diagnosis and treatment of GCA, which were published in January 2020 and accredited by the UK National Institute of Health and Care Execellence (NICE). BSR guidelines addressed the limitations of the assessment methods by recommending that each patient is referred to a specialist who has experience of diagnosing GCA (a rheumatologist), and an ultrasound, or biopsy, or both should be obtained.
Unlike GCA, before engagement with rheumatology, polymyalgia rheumatica is usually treated by GPs with steroids. While MRI, PET-CT and PET-MRI can help in diagnosis, practical limitations mean that not all patients in the community receive such screening. As such, approximately 3 per cent of polymyalgia rheumatica patients in the UK are treated with disease-modifying antirheumatic drugs (DMARDs) and the level of care is inconsistent. It is possible that some of these patients will go on to develop GCA.
To ascertain how many patients with GCA or polymyalgia rheumatica go on to develop diabetes, Dr Mackie carried out a meta-analysis of observational studies and trials. This meta-analysis involved 3,743 patients and revealed that 30 per cent of the GCA patients go on to develop diabetes, while 6 per cent of patients with polymyalgia rheumatica do likewise.
A further study of a dataset from the Clinical Practice Research Datalink involved a group of 100,722 patients without diabetes, 32 per cent of whom had either GCA or polymyalgia rheumatica. In the 10 years since diagnosis, 13.9 per cent of these patients had developed diabetes.
Given that treatment of both conditions involves the use of high doses of steroids, which can cause multisystem toxicity, Dr Mackie stated that diabetes screening is needed in patients with GCA and polymyalgia rheumatica.
Conference Coverage THE MEDICAL INDEPENDENT | 10 JUNE 2021 28
Dr Sarah Mackie
While MRI, PET-CT and PET-MRI can help in diagnosis, practical limitations mean that not all patients in the community receive such screening
Abbreviated Prescribing Information. Consult the Summary of Product Characteristics for full information. Additional information is available on request. Idacio (adalimumab) 40 mg This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See below for how to report adverse reactions. Idacio 40 mg solution for injection in pre-filled syringe Idacio 40 mg solution for injection in pre-filled pen Idacio 40 mg solution for injection in vial for paediatric use Presentation and method of administration: Each single dose 0.8 ml pre-filled
and Fresenius Kabi supported me all the way"
IDACIO® is an adalimumab biosimilar, which is approved for use in the same conditions as the biologic reference product, including the treatment of moderate to severe, active rheumatoid arthritis 1, 2 Patients prescribed IDACIO can access KabiCare, a web-based resource developed with a holistic approach to patient support.
IDACIO® is an adalimumab biosimilar, which is approved for the same indications as the biologic reference product, including the treatment of moderately to severely active Crohn’s disease and ulcerative colitis in adult patients.1, 2 Patients prescribed IDACIO can access KabiCare, a web-based resource developed with a holistic approach to patient support.
The indications for IDACIO include the treatment of moderately to severely active Crohn’s disease and ulcerative colitis in adults who have had inadequate response to conventional therapies or who are intolerant to or have contraindications to such therapies.1 Before prescribing IDACIO please consult the Summary of Product Characteristics. Patients prescribed IDACIO should receive a patient alert card. For more information about IDACIO and KabiCare, please contact your local Fresenius Kabi representative.
The indications for IDACIO in adults include, in combination with methotrexate, the treatment of moderate to severe, active rheumatoid arthritis when the response to DMARDs* has been inadequate and also the treatment of severe, active and progressive rheumatoid arthritis without previous methotrexate treatment.1 IDACIO can be given as monotherapy in case of intolerance to methotrexate, or when continued methotrexate treatment is inappropriate.1 Before prescribing IDACIO please consult the Summary of Product Characteristics. Patients prescribed IDACIO should receive a patient alert card. For more information about IDACIO and KabiCare, please contact your local Fresenius Kabi representative.
1. IDACIO Summary of Product Characteristics. Fresenius Kabi Ltd.
1. IDACIO 40mg solution for injection in pre-filled syringe and pre-filled pen. Summary of Product Characteristics. Fresenius Kabi Deutschland GmbH.
2. Humira Summary of Product Characteristics. Abbvie Ltd. KabiCare is funded and developed by Fresenius Kabi. IDACIO and KabiCare are registered trademarks of Fresenius Kabi.
syringe, 0.8 ml prefilled pen or 0.8 ml vial contains 40 mg of adalimumab for subcutaneous injection. Indications and
Dosage: Please refer to SmPC for full information. Idacio treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of conditions for which Idacio is indicated. Ophthalmologists are advised to consult with an appropriate specialist before initiation of treatment with Idacio. Patients treated with Idacio should be given a patient alert card. After proper training in injection technique, patients may self-inject with Idacio if their physician determines that it is appropriate and with medical follow-up as necessary. During treatment with Idacio, other concomitant therapies (e.g., corticosteroids and/or immunomodulatory agents) should be optimised. Rheumatoid arthritis (RA), adults: In combination with methotrexate (MTX) for moderate to severe, active RA with inadequate response to disease-modifying antirheumatic drugs (DMARDs) including MTX. In combination with MTX for severe, active and progressive RA when not previously treated with MTX. Can be given as monotherapy if intolerance to or when continued treatment with MTX is inappropriate. Reduces rate of progression of joint damage on X-ray and improves physical function, in combination with MTX. Dosage:40 mg single dose every other week (EOW). Concomitant MTX should be continued. In monotherapy, patients may require 40 mg every week or 80 mg EOW if they experience a decrease in clinical response. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Consider need for dose interruption, e.g. before surgery or if serious infection occurs. Reintroduction after 70 days or longer of discontinuation gave same magnitudes of clinical response and similar safety profile as before dose interruption. Polyarticular juvenile idiopathic arthritis (pJIA), paediatrics 2 years and above:
In combination with MTX for active pJIA with inadequate response to one or more DMARDs. Can be given as monotherapy if intolerance to or when continued treatment with MTX is inappropriate.
Patients with no response by Week 4 may benefit from continued maintenance therapy to Week 12.
Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Paediatric
Crohn’s disease (CD), 6 years and above: For moderately to severely active CD with inadequate response to, intolerance to or contraindication for conventional therapy including primary nutrition therapy and a corticosteroid and/or an immunomodulator. Dosage: < 40 kg: Induction: 40 mg dose at Week 0, followed by 20 mg at Week 2. For a more rapid response: 80 mg at Week 0, followed by 40 mg at Week 2; risk of adverse events higher during rapid induction. Maintenance: 20 mg dose EOW from week 4. If insufficient response, consider an increase in dosing frequency to 20 mg every week. If ≥ 40 kg: Induction: 80 mg dose at Week 0, followed by 40 mg at Week 2. For a more rapid response: 160 mg dose at Week 0, followed by 80 mg at Week 2; risk of adverse events higher during rapid induction.
Maintenance: 40 mg dose EOW from week 4. If insufficient response, consider an increase in dosage to 40 mg every week or 80 mg EOW. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Ulcerative colitis (UC), adults: For moderately to severely active UC with inadequate response to, intolerance to or contraindication for conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA). Dosage: Induction: 160 mg dose at Week 0, followed by 80 mg at Week 2. Maintenance: 40 mg dose EOW. During maintenance, corticosteroids may be tapered in accordance with clinical guidelines. If insufficient response, consider an increase in dosage to 40 mg every week or 80 mg EOW. Treatment beyond 8 weeks should not be continued if no clinical response in that time. Uveitis, adults: For non-infectious intermediate, posterior and panuveitis with inadequate response to corticosteroids, in patients in need of corticosteroid-sparing, or in whom corticosteroid treatment is inappropriate. Dosage: 80 mg initial dose at Week 0, followed by 40 mg EOW from Week 1. Treatment can be initiated in combination with corticosteroids and/or with other non-biologic immunomodulatory agents. Concomitant corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating treatment with Idacio. Evaluate on a yearly basis the benefit and risk of continued longterm treatment. Paediatric Uveitis, 2 years and above: For chronic non-infectious anterior uveitis with inadequate response to or intolerance to conventional therapy, or in whom conventional therapy is inappropriate. Dosage: < 30 kg: 20 mg dose EOW in combination with MTX. Optional 40 mg (for patients < 30 kg) or 80 mg (for patients ≥ 30 kg) loading dose one week prior to start of maintenance therapy. No clinical data in use of loading dose < 6 years of age (see SmPC). If ≥ 30 kg: 40 mg dose EOW in combination with MTX. Evaluate on a yearly basis the benefit and risk of continued long-term treatment. Idacio may be available in other strengths and/or presentations depending on the individual treatment needs. Contraindications: Hypersensitivity to the active substance or to any excipients (see SmPC); Active tuberculosis (TB) or other severe infections such as sepsis and opportunistic infections; Moderate to severe heart failure (NYHA class III/IV). Warnings and precautions: Clearly record the name and batch number of administered product to improve
traceability of biological products. Infections: Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may increase the risk for developing infections. Monitor for infections, including TB, before, during and for at least 4 months after treatment. Treatment with Idacio should not be initiated in patients with active infections including chronic or localised infections until infections are controlled. In patients who have been exposed to tuberculosis and patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis, the risk and benefits of treatment with Idacio should be considered prior to initiating therapy. Evaluate new infections during treatment and monitor closely. Stop treatment if new serious infection or sepsis and treat appropriately. Exercise caution in patients with a history of recurring infections or who are predisposed to infections, including the use of concomitant immunosuppressive medications. Serious infections: Serious infections, including those associated with hospitalisation or death, were reported in patients receiving treatment. TB: Consult SmPC for details. Reactivation and new onset TB, both pulmonary and extra-pulmonary (disseminated), were reported. Screen all patients before therapy initiation for active or inactive (latent) TB. Appropriate screening tests (i.e. tuberculin skin test and chest X-ray) should be performed in all patients. If latent TB is suspected, consult physician with appropriate expertise and follow local treatment recommendations for prophylaxis prior to initiation of Idacio. Despite prophylaxis, TB reactivation has occurred on adalimumab. If active TB is diagnosed, do not initiate Idacio treatment. Other opportunistic infections: Opportunistic infections were observed in patients receiving adalimumab. Stop treatment in patients with signs and symptoms of such infections. Consult with physician with appropriate expertise for diagnosis and administration of empiric antifungal therapy in these patients. Hepatitis B reactivation: Reactivation of HBV has occurred in chronic carriers (surface antigen positive). Patients should be tested for HBV infection before initiating treatment. HBV carriers should consult a specialist physician and be closely monitored for reactivation of HBV infection throughout therapy and for several months following termination of treatment. If reactivation occurs, stop treatment and initiate appropriate antiviral and supportive treatment. Neurological events: Caution in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders. Discontinuation of treatment should be considered if any of these disorders develop. Neurologic evaluation should be performed in patients with non-infectious intermediate uveitis prior to initiation of treatment and regularly during treatment, to assess for pre-existing or developing central demyelinating disorders. Allergic reactions: Reports of serious allergic reactions including anaphylaxis received. For serious allergic or anaphylactic reaction, stop Idacio immediately and initiate appropriate therapy. Malignancies and lymphoproliferative disorders: A possible risk has been reported of malignancy, including lymphomas and leukaemia, in all patients, including paediatric patients, treated with Tumour Necrosis Factor (TNF) antagonists. Examine all patients, especially those with a medical history of extensive immunosuppressant or PUVA treatment, for non-melanoma skin cancer prior to and during treatment; caution in COPD patients, and in patients with increased risk for malignancy due to heavy smoking. Consider the potential risk with the combination of azathioprine or 6-mercaptopurine and adalimumab (hepatosplenic T-cell lymphoma has occurred). Risk of hepatosplenic T-cell lymphoma cannot be excluded. Caution in patients with a history of malignancy. Risk of developing dysplasia or colon cancer is unknown. Patients with UC with increased risk of dysplasia or colon carcinoma, or history of dysplasia or colon carcinoma, to be screened for dysplasia before treatment and throughout disease course. Haematological reactions: Adverse events of the haematological system reported with adalimumab. Patients should seek immediate medical attention if signs and symptoms of blood dyscrasias develop while on treatment. Vaccinations: Patients may receive concurrent vaccinations, except for live vaccines. Bring paediatric patients up to date with all immunisations prior to initiating Idacio treatment. Congestive heart failure: See contraindications. Caution is advised with mild heart failure (NYHA class I/II). Discontinue treatment if new or worsening symptoms of congestive heart failure. Autoimmune processes: Autoimmune antibodies may form with Idacio. Stop treatment if development of a lupus-like syndrome with positive antibodies against double-stranded DNA. Surgery: Consider the long half-life of Idacio for planned surgical procedures. Monitor closely for infections. Elderly patients: Serious infections were higher in patients over 65
Fresenius Kabi Ireland
Fresenius Kabi Ireland
Unit 3B Fingal Bay Business Park, Balbriggan, Co.Dublin, Ireland
Unit 3B Fingal Bay Business Park, Balbrigga, Co.Dublin, Ireland
T: +353 (0)1 8413030
F: +353 (0)1 8496949
T: +353 (0)1 8413030 F: +353 (0)1 8496949
Date of preparation: July 2020
Date of preparation: July 2020
Job code: BIO/IDACIO/011.20
Job code: BIO/IDACIO/007.20
Additional information is available on request
years of age, some of which had a fatal outcome. Consider risk of infections in these patients.
Way, Manor Park, Runcorn, Cheshire, WA7 1NT. Tel +44 (0)1928 533 533 Date of preparation of PI: April 2020 001/API/IDACIO/FKUK-IRL Adverse events should be reported. Reporting forms and information can be found at: yellowcard.mhra.gov.uk www.hpra.ie/homepage/about-us/report-an-issue Adverse events should also be reported to Fresenius Kabi Ltd. Cestrian Court, Eastgate Way, Manor Park, Runcorn, Cheshire, WA7 1NT Tel +44 (0)1928 533 533
Additional information is available on request 24,
2. Humira 40mg solution for injection in pre-filled syringe and pre-filled pen. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG. *DMARDs = disease-modifying anti-rheumatic drugs, including methotrexate KabiCare is funded and developed by Fresenius Kabi. IDACIO and KabiCare are registered trademarks of Fresenius Kabi.
If ≥ 30 kg: 40 mg dose initially followed by 40 mg EOW starting one week after initial dose. Treatment beyond 16
Dosage: 10 kg to < 30 kg 20 mg single dose EOW. If ≥ 30 kg: 40 mg single dose EOW. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Enthesitis-related arthritis (ERA), paediatrics 6 years and above: For active ERA with inadequate response to or intolerance to conventional therapy. Dosage: 15 kg to 30 kg: 20 mg single dose EOW. If ≥ 30 kg: 40 mg single dose EOW. Ankylosing spondylitis (AS), adults: For severe active AS with inadequate response to conventional therapy. Dosage: adults: 40 mg single dose EOW. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Axial spondyloarthritis without radiographic evidence of AS (nr-axSpA), adults: For severe nr-axSpA with objective signs of inflammation (elevated CRP and/or MRI), and an inadequate response to or intolerance to nonsteroidal antiinflammatory drugs. Dosage: 40 mg single dose EOW. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Psoriatic arthritis (PsA), adults: For active and progressive PsA with inadequate response to DMARDs. Reduces rate of progression of peripheral joint damage on X-ray in polyarticular symmetrical subtypes of the disease and improves physical function. Dosage: 40 mg single dose EOW. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Psoriasis, adults: For moderate to severe chronic plaque psoriasis in candidates for systemic therapy. Dosage: 80 mg initial dose at Week 0, followed by 40 mg EOW from Week 1. Treatment beyond 16 weeks should be reconsidered if no clinical response in that time (refer to SmPC). Paediatric Plaque Psoriasis, 4 years and above: For severe chronic plaque psoriasis with inadequate response to or if topical therapy and phototherapies are
15 kg to
followed by 20 mg
starting one week after initial dose.
weeks should be reconsidered if no clinical response in that time. Hidradenitis suppurativa (HS), adults and adolescents from 12 years and above: For active moderate to severe HS (acne inversa) with inadequate response to conventional systemic HS therapy. Dosage: HS, adults: 160 mg dose initially at Day 1, followed by 80 mg two weeks later at Day 15. Two weeks later (Day 29) continue with a dose of 40 mg every week or 80 mg EOW.HS, adolescents 12 years and above ≥ 30 kg: 80 mg initial dose at Week 0, followed by 40 mg EOW from Week 1. If there is inadequate response to 40 mg EOW, an increase in dosage to 40 mg every week or 80 mg EOW may be considered. Antibiotics may be continued if necessary. Concomitant topical antiseptic wash on HS lesions is recommended to be used on a daily basis. Treatment beyond 12 weeks should be reconsidered if no improvement in that time. Reintroduction of Idacio after treatment interruption as appropriate. Evaluate periodically the benefit and risk of continued long-term treatment. Crohn’s disease (CD), adults: For moderately to severely active CD with no response despite a full and adequate course of, intolerance to or contraindication for a corticosteroid and/or an immunosuppressant therapy. Dosage: Induction: 80 mg dose at Week 0, followed by 40 mg at Week 2. For a more rapid response: 160 mg at Week 0, followed by 80 mg at Week 2; risk of adverse events higher during rapid induction. Maintenance: 40 mg dose EOW. During maintenance, corticosteroids may be tapered in accordance with clinical guidelines. If decrease in clinical response, can increase dosage to 40 mg every week or 80 mg EOW.
Interactions: Antibody formation was lower when adalimumab was given together with MTX in comparison with use as monotherapy. Combination of Idacio with other biologic DMARDs (e.g. anakinra and abatacept) or other TNF-antagonists is not recommended. Fertility, pregnancy and lactation: Idacio should only be used during pregnancy if clearly needed. Women of childbearing age should consider the use of adequate contraception and continue its use for at least 5 months after the last treatment. No administration of live vaccines (e.g. BCG) to infants exposed to Idacio in utero for 5 months following mother’s last Idacio treatment during pregnancy. Idacio can be used during breast-feeding. Adverse Reactions: Very common ≥ 1/10: Respiratory tract infections (including lower and upper respiratory tract infection, pneumonia, sinusitis, pharyngitis, nasopharyngitis and pneumonia herpes viral), leukopenia (including neutropenia and agranulocytosis), anaemia, lipids increased, headache, abdominal pain, nausea and vomiting, elevated liver enzymes, rash (including exfoliative rash), musculoskeletal pain, injection site reaction (including injection site erythema). Common ≥ 1/100 to < 1/10: Systemic infections (including sepsis, candidiasis and influenza), intestinal infections (including gastroenteritis viral), skin and soft tissue infections (including paronychia, cellulitis, impetigo, necrotising fasciitis and herpes zoster), ear infections, oral infections (including herpes simplex, oral herpes and tooth infections), reproductive tract infections (including vulvovaginal mycotic infection), urinary tract infections (including pyelonephritis), fungal infections, joint infections, skin cancer excluding melanoma (including basal cell carcinoma and squamous cell carcinoma), benign neoplasm, leucocytosis, thrombocytopenia, hypersensitivity, allergies (including seasonal allergy), hypokalaemia, uric acid increased, blood sodium abnormal, hypocalcaemia, hyperglycaemia, hypophosphatemia, dehydration, mood alterations (including depression), anxiety, insomnia, paraesthesias (including hypoesthesia), migraine, nerve root compression, visual impairment, conjunctivitis, blepharitis, eye swelling, vertigo, tachycardia, hypertension, flushing, haematoma, asthma, dyspnoea, cough, GI haemorrhage, dyspepsia, gastroesophageal reflux disease, sicca syndrome, worsening or new onset of psoriasis (including palmoplantar pustular psoriasis), urticaria, bruising (including purpura), dermatitis (including eczema), onychoclasis, hyperhidrosis, alopecia, pruritus, muscle spasms (including blood creatine phosphokinase increased), renal impairment, haematuria, chest pain, oedema, pyrexia, coagulation and bleeding disorders (including activated partial thromboplastin time prolonged), autoantibody test positive (including double stranded DNA antibody), blood lactate dehydrogenase increased, impaired healing. Serious, including fatal, adverse reactions have been reported including infections/sepsis, TB, opportunistic infections, allergic reactions (including anaphylaxis), HBV reactivation and malignancies (including leukaemia, lymphoma and hepatosplenic T-cell lymphoma). Serious haematological, neurological and autoimmune reactions have also been reported. These include rare reports of pancytopenia, aplastic anaemia, central and peripheral demyelinating events and reports of lupus, lupus-related conditions and Stevens-Johnson syndrome. Other less common and rarely reported adverse reactions are listed in the SmPC. Legal Category: POM. Marketing Authorisation Holder: Fresenius Kabi Deutschland GmbH, Else-Kröner-Straße 1, 61352 Bad Homburg v.d.Höhe, Germany. Marketing authorisation numbers: EU/1/19/1356/001, EU/1/19/1356/002, EU/1/19/1356/003 Package size and cost: UK / ROIIdacio 40mg/0.8ml vial x 1: £316.93 / €309.31, Idacio 40mg/0.8ml pre-filled syringe x 2: £633.86 / €618.63, Idacio 40mg/0.8ml pre-filled pen x 2: £633.86 / €618.63 Further information: available from Fresenius Kabi Ltd., Cestrian Court, Eastgate
An overview of bone marrow oedema syndromes –diagnosis to treatment
In his presentation at the ISR Spring Meeting titled ‘Primary bone marrow oedema syndromes’, Dr Sanjeev Patel, Consultant Rheumatologist at King's College Hospital, London, provided a comprehensive overview of a topic whose significance has been under-appreciated in the past.
Bone marrow oedema is a non-specific finding on an MRI arising from the replacement of marrow fat by material with H+ ions in water form. The term bone marrow oedema was first used in the absence of other appropriate terminology. However, Dr Patel noted that the terminology continues to be ill-defined and overlapping today.
Primary bone marrow oedema is a bone-based pathology, while secondary bone marrow oedema is a joint-based pathology, different to osteonecrosis. Whereas osteonecrosis results in permanent, irreversible damage, bone marrow oedema can be treated.
Dr Patel provided a hypothesis of aetiology, but stressed that is uncertain, as is the epidemiology. It is, however, more prevalent in adults, with no reported gender difference. It tends to appear on the lower limbs and predominantly on the hips, followed by knees, and then the feet. Further, there is an association with pregnancy, but not with osteoporosis.
Patients present with spontaneous onset musculoskeletal pain that is exacerbated when weight is put on the affected area. Examination reveals irritability in the affected joint with specific findings in each of the three most common affected areas.
When it comes to diagnosis, Dr Patel explained that primary bone marrow
oedema involves a diagnosis of exclusion, starting with excluding jointbased pathology and a number of other conditions. He shared a 'tapping test', which he has found useful in practice. In this simple test, the affected joint is tapped at each of the four quadrants and the shockwave generated results in pain. This is useful because with primary bone marrow oedemas the joint can look, feel, and manoeuvre normally. The quadrant, which experiences the most pain, will be in line with the MRI findings. The usefulness of the tapping test, Dr Patel continued, extends to monitoring improvement and resolution of the condition to avoid repeated MRIs.
The treatments used in primary bone marrow oedema syndromes include analgesia, steroid injections for synovitis, bisphosphonates to reduce bone turnover, the use of statins to improve blood flow and surgical decompression, although Dr Patel noted that the literature is not robust on all of these areas. Removing weight from the joint in question, followed by graduated weight-bearing after recovery, is a key part of the treatment, he added.
MRI indications of haemochromatosis arthropathy in the ankle
Prof Patrick Kiely, Consultant Rheumatologist at St George’s University Hospital, London, UK, is leading a European League Against Rheumatism (EULAR) initiative to establish guidelines for haemochromatosis arthropathy in association with the Mater Misericordiae University Hospital, Dublin, and the ISR. As such, it was fitting that he presented at the ISR Spring Meeting on the topic.
Prof Kiely shared how he established a clinic for haemochromatosis arthropathy at St George’s in 2012, with the aim of finding out more about the condition, which currently takes between seven-to-eight years from first presentation to diagnosis.
To date, he has seen 135 patients from across the country and was able to gather data from these patients. In association with the UK Haemochromatosis Society, Prof Kiely gathered 470 responses to a widespread patient survey, the majority of whom were UKbased. The results of this study revealed that joint pain and fatigue were, by far, the most prevalent symptoms present at the time of diagnosis. The areas most affected by the condition are the knee, ankle, metacarpophalangeal joint, and proximal interphalangeal joint in descending order.
Examining the ankle in more detail, ankle osteoarthritis (OA) is rare and while Prof Kiely’s research revealed that 35 per cent of patients self-reported symptoms in the ankle, a cross-sectional study of 199 patients in Germany and Austria had a similar finding of 32.9 per cent. On further examination Prof Kiely noted that re -
search out of the US found that only 7.5 per cent of all cases of Kellgren grade 3 or 4 OA in a particular centre in the US in one year were ankle-related. The majority of hip and knee OAs were primary, but the ankle cases were post-traumatic. Follow-up data collected over the next 13 years revealed the same findings, the majority of OA ankle cases are post-traumatic.
Following on from this, and Prof Kiely’s repeated observation regarding ankle cysts that resembled “bunches of grapes”, he embarked on a research topic, which asked: “Are there features on MRI that could distinguish HA [haemochromatosis arthropathy] from primary OA in the hindfoot?” The study comprising 30 hindfoot MRIs from 22 genetic haemochromatosis patients found that this group have a higher score at the ankle and middle facet subtalar joints for OA features, including large bone marrow lesions or cysts, extensive cartilage loss and large osteophytes, which all indicate genetic haemochromatosis could be at play.
Three ophthalmic imaging modalities and rheumatological case studies
Dr Duncan Rogers, Consultant Medical Ophthalmologist at the Mater Hospital, was the first speaker to present at an ISR Spring Meeting session on how ophthalmological imaging can assist in rheumatological diagnosis. Dr Rogers’ presentation spoke directly to the application of ocular imaging in rheumatic disease.
Dr Rogers presented three types of ocular imaging and three cases alongside each to illustrate their application in rheumatological diagnosis.
The first case involved a 34-year-old female presented with floaters and distortion in both eyes. Her symptoms had been present for approximately a month, before deteriorating rapidly in the two days prior to presentation. The patient reported significant fatigue and weight loss over the previous two months. The modality employed was a fundus photo which revealed abnormalities, including scattered haemorrhaging, indicating ischaemia and retinitis. Overall, the fundus photo revealed arterial dominant occlusive retinal vasculitis with retinitis, the most common cause of which is lupus retinitis. Following positive results for both anti-double stranded DNA (anti-dsDNA) and antinuclear antibodies, the patient was diagnosed with systemic lupus and referred to rheumatology.
Optical coherence tomography (OCT) imaging was em-
ployed in the second case. OCT imaging creates a picture of the retina and choroid at the back of the eye. The patient was a 76-year-old female who presented with a sudden unilateral loss of vision, reduced sensation and paraesthesia in her hands and feet, in addition to a rash on her lower limbs. While the fundus photos for this patient were normal, the OCT pointed to the circulation in the inner retina as paracentral middle maculopathy. Her erythrocyte sedimentation rate (ESR) was found to be significantly raised and a dermatologist confirmed that the rash was necrotising arteritis. This patient was diagnosed with polyarteritis nodosa.
The final ocular imaging modality presented by Dr Rogers was fundus fluorescein angiography (FFA). In this modality, fluorescein is injected into a vein on the back of the hand and its progress to the eye is monitored. In this case, an 85-year-old male presented with a history of purple flashing lights in his right eye, accompanied by a flickering loss of vision. Both the fundus photo and OCT were normal. Proceeding to FFA, at 26 seconds, the patient’s arterial tree was just beginning to register, in delayed choroidal and retinal filling. Serology showed that the patient’s ESR was 110 and with a C-reactive protein (CRP) level of 90. Histopathology of a temporal artery biopsy then confirmed giant cell arteritis in this patient.
Conference Coverage THE MEDICAL INDEPENDENT | 10 JUNE 2021 32
Prof Patrick Kiely
Irish Society for Rheumatology Spring Meeting, virtual, 13 May 2021
Dr Sanjeev Patel
Treat to target. Daily.1,2
ADENURIC 80 mg and 120 mg film-coated tablets: Abbreviated Prescribing Information Please consult the Summary of Product Characteristics (SmPC) for full prescribing information. Presentation: Film-coated tablets containing 80 mg or 120 mg febuxostat. Also contains lactose monohydrate. Use: Treatment of chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history, or presence of, tophus and/or gouty arthritis) in adults. Dosage and administration: Oral use with or without food. Recommended dose is 80 mg once daily. If serum uric acid is > 6 mg/dL (357 µmol/L) after 2-4 weeks, 120 mg once daily may be considered. Older people: No dose adjustment required. Renal impairment: No dosage adjustment necessary in patients with mild or moderate renal impairment. Efficacy and safety not fully evaluated in patients with severe renal impairment. Hepatic impairment: Recommended dosage in patients with mild hepatic impairment is 80 mg. Limited information available in patients with moderate hepatic impairment. Efficacy and safety has not been studied in patients with severe hepatic impairment. Children and adolescents: Safety and efficacy in children under 18 has not been established. Organ transplant recipients: No experience therefore not recommended. Contraindications: Hypersensitivity to the active ingredient or to any of the excipients. Warnings and precautions: Cardio-vascular disorders: Treatment with febuxostat in patients with pre-existing major cardiovascular diseases (e.g. myocardial infarction, stroke or unstable angina) should be avoided, unless no other therapy options are appropriate. Product allergy/hypersensitivity: Advise patients of signs/symptoms of allergic/hypersensitivity reactions and monitor closely for symptoms. Stop treatment immediately if serious reactions occur, including Stevens-Johnson syndrome, Toxic epidermal necrolysis and acute anaphylactic reaction/shock; do not re-start febuxostat at any time. Severe hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with fever, haematological, renal or hepatic involvement in some cases. Acute gouty attacks (gout flare): Do not start treatment until an acute attack of gout has completely subsided. As with other urate lowering medicinal products, gout flares may occur during initiation of treatment. At treatment initiation flare prophylaxis for at least 6 months with an NSAID or colchicine is recommended. If a gout flare occurs during treatment, do not discontinue. Manage the gout flare concurrently as appropriate. Continuous treatment decreases frequency and intensity of gout flares. Xanthine deposition: As with other urate lowering medicinal products, in patients in whom the rate of urate formation is greatly increased (e.g. malignant disease and its treatment, Lesch-Nyhan syndrome), the absolute concentration of xanthine in urine could, in rare cases, rise sufficiently to allow deposition in the urinary tract. As there has been no experience of treating gout in these patients with febuxostat such use is not recommended. Mercaptopurine/azathioprine: Not recommended in patients concomitantly treated with mercaptopurine/azathioprine. Where combination cannot be avoided, monitor patients closely. Dose reduction for mercaptopurine/ azathioprine is recommended. Theophylline: No pharmacokinetic interaction shown with febuxostat 80 mg, no data for 120 mg. Liver disorders: Liver function test is recommended prior to the initiation of therapy and periodically thereafter based on clinical judgement. Thyroid disorders: Caution in patients with alteration of thyroid function. Lactose: Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Interactions: Mercaptopurine/azathioprine: On the basis of the mechanism of action of febuxostat on xanthine oxidase inhibition concomitant use is not recommended. Where the combination cannot be avoided see SmPC for dosing instructions.
Rosiglitazone/CYP2C8 inhibitors: No dosage adjustment required. Theophylline: No special caution advised for 80 mg febuxostat, no data available for 120 mg. Naproxen and other inhibitors of glucuronidation: Can be co-administered with naproxen with no dose adjustments necessary.
Inducers of glucuronidation: Monitoring of serum uric acid is recommended 1-2 weeks after start of treatment with a potent inducer of glucuronidation. Cessation of treatment of an inducer might lead
ADENURIC® is a trademark of Teijin Limited, Tokyo, Japan
Date of item: October 2019
to increased plasma levels of febuxostat. Colchicine/indometacin/hydrochlorothiazide/warfarin: Can be co-administered with colchicine or indomethacin with no dose adjustments necessary. No dose adjustment necessary when administered with hydrochlorothiazide. No dose adjustment necessary for warfarin when administered with febuxostat. Desipramine/CYP2D6 substrates: Co administration with other CYP2D6 substrates is not expected to require any dose adjustment for those compounds. Antacids: May be taken without regard to antacid use. Pregnancy and lactation: Do not use during pregnancy or breast-feeding. Effect on fertility unknown. Side-Effects: Clinical Studies and postmarketing experience: Common (1-10%): Gout flares, headache, diarrhoea*, nausea, liver function test abnormalities*, rash, oedema. Uncommon (0.1–1%): Blood thyroid stimulating hormone increased, diabetes mellitus, hyperlipidemia, decrease appetite, weight increase, decreased libido, insomnia, dizziness, paraesthesia, hemiparesis, somnolence, altered taste, hypoaesthesia, hyposmia, atrial fibrillation, palpitations, ECG abnormal, hypertension, flushing, hot flush, dyspnoea, bronchitis, upper respiratory tract infection, cough, abdominal pain, abdominal distension, gastrooesophageal reflux disease, vomiting, dry mouth, dyspepsia, constipation, frequent stools, flatulence, gastrointestinal discomfort, cholelithiasis, dermatitis, urticaria, pruritus, skin discolouration, skin lesion, petechiae, rash macular, rash maculopapular, rash papular, arthralgia, arthritis, myalgia, musculoskeletal pain, muscle weakness, muscle spasm, muscle tightness, bursitis, renal failure, nephrolithiasis, haematuria, pollakiuria, proteinuria, erectile dysfunction, fatigue, chest pain, chest discomfort, blood amylase increase, platelet count decrease, WBC decrease, lymphocyte count decrease, blood creatine increase, blood creatinine increase, haemoglobin decrease, blood urea increase, blood triglycerides increase, blood cholesterol increase, haematocritic decrease, blood lactate dehydrogenase increased, blood potassium increase. Rare (0.1-0.01%): Pancytopenia, thrombocytopenia, agranulocytosis**, anaphylactic reaction**, drug hypersensitivity**, blurred vision, weight decrease, increase appetite, anorexia, nervousness, tinnitus, sudden cardiac death**, pancreatitis, mouth ulceration, hepatitis, jaundice**, liver injury**, Toxic epidermal necrolysis**, Stevens-Johnson Syndrome**, DRESS**, angioedema**, generalized rash (serious)**, erythema, exfoliative rash, rash follicular, rash vesicular, rash pustular, rash pruritic**, rash erythematous, rash morbillifom, alopecia, hyperhidrosis, rhabdomyolysis**, joint stiffness, musculoskeletal stiffness, tubulointerstitial nephritis**, micturition urgency, thirst, blood glucose increase, activated partial thromboplastin time prolonged, red blood cell count decrease, blood alkaline phosphatase increase, blood creatine phosphokinase increase**. *Treatment-emergent non-infective diarrhoea and abnormal liver function tests in combined Phase III studies more frequent in patients concomitantly treated with colchicine. **Adverse reactions coming from post-marketing experience. Rare serious hypersensitivity reactions including Stevens-Johnson Syndrome and anaphylactic reaction/shock have occurred in post-marketing experience. Hypersensitivity reactions to febuxostat can be associated with the following symptoms: skin reactions characterised by infiltrated maculopapular eruption, generalised or exfoliative rashes, also skin lesions, facial oedema, fever, haematologic abnormalities such as thrombocytopenia and eosinophilia, and single or multiple organ involvement (liver and kidney including tubulointerstitial nephritis). Gout flares commonly observed soon after treatment start and in first months. Frequency decreases after time. Gout flare prophylaxis is recommended.
for further information. Pack sizes: 80 mg and 120 mg tablets: 28 film-coated tablets. Legal category: POM. Marketing authorization number: EU/1/08/447/014, 020. Marketing authorization holder: Menarini International Operations Luxembourg S.A., Avenue de la Gare, L-1611 Luxembourg, Luxembourg. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd. Further information is available on request to A. Menarini Pharmaceuticals Ireland Ltd, 2nd Floor, Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924 or may be found in the SmPC. Last updated: August 2019. References: 1. Adenuric 80 mg SmPC. July 2019. 2. Adenuric 120 mg SmPC. July 2019.
Irish Society for Rheumatology Spring Meeting, virtual, 13 May 2021
A review of studies in the use of tocilizumab in treating Covid-19
Consultant Paediatric Rheumatologist at the Bristol Royal Hospital for Children and Royal National Hospital for Rheumatic Diseases, Prof A V Ramanan, is currently leading clinical trials of tocilizumab, a biologic usually associated with the treatment of rheumatoid arthritis, for the treatment of Covid-19.
Prof Ramanan spent 20 years working on haemophagocytic syndrome (HPS), a rare immune disease, which is
seen mostly in children, but increasingly in adults. Primary manifestations of the condition appear in children, while the secondary haemophagocytic syndrome occurs as a cytokine storm in adults.
During his presentation at the ISR Spring Meeting, Prof
Ramanan highlighted that there is a clear case for IL-6 playing a key role in the pathophysiology of Covid-19. He proceeded to review a number of important papers published on the connection between tocilizumab and Covid-19. The first paper to pique his interest was published in October 2020 and titled ‘Association between early treatment with tocilizumab and mortality among critically-ill patients with Covid-19’. In this study, almost 4,000 critically-ill patients with laboratory confirmed Covid-19 were studied. Of this number, 433 received tocilizumab within two days of being admitted to ICU. This study showed that those who were treated with tocilizumab had a much higher survival rate than those who did not receive it.
Another study, carried out in France, titled ‘Effect of tocilizumab vs usual care in adults hospitalised with Covid-19 and moderate or severe pneumonia’ involved 130 patients, 63 of whom were administered tocilizumab. In this group, by day 14 there was less need for invasive mechanical ventilation or non-invasive ventilation and fewer members of the tocilizumab group died compared to the control group. Prof Ramanan noted that this was “a significant result, even though it was a small sample size”, as the first controlled trial data in relation to tocilizumab in Covid-19.
Other studies were less positive. For example, a study of 243 patients from Boston, published in the New England Journal of Medicine, reported no significant effect on disease progression, reduction in the need for ventilation or death. Yet another, in 452 patients with severe Covid-19 pneumonia, revealed mixed results. The primary endpoint was not achieved and they did not find a difference in mortality. However, there was an improvement in the discharge time and a lower risk of clinical failure. Furthermore, this study found that there were no new risks introduced through the use of tocilizumab.
Conference Coverage THE MEDICAL INDEPENDENT | 10 JUNE 2021 34 Rx Methoﬁll® by brand.
Prof A V Ramanan
Primary manifestations of the condition appear in children, while the secondary haemophagocytic syndrome occurs as a cytokine storm in adults.
Irish Society for Rheumatology Spring Meeting, virtual, 13 May 2021
Neuropsychiatric events in discussedlupus
In the first of two presentations at the 2021 ISR Spring Meeting delivered by transatlantic speakers, Dr John Hanly, Professor of Medicine and Pathology at Dalhousie University and Attending Staff Physician at the Queen Elizabeth II Health Sciences Centre at Halifax, Nova Scotia, Canada, dedicated his talk on lupus and the nervous system to his late mentor, Irish rheumatologist Dr Barry Bresnihan, who passed away in 2010.
Dr Hanly began by highlighting the discrepancy between the recent EULAR/American College of Rheumatology (ACR) classification criteria, of which there are three, compared to the ACR case definitions of 1999, which describe 12 central and seven peripheral manifestations of neuropsychiatric (NP) events. Dr Hanly explored the findings of an inception cohort of over 1,800 systemic lupus erythematosus (SLE) pa tients established by Systemic Lupus International Collab orating Clinics (SLICC), an international research network spanning 16 countries, which would study a range of out comes, including NP events.
When the ACR classification criteria were applied to the SLICC cohort, just 5 per cent presented with NP SLE and displayed little change over five years. However, this increased to 30 per cent when the ACR case definitions for 19 events were used, rising to 47 per cent over a fiveyear period. The most common NP event registered in the SLICC cohort was headache, followed by mood dis order and seizures.
Dr Hanly noted that when SLICC attribution rules were applied, most manifestations have a mixed attribution pat tern, with some never being attributed to SLE and some al ways being attributed. Within the SLICC cohort, 47 per cent of patients had at least one type of NP event, although only one-third of these were attributable to lupus. Regardless of attribution, a multistate model approach revealed that the majority of NP events occur early in the course of the disease and drop off over time.
Headache was the most frequent NP event in the SLICC inception cohort. It was seen in over 58 per cent of patients, usually in the form of migraine or tension headaches. The majority of patients saw a resolution of this event over time. Discussing lupus headache, Dr Hanly noted that it is a controversial topic, which has been poorly defined. It was identified in just 1.5 per cent of patients within the SLICC inception cohort. Dr Hanly referred to the International Headache Society system of classification, which shows no uniformity of characteristics in lupus headache. Dr Hanly referenced an editorial which, in light of the above, called for the concept to be discarded from use.
opathy, the use of OCT ocular imaging can be used to detect this at an early stage, avoiding any loss of visual acuity.
The current use of immunosuppressant drugs in the treatment of lupus is predominantly organ-based, with methotrexate, mycophenolate, leflunomide, and azathioprine noted for different organs. Prof Petri raised some interesting new developments of note. Anifrolumab, which is awaiting US FDA approval, showed a positive BILAG-Based Composite Lupus Assessment response after four weeks, a positive SRI (4) response after eight weeks and a clear benefit for skin with Cutaneous Lupus Erythematosus Disease Area and Severity Index activity increasing at four weeks. Prof Petri observed this in her own patients and noted durable results for skin.
Regarding the ongoing pandemic, Prof Petri also ad-
dressed current considerations in light of Covid-19. She advised that prednisone needs to be limited, something she would advise in any case due to the increased risk of cardiovascular events it poses. However, rituximab also needs to be limited, where possible, to avoid any increased risk to the patient. In relation to vaccination, there were fears that the mRNA vaccines may cause lupus flares, but this has not materialised in Prof Petri’s experience. Further, it was thought that renal transplant literature suggests that patients being administered mycophenolate may not have the expected antibody response to the Covid-19 vaccines.
To attempt to address this in her own patients, Prof Petri has held off on the use of the major immunosuppressive medications for one week post vaccination, although success cannot be confirmed at this point.
Prof Michelle Petri, Professor Division of Rheumatology at Johns Hopkins University, US, closed the ISR Spring Meeting with her presentation providing an overview of modern lupus treatment. Prof Petri is the Director of the Hopkins Lupus Cohort, a longitudinal cohort of morbidity and mortality in systemic lupus erythematosu (SLE) patients and Co-Director of the Hopkins Lupus Pregnancy Centre.
Asserting that “we cannot continue to rely on corticosteroids” in the treatment of lupus given their negative impact, Prof Petri referenced a cohort study by the Toronto Lupus Group, which showed that after 10 years from the date of diagnosis with lupus, 80 per cent of patients in the cohort suffered from permanent organ damage as a result of steroids.
Prof Petri strongly advocates for the use of hydroxychloroquine as a background therapy in all SLE patients. Although it has been found to increase the incidence of retin-
Taper dose gradually to prevent withdrawal symptoms. Renal/hepatic impairment: Not recommended in patients with severe cases. Caution and dose adjustments with moderate hepatic impairment. Elderly: May need dose adjustments. Children below 18 years: Not recommended. Contraindications: Hypersensitivity to ingredients, suspected or having paralytic ileus, acute intoxication with alcohol, hypnotics, centrally acting analgesics or psychotropics. Not for use when mu-opioid receptor agonists are contraindicated (e.g. significant respiratory depression, acute or severe bronchial asthma or hypercapnia). Special warnings and precautions: Abuse and addiction potential of Palexia should be considered where there is increased risk of misuse, abuse, addiction or diversion. All patients should be carefully monitored for signs of abuse and addiction. Concomitant use with sedating medicinal products such as benzodiazepines or related substances may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedating medicinal products should be reserved for patients for whom alternative treatment options are not possible. If used concomitantly, reduction of dose of one or both agents should be considered and the duration of the concomitant treatment should be as short as possible. The patients should be followed closely for signs and symptoms of respiratory depression and sedation. It is strongly recommended to inform patients and caregivers to be aware of these symptoms. At high doses or in mu-opioid receptor agonist sensitive patients, dose-related respiratory depression may occur. Caution and monitoring required with impaired respiratory function. Should not use in patients susceptible to intracranial effects of carbon dioxide retention (e.g. increased intracranial pressure, impaired consciousness or coma). Use with caution with head injury, brain tumors, moderate hepatic impairment, biliary tract disease including acute pancreatitis. Not recommended if history of or at risk of seizures. May increase the seizure risk in patients taking medicinal products that lower the seizure threshold. Not recommended in severe renal or hepatic impairment. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage. Care should be taken when combining with mixed muopioid agonists/antagonists (e.g. pentazocine, nalbuphine) or partial mu-opioid agonists (e.g. buprenorphine). Should not use with hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Interactions: The concomitant use with sedating medicinal products such as benzodiazepines or other respiratory or CNS depressants (other opioids, antitussives or substitution treatments, barbiturates, antipsychotics, H1-antihistamines, alcohol) increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. When combined therapy with a respiratory or CNS depressant is contemplated, the reduction of dose of one or both agents should be considered and the duration of the concomitant use should be limited. Can induce convulsions and increase the potential for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other medicinal products that lower the seizure threshold to cause convulsions. There have been reports of serotonin syndrome in a temporal connection with the therapeutic use of tapentadol in combination with serotoninergic medicinal products (e.g. SSIRs, SNRIs and tricyclic antidepressants). Use with strong inhibitors of uridine diphosphate transferase isoenzymes (involved in glucuronidation) may increase systemic exposure of Palexia SR. Caution if concomitant administration of strong enzyme inducing drugs (e.g. rifampicin, phenobarbital, St John’s Wort) starts or stops as this may lead to decreased efficacy or risk for adverse events, respectively. Avoid use in patients who have taken monoamine oxidase inhibitors (MAOIs) within the last 14 days, due to cardiovascular events. Pregnancy and lactation: Use in pregnancy only if the potential benefit justifies the potential risk to the foetus. Not recommended during and immediately before labour and delivery. Do not use during breast feeding. Driving and using machines: May have major effect on ability to drive and use machines, especially at the beginning or change in dosage, in connection with alcohol or tranquilisers. Undesirable effects: Very common (≥1/10): dizziness, somnolence, headache, nausea, constipation. Common (≥1/100, <1/10): decreased appetite, anxiety, depressed mood, sleep disorder, nervousness, restlessness, disturbance in attention, tremor, involuntary muscle contractions, flushing, dyspnoea, vomiting, diarrhoea, dyspepsia, pruritus, hyperhidrosis, rash, asthenia, fatigue, feeling of body temperature change, mucosal dryness, oedema. Other important undesirable effects observed in clinical trials and/or postmarketing: drug hypersensitivity, depressed level of consciousness, mental impairment, syncope (uncommon ≥1/1000, <1/100), impaired gastric emptying, respiratory depression, convulsion, angioedema, anaphylaxis and anaphylactic shock, drug dependence (rare ≥1/10,000, <1/1000), delirium
Coverage Conference THE MEDICAL INDEPENDENT | 10 JUNE 2021 35
Developments in the treatment of SLE and Covid-19 considerations
tapentadol (as hydrochloride) respectively. Indication: Palexia SR is indicated for the management of severe chronic pain in adults, which can be adequately managed only with opioid analgesics. Dosage and method of administration: Individualise according to severity of pain, the previous treatment experience and the ability to monitor the patient. Swallowed whole with sufficient liquid, not divided or chewed, with or without food. The tablet shell may not be completely digested and eliminated / seen in the patient’s stool which has no clinical significance as the active substance will have already been absorbed. Initial dose 50 mg twice a day. Switching from other opioids may require higher initial doses. Titrate in increments of 50 mg twice a day every 3 days for adequate pain control. Total daily doses greater than 500 mg not recommended. Discontinuation of treatment:
is available on
Overdose: Seek specialist treatment (see SmPC). Legal classification: POM, CD (Schedule II). Marketing Authorisation numbers and pack sizes: 50 mg: PA 2242/12/4, 28 and 56 packs; 100 mg: PA 2242/12/5, 56 pack; 150 mg: PA 2242/12/6, 56 pack; 200 mg: PA 2242/12/7, 56 pack and 250 mg: PA 2242/12/8, 56 pack. Marketing Authorisation Holder: Grünenthal Pharma Ltd, 4045 Kingswood Road, Citywest Business Park, Citywest, Co. Dublin, Ireland. M-PLX-IE-03-20-0004. Date of Preparation: March 2020. References: 1. Palexia SR Summary of Product Characteristics. 2. Baron R, et al. Tolerability, Safety, and Quality of Life with Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR in Patients with Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Openlabel, Phase 3b/4 Trial. Pain Practice. 2016;16(5):600-619. M-PLX-IE-11-20-0010 – November 2020 PALEXIA® SR Tablets are indicated for the management of severe chronic pain in adults, which can be adequately managed only with opioid analgesics1
cycle of chronic pain significant improvements as measured by the Short Form-12 (SF-12) health survey and the EuroQol-5 Dimension (EQ-5D) health status questionnaire in patients with severe chronic low back pain with a neuropathic component2
suicidal ideation or
SPORTS QUIZ WIN €50 10 June 2021
Q1 Who was named as the new manager of Real Madrid after Zinedine Zidane’s surprise departure?
Q2 Name the Japanese ladies tennis star who withdrew from the French Open earlier this month?
Q3 The European Football Nations Cup will commence later this month. Who are the defending champions from 2016?
Q4 Name the Irish 400 metre hurdler who hopes to go one place better than his fourth position in Rio at the 2016 Olympic games and collect a medal in Tokyo?
Q5 Which cyclist won the coveted Giro D’Italia last month?
Q6 Name the Ferrari Formula One driver who did not make it to the starting grid, having finished in pole position, for the Monaco Grand Prix?
10 June 2021
The winner of the 20 May 2021 Sporting Quiz Competition is Dr Errol Thomas, Dublin 15
The winner of the 20 May 2021 Crossword is Dr Sami Musa, Co Westmeath
Q1 Which Irish golfer will defend his British Open title, two years after he won it, later in the summer? A: Shane Lowry
Q2 Who will captain the British and Irish Lions squad on their upcoming tour of South Africa?A: Alun Wyn Jones
Q3 Which Irish International footballer won his case for wrongful dismissal against his club Derby County in 2019? A: Richard Keogh
Q4 Rafael Nadal will defend his French Open title which commences later this month. How many times has he won this grand slam event? A: 13
Q5 Who will the Irish rugby team play in two summer test matches in the coming weeks? A: Japan and the USA
Q6 Which county play GAA home fixtures in MacHale Park? A: Mayo
Life Mindo Quizzes THE MEDICAL INDEPENDENT | 10 JUNE 2021 36 Post your answers to: Mindo Quizzes, The Medical Independent, Greencross Publishing Ltd, Top Floor, 111 Rathmines Road Lr, Dublin 6. Closing date for entries is 24 June 2021 Solution to Crossword Competition
Answers to Sports Quiz Competition Solution to Sudoku A S S E S S T E A C E C E R E M O N Y C A R R A P N E I T S E L F L O U D N E W F O A T A S T E B I C Y C L E E M C E S P E A K E R A R E N A L C S S L G B A T H S P H E R E E N I A I V A N T E E N A G E R E C T G E T W E N T Y 3 4 8 6 7 2 1 5 9 1 2 5 3 8 9 6 4 7 7 9 6 1 5 4 2 3 8 4 8 3 7 2 1 5 9 6 5 7 9 8 3 6 4 2 1 2 6 1 9 4 5 8 7 3 8 5 7 4 1 3 9 6 2 9 1 4 2 6 7 3 8 5 6 3 2 5 9 8 7 1 4 6 1 1 6 5 2 7 6 4 6 8 2 9 5 6 7 2 4 8 9 3 5 1 2 7 8 SUDOKU SCRIBBLE BOX 20 MAY 2021 ANSWERS, SOLUTIONS, AND WINNERS WIN €50 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Across 1 - Portray (6) 4 - Right to enter (6) 9 - Make from raw materials (7) 10 - Visual display unit (7) 11 - Swift (5) 12 - Machine; automaton (5) 14 - Beastly (5) 15 - Additional (5) 17 - Alert (5) 18 - Prescription (7) 20 - Average (7) 21 - Place of worship (6) 22 - Seller (6) Down 1 - Leave (6) 2 - Search for minerals (8) 3 - Cloud (anag) (5) 5 - Nation (7) 6 - Modify (4) 7 - Ghost (6) 8 - Show (11) 13 - Well-rounded (8) 14 - Not artificial (7) 15 - Special ___ : film illusion (6) 16 - Buyer and seller (6) 17 - Common edible fruit (5) 19 - Space; part of a building (4) ACROSS 1 Portray (6) 4 Right to enter (6) 9 Make from raw materials (7) 10 Visual display unit (7) 11 Swift (5) 12 Machine; automaton (5) 14 Beastly (5) 15 Additional (5) 17 Alert (5) 18 Prescription (7) 20 Average (7) 21 Place of worship (6) 22 Seller (6) DOWN 1 Leave (6) 2 Search for minerals (8) 3 Cloud (anag) (5) 5 Nation (7) 6 Modify (4) 7 Ghost (6) 8 Show (11) 13 Well-rounded (8) 14 Not artificial (7) 15 Special ___ : film illusion (6) 16 Buyer and seller (6)
Common edible fruit (5) 19 Space; part of a building (4)
Changing how we think about cancer
TITLE: The Cancer Code: A Revolutionary New Understanding of a Medical Mystery
AUTHOR: Dr Jason Fung
PUBLISHER: Thorsons (2020)
REVIEWER: George Winter
Writing in the journal Cell (2014, 157: 267–271), biologist Robert Weinberg “lamented that cancer research was held in ‘ill-disguised contempt’ and that “one should never, ever confuse cancer research with science!’”. This farfrom-ringing endorsement of the lack of progress in what has been called “the last great medical mystery” is cited in Dr Jason Fung’s The Cancer Code (p129), and it is a corrective to those of us who too readily mistake opinion, and sometimes dogma, for fact.
Fung’s plain-spoken commentary does for cancer and its associated research what Clive James observed of the humanities in Cultural Amnesia (2007): “… a complete picture of reality is not to be had. If we realise that, we can begin to be realistic.”
Fung’s realism is supported by 467 references that are adduced during his tracing the historical arc of cancer research; explaining why its contemporary focus should be on environmental risk factors rather than genetics; and in suggesting how a novel paradigm of cancer medicine “means that for the first time… we stand a real chance in making real progress in our decades-long war on cancer”. Three paradigms emerge from Fung’s six-part narrative – cancer as excessive growth (paradigm 1); cancer as a genetic disease (paradigm 2); transformation; progression; metastasis; and treatment implications – with the third paradigm an evolutionary one: “Cancer
is, improbably, a backward evolution, or atavism, toward the single-cell organism from our evolutionary past.”
This forward-thinking appraisal of cancer’s backward-leaning roots encourages those readers with perhaps entrenched views on the genesis of cancer to show a willingness to heed a reminder from English historian FW Maitland (1850–1906) that “what is now in the past was once in the future”. It is a maxim, writes Ramachandra Guha in his India After Gandhi (2007), that is perfect for “the historian of the recent past, who addresses an audience with very decided views on the subjects about which he presumes to inform them”.
And it is also applicable to cancer. For example, Fung cites the first line of a paper by Hyman et al in the journal Cell (2017, 168: 584): “Cancer is a disease of the genome….” Unsurprising,
perhaps, given the paper’s title: ‘Implementing genome-driven oncology.’ Such certainty was also uncovered by Daniel J Kelves, writing in Hidden Histories of Science (2007), noting that in the 1930s when Dr John J Bittner – working at the Jackson Laboratory, Maine – identified what was later named the Mouse Mammary Tumour Virus, Bittner was “hesitant to challenge the genetic model of oncogenesis at the Jackson Laboratory…”. The Cancer Code demonstrates the fragility of such certainty.
Chapter four considers chemical and physical carcinogens – tobacco, soot, asbestos, radiation – with chapter five outlining the carcinogenic potential of
Epstein-Barr virus (EBV), H. pylori, human papilloma virus (HPV) and the viruses of hepatitis B and hepatitis C. Yet again, an historical perspective enriches understanding, with Fung’s account reminding me of Kelves’s revelation that shortly after the United States National Cancer Institute was founded in 1937, “an advisory committee to the Surgeon General concluded that viruses as well as other microorganisms could be disregarded as causes of the disease.” Those who assert “settled science” in whatever discipline might bear this in mind.
Although chemical, physical, and infectious agents established a causative role in cancer, Fung places the word “mechanism” beneath a big question mark before ushering in the genetic revolution and its associated somatic mutation theory (SMT). The SMT postulates that cancer is caused by the acquisition of multiple DNA mutations that accumulate randomly, and that tumour cells are derived from one original clone. Citing the oncogene HER2/neu in breast cancer and its treatment with trastuzumab, together with the Philadelphia chromosome, its role in chronic myelogenous leukaemia (CML) and the success of imatinib in treating CML, Fung acknowledges that “[t]he genetic paradigm of cancer had proven its mettle in the crucible of battle”. Yet, while trastuzumab and imatinib “were instant hits… like so many other one-hit wonders, the first hit turned out to be the best”.
Paradigm 1, which portrays cancer as a disease of uncontrolled growth, was addressed by killing excessively growing areas with chemotherapy, radiation and/or surgery. Paradigm 2 held that accumulated genetic mutations caused excessive growth, but as these mutations were pursued, “there were more than just the expected few. There were millions,” and this paradigm, contends, Fung, “had reached its limits by the early 2000s.” Paradigm 3, however, does not negate the importance of cancer genetics, but “links carcinogenesis, progression, and metastasis, whereas genetics considers them all as separate issues”. And Fung is clear that this idea is not new, but needed to be rediscovered, citing a cancer researcher’s observation that cancer is no more a disease of cells than a traffic jam is a disease of cars, with the environment having a role in determining whether a cancer grows: For example, hyperinsulinaemia, diet etc.
Dr Fung’s The Cancer Code makes the point, at least to this reviewer, that it is not so much what we think, but how we think that contributes to progress, and I warmly recommend it.
Book Review Life THE MEDICAL INDEPENDENT | 10 JUNE 2021 37
Dr Jason Fung
Although chemical, physical, and infectious agents established a causative role in cancer, Fung places the word ‘mechanism’ beneath a big question mark before ushering in the genetic revolution and its associated somatic mutation theory
REFRESHED ATECA FOR ALL YOUR FAMILY CAR NEEDS
Back in 2017 I road-tested the SEAT Ateca FR for the Medical Independent. It was a sporty affair, with huge wheels, Alcantara seats, a sleek body and a very responsive, sprightly motor. At the time I found it to be a real ‘blow your skirt up’ introduction to SEAT’s first crossover.
Now, five years after its launch, I was given the keys to the face-lifted Ateca. But this time it was the less sporty Xperience model, instead of the barnstorming FR. Specifically, it was a grey, 2.0-litre diesel, 150hp, version, which, again, came as quite the change in direction from the 2.0-litre petrol, 190hp, engine I had tested previously. For those who don’t know, SEAT has launched its own premium, sporty marque called Cupra, where it seems all the goodies have been placed, as they are offering a Cupra Ateca with 300hp. But that’s for another day.
SEAT is selling its Ateca in a very competitive market, with the likes of the Peugeot 3008, VW Tiguan, Skoda Karoq, Kia Sportage and the best-selling Nissan Qashqai to compete against. So, it comes as no wonder that they have refreshed the look of their successful crossover five years into its production. But it’s not just the aesthetics they have up-
graded, as this new model boasts some upgraded infotainment technology, like the full link wireless access to both Android auto and Apple’s CarPlay and, online-based functions and services as well as in-car apps. The model I tested came with a high-resolution 10.25” user instrument cluster and infotainment system, as well as illuminated type C USB connectors, making it easier to plug in, connect, and charge.
If you’re used to talking to Alexa or Siri, you’ll be happy to know that the Ateca is fitted with a voice recognition system so you can make voice commands to your hearts content. Using an embedded SIM card, SEAT’s Connect system means the driver will never lose connection to the digital world, and, I’m told that in future developments, the system will allow users to access the latest infotainment apps. This means the number of in-car and online services will grow through the life of the vehicle.
The Ateca also now integrates some of the most advanced driver assistance systems available, including predictive adaptive cruise control, pre-crash assist, travel assist, and side assist. According to the team at SEAT, these technologies make the compact SUV safer and more convenient for all drivers.
The Ateca is offered with three engines: A 1.0, A 1.5, and
A 2.0 diesel, offering up 100, 115, and 150 horsepower respectively. The entry level is the SE, followed by the SE Plus, Xperience, Xperience Plus, FR, and FR Plus. These range in recommended retail price from €32,660 to €43,515. The road tax rates for the Ateca range between €210 and €280, while the fuel economy falls between 4.8-5.4l/100km and 6.8-7.1l/100km. Currently, there is no hybrid or electric model on offer, but I’d be very surprised if we didn’t see one popping up in the next few years.
According to SEAT Ireland’s Brand Director Niall Phillips: “The new Ateca has been redesigned for an improved, more robust feel – the same great model brought up to date with the needs of today’s driver in mind. We want to provide our customers with everything they need for a more convenient drive and so the Ateca has become fully connected for the driver, integrating in-car connectivity with SEAT Connect. The new Ateca marks another milestone for our brand’s evolution, particularly for our SUV range.”
Five years on it’s clear that the Ateca is still a capable family all-rounder, with space, durability and frugality to suit many households. If you’re going to take one of these for a test drive, my advice would be to also request a spin in the Cupra Ateca.
THE MEDICAL INDEPENDENT | 10 JUNE 2021 Life Motoring
Read more at www.mindo.ie @MorganFlanaganC
MORGAN FLANAGAN CREAGH
Ateca PA 2.0TDI 150hp DSG Xperience
Colour: Rodium Grey (Metallic)
CO2 (Combined):153g/km (WLTP)
18” Alloy wheels
9.2” Navigation system
Bluetooth (phone and media)
Digital radio (DAB)
Full LED headlights
Wireless phone charger
Rear view camera
Adaptive cruise control
Light assist (auto high beam)
Traffic sign recognition
Front and rear parking sensors
Full link (Android auto, Apple CarPlay, Mirrorlink)
Black leather interior
Heated front seats
Dark tinted rear windows
Advanced interior ambient lighting
Keyless entry and start
Brushed metal roof rails
Door scuff plates (Illuminated)
Chrome interior detailing
Grey interior roof cloth
Leather gear knob and steering wheel
Front assist (emergency auto braking)
Drive profile selection
Reading lights (front and rear)
2-Zone air conditioning
Air quality sensor and airCare
Dynamic rear indicators
XDS differential lock (dynamic traction control)
Light and rain sensor
Auto dimming rear view mirror
Electric folding and heated mirrors
USB C ports (front and back)
LED front fog lights
Front and rear seatbelt reminder
Motoring Life THE MEDICAL INDEPENDENT | 10 JUNE 2021 39
The Ateca also now integrates some of the most advanced driver assistance systems available, including predictive adaptive cruise control, pre-crash assist, travel assist, and side assist
ATECA PA – XPERIENCE
LAUNCH OF TRINITY CENTRE FOR NATURAL PRODUCTS RESEARCH (NATPRO)
IRELAND LAGS EUROPEAN PEERS ON SPEED OF ACCESS TO NEW MEDICINES – SURVEY
Ireland is behind most of western Europe in making innovative new medicines available to patients, according to a survey commissioned by the originator biopharmaceutical industry.
NatPro, the new Trinity Centre for Natural Products Research, based at the School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, had been officially launched. Its mission is to advance research and innovation of naturally derived products to deliver human health benefits and innovative life science solutions across sectors.
The global natural product market continues to grow and is becoming pivotal to social, economic and environmental strategies. Driven by health, economic and climate concerns, consumers increasingly demand sustainable and natural plant-based products. Innovation is the key to addressing this urgency.
The multi- and inter-disciplinary academic, regulations and commercial expertise of NatPro’s staff and principal investigator network, applies a transformative, science-led lens to unlock the power of natural products from existing and potentially new terrestrial and marine biodiversity sources.
NatPro Founder and Academic Director Prof Helen Sheridan, who is Associate Professor of Natural Product Chemistry at Trinity College, said: “The tide is rising in the natural product sectors globally and in Ireland. We at NatPro are excited to use a creative scientific lens to lead the pursuit of innovation in this sector. Interdisciplinarity is the key to our strategy and success. NatPro harnesses the power of academic rigor to drive natural product-based science from discovery through to a breath of applications.”
Nevertheless, there are challenges to the exploitation of natural products. These range from sustainable production, consistent quality, large scale biomass drying to standardising bioactivity, formulation for targeted delivery and reg-
ulatory challenges to entering different markets.
NatPro partners with industries and other stakeholders in this arena to deliver “breakthrough solutions”. The centre identifies key bioactives from natural sources (macro and microalgae, cereals, bioactive herbs and plants, and residual commercial biomass such as brewer’s spent grain) and transforms them towards new therapeutics, functional foods, supplements and cosmetic applications.
Dr Gaia Scalabrino, NatPro Executive Director, said: “We strive for Ireland to lead at the forefront of innovation in the global natural products ecosystem, advancing its natural resources, key expertise and commercial opportunities. NatPro’s edge is its interdisciplinary technology platforms, which promote a gateway for synergistic partnerships across industry and academia. We operate an integrated approach at the interface between discovery science, product development and regulations. Our drive is to create innovative products and provide strategic, scientific advice to our partners. Our team discovers value-added use of natural resources to deliver evidence-based solutions, which are derived from nature and translated into disruptive and sustainable practices.”
Prof Anne-Marie Healy, Professor of Pharmaceutics and Pharmaceutical Technology at Trinity College and NatPro Co-Director, commented: “The opportunities provided by the NatPro Centre to progress natural product research from discovery and analysis of new chemical entities through to formulation, processing and manufacture is very exciting, and really unique in the Irish research landscape.”
NatPro’s website is now live at www.tcd.ie/natpro
The survey of 34 countries shows that Ireland ranks around mid-table in Europe, and near the bottom among western European countries, for the time it takes to give patients access to the latest treatments by agreeing reimbursement in the health services.
The figures, gathered by data analysts IQVIA for the European Federation of Pharmaceutical Industries and Associations (EFPIA), place Ireland in 18th place for time to availability for 152 medicines, with an average of 477 days to reimbursement.
That is considerably short of the standard set in Irish and European law of 180 days after a request for reimbursement.
Among western European countries, only France and Portugal are slower than Ireland. Other countries, including Austria, Belgium, Denmark, Finland, Norway, Sweden, Germany, Greece, Italy, Spain, The Netherlands, England, and Scotland, are faster. Germany is four times faster than Ireland to make new medicines available to patients through public reimbursement.
For cancer medicines, Ireland is in 21st place for time to availability, with an average of 606 days to reimbursement. Furthermore, this country is in 24th place for time to availability for orphan medicines, which treat rare conditions, with an average of 756 days to reimbursement.
An analysis by the Irish Pharmaceutical Healthcare Association (IPHA), which represents the industry nationally, shows that of 13 new medicines funded in 2020, mostly for cancer, it took over 2.7 times longer, on average, to reimburse them in Ireland compared to 14 western European countries, including the UK.
According to IPHA, a new supply agreement and a Budget funding announcement can “begin to address
Ireland’s problem with introducing innovative new medicines in the health services”.
Mr Oliver O’Connor, Chief Executive of IPHA, said: “This Government, especially the Taoiseach, Micheál Martin, the Minister for Public Expenditure Michael McGrath, and the Minister for Health Stephen Donnelly, deserve credit for providing €50 million for new medicines this year. The allocation is releasing a backlog of medicines that had gathered due to a funding freeze imposed in 2019.
“But data shows Ireland still has a major problem with speed of access to new medicines, compared with peer countries in western Europe. It is not because all these countries’ assessment processes are somehow less stringent than ours. Our processes are not organised to deliver fast access for patients. A funding shortfall in previous years has meant medicines were left unfunded, even when they were deemed cost-effective after price negotiations. We need to fix these problems, together, through a new supply agreement and in Budget 2022.
“Innovative medicines have significantly improved survival, delivering treatments to patients with chronic diseases, tackling previously untreatable cancers and genetic conditions, eliminating some infectious diseases, and addressing unmet medical needs.
“In recent years, innovation in medicines has been fast. The industry’s pipeline is strong. The true value of innovation is realised when patients have access to it. So, we need to design a reimbursement process that works better and to build a funding framework that is sustainable for the health system and delivers faster access to innovation for patients. These should be urgent priorities for both industry and the State.”
In February, the industry agreed with the State a second roll-over of the existing supply agreement. It runs until the end of July, with an option to extend it to the end of September. In the meantime, negotiations are to start on a new supply agreement.
HIGH LEVELS OF DISTRESS EXPERIENCED BY CAREGIVERS TO SURVIVORS OF LUNG CANCER
New research by Dublin City University’s (DCU) School of Psychology, funded by the Irish Cancer Society, has shown many informal caregivers of people with lung cancer experience high levels of depression and anxiety. This highlights the need to screen caregivers and identify those who may benefit from psychological support, according to the research team.
The research, which involved a comprehensive review of 27 studies involving lung cancer caregivers, found that psychological distress is associated with several factors including the stage of cancer, level of social support, perceptions of burden and self-efficacy in managing the caregiver role.
As a consequence, mitigating any distress experienced by caregivers would not only be important for their own wellbeing, but could also improve patient outcomes.
As lung cancer patients are frequently treated as outpatients whenever possible, informal caregivers can face considerable responsibilities. The tasks associated with caregiving can include assisting with activities of living, coordinating care, monitoring treatment
and managing side-effects and symptoms, seeking information, and provision of emotional, social, and spiritual support.
Lung cancer is the second most commonly diagnosed cancer worldwide (11.4 per cent of the total cases) and the leading cause of cancer death (18.4 per cent). Symptoms associated with the disease and treatment side-effects include pain, dyspnoea, fatigue, and anorexia. The symptom burden of people with lung cancer has been reported as greater than that experienced with other types of cancer and is associated with impaired functioning and has a negative impact on quality-of-life. Additionally, lung cancer is associated with high levels of distress and an increased suicide risk, compounded by perceived stigma and shame related to smoking behaviours.
The research has suggested that the development and provision of well-designed interventions, such as those that aim to increase self-efficacy, develop effective coping strategies, and enhance support networks may help to reduce distress.
LOW LEVELS OF OMEGA-3 ASSOCIATED WITH HIGHER RISK OF PSYCHOSIS – RCSI RESEARCH
New research has found adolescents with higher levels of an omega-3 fatty acid in their blood were less likely to develop psychotic disorder in early adulthood, suggesting that it may have a potential preventative effect of reducing the risk of psychosis.
The study, led by researchers from RCSI University of Medicine and Health Sciences, was published in Translational Psychiatry
Over 3,800 individuals in Bristol’s ‘Children of the 90s’ health study were assessed for psychotic disorder, depressive disorder and generalised anxiety disorder at ages 17 and 24.
During these assessments, blood samples were collected and the researchers measured the levels of omega-6 fat-
ty acids, which generally increase inflammation in the body and omega-3 fatty acids, which generally reduce inflammation. While there was little evidence that fatty acids were associated with mental disorders at age 17, the researchers found that 24-year-olds with psychotic disorder, depressive disorder and generalised anxiety disorder had higher levels of omega-6 than omega-3 fatty acids compared to those without these disorders.
The researchers also found that 24-year-olds with psychotic disorder had lower levels of DHA, an omega-3 fatty acid typically found in oily fish or dietary supplements, than 24-year-olds without psychotic disorder.
RXDX Product Focus THE MEDICAL INDEPENDENT | 10 JUNE 2021 40
Pictured L-R: Prof Anne-Marie Healy, Prof Helen Sheridan, and Dr Gaia Scalabrino
Due to an error in a photograph issued by NUI Galway, an article in the 31 May issue (‘NUI Galway to expand clinical trials for diabetes and chronic disease’) included a photograph captioned as Prof Andrew Murphy, who is leading the Primary Care Clinical Trials Network. However, the person pictured was Prof Andrew Smyth. We are happy to clarify this.
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A round-up of news and oddities from left field by Dr
Current affairs – new research shows that Nikola Tesla is the gift that keeps giving I
t ’s so easy to take the genius of Nikola Tesla for granted, even now. A man of modest means and demeanour who regularly had his inventions hijacked and patented by the likes of Edison, Tesla was, you could say, ‘no ordinary genius ’
Learned Dorsal View readers will be well aware of his list of achievements, but forgive me for recapping on one or two here, as well as a recent finding that suggest it’s more than his AC current that still has immense practical implications even today.
In the medical arena, his body of work included contributing significantly to the development of radiology that has resulted in the now-familiar 1T, 1.5T, and 3T designations, with the ‘T’ of course referring to Tesla, and he was also a pioneer of high-frequency electrotherapy.
He pioneered the use of x-rays for medical purposes, beginning on an experimental basis in 1887, when they were referred to as ‘shadowgraphs’. He was also the first to copon that too much radiation might be dangerous.
He also designed an oscillator to relieve fatigue in leg muscles, not to mention he was an overall proponent of wireless technology, which is now widely used in medicine, as well as pretty much everything else. An example of this was a demonstration where he remote-controlled a small boat using wireless technology. The attendees were so outraged and dumbfounded that they insisted he dismantle it on the spot to prove there weren’t ‘little people’ inside controlling it. This was in 1898. Perhaps the world’s first ever look at a drone.
In any event, just last month, a paper in Nature Communi- Nikola Tesla
cations told of how scientists have re-examined Tesla’s ‘valvular conduit’, known as the Tesla Valve, for which he obtained a patent in 1920, and which it now appears has previously unknown applications. The researchers found that the device works something like a switch – only when there is enough liquid coming through does it work to resist flows coming in the wrong direction. This, of course, presents a wealth of potential engineering and machinery applications.
Senior author and Associate Professor at New York University’s Courant Institute of Mathematical Sciences, Prof Leif Ristroph, commented: “Crucially, this turn-on comes with the generation of turbulent flows in the reverse direction, which ‘plug’ the pipe with vortices and disrupting currents.”
“Moreover, the turbulence appears at far lower flow rates than have ever previously been observed for pipes of more standard shapes – up to 20 times lower speed than conventional turbulence in a cylindrical pipe or tube. This shows the power it has to control flows, which could be used in many applications.”
Prof Ristroph thinks this is exactly what Tesla was trying to get at: “We think this is what Tesla had in mind for the device, since he was thinking about analogous operations with electrical currents. He, in fact, is most famous for inventing the AC motor, as well as an AC-DC converter.”
He continued: “Tesla’s device is an alternative to the conventional check valve, whose moving parts tend to wear out over time. And now we know it is very effective at mixing, and it could be used to harness the vibrations in engines and machinery to pump fuel, coolant, lubricant, or other gases and liquids.” No doubt to the dabbling engineers reading, a number of medical applications are jumping out at you.
It’s really only as time has passed that the full realisation of Tesla’s genius has been increasingly appreciated. In contrast to when he was alive, it has been desirable to attach Tesla’s name to one’s product or system; just ask Elon Musk.
And there are still many of his mysteries to unravel, such as his comment on certain numbers: “If you only knew the magnificence of the 3, 6, and 9, then you would have the key to the universe.”
While there is debate around the sincerity – or even existence – of the following comment, when Einstein was once asked how it felt to be the smartest man alive, his reply reputedly was: “I don’t know, you'll have to ask Nikola Tesla.”
While I’m not kicking the hornet’s nest that is the Tesla vs Einstein debate – Tesla was disdainful of purely mathematical theories – I’d welcome your opinions/letters via the email address above.
With all the disruption caused by the recent HSE technology hack, it’s more important than ever to be aware of potential electronic security threats.
Therefore, I feel it my responsibility to bring to your attention a text message I received which may or may not be a scam, but I feel duty-bound to bring it to your attention. I received a text recently, informing me that I had won a cash prize of €250 and front-seat tickets to an upcoming Elvis Presley tribute concert.
To collect my prize, I was instructed to “Press 1 for the money, 2 for the show...”.
The Dorsal View THE MEDICAL INDEPENDENT | 10 JUNE 2021 44