Feature

Expanding horizons — the new autism is on the broader spectrum

By sa | Aug 20, 2018 | 0 Comments

Autism is defined in the ICD-10 as an abnormal or impaired development before the age of three years, in at least one of the following areas: Reciprocal or expression of language as used in social communication; the development of selective social attachments or of reciprocal social interaction; and functional or symbolic play.

To get the diagnosis of autism, you have to have at least two of the following four features: (a) Failure to adequately use eye-to-eye gaze; (b) failure to develop peer relationships; (c) lack of socio-emotional reciprocity; and (d) lack of spontaneous seeking to share enjoyment. 

This must be followed by at least one item from the following list: (i) Delay or total lack of development of spoken language; (ii) relative failure to initiate or sustain conversational interchange; (iii) stereotyped and repetitive use of language; and (iv) lack of variate spontaneous make-believe play.

This has to be followed by at least one of the following items: (a) An encompassing preoccupation with one or more stereotyped and restricted patterns of interest; (b) preservation of sameness; (c) stereotyped and repetitive motor mannerisms; and (d) preoccupations with part-objects or non-functional elements of play materials.

Asperger’s syndrome, as per ICD-10, has similar features, except that there is no clinically significant general delay in spoken or receptive language or cognitive development. This has been deleted from the American Psychiatric Association’s DSM-5, and will be deleted from ICD-11, most likely, in its final approved version (draft version now available for debate).

History of diagnosis of autism

There has been a massive broadening and evolution of the concept of autism over the past three-quarters of a century. Hans Asperger described it first in modern times, in 1938. Leo Kanner published a classic account in 1943, having got the features from two of Asperger’s colleagues who had emigrated to America at the time of World War II to work with Kanner. The prevalence of autism depends on whether you use old, narrow, out-of-date concepts of autism or new, broader concepts of the condition.

The original prevalence studies of autism in Ireland were conducted by McCarthy, Fitzgerald and Smith and showed a prevalence of 4 per 10,000 in the old Eastern Health Board in Ireland. The current prevalence from the US Centers for Disease Control and Prevention (CDC) in 2016 put the prevalence of autism at one-in-68. I believe that is the correct prevalence.

Autism is under-diagnosed in Ireland and often comorbidities, (which often co-occur) — like attention deficit hyperactive disorder (ADHD), oppositional defiant disorder, dyspraxia or depression — are often diagnosed first and the fundamental problem of autism is missed, with serious and detrimental consequences for the child.

Early diagnosis is critical for a good outcome and there is universal agreement on the critical importance of this early diagnosis and interventions. One of the problems is that the UK National Institute for Health and Care Excellence (NICE) guidelines are not followed. They are very clear that the diagnosis of autism is a clinical diagnosis by an expert in the area of autism. They do not recommend any current test, questionnaire, or structured interview for the diagnosis of autism. Unfortunately, in Ireland, the Autism Diagnostic Interview-Revised (ADI-R) is often regarded as the gold standard diagnosis. It is far from this. It is a very reasonable instrument to use in research, because researchers can compare their findings on this instrument between countries. Unfortunately, in clinical practice, it is often not suitable because parents come to me saying that their child is ‘ADI-R negative’, which to them and to everyone else means that the child does not have autism. Of course, the parents themselves, the schools and everybody else can see clearly that they have autism, as defined by the broader autism phenotype, which is accepted throughout the world now.

If they do not get a diagnosis, then it is a tragedy for the parents, for the child themselves and for the schools, because the child is deprived of early intervention services, special needs assistants and home tuition if necessary, if they are at a very young age. They are also then deprived of the specialised speech and language therapy and occupational therapy they so urgently need.

It is hardly surprising that this leads to massive frustration for parents, teachers and for the child themselves and these children often become very depressed, very anxious, etc. They also develop behavioural disorders, particularly oppositional defiant disorder. Prof Dorothy Bishop, Professor of Developmental Neuropsychology at the University of Cambridge told Adam Feinstein, who wrote a book called Autism in History, that, “the main problem with the ADI-R is not just the financial cost (though that is certainly prohibitive), but also the cost in time; time for training, time for administration, and time for scoring and consensus coding”. Prof Bishop also stated that “if it could be shown that there were real benefits in accuracy of diagnosis from adopting this lengthy procedure, then I would be happy to say, ‘okay’, but, the originators of this instrument have never demonstrated that you actually need such a long process; it is really more an article of faith with them”.

For me, faith is a religious concept. The real issue is that the concept of autism has greatly expanded, as research into what autism is has been carried out. Old-fashioned narrow concepts, which are still being used, have no place in autism diagnosis today. The International Meeting for Autism Research in London in May 2008, which many of the most experienced researchers in autism in the world attended, “lambasted the tool (ADI-R) for missing many cases of autism” and maintained that it was an expensive and “ineffective instrument”. Prof Bishop stated that even after using this instrument, there was no choice but “to seek expert clinical opinion”.

The British Journal of Psychiatry stated in August 2017 that the ADI-R was significantly “under-diagnosing toddlers”.

Prof Gillian Baird previously showed that if you use narrow criteria for autism, “you get a prevalence of 25 per 10,000 and when you use the broader, current criteria, you get a truer rate of 116 per 10,000”. The tragedy is that you miss over three-quarters of the patients with autism if you use narrow criteria and deprive these children of critical early interventions.

Another tragedy in relation to autism was that Bruno Bettelheim propagated the ‘Refrigerator Mother’ theory, first proposed by Kanner, as a cause of autism. This was a total tragedy for parents with children with autism. Sometimes now children with autism are diagnosed as having attachment disorders and the autism is missed and again, this allows the blaming of the mother to enter by the ‘back door’. 

Autism is a neurodevelopmental disorder and indeed, the major portion of psychiatry is now dealing with neurodevelopmental disorders, which also include ADHD, global developmental delay, communication disorders, language disorders, speech-sound disorders, specific learning disorder, developmental co-ordination disorder, stereotypic movement disorder and tic disorder, according to the DSM-5. Indeed, many psychiatrists see schizophrenia and bipolar disorder as also neurodevelopmental in origin.

There is a huge amount of overlap between these disorders. Indeed, these disorders need to be checked for by a child psychiatrist every time they see a patient referred for child psychiatric assessment.

The future of psychiatry will be neurodevelopmental. Unfortunately today, there is massive emphasis on parenting skills, both in child psychiatry and in the wider media. A great deal of this is misguided and is simply blaming the mother from a new position. In my view, over 95 per cent of parents are good enough in their parenting. Heritability of autism is about 90 per cent, although various figures are given around that position. It is nothing to do with poor parenting; it has major neurobiological underpinnings. Neurochemical abnormalities at the synaptic cleft are important, as indeed are connectivity issues in the brain. The pathophysiology involves discussions of the serotonin system, the GABA system, reelin, neurotrophins, neuroligins and neurexins.

Autism is neurobiologically heterogeneous and areas researchers are focusing on include the limbic system, cerebellum, brain stem and prefrontal cortex, as well as the amygdala. 

Treatment

There is no aetiology-based intervention for autism spectrum disorders, but there are many interventions that are extremely valuable, and even more valuable if the child gets an early diagnosis with the possibility of these earlier treatments. I am being referred patients now around one-and-a-half years old, or indeed younger, for diagnosis. Many of these early referrals would be siblings of patients with autism who have an increased risk. There remains no definitive treatment for autism, although many make such claims, but there is no scientific evidence for them. At the same time, there is no doubt that various interventions — including speech and language therapy, occupational therapy, behavioural therapy and high-quality early intervention education — all play a significant role and are very valuable when applied as a group of interventions.

Extraordinary claims were made for applied behavioural analysis and claims of amazing results with this treatment were made in 1987, when Lovaas carried out a study which, according to Dr Catherine Lord, a psychologist who specialises in autism, “produced extraordinary results, both in the scope of improvement of some children”, who are described as, “indistinguishable from normal”. Others found it impossible to replicate these findings in follow-up research. Some of these children were noted to show robotic behaviour, lack of emotion and an inability to use trained skills outside the school where these were applied. At the same time, as part of a multidisciplinary package, applied behaviour therapy does have a role. It is the excessive claims that have been the problem.

Another programme that has been of benefit is Treatment and Education of Autistic and Related Communication Handicapped Children (TEACH). This programme helps workers to understand the autism culture and identifies emerging skills, providing a basis for individual educational programmes. It breaks down complex behaviour into basic components and skills, which are taught in a hierarchical manner with repeated practice. It involves a great deal of visual learning. Carol Gray’s Social Stories, which explain the why and how of trouble social situations, can be of use. These involve short scripts tailored to the needs, interests and abilities of the child.

In addition, programmes like the Hanen Speech and Language Programme for Autism and pragmatic language therapy can also be useful. Other interventions that make clinical sense, including using the Mind Reading Skills CD-ROM of Simon Baron-Cohen, helping persons on the autism spectrum to read non-verbal behaviour and to understand emotions and to see things from other people’s perspective.

Occupational therapy is valuable for sensory issues, which are extremely common in autism and indeed are part of the diagnostic process now in DSM-5. These sensory problems often cause huge behavioural problems in school and outside school, when children with autism become overwhelmed by sensory inputs.

References on request

Managing patients following the valsartan recall and shortage

By sa | Aug 7, 2018 | 0 Comments

Valsartan is an angiotensin receptor blocker (ARB) that prevents angiotensin II from binding to angiotensin II receptors, and thereby reduces blood pressure (BP). Valsartan can be used as monotherapy, but most often it is combined with a diuretic and/or calcium channel-blocking drug in a single-pill combination (SPC) for the treatment of hypertension and heart failure. Some 13 valsartan drugs are listed in MIMS, many of which are SPCs allowing for increasing doses of the ingredient drugs within the SPC combinations. Estimates vary, but perhaps between 50,000 and 60,000 patients in Ireland will have had a valsartan-containing drug prescribed.

Valsartan recall

Within the last few weeks, the Health Products Regulatory Authority (HPRA) has issued a precautionary recall of 15 drugs containing the active ingredient valsartan. These drugs are provided by Clonmel Healthcare Ltd, Rowex Ltd and the Actavis Group PTC. The reasons for this highly unusual action can be studied on the HPRA website and in ‘Dear Doctor’ letters issued by the HPRA.  I have listed the salient points from this letter, followed by my response and queries:

These drugs are being recalled as a precautionary measure because the Chinese manufacturer has reported contamination with a probable human carcinogen, N-nitrosodimethylamine (NDMA). This statement from the HPRA raises the question as to whether valsartan drugs from other manufacturers might also be contaminated, or put another way, is this carcinogenic substance a common, or even essential, ingredient from the manufacture of valsartan (and possibly other ARBs)?

The HPRA is actively involved with the European Medicines Agency and with other medicines regulators to determine any possible impact on patients who have been taking these medicines.   Presumably the answer to this conundrum will be influenced by the dosage of valsartan prescribed and the duration of exposure to the drug?

It is stated that pharmacists will be able to identify patients on the contaminated drugs and that they should be able to provide an alternative valsartan-containing medicine. This can only be done if valsartan is used as monotherapy, or if there is an exact SPC valsartan equivalent to the one prescribed, because pharmacists in Ireland are not authorised to change prescriptions, and patients taking the contaminated drugs must be referred to their general practitioners if an alternative drug is to be prescribed.

It is possible (perhaps likely) that there will not be sufficient current stock levels of non-contaminated valsartan-containing medicines for doctors and/or pharmacists to provide patients with an alternative valsartan-containing medicine and in this case, patients will also be advised by to attend their doctor.  This recommendation, like the one above, may not be immediately feasible because general practitioners, who are often stretched to capacity, may not be able to see patients for some time. In either situation, it would be good clinical practice for general practitioners to assess BP control with 24-hour ambulatory blood pressure measurement (see below).

On 13 July, the US Food and Drug Administration (FDA) recalled valsartan-containing drugs from five companies. The FDA statement reads: “The FDA is currently investigating the levels of NDMA in the recalled products, assessing the possible effect on patients who have been taking them and what measures can be taken to reduce or eliminate the impurity from future batches produced by the company.”

How should patients on valsartan-containing drugs be managed?

The above-listed events are likely to cause much concern for patients taking valsartan drugs for hypertension, and the following recommendations seem reasonable in these difficult and evolving circumstances:

Patients should not stop medication without medical consultation because of the danger of uncontrolled BP predisposing to the cardiovascular complications of hypertension, such as stroke and heart attack.

Pharmacists should be able to determine if the patient is on a contaminated product, and unless a direct alternative is available, patients must be referred to their general practitioner so that an alternative drug can be prescribed.  If the valsartan product is not contaminated, there is a possibility that pharmacists will have insufficient valsartan products to satisfy the sudden demand, and it will be necessary to consider changing treatment. It is also possible that patients will ask to be taken off valsartan drugs, even if they are not on the contaminated list, because of anxiety resulting from the valsartan recall.  

As to which drug to select as an alternative to valsartan as monotherapy or in an SPC, clearly the choice should be to select another non-valsartan ARB, as presumably the reason for selecting an ARB originally was for the efficacy of this class of drug and freedom from cough, which may occur frequently with an ACE inhibitor.

I have written before on the benefits of using SPCs for the treatment of hypertension,1,2,3 on the basis that the rationale for incorporating a number of drugs within one tablet is based on the following evidence-based facts: Most patients with hypertension require more than one drug to achieve BP control; combination preparations improve BP control; prescribing low-dose drugs in combination causes fewer adverse effects than prescribing maximum doses of any one drug; patient adherence to medication is improved by combination tablets, and finally, the combination approach is cost-effective.

There are excellent SPC combinations of alternative ARBs combined with calcium-channel blocking drugs, and thiazide diuretics in differing strengths, which allow treatment to be increased a number of times while only prescribing one tablet.2

Faced with the inevitable necessity to change medication in many patients with hypertension, we should avail of the opportunity to re-evaluate BP control on the replacement drug by performing 24-hour ABPM. ABPM is recommended by international guidelines as the technique of choice for the diagnosis and management of hypertension.3 ABPM is now reimbursed in general practice and this crisis provides a very positive indication for utilising the technique to achieve 24-hour BP control in patients whose medication with contaminated valsartan drugs must be changed. 

Prof  Eoin O’Brien is Adjunct Professor of Molecular Pharmacology, The Conway Institute, University College Dublin, Ireland.

References

1.    O’Brien, E. If I Had Resistant Hypertension. Hypertension. 2014;64:e3-6.

2.    Dolan E, O’Brien E. Blood pressure variability: Clarity for clinical practice. Hypertension. 2010;56:179-81.

3.    O’Brien E, Stergiou GS. Blood Pressure Measurement: A Reappraisal for 21st Century Practice. J Clin Hypertens 2018. In press.

Annual European Congress of Rheumatology (EULAR) 2018, Amsterdam

By sa | Jul 17, 2018 | 0 Comments

Results of study suggest siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome

The results of a study presented at the Annual European Congress of Rheumatology (EULAR 2018) demonstrate an increased risk of acute coronary syndrome (ACS) in siblings of individuals with rheumatoid arthritis (RA), suggesting shared susceptibility between the two diseases.

Recent studies have demonstrated that severity of RA is associated with the risk of ACS, suggesting that it is the RA disease itself contributing to the excess risk.

A recently-published report demonstrated that despite more efficient control of inflammation in RA during recent years, the excess risk for ACS among patients with RA compared to the general population remains elevated. This suggests there may be a shared susceptibility between the two conditions.

To examine this, study authors investigated the risk of ACS in siblings of individuals with RA. If there were shared susceptibility between the two conditions, non-RA siblings would also have an increased risk of ACS due to their similar genetic set-up and background.

This Swedish Rheumatology Quality (SRQ) register is linked to the Swedish Multigeneration Register, Patient Register, the Cause of Death Register, and the Total Population Register. Through this, investigators identified 7,492 patients with RA from the SRQ (1996-2015) who had 10,671 full siblings; the patients with RA were matched for age and gender with 35,120 comparator subjects, along with their 47,137 full siblings.

Results showed that patients with early RA and their siblings were 44 per cent and 23 per cent more likely to suffer from an ACS event than matched comparator subjects from the general population. A direct comparison of patients with RA to their siblings demonstrated that those with RA had a 19 per cent higher risk of ACS than their siblings.

“Our results provide evidence of shared susceptibility between RA and ACS,” said study author Dr Helga Westerlind, Karolinska Institutet, Sweden. “Although the nature of this needs to be further investigated, we believe that to bring down the cardiovascular risk in patients with RA, cardio-preventive measures must go beyond optimised RA disease control.”

Gout in the elderly linked to higher risk of dementia

The results of a US study presented at EULAR 2018 suggest that gout is associated with a 17-to-20 per cent higher risk of dementia in the elderly.

The study included 1.23 million Medicare beneficiaries, of which 65,325 had incident dementia. In an analysis, which was adjusted for various potential confounding variables, including demographics, comorbidities and commonly-used medications (HR 1.17, 95 per cent CI 1.13-1.21), the results showed that gout is independently associated with a significantly higher risk of dementia. The association was larger in older age groups, females, African-American race and people with higher medical comorbidity.

Subgroup analyses indicated that gout was associated with a significant 20-to-57 per cent (p<0.0001) increase in dementia in patients without key comorbidities: Coronary artery disease (CAD); hyperlipidaemia; cardiovascular disease; diabetes; or hypertension. However, this was not the case in patients with each of these comorbidities, except in patients with CAD.

“Our study found a considerable increased risk of dementia associated with gout in the elderly,” said study author Dr Jasvinder Singh, Professor of Medicine and Epidemiology at the University of Alabama, Birmingham, US. “Further study is needed to explore these relationships and understand the pathogenic pathways involved in this increased risk.”

“We welcome these results, as they contribute to our understanding of the relationship between uric acid and dementia,” said Prof Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. “Previous studies have shown contradictory results, with some indicating an increased risk of dementia, while others reporting the opposite.”

Combining NSAIDs and TNF inhibitors may reduce radiographic progression in ankylosing spondylitis

The results of a cohort study presented at EULAR 2018 showed that, in patients with ankylosing spondylitis (AS) taking TNF inhibitors, the addition of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with significantly less radiographic progression in a dose-related manner at four years.

When looking at specific NSAIDs, celecoxib in combination with TNF inhibitor use was associated with the greatest reduction in radiographic progression, which was significant at both two and four years.

NSAIDs remain first-line therapy for patients with AS. If patients have a poor response, contraindications or intolerance to NSAIDs, they may then be given TNF inhibitors. Current treatment practice is based on symptomatic relief, however there is also some evidence that NSAIDs slow radiographic progression if taken continuously.

The evidence for the impact of TNF inhibitors on radiographic progression is unclear despite their good clinical efficacy. Many patients discontinue NSAIDs when they are put onto TNF inhibitors due to good symptom control; therefore there is very limited data on the impact of combined therapy on radiographic progression.

“Radiographic progression has an important bearing on patient mobility, as well as affecting their general wellbeing and day-to-day living,” said Prof Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. “We welcome these results that support a potential disease-modifying effect in patients with ankylosing spondylitis taking current therapies.”

This prospective cohort study included 519 patients with AS who met the modified New York criteria with at least four years of clinical and radiographic follow-up. The average age of participants was 41.4 years, with an average symptom duration of 16.8 years and three-quarters were male. NSAIDs were used in 66 per cent of patients (half using an index below 50 and half above). TNF inhibitors were used in 46 per cent of patients.

After baseline measures, clinical and medication data were collected every six months and radiographs performed every two years. Radiographic progression was measured using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Statistical analysis, which accounted for time-varying covariates, was used to estimate the causal effect of TNF inhibitors and NSAIDs on radiographic progression. The analysis was adjusted for gender, race/ethnicity, education, symptom duration, enrolment year, number of years on TNF inhibitors, symptom duration at time of TNF inhibitor start, baseline measurement scores (mSASSS, ASDAS-CRP), current smoking, and missed visit status.

In patients taking TNF inhibitors, the addition of NSAID therapy was associated with less radiographic progression in a dose-related manner at four years. Mean difference in mSASSS between TNF inhibitor use and no TNF inhibitor use at four years was 0.50 (p=0.38), -1.24 (p<0.001), and -3.31 (p<0.001) for no NSAID, low NSAID, and high NSAID use. The mean difference in mSASSS between TNF inhibitor and no TNF inhibitor use for celecoxib was -3.98 (p<0.001) and -4.69 (p<0.001) at two and four years, respectively.

“Our results suggest that the use of TNF inhibitors and NSAIDs, particularly celecoxib, have a synergistic effect to slow radiographic progression in AS patients, particularly at higher doses,” said study author Prof Lianne Gensler, Associate Professor of Medicine, University of California, San Francisco, US.

“This is the first study to compare whether effects are comparable among different NSAIDs in this setting.”

Positive clinical advances in systemic lupus erythematosus

The results of two studies presented at EULAR 2018 demonstrate exciting advances for individuals suffering from systemic lupus erythematosus (SLE).

The first is a phase 2 clinical study of a promising oral treatment, baricitinib. The second demonstrates the effective use of the shingles vaccine in SLE patients who are particularly prone to this infection.

“Novel therapeutic strategies are needed for SLE, which causes significant morbidity and mortality, and so we are delighted to see the positive results from the phase 2 trial of baricitinib,” said Prof Thomas Dörner, Chairperson of the Abstract Selection Committee, EULAR. “In addition, we welcome data on the vaccination of SLE patients against shingles, as currently, there is considerable clinical uncertainty around this issue.”

Treatment of SLE traditionally involves non-specific anti-inflammatory or immunosuppressive medications. However, this approach is ineffective in many patients and can be associated with many undesirable side-effects.

In the new phase 2 study, SLE patients taking baricitinib (an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 approved for the treatment of rheumatoid arthritis in Europe and Japan) had a significant improvement in several clinical outcomes compared to placebo.

This study included 314 patients with SLE receiving stable background therapy who were randomised 1:1:1 to placebo, baricitinib 2mg or 4mg once daily. Patients on baricitinib 4mg achieved significant resolution of arthritis or rash (Systemic Lupus Erythematosus Disease Activity Index 2000, SLEDAI-2K) compared with placebo (67 per cent vs 53 per cent, p<0.05), which was the primary end-point of the study. Patients on baricitinib 4mg also achieved a significantly greater SLE Responder Index (SRI-4) response (64 per cent vs 48 per cent, p<0.05), as well as flare reduction (SELENA-SLEDAI Flare Index), improvement in Lupus Low Disease Activity State (LLDAS) and reduced tender joint count. Rates of adverse events leading to treatment discontinuation and serious adverse events were higher for both baricitinib doses compared to placebo. There were no deaths, malignancies, major adverse cardiovascular events, tuberculosis, or serious herpes zoster infections; one case of deep-vein thrombosis was reported in a patient with risk factors.

“Our results demonstrated significant clinical improvements in SLE patients taking baricitinib versus placebo with an acceptable side-effect profile,” said Prof Daniel Wallace, Professor of Medicine, University of California and Associate Director, Rheumatology Fellowship Programme at Cedars-Sinai Medical Centre in California, US. “We look forward to progressing baricitinib in further clinical studies as a promising new treatment for people suffering with SLE.”

Meanwhile, a separate study showed that the live attenuated shingles vaccine was well tolerated and provoked an expected antibody response in stable SLE patients not receiving intensive immunosuppression.

Patients with SLE are 10 times more likely to contract shingles compared to healthy individuals and it can also affect them at an earlier age.

However, specific guidelines on the use of the shingles vaccine in SLE patients have been lacking, largely due to a theoretical concern of vaccine-induced infection, as well as a lack of clinical or experimental data upon which to base recommendations.

The study presented at EULAR 2018 included 90 patients with stable SLE who were not receiving intensive immunosuppression. All participants had a history of herpes zoster/chickenpox and were randomised to receive shingles vaccine or placebo. After six weeks, antibody levels in the vaccine group increased by 59.8 per cent versus a reduction of 2.1 per cent in the control group (p=0.01) demonstrating the effect of the vaccine. No serious adverse events were reported and none of the patients had clinical shingles infection post-vaccination.

“This is the first randomised, controlled trial to study the shingles vaccine in individuals with SLE. We hope our results will inform guidelines and ultimately lead to the safe administration of the vaccine in appropriate SLE patients to reduce the burden of shingles in these individuals,” said study author Dr CC Mok, Department of Medicine, Tuen Mun Hospital, Hong Kong.

Early, intensive treatment of RA provides long-term benefits and may normalise mortality rates — long-term follow-up study

The results of a 23-year, follow-up study presented at the European League Against Rheumatism (EULAR) Annual Congress 2018 suggest early, intensive treatment of rheumatoid arthritis (RA) has long-term benefits including the normalisation of mortality to levels consistent with the general population.

“We know that the adverse effects of rheumatoid arthritis on the body only become truly apparent after more than a decade,” said Prof Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. “Therefore, it is really interesting to see these data supporting early therapy after such a long period of follow-up.”

Mortality in patients with RA is higher than in the general population. There have been many advances in management which have demonstrated improved morbidity rates, however, evidence of improved mortality rates has remained elusive.

“Our results confirm that early, intensive treatment of rheumatoid arthritis, including use of glucocorticoids, has long-term benefits,” said Prof Maarten Boers, VU University Medical Centre, Amsterdam, The Netherlands (study author).

“Importantly, this study is one of the first to show a normalisation of RA mortality compared to the general population after 23 years of follow-up.”

This prospective study looked at the rate of mortality after 23 years follow-up of the COBRA (COmbinatietherapie Bij Reumatoide Artritis) trial.

In the original study, patients with early RA were treated with sulphasalazine (SSZ) monotherapy or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone.

Results demonstrated the combined therapy regimen offered additional disease control over SSZ alone.

In 2010, after 11 years of follow up, another study showed numerically (but not significantly) lower mortality in patients on the combined therapy regimen compared to patients with SSZ monotherapy.

NSAIDs shown to have causal role in cardiovascular risk of patients with osteoarthritis

The results of a study presented at EULAR 2018 suggest that over two-thirds of the increased cardiovascular risk associated with osteoarthritis is linked to the use of non-steroidal anti-inflammatory drugs (NSAIDs), a mainstay of treatment for this condition.

Recent research suggests that osteoarthritis is an independent risk factor for cardiovascular disease (CVD) and several mechanisms have been suggested to account for this association. One of these is the frequent use of NSAIDs in the treatment of osteoarthritis as they have been shown to be a proven risk factor for CVD.

“The examination of cardiovascular risk among individuals with osteoarthritis is an important area of research as very little is known about the association, despite osteoarthritis being the most common rheumatic disease with high prevalence among the elderly,” said Prof Thomas Dörner, Chairperson of the Abstract Selection Committee, EULAR.

“This study is important because it provides new information about the potential causal role of NSAIDs for the observed cardiovascular complications among individuals with osteoarthritis.”

Results of the study demonstrate that people with osteoarthritis had a 23 per cent higher risk of developing CVD. The increased risk of congestive heart failure (CHF), ischaemic heart disease (IHD), and stroke was 42 per cent, 17 per cent and 14 per cent respectively. Investigators then calculated the impact of NSAID use on the increased risk and found that 68 per cent of the total effect of osteoarthritis on CVD risk was due to NSAID use. The proportion of the increased risk due to NSAIDs seen in CHF was calculated at 45 per cent and more than 90 per cent for IHD and stroke respectively.

This population-based cohort study used data from 7,743 osteoarthritis patients and 23,229 non-osteoarthritis controls matched for age and gender from health administrative data from British Columbia, Canada. Statistical analysis was used which adjusted the results for age, gender, socioeconomic status, body mass index, and several conditions known to be associated with CVD, such as chronic obstructive pulmonary disease (COPD), high blood pressure, diabetes, high cholesterol, and Romano comorbidity score.

“To the best of our knowledge, this is the first longitudinal study to evaluate the mediating role of NSAID use in the relationship between osteoarthritis and CVD in a large population-based sample,” said study author Prof Aslam Anis, School of Population and Public Health, University of British Columbia.

“Our results indicate that osteoarthritis is an independent risk factor for CVD and suggest a substantial proportion of the increased risk is due to the use of NSAIDs.

“This is highly relevant because NSAIDs are some of the most commonly used drugs to manage pain in patients with osteoarthritis.”

New resources for psoriasis patients

By sa | Jul 3, 2018 | 0 Comments

The Irish Skin Foundation (ISF) has published a revised and expanded psoriasis patient support booklet.

With up to 100,000 people in Ireland affected by psoriasis, and up to 20,000 of these living with a severe form, the ISF has updated its ‘What you need to know about psoriasis’ support booklet, which is a useful resource to give to patients with psoriasis.

The new edition provides revised information on understanding, managing and living with psoriasis. Updated sections include, what psoriasis is, the different types of psoriasis, treatments available, associated conditions, self-care tips and more.

This booklet, which first appeared in 2014, was extensively revised after wide consultation with people with psoriasis who have contacted the ISF Helpline, dermatology nurses and consultant dermatologists.

Although there is no cure for psoriasis, there are a range of effective treatment options available, which can be offered on a stepladder approach, including dithranol, tar, and UVB phototherapy. For those with moderate- to-severe psoriasis who have not responded to milder treatments, systemic treatment may be needed (eg, ciclosporin, methotrexate, acitretin and fumaric acid esters).

A number of biologic agents have been licenced for the treatment of psoriasis, including TNF inhibitors (eg, adalimumab, etanercept and infliximab), the interleukin (IL) 12/23 compound ustekinumab, and the IL-17A antagonist, secukinumab. These agents have significantly broadened the range and efficacy of treatment options available and revolutionised the care of more severe psoriasis patients.

Key symptoms in psoriasis include:


Red, scaly plaques or lesions with sharply defined edges, that occur most commonly on both elbows, both knees, the scalp, under arms, under breasts, natal cleft and genitalia, or at the site of an injury.

If the scales are gently scraped off, a number of small, bleeding points can be seen underneath.

Nail changes – loosened, thickened or pitted nails.

Plaque psoriasis is the most common form of psoriasis, affecting approximately 90 per cent of patients. The plaques can vary in number, size, and location but the sites most frequently affected, are the knees, elbows, scalp and sacrum. The plaques are often itchy and painful, and can crack and bleed.

Guttate psoriasis usually has a sudden onset with the widespread appearance of small, red teardrop shaped patches less than 1.5cm in size. The onset is often preceded by a streptococcal throat infection. In many cases, the condition disappears by itself after a few weeks or months.

Flexural psoriasis occurs in skin flexures such as under the breasts, in the armpits or the groin. The plaques are usually red, smooth and shiny. There is very little or no scale, due to the presence of sweat. Painful superficial skin fissures sometimes occur in skin creases. Candida albicans can also develops, due to the naturally warm moist environment found in these areas.

Scalp psoriasis affects up to 80 per cent of people with psoriasis and sometimes is the only area of involvement.

A new step-by-step section on treatments for scalp psoriasis has been included in the ISF booklet. This new section includes some useful techniques patients can use at home to treat their scalp psoriasis with over-the-counter and prescribed treatments.

Psoriatic arthritis

There are a number of other conditions that have been associated with psoriasis including psoriatic arthritis (PsA), which is covered in the booklet.

Studies indicate a wide prevalence rate of PsA among people with psoriasis; anything between 6 and 42 per cent.

Key symptoms associated with psoriatic arthritis include joint pain, especially with redness, swelling, and tenderness; pain in the heel(s) or tennis elbow; finger or toe that is completely swollen (sausage shaped) and painful for no apparent reason; and morning stiffness/pain in the back that improves with movement.

Support

The ISF’s ‘What you need to know about Psoriasis’ support booklet is available free of charge by post or can be downloaded from the ISF website at www.irishskin.ie.

The ISF also operates a free helpline (01 486 6280) and web questionnaire service, providing direct, accessible and specialist guidance and support to skin condition patients.

The ISF also holds regular information and awareness events on various skin conditions, including psoriasis.

Meanwhile, the ISF has pointed out that patients may not be aware that they can claim back money from Revenue for over the counter items used to treat their psoriasis like creams, medications or other aids and appliances in certain circumstances.

Revenue allows for tax back on health expenses incurred in the provision of healthcare, which is defined as the prevention, diagnosis, alleviation or treatment of an ailment, infirmity, defect or disability.

In addition, it also covers cosmetic surgery only as a result of a physical deformity arising from, or directly related to, a congenital abnormity, personal injury or disfiguring disease.

Medicines and associated items that qualify for tax back must be:

(a) Supplied by a pharmacist and

(b) Be written on the medical practitioner’s medical / prescription pad.

Thus, any relevant over-the-counter items prescribed by a medical practitioner can be claimed back under the tax system, at 20 per cent of the cost of the item, once the relevant prescription and pharmacy receipts are kept.

Breast cancer in young women

By sa | Jul 3, 2018 | 0 Comments

Breast cancer is the commonest, potentially fatal cancer diagnosed in women in Ireland, according to the latest National Cancer Registry Ireland (NCRI) statistics. The median age at diagnosis is 60 – 64 years. Women under the age of 40 have an incidence of 11.93 diagnoses per 100,000 women per year. This patient population poses specific challenges and here we attempt to address some of these, namely pregnancy-associated breast cancer, optimum adjuvant endocrine treatment, fertility post-treatment and inherited breast cancer syndromes.

Pregnancy-associated breast cancer

Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy or in the first postpartum year. With most pregnancies occurring in women under the age of 40 years, it is this age group that is at risk of pregnancy-associated breast cancer. The incidence of breast cancer increases with age and as increasing numbers of women delay pregnancy, it is possible that pregnancy-associated breast cancer will increase. Several studies have indicated a worse prognosis in those with pregnancy-associated breast cancer; these cancers tend to have higher T and N stages. Even allowing for this, some studies have demonstrated worse cancer-related outcomes for those with pregnancy-associated breast cancer.

No statistics are available at present for the incidence in Ireland, but it is estimated that approximately one-in-3,000 pregnant women will be diagnosed with breast cancer, making it the second most common malignancy in pregnancy. Several challenges arise in this setting, including difficulties in diagnosis, optimum timing of surgery, scheduling of systemic treatment and maximising neonatal outcomes. The Royal College of Obstetrics and Gynaecology recommends that all women presenting with a breast mass during pregnancy be referred for evaluation to a specialist breast unit. Surgery is safe during all stages of pregnancy, but should be delayed until after the first trimester, when the risk of miscarriage diminishes. Radiation is not recommended for patients who are pregnant. Cytotoxic chemotherapy use is generally initiated in the second trimester, with evidence for good neonatal outcomes with the use of anthracycline/cyclophosphamide combinations. Due to the risk of oligohydramnios, trastuzumab is not given during pregnancy. In general, cytotoxic chemotherapy is held at 35 weeks to reduce the risk of neonatal neutropaenia. Endocrine therapy is not given until after delivery.

Optimum adjuvant endocrine treatment

Tamoxifen is a selective oestrogen receptor modulator and has been a mainstay of treatment for women with oestrogen receptor-positive breast cancer for decades. Its use has been refined over this time, with it now being used primarily in pre-menopausal women. However, even with five years of adjuvant tamoxifen therapy, some patients will relapse and so strategies to optimise adjuvant endocrine treatment in patients have been further explored. Such strategies include prolonging the duration of therapy or more aggressive suppression of hormonal function.

Two large multicentre randomised studies evaluated the utility of extended tamoxifen therapy, beyond the standard five years, ATLAS and ATTOM. Initial results of both studies suggested that there was no survival benefit to this therapy. Follow-up survival data, however, demonstrated a benefit to extended adjuvant tamoxifen, which appeared after the 10-year period of treatment and, therefore, this is a potential therapeutic strategy for these patients. Such a prolonged course of therapy might be best targeted at patients with a persistent elevated risk of relapse after five years of therapy, eg, those patients with pathologically involved lymph nodes at diagnosis.

Two other large studies have evaluated the optimum intensity of adjuvant endocrine treatment. The TEXT and SOFT studies sought to establish if further oestrogen suppression with triptorelin, a GnRH agonist, in combination with either exemestane (an aromatase inhibitor) or tamoxifen would improve survival. The TEXT study evaluated exemestane, a steroidal aromatase inhibitor, in combination with triptorelin, a GnRH agonist compared to tamoxifen and triptorelin. This trial demonstrated an improvement in disease-free survival in those patients on exemestane and triptorelin compared to tamoxifen and triptorelin. No overall survival benefit was seen. In the SOFT study, when compared to tamoxifen alone, tamoxifen and triptorelin demonstrated a 4 per cent disease-free survival benefit, with a 7 per cent disease-free survival benefit in those on exemestane and triptorelin. Unlike the TEXT study, an overall survival benefit was seen, largely coming from the higher risk group (those patients requiring adjuvant chemotherapy). There is, however, a higher adverse effect rate, with increased vasomotor symptoms, decreased libido, vaginal dryness, and musculoskeletal symptoms among others. Given the modest benefit, this combination approach is usually offered to those patients at higher risk of recurrence (especially very young patients, ie, those under 35 years of age).

Fertility post-treatment

In younger breast cancer patients, preservation of fertility is often a key priority. There are several concerns at this time – preventing premature ovarian failure, timing of future pregnancies to maximise oncologic and fertility outcomes and the need to avoid teratogenicity with ongoing treatment.

Fertility preservation prior to embarking upon treatment can be considered in those patients who wish to do so. There are two main techniques that are available to patients: Oocyte or embryo preservation. Oocyte preservation requires a short cycle of stimulatory hormonal therapy, after which the oocytes are retrieved and rapidly frozen. In Ireland, embryo preservation is offered to those with a long-term partner. The first step is as for oocyte preservation, with subsequent fertilisation and embryos are then frozen. With modern oocyte stimulation techniques, delays to the initiation of chemotherapy can be kept to a minimum.

Administration of GnRH analogues during chemotherapy may help preserve ovarian function. A recent meta-analysis of the use of GnRH analogues, pooling the data from several international studies, demonstrated improved post-chemotherapy fertility. The authors classified this as (1) improved premature ovarian insufficiency rate (variously identified as failure to return to normal menstruation within six-24 months depending on the study), (2) higher pregnancy rate, and (3) reduced rates of amenorrhoea at two years. They did not find any evidence of excess cancer-related mortality in those who received the GnRH analogue. Thus, this provides a potential option for these patients.

Pregnancy post-breast cancer diagnosis poses challenges in treatment continuity and risks of recurrence. Data is sparse, but a recently reported retrospective study examining 1,200 patients did not demonstrate any increased risk of recurrence in those women who became pregnant post-early breast cancer diagnosis.

Timing of pregnancy can be a challenge. The risk of recurrent cancer in patients with triple negative and HER2-positive breast cancer is highest in the first two years after diagnosis and the advice for these women is generally to avoid pregnancy until this period has passed. The situation is more complex for those with oestrogen receptor-positive breast cancer. For these patients, adjuvant endocrine therapy is an essential part of treatment, with the goal of treatment being oestrogen suppression. However, tamoxifen is contraindicated in those planning a pregnancy due to the risk of teratogenicity. It is therefore recommended that such women stop tamoxifen for three months prior to attempting to conceive. The reduced duration of therapy may expose the patient to a higher risk of relapse and patients must be counselled on this risk. 

Another factor to consider in the young woman post breast cancer diagnosis is the potential teratogenicity of therapies. As outlined in this article, cytotoxic treatments are carefully scheduled. Once commenced on adjuvant endocrine therapy, patients should be advised to use effective contraception. Available data on tamoxifen suggests there is a risk of congenital malformations and a three-month washout period is advised.

Inherited breast cancer syndromes

When a young woman is diagnosed with breast cancer, the question of an underlying genetic predisposition often arises. Most cases of breast cancer are not caused by an identifiable inherited predisposition, instead having a multifactorial origin. However, 5-10 per cent of breast cancers can be attributed to a single gene mutation, which significantly increased the predisposition to cancer development. Between 80-90 per cent of all hereditary breast cancers are associated with mutations within the BRCA1 and BRCA2 genes, with less common syndromes including Li Fraumeni syndrome, Peutz-Jeghers syndrome, Cowden syndrome and ataxia/telangiectasia also causing an increased risk. To identify those at risk, a complete, three-generation family history must be obtained from patients. A complete discussion of the intricacies of each syndrome is beyond the scope of this article and we will focus on BRCA syndromes. Various testing platforms exist, ranging from those examining specific targets (such as in a family with a known BRCA mutation) and those offering panel testing, assessing risk associated with more than one syndrome.

BRCA1 and BRCA2 function as tumour-suppressor genes, playing a role in DNA repair and are inherited in an autosomal dominant fashion with incomplete penetrance. Testing for BRCA1/2 mutations should be performed in the context of pre- and post-treatment counselling. The Manchester Criteria are used to help determine which patients should be offered testing. Those patients who are found to be carriers can then discuss appropriate surveillance and potential risk-reducing procedures. More widespread population-based screening is considered in some centres. In this instance, BRCA1/2 testing is offered to all patients under 40 years, or all those with triple-negative breast cancer.

In summary

Managing breast cancer in young women is a complex challenge, requiring balancing of multiple factors. When breast cancer complicates pregnancy, co-ordination between the oncologist and obstetrician is imperative to optimise outcomes. Close communication between all members of the multidisciplinary team helps to facilitate fertility preservation and genetic testing. The most recent data available offers several combination strategies to optimise adjuvant endocrine therapy for these patients.  

References on request

Peritoneal malignancy in Ireland — current status and update on surgical management

By sa | Jul 3, 2018 | 0 Comments

Peritoneal malignancy is diagnosed in approximately 500 patients annually in Ireland. The incidence is increasing, having approximately doubled in the last decade. The vast majority of cases arise as a result of metastatic spread from intra-abdominal primary cancer (colorectal, appendiceal, ovarian, gastric, pancreatic).

Approximately 10 per cent of cases are the result of metastatic spread from extra-abdominal cancer, in particular breast cancer, lung cancer and malignant melanoma. Primary peritoneal malignancy (eg, peritoneal mesothelioma and primary peritoneal cancer) is extremely rare, affecting only a hand-ful of patients annually. Symptoms are difficult to manage and typically include: Abdominal distension, anorexia, vomiting and abdominal pain due to the progressive intra-abdominal tumour burden and secondary ascites. Once established, peritoneal malignancy is invariably a fatal diagnosis, with median survival in Ireland of six months (source National Cancer Registry Ireland (NCRI), 2012). Patients with metastatic spread to the peritoneum have worse outcomes than their counterparts with stage IV disease not involving the peritoneum.

Palliative chemotherapy has traditionally been the mainstay of treatment. Supporting data in this setting is however limited, as few studies have been specifically performed in patients with stage IV disease involving the peritoneum.  Surgery, termed cytoreduction, may be considered in highly-selected patients with resectable disease. Cytoreductive surgery (CRS) may require all or a combination of total abdomino-pelvic peritonectomy, greater and lesser omentectomy, colectomy, rectal resection, small bowel resection, hysterectomy with bilateral salpingo-oophorectomy, cholecystectomy, splenectomy, liver capsulectomy and occasionally gastrectomy.

This surgery is performed with the intention of removing all macroscopic tumour and the surgical cytoreduction may be augmented by the delivery of intra-peritoneal chemotherapy (typically mitomycin C or oxaliplatin as a single dose for 60-to-90 minutes) at the end of the procedure, with the aim of eradicating any residual microscopic tumour. The chemotherapy is typically heated to 41-to-43°C in order to improve cytotoxicity and increase chemopenetration, hence the term ‘HIPEC’ (heated intra-peritoneal chemotherapy). The entire procedure can take up to 10 hours and is typically followed by a two-week inpatient stay. Multidisciplinary input is required, including a team of surgeons from different disciplines, critical care, radiology, and the allied disciplines including nursing, dietetics and physiotherapy. With evolving international experience, the risk of major morbidity after CRS HIPEC has reduced significantly to approximately 4-to-8 per cent, with a postoperative mortality rate of less than 1 per cent. After surgery, patients typically require three months or more to make a complete recovery. Approximately 50 patients in Ireland are suitable for and undergo CRS combined with HIPEC annually at the Mater University Hospital, Dublin. The vast majority of these patients have either colorectal cancer peritoneal metastases or a condition known as pseudomyxoma peritonei (PMP). Peritoneal mesothelioma is a very rare indication for CRS HIPEC, while the approach is not as yet established in patients with peritoneal spread from upper gastrointestinal or extra-abdominal cancer.

Colorectal cancer peritoneal metastases (CRC PM)

Peritoneal metastases are seen in approximately 5 per cent of patients with colorectal cancer at initial diagnosis (synchronous disease), while a further 10 per cent subsequently develop metachronous peritoneal spread. Surgery may be considered in medically-fit patients with fully-resectable disease of low-to-moderate volume, as determined by a scoring system known as the peritoneal carcinomatosis index (PCI).

This system divides the abdomen into 13 regions and allocates a score of 0-3 to each region proportionate to its disease volume. The PCI may be estimated using a combination of imaging (contrast-enhanced CT and in selected cases, diffusion-weighted MRI) and staging laparoscopy but ultimately, can only be reliably determined at exploratory laparotomy.

Disease progression during systemic therapy, the presence of non-peritoneal distant metastases, multi-focal small bowel involvement, biliary and/or ureteric obstruction, signet ring features and PCI greater than 20 are considered relative contraindications to surgery. Patients are selected following multidisciplinary discussion with input from surgeons, oncologists, radiologists and pathologists. Based on current criteria, approximately 40 per cent of patients referred to a peritoneal malignancy centre with CRC PM will be candidates for CRS. The evidence supporting this multimodal approach first came from a randomised, controlled trial performed by Verwaal in the Netherlands and published in 2003. Patients in the treatment arm underwent CRS with HIPEC, followed by systemic chemotherapy, while those in the control arm received systemic chemotherapy, with or without palliative surgery. In the CRS HIPEC group, median survival was 22 months, compared to 13 months in patients randomised to systemic chemotherapy only.

In the same study, median survival in the subgroup of patients who had a complete cytoreduction (all tumour removed) was 48 months (45 per cent five-year survival), emphasising the importance of selecting those patients with fully-resectable disease. Multiple observational studies have since been performed, including large national cohorts, and have reported median survival following CRS HIPEC in selected patients of up 47 months. The best available data suggest a cure rate (disease-free at five years) of approximately 15 per cent. The majority of patients will, however, relapse and of those who do, one-third will recur in the peritoneum, one-third in non-peritoneal distant organs, and one-third at both sites. Reported survival in patients treated with modern systemic chemotherapy only is in the order of 24 months, however the lack of recent controlled studies should be emphasised.

The long-awaited PRODIGE 7 study was reported at ASCO in June of this year. This multi-centre, randomised, controlled trial compared CRS alone to CRS with HIPEC (oxaliplatin-based) in patients with resectable colorectal peritoneal metastases. Nearly all patients also received systemic chemotherapy.

Median overall survival in both arms was excellent (approximately 42 months), however, there was no additional survival benefit with the addition of HIPEC to cytoreductive surgery. The subgroup analysis suggested a potential gain from HIPEC in those patients with intermediate volume disease, as scored by the PCI system. Overall, the findings support a multimodal approach of systemic chemotherapy and CRS, combined with a more selected and tailored use of HIPEC in patients with CRC PM.

Pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP), commonly referred to as ‘jelly-belly’, is a rare condition characterised by the formation of mucinous tumour plaques throughout the abdominal cavity, which produce large volumes of gelatinous ascites. The primary source is most commonly a mucinous tumour of the appendix, from which cells were shed during asymptomatic perforation. Over time, these cells, transported by normal physiological movement of peritoneal fluid, deposit and replicate at predictable sites, including the sub-diaphragmatic spaces, the omentum, the pelvic cul-de-sac, and the ovaries in females. While invasive features are unusual, a spectrum of low-to-high cytological grade is seen. Elevation in tumour markers (CEA, Ca 19-9, Ca125) is a predicator of a more aggressive phenotype and worse prognosis. Traditionally, the incidence of PMP was thought to be approximately one/million/year, however the Mater experience would suggest that the true rate is at least four times higher.

A low-grade mucinous tumour of the appendix is a relatively common incidental finding following appendicectomy performed for acute appendicitis. A subset of these patients are at future risk of developing PMP and as a precaution, should be kept under surveillance with regular clinical assessment and imaging.

Once established, PMP is invariably a progressive and fatal condition which responds poorly to systemic therapy. It was for this reason that Sugarbaker pioneered surgical approaches to PMP, and the concept of CRS HIPEC was born. The largest single-centre experience stems from Basingstoke, UK, where more than 1,000 patients with PMP have undergone CRS HIPEC. Their results show that after complete cytoreduction (all tumour resected), approximately 80 per cent of patients will be alive and disease-free at 10 years. Patients with unresectable disease may also benefit from surgery in the form of maximal tumour debulking, combined with HIPEC.

Future directions in peritoneal malignancy

In recent years, there has been a significant increase internationally in the number of centres offering CRS HIPEC, with a corresponding increase in the number of patients undergoing surgical treatment for peritoneal malignancy. This development is to be welcomed and should act as an impetus for increased focus on improving outcomes in patients with peritoneal cancer. There is, however, also an onus on the peritoneal malignancy community to standardise approaches and generate robust data to support patient selection for surgery and document outcomes.

Patient selection for CRS HIPEC remains a crucial and challenging area. For certain conditions, such as PMP, the decision to proceed to surgery is often reasonably straightforward. For patients with CRC PM, on the other hand, the decision is often difficult. Current criteria are a useful means of identifying those patients who might benefit from surgery, however our knowledge of disease behaviour in this heterogenous group is still in its infancy. Improved understanding of the histopathological and molecular subtypes of both colorectal cancer and the corresponding peritoneal disease should in time allow us to better tailor treatment for patients with CRC PM and select those who are most likely to benefit from CRS, with or without HIPEC. It would also now seem timely to re-examine the relative merits of systemic chemotherapy and surgery (with or without HIPEC) in the management of CRC PM by repeating the original Dutch study using modern agents and current selection criteria.

The results of a number of randomised, controlled trials are eagerly awaited and have the potential to significantly influence practice, particularly for CRC PM. The full report from PRODIGE 7 is awaited and will likely lead to a more selected use of HIPEC in patients undergoing CRS for colorectal peritoneal metastases. Other randomised trials have examined the application of CRS HIPEC as a prophylactic intervention in patients at high risk of developing peritoneal metastases (eg, T4 right colon cancer). These studies have finished recruiting and results are awaited. The role of intensive systemic treatment aimed at down-staging patients with a large tumour burden with a view to making them candidates for surgery has also been examined and again, results are awaited.

The future may bring an expansion beyond the current established indications for CRS HIPEC. For example, recently-published randomised data has shown a survival benefit to CRS HIPEC for patients with stage III epithelial ovarian cancer. In this study, and unlike PRODIGE 7, the addition of (cisplatin-based) HIPEC to CRS was found to significantly improve survival when compared to CRS alone (median overall survival, 45.7 vs 33.9 months). Many of these and other issues will be debated at the 11th International Workshop on Peritoneal Surface Malignancy to be held in Paris later this year.

Consigning hepatitis C to history

By sa | Jun 20, 2018 | 0 Comments

The Hepatitis C Conference 2018, which was supported by Gilead, was held under the theme ‘Hidden Disease: The Future of Hepatitis C Treatment in Community and Primary Care’. The Irish College of General Practitioners (ICGP) convened a distinguished panel of national and international speakers to share their expertise and discuss treatment advances with a packed auditorium.

‘Hidden diseases’

The meeting was attended by Minister of State with Responsibility for Health Promotion and the National Drugs Strategy, Ms Catherine Byrne. She told the attendees that Ireland is seeing “the tip of the iceberg” in terms of treating “hidden diseases”. Ms Byrne also stressed the importance of treating hepatitis C in the community, based on the fact that “70 per cent of hep C sufferers acquire the virus by injecting drugs and often, these people do not engage with hospital services”.

The keynote address was delivered by Prof John Dillon, who spoke on the theme of  ‘Models of HCV Screening and Treatment: An Evidence-Based International Perspective’.

Prof Dillon, who is Professor of Hepatology and Gastroenterology at Dundee University, UK, provided an outline of the screening model in Dundee, which involves a flexible and creative approach. “There is no ‘one-size-fits-all’ approach to this; you have to choose the screening model that’s right for your area,” he told the Conference.

“At every step in a care pathway, you lose people [from treatment],” he explained, “so the less steps there are, the less people you lose.” He provided an overview of the WHO target to make hepatitis C a disease of the past by the year 2030 and explained that there are currently only eight nations “who are even close to being on track for that, and the UK and Ireland are not among those nations”.

He also showed figures from his area in Tayside that emphasised the need for early treatment to reduce a wide range of mortalities that result from hepatitis C.

Prof Dillon gave an overview of statistics to show dramatic improvements in screening efficiency and treatment outcomes: “If we can do it in our area, with our geography and resources, anyone can do it,” he said. “It’s about detailing your plans and then addressing how you actually implement them,” he concluded.

The next section of the conference was dedicated to the theme of ‘Epidemiology, Screening and Treatment — The Irish Context’ and heard from Ms Michele Tait, Manager of the National Hepatitis C Treatment Programme. Ms Tait delivered a presentation on ‘Update on Plans for HCV Treatment in Ireland for 2018’, and explained that there has been difficulty in obtaining hard, accurate data on the prevalence of the condition.

Ms Tait outlined the National Hepatitis C Strategy, which was published in 2012, noting that the treatments available now were not available at that time. Ms Tait added that a set of clinical treatment guidelines have been produced and the hope is to integrate treatment in other facilities outside the hospital setting.

She also pointed out that data protection legislation presents difficulties in terms of collating data but efforts are ongoing to build a full, national disease registry. More than 2,000 people have been successfully treated since 2015, she added.

Pilot programmes are in operation and meetings are being held with prison services representatives to expand care in that setting, said Ms Tait.

Point of care

The meeting also heard from Dr Margaret Bourke, GP Co-Ordinator in Addiction, CHO7, who addressed the meeting on the subject of the ‘HCV Community Treatment Pilot’ and described her “new vision for HCV treatment, which would involve “community-based general practice, central service and prisons, all linking to provide HCV treatment at the point of care”.

Speaking about stigma, Dr Bourke explained that in her practice, the term ‘liver nurse’ is used, rather than the title ‘hepatitis nurse’, as this carries less stigma from the patients’ point of view.

She told the Conference: “The WHO recommends reducing the pool of infection by treating localised areas to contain infection. With this in mind, we are now investigating the level of PCR-positive patients in three Dublin 8 clinics with a view to treating them at the Castle Street pilot site, possibly in a joint venture with their addiction treatment clinic.”  

The conference then heard from Prof Walter Cullen, Professor of Urban General Practice in University College Dublin, on the topic of ‘HCV Disease in Irish General Practice’. Prof Cullen noted that when GPs receive resources and support, there is a more than 2.5-fold increase in screening rates for HCV, as well as a significant increase in the numbers of patients referred to hospital for treatment. He also cited the current improved access to direct-acting antivirals and their advantages over older treatment regimens — but reiterated that stigma still exists around hepatitis C, which deters many patients from seeking treatment.

Dr Cullen also presented research to illustrate how a strong relationship between a patient and their healthcare provider improves treatment compliance and emphasised the importance of shared-care models in screening, prevention and treatment.

He explained that his team in UCD has been working with several hospitals in the Mater Hospital, Dublin, catchment area and a follow-up evaluation of 35 patients referred to hospital services is planned for spring 2018. “What we do know is that general practice has a major role to play in addressing hepatitis C,” said Prof Cullen, who also noted that nurse support is vital in ensuring that patients attend their appointments and comply with treatments.

“We need to resource primary care,” he said. “In the new GP contract, we need to include substance misuse in general as well as mental health and we need to find ways to support and incentivise GPs to systematically and routinely address these issues. These have been a ‘Cinderella aspect’ of general practice in the past.

“But we also need to resource secondary care and make sure that acute hospitals have more doctors, more nurses, more machines, more pharmacists and peer-support workers, all to support the patients who need assessments in those units.”

The meeting also heard from Dr Magdalena Harris, Associate Professor in the Sociology of Health at the London School of Hygiene and Tropical Medicine, UK, on the topic of ‘Peer Involvement in HCV Management: An International Perspective’. She stated: “As we have heard today, direct-acting antivirals can transform hepatitis C treatment access, primarily for the most marginalised groups, and there is an important role for primary care in that regard.”

She gave an overview of peer intervention programmes put in place in three drug treatment centres in the UK and also referred to the Australian model of care for those with HCV, whereby direct-acting antiviral therapy is fully reimbursable and there are no restrictions in terms of liver disease staging or substance misuse. This has resulted in the removal of many barriers to treatment for these marginalised groups in the community, she said.

The need for trust is heightened among very vulnerable patients, which is compounded by a “power imbalance” that occurs between the patient and doctor in a clinical setting. This is where peers can be instrumental, Dr Harris added.

She outlined a study comparing two models of peer involvement — a community-controlled model, and a service-generated model.

A broad conclusion was made that larger numbers of patients could be engaged by the service-generated model, but the community-based model was shown to create strong levels of trust between the peer and the patient.

HCV/UK/18-05/MA/1723

Date of preparation: May 2018

Irish Neurological Association Annual Meeting 2018

By sa | Jun 20, 2018 | 0 Comments

Repeat electroencephalography (EEGs) are overused and uncommonly result in a change in electroclinical diagnosis, the Irish Neurological Association annual meeting heard. Speaking on behalf of members of the Department of Clinical Neurophysiology and Neurology at Our Lady’s Children’s Hospital, Crumlin, Ms Aisling McCarthy presented a study titled  ‘Understanding the Value of Repeat EEG Testing in Children’.

Ms McCarthy, who was soon to graduate from her medical undergraduate course, explained that the research was a prospective, five-year outpatient study running from 2012 to 2017. The study analysed 4,162 consecutive outpatient EEGs and found that sleep was achieved in more than 93 per cent of cases and repeat tests were identified.

””

Ms Aisling McCarthy

“The results of this study can be considered based on departmental activity and patient experience,” she told members of the audience.

Ms McCarthy added that one-in-four EEG studies carried out was a duplicate study and one-in-six patients attending for an EEG will have multiple EEG studies.

The primary role of EEG in children is the investigation of seizures, where it can assist in both the diagnosis and classification of different epileptic syndromes.

Key observations

While EEG is useful in assessing childhood seizures, Ms McCarthy told the meeting that the team identified a number of key observations during their research. There is a high volume of requests for repeat EEGs, but most do not result in material diagnostic change or treatment modification. Furthermore, most of these repeat tests are requested without specifying any particular question. Indications for repeating routine EEGs in children are also not clearly defined in international guidelines.

“This can lead to overuse of the resource, wasted time for the patient and parent and health professionals involved. And most importantly, delayed access to EEG for those who need it more urgently,” she said.

While NICE guidelines recommend that early EEG be performed within six weeks of referral, the majority of centres in Ireland struggle to meet this recommendation.

“Seeing that there is rarely a diagnostic change on a repeat EEG, it is important to question the utility of repeat investigation, she added.

Citing Camfield et al’s 2000 study ‘How Often Does Routine Paediatric EEG Have an Important Unexpected Result?’, she said that if a test’s result is predictable, then the test may be unnecessary. She also highlighted an example of a repeat request where the EEG was asked to provide information that belongs in the collateral history.

But she stressed it is important to acknowledge that repeating an EEG is justifiable in certain cases where a change in the underlying diagnosis is not expected.

The aim of the study was to quantify the practice and pattern of repeat EEG requests and to analyse the outcomes of follow-up EEGs in relation to prior EEG study. The primary outcome measure was to identify how often a significant outcome change takes place.

“This was defined as a shift from an abnormal code or diagnosis to normal and vice-versa. We tried to identify factors that might predict when repeat EEG is most likely to produce change and thus would be of most clinical value,” she said. The team also tried to identify factors that might predict when repeat EEG is more likely to produce change.

Repeated studies were identified and these EEGs were outcome-coded by a single consultant reporter in a nine-point scheme that identified normal studies, non-epileptiform and epileptiform abnormal studies, and EEGs of uncertain clinical significance.

Correlations

“A further subdivision of this scale identified detailed electro-clinical correlations, including infantile spasm,” she said. “If you are working in the neurophysiology lab, one-in-four of the EEGs you perform are duplicates. If you are a patient in the waiting room, you have a one-in-six chance of returning for a repeat exam.

“If you do return for a further study, 85 per cent of you will have one repeat study, or two in total.”

The most frequent interval for the repeated EEG is within the first six months of the previous one. The median interval is 12 months and the mean is 15 months.

In the majority of cases, the outcomes do not change with both focal and generalised epilepsy. She also highlighted the low rate of normalisation for juvenile myoclonic epilepsy (JME).

“There is an important clinical point here. Transient EEG normalisation can occur in JME; however, JME is regarded as a life-long or enduring seizure liability. So EEG normalisation is materially irrelevant, because it does not and should not alter the way epilepsy is managed in childhood.”

In terms of the normal studies (‘normal with certainty’, the other being ‘normal in all probability’), the key finding was that “definitely normal EEGs are highly likely to stay the same in repeat testing, whereas EEGs which showed a minor change but were otherwise within normal limits are more likely to become abnormal,” Ms McCarthy said. “If an EEG that is within normal limits becomes abnormal, it is most likely to show an epileptiform abnormality.”

Duplicated EEGs

In terms of the overall value of repeating an outpatient EEG, the study looked at 555 duplicated EEGs. Only 15 per cent resulted in a consecutive change from normal to abnormal code, or vice-versa. There was an 11 per cent change from normal to abnormal and a 16 per cent change from abnormal to normal

“Based on this information, is it more helpful to repeat an EEG if the initial EEG is normal or abnormal?” she asked the audience. “It is more helpful to repeat a normal EEG, as chi square analysis shows that a higher proportion of normal EEGs become abnormal. In fact, a normal EEG is twice as likely to change to abnormal than vice-versa.”

Of the normal EEGs that become abnormal, the most common change is to an epileptiform abnormality.

“This provides justification for repeating EEG when suspicion of epilepsy is high, but the first EEG is normal.”

The overall rate of normalisation of repeat EEG in the time frame of this study is modest, at 24 per cent; broadly similar rates of normalisation are seen across the epilepsy groups, although the rates of normalisation are higher for focal rather than generalised epilepsy, as expected.

“We were surprised by the relatively high rates of normalisation of generalised infantile epilepsy, at 13 per cent. In general, these children have severe brain injuries and severe epilepsy, which persists into later childhood.”

Only one-in-five patients with a defined epilepsy syndrome normalised, whereas two-in-five with non-epileptiform or unclassifiable epileptiform abnormalities showed normalisation on EEG, the study found.

‘Significant’

“This is significant as it calls into question the utility of the repeat EEGs in many of these defined epilepsy syndromes. If an EEG is unlikely to change, then it is unlikely to guide management or provide new information. Again, if the test is predictable, then the test may be unnecessary.”

The study also found that 38 per cent of non-epileptiform or unclassifiable epileptic abnormalities normalise, whereas only 20 per cent of specified epileptic abnormalities normalise.

The study concluded that EEG is a valuable resource in the investigation of childhood epilepsy but guidelines on indications for repeat EEG are lacking, which is contributing to EEG overuse.

It is more useful to repeat a normal EEG than an abnormal EEG, especially when the suspicion is high. Abnormal EEGs normalise less frequently than normal EEGs, with the lowest rates of normalisation seen in infantile spasm and JME.

“Based on this study, we found more utility in repeating a normal EEG when the suspicion of epilepsy is high, compared to an abnormal EEG, as a normal EEG is twice as likely to change to abnormal than vice-versa,” Ms McCarthy said.

Take-home message

“The take-home message of this study is, when requesting EEG, recognise that the rates of significant change are low and that you should have a clear clinical question to be answered.”

She hoped that the study would lead to more research on the indications for repeat EEGs on children and contribute to the development of guidelines on appropriate EEG referral.

During the questions and answers section, it was asked why repeat tests for abnormal results were being ordered.

“A lot of the time, people are referring in to show that the EEG is normal if the patient is seizure-free for two years and off medication, and that shouldn’t happen.  And that’s why we think there needs to be guidelines on this to stop that kind of inappropriate referral burdening the service.”

It was also mentioned during the Q&A that patients with IGE [idiopathic generalised epilepsy] and whose symptoms may be subtle could be a reason to repeat an EEG in someone where the diagnosis is established.

Irish College of Ophthalmologists 2018

By sa | Jun 5, 2018 | 0 Comments

Biologics an exciting new option in uveitis

Rheumatology and ophthalmology should improve their interdisciplinary working relationships to improve patient outcomes for those with crossover conditions, the Irish College of Ophthalmologists (ICO) 2018 Annual Conference heard.

Speaking during the dedicated uveitis symposium was Dr Millicent Stone, a Consultant Rheumatologist in the Department of Ophthalmology, Guys and St Thomas Hospital, UK, who was recruited in 2014 to create a programme to support patients with inflammatory eye diseases who require immunosuppressant drugs, the first of its kind in the UK.

Not only may uveitis lead to loss of sight, it may be associated with loss of life because of underlying life-threatening systemic diseases that drive the inflammation in the eye, Dr Stone explained. 

She noted that biologic agents have revolutionised the care of rheumatoloid conditions such as rheumatoid arthritis, ankylosing spondylitis and Behcet’s disease since their introduction to clinical care over two decades ago.

The treatment paradigm and approach to management of inflammatory eye diseases is now undergoing “a revolutionary change” because of the recent approval of adalimumab, an anti-TNF for use in adult- and childhood-onset uveitis, Dr Stone said.

She outlined a number of case examples where systemic disease was an important driver behind sight-threatening inflammatory eye disease and how biologic agents may help dramatically.

“Gone are the days, for instance, when our rheumatoid patients end up with a life in a wheelchair. They can live full, normal, healthy, productive lives when these drugs are used in the right context. The biologic drugs achieve this for our patients by reducing disease activity, preventing damage and improving quality of life, and now perhaps gone will be the days when people lose their sight from uveitis.”

She also discussed the benefits and learning points for ophthalmologists when setting-up their own biologic services, particularly rapid access to services like rheumatology, who are familiar with dealing with complex cases and potentially toxic drugs.

“Together with new drugs, novel technologies and a more effective multidisciplinary way of working, we can all greatly enhance how we manage our uveitis patients with systemic disease and improve their outcomes,” she said.

Speaking to the Medical Independent (MI), Dr Stone said: “As a rheumatologist, make sure you ask the patient if they have any visual problem or any blurred vision, or does the light affect their eyes. As an ophthalmologist, it is always worthwhile asking them about back pain.”

Dr Stone carried out a survey a number of years ago on 300-plus ophthalmology patients to figure out if they had inflammatory back pain, with a useful questionnaire that could help trigger earlier referral.

“So awareness is the key component here and thinking about associated diagnosis and being willing to refer onwards and develop good working relationships with each other, ” she told MI.

Uveitis third-leading cause of blindness in the modern world

Uveitis is the third-leading cause of blindness in the modern world, with a disproportionate socioeconomic impact, as it primarily affects the working age population, the 2018 ICO Annual Conference heard.

Dr Dara Kilmartin, Consultant Ophthalmologist, Royal Victoria Eye and Ear Hospital, and immediate past Honorary Secretary of the International Uveitis Study Group, the oldest international society of uveitis specialists, chaired a dedicated session on uveitis and gave a comprehensive talk on the latest management approaches to the disease.

Once diagnosed (after answering the infectious versus not infectious or masquerade questions), uveitis treatment usually involves some form of local or systemic therapy, he said.

“We’ve been using oral steroids now for over 60 years and they are the main way of controlling sight-threatening anterior uveitis. For about 30 years, we’ve been using systemic immunosuppressive therapy (IST) of all classes,” Dr Kilmartin stated. He noted that there has been a move from using cyclosporine to tacrolimus, while intravitreal IST like methotrexate or sirolimus are promising, but there is a fear of alkylating agents due to their DNA-altering effects, and they are used in a stepladder approach to minimise the side-effects.

As IST can have significant toxic side-effects, it is hoped that the advent of biologic therapies and more targeted treatment will mean less risk for patients, though real-world efficacy and cost are current issues.

Local intravitreal therapy has many advantages, including rapid and targeted delivery and avoidance of systemic side-effects, but is restricted to uniocular disease or marked asymmetry, which is uncommon, he noted, while intraocular implants do not have superior visual outcomes versus systemic treatment and have more adverse side-effects, according to the latest studies.

Dr Kilmartin also highlighted the value of therapeutic vitrectomy, particular in paediatric patients, for suitable uveitis cases.

The uveitis session also heard how a highly malignant but rare form of lymphoma can be mistakenly diagnosed as uveitis, representing a major diagnostic and therapeutic challenge.

Prof Conor Murphy, Professor of Ophthalmology, RCSI, spoke about primary intraocular lymphoma, a very rare intraocular malignancy that masquerades as autoimmune uveitis, and he outlined a detailed case study, which highlighted the difficulty of diagnosing and treating this disease.

This form of lymphoma represents a significant diagnostic challenge for the ophthalmologist and pathologist, as it requires cytological analysis of ocular fluid samples of limited size and cellularity, he explained. A lack of prospective studies to identify optimum therapy adds further complexity to this disease, which frequently spreads to the central nervous system (CNS), giving it a poor long-term prognosis, which is not helped by delays in diagnosis, Prof Murphy added.

Notable symptoms to watch out for include behavioural and cognitive changes and a contrast MRI should be carried out, he said. Once diagnosed, a key management goal is eradication of the reservoir of malignant cells in the eye that can lead to fatal CNS dissemination and to preserve vision.  

Treatment options include orbital and ocular radiotherapy, intravitreal methotrexate or rituximab, and high-dose chemotherapy with autologous stem cell Tx, but efficacy versus toxicity must be carefully considered and multidisciplinary team management is vital, “although contrasting views exist, even among experts,” Prof Murphy noted.

Cataract surgery best value for quality-of-life

Cataract surgery is the best surgical value for improving quality-of-life for patients, but this so-called ‘simple operation’ is down to extensive training, experience and teamwork, according to the immediate past-President of the American Academy of Ophthalmology.

Dr Cynthia Bradford, Professor of Ophthalmology at the Dean A McGee Eye Institute/Department of Ophthalmology at the University of Oklahoma Health Sciences Centre gave the annual Mooney Lecture at this year’s 2018 ICO Annual Conference, on the challenges of cataract surgery.

“There have been remarkable advances in cataract surgery and the public perception is often that the procedure itself is ‘nothing’.  Do we as surgeons trivialise the procedure or are ophthalmologists victims of their own success?” Dr Bradford asked.

””

Dr Cynthia Bradford

She noted that making cataract surgery so successful requires years of training, likening the process to athletic training.

In contrast to professional athletes, however, every surgery is expected to be a ‘win’. In order to have a win, the surgeon must understand the patient’s needs, what is possible to achieve and offer the spectrum of options available to achieve their goals, Dr Bradford outlined.

There are a multitude of possible complicating factors, with some patients having several complex problems. It takes teamwork with operating staff and anaesthesia to give every patient a win, she commented, showing the audience video clips of what surgical complications can occur.

Dr Bradford also stressed the importance of listening to the patient and finding out what they want the outcome of their eye surgery to be.

“It is important to know all about the patient. We have to know what really bothers the patient about their vision. In other words, if they have surgery, what do they want improved?”

Cataracts were a hot topic at the conference, following the revelation that the average wait for public cataract surgery across the country is now 28 months — and up to five years in some parts of the country — according to a survey carried out by the Association of Optometrists (AOI) and released on the opening day of the ICO conference.

The ICO told the Medical Independent (MI) that it has been working and collaborating with the HSE to “provide our medical expertise and proposed solutions required to tackle the cataract waiting times for patients. There needs to be an investment in ophthalmology services and an increase in theatre capacity to facilitate the patient numbers and demands for this procedure.”

Currently, approximately 12,000 cataract operations are carried out by the HSE annually; nowhere near enough to meet increasing demand.

Speaking to MI, HSE Clinical Lead for Ophthalmology Prof William Power said that dedicated cataract theatres are key to helping reduce cataract waiting lists.

He confirmed that a new dedicated cataract theatre is due to open in Nenagh during the summer, where ophthalmic surgeons from Limerick will rotate on a daily basis, with a new modular, dedicated cataract theatre also planned for Waterford.

These dedicated theatres should reduce cataract operation waiting times in the mid west and south east, which have particularly long waiting lists, he said.

Prof Power, an ophthalmic surgeon in the Royal Victoria Eye and Ear Hospital (RVEEH), Dublin, and former President of the ICO, said surgeons can usually perform about one cataract procedure every 30 minutes in a dedicated theatre. The RVEEH opened one such theatre last year, which it had to fund itself, and now also treats public cataract patients waiting very long times through NTPF funding.

According to the latest NTPF public hospital waiting list figures, there were 11,070 people waiting for an ophthalmology inpatient procedure, while the outpatient waiting list was 40,928 at the end of April.

This does not capture the community waiting lists, where there are nearly another 30,000 wait listed, the ICO noted.

ICO frustrated at lack of roll-out of Primary Care Eye Services Review plan

The ICO has called on the HSE and Department of Health to expedite the roll-out of the Primary Care Eye Services Review Group Report.

Under the review, published last June after a number of delays, each HSE Community Health Organisation (CHO) will have a community ophthalmic physician-led primary care eye team, with dedicated premises and equipment, and staffed with optometrists, orthoptists, nurses and ophthalmic technicians.

New revenue funding of approximately €23 million is required to implement the recommendations of the report, which would see approximately 60 per cent of the current adult and paediatric outpatient ophthalmology work transition to the community. However, despite positive praise for the review by Minister for Health Simon Harris, only €1 million in extra funding was allocated to the roll-out of the report last year, with no extra funding given this year.

“It is of huge frustration to the College that despite the public approval by the Minister for Health last year to the implementation of the recommendations contained in the Primary Care Eye Services Review Group Report, the funding required has not been forthcoming,” said the ICO.

The College called on the HSE and the Minister “to ensure implementation of this approved care pathway by all stakeholders gets underway without further delay in the interest of patient care and ensuring patients are not losing vision unnecessarily. The ICO has made the proposed solutions… ”

In terms of investment, primary care centres are in situ around the country and require just the primary care eye teams to be put in place, the College pointed out.

HSE Clinical Lead for Ophthalmology Prof William Power also expressed disappointment that the plan did not receive any extra funding for 2018, after only receiving €1 million in 2017. He called on the HSE to prioritise rolling-out the plan, adding that dedicated cataract theatres are also key to reducing waiting lists.

“Ophthalmology is a small specialty but we have a huge number of patients. After death, patients fear blindness most,” ICO President Dr Alison Blake told MI at the ICO 2018 Annual Conference in Kilkenny, calling for the HSE to prioritise eye care and fund the roll-out of the plan.

Responding to questions from MI about the issue, HSE National Director of Quality Improvement Dr Philip Crowley said he hoped the plan would be implemented, and there had been some progress but “I will be asking why it is stalling”.

Burnout and uncertainty on workforce plans an issue for ophthalmologists

Risk of burnout, uncertainty about what the future holds, and the need for more investment in ophthalmology were the focus of a very lively session on the future of the specialty at this year’s ICO Annual Conference in Kilkenny.

Dr Cynthia Bradford, Professor of Ophthalmology, Dean McGee Eye Institute, Department of Ophthalmology, University of Oklahoma Health Sciences Centre, US, gave a sobering presentation on the impact and reasons for doctor burnout. Burnout can lead to depression and worse; around 400 doctors a year die by suicide in the US, she said.

Factors leading to medical burnout include lack of control over working conditions and decision-making, excessive workload pressures, chaotic and inefficient work environments, and onerous administration tasks, Dr Bradford outlined. The most susceptible doctors are dedicated, conscientious, responsible, motivated and often idealistic with perfectionist qualities, she said.

Burnout not only impacts doctors, it also impacts patients negatively in relation to the quality of care they receive, and leads to higher healthcare costs. Primary care doctors are worst affected by burnout in the US, Dr Bradford reported.

Concluding, she said a major culture change is needed to help better support doctors, which would include returning trust to doctors, with less-onerous regulation and administrative processes, and “letting them concentrate on the work only they can do”.

Some of Dr Bradford’s points were echoed by ICO Dean of Education and Ophthalmic Surgeon Miss Yvonne Delaney during her presentation on educating the doctors of tomorrow and building resilience.

“People love their job — they just want to be able to do it,” Miss Delaney told delegates. She discussed how training and performance assessments are being improved to be less about box-ticking, and made more reflective and thorough in relation to competence assessment.

Simulation is going to be an increasing feature of medical and surgical training in the future, including ophthalmology, but it has to be carefully developed and its value reviewed and assessed, as people can react very differently in real-life situations, she noted.

Miss Delaney also highlighted the importance of communication in medicine. Around 50-to-65 per cent of complaints against doctors are related to communication errors, and 10 per cent of health budgets are spent on error/negligence.

During his presentation in this session, HSE National Director of Quality Improvement Dr Philip Crowley noted that Ireland has one of the lowest numbers of ophthalmologists per head of population compared to other Western countries.

He acknowledged that ophthalmology waiting lists are high and more staff are needed but added that health funding is finite, so we must try and learn from those with less resources about how they maximise services and outcomes.

””

Dr Philip Crowley, HSE

Dr Crowley stressed it is vital that healthcare staff are involved in health service decision-making and that roles for clinical leaders are developed and supported. “While it is important to learn from our mistakes, we must also learn from excellence,” he commented.

UK Royal College of Ophthalmologists (RCO) President Mr Michael Burdon also spoke during this session and called for increased collaboration between the two countries, saying that the UK currently has similar issues regarding ophthalmology waiting lists, staff shortages and a lack of political interest in eye care.

The final speaker in this session was Dr Michael O’Rourke, SpR in Ophthalmology at the Royal Victoria Eye and Ear Hospital, Dublin.

He noted that while it is a very exciting time for ophthalmology in terms of ongoing treatment and diagnostic advances, being able to meet increasing patient expectations and needs is a challenge. Excessive HSE ophthalmology waiting lists, inadequate staffing and uncertainty over contracts, career pathways and the implementation of the Primary Care Eye Services Review Report must be addressed, he said, adding that the specialty must advocate for its patients, and the HSE must realise it is not all about money, but also about different ways of doing things.

Chairing the session, ICO President Dr Alison Blake said the speakers gave much food for thought and while there are many challenges, the future of ophthalmology is bright.

“I think, as Philip [Crowley] said, and as I commented, there will never be enough ‘health euro’. We have to find a way to make the most of what we have, to do the best for the most people. That is not easy,” she told the Medical Independent (MI).

100 year anniversary celebrated by ICO

The three-day ICO Annual Conference took place in Kilkenny from 16-18 May. Over 200 ophthalmologists from across the country gathered for the three-day meeting to hear the latest clinical and scientific updates and developments in the specialty from national and international eye experts.

2018 marks the 100th anniversary of the founding of the Irish Ophthalmological Society, the forerunner of the ICO, and the centenary and what the next 100 years will bring was a key theme of this year’s Annual Conference.

The College said the “centenary provided an opportune time for the College to reflect on how practice and training, both within the specialty and in the wider context of healthcare delivery, has evolved to where we are now and most importantly, to consider what the direction of travel will be over the coming years”.

“During the past 100 years, there have been many changes in ophthalmology, in Ireland and in Irish ophthalmology. This does not stop now; one of the qualities we have as doctors is how we adapt to change and incorporate it in our practice and care of patients, not impulsively, but with evidence and experience,” ICO President Dr Alison Blake said during her opening address to the conference.

Speaking to the Medical Independent (MI) about the challenges facing the specialty, including frustration at the stalled roll-out of the Primary Care Eye Services Review Report, Dr Blake also raised concern about treatment waiting times for aged-related macular degeneration (AMD) patients, who have to be injected with anti-VEGF agents promptly and at regular intervals to maximise vision outcomes.

Acknowledging the costs of anti-VEGF agents, which are in increasing demand, Dr Blake said how Ireland pays for expensive medicines has to be examined, and suggested negotiating European-wide deals could be a potential option to reduce costs.

The impact of Brexit on healthcare is also an issue that is being considered by the ICO. The UK RCO has reached out to the ICO to talk about working more closely together, and ensure future joint recognition of exams and training with that process now ongoing, Dr Blake said, as well as ensuring that the UK remains an option for employment for Irish doctors. 

The research winners were as follows:

Sir William Wilde Medal —Best Poster 2018

‘Lamina Cribrosa Cell Bioenergetics in Glaucoma: Role of Glycolysis and Glutaminolysis.’

Dr Diamaid Hickey

Barbara Know Medal — Best Paper 2018

‘Predisposing Risk factors, Clinical and Microbiological Characteristics of Moraxella Keratitis.’

Dr Terence MacSwiney

When to believe what you’re seeing — unusual visual symptoms

Unexplained, unusual and unexpected visual symptoms were the focus of a fascinating session dedicated to neuro-ophthalmology, chaired by Miss Patricia Logan, Consultant Ophthalmic Surgeon specialising in Neuro-ophthalmology at Beaumont Hospital, Dublin, at this year’s ICO Annual Conference.

Eminent Irish-born US speaker Prof Patrick Lavin, Professor of Neurology and Neurosciences and Vanderbilt Headache Tennessee, US, gave three presentations at the conference.

After delivering an interactive neuro-ophthalmology workshop with a number of useful video case studies, Prof Lavin’s next talk focused on patients who appear to be faking their disease but have real problems that may be overlooked because of the rarity or subtlety of the disorders, complicated by behavioural characteristics that might be misinterpreted as simulating real disease or exaggeration of minor problems for pecuniary gain.

His final talk focused on unusual visual symptoms that can be normal but occasionally herald serious disease. These included entopic phenomenon such as benign floaters, more serious floaters, and migraine aura, which can be present in 25 per cent of migraines and is not harmful.

Prof Lavin discussed visual conditions like palinopsia, the persistent recurrence of a visual image after the stimulus has been removed which can be brought on by certain medications, and synaesthesia, a perceptual phenomenon in which stimulation of one sensory or cognitive pathway leads to automatic, involuntary experiences in a second sensory or cognitive pathway, eg, words and numbers can have certain colours for those with the condition.

While visual hallucinations can be caused by drug and alcohol abuse, some visual symptoms may be the manifestation of various serious health issues like stroke, brain tumours or seizures (epilepsy) or certain psychiatric disorders, he explained.

Speaking to the Medical Independent (MI), Prof Lavin said the key to trying to determine the cause of any unusual visual symptoms is taking a thorough patient history and symptom review.

“Listen to your patient. They are trying to tell you what’s wrong and it up to you to interpret the clues. Examine the patient based on their complaint, and, generally speaking, don’t get side-tracked by other issues, unless they’re relevant. If you don’t know what is wrong, don’t be afraid to ask for help.”

Also speaking during this session was Mr Michael Burdon, Consultant Ophthalmologist, Queen Elizabeth Hospital, Birmingham, who discussed how a few of his cases with unusual visual symptoms turned out to be Creutzfeldt-Jacob Disease (CJD).

Cortical blindness, dysmetria and hallucinations are among the visual issues that can signal a potential diagnosis of this very rare but devastating disease.

“I also noticed very distinct anxiety in these cases. Patients experiencing visual loss are anxious, or depressed or worried, but this acute anxiety of  ‘I can’t see, I can’t see’; that repetitive concern on their vision I’ve never seen in any other neurological disease,” Mr Burdon told MI.

Another unusual visual issue he discussed was night-vision blindness caused by vitamin A deficiency, which can often occur in patients who have had bariatric surgery.

Also during the neuro-ophthalmology symposium there was an interesting paper study presented on ‘visual snow’, which was carried out by Dr Emer Doolin under Miss Logan’s supervision at Beaumont Hospital.

Although seldom recorded in the medical literature, visual snow can be distressing for patients and often lead to multiple unnecessary investigations and inappropriate treatments. Visual snow is syndromically consistent from one case to the next and this phenomenon is reported by young and healthy individuals, with neither ophthalmic nor neurological disease, said Dr Doolin.

Her study of eight patients confirmed that all had normal ocular examinations, normal neuroimaging, and normal electrophysiological studies.

The study concluded that patients could be reassured that the condition, although sometimes disabling, is benign, in the sense that it does not lead to visual loss. Special investigations may still be required for patient reassurance, but in this group of patients did not assist in the diagnosis, which must be made on a clinical basis, the study found.

The latest updates in genitourinary cancer from JFIGUCC 2018

By sa | May 24, 2018 | 0 Comments

Now in its fourth year, the John Fitzpatrick Irish Genitourinary Cancer Conference continues to attract an international faculty of leading multidisciplinary specialists across a range of specialties, from urology, medical and radiation oncology, to pathology, scientific and allied health professionals, all of whom are committed to delivering state-of-the-art care for the urological cancer patient.

The meeting is dedicated to Prof John M Fitzpatrick (1948-2014), Professor Emeritus of Surgery, University College Dublin, Consultant Urologist and Chair of the Department of Surgery at the Mater Misericordiae University Hospital, Dublin. He was an Irishman with a truly global reputation in urology and fondly remembered by his colleagues, at home and abroad, many of whom were delegates at the two-day meeting in the Aviva Stadium.

Initially a prostate cancer meeting, the scope was broadened last year to include all urological cancers and this format was continued once again, with faculty from Ireland, the UK, France, Spain, the US and Australia participating in the meeting.

Following a welcome address by Dr Jerome Coffey, Director of the National Cancer Control Programme, the first session on prostate cancer was opened by Prof David Gallagher, St James’s Hospital, Dublin, who provided an overview of the current state of genetic testing in genitourinary cancers in Ireland. While this area has witnessed considerable evolution, the challenge of direct consumer genetic testing poses potential problems in the future and there is clearly a need for regulation.

Dr Niall Corcoran, Royal Melbourne Hospital, Australia, both a urologist and research scientist, provided some emerging evidence from translational studies on the persistence of castration disease in high-risk prostate cancer.

Mr Rick Popert, Guy’s Hospital, London, challenged the 40-year-old dogma of obtaining prostate biopsies using the transrectal route and discussed the implementation of ambulatory day case transperineal prostate biopsy performed under local anaesthetic in Guy’s Hospital. This is an exciting advance in prostate cancer diagnostics and Mr Popert provided a very compelling argument that transperineal prostate biopsies improve detection of clinically-significant prostate cancer and a general anaesthetic is no longer a barrier to performing these biopsies.

Dr Thomas Keane, Medical University of South Carolina, Charleston, US, closed the session with a very engaging review of the current controversies in androgen-deprivation therapy, advocating that androgen deprivation in prostate cancer should be carefully tailored to a man’s cardiovascular risk. The risk of a cardiovascular event is highest in the first six months after commencing androgen deprivation and the use of luteinising hormone-releasing hormone (LHRH) antagonists have a better cardiovascular risk profile compared to LHRH agonists.

Bladder cancer

The second session focused on bladder cancer and was opened by Dr Nuria Malats, Spanish National Cancer Research Centre, Madrid, Spain, who provided some emerging data from the Spanish Bladder Cancer/EPICURO Study, of which she is a co-Principal Investigator. This is a hospital-based case-control study being conducted in 17 Spanish hospitals to evaluate clinical, environmental, molecular and genetic factors associated with bladder cancer. Data from this study suggests that asthma is associated with a decreased risk of bladder cancer, whereas low levels of vitamin D may be associated with an increased risk of bladder cancer.

Prof Shamim Khan discussed the development of the innovative robot-assisted radical cystectomy programme in Guy’s and St Thomas’s Hospital, London, advocating that this will become the standard of care in the future, whereas open radical cystectomy will be reserved for highly-selected patients unsuitable for robotic surgery. He argued that the robot is just another surgical tool and the surgeon is still the most important factor in these challenging and difficult surgeries.

Dr Andrea Apolo from the National Cancer Institute, Bethesda, US, provided an overview of some of the novel drugs for the treatment of locally-advanced and metastatic bladder cancer, which target PD-1/PD-L1 pathway, including atezolizumab, nivolumab, durvalumab and pembrolizumab. These novel ‘checkpoint’ inhibitors are an exciting development in the treatment of bladder cancer, an area that has seen relatively little novel drug development until recently.

The session closed with a summary from Prof Ray McDermott, St Vincent’s Hospital, Dublin, on the valuable contribution that Clinical Trials Ireland (CTI) has made in recruiting Irish patients with genitourinary cancers to a number of important landmark international clinical trials.

Day two

The second day of the conference opened with a further session on prostate cancer, with another outstanding talk from Dr Niall Corcoran, Royal Melbourne Hospital, Australia, on the genomic drivers of prostate cancer metastasis.

Ms Netty Kinsella, a uro-oncology nurse consultant from the Royal Marsden Hospital, London, discussed the development of a ‘pre-habilitation’ programme for men prior to radical prostatectomy. This novel programme uses patient-reported outcome measures pre- and post-operatively, blending patient seminars, telephone contact and multi-professional survivorship clinics at regular intervals to enable men to be transferred back to their GPs earlier following their surgery for prostate cancer.

Mr Jim Adshead, the Lister Hospital, Stevenage, Hertfordshire, UK, reviewed his experience and validation of the NeuroSAFE method of nerve-sparing during radical prostatectomy. This innovative method, developed at the Martini-Klinik in Hamburg, Germany, uses intra-operatively frozen section analysis of the prostate specimen to ensure negative surgical margins, while allowing the urologist to preserve the neurovascular bundle critical for post-operative erectile function without compromising the oncological outcome. Using this method, Mr Adshead has been able to achieve almost 80 per cent potency rates if bilateral nerve-sparing is performed. The session was closed with a very succinct and clear description of the more unusual subtypes of prostate cancer by a recognised leader in the field of urological pathology, Prof Jonathan Epstein, Johns Hopkins Hospital, Baltimore, US.

The plenary session of the meeting opened with Dr Darren Feldman, Memorial Sloan Kettering Cancer Centre, New York, US, outlining some of the many contemporary challenges in the management of testicular germ cell tumours, particularly relating to the salvage treatment of relapsed metastatic germ cell tumours.

Dr Bernard Escudier, Institut Gustave Roussy, Paris, France, gave an in-depth insight into the current and rapidly-evolving landscape of treatments for metastatic kidney cancer and in particular, discussed the emergence of the novel agents nivolumab and cabozantinib as second-line treatment.

Dr William Dahut, National Cancer Institute, Bethesda, US, outlined the contemporary role for immunotherapy in prostate cancer, proposing that chemotherapy and radiotherapy can synergise with immunotherapy in prostate cancer.

Keynote address

The keynote address of the plenary session was delivered by Prof Anthony Costello, Royal Melbourne Hospital, Australia, who vividly reviewed the surgical advances in performing radical prostatectomy over a 40-year period from the late 1970s, when men spent three weeks in hospital post-operatively having sustained a major blood loss with very poor functional outcomes, to the advent of contemporary robot-assisted surgery, with a 24-hour stay in surgery, minimal blood loss and excellent functional outcomes. Prof Costello eloquently debunked several prostatectomy surgical ‘gimmicks’ and techniques which have gained popularity without any solid evidence of benefit, including that performing pelvic node dissection in high-risk disease has no oncological benefit; nerve-sparing is not related to continence outcomes; posterior bladder-neck repair does not improve continence outcomes; and seminal vesicle tip-sparing does not affect functional outcomes. The advent of modern imaging techniques in prostate cancer, such as multi-parametric MRI and PSMA-PET, remain a challenge for the clinician to determine their role in current practice. Prof Costello challenged the premise that men with a ‘negative’ multi-parametric MRI prostate can safely avoid a prostate biopsy. He also proffered that PSMA-PET is a useful adjunct in both the pre-surgical setting and following biochemical recurrence prior to considering salvage radiotherapy or metastasis-directed therapy. He cautioned that metastasis-directed therapy should be performed in the context of a clinical trial and a multidisciplinary setting. Finally, Prof Costello advocated that the future of robotic surgery is dependent on urology residency programmes embracing the technology by harnessing simulation, virtual reality and emerging, cheaper robotic platforms.

Final session

The final session was opened by Dr Paul Kelly, Cork University Hospital, who recounted the varied, and at times very colourful, history of the isotope radium-223. Traditionally, the indications of radium-223 have centred on treating castration-resistant metastatic bone disease, however, there are now ongoing trials in Ireland using radium-223 in combination with enzalutamide.

Dr Chris Sweeney, Dana-Farber Cancer Institute, Boston, US, summarised the data from the many trials using androgen deprivation in combination with docetaxel or abiraterone in the setting of metastatic castration-sensitive prostate cancer. He concluded by providing rational advice on the many complex treatment choices now available for men with hormone-sensitive metastatic prostate cancer and which men may benefit most from chemotherapy.

Prof Epstein summarised the deficiencies with the current Gleason grading system for prostate cancer needle biopsies, which dates from the 1960s. He discussed the new, simplified system of five grades adopted by the World Health Organisation (WHO) in 2016, which he was instrumental in developing. This was developed based on a study of  over 20,000 prostate cancer cases treated with radical prostatectomy and  over 5,000 cases treated by radiotherapy. The new system distils the grades of prostate cancer down to five grades, each with a unique prognosis.

The final speaker of the session, Dr Alberto Bossi, Institut Gustave Roussy, Paris,  outlined the current evidence for utilising radiotherapy in advanced prostate cancer.

The meeting concluded with a lively panel discussion of some challenging genitourinary cancer cases provided by Mr Kilian Walsh, University Hospital Galway.

Once again, the meeting combined some impressive scientific and clinical insights on the latest advances in genitourinary cancer from an outstanding international faculty and is a wonderful, enduring tribute to the memory of Prof John Fitzpatrick.

Working towards the elimination of hepatitis C in Ireland

By sa | May 14, 2018 | 0 Comments

Nearly 30 years after the hepatitis C virus (HCV) was first discovered by scientists, we now have a cure — in fact, we have a few. Dubbed the ‘silent killer’ — it does not have any noticeable symptoms until the liver has been significantly damaged — many people do not even know they are infected. The next challenge for the National Hepatitis C Treatment Programme (NHCTP) is to find these infected people and offer them the cure and wipe out this deadly virus.

HCV is a major cause of liver disease worldwide, with an estimated 80 million people chronically infected. Tackling this issue, the World Health Assembly adopted the first Global Health Sector Strategy on Viral Hepatitis, 2016-2021 in 2016. This strategy highlights the critical role of universal health coverage and the targets of the strategy are aligned with those of the Sustainable Development Goals. The Strategy’s vision is eliminating viral hepatitis as a public health problem. This is encapsulated in the global targets of reducing new viral hepatitis infections by 90 per cent and reducing deaths due to viral hepatitis by 65 per cent by 2030. The World Health Organisation (WHO) European region adopted the first ever Action Plan for Viral Hepatitis in September 2016. The Action Plan follows the 2016 WHO Global Health Sector Strategy on Viral Hepatitis. It addresses viral hepatitis as a public health threat and paves the way towards its elimination from the European region by 2030.

The current estimate of HCV prevalence in Ireland is somewhere in the region of 20,000-30,000 persons. At the end of 2017, a total of 14,704 cases of HCV were notified to the Health Protection Surveillance Centre (HPSC) since it became a notifiable disease in 2004.

Programme background

The HSE’s NHCTP was established in 2015, following a key recommendation from the 2014 Department of Health (DoH) report, A Public Health Plan for the Pharmaceutical Treatment of Hepatitis C. The Programme is a multi-annual public health plan, which aims to provide treatment across a range of healthcare settings to all persons living with HCV in Ireland. The programme’s ultimate goal is to make HCV a rare disease in Ireland by 2026. 

This goal is now within grasp, as transformative therapeutic drug regimens become available for HCV. Advancements in therapeutic treatments for HCV have allowed patients to be successfully treated and fully cured from the blood-borne virus using a range of direct-acting antiviral medicines (DAAs) and therefore, making it a rare disease in Ireland is a reality.

There are numerous challenges facing the Programme that persist, despite the introduction of all-oral therapies. People at risk of contracting HCV are often the most vulnerable and hard to reach in society. High-risk groups can cover populations from a wide range of backgrounds. The Programme is currently rolling out a new model to integrate screening and treatment in the community setting, to specifically target populations that have a high risk of infection, in a number of pilot sites based within the HSE addiction services. The Programme also aims to treat significantly more patients during 2018 in the acute hospital setting.

Progress 

Prof Aiden McCormick, Clinical Lead for the NHCTP, reports that in the two years since the formal establishment of the National Programme, a lot of progress has been made.

Plans for 2018 include the further development of community-based HCV treatment programmes and extending treatment to greater numbers of patients generally. 

Over 2,500 patients have been commenced on treatment since 2015 using DAAs, beginning with those most in critical need. All patients with haemophilia who were infected with HCV through contaminated blood products have been offered treatment and since the end of 2016, HCV has been eradicated in this community. All patients infected with HCV through contaminated blood transfusions and other blood products such as anti-D immunoglobulin have been offered treatment since the end of 2017, with over 95 per cent rates of cure within this population.

Treatment for HCV using DAA medicines has been extended to paediatric patients through the Rainbow Clinic in Our Lady’s Children’s Hospital, Crumlin, and the Children’s University Hospital in Temple Street, Dublin.

Criteria for access to treatment have been expanded so that clinicians can prioritise patients for treatment based on a number of factors and not solely on disease severity. A treatment as prevention (TasP) approach has been endorsed by the NHCTP Advisory Group (PAG), which allows clinicians to treat infection and reduce the risk of onward transmission, in addition to treating disease.

The PAG is the Programme’s oversight group, whose role is to advise strategically in relation to the implementation of the multi-annual treatment plan and has representation across a number of specialist areas, including public health, patient advocacy, research, clinicians and service planners.

The NHCTP CAG, which is chaired by Prof McCormick and includes representation from all treatment sites across a number of disciplines, meets monthly and actively advises the Programme on issues such as clinical treatment guidelines, prioritisation criteria, appropriate drug regimens, and models of care in the context of international best practice. Treatment sites are all working to a national set of treatment guidelines, which support equity of access for patients, regardless of where the treatment is provided.

The Programme has worked extensively to achieve improved commercial terms in the costs of the DAAs and is in the final stages of agreeing commercial terms with suppliers for 2018, following a public procurement exercise. This process, along with other drug procurement processes in 2016 and 2017, has allowed expanded access to treatment for greater numbers of patients and the Programme hopes that the numbers of patients accessing treatment can continue to rise in the coming years.

Further treatment access

In order to continue growing access to treatment for patients and work towards eliminating HCV in Ireland, the Programme has undertaken to concentrate on two particular areas in 2018.

Firstly, the Programme intends developing the extension of HCV treatment away from the traditional hospital-based model (where appropriate) and integrating it into community-based healthcare.

Given that a significant proportion of those infected with HCV acquired their infection through current or former injecting drug use, the Programme has been working initially with opiate substitution therapy (OST) clinics within the HSE addiction services to identify patients who could be provided with their treatment for HCV in the same place as their OST clinic. 

A model for HCV treatment in the community setting has been developed by a steering group, reporting to the PAG, and two pilot treatment sites commenced in Q2 and Q3 2017 where patients infected with HCV and who are engaged in OST programmes have been commenced on treatment. The sites are based in the National Drug Treatment Centre in Trinity Court and Castle Street Clinic in Dublin 8. Over 40 patients have been commenced on treatment across the two sites, with further patients being commenced each week.

While a full evaluation of the feasibility, acceptability and sustainability of these pilot programmes has yet to be carried out, initial outcomes from these programmes are extremely positive, with each patient engaging fully with their treatment and for those who have completed their treatment, they have each received a sustained virological response (SVR).

A third community treatment site is due to commence during May 2018 in Patrick Street Clinic in Dun Laoghaire and plans for further similar treatment sites within the community setting are being considered by the Programme. Additionally, the Programme is hoping to begin looking at GP prescribing within the community setting outside of OST clinics and how it might work with community pharmacies, similar to work already underway in other countries, such as Scotland and Australia.

Secondly, the Programme is looking at ways in which patients can be identified for treatment. It is estimated that at least 50-to-60 per cent of the potential number of people in Ireland with HCV are not aware of their diagnosis and so therefore, in order for the Programme to achieve its aim of making HCV a rare disease by 2026, focus needs to turn to identifying the population and case-finding.

Globally, the availability of DAAs has shifted the focus towards elimination of HCV. The WHO has stated that national testing policies, in addition to increased screening, are essential so that the goal of elimination can be reached.

A set of National Screening Guidelines for Hepatitis C were developed by the HPSC and the National Centre for Clinical Effectiveness of the Department of Health and published in 2017, and their implementation will be critical to the successful implementation of the National Programme.

So where are we with the roll-out of the NHCTP?

When the NHCTP was established in 2016, one of the first tasks was to outline a plan for rolling-out the programme over the coming years, with the ultimate objective of making HCV a rare disease in Ireland by 2026. The Programme has achieved many of its objectives planned for 2016-2017 and has commenced the second major phase of the Programme, which will see an extension of treatment availability within the community setting through a number of pilot sites based within the HSE addiction services. The NHCTP also aims to treat significantly more patients during 2018 in the acute hospital setting.

Making HCV a rare disease in Ireland by 2026 — are we on track?

The Centre for Disease Analysis (CDA) is an international public health body with expertise in epidemiology and disease modelling. The CDA has conducted research internationally in relation to HCV elimination strategies and has provided data/evidence-based models to the EU as part of its support of the WHO Global Hepatitis Strategy. Data from Ireland relating to HCV prevalence, rates of treatment, screening, etc, have been incorporated into the CDA studies, which have allowed an assessment of the potential impact of an interventional strategy for HCV treatment in Ireland to be developed. The methodology used was a combination of analysis of published data, experts’ input, review of unpublished data, and modelling. The CDA recommended a treatment interventional strategy for Ireland (and internationally) that supports the implementation of the Department of Health model, including:

Continued treatment using DAAs that have a significantly higher rate of patients achieving SVR or cure.

Increase in numbers of patients being treated to achieve >60 per cent reduction in liver-related deaths and 90 per cent reductions in total and new infections.

Expansion of screening programmes to identify all infected patients.

Expansion of treatment criteria to treat all infected patients, ie, treatment as prevention and treatment to elimination.

CDA data (for Ireland) indicates that Ireland is on the road to achieving elimination of hepatitis C by 2026. This is an extremely positive development (http://cdafound.org/polaris/).

More information

More information on the NHCTP can be found at www.hse.ie/hepc or by contacting NHCTP Manager Ms Michele Tait at michele.tait@hse.ie.

Personality and its disorder

By sa | May 4, 2018 | 0 Comments

As a psychiatrist, when I am invited to lecture non-psychiatric medical colleagues, the topic that I get asked about more than others is that of personality disorders. These conditions, which are not rare (4-to-15 per cent of the general population and 25 per cent of those attending general practice), cause so much distress and are also associated with a reduced life expectancy of up to 19 years.

Yet despite the common prevalence (much higher than diabetes, for example), doctors can have difficulties in conceptualising where the disorder sits within the medical framework. In my opinion, the main reason for this is that the basic background on personality theory is almost completely ignored in most undergraduate medical programmes. In the following article, I hope to provide some context to the theory of what ‘personality’ is and show that it is an important factor in general health, as well as in mental health.

This will be a whistle-stop tour rather than a comprehensive review and, at times, I have taken a few liberties for the sake of clarity. However, I do hope that after reading this, one will have a better understanding of the basics of what is probably the single-most fascinating aspect of human biology, that is, what makes us all so different.

What is a ‘personality’?

‘Personality’ is a word and concept that we all use in conversation every day. We all have a sense of what it means, but when put on the spot to define it and identify what the core elements are, it can become a little difficult. The concept that different people have an individual way of reacting to events has been well understood since ancient times. The father of medicine himself, Hippocrates, wrote about four fundamental temperaments (sanguine; choleric; melancholic; and phlegmatic) and also associated each one with particular illnesses, as well as physical characteristics.

Despite the awareness of personality as a concept for such a long time, it has been difficult for experts and researchers to arrive at a common definition. There have been over 50 different definitions proposed in the academic literature. The definition below is one that is clear and sufficiently precise to act as a base in this discussion.

Personality is “a person’s characteristic pattern of behaviours in the broad sense (including thoughts, feelings and motivation)”, which is “relatively stable across time and can be used to differentiate this individual from others” (Bauert et al, (2017)).

There have been many different theories of personality proposed, such as ‘type theories’, which would define each person’s personality as having to sit in one or other of a small number of distinct categories (ie, you were either sanguine or phlegmatic); there are theories rooted in psychoanalysis and other schools of psychology. Multiple theories throughout history trying to link personality to body shape have also come and gone (such as ectomorphs); however, these were not supported by systematic research.

Over time, the ‘trait model’ has come to be the most accepted model within the literature and the one that is used in most research. This theory first proposes that human personality can be broken down into a number of distinct ‘traits’ or ‘characteristics’. This model underwent a number of evolutions throughout the 20th Century, until the work of Costa and McCrea produced the ‘five-factor model’ (FFM), which has achieved predominance as the most accepted theory (see Figure 1). In essence, the model proposes that the human personality can be divided into five higher-order factors (or domains).

Of note, each factor is named after one end of the spectrum that it describes. So, for example, extraversion could just as easily be called ‘introversion or agreeableness antagonism’. The five factors can be further divided into lower order factors as well.

Based on this model, each person’s personality is thus a blend of different positions on a number of different spectra, with different traits interacting in ways specific to each individual. For example, if we encountered someone with a high level of extraversion but a higher level of neuroticism, their natural anxiety could seriously temper their desire to socialise and in certain environments, they may appear quite introverted or ‘shy’. However, in environments where their neuroticism is calmed, they may be able to display their extraversion more.

The above description is a very crude and simple explanation to show that while people have certain personality traits, how these are manifested is significantly affected by their environment; learned patterns of behaviour and other factors that may be meaningful to them but not to others.

How and where do we develop our personalities?

The question: ‘Are we born with a predetermined personality or are we shaped by our experiences into the people we become?’ is one that has burned for centuries and remains contentious. The short answer is, there are definite genetic influences over the personality traits that we have; however, how these are shaped and manifested over time depends on the experiences that we encounter (with childhood experiences probably being more important than those in our adult life).

Interaction of personality and medicine

One of the reasons I feel it is important that doctors have a basic understanding of personality theory is that evidence shows that even outside the realm of personality disorder, personality can have a significant bearing on our health.

One of the best-studied areas where personality and health interact is in cardiovascular disease. Multiple studies have shown relationship features, such as neuroticism and extraversion, with a higher risk of stroke and coronary artery disease. As expected, high levels of conscientiousness are associated with a lower risk.

Often, this difference in risk has been explained through different personalities being more or less likely to result in different lifestyle choices (eg, a very extraverted person living in Western Europe is more likely to drink and smoke, as they are more likely to socialise). However, in a study published by Jokela et al in 2014, it was reported that the associations between personality and vascular disease (the study looked at both stroke and coronary artery disease) were only partially explained by the major cardiovascular risk factors. Other possible mechanisms proposed were via physiological pathways, such as dysregulation of the autonomic nervous system and abnormalities of the hypothalamic-pituitary-adrenocortical axis. It was also proposed that there might be some common developmental factors between personalities and cardiovascular health.

The importance of these studies is that they show identifying people who have certain personality traits, and encouraging them to engage in exercises or practices to modify how the traits are manifested (ie, mindfulness, relaxation, etc) may have longer-term benefits in physical as well as mental health.

Functional disorders

The other area of medicine where personality factors are of interest has been in the areas of somatisation (or medically-unexplained symptoms) and disorders where pain plays a central role, such as fibromyalgia and irritable bowel syndrome. Given that neuroticism is linked with our ability to feel negative emotions, it is not surprising that patients who present with these problems tend to score higher than control groups.

Personality affects our perception, not just of the outside world, but also of our internal environment. Those with higher levels of neuroticism are more likely to catastrophise when experiencing discomfort, which can lead to seeking out medical assistance more than others. Also, they are more sensitive to comments about them and are more likely to remember negative statements.

How these patients are communicated to and interacted with can be very important in their journey through the health service. An understanding of personality theory allows doctors to realise that when interacting with patients, not only does the content of the consultation need to be planned, but also the style and manner in which it is delivered. Personality theory teaches us that people are different and while there are definite wrong ways to communicate with patients, there are often many different correct ways and choosing which one to use, at which time, is important.

Conclusion

I have often thought that one of the key skills we learn as doctors is the ability to break down and describe what everybody can spot is obviously wrong. For example, which patient will come into the clinic with a rash and know it is abnormal, but the doctor’s job is to be able to describe it as macular or papular, etc, and then, from those descriptions, work out a diagnosis and eventually a treatment.

The fact that people are different is also obvious to every person once they have gone past the age of about five years. We quickly work out that one aunt is jolly and will always listen to a joke, while another aunt is more serious and will ask us about our homework. As clinicians, we work out that one patient is a short consultation and ‘just wants the facts’, while another patient takes longer and needs more reassurance. A better understanding of personality theory, I feel, arms a doctor with the ability to break down and analyse why those patients are different and how we can better help them.

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