All reports by Paul Mulholland
Ironically as a population we are now expected to live longer and this combined with improved cancer survival rates means it is likely that more individuals will require thoracotomy surgery. Therefore we will face the challenge of dealing with a significant chronic pain issue for many years to come. As clinicians we must strive to deliver the best treatment options for our patients. We must be aware of the high probability that at least one-in-five individuals will develop post-thoracotomy pain syndrome (PTPS) so we should be aware of the physical and psychological impact it will have on those concerned. It is hoped that after this overview individuals who are not familiar with PTPS will recognise the condition sooner and appreciate that there are several treatment options.
There are many reasons why thoracic surgery may be required. Video-assisted or open procedures for lung biopsy, pneumothorax or lung resection are techniques used daily. Very often when these individuals head home from hospital they are often left in analgesic limbo, where they struggle to deal with significant surgery and frequently with inappropriate or sometimes no analgesics planning. In the weeks that follow, the focus of care is centred on the surgical outcome, pain management is seen as ‘short-lived’ consequence of the surgery.
More often than not patients are so relieved to hear the result of the surgery the fear of persistent pain seems fictitious. In fact many feel as if it is their ‘obligation’ to suffer, as they are ‘lucky to be alive’. Yet the pain continues. It may be several weeks or months later that they attend their GP and reveal the impact the chronic pain is having on their daily function.
What should we do?
While there are limited evidence-based clinical guidelines to help plan treatment, it is clear that if we can improve awareness surrounding acute pain management then individuals can have an improved outcome. There are many perioperative analgesic regimes and surgical techniques aimed at reducing the occurrence and severity of acute postoperative pain. This is very important in controlling the cascade of biochemical events associated with the development of chronic pain. It has proven very useful in the short-term and sets the bar for future developments.
GPs, thoracic surgeons and pain physicians must be familiar with the range of conservative and interventional options available from the simple trigger point injection, intercostal nerve blocks, advanced radiofrequency denervation and neuromodulation. Modern medicine means we have more specialist areas than ever before, however, the art of communication between these specialists is sometimes lost. While pain management is a relatively new discipline there are many treatment options to deal with PTPS. The problem is spreading the gospel!
Diagnosis of PTPS
PTPS is not always unambiguously derived from the clinical history or physical examination, therefore additional examination or investigation is often indicated. As with any clinical situation a complete history and examination is important to understand the nature of the symptoms and to identify any possible physical signs. Unfortunately there are few patient or surgical factors that can help identify those individuals more at risk. Table 1 highlights some common causes that the GP could consider.
Exclusion of red flags is a very important element of the diagnosis and investigations should focus around clinical suspicion.
Investigation could include:
a) In the event of a collapsed vertebra, an x-ray of the spinal column may sufficient. Along with a clinical history of a trauma, with or without a history of osteoporosis, the diagnostics can be completed.
b) MRI could be necessary to rule out malignant causes of the pain or metastases. This is particularly important if there is a history of malignancy, or in cases of acute development of severe pain or progressive pain symptoms including the development of symptoms suggestive of neurological impairment.
c) A thoracic x-ray can be useful in the event of thoracic wall pathology. If there are abnormalities, the patient should be referred to a pulmonary physician for further evaluation.
d) Additional work-up could include CT-scan or pelvic ultrasound if there is abdominal element to the symptoms.
e) Blood tests for biomarkers, liver function and full blood screen including coagulation and infective screening should always be considered.
This not an exhaustive list and each case needs to be considered individually.
Conservative treatment options
Pain aggravated by movement usually indicates a role for agents such as regular paracetamol, tramadol, codeine or non-steroidal inflammatory agents once these are not contraindicated. The dual action of tapentadol (an opioid and noradrenaline reuptake inhibitor) has been shown to be very useful in providing analgesia while offering steady analgesic in PPTS. In general the choice of the agents and the dosage required needs to be established in most cases.
If features of neuropathic pain (burning/pins and needles, etc) are present then one should consider pregabalin or gabapentin as a treatment option. These agents may take a number of weeks to control the situation and may need the dose titration
Hypersensitivity over healed scar tissue would suggest a role for lignocaine patches. Transcutaneous electrical nerve stimulation (TENS) is an option for the treatment of thoracic radicular pain. Hydrotherapy and acupuncture can be considered depending on the degree of pain intensity. Physical therapy is usually applied in the form of manual therapy and can be very helpful
Interventional pain procedures
For individuals who fail or respond poorly to oral medication pain procedures can offer the control they require to improve their functional capacity and quality-of-life. Referral to a pain consultant can often be of great value. Table 2 outlines some of the possible options that exist.
For example, intercoastal nerve injection can provide 50 per cent improvement very quickly. The option of using advanced radiofrequency denervation (RF) can be considered depending on the outcome following the injections. Good results are reported following RF treatment in thoracic radicular pain management. A significant and prolonged (>12 months) reduction in pain can be expected in 52-to-70 per cent cases. The more segments involved, the effectiveness of the treatment is smaller. Other targeted injections to the facet joint, thoracic nerve roots or infiltration to the scar site can make a significant difference for each individual. Details and outcome are outlined in the reference papers at the end of this article.
PTPS is a very challenging chronic pain condition that affects many patients on a daily basis. All healthcare providers working in this area ought to be alert to the possibility of this syndrome and must be prepared to recognise the treatment options. GPs, surgeons and pain physicians must be familiar with the range of conservative and interventional options from the simple intercostal blocks to neuromodulation. When treatment is utilised rationally, they have the most probability to alleviate pain and finally to improve the quality-of-life for patients.
Hegarty D (2017) Post Thoracotomy Pain Syndrome: What Pain Management Options do we have? J Surge Transplant Sci 5(3): 1059.
Hegarty D (2017) Post Thoracotomy Pain Management: time to spread the gospel! J Surg Transplant Sci 5(3): 1058.
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It is an experience that affects, and is affected by, both the mind and the body. It involves the perception of a painful stimulus by the nervous system and the reaction of the individual patient to this.
It is increasingly recognised that pain encompasses not only physical aspects, but also a psychological component. Understanding pain fully involves understanding the psychological factors that influence the perception of pain, in addition to just the pathological mechanisms of pain conduction.
Psychological aspects that often lead to pain intensification have been found to include:
Distress surrounding change in body function
A patient’s perception of pain following a cruciate tear may be intensified by the fear that they may not be able to play sport again.
Fear of pain
Patients may anticipate or expect pain, such as when a dressing is being changed, which has previously been painful. The fear of pain may lead to the pain sensation being more severe than the local trauma should precipitate.
Feelings of helplessness and dependency
Patients with pain that is disabling may be further burdened by a sense of helplessness and dependency on others. This is often seen in pain at end-of-life, where overall distress about burdening family members can lead to pain intensification.
Mood disturbance and anxiety
Often, where patients are hormonal, or perhaps intensely hungry, their pain — irrespective of the location — may become more severe. This is thought to be a psychological phenomenon, such that when the mood disturbance or hunger is reversed, the pain will recede.
Social and spiritual aspects are also considered to impact on the experience of pain.
Experience in palliative care has taught this author that often, patients experience physical pain as a result of social changes, including a sense of loss of their role in a family, loss of their career or loss of their interpreted status in society. Spiritual aspects that contribute to physical pain may include a patient’s distress at the search for the meaning of their illness or injury.
Chronic pain may be associated with significant changes in lifestyle, functional ability and personality. Management is challenging, as it requires careful assessment, not only of the intensity and nature of pain, but also of the degree of psychological distress that is present. In essence, pain is a subjective experience and the severity of an individual’s pain is relative to their own perception and tolerance.
Accurate assessment of a patient’s perceived pain is recommended before a decision is made on the choice of analgesic to administer. The natural history of the patient’s pain should always be assessed.
Figure 1 is a useful pain assessment tool, which combines two well-known pain assessment tools — a numerical rating scale (NRS), and a visual analogue scale (VAS). The patient can demonstrate their pain in a number of ways:
1) A number between 0 and 10 can be chosen, with 0 indicating no pain, and 10 indicating the most severe pain possible.
2) A colour on the scale from green (no pain) to deep red (severe pain) can be selected.
3) One of the faces that express mild-to-severe symptoms of pain can be chosen, as patients may identify best with an expression, rather than a number or colour.
This is a universal pain scale, as it can be used for pain assessment in children, as well as in individuals with learning difficulties. Those with speech difficulties, for example due to aphasia or dysphasia, can point to the tool to describe their pain. The use of colour, as well as ‘happy’-‘sad’ faces and numbers, makes this tool visually appealing and adaptable to different patient needs.
LESS PAIN patient interview
It is important to listen to patients when discussing pain and ask careful, targeted questions. Often, patients will use familiar expressions to describe their pain, and these may not always be accurate. For example, often a patient will report that they are ‘in pain all the time’.
It is important to explore such statements further with the patient. Careful questions should be asked to establish the true level and frequency of pain — including questions about the patient’s lifestyle and mood and how their pain affects them.
The University College London School of Pharmacy has devised an effective questioning tool — ‘LESS PAIN’ — to enable fruitful conversations about pain by asking eight key questions.
The LESS PAIN tool (see Figure 2) has been developed to aid in the assessment of pain and to guide the provision of appropriate pain relieving interventions.
Mild-to-moderate pain can be managed in the community setting, using basic non-pharmacological pain management advice and over-the-counter analgesics.
Particularly where pain is thought to have a psychological component, non-pharmacological interventions play an important role in the management and resolution of pain. ‘Comfort therapy’ is a broad term which refers to the provision of soothing therapies that often aid with emotional distress or psychological factors, towards improving pain control.
Examples of comfort therapy include:
Companionship (where patients experience heightened pain due to feeling lonely or isolated).
Lotions/massage therapy (demonstrated to reduce anxiety).
Meditation (mindfulness has demonstrated analgesic benefit).
Music, art, or drama therapy.
Pastoral counselling (particularly for those with spiritual distresses).
Individual, family or group counselling.
Transcutaneous electrical nerve stimulation (TENS; thought to provide relaxation and reduce psychological distress).
The World Health Organisation (WHO) Pain Ladder (Figure 3) was originally designed for relief from cancer pain, but the step-wise approach has been used for relief of non-cancer pain as well. The pain ladder suggests using non-opioids and adjuvants initially, including paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and topical agents.
Importantly, if one ‘Step 1’ agent is not found to control pain, an alternative from this Step can be used, unless contraindicated. As a general rule, topical analgesic agents are the least likely to cause side-effects due to their limited systemic absorption. Paracetamol is also very well tolerated by the young, as well as the elderly, and is a useful choice for patients who are unable to take NSAIDs.
Use of NSAIDs is cautioned in patients with a history of cardiac disease, asthma, renal impairment or gastric ulceration. As a general rule, their utility decreases with increasing age, given that cardiac disease, renal impairment and gastric ulceration are all associated with increasing age.
Certain over-the-counter preparations also contain codeine, which is a weak opioid that may be introduced at Step 2 of the WHO Pain Ladder. The codeine content of over-the-counter products differs, with the best-known products containing codeine as follows:
Solpadeine (soluble/capsules): 8mg of codeine per tablet.
Nurofen Plus: 12.9mg of codeine per tablet.
As per the national guidelines, codeine products should only be used when necessary and only when a non-opioid analgesic, eg, paracetamol, aspirin or ibuprofen, have not proven sufficient to relieve symptoms. If recommended, codeine medicines should be used for the shortest time possible and for no longer than three days without medical supervision.
Urinary incontinence is largely a ‘hidden’ condition. Patients do not readily admit to symptoms and some doctors are still to this day unaware of their prevalence. Within the general population, up to 19 per cent of children and at least 20 per cent of women and 10 per cent of men may be affected by some form of urinary incontinence.
It is estimated that about one-third of the population in Ireland is affected by one or more of the different aspects of incontinence, with the incidence increasing with age, and an estimated 350,000 people over the age of 40 years are affected with overactive bladder (OAB) alone.
The term ‘urinary incontinence’ refers to the complaint of any involuntary loss of urine. Urinary incontinence can be categorised into several distinct subtypes based on associated characteristics and circumstances surrounding episodes of urine leakage. Although defining the type of incontinence will not establish a definitive underlying diagnosis, it will ultimately guide investigation and treatment (see Table 1).
Initial assessment of urinary incontinence
Patients with urinary incontinence can be identified through routine screening, or if the patient initiates a discussion about their urinary symptoms. The initial assessment should help with understanding the type of incontinence, while identifying potentially modifiable contributing factors. Most primary treatment options, such as lifestyle modifications and behavioural treatments, are the same for different types of incontinence.
Should include questions in relation to aggravating factors of urinary loss, onset, duration of symptoms, and degree of bother. Acute symptoms can be related to patterns of fluid intake and output, acute urinary tract infection, or recent surgery or trauma. Chronic symptoms should prompt queries about a history of congenital abnormalities, neurological disease, relevant surgery or general health. A detailed history of medications with known or possible effects on the lower urinary tract should also be obtained.
Use of questionnaires may help with disclosure of embarrassing symptoms and ensure that symptoms are not omitted. In the absence of a questionnaire, we would recommend the use of a standardised table of questions (see Table 2).
A bladder diary is recommended in order to document and communicate objective information and observations by the patient during the diary period. Despite the fact that diaries are never completely diagnostic, they may demonstrate both normal and abnormal patterns.
The ideal duration of a bladder diary is not yet clear; the recommended duration is three days for accurate assessment of lower urinary tract symptoms (LUTS). However, a seven-day diary is recommended in atypical clinical patterns.
It is considered standard to do a urinalysis by either a dipstick or sending a mid-stream urine sample at each visit to the clinic.
Secondary investigations include urodynamic testing, a cystoscopy, and imaging of the upper urinary tract. These should be considered in patients with neurological disease, refractory OAB, or those in whom initial investigations raise the suspicion of an underlying problem that may require further evaluation or treatment.
Treatment of OAB
This involves maintaining an adequate intake of 1.5-to-2 litres of fluid per day (six-to-eight cups), decreasing evening fluid intake, in particular when there is nocturia. An important part of this is reducing caffeine intake, present in coffee, tea and green tea, and also reducing other types of fluid that cause irritation to the bladder, such as alcohol, carbonated drinks, citrus, tomato, and spicy food.
Weight loss has been proven to improve both stress and urge incontinence, and it is also recommended to quit smoking and avoid constipation by increasing dietary fibres.
Pelvic floor exercises
These are aimed at strengthening the pelvic floor musculature. The rehabilitation programmes may include simple oral or written information, exercises performed with biofeedback, pelvic muscle contractions stimulated by functional electrical stimulation (FES), motor relearning exercises, or any combination of the above. Success is dependent on a continuous, regular home exercise programme to avoid deconditioning. Pelvic floor muscle training can also help improve prolapse symptoms and severity. They can also help improve quality-of-life prior to surgery.
The target is increasing the voiding interval and decreasing urgency and associated urge incontinence. The three components to the training are patient education, scheduled voiding, and positive reinforcement.
This should be undertaken in small steps. For example, if the patient is going to the toilet every half an hour, they should try extending the time (or ‘holding on’) by 10 minutes for a week, then by 15 minutes for a week, and then 30 minutes, etc. The aim is to eventually be able to hold on for three-to-four hours between toilet visits.
There are many options of anticholinergic medications to choose from, which are demonstrated in Table 3.
Another relatively new drug used is mirabegron, which is a β3-adrenoreceptor agonist, and because its receptors are more specific to the bladder, it has fewer side-effects. It is considered as a second-line therapy when patients are intolerant to anticholinergics.
The choice of anticholinergic therapy should be guided by individual patient comorbidities, as objective efficacy of anticholinergic drugs is similar.
Absolute contraindications to anticholinergic use include urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and known hypersensitivity to the individual drugs or any of their ingredients.
Elderly patients in particular should be monitored for drug interactions or polypharmacy of drugs with anticholinergic effects (ie, antidepressants, antipsychotics, anxiolytics), as the overall anticholinergic load is associated with confusion, falls and fractures. Anticholinergics are category C drugs in pregnancy, to be used only if the benefits clearly outweigh the risk.
Intravesical botox injections
Intravesical botulinum toxin A prevents acetylcholine release at the neuromuscular junction, resulting in temporary chemodenervation and muscle relaxation for up to six months. The usual technique is using 100IU of botulinum toxin diluted in 20ml of normal saline, and then injected into a non-trigonal area of the bladder wall in 20 different places.
Complete continence can be achieved in 40-to-80 per cent of patients and bladder capacity improves by 56 per cent for up to six months. Maximal benefit is between two and six weeks, maintained over six months. The injections can be repeated according to degree of improvement or relief of symptoms.
It is important to teach the patient how to do intermittent self-catheterisation beforehand, as the risk for the development of urinary retention is between 10-to-15 per cent.
Other treatment modalities
Other options also include posterior tibial nerve stimulation and sacral nerve stimulation, which involves an implantable electrode in the S3 foramen continuously stimulating the S3 nerve root, in order to stimulate the pudendal nerve. There is a potential benefit for up to five years in patients with OAB.
Some more radical methods of treatment include augmentation cystoplasty and urinary diversion. Indications for bladder augmentation include a small, contracted bladder and a dysfunctional bladder with poor compliance. Urinary diversion should be considered only when conservative treatments have failed, and if sacral nerve stimulation and augmentation cystoplasty are not appropriate or unacceptable to the patient.
Management of stress urinary incontinence
Pelvic floor exercises
Pelvic floor muscle training is considered the first-line treatment for urinary incontinence and aims to strengthen the levator ani and pubococcygeal muscles, which affect the urethral closure mechanism.
Today, there is a huge body of evidence from randomised, controlled trials and systematic reviews concluding that pelvic floor muscle training is effective in the treatment of stress incontinence. Several systematic reviews have recommended conservative treatment and especially pelvic floor muscle training as first-line treatment.
However, many surgeons seem to regard minimally-invasive surgery a better first-line option than pelvic floor muscle training. The scepticism against pelvic floor muscle training may be based on inappropriate knowledge of exercise science and physiotherapy, beliefs that there is still insufficient evidence for the effect of pelvic floor muscle training, that evidence for long-term efficacy is lacking or poor, and that women are not motivated to regularly perform pelvic floor muscle training.
An incontinence pessary is a silicone ring device with a knob placed in the vagina, with the goal of stabilising the urethra to eliminate hypermobility and increase urethral pressure during increases in intra-abdominal pressure. This is a safe and effective conservative treatment.
Periurethral bulking agents
Periurethral bulking injections are performed via the urethral route using a cystoscope, and demonstrate highly variable success rates ranging between 26 per cent and 75 per cent.
A wide variety of material can be used; most commonly used is Bulkamid, which is a homogenous hydrophilic gel consisting of 2.5 per cent polyacrylamide and 97.5 per cent water. Bulkamid appears to be a relatively safe and minimally-invasive means of narrowing the lumen of the urethra. It seems to have a positive effect for at least six months to two years, and it is possible to re-inject patients. No material has proved better than another. This appears to be a good option for older, unfit patients, or those who have failed other incontinence treatments.
Through the years, hundreds of different surgical options have been developed for the management of stress incontinence, but nowadays, midurethral slings utilising synthetic mesh remain the gold standard.
The retropubic tension-free vaginal tape sling (TVT) was the first to be introduced. It was developed based on the theory that the tape should substitute the pubourethral ligament that is responsible for the support of the mid-urethra. There is a small risk of perforating the bladder while inserting a TVT, which can be assessed by doing a cystoscopy.
Later on in 2001, the transobturator tape (TOT) sling approach was introduced with the hope of avoiding vascular, bladder, and bowel injuries. TOT sling trocars traverse the obturator canal instead of the retropubic space and enter through small groin incisions at the level of the clitoris bilaterally.
Mesh complications from midurethral slings are uncommon and are reported to be less than 4 per cent but can include mesh erosions into the bladder or urethra, mesh exposures in the vagina, pain, dyspareunia, and rare complications, such as severe infections.
See www.continence.ie for more information and resources.
Lower urinary tract symptoms (LUTS) are a common complaint in adult men with a major impact on quality-of-life and substantial economic burden.
The present EAU Non-neurogenic Male LUTS Guidelines are symptom-orientated and offer practical evidence-based guidance on the assessment and treatment of men aged 40 years or older with various non-neurogenic benign forms of LUTS.
The understanding of the LUT as a functional unit, and the multifactorial aetiology of associated symptoms, means that LUTS now constitute the main focus, rather than the former emphasis on benign prostatic hyperplasia (BPH), and secondary to benign prostatic obstruction (BPO), detrusor overactivity (DO)/overactive bladder (OAB), or nocturnal polyuria in men over 40 years.
The high prevalence and the underlying multifactorial pathophysiology of male LUTS mean that an accurate assessment of LUTS is critical to provide best evidence-based care.
A practical algorithm has been developed by the EAU for guidance (see Figure 2).
LUTS management (summary)
Conservative and pharmacological treatment
Watchful waiting is suitable for mild-to-moderate uncomplicated LUTS. It includes education, reassurance, lifestyle advice, and periodic monitoring.
First choice of therapy is behavioural modification, with or without pharmacological treatment. A flow chart illustrating conservative and pharmacological treatment choices according to evidence-based medicine and patients’ profiles is provided in the guidelines.
Prostate surgery is usually required when patients have experienced recurrent or refractory urinary retention, overflow incontinence, recurrent urinary tract infections, bladder stones or diverticula, treatment-resistant macroscopic haematuria due to BPH/BPE, or dilatation of the upper urinary tract due to BPO, with or without renal insufficiency (absolute operation indications, need for surgery). Surgery is usually needed when patients have had insufficient relief in LUTS or post-void residual after conservative or pharmacological treatments (relative operation indications).
The choice of the surgical technique depends on prostate size, comorbidities, ability to undergo anaesthesia, patient’s preference/willingness to accept surgery-associated side effects, etc.
In relation to the management of nocturia in male LUTS patients, the guidelines state that assessment must establish whether the patient has polyuria, LUTS, sleep disorder or a combination. Therapy may be driven by the bother it causes, but non-bothersome nocturia may warrant assessment of a frequency volume chart (FVC), depending on history and clinical examination, since potential presence of a serious underlying medical condition must be considered.
EAU guidelines recommended male LUTS patients follow-up strategy:
Patients with watchful waiting should be reviewed at six months and then annually, provided symptoms do not deteriorate or absolute indications develop for surgical treatment.
Patients receiving beta-1-blockers, muscarinic receptor antagonists, beta-3 agonists, phosphodiesterase-5 inhibitors, or a combination should be reviewed four-to-six weeks after drug initiation. If patients gain symptomatic relief without troublesome side-effects, drug therapy may be continued. Patients should be reviewed at six months and then annually, provided symptoms do not deteriorate or absolute indications develop for surgical treatment.
Patients receiving 5α-reductase inhibitors should be reviewed after 12 weeks and six months to determine their response and adverse events.
Patients receiving desmopressin: Serum sodium concentration should be measured at day three and seven and after one month and, if serum sodium concentration has remained normal, every three months subsequently; the follow-up sequence should be restarted after dose escalation.
Patients after prostate surgery should be reviewed four-to-six weeks after catheter removal to evaluate treatment response and side effects. If patients have symptomatic relief and there are no side effects, further assessment is not necessary.
The Non-neurogenic Male LUTS Guidelines can be accessed at the EAU website at http://www.uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/.
Being able to effectively obtain and use health information is an essential element of empowering and supporting patients to self-manage their chronic conditions. Supporting people to self-manage their health conditions through systematic provision of education and supportive interventions increases their skills and confidence and improves outcomes for patients – ranging from quality-of-life and clinical outcomes, to reduced healthcare utilisation including hospitalisation.
The Migraine Association of Ireland (MAI) is Ireland’s only patient organisation for people suffering from migraine and other headache disorders. It is estimated that over 500,000 people suffer from migraine in Ireland. While 14-15 per cent of these people are chronic migraine patients (more than 15 days migraine per month) and will require specialist treatment and preventative medications, most migraine sufferers experience episodic attacks. Episodic migraine attacks can be effectively reduced and managed with lifestyle and dietary adaptations. Learning to identify triggers is a key element of an effective migraine management programme.
Self-education and self-management can also prevent an over-reliance on over-the-counter medications, which can give rise to medication overuse headache. In 2011, the Dublin Neurological Institute undertook an audit of patients attending their specialist migraine clinic and they found that medication overuse headache was present in 52 per cent of patients attending the clinic.
Education and self-management supports
The MAI provides a number of free seminars for migraine sufferers throughout the year covering a variety of themes from ‘Hormonal Migraines in Women’, ‘Migraine in Children and Teens’ to general migraine seminars helping people better understand their condition. We also run a self-management course, over three weeks, one evening a week and during this course patients are connected with medical experts from the national migraine clinics to receive specialist training and advice on their condition. The course also equips people with the skills and strategies to better manage their condition. Modules include the migraine friendly diet, supplements for migraine prevention, identifying triggers, exercise and stress reduction techniques. We have also incorporated cognitive behavioural therapy (CBT) techniques in our programme so we can help people accept that migraine is a neurological condition they may always have and to adapt their expectations and lifestyle choices around the condition rather than always searching for a cure.
If GPs have patients who are suffering regular migraines, a referral to the MAI can be a positive first step in achieving better patient outcomes. The MAI also operates an information and support line that patients can call for support and advice and through this they can also be referred to a specialist migraine nurse.
Another key challenge for migraine sufferers internationally is that migraine remains undiagnosed and undertreated in at least 50 per cent of patients. On average migraine sufferers are taking six-to-seven years to receive a proper diagnosis of migraine.
Irish GPs currently only receive four hours training in headache as part of their undergraduate training. This is despite the fact that migraine is the most common primary headache seen by GPs. Three-quarters of the patients presenting to the Migraine Clinic at the Dublin Neurological Institute in the Mater Hospital, Dublin, have never been prescribed a preventative therapy, which indicates there is a serious lack of knowledge about chronic migraine in the primary care setting.
Resources for healthcare professionals
The MAI in recognition of this challenge provides a number of specialist health professional training seminars, for GPs and other healthcare professionals throughout the year. We have been in existence for nearly 25 years and through our network of contacts at a national and international level we have the ability to attract a high calibre of headache and migraine experts. The events are free to attend and carry RCPI and NMBI CPD points. We also have a comprehensive health professional section on our website, www.migraine.ie, which provides in depth diagnostic materials and resources. The patient section of our website is also a good referral tool for GPs to direct migraine patients to so they can better understand their condition.
You can email or contact the MAI on email@example.com or 01 894 1280. The MAI Information and Support Line operates Monday to Friday 10-4 pm and the number is 1850 200 378.
Our book Migraine Not Just Another Headache is also available to buy from local bookshops and from our website.
Written by experts, this book describes the role of the GP, nurse, pharmacist, paediatrician, physiotherapist and psychologist in the treatment of migraine. It advises about the management of migraine in the home, at school, in the sports centre and workplace. It gives crucial information from neurology and from specialist migraine clinics about pain management, migraine in children and adolescents, and the legislation to support people in educational and employment contexts.
The Migraine Association of Ireland hosted a health professional education seminar in Dublin last month, which offered attendees the opportunity to acquaint themselves with current and emerging therapies applied in the management and treatment of migraine and featured presentations from two of the world’s leading migraine and headache experts – Dr Lars Edvinsson and Dr Allan Purdy.
Dr Edvinsson was the main researcher in the discovery and development of the new Calcitonin Gene Related Peptide (CGRP) antibodies and is a Neurologist at the Department of Emergency and Internal Medicine, Skåne University Hospital and Professor of Internal medicine at Lund University in Sweden. He is chairman of the Swedish Migraine Society and the current President of the International Headache Society.
Recently retired Dr Purdy was a Neurologist and Professor in the School of Medicine at Dalhousie University in Nova Scotia, Canada. He is the immediate Past President of the American Headache Society and has also served as President of the Canadian Headache Society and on the Board of Directors of the International Headache Society.
In his opening remarks to the meeting, Mr Patrick Little, CEO of the Association, noted that GPs and medical students receive very little training in migraine and he detailed the work of the Association in helping provide high quality education for clinicians on the topic in order to optimise the management of migraine patients in Ireland.
The development of CRGP
Dr Edvinsson recounted the early steps and milestones in the understanding of the neuropeptide CGRP in the trigeminovascular system and its role in migraine and the journey to develop blockers of CGRP effects.
Essentially, CGRP is released into the blood stream during a migraine attack and has a central role in the underlying mechanisms of a migraine attack. It is known to cause blood vessels to dilate and cause inflammation at nerve endings.
His groundbreaking work on the sensory system has now resulted in the development of new migraine therapies, including small molecular CGRP-blockers for acute attacks and antibodies towards CGRP or CGRP-receptors as prophylaxis for chronic migraine.
Recent results from clinical trials on monoclonal antibodies targeting CGRP are encouraging (one study found 50 per cent of those given the antibody injections halved their number of migraine days per month) with the EU Commission recently granting a marketing authorisation for the first drugs (Erenumab and galcanezumab) in the EU. Both are primarily prescribed for the prevention of migraine in adults with chronic refractory migraine and it is hoped they will be available in Ireland in the next year.
Speaking to the Medical Independent (MI), Dr Edvinsson said it was an exciting time with the new class of drugs on the verge of becoming widely available for migraine patients in Europe.
He acknowledged the long gestation period and delays in their development was somewhat frustrating, but he believes they will have a dramatic impact on the prophylaxis and treatment landscape for migraine patients; “they will with certainty”.
Diagnosing and treating migraine
Dr Purdy gave an engaging overview of the different migraine types, diagnosis and treatment options and ‘pearls of wisdom’ on treating this headache disorder, which “while it seems straightforward it is anything but and anyone who has to deal with migraine patients recognises it is very complex”.
Dr Purdy emphasised that listening to the patient and having that knowledge of their individual experiences and reactions to various therapies remains the key to successful management: “Even though there have been tremendous advances in the science of migraine and understanding of the pathophysiology and that it is a true neurological disorder and the new and exciting advances detailed by Dr Edvinsson, if you really see what is going on in the world of migraine this still becomes the cardinal interaction with the patient.”
He noted the third edition of the International Headache Society (IHS) International Classification of Headache Disorders (ICHD-3) is a useful tool for clinicians dealing with migraine patients.
Looking at the presentation and diagnosis of various types of migraine, Dr Purdy commented that “migraine hijacks all of the brain” and “you should think everything is migraine until it isn’t”.
However, he also stressed the importance of thorough diagnosis and investigation of red flags noting that migraine can mimic many other issues such as a brain tumour.
When correctly diagnosed the basis of traditional migraine treatment remains reducing attack frequency and eliminating acute-attack symptoms: “So acute therapy, preventative therapy and behavioural therapy. But then you also have to manage the co-morbid disorders that go along with migraine as these will determine disease progression. And migraine is a disease; it is not simply a disorder…”
He stressed the importance of asking patients what they want treatment to ideally achieve, and recognising the specific risk factors of which treatments are prescribed for which patient, ie, if the patient is female, smokes, is aged over 35, is obese, etc.
Summarising the data on triptans to date (Lancet meta-analysis), Dr Purdy said all oral triptans are well tolerated, none are demonstrably safer than the others and at marketed doses all are effective and well-tolerated.
“The secret is that patients are more different than individual triptans” so trial and error is part and parcel of finding the best one for individual patients, Dr Purdy stated.
Discussing the various preventative therapies (betablockers, anti-epileptics, antidepressants, NSAIDs, calcium channel blockers, etc), he acknowledged that they are underused in general though efficacy can be mixed/disappointing. They also present issues with compliance – patients want them to be effective, not to have side effects and be easy to take, while knowing how long to take them is an issue and patients can stop taking them when their migraine occurrence reduces and then relapse.
Looking at the newer medical devices and alternative treatments, he said there is some promise in neuromodulation, but many devices are overhyped and ineffective. However, he expressed optimism about the forthcoming CGRP-related therapies, which could make a significant impact for patients and address a previously unmet need.
Speaking to MI after his presentation, Dr Purdy reiterated the importance of all doctors, particularly primary care physicians, having a good knowledge of migraine.
“If I was a physician in this era, the 21 century, I’d get very interested in migraine and the reason being that migraine tells you how the brain works. Every time a patient tells you a symptom, they are telling you how the brain works and exactly what is going on and that is fascinating. There are very few other disorders that I can think of that explore how the human behaviour and condition is affected by this very unique neuro-biological disorder.”
He said taking the time to listen to the patient and taking a thorough history and detailing of their symptoms is absolutely key, and this can take an hour or two: “The real secret is to nail the diagnosis and if you can’t do it in 10-15 minutes, bring them back three or four times, which adds up to an hour. Because if the diagnosis is incorrect everything else from there is downhill. But if it is absolutely pristine or the best you can do then there are really good options to treat migraine and they are getting better.”
Dr Purdy acknowledged that many doctors lack adequate knowledge of migraine and the best treatment approaches and prefer to refer to a specialist but he said most patients can be well managed in the community.
“A lot of doctors manage the patients very well, but a lot don’t want to manage them… It takes time and effort. But you have to understand that if you get a migraine patient and you spend the time with them and you train them to learn these things [prevention and management strategies] you can get a win; in other words you’ll make them better and you will hopefully prevent them for getting into these patterns later in life.
“That might be too hopeful, but it’s not cynical to say that I spent a lot of time in my 40-year career, which has just ended clinically, seeing new patients because I thought they could be helped and I spent a lot of time seeing chronic ones because that is what we do as neurologists, so what I’m saying is learn about migraine – learn all about it, go to some meetings, spend some time with them [migraine patients] and get to know your local neurologist and call them up and ask ‘what can I do’.
“I think education is the key here.”
The Irish Society for Rheumatology (ISR) Autumn Meeting 2018 takes place on 19-21 September in the Killashee Hotel, Naas, Co Kildare.
According to ISR President Dr Sinead Harney, Consultant Rheumatologist at Cork University Hospital (CUH), the meeting agenda is “really varied” and there is “something for everyone”.
“I think it will be good,” Dr Harney told the Medical Independent (MI).
“The programme is exciting. It is an international programme and the reason we can get international speakers is the generosity of all industry, so we are always grateful for that. And the attendance is always very high, and the role of the allied health professionals — the fact we are tight with them — is good as well. We are looking forward to it.”
Dr Sinead Harney, ISR President
Among the highlights will be a presentation by Prof Dirk Elewaut, Consultant Rheumatologist, Ghent University, Belgium, who will speak on ‘The gut in spondyloarthritis vs the joint in inflammatory bowel disease: Two sides of the same coin?’, while Dr Ian Giles, Consultant Rheumatologist, University College Hospital, London, UK, will discuss the topic ‘Optimising the management of women of child-bearing potential living with rheumatic disease’.
“A lot of our patients are women aged between 30 and 45-50; it is an important time in their life and a lot of our drugs can be used safely [in pregnancy] so [Dr Giles] is going to speak on this area,” noted Dr Harney.
Prof Luke O’Neill, Professor of Biochemistry in the School of Biochemistry and Immunology, Trinity College Dublin (TCD), will deliver a presentation titled ‘Krebs Cycle reprogrammed for cytokines: New therapeutic options for inflammatory diseases?’
Prof O’Neill is “always really good”, said Dr Harney, “and he brings immunology back to basics”.
Another eagerly-anticipated presentation will be that of Prof Lihi Eder, Professor of Rheumatology, University of Toronto, Canada, who will speak on cardio-metabolic diseases in psoriatic arthritis.
Rheumatology Patient Initiative Fund (RPIF)
One of the important facets of the meeting will be presentations by winners of the Rheumatology Patient Initiative Fund (RPIF).
The RPIF is intended for innovative researchers undertaking a body of research in rheumatology in Ireland that will directly impact on patient care and quality-of-life.
According to Dr Harney, five winners will present their research. This initiative is particularly important, as it supports basic clinical research that will impact on patients and it has been made possible by an educational grant from UCB, outlined Dr Harney.
The meeting will also feature the presentation of the Bernard Connor Medal 2018, which is aimed at encouraging medical student participation in rheumatology during their undergraduate education and supporting student engagement with the activities of the ISR.
The medal is named in honour of Dr Bernard Connor, an Irish physician who observed and described the characteristic skeletal and clinical features of ankylosing spondylitis in 1693, while himself a medical student in Paris.
Funding, manpower and infrastructural constraints affecting the specialty will not be far from delegates’ thoughts, according to Dr Harney.
Dr Tim Jones, Associate Lecturer at Oxford Brookes University, UK, will be presenting on building a business case for funding, and Dr Harney expects that this will be useful for delegates.
She said rheumatology has been “grossly under-funded in respect of consultants and infrastructure for the last 20 years”.
Dr Harney underlined that “we are always fighting for funding and we are grossly under-funded”.
“As President [I can say], we are all a bit demoralised, in that we need more consultants to keep pace with the workload…. also, the fact that general medicine over-impacts on our week. I spend more than 50 per cent of my week doing general medicine, so although there are 2.8 of us, there are actually only 1.4 here for this end of the country, in our department [at CUH],” said Dr Harney.
Levels of infrastructure vary across units, according to Dr Harney, who considered Cork as “probably the worst part of the country” in this respect.
At CUH, she said, lack of infrastructure to undertake day cases is causing huge problems in respect of patient care.
“In CUH, we have a prefab that was funded by industry and other than that, we have no physical footprint in the hospital,” she stated.
Insofar as possible, patients with private health insurance who have been attending CUH and require infusions have been referred to private hospitals in the area, she outlined.
“But our public patients are waiting for up to nine months to get an infusion,” said Dr Harney, adding that this care should be accessed within six months. “We are now stretching out to nine months of the year for six-month infusions, so we are on the verge of clinical risk and potentially leaving ourselves open to risk.”
These service deficits are impacting on retention of trainees, as is the new-entrant consultant salary.
“Some who have gone to the UK who I thought would come back, haven’t, for that reason [of new-entrant salary]. And then, they see how hard we have to work just to get slots for our patients to come in, and we do have to admit people overnight. We wasted 100 bed days here last year by having to admit people because we couldn’t get them day beds, so the lack of day beds is critical in CUH.”
Dr Harney said one of the helpful developments achieved through the National Clinical Programme for Rheumatology in recent years has been access to physiotherapists to undertake back pain clinics. But there remain many areas for improvement in respect of resourcing, she underlined.
Meanwhile, there will be a number of industry-supported satellite events on topical issues at the meeting, namely the MSD Satellite Meeting, where Consultant Gastroenterologist Dr Anthony O’Connor, Consultant Rheumatologist Prof Trevor Duffy and Senior Research Fellow in Psychology at TCD Dr Derek Richards will discuss the topic of ‘Identifying and managing mental health symptoms in patients with chronic disease’; the Novartis Satellite Meeting, where Prof Peter Nash, University of Queensland, Australia, will provide an update on IL-17a in spondyloarthritis; and the AbbVie Satellite Meeting, where Prof Lihi Eder of the University of Toronto will deliver a presentation titled ‘From psoriasis to psoriatic arthritis — can we improve early detection?’
ISR: Driving the specialty forward
The Irish Society for Rheumatology (ISR) is an organisation of about 150 members with specialist training in rheumatology. Members include consultants, trainees, scientists and researchers. The Society includes those who are based in the Republic of Ireland, Northern Ireland, the rest of the UK and some from further afield.
The ISR is a registered charity that organises and hosts regular platforms and conferences allowing members to present clinical and scientific material. It also promotes ongoing education and training in rheumatology at all levels and, in particular, in the postgraduate areas of professional training and higher medical training.
International links are maintained and developed to assist with the flow of information in the field. Currently, the Society enjoys links with a number of international bodies, including the American College for Rheumatology (ACR), the British Society for Rheumatology (BSR) and the European League against Rheumatism (EULAR).
For further information, visit www.isr.ie.
Dysphagia is one of the many complications of stroke and approximately 10,000 people in Ireland have a stroke-related event annually. Furthermore, an estimated 30,000 people are living in the community with disabilities as a result of a stroke.
It is also a frequent symptom in frail, older people or in individuals with any impairment of oral structure, or their respiratory or neurological systems, and is observed in a large proportion of people with dementia. It can also occur in patients with Chronic Obstructive Pulmonary Disease (COPD) and those with head and neck cancers.
Dysphagia refers to the sensation of not being able to swallow, food ‘sticking’ or not passing, choking episodes, or aspiration of food and/or liquids. It can also affect a patient’s ability to take medication and therefore can result in practices such as crushing and/or mixing, which can adversely affect the pharmacodynamics of the drug.
Dysphagia is also a strong predictor of malnutrition risk and dysphagic stroke patients are 2.4 times more likely to be malnourished compared with those who have normal swallowing function.
According to the Irish Heart Foundation, one-in-five people will have a stroke at some time in their life and approximately 50 per cent of people who have a stroke have swallowing problems. Other figures put the prevalence at up to 60 per cent, “which may rise to 100 per cent if minor deficits such as minor tongue weakness are accepted as evidence of dysphagia”, according to a 2016 paper in the journal Current Physical Medicine and Rehabilitation Reports (‘Dysphagia Management and Stroke Units,’ Dr David G Smithard).
“In many cases, dysphagia resolves fairly quickly, but in others, the swallow will vary in function,” states the same paper. “Management, at present, is based around texture modification of food/liquids and swallowing manoeuvres. Rehabilitation of swallowing remains in its infancy, but there is a lot of promising research with neurostimulation, medication and devices to strengthen muscles involved in swallowing.”
The HSE’s National Clinical Programme for Stroke has produced a National Guideline for Swallow Screening in Stroke (2017), which aims to support all acute stroke services in the development of a swallow screening service for stroke patients within their organisation.
Worryingly, where dysphagia is not identified and managed, it can severely impact on a patient’s health, with consequences ranging from unintended medication non-adherence, to choking, aspiration pneumonia and even death.
However, many healthcare professionals are unaware when patients may be having difficulties with swallowing their medicines. Furthermore, patients living in the community may not report dysphagia to their GP or pharmacist.
The Society of Hospital Pharmacists of Australia has stated that, where possible, dose alteration should be avoided and alternate dose forms or routes of administration should be found. Likewise, the National Institute for Health and Care Excellence (NICE), UK, recommended for patients with dysphagia that fluids and food should be administered in a form that can be swallowed without aspiration.
Gloup is an OTC swallowing gel for oral medication and it may be able to help patients maintain their treatment regimen. It facilitates the intake of medication in solid form, including tablets and capsules. It works by moistening the mucous membranes in the mouth and throat cavity and allowing the tablets to pass smoothly via the oesophagus to the stomach.
Some preliminary work from The University of Queensland, Australia, has assessed the effect of Gloup on drug dissolution (Crino L, Manrique YJ, Cichero JA, Steadman KJ, eds. Characterisation of Gloup: is it suitable for medication delivery in dysphagic patients? APSA-ASCEPT, 2015).
The authors concluded that Gloup had no effect on drug dissolution, unlike some gum-based thickeners designed to ensure safe fluid delivery in dysphagia.
Symptoms of dysphagia
Being unable to swallow.
Recurrent chest infections.
Patient having the sensation of food getting stuck in their throat or chest or sternum.
Hoarse or wet mouth.
Unexpected weight loss.
Coughing or gagging when swallowing.
Taking longer than usual to finish a meal.
Age-related macular degeneration is the leading cause of sight loss in the over-50s in Ireland, according to the Irish College of Ophthalmologists (ICO).
Without treatment, it is also the commonest cause of legal blindness, affecting over 60,000 Irish people.
AMD awareness week 2018 ‘SightSee with me’ will take place from the 10-14 September. It aims to generate greater public awareness and understanding of AMD and encourage those aged 50 and over to get their eyes tested regularly.
This year marks the beginning of a new decade for the awareness campaign, representing the 11th anniversary of the multi eye-care stakeholder group initiative, supported by the ICO.
Consultant Ophthalmic Surgeon and ICO spokesperson Mr Mark Cahill believed the campaign had been “very effective”. He added, however, that the importance of the symptom of distortion may require better awareness.
Macular degeneration occurs when the macula is unable to function as effectively as it used to.
Dry macular degeneration (non-neovascular), which constituted around 90 per cent of cases, affects the eyes gradually, while wet macular degeneration (neovascular) can develop very quickly and is more serious.
Before the mid-2000s, the treatment possibilities for wet AMD were limited to photodynamic therapy and laser therapy and these were only applicable in a small number of patients. However, wet AMD is now usually treated with intravitreal injections.
According to the ICO, intravitreal injection therapy has proven to be a major advance for patients with wet AMD.
It is known that when wet AMD develops, abnormal blood vessels grow under the macula due to a chemical stimulant called vascular endothelial growth factor (VEGF). Intravitreal injections of anti-VEGF drugs, which block vascular endothelial growth factor, can break the cycle of leakage, bleeding and scar tissue growth. Anti-VEGF treatment offers stabilisation and very often improvement in vision.
Anti-VEGF treatment will be around for “many years to come”, predicted Mr Cahill. He also pointed out that a phase 2 trial had recently finished, which centred on a six-month implant of ranibizumab. Three different concentrations were used and the data showed that “the higher concentration was very effective for up to six months in 80 per cent of people and that is a big step forward”.
He added: “Now, that is only a phase 2 trial so it’s got to go through a third phase and then it has to go through a real world period to see if it will get approval.” It would be a game-changer according to Mr Cahill, who also acknowledges that it would entail a surgical procedure, which is not without risk.
Mr Cahill said there is huge demand for AMD treatment and it may be one of the reasons why the cataract surgery waiting list has not been addressed, as available resources have to be targeted towards patients at risk of rapidly losing their vision. Staff in eye care services have worked incredibly hard to ensure greater volumes of patients are seen, he added.
The ICO advises that “regular eye examination with the eye doctor are recommended especially if there is a family history of the condition. This should be done every two years for the over-55s and annually if there is any hint of AMD. It is important that patients self-monitor using an AmSler grid between visits.
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.
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
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.
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.
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.