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Dr Linda Calabresi

Dr Linda Calabresi

GP; Medical Editor, Healthed
Dr Linda Calabresi is an Australian-based health professional. Linda is trained as a GP (General Practitioner) and has practices located in North Ryde, Artarmon.

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Fatter mothers behind rise in perinatal complications

The increasing BMI of first-time pregnant women is behind a rise in adverse perinatal outcomes over a 25 year time period, a new retrospective Australian study suggests. Analysing data from one major Sydney teaching hospital, researchers found that the prevalence of overweight among women having their first baby increased from 12.7% in 1990-94 to 16.4% in 2010-14, and that of obesity rose from 4.8% to 7.3%. More importantly they found this increase in BMI was associated with a range of adverse perinatal outcomes particularly pre-eclampsia, macrosomia and gestational diabetes. Other complications believed to have increased as a result of the maternal weight gain included caesarean deliveries, post partum haemorrhage, prematurity, admission to the special care nursery and fetal abnormalities. “We found that a substantial proportion of the burden of adverse perinatal outcomes for Australian women is linked to maternal overweight and obesity, and that this proportion has steadily increased over the past 25 years,” the Sydney researchers said. The study involved the analysis of the data recorded on over 42000 singleton births delivered to previously nulliparous women at the Royal Prince Alfred Hospital Sydney between 1990 and 2014. Interestingly over the course of the study period, the mean age for first time mothers rose from 28.7 to 31.6 years, however having adjusted for this as well as other possible confounders such as changing smoking rates, socioeconomic status, and country of birth of the mother the findings confirmed the relative risks of adverse perinatal outcomes had increased in association with rising prevalence of overweight and obesity. Researchers calculated that should overweight or obese women move down one BMI category (for example from obese to overweight) 19% of pre-eclampsia, 15.9% of macrosomia and 14.2% of gestational diabetes could be averted. “Our results indicate that the frequency of adverse perinatal outcomes could be reduced by shifting the distribution of overweight and obesity among first-time mothers by a single BMI class. Investing in obesity prevention strategies that target women prior to their becoming pregnant is likely to provide the greatest benefit,” they concluded. Ref: MJA doi:10.5694/mja17.00344

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Change in advice for abscess drainage

Skin abscesses are best treated with incision and drainage plus antibiotics, rather than just incision and drainage alone, recommends an international guideline panel in the BMJ. After critically appraising all the current evidence, the panel found adjuvant antibiotic therapy in addition to incision and drainage of uncomplicated skin abscesses reduced the risk of treatment failure and abscess recurrence by approximately 13% compared to treatment without additional antibiotics. In particular the randomised controlled trials included in the review, were evaluating the use of clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) in addition to incision and drainage. “TMP-SMX or clindamycin modestly reduces pain and treatment failure and probably reduces abscess recurrence, but increases the risk of adverse effects including nausea and diarrhoea,” they said. TMP-SMX is the more preferable option over clindamycin as it is less likely to cause diarrhoea, they added. The recommendation is in contrast to most of the current guidelines that generally advise uncomplicated skin abscesses be treated with incision and drainage alone except in cases where there is systemic illness, extensive tissue damage, immunocompromising conditions, an artificial joint or a high risk of endocarditis. And while the panel concedes that the benefit of adjuvant antibiotic therapy is modest, they anticipate that most fully informed patients would consider it large enough to choose it over incision and drainage alone. Of course, the major counter argument against increasing antibiotic use would be the possible increased risk of antimicrobial resistance. “From a societal perspective, it is possible that the modest benefits from adjuvant antibiotics in this scenario would not outweigh the risk of antimicrobial resistance in the community,” they said. However, the impact of a single course of antibiotics on this public health problem remains unknown, so any conclusion about net benefit versus net harm can only be speculative, they concluded, even though the issues are worth considering as part of the shared decision making. The panel also considered evidence for using cephalosporins for adjuvant treatment of skin abscesses, however they concluded that this class of antibiotics was unlikely to provide any benefit over incision and drainage in the majority of cases of skin abscesses, and therefore could not be recommended. Ref: BMJ 2018; 360: k243 doi.org/10.1136/bmj.k243

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Opioids offer little over NSAIDs for chronic severe pain

Opioids have really fallen out of favour as a chronic pain relief option. Even for patients with severe chronic back pain, or severe pain from their osteoarthritis in their hip or knee, opioids will not offer any better relief in terms of pain-restricted function that non-opioid medication, a recent study published in JAMA has shown. The US clinical trial involved 240 US adults with moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic.  Researchers compared whether treatment with opioids such as morphine, oxycodone or hydrocodone/paracetamol improved pain-related function over a 12-month period over treatment with nonopioid such as paracetamol or an NSAID. Surprisingly, the results showed no significant difference in terms of pain related function over the course of the study. In fact, the pain intensity was significantly better in the nonopioid group over the 12-month period, however the study authors said the clinical importance of this finding was unclear. As was perhaps more expected, the group that took opioids had more side effects. “Overall, opioids did not demonstrate any advantage over nonopioid medication that could potentially outweigh their greater risk of harms,” the researchers said. When looking at all the results – even including secondary outcomes,  the only area where opioids were found to be superior to nonopioids in this study of chronic pain patients was in the area of anxiety. The opioid group had fewer anxiety symptoms – so they had just as little function, and even more intense pain but they worried about it less. The study authors said their findings added to the growing body of evidence that opioids offer little benefit over other medications and even placebo in the management of chronic pain conditions, especially when their side effect profile is taken into consideration. “Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain”, they concluded. Ref: JAMA 2018;319(9) 872-882. doi:10.1001/jama.2018.0899

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Advice for shift workers

We know night shift work is not good for your health. Evidence shows night shift work is associated with an increased risk of sleep loss, occupational accidents, obesity and weight gain, type 2 diabetes, coronary heart disease, and breast, prostate and colorectal cancers, according to a review in the BMJ by two intensive care specialists. But what of strategies to help night shift workers mitigate these risks? What does the research say we should be advising these patients to do to optimise their health, remembering that many health professionals will be involved in this type of shift work? According to the review, there is a ‘paucity of adequately powered, well designed, randomised controlled trials’ on the subject however from what there was and with the addition of expert opinion the review authors recommended the following.
  • Try and make sure you’re not sleep-deprived before a night shift. Try and wake the morning before naturally (without an alarm) and, if possible have a daytime nap maybe taking advantage of that ‘circadian dip’ between 2 and 6pm the afternoon before you front up for night duty.
  • If you get the opportunity to nap during the night shift, try to limit the duration of these to less than 30 minutes, “to avoid slow wave sleep followed by grogginess on waking, known as ‘sleep inertia’”, the authors advise.
  • Caffeine reduces sleepiness and improves performance 20-45 minutes after taking it, with the effect lasting up to five hours.
  • There is evidence that drugs such as modafinil are effective in reducing sleepiness in night shift workers compared with placebo but these drugs have been associated with skin reactions and their long-term safety is yet to be established. Similarly, exposure to bright light has been proposed as a possible means of inhibiting melatonin, reducing sleepiness and perhaps reducing the cancer risk associated with shift work but neither these drugs nor bright light exposure is supported by sufficient evidence to be conclusively recommended.
  • Hunger and digestion are both affected by circadian rhythm. There is some evidence to suggest if you don’t eat you’ll perform better over the duration of the night shift than if you eat, however it is likely you will experience hunger and will be more likely to get GI symptoms leading the authors to recommend a main meal immediately before the shift and then small snacks as required to stave off hunger overnight.
  • And the big one. How to optimise sleep between night shifts? Well- the recommendations are fairly predictable – avoid bright light on the way home (wear sunglasses), employ blue screens on your computer and phone, use eye masks and ear plugs and develop a predictable pre-bed routine. Avoid caffeine for at least six hours before sleep time and perhaps consider taking melatonin the morning after a night shift –some evidence suggests that this increases sleep duration by up to 24 minutes.
“A meta-analysis of 66 studies concluded that regular exercise leads to improvement in sleep quantity and quality, but the optimum timing, duration, and type of exercise for sleep promotion have yet to be determined,” they said. In addition, the review authors didn’t recommend any other sleeping tablets due to a lack of quality evidence of their effectiveness and the risk of dependency. Finally, the researchers advised night shift workers to be aware their performance is likely to be reduced especially in that particularly vulnerable time between 3 and 5am and therefore they should seek support when required to do critical tasks at this time. They also warned workers to be aware of their vulnerability when driving home after night shift and referred to a patient, the inspiration for this review, who experienced the life-changing consequences of being involved in a road traffic accident while on a set of night shifts in 2005. Ref: BMJ 2018; 360:j5637 doi: 10.1136/bmj.j5637

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Don’t pickle old brains

Want to preserve your brain function into old age? Cut down on the booze. That’s the conclusion of a large, longitudinal study just published in JAMA Psychiatry. After comparing more than 200 alcohol dependent adults with a similar number of healthy adults, over a 14 year period, the US researchers concluded alcohol-dependence accelerated the cortical ageing process even if the alcohol habit developed later in life. They found, through a series of MRIs that alcohol dependence (as per the DSM-IV criteria) resulted in more rapid frontal lobe deterioration than that which just occurred with age, regardless of gender. As part of the study the researchers also looked at whether comorbidities such as drug use or hepatitis C infection made a difference to the decline in cognitive function. And while they found they compounded the shrinkage of the frontal lobe, the actual deficits in the frontal cortex seemed to be associated chiefly with the alcohol. “We observed a selectivity of frontal cortex to age-alcoholism interaction beyond normal aging effects and independent of deficits related to drug dependence,” they said. Also, the researchers found that the deterioration was more associated with current drinking habits  than the cumulative effect of many years of alcohol abuse. People who had become alcohol dependent later in life were just as vulnerable as people whose alcohol use disorder started when they were younger. “The accelerated volume deficits in the older alcohol-dependent participants could not readily be attributed to more years of heavy drinking, given that many had a late onset of their disorder and lower lifetime alcohol consumption estimates than their early-onset counterparts,” the study authors said. So, it appears the frontal cortex, which is that part of brain that helps people plan, reason, modify behaviours and problem solve is the most vulnerable to damage in people with alcohol use disorder. Add this to the fact the frontal cortex deterioration associated with aging, is fundamentally responsible for the deterioration in executive function that limits an elderly person’s ability to function and live independently, and you have a recipe for disaster for those older people who drink to excess. What does this all mean? An accompanying editorial makes the take home message quite clear. “Given the rapidly growing aging population… it is critical that we improve and implement strategies to address alcohol misuse among older drinkers. As Yoda might say, “Protect their brains, we must.” Ref: JAMA Psychiatry. Published online March 14, 2018. doi:10.1001/jamapsychiatry.2018.002 JAMA Psychiatry. Published online March 14, 2018. doi:10.1001/jamapsychiatry.2018.0009

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Cheapest Option Just as Good for Vaginal Atrophy

Post-menopausal women experiencing vulvovaginal symptoms will benefit just as much from using the cheapest over-the-counter lubricant or moisturiser as using topical oestrogen, a new study suggests. The 12-week randomised clinical trial, published in JAMA Internal Medicine, compared the efficacy of a low-dose vaginal oestradiol tablet and a vaginal moisturiser, each versus placebo among a group of over 300 post-menopausal women with moderate to severe vulvovaginal symptoms. To determine the effectiveness of the treatment women were asked to report on the severity of their ‘most bothersome symptom’ which included pain with vaginal penetration (60%), dryness (21%), itching (7%), irritation (6%) and pain (5%). Across the board, regardless of which treatment was used, most women had a decrease of at least 50% in symptom severity over the course of the study. This was significant in light of the fact that most women said they ‘frequently’ or ‘always’ distressed about their sex life at enrolment, whereas after the 12-week study nearly half said they were ‘rarely’ or ‘never’ distressed. “No treatment group differences in symptom reduction were observed for vaginal oestradiol tablet plus placebo gel vs dual placebo, or vaginal moisturiser plus placebo tablet vs dual placebo”, the US researchers reported. And it didn’t matter if the most bothersome symptom was dyspareunia or itching, it appeared the hormone treatment or the specific vaginal moisturiser (Replens) had no advantage over the placebo combination. According to the study authors, the placebo gel used in the study had a similar pH and viscosity as the vaginal moisturiser (Replens) but was less mucoadhesive. The fact that both formulations were equally effective in reducing symptoms suggests that the mucoadhesive properties are less important than previously thought. Similarly, markers of vaginal oestrogenisation such as the vaginal maturation index, did, naturally improve more with the topical oestrogen but this did not translate into a greater benefit in terms of symptoms over placebo. As an accompanying editorial points out, “ultimately, it is improvement in symptoms rather than surrogates such as tissue markers that should define the goal of care.” And while the study authors conclude that treatment choice for women with troublesome postmenopausal vulvovaginal symptoms should be ‘based on individual patient preferences regarding cost and formulation’ the editorial authors go in much stronger. “[P]ostmenopausal women experiencing vulvovaginal symptoms should choose the cheapest moisturiser or lubricant available over the counter – at least until new evidence arises to suggest there is any benefit to doing otherwise.” Ref: JAMA Intern Med. doi:10.1001/jamainternmed.2018.0116 JAMA Intern Med. doi:10.1001/jamainternmed.2018.0094

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A Missed Opportunity

Patients are still not consistently being prescribed exercise despite the wealth of evidence that shows its health benefit, according to an editorial in the latest issue of the MJA. The authors, all sports medicine specialists point to statistics showing physical inactivity being the fourth leading cause of morbidity and mortality worldwide. And they reiterate the well-proven benefits of exercise in helping to manage a wide array of chronic diseases from diabetes to depression. Even though physicians have a good track record of influencing lifestyle factors as evidenced by smoking cessation rates, it appears when it comes to exercise GPs are dropping the ball. “Most physicians do not regularly assess or prescribe physical activity or specific exercises,” said the editorial authors who included GP, Dr Anita Green, Chief Medical Officer of the Gold Coast Commonwealth Games. “Even when exercise is advised by physicians, the advice is often not specific or in depth, and simple evidence-based behaviour modification techniques are not routinely used.” But why is this advice, which is also recommended in the RACGP Handbook of non-drug interventions not being given to patients as a matter of routine? One of the greatest barriers to the dispensing of this advice, according to the editorial, is the clinician not practising what he or she should be preaching. “It has been consistently shown that physically active clinicians are more likely to provide physical activity counselling to their patients,” the authors said. And apparently the medical profession could do better in terms of regular exercise. Physical activity levels have been shown to decline during medical training and through residency, perhaps unsurprisingly. More emphasis needs to be placed on the importance of physical activity and exercise prescription as part of both undergraduate and postgraduate training, not only to help clinicians to help their patients but also to help clinicians help themselves. According to the editorial, the current Gold Coast 2018 Commonwealth Games are likely to inspire the next generation of elite athletes to commit to specialised exercise regimens and dedicated training rituals. However, for the vast majority of the sports-viewing population, the spectacle is unlikely to prove sufficiently inspirational to prize them off the couch. If the medical profession really wants to achieve better health outcomes for their inactive patients, it appears they need to lead by example. “Physicians should unequivocally incorporate physical activity into their own daily routine, for their own health benefit, and to become an exercise role model, more confident in prescribing exercise to their patients,” the authors concluded. Ref: MJA doi: 10.5694/mja18.00033

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Reflux Meds in Infants Doubles Risk of Allergy

Infants receiving acid suppressive medications are more than twice as likely to develop food allergies later in life, US researchers say. Findings from a large retrospective study, analysing data from almost 800,000 children, showed that being prescribed either an H2 receptor antagonist or a proton pump inhibitor in the first six months more than doubled the risk of developing a food allergy (hazard ratios of 2.18 and 2.59 respectively) when they got older. Similarly, the use of these medications was also found to associated with an increased risk of other allergies as well, including medication allergy (HR 1.70 and 1.84), anaphylaxis (HR 1.50 and 1.45) and, to a lesser extent, allergic rhinitis and asthma. As part of the same study, the researchers also looked at antibiotics in the first six months and, perhaps unsurprisingly found a link between this type of medication and developing an allergic condition. In the case of antibiotics, children were more likely to develop allergic respiratory conditions such as asthma and allergic rhinitis than food allergies. The findings have biological plausibility, the researchers said in JAMA. Acid suppressive medications inhibit the breakdown of ingested protein which, in turn facilitates IgE antibody production increasing the sensitivity to ingested antigens. The medications also, by definition, interfere with histamine which researchers now believe has a greater role in modulating immune system functioning than previously thought. The association between increased allergy and antibiotics, on the other hand supports findings from previous studies, and is thought to be related to the effect of the antibiotics on the gut bacteria or microbiome. It is one of a number of reasons why there has been growing pressure on clinicians to try to avoid prescribing antibiotics to infants. “While there has been increasing recognition of the potential risks of antibiotic use during infancy, H2 [receptor antagonists] and PPIs are considered to be generally safe and are commonly prescribed for children younger than a year,” the study authors say. Among the almost 800,000 children included in the study, 7.6% had been prescribed a H2 receptor antagonist in infancy and 1.7% had had a PPI. The researchers did concede that a limitation of this study could be ‘the potential bias from reverse causality’. Namely an infant’s symptoms of a food allergy could have originally been misdiagnosed as gastro-oesophageal reflux necessitating acid suppression, or early symptoms of asthma could have mistakenly been thought to be an indicator of a bacterial respiratory infection. However, the authors say, this is unlikely to be the whole story. Such scenarios cannot explain the increased rates of anaphylaxis or urticaria or medication allergy. And many food allergies don’t develop until well after the first six months so it would be unlikely that allergy would have caused the symptoms experienced by an infant. All in all, best practice, according to these researchers is to minimise the use of acid suppressive medications and antibiotics in children, particularly in children less than six months old. “This study provides further impetus that antibiotics and anti-suppressive medications should be used during infancy only in situations of clear clinical benefit,” they concluded.

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Avoid AF, Eat Nuts

Eating nuts at least three times a week reduces the risk of developing atrial fibrillation, Swedish researchers report. For the first time it has been shown that nut consumption has a linear, dose-response association with atrial fibrillation. The findings of this long-term, prospective study of over 60,000 adults, showed people who ate nuts three or more times a week were 18% less likely to develop AF than their non-nut-consuming counterparts. The study, published in the BMJ journal, Heart also found those adults with a moderate consumption of nuts (defined as up to 1-2 times a week) had a reduced risk of heart failure, but this benefit disappeared if the intake was greater than this. The study authors said it was already known that nut consumption was beneficial to heart health. “Meta-analyses of prospective studies have shown that nut consumption is inversely associated with death from cardiovascular disease, total coronary heart disease and total stroke,” they wrote. However, what was not known was exactly which cardiac conditions nut consumption affected and which outcomes it influenced. So back in 1997, they got this large cohort of men and women to complete a Food Frequency Questionnaire and then followed them up for the next 17 years utilising data from the much-admired Swedish National Patient and Death registers. In addition to nuts’ protective effect against atrial fibrillation and, to some degree heart failure, the study findings also seemed to suggest that eating nuts reduced the risk of non-fatal myocardial infarction and abdominal aortic aneurysm but this association did not hold true once confounders were taken into account. There was no link found between nut consumption and any other cardiovascular condition namely aortic valve stenosis, ischaemic stroke or intracerebral haemorrhage. Researchers suggested that nuts were effective through their anti-inflammatory and antioxidant effect, their ability to improve endothelial function and reduce LDL-cholesterol levels. They also said that the overall consumption of nuts among this study population was very low, maybe too low to have a meaningful effect on cholesterol levels. By far the majority of participants either didn’t report eating nuts at all or ate them only one to three times a month. But this may represent an opportunity for intervention. “Since only a small percentage of this population had moderate (about 5%) or high (<2%) nut consumption, even a small increase in nut consumption may have large potential to lead to a reduction in incidence of atrial fibrillation and heart failure in this population,” the study authors concluded. Ref: doi:10.1136/heartjnl-2017-312819

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Ketamine to prevent suicide?

Ketamine’s controversial role in treating depression has been boosted by a new randomised controlled trial showing it significantly and rapidly reduces suicidal ideation. Among a group of 80 severely depressed individuals already on pharmacotherapy, the US researchers found that a single, subanaesthetic infusion of ketamine was associated with a greater reduction in clinically significant suicidal ideation within 24 hours than a control midazolam infusion. After one day, 55% of the patients who received the ketamine infusion had more than halved the severity of their suicidal ideation, compared with 30% in the midazolam group. What’s more, and in contrast to previous studies on ketamine infusions, the improvement appeared to persist for at least six weeks combined with optimised pharmacotherapy, the study authors wrote in the American Journal of Psychiatry. Ketamine was first mooted as having antidepressant properties back in the 1990s, after having first been approved by the US FDA for anaesthetic use in 1970.There had been reports that it could reduce suicidal ideation, but to date the evidence to support this has been lacking. In this study, researchers used the validated Scale for Suicidal Ideation to monitor the participants who were all psychiatric outpatients. The scale categorises a score of over two as predictive of suicide in the next 20 years. The depressed adults enrolled in this study were rated as having a score of at least four– ‘a clinically significant cut-off for suicidal ideation.’ Midazolam was chosen as the comparator in the trial because, like ketamine it is a psychoactive anaesthetic agent with a similar half-life but no established antidepressant or antisuicidal effects. The finding that only four patients needed to be treated with ketamine to see a benefit over midazolam was described as a ‘medium effect’, but nonetheless significant given the lack of evidence-based pharmacotherapy currently available for suicidal patients with major depressive disorders. “Suicidal depressed patients need rapid relief of suicidal ideation,” the study authors said. And yet, despite suicidal behaviour often being associated with depression, most antidepressant trials have excluded suicidal patients and did not assess suicidal ideation and behaviour. “Standard antidepressants may reduce suicidal ideation and behaviour in depressed adults …. but this effect takes weeks,” they said. Consequently, for many, the findings of this study represent a promising new option for an area of medicine that has been notoriously difficult to treat. An accompanying editorial, also acknowledges the hope this study represents. “[T]he excitement about ketamine in our field is a reflection of the serious challenges we face in managing treatment-resistant depression,” said Dr Charles Nemeroff, leading US psychiatrist in his editorial. But he says significant concerns still exist with regard the inclusion of ketamine in the psychiatrist’s toolkit. Who regulates the use of ketamine? How do we handle its potential as a drug of abuse? Exactly how does it work? These are just some of the questions that need to be answered before it can be seriously considered as part of mainstream psychiatric medicine, Dr Nemeroff suggests. In addition, he says we may looking for a new, quick fix solution for patients too early – before having really tried all other possible treatments. “When treated with monoamine oxidase inhibitors, tricyclic antidepressants, ECT, repetitive transcranial magnetic stimulation, or augmentation with lithium, T3, atypical antipsychotics, or pramipexole, many patients with treatment-resistant depression show remarkable improvement,” he said. He suggests a ‘wait and see’ attitude be adopted, as the research and study results come in, and the evidence to support ketamine’s exact role in the world of mental illness becomes clearer. Ref: Am J Psychiatry 2018; 175: 327-335; doi:10.1176/appi.ajp.2017.17060647 Am J Psychiatry 2018; 175: 297-299; doi:10.1176/appi.ajp.2018.18010014

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New Virus Putting Babies in Hospital

In the last few months of 2017, over 200 Australian infants were hospitalised due to infection with the little known human parechovirus, say Australian public health experts in the latest issue of the MJA. The infected infants were admitted with conditions such as severe sepsis and meningoencephalitis. Less common presentations included acute abdomen from intussusception, pseudo-appendicitis and even bowel perforation. According to the MJA review, parechovirus was originally included under the echovirus umbrella back in the 1960’s, but became an entity in its own right, in the 90’s. There are close to 20 genotypes of the virus, but to date only three (genotypes 1,3 and 6) are thought to cause human disease. For the most part parechovirus causes mild gastro or respiratory tract infections. However, one of the genotypes – genotype 3  - has been found to be considerably more dangerous, especially in babies. “It is now recognised as a leading cause of sepsis-like illness and central nervous system infection, particularly in young infants,” the review authors wrote. The first ‘epidemic’ in Australia of this parechovirus genotype occurred in spring-summer of 2013-2014. Another outbreak occurred two years later – the spring-summer of 2015-2016. This most recent ‘epidemic’ appeared to start in Victoria last August and has now spread nationwide with over 200 infants hospitalised to December. For GPs, the key presenting features to be on the lookout for are fever, irritability and sepsis-like illness – which aren’t very specific. More helpfully - while not all infected children will have a rash, if the presenting infant is ‘red, hot and angry’ -think parechovirus, the authors recommend. Infants younger than three months are most likely to be hospitalised and, of course, really young infants (less than a month old) are at greatest risk of complications so should be sent to hospital earlier rather than later. To diagnose this infection, specific PCR testing needs to be requested of either stool or CSF. Just testing for enteroviruses will not be sufficient. Unfortunately, as yet there is no specific treatment for parechovirus. Given the presentation is the same as that of bacterial sepsis, the review authors suggest antibiotics be commenced until cultures come back negative and bacterial infection is excluded. But other than that, the treatment is mainly supportive and close monitoring and perhaps hospitalisation is required. Of particular concern are a number of studies that suggest infection that is severe enough to require the child be hospitalised is associated with high risk of neurological sequelae. As a consequence, the authors recommend that all children hospitalised with parechovirus be followed up with a paediatrician – at least until they start school- ‘to monitor development and learning, and manage complications including seizures.’ In terms of a vaccine, there is not one yet developed against parechovirus. They suggest research efforts should focus on developing vaccines that target the most pathogenic genotypes of a virus rather than trying to eradicate the entire genus such as has occurred in China with the vaccine against EV71 – a specific enterovirus that causes a complicated hand, foot and mouth disease. Regardless the need to find a vaccine is a priority. “The high morbidity in young children provides a strong case for prevention,” they concluded. Ref: MJA doi: 10.5694/mja18.00149

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Get Depressed Patients to Lift Weights

Resistance exercise training significantly reduces depressive symptoms, a new meta-analysis has found. According to international researchers who looked at over 30 randomised clinical trials on the subject, resistance exercise training including activities such as weight lifting reduced depressive symptoms by an average of a third. In fact, the meta-analysis findings suggested that resistance exercise training may be particularly helpful for reducing symptoms in patients with more severe depression. The study results, published in JAMA Psychiatry, concluded that only four people needed to be treated in order to have one to show significant benefit from the intervention. And the improvement inn depressive symptoms occurred regardless of the patient’s overall health status, the volume of resistance training exercise the patient undertook or any improvements in strength the patient experienced. And while the study authors made sure to point out their analysis was not comparing this exercise program with other treatments for depression, reducing symptoms by an average of a third certainly compares with other treatments currently available for this condition. “The available empirical evidence supports [resistance exercise training) as an alternative or adjuvant therapy for depressive symptoms,” the researchers said. What we still don’t know, apparently is exactly what sort of exercise, at what intensity, how frequently and for how long is required until a significant improvement in the depression is achieved. Many of the randomised controlled trials included in the meta-analysis did not measure all these parameters. What the researchers did find was that supervised training programs appeared more effective than non-supervised, which may reflect adherence to the exercise regimen. They also said the most common frequency of resistance exercise training was three times a week. The study authors suggested the limitations of the studies included in this analysis should help direct further research. “Future trials, matching different exercise modes on relevant features of the exercise stimulus, will allow more rigorous and controlled comparisons between exercise modalities, and the examination of interactions between factors such as frequency, intensity, duration and exercise modality,” they said. But regardless of the lack of fine print, the results of this moderate-sized effect of resistance exercise training reported in this study and the complete lack of adverse effects, would seem sufficient to justify recommending it to patients with depression, at least as an adjunctive treatment for one of Australia’s most common mental illnesses. Ref: JAMA Psychiatry doi:10.1001/jamapsychiatry.2018.0572

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Fatter mothers behind rise in perinatal complications

The increasing BMI of first-time pregnant women is behind a rise in adverse perinatal outcomes over a 25 year time period, a new retrospective Australian study suggests. Analysing data from one major Sydney teaching hospital, researchers found that the prevalence of overweight among women having their first baby increased from 12.7% in 1990-94 to 16.4% in 2010-14, and that of obesity rose from 4.8% to 7.3%. More importantly they found this increase in BMI was associated with a range of adverse perinatal outcomes particularly pre-eclampsia, macrosomia and gestational diabetes. Other complications believed to have increased as a result of the maternal weight gain included caesarean deliveries, post partum haemorrhage, prematurity, admission to the special care nursery and fetal abnormalities. “We found that a substantial proportion of the burden of adverse perinatal outcomes for Australian women is linked to maternal overweight and obesity, and that this proportion has steadily increased over the past 25 years,” the Sydney researchers said. The study involved the analysis of the data recorded on over 42000 singleton births delivered to previously nulliparous women at the Royal Prince Alfred Hospital Sydney between 1990 and 2014. Interestingly over the course of the study period, the mean age for first time mothers rose from 28.7 to 31.6 years, however having adjusted for this as well as other possible confounders such as changing smoking rates, socioeconomic status, and country of birth of the mother the findings confirmed the relative risks of adverse perinatal outcomes had increased in association with rising prevalence of overweight and obesity. Researchers calculated that should overweight or obese women move down one BMI category (for example from obese to overweight) 19% of pre-eclampsia, 15.9% of macrosomia and 14.2% of gestational diabetes could be averted. “Our results indicate that the frequency of adverse perinatal outcomes could be reduced by shifting the distribution of overweight and obesity among first-time mothers by a single BMI class. Investing in obesity prevention strategies that target women prior to their becoming pregnant is likely to provide the greatest benefit,” they concluded. Ref: MJA doi:10.5694/mja17.00344

By Dr Linda Calabresi
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Change in advice for abscess drainage

Skin abscesses are best treated with incision and drainage plus antibiotics, rather than just incision and drainage alone, recommends an international guideline panel in the BMJ. After critically appraising all the current evidence, the panel found adjuvant antibiotic therapy in addition to incision and drainage of uncomplicated skin abscesses reduced the risk of treatment failure and abscess recurrence by approximately 13% compared to treatment without additional antibiotics. In particular the randomised controlled trials included in the review, were evaluating the use of clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) in addition to incision and drainage. “TMP-SMX or clindamycin modestly reduces pain and treatment failure and probably reduces abscess recurrence, but increases the risk of adverse effects including nausea and diarrhoea,” they said. TMP-SMX is the more preferable option over clindamycin as it is less likely to cause diarrhoea, they added. The recommendation is in contrast to most of the current guidelines that generally advise uncomplicated skin abscesses be treated with incision and drainage alone except in cases where there is systemic illness, extensive tissue damage, immunocompromising conditions, an artificial joint or a high risk of endocarditis. And while the panel concedes that the benefit of adjuvant antibiotic therapy is modest, they anticipate that most fully informed patients would consider it large enough to choose it over incision and drainage alone. Of course, the major counter argument against increasing antibiotic use would be the possible increased risk of antimicrobial resistance. “From a societal perspective, it is possible that the modest benefits from adjuvant antibiotics in this scenario would not outweigh the risk of antimicrobial resistance in the community,” they said. However, the impact of a single course of antibiotics on this public health problem remains unknown, so any conclusion about net benefit versus net harm can only be speculative, they concluded, even though the issues are worth considering as part of the shared decision making. The panel also considered evidence for using cephalosporins for adjuvant treatment of skin abscesses, however they concluded that this class of antibiotics was unlikely to provide any benefit over incision and drainage in the majority of cases of skin abscesses, and therefore could not be recommended. Ref: BMJ 2018; 360: k243 doi.org/10.1136/bmj.k243

By Dr Linda Calabresi
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Opioids offer little over NSAIDs for chronic severe pain

Opioids have really fallen out of favour as a chronic pain relief option. Even for patients with severe chronic back pain, or severe pain from their osteoarthritis in their hip or knee, opioids will not offer any better relief in terms of pain-restricted function that non-opioid medication, a recent study published in JAMA has shown. The US clinical trial involved 240 US adults with moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic.  Researchers compared whether treatment with opioids such as morphine, oxycodone or hydrocodone/paracetamol improved pain-related function over a 12-month period over treatment with nonopioid such as paracetamol or an NSAID. Surprisingly, the results showed no significant difference in terms of pain related function over the course of the study. In fact, the pain intensity was significantly better in the nonopioid group over the 12-month period, however the study authors said the clinical importance of this finding was unclear. As was perhaps more expected, the group that took opioids had more side effects. “Overall, opioids did not demonstrate any advantage over nonopioid medication that could potentially outweigh their greater risk of harms,” the researchers said. When looking at all the results – even including secondary outcomes,  the only area where opioids were found to be superior to nonopioids in this study of chronic pain patients was in the area of anxiety. The opioid group had fewer anxiety symptoms – so they had just as little function, and even more intense pain but they worried about it less. The study authors said their findings added to the growing body of evidence that opioids offer little benefit over other medications and even placebo in the management of chronic pain conditions, especially when their side effect profile is taken into consideration. “Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain”, they concluded. Ref: JAMA 2018;319(9) 872-882. doi:10.1001/jama.2018.0899

By Dr Linda Calabresi
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Advice for shift workers

We know night shift work is not good for your health. Evidence shows night shift work is associated with an increased risk of sleep loss, occupational accidents, obesity and weight gain, type 2 diabetes, coronary heart disease, and breast, prostate and colorectal cancers, according to a review in the BMJ by two intensive care specialists. But what of strategies to help night shift workers mitigate these risks? What does the research say we should be advising these patients to do to optimise their health, remembering that many health professionals will be involved in this type of shift work? According to the review, there is a ‘paucity of adequately powered, well designed, randomised controlled trials’ on the subject however from what there was and with the addition of expert opinion the review authors recommended the following.
  • Try and make sure you’re not sleep-deprived before a night shift. Try and wake the morning before naturally (without an alarm) and, if possible have a daytime nap maybe taking advantage of that ‘circadian dip’ between 2 and 6pm the afternoon before you front up for night duty.
  • If you get the opportunity to nap during the night shift, try to limit the duration of these to less than 30 minutes, “to avoid slow wave sleep followed by grogginess on waking, known as ‘sleep inertia’”, the authors advise.
  • Caffeine reduces sleepiness and improves performance 20-45 minutes after taking it, with the effect lasting up to five hours.
  • There is evidence that drugs such as modafinil are effective in reducing sleepiness in night shift workers compared with placebo but these drugs have been associated with skin reactions and their long-term safety is yet to be established. Similarly, exposure to bright light has been proposed as a possible means of inhibiting melatonin, reducing sleepiness and perhaps reducing the cancer risk associated with shift work but neither these drugs nor bright light exposure is supported by sufficient evidence to be conclusively recommended.
  • Hunger and digestion are both affected by circadian rhythm. There is some evidence to suggest if you don’t eat you’ll perform better over the duration of the night shift than if you eat, however it is likely you will experience hunger and will be more likely to get GI symptoms leading the authors to recommend a main meal immediately before the shift and then small snacks as required to stave off hunger overnight.
  • And the big one. How to optimise sleep between night shifts? Well- the recommendations are fairly predictable – avoid bright light on the way home (wear sunglasses), employ blue screens on your computer and phone, use eye masks and ear plugs and develop a predictable pre-bed routine. Avoid caffeine for at least six hours before sleep time and perhaps consider taking melatonin the morning after a night shift –some evidence suggests that this increases sleep duration by up to 24 minutes.
“A meta-analysis of 66 studies concluded that regular exercise leads to improvement in sleep quantity and quality, but the optimum timing, duration, and type of exercise for sleep promotion have yet to be determined,” they said. In addition, the review authors didn’t recommend any other sleeping tablets due to a lack of quality evidence of their effectiveness and the risk of dependency. Finally, the researchers advised night shift workers to be aware their performance is likely to be reduced especially in that particularly vulnerable time between 3 and 5am and therefore they should seek support when required to do critical tasks at this time. They also warned workers to be aware of their vulnerability when driving home after night shift and referred to a patient, the inspiration for this review, who experienced the life-changing consequences of being involved in a road traffic accident while on a set of night shifts in 2005. Ref: BMJ 2018; 360:j5637 doi: 10.1136/bmj.j5637

By Dr Linda Calabresi
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Don’t pickle old brains

Want to preserve your brain function into old age? Cut down on the booze. That’s the conclusion of a large, longitudinal study just published in JAMA Psychiatry. After comparing more than 200 alcohol dependent adults with a similar number of healthy adults, over a 14 year period, the US researchers concluded alcohol-dependence accelerated the cortical ageing process even if the alcohol habit developed later in life. They found, through a series of MRIs that alcohol dependence (as per the DSM-IV criteria) resulted in more rapid frontal lobe deterioration than that which just occurred with age, regardless of gender. As part of the study the researchers also looked at whether comorbidities such as drug use or hepatitis C infection made a difference to the decline in cognitive function. And while they found they compounded the shrinkage of the frontal lobe, the actual deficits in the frontal cortex seemed to be associated chiefly with the alcohol. “We observed a selectivity of frontal cortex to age-alcoholism interaction beyond normal aging effects and independent of deficits related to drug dependence,” they said. Also, the researchers found that the deterioration was more associated with current drinking habits  than the cumulative effect of many years of alcohol abuse. People who had become alcohol dependent later in life were just as vulnerable as people whose alcohol use disorder started when they were younger. “The accelerated volume deficits in the older alcohol-dependent participants could not readily be attributed to more years of heavy drinking, given that many had a late onset of their disorder and lower lifetime alcohol consumption estimates than their early-onset counterparts,” the study authors said. So, it appears the frontal cortex, which is that part of brain that helps people plan, reason, modify behaviours and problem solve is the most vulnerable to damage in people with alcohol use disorder. Add this to the fact the frontal cortex deterioration associated with aging, is fundamentally responsible for the deterioration in executive function that limits an elderly person’s ability to function and live independently, and you have a recipe for disaster for those older people who drink to excess. What does this all mean? An accompanying editorial makes the take home message quite clear. “Given the rapidly growing aging population… it is critical that we improve and implement strategies to address alcohol misuse among older drinkers. As Yoda might say, “Protect their brains, we must.” Ref: JAMA Psychiatry. Published online March 14, 2018. doi:10.1001/jamapsychiatry.2018.002 JAMA Psychiatry. Published online March 14, 2018. doi:10.1001/jamapsychiatry.2018.0009

By Dr Linda Calabresi
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Cheapest Option Just as Good for Vaginal Atrophy

Post-menopausal women experiencing vulvovaginal symptoms will benefit just as much from using the cheapest over-the-counter lubricant or moisturiser as using topical oestrogen, a new study suggests. The 12-week randomised clinical trial, published in JAMA Internal Medicine, compared the efficacy of a low-dose vaginal oestradiol tablet and a vaginal moisturiser, each versus placebo among a group of over 300 post-menopausal women with moderate to severe vulvovaginal symptoms. To determine the effectiveness of the treatment women were asked to report on the severity of their ‘most bothersome symptom’ which included pain with vaginal penetration (60%), dryness (21%), itching (7%), irritation (6%) and pain (5%). Across the board, regardless of which treatment was used, most women had a decrease of at least 50% in symptom severity over the course of the study. This was significant in light of the fact that most women said they ‘frequently’ or ‘always’ distressed about their sex life at enrolment, whereas after the 12-week study nearly half said they were ‘rarely’ or ‘never’ distressed. “No treatment group differences in symptom reduction were observed for vaginal oestradiol tablet plus placebo gel vs dual placebo, or vaginal moisturiser plus placebo tablet vs dual placebo”, the US researchers reported. And it didn’t matter if the most bothersome symptom was dyspareunia or itching, it appeared the hormone treatment or the specific vaginal moisturiser (Replens) had no advantage over the placebo combination. According to the study authors, the placebo gel used in the study had a similar pH and viscosity as the vaginal moisturiser (Replens) but was less mucoadhesive. The fact that both formulations were equally effective in reducing symptoms suggests that the mucoadhesive properties are less important than previously thought. Similarly, markers of vaginal oestrogenisation such as the vaginal maturation index, did, naturally improve more with the topical oestrogen but this did not translate into a greater benefit in terms of symptoms over placebo. As an accompanying editorial points out, “ultimately, it is improvement in symptoms rather than surrogates such as tissue markers that should define the goal of care.” And while the study authors conclude that treatment choice for women with troublesome postmenopausal vulvovaginal symptoms should be ‘based on individual patient preferences regarding cost and formulation’ the editorial authors go in much stronger. “[P]ostmenopausal women experiencing vulvovaginal symptoms should choose the cheapest moisturiser or lubricant available over the counter – at least until new evidence arises to suggest there is any benefit to doing otherwise.” Ref: JAMA Intern Med. doi:10.1001/jamainternmed.2018.0116 JAMA Intern Med. doi:10.1001/jamainternmed.2018.0094

By Dr Linda Calabresi
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A Missed Opportunity

Patients are still not consistently being prescribed exercise despite the wealth of evidence that shows its health benefit, according to an editorial in the latest issue of the MJA. The authors, all sports medicine specialists point to statistics showing physical inactivity being the fourth leading cause of morbidity and mortality worldwide. And they reiterate the well-proven benefits of exercise in helping to manage a wide array of chronic diseases from diabetes to depression. Even though physicians have a good track record of influencing lifestyle factors as evidenced by smoking cessation rates, it appears when it comes to exercise GPs are dropping the ball. “Most physicians do not regularly assess or prescribe physical activity or specific exercises,” said the editorial authors who included GP, Dr Anita Green, Chief Medical Officer of the Gold Coast Commonwealth Games. “Even when exercise is advised by physicians, the advice is often not specific or in depth, and simple evidence-based behaviour modification techniques are not routinely used.” But why is this advice, which is also recommended in the RACGP Handbook of non-drug interventions not being given to patients as a matter of routine? One of the greatest barriers to the dispensing of this advice, according to the editorial, is the clinician not practising what he or she should be preaching. “It has been consistently shown that physically active clinicians are more likely to provide physical activity counselling to their patients,” the authors said. And apparently the medical profession could do better in terms of regular exercise. Physical activity levels have been shown to decline during medical training and through residency, perhaps unsurprisingly. More emphasis needs to be placed on the importance of physical activity and exercise prescription as part of both undergraduate and postgraduate training, not only to help clinicians to help their patients but also to help clinicians help themselves. According to the editorial, the current Gold Coast 2018 Commonwealth Games are likely to inspire the next generation of elite athletes to commit to specialised exercise regimens and dedicated training rituals. However, for the vast majority of the sports-viewing population, the spectacle is unlikely to prove sufficiently inspirational to prize them off the couch. If the medical profession really wants to achieve better health outcomes for their inactive patients, it appears they need to lead by example. “Physicians should unequivocally incorporate physical activity into their own daily routine, for their own health benefit, and to become an exercise role model, more confident in prescribing exercise to their patients,” the authors concluded. Ref: MJA doi: 10.5694/mja18.00033

By Dr Linda Calabresi
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Reflux Meds in Infants Doubles Risk of Allergy

Infants receiving acid suppressive medications are more than twice as likely to develop food allergies later in life, US researchers say. Findings from a large retrospective study, analysing data from almost 800,000 children, showed that being prescribed either an H2 receptor antagonist or a proton pump inhibitor in the first six months more than doubled the risk of developing a food allergy (hazard ratios of 2.18 and 2.59 respectively) when they got older. Similarly, the use of these medications was also found to associated with an increased risk of other allergies as well, including medication allergy (HR 1.70 and 1.84), anaphylaxis (HR 1.50 and 1.45) and, to a lesser extent, allergic rhinitis and asthma. As part of the same study, the researchers also looked at antibiotics in the first six months and, perhaps unsurprisingly found a link between this type of medication and developing an allergic condition. In the case of antibiotics, children were more likely to develop allergic respiratory conditions such as asthma and allergic rhinitis than food allergies. The findings have biological plausibility, the researchers said in JAMA. Acid suppressive medications inhibit the breakdown of ingested protein which, in turn facilitates IgE antibody production increasing the sensitivity to ingested antigens. The medications also, by definition, interfere with histamine which researchers now believe has a greater role in modulating immune system functioning than previously thought. The association between increased allergy and antibiotics, on the other hand supports findings from previous studies, and is thought to be related to the effect of the antibiotics on the gut bacteria or microbiome. It is one of a number of reasons why there has been growing pressure on clinicians to try to avoid prescribing antibiotics to infants. “While there has been increasing recognition of the potential risks of antibiotic use during infancy, H2 [receptor antagonists] and PPIs are considered to be generally safe and are commonly prescribed for children younger than a year,” the study authors say. Among the almost 800,000 children included in the study, 7.6% had been prescribed a H2 receptor antagonist in infancy and 1.7% had had a PPI. The researchers did concede that a limitation of this study could be ‘the potential bias from reverse causality’. Namely an infant’s symptoms of a food allergy could have originally been misdiagnosed as gastro-oesophageal reflux necessitating acid suppression, or early symptoms of asthma could have mistakenly been thought to be an indicator of a bacterial respiratory infection. However, the authors say, this is unlikely to be the whole story. Such scenarios cannot explain the increased rates of anaphylaxis or urticaria or medication allergy. And many food allergies don’t develop until well after the first six months so it would be unlikely that allergy would have caused the symptoms experienced by an infant. All in all, best practice, according to these researchers is to minimise the use of acid suppressive medications and antibiotics in children, particularly in children less than six months old. “This study provides further impetus that antibiotics and anti-suppressive medications should be used during infancy only in situations of clear clinical benefit,” they concluded.

By Dr Linda Calabresi
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Avoid AF, Eat Nuts

Eating nuts at least three times a week reduces the risk of developing atrial fibrillation, Swedish researchers report. For the first time it has been shown that nut consumption has a linear, dose-response association with atrial fibrillation. The findings of this long-term, prospective study of over 60,000 adults, showed people who ate nuts three or more times a week were 18% less likely to develop AF than their non-nut-consuming counterparts. The study, published in the BMJ journal, Heart also found those adults with a moderate consumption of nuts (defined as up to 1-2 times a week) had a reduced risk of heart failure, but this benefit disappeared if the intake was greater than this. The study authors said it was already known that nut consumption was beneficial to heart health. “Meta-analyses of prospective studies have shown that nut consumption is inversely associated with death from cardiovascular disease, total coronary heart disease and total stroke,” they wrote. However, what was not known was exactly which cardiac conditions nut consumption affected and which outcomes it influenced. So back in 1997, they got this large cohort of men and women to complete a Food Frequency Questionnaire and then followed them up for the next 17 years utilising data from the much-admired Swedish National Patient and Death registers. In addition to nuts’ protective effect against atrial fibrillation and, to some degree heart failure, the study findings also seemed to suggest that eating nuts reduced the risk of non-fatal myocardial infarction and abdominal aortic aneurysm but this association did not hold true once confounders were taken into account. There was no link found between nut consumption and any other cardiovascular condition namely aortic valve stenosis, ischaemic stroke or intracerebral haemorrhage. Researchers suggested that nuts were effective through their anti-inflammatory and antioxidant effect, their ability to improve endothelial function and reduce LDL-cholesterol levels. They also said that the overall consumption of nuts among this study population was very low, maybe too low to have a meaningful effect on cholesterol levels. By far the majority of participants either didn’t report eating nuts at all or ate them only one to three times a month. But this may represent an opportunity for intervention. “Since only a small percentage of this population had moderate (about 5%) or high (<2%) nut consumption, even a small increase in nut consumption may have large potential to lead to a reduction in incidence of atrial fibrillation and heart failure in this population,” the study authors concluded. Ref: doi:10.1136/heartjnl-2017-312819

By Dr Linda Calabresi
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Ketamine to prevent suicide?

Ketamine’s controversial role in treating depression has been boosted by a new randomised controlled trial showing it significantly and rapidly reduces suicidal ideation. Among a group of 80 severely depressed individuals already on pharmacotherapy, the US researchers found that a single, subanaesthetic infusion of ketamine was associated with a greater reduction in clinically significant suicidal ideation within 24 hours than a control midazolam infusion. After one day, 55% of the patients who received the ketamine infusion had more than halved the severity of their suicidal ideation, compared with 30% in the midazolam group. What’s more, and in contrast to previous studies on ketamine infusions, the improvement appeared to persist for at least six weeks combined with optimised pharmacotherapy, the study authors wrote in the American Journal of Psychiatry. Ketamine was first mooted as having antidepressant properties back in the 1990s, after having first been approved by the US FDA for anaesthetic use in 1970.There had been reports that it could reduce suicidal ideation, but to date the evidence to support this has been lacking. In this study, researchers used the validated Scale for Suicidal Ideation to monitor the participants who were all psychiatric outpatients. The scale categorises a score of over two as predictive of suicide in the next 20 years. The depressed adults enrolled in this study were rated as having a score of at least four– ‘a clinically significant cut-off for suicidal ideation.’ Midazolam was chosen as the comparator in the trial because, like ketamine it is a psychoactive anaesthetic agent with a similar half-life but no established antidepressant or antisuicidal effects. The finding that only four patients needed to be treated with ketamine to see a benefit over midazolam was described as a ‘medium effect’, but nonetheless significant given the lack of evidence-based pharmacotherapy currently available for suicidal patients with major depressive disorders. “Suicidal depressed patients need rapid relief of suicidal ideation,” the study authors said. And yet, despite suicidal behaviour often being associated with depression, most antidepressant trials have excluded suicidal patients and did not assess suicidal ideation and behaviour. “Standard antidepressants may reduce suicidal ideation and behaviour in depressed adults …. but this effect takes weeks,” they said. Consequently, for many, the findings of this study represent a promising new option for an area of medicine that has been notoriously difficult to treat. An accompanying editorial, also acknowledges the hope this study represents. “[T]he excitement about ketamine in our field is a reflection of the serious challenges we face in managing treatment-resistant depression,” said Dr Charles Nemeroff, leading US psychiatrist in his editorial. But he says significant concerns still exist with regard the inclusion of ketamine in the psychiatrist’s toolkit. Who regulates the use of ketamine? How do we handle its potential as a drug of abuse? Exactly how does it work? These are just some of the questions that need to be answered before it can be seriously considered as part of mainstream psychiatric medicine, Dr Nemeroff suggests. In addition, he says we may looking for a new, quick fix solution for patients too early – before having really tried all other possible treatments. “When treated with monoamine oxidase inhibitors, tricyclic antidepressants, ECT, repetitive transcranial magnetic stimulation, or augmentation with lithium, T3, atypical antipsychotics, or pramipexole, many patients with treatment-resistant depression show remarkable improvement,” he said. He suggests a ‘wait and see’ attitude be adopted, as the research and study results come in, and the evidence to support ketamine’s exact role in the world of mental illness becomes clearer. Ref: Am J Psychiatry 2018; 175: 327-335; doi:10.1176/appi.ajp.2017.17060647 Am J Psychiatry 2018; 175: 297-299; doi:10.1176/appi.ajp.2018.18010014

By Dr Linda Calabresi
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New Virus Putting Babies in Hospital

In the last few months of 2017, over 200 Australian infants were hospitalised due to infection with the little known human parechovirus, say Australian public health experts in the latest issue of the MJA. The infected infants were admitted with conditions such as severe sepsis and meningoencephalitis. Less common presentations included acute abdomen from intussusception, pseudo-appendicitis and even bowel perforation. According to the MJA review, parechovirus was originally included under the echovirus umbrella back in the 1960’s, but became an entity in its own right, in the 90’s. There are close to 20 genotypes of the virus, but to date only three (genotypes 1,3 and 6) are thought to cause human disease. For the most part parechovirus causes mild gastro or respiratory tract infections. However, one of the genotypes – genotype 3  - has been found to be considerably more dangerous, especially in babies. “It is now recognised as a leading cause of sepsis-like illness and central nervous system infection, particularly in young infants,” the review authors wrote. The first ‘epidemic’ in Australia of this parechovirus genotype occurred in spring-summer of 2013-2014. Another outbreak occurred two years later – the spring-summer of 2015-2016. This most recent ‘epidemic’ appeared to start in Victoria last August and has now spread nationwide with over 200 infants hospitalised to December. For GPs, the key presenting features to be on the lookout for are fever, irritability and sepsis-like illness – which aren’t very specific. More helpfully - while not all infected children will have a rash, if the presenting infant is ‘red, hot and angry’ -think parechovirus, the authors recommend. Infants younger than three months are most likely to be hospitalised and, of course, really young infants (less than a month old) are at greatest risk of complications so should be sent to hospital earlier rather than later. To diagnose this infection, specific PCR testing needs to be requested of either stool or CSF. Just testing for enteroviruses will not be sufficient. Unfortunately, as yet there is no specific treatment for parechovirus. Given the presentation is the same as that of bacterial sepsis, the review authors suggest antibiotics be commenced until cultures come back negative and bacterial infection is excluded. But other than that, the treatment is mainly supportive and close monitoring and perhaps hospitalisation is required. Of particular concern are a number of studies that suggest infection that is severe enough to require the child be hospitalised is associated with high risk of neurological sequelae. As a consequence, the authors recommend that all children hospitalised with parechovirus be followed up with a paediatrician – at least until they start school- ‘to monitor development and learning, and manage complications including seizures.’ In terms of a vaccine, there is not one yet developed against parechovirus. They suggest research efforts should focus on developing vaccines that target the most pathogenic genotypes of a virus rather than trying to eradicate the entire genus such as has occurred in China with the vaccine against EV71 – a specific enterovirus that causes a complicated hand, foot and mouth disease. Regardless the need to find a vaccine is a priority. “The high morbidity in young children provides a strong case for prevention,” they concluded. Ref: MJA doi: 10.5694/mja18.00149

By Dr Linda Calabresi
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Get Depressed Patients to Lift Weights

Resistance exercise training significantly reduces depressive symptoms, a new meta-analysis has found. According to international researchers who looked at over 30 randomised clinical trials on the subject, resistance exercise training including activities such as weight lifting reduced depressive symptoms by an average of a third. In fact, the meta-analysis findings suggested that resistance exercise training may be particularly helpful for reducing symptoms in patients with more severe depression. The study results, published in JAMA Psychiatry, concluded that only four people needed to be treated in order to have one to show significant benefit from the intervention. And the improvement inn depressive symptoms occurred regardless of the patient’s overall health status, the volume of resistance training exercise the patient undertook or any improvements in strength the patient experienced. And while the study authors made sure to point out their analysis was not comparing this exercise program with other treatments for depression, reducing symptoms by an average of a third certainly compares with other treatments currently available for this condition. “The available empirical evidence supports [resistance exercise training) as an alternative or adjuvant therapy for depressive symptoms,” the researchers said. What we still don’t know, apparently is exactly what sort of exercise, at what intensity, how frequently and for how long is required until a significant improvement in the depression is achieved. Many of the randomised controlled trials included in the meta-analysis did not measure all these parameters. What the researchers did find was that supervised training programs appeared more effective than non-supervised, which may reflect adherence to the exercise regimen. They also said the most common frequency of resistance exercise training was three times a week. The study authors suggested the limitations of the studies included in this analysis should help direct further research. “Future trials, matching different exercise modes on relevant features of the exercise stimulus, will allow more rigorous and controlled comparisons between exercise modalities, and the examination of interactions between factors such as frequency, intensity, duration and exercise modality,” they said. But regardless of the lack of fine print, the results of this moderate-sized effect of resistance exercise training reported in this study and the complete lack of adverse effects, would seem sufficient to justify recommending it to patients with depression, at least as an adjunctive treatment for one of Australia’s most common mental illnesses. Ref: JAMA Psychiatry doi:10.1001/jamapsychiatry.2018.0572

By Dr Linda Calabresi
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