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Oncology

Clinical Articles

Detecting Liver Cancer Early

GPs can make a significant difference in curbing the rising rates of liver cancer deaths in Australia, experts say. According to an analysis of over 270 cases of newly diagnosed cases of hepatocellular cancer presenting at seven Melbourne tertiary hospitals over one year, researchers say survival rates could be improved with earlier diagnosis of cirrhosis and better adherence to recommended screening schedules among those known to be at high risk. “[T]he number of liver cancer-related deaths has been the most rapid for any cancer type in Australia over the past 40 years,” the study authors said in the MJA. And of all the types of liver cancer, hepatocellular carcinoma is by far the most common, accounting for 82%. Even though treatments are available, both curative and palliative survival remains very poor with the Australian 12-month survival rate estimated to be only 62%. In this particular study, conducted over 2012/2013 the mean survival was only 18 months. As one would expect, the patients who did better, who generally survived the longest were those whose tumours were detected at an earlier stage. These were usually the patients who were known to be at high risk of developing liver cancer and were participating in a surveillance program. But this was only 40% of the 272 cases, even though 89% would have qualified for surveillance based on their risk factors. Why was this? Well firstly, many of these people did not know they were at risk. And that’s where GPs fit in. In the study the most common risk factors for liver cancer were found to be hepatitis C infection (41%), alcohol-related liver disease (39%), hepatitis B infection (22%) and non-alcoholic fatty liver disease (14%). Many had more than one risk factor. Most telling was the finding that, even though the vast majority of patients (83%) had cirrhosis when they were diagnosed with hepatocellular carcinoma, for one third of them that was the first they knew of it. The study authors suggest clinicians need to be alert for risk factors for chronic liver disease such as excess alcohol use, chronic HCV and HBV infections and even non-alcoholic liver disease in certain groups. In these people, checking for cirrhosis is likely to be worthwhile. “An aspartate transaminase to platelet ratio index (APRI) value greater than 1.0 predicts cirrhosis with 76% sensitivity and 72% specificity, and the test is simple to undertake,” the researchers said. The other major barrier to the earlier detection of liver cancer identified in the study was the poor adherence to surveillance among those people identified as being at high risk. Researchers found patients with alcohol-related liver disease or decompensated liver disease were the least likely to get regular monitoring. A surveillance program for this particular cancer involves a 6-monthly liver ultrasound and serum alpha-fetoprotein assessment. The study authors are advocating a national hepatocellular cancer surveillance program for those who are at high risk of developing the disease, which would include all patients with cirrhosis, Asian men over 40, women over 50, Africans over 20 years of age, and patients with a family history of [hepatocellular carcinoma] without cirrhosis but with chronic HBV infections. A national program to screen for hepatocellular carcinoma amongst this particular group would be worthwhile, the researchers said, as the incidence of the cancer is high, the screening is non-invasive and inexpensive and, perhaps most importantly early detection has been shown to improve survival. However, until such a national program is developed, researchers are encouraging GPs to ensure that their at-risk patients are enrolled in a surveillance program in order to hopefully improve their health outcomes. Reference: Hong TP, Gow PJ, Fink M, Dev A, Roberts SK, Nicoll A, et al. Surveillance improves survival of patients with hepatocellular carcinoma: a prospective population-based study. Med J Aust [Internet]. 2018 Sep 24; 209(8): 1-7. Available from: https://www.mja.com.au/journal/2018/209/8/surveillance-improves-survival-patients-hepatocellular-carcinoma-prospective doi: 10.5694/mja18.00373

By Dr Linda Calabresi

Rheumatology

Kevin Davies, Jessica Eccles & Neil Harrison

Clinical Articles

What Causes Fibromyalgia?

Fibromyalgia is something of a mystery. It can’t be detected with scans or blood tests, yet it causes lifelong pain for millions of people. The disease mainly affects women (about 75-90% of cases), causing pain all over the body. Because not all healthcare professionals are adept at identifying and diagnosing fibromyalgia, reported rates of the condition vary greatly from country to country. In China, it affects only 0.8% of people, in France around 1.5%, in Canada 3.3%, and in Turkey 8.8%. Estimates in the US range from 2.2% to 6.4%, and in Russia, about 2% of the population is affected. People with the condition are often diagnosed if they have longstanding muscle pain, bone or joint pain and fatigue. Fibromyalgia can also cause insomnia, “brain fog”, some symptoms of depression or anxiety, as well as a range of other complaints, including irritable bowel syndrome and headache. Many patients are also hypermobile (“double-jointed”), and there is some overlap with chronic fatigue syndrome (also known as ME). Guidelines from the American College of Rheumatology make it clear that the diagnosis should be made using defined criteria based on the “widespread pain index” (which scores the number of painful regions out of 19) coupled with a symptom severity scale. The diagnosis also takes fatigue, generalised pain, unrefreshing sleep and cognitive symptoms into account. It doesn’t matter if the patient has another rheumatic disease, they can still be diagnosed with fibromyalgia. The scoring system, recommended by the American College of Rheumatology, is often used in clinical trials, but in the clinic, most doctors rely on detecting tender points in specific places and on excluding other medical conditions, including rheumatic conditions. Unlike say, rheumatoid arthritis or lupus, the tests do not show clear evidence of inflammation or autoimmunity (when the body’s immune system attacks itself) and scans are normal. The lack of inflammation or structural abnormality in muscles or joints – aside from making diagnosis difficult – is the main reason there are no widely accepted or effective treatments. In rheumatic diseases, where we understand the mechanisms that underlie the condition, we have the most effective treatments. In rheumatoid arthritis, for example, we know that much of the inflammation is caused by a cell-signalling protein (cytokine) called tumour necrosis factor and that blocking the activity of this protein switches off the disease in most patients. A number of possible mechanisms have been proposed in fibromyalgia, including abnormal muscle metabolism, reduced levels of steroid hormones such as cortisol, or abnormal small nerve fibres. But these abnormalities aren’t found in all patients with the condition. As such, they can’t be used as part of a diagnostic test, nor can they help develop treatments. Some experts have suggested that fibromyalgia may be related to abnormalities in the autonomic nervous system – the part of the nervous system that controls bodily functions, such as heart rate and blood pressure – and how the brain responds to pain signals and reacts to external stressors (such as infections). But there is currently no hard evidence to back up this theory. Looking for clues To fill in some of the gaps in our knowledge about this devastating condition, our research team at Brighton and Sussex Medical School is investigating the potential role of the autonomic nervous system and inflammation in fibromyalgia and chronic fatigue syndrome. For our study, we have two groups of patients: one with pain as the main symptom and the other with fatigue as the main symptom. We also have matched controls – people without the disease, but otherwise similar characteristics – to make meaningful comparisons. The study is in two parts. First, we will test the patients’ autonomic nervous system using a tilt-table. This involves tilting the person head downwards to see how well their body adapts to this change in posture by changing heart rate and blood pressure (both of which are monitored during the test).Second, we will stimulate patients’ immune systems with a typhoid vaccine (the normal type used in travellers) and perform magnetic resonance brain scans to look for changes in blood flow and also measure the levels of “inflammatory mediators” (the chemicals the body produces in response to stimuli of this type), to see whether these are higher in the fibromyalgia patients. Our study should, for the first time, help us to address the question of whether there really is an abnormal brain response to inflammation or infection in these patient groups and enable us to explore the relationship between the abnormal functioning of the autonomic nervous system and fibromyalgia and chronic fatigue syndrome. Fibromyalgia rarely goes away and treatment options are limited. Only by developing a proper understanding of the disease processes underlying this condition will doctors be able to make a clear, positive diagnosis, and most importantly, offer effective therapy. Disclosure Statement Kevin Davies receives funding from AR-UK. Jessica Eccles receives funding from Academy of Medical Sciences, National Institute of Health Research, MQ Neil Harrison receives funding from the Wellcome Trust, Medical Research Council (MRC), Arthritis Research UK, and Janssen Pharmaceuticals.

By Kevin Davies, Jessica Eccles & Neil Harrison

Psychiatry

Clinical Articles

Fatty Acids of Value in Anxiety

The value of omega-3 fatty acids has come under fire lately. But now a new systematic review suggests they might have benefits beyond the previous therapeutic targets of depression, cardiac health, eye health and arthritis. Researchers have found that omega-3 polyunsaturated fatty acids (PUFA) might reduce the symptoms of clinical anxiety, particularly among those people who had a specific clinical condition be it medical (such as Parkinson disease) or psychological (premenstrual syndrome). “This systematic review…provides the first meta-analytic evidence, to our knowledge, that omega-3 PUFA treatment may be associated with anxiety reduction, which might not only be due to a potential placebo effect, but also from some associations of treatment with reduced anxiety symptoms,” the review authors said in JAMA. The finding is likely to be welcome news for patients with this condition. Be it the potential side-effects of medications or the cost and accessibility of psychological therapy, patients with anxiety, especially those with comorbid medical conditions are keen for alternative or at least supplementary safe, evidence-based treatments for their symptoms. Previous research, in both human and animal studies had found that a lack of omega-3 PUFAs could induce various behavioural and neuropsychiatric disorders. What had not been shown was whether taking this supplement was effective in reducing the specific anxiety symptoms. The review involved an extensive literature search through a wide range of databases including PubMed and Cochrane looking for trials that had assessed the anxiolytic effects of these fatty acids in humans. In the end they found 19 trials that matched their eligibility criteria, which allowed researchers to analyse the effect of supplementation in just over 1200 participants and compare it with about 1000 matched controls who didn’t take the fatty acids. Overall, they found ‘there was a significantly better association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it.’ Subgroup analysis also showed that those taking at least 2000mg or more of the omega-3 PUFA treatment were more likely to have reduced anxiety. And somewhat surprisingly, those patients receiving supplements containing less than 60% EPA did better than those taking formulations with a greater concentration of EPA. The studies in the review included very different cohorts, and because of this and the limited number of studies included, the authors understandably say the results need to be interpreted with caution. However, while bigger, better studies are still needed to prove the benefit of omega-3 PUFAs in patients with clinical anxiety, this research certainly does suggest that higher dose formulations of less than 60% concentration of EPA might have a role as at least adjunctive treatment to standard therapy. Reference: Su KP, Tseng PT, Lin PY, Okubo R, Chen TY, Chen YW, et al. Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms; A Systematic Review and Meta-analysis. JAMA Network Open [Internet]. 2018 Sep; 1(5): e182327. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701735 doi:10.1001/jamanetworkopen.2018.2327.

By Dr Linda Calabresi

Diet and nutrition

Clinical Articles

Five Types of Food to Increase Your Psychological Well-Being

We all know eating “healthy” food is good for our physical health and can decrease our risk of developing diabetes, cancer, obesity and heart disease. What is not as well known is that eating healthy food is also good for our mental health and can decrease our risk of depression and anxiety. Mental health disorders are increasing at an alarming rate and therapies and medications cost $US2.5 trillion dollars a year globally. There is now evidence dietary changes can decrease the development of mental health issues and alleviate this growing burden. Australia’s clinical guidelines recommend addressing diet when treating depression. Recently there have been major advances addressing the influence certain foods have on psychological well-being. Increasing these nutrients could not only increase personal well-being but could also decrease the cost of mental health issues all around the world. 1. Complex carbohydrates One way to increase psychological well-being is by fuelling brain cells correctly through the carbohydrates in our food. Complex carbohydrates are sugars made up of large molecules contained within fibre and starch. They are found in fruit, vegetables, and wholegrains and are beneficial for brain health as they release glucose slowly into our system. This helps stabilise our mood. Simple carbohydrates found in sugary snacks and drinks create sugar highs and lows that rapidly increase and decrease feelings of happiness and produce a negative effect on our psychological well-being. We often use these types of sugary foods to comfort us when we’re feeling down. But this can create an addiction-like response in the brain, similar to illicit drugs that increase mood for the short term but have negative long-term effects. Increasing intake of complex carbohydrates and decreasing sugary drinks and snacks could be the first step in increased happiness and well-being. 2. Antioxidants Oxidation is a normal process our cells carry out to function. Oxidation produces energy for our body and brain. Unfortunately, this process also creates oxidative stress and more of this happens in the brain than any other part of the body. Chemicals that promote happiness in the brain such as dopamine and serotonin are reduced due to oxidation and this can contribute to a decrease in mental health. Antioxidants found in brightly coloured foods such as fruit and vegetables act as a defence against oxidative stress and inflammation in the brain and body. Antioxidants also repair oxidative damage and scavenge free radicals that cause cell damage in the brain. Eating more antioxidant-rich foods can increase the feel-good chemicals in our brain and heighten mood. Antioxidants can help restore the happy chemicals in the brain. www.shutterstock.com.au 3. Omega 3 Omega 3 are polyunsaturated fatty acids that are involved in the process of converting food into energy. They are important for the health of the brain and the communication of its feel-good chemicals dopamine, serotonin and norepinephrine. Omega 3 fatty acids are commonly found in oily fish, nuts, seeds, leafy vegetables, eggs, and in grass fed meats. Omega 3 has been found to increase brain functioning, can slow down the progression of dementia and may improve symptoms of depression. Omega 3 are essential nutrients that are not readily produced by the body and can only be found in the foods we eat, so it’s imperative we include more foods high in omega 3 in our everyday diet. 4. B vitamins B vitamins play a large role in the production of our brain’s happiness chemicals serotonin and dopamine and can be found in green vegetables, beans, bananas, and beetroot. High amounts of vitamins B6, B12, and folate in the diet have been known to protect against depression and too low amounts to increase the severity of symptoms. Vitamin B deficiency can result in a reduced production of happiness chemicals in our brain and can lead to the onset of low mood that could lead to mental health issues over a long period. Increasing B vitamins in our diet could increase the production of the feel good chemicals in our brain which promote happiness and well-being. 5. Prebiotics and probiotics The trillions of good and bad bacteria living in our tummies also influence our mood, behaviour and brain health. Chemical messengers produced in our stomach influence our emotions, appetite and our reactions to stressful situations. Prebiotics and probiotics found in yoghurt, cheese and fermented foods such as kombucha, sauerkraut and kimchi work on the same pathways in the brain as antidepressant medications and studies have found they might have similar effects. Prebiotics and Probiotics have been found to suppress immune reactions in the body, reduce inflammation in the brain, decrease depressed and anxious states and elevate happy emotions. Incorporating these foods into our diet will not only increase our physical health but will have beneficial effects on our mental health, including reducing our risk of disorders such as depression and anxiety. Disclosure Statement Megan Lee receives funding from Southern Cross University and Santos Organics Joanne Bradbury receives funding from the Australian Traditional-Medicinal Society (ATMS), Santos Organics, and Metagenics to support academic research

By Megan Lee & Joanne Bradbury

Neurology

Clinical Articles

Predicting and Preventing Dementia

Adolescent boys who struggle to understand how basic machines work and young girls who have difficulty remembering words are at increased risk of developing dementia when they’re older, new research has found. According to the longitudinal study published in The Journal of the American Medical Association, lower mechanical reasoning in adolescence in boys was associated with a 17% higher risk of having dementia when they were 70. With girls it was a lower memory for words in adolescence that increased the odds of developing the degenerative disease. It has been known for some time that the smarter you are throughout life, even as a child the less likely it is that you will develop dementia. Not a guarantee of protection – just a general trend. It has to do with cognitive reserve, the US researchers explain. “Based on the cognitive reserve hypothesis, high levels of cognitive functioning and reserve accumulated throughout the life course may protect against brain pathology and clinical manifestations of dementia,” they wrote. This theory has been supported by a number of studies such as the Scottish Mental Health Survey that showed that lower mental ability at age 11 increased the risk of dementia down the track. But what had been less well-defined was whether there were any particular aspects of intelligence in young people that were better predictors (or protectors) of dementia than others. This study goes some way to addressing this. Researchers were able to link sociobehavioural data collected from high school children back in 1960 with Medicare claims data over 50 years later that identified those people who had been diagnosed with Alzheimer's disease and related disorders. Interestingly, poor adolescent performance in other areas of intelligence such as mathematics and visualisation were also associated with dementia but not nearly to the extent of mechanical reasoning and word memory. So why is this so? The study authors say there are a few possible explanations. Maybe the poor performance in adolescence reflected poor brain development earlier in life, a risk factor for dementia. Or maybe these adolescents are more susceptible to neuropathology as they get older? Or maybe they are the adolescents who adopt poor health behaviours such as smoking and little exercise? “Regardless of mechanism, our findings emphasise that early-life risk stretches across the life course,” they said. And what can be done about it? That’s the million-dollar question. The researchers say the hope is if we know the at-risk group we can get aggressive with preventive management early. “Efforts to promote cognitive reserve-building experiences and positive health behaviours throughout the life course may prevent or delay clinical symptoms of Alzheimer's disease and related disorder.” An accompanying editorial takes this concept a little further. Dr Tom Russ, a Scottish psychiatrist says interventional research has identified a number of factors that can potentially influence cognitive reserve. These include modifiable health factors, education, social support, positive affect, stimulating activities and/or novel experiences, and cognitive training. As Dr Russ says, you can’t necessarily change all of these risk factors, and even the ones you can change may become less modifiable later in life. But as this study demonstrates, you may be able to work on a person’s cognitive reserve at different stages throughout their life to ultimately lower their risk of dementia. Reference

Huang AR, Strombotne KL, Horner EM, Lapham SJ, Adolescent Cognitive Aptitudes and Later-in-Life Alzheimer Disease and Related Disorders. JAMA Network Open [Internet]. 2018 Sep; 1(5): e181726. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701735 doi:10.1001/jamanetworkopen.2018.1726.

Russ TC, Intelligence, Cognitive Reserve, and Dementia: Time for Intervention? JAMA Network Open [Internet]. 2018 Sep; 1(5): e181724. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701735 doi:10.1001/jamanetworkopen.2018.1724.

By Dr Linda Calabresi

Obstetrics and gynaecology

Clinical Articles

Fetal Fraction – The Essential Factor in Non-Invasive Prenatal Testing

Non-Invasive Prenatal Testing (NIPT), the cell-free DNA-based blood test that screens for fetal chromosomal abnormalities, is fast becoming a routine part of obstetric care. NIPT at a glance During pregnancy, maternal plasma contains fragments of DNA from the mother and from the placenta (fetal DNA). The proportion of DNA fragments from particular chromosomes is usually very stable throughout pregnancy. If there is an excess of fetal fragments from one chromosome, the proportion of fragments from that chromosome will be changed. Inconclusive tests A key reason that NIPTs should precisely measures the amount of fetal DNA in the sample – the fetal fraction – is if there is insufficient fetal DNA, the result may merely reflect the genetic status of the mother. NIPT assays should report a result only if there is sufficient fetal DNA to be confident of accuracy. Rarely, a test for trisomy 21,18 and 13 cannot be reported. This occurs in 3% of women tested by Sonic Genetics and is usually because there is insufficient fetal DNA compared with maternal DNA in the mother’s plasma. This low fetal fraction can be due to a relative excess of maternal DNA and this can vary over time. It is more common in women with increased body weight, and more likely in the presence of infection and inflammation, or after exercise. It also occurs if the mother or fetus has some subtle benign variations in chromosome structure (copy number variants) that make estimating the proportion of fragments from a chromosome unreliable. In some instances, the DNA in the sample has degraded during collection and shipping to the laboratory, and the quality is insufficient for a reliable result. These factors interfere with quality control of the test. Two thirds of women will get a result on re-testing. However, if the second test is inconclusive, it should not be repeated. This occurs in 1% of pregnant women screened. It is also not worth using another form of non-invasive prenatal test. Other tests do not estimate the fetal fraction accurately and may provide false reassurance. A decision about other test modalities (combined first trimester screen, second trimester serum screen, detailed ultrasonography or invasive genetic testing such as CVS/amniocentesis) should be based on assessment of all identified risk factors and may require specialist consultation. More rarely (in 0.5 –1% of women) the test reports a result for trisomy 21, 18 and 13 but not for fetal gender and sex chromosome abnormalities. It is unlikely that a repeat test will provide a result. A decision about using fetal ultrasound or invasive genetic testing to document fetal gender should be based on assessment of need and any identified risk factors. General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

By Dr James Harraway, Sullivan Nicolaides Pathology

Genetics

Clinical Articles

New Medicare-Funded BRCA Testing – Use With Caution

GPs may have to correct some patients’ misunderstanding following reports in the general media suggesting that testing for high risk cancer genes was now available to everyone free of charge. Writing in the latest issue of the MJA, Australian genetics experts say that testing for specific high- risk genetic mutations, especially BRCA1 and BRCA2 has been available to appropriate patients free of charge (but not Medicare-rebated) by genetic specialists in public clinics for over 20 years. What’s new is that these tests now attract a Medicare rebate and you don’t have to be a genetic specialist to order them, but they are still only available to selected patients. “Testing is appropriate when there is at least a 10% chance of identifying a gene mutation responsible for the personal or family history of cancer,” the authors of the article wrote. There are a number of algorithms available to help clinicians calculate whether the likelihood of having one of these cancer-causing genetic mutations is at least 10%. Usually testing is initially considered for patients who have been diagnosed with either breast or ovarian cancer, and because of their young age and/or their strong family history are considered at high possibility of having a genetic mutation that explains their condition. The new item numbers (73295,73296 and 73297) cover testing for heritable germline mutations in seven genes including BRCA1 and BRCA2. If such a mutation is found, then at risk adult relatives will be justified in also accessing testing. However, as the article authors point out there are limitations with this type of genetic testing. Firstly most breast and ovarian cancers occur in people without an identifiable underlying genetic variant. “Only 5% of female breast cancers, 15% of invasive epithelial ovarian cancers and up to 14% of male breast cancers are related to BRCA1 or BRCA2 mutations, thus, most patients with breast cancer do not need, nor will they benefit from, a genetic test,” they said. That’s not to say the absence of BRCA1 or BRCA2, or one of the other rarer high-risk mutations currently tested for, excludes the possibility that the patient has inherited a predisposition to the cancer. Families that appear to have a high prevalence of these types of cancer may indeed have an inherited genetic mutation, it is just that because of limitations of technology and knowledge it is yet to be isolated. What’s more, the sensitivity of the current testing methods, means that a number of incidental genetic mutations may be noted, but the significance of these is as yet unknown. It is critical that when testing is requested for a relative of an affected patient, the laboratory is informed of the exact genetic variation found in the original affected patient, to ensure pathologists distinguish between the disease-causing mutation and variants of undetermined significance. The authors also suggest confining testing to only the most likely variant/s rather than requesting testing for mutations in multiple genes. “[T]he testing of multiple genes may uncover unclassified variants, variants outside the usual clinical context, variants unrelated to the current cancer, or unexpected important variants for which the patient has not been well prepared,” they said. They also suggest education and counselling be given to patients considering this genetic testing, and written consent obtained. The new Medicare item numbers represent a major step forward in terms of genetic and genomic testing becoming mainstream, but, as the current incorrect media headlines demonstrate, this transition is going to require information and education. Clinicians who order these tests are likely to benefit from establishing close ties with genetic services and specialists to ensure best and appropriate practice in this ever-expanding area of medicine. Ref: Med J Aust 2018; 209 (5): 193-196. || doi: 10.5694/mja17.01124

By Dr Linda Calabresi

Infectious diseases

Clinical Articles

Health Check: How Long are You Contagious with Gastro?

There’s no way you’d want to go to work when you’ve got the telltale signs of gastro: nausea, abdominal cramps, vomiting and diarrhoea. But what about when you’re feeling a bit better? When is it safe to be around colleagues, or send your kids to school or daycare? The health department recommends staying home from work or school for a minimum of 24 hours after you last vomited or had diarrhoea. But the question of how long someone is contagious after recovering from gastro is a very different question. What causes gastro? To better understand how long you can be contagious with gastro, we need to look at the various causes. Viruses are the most common causes of gastro. Rotavirus is the leading cause in infants and young children, whereas norovirus is the leading cause of gastro in adults. There are around 1.8 million cases of norovirus infection in Australia each year. This accounts for almost 40% of the total cases of gastro. Bacterial gastroenteritis is also common and accounts for around 1.6 million cases a year. Of those cases, 1.1 million come from E. coli infections. Other bacteria that commonly cause gastro include salmonella, shigella and campylobacter. These bacteria are often found in raw or undercooked meat, seafood, and unpasteurised milk. Parasites such as giardia lamblia, entamoeba histolytica and cryptosporidium account for around 700,000 cases of gastro per year. Most of the time people recover from parasitic gastroenteritis without incident, but it can cause problems for people with weaker immune systems. Read more: Health Check: I feel a bit sick, should I stay home or go to work? Identifying the bug Most cases of diarrhoea are mild, and resolve themselves with no need for medical attention. But some warrant further investigation, particularly among returned travellers, people who have had diarrhoea for four or five days (or more than one day with a fever), patients with bloody stools, those who have recently used antibiotics, and patients whose immune systems are compromised. The most common test is the stool culture which is used to identify microbes grown from loose or unformed stools. The bacterial yield of stool cultures is generally low. But if it does come back with a positive result, it can be potentially important for the patient. Some organisms that are isolated in stool cultures are notifiable to public health authorities. This is because of their potential to cause serious harm in vulnerable groups such as the elderly, young children, pregnant women and those with weakened immune systems. The health department must be notified of gastro cases caused by campylobacter, cryptosporidium, listeria, salmonella, shigella and certain types of E.coli infection. This can help pinpoint outbreaks when they arise and allow for appropriate control measures. You might feel better but your poo isn’t Gastro bugs are spread via the the faecal-oral route, which means faeces needs to come into contact with the mouth for transmission to occur. Sometimes this can happen if contaminated faecal material gets into drinking water, or during food preparation. But more commonly, tiny particles of poo might remain on the hands after going to the toilet. Using toilet paper to wipe when you go to the toilet doesn’t completely prevent the contamination of hands, and even more so when the person has diarrhoea. The particles then make their way to another person’s mouth during food preparation or touching a variety of contaminated surfaces and then putting your fingers in your mouth. After completely recovering from the symptoms of gastro, infectious organisms can still be shed into stools. Faecal shedding of campylobacter, the E. coli O157 strain, salmonella, shigella, cryptosporidium, entamoeba, and giardia can last for many days to weeks. In fact, some people who have recovered from salmonella have shed the bacteria into their stools 102 days later. Parasites can remain alive in the bowel for a long period of time after diarrhoea finishes. Infectious cryptosporidium oocysts can be shed into stools for up to 50 days. Giardia oocysts can take even longer to be excreted. So, how long should you stay away? Much of the current advice on when people can return to work, school or child care after gastro is based on the most common viral gastroenteritis, norovirus, even though few patients will discover the cause of their bug. For norovirus, the highest rate of viral shedding into stools occurs 24 to 48 hours after all symptoms have stopped. The viral shedding rate then starts to quickly decrease. So people can return to work 48 hours after symptoms have stopped. Yes, viral shedding into stools can occur for longer than 48 hours. But because norovirus infection is so common and recovery is rapid, it’s not considered practical to demand patients’ stools be clear of the virus before returning to work. While 24 hours may be appropriate for many people, a specific 48-hour exclusion rule is considered necessary for those in a higher-risk category for spreading gastro to others. These include food handlers, health care workers and children under the age of five at child care or play group. If you have a positive stool culture for a notifiable organism, that may change the situation. Food handlers, childcare workers and health-care workers affected by verotoxin E.coli, for example, are not permitted to work until symptoms have stopped and two consecutive faecal specimens taken at least 24 hours apart have tested negative for verotoxin E. coli. This may lead to a lengthy exclusion period from work, possibly several days. How to stop the spread Diligently washing your hands often with soap and water is the most effective way to stop the spread of these gastro bugs to others. Consider this: when 10,000 giardia cysts were placed in the palm of a hand, handwashing with soap eliminated 99% of them. To prevent others from becoming sick, disinfect contaminated surfaces thoroughly immediately after someone vomits or has diarrhoea. While wearing disposable gloves, wash surfaces with hot water and a neutral detergent, then use household bleach containing 0.1% hypochlorite solution as a disinfectant.

By Healthed

Orthopaedic and sports medicine

Clinical Articles

Inpatient Rehab After Knee Surgery – a Rort?

Why are Australians having rehabilitation as an inpatient after their total knee replacements rather than as an outpatient at a rate higher than any other country in the world? And why are our rates of inpatient rehabilitation as opposed to community or home-based rehab increasing? That’s what researchers were investigating in a study just published in the MJA. Could it be inpatient rehab was associated with better health outcomes for the patient than the other options? Or were patients too complex, lived too far away or needed greater supervision to allow them to have their rehab off-site? As it turns out, the reason inpatient rehabilitation rates are increasing has much more to do with private hospitals being able to access funding than any patient factors. According to the study authors, more than 50,000 total knee replacement operations were performed in Australia in 2016, about 70% of which took place in a private hospital. In that year, 2016, 45% of patients underwent inpatient rehabilitation following surgery. This represents a substantial increase from the 31% who had the same inpatient service back in 2009. This bucks an international trend. “Inpatient rehabilitation rates in the United States decreased from a peak of 35% in 2003 to 11% in 2009, with a mean rate during 2009-2014 of 15%,” the researchers said. Randomised controlled trials have failed to show the functional improvements achieved through inpatient rehabilitation are superior to those achieved with home- or community-based rehabilitation. However, the cost was significantly more. A recent analysis including almost 260 privately insured patients at 12 Australian hospitals put the cost differential at an average of $9500. And even though the mean age for patients undergoing inpatient rehab was slightly higher than for those who did not (71.0 vs 67.3 years), and they were more likely to have comorbidities and live alone, the study authors said the differences didn’t explain the wide variation in admission rates from hospital to hospital. “Patients in hospitals with high rates of inpatient rehabilitation were similar to those in hospitals with low rates, eliminating patient complexity as the reason,” they said. It seems the greatest determinant of whether a person had inpatient rehabilitation was the hospital in which the total knee replacement took place. “This factor was substantially more important than the clinical profile of the patient,” the study authors said. They suggested some private hospitals were encouraging inpatient rehabilitation because they were able to access funding on a per day basis for the rehab, in addition to the payment received for the knee surgery. The study authors concede it is an attractive business model, but while these hospitals may be offering excellent rehab in terms of services and facilities, it all comes at a cost ‘that, for many patients, is not justified by better outcomes.’ They suggest the proportion of patients receiving inpatient rehabilitation after a total knee replacement could be reduced, improving health care efficiency without harming health outcomes. “Reducing low value care will require system-level changes to guidelines and incentives for hospitals, as hospital-related factors are the major driver of variation in inpatient rehabilitation practices,” they concluded. Reference: Schilling C, Keating C, Barker A, Wilson SF, Petrie D, Predictors of inpatient rehabilitation after total knee replacement: an analysis of private hospital claims data. Med J Aust. 2018 August 27. 209(5): 222-7. Available from: https://www.mja.com.au/journal/2018/209/5/predictors-inpatient-rehabilitation-after-total-knee-replacement-analysis doi:10.5694/mja17.01231

By Dr Linda Calabresi

Sexual health

Clinical Articles

Detecting and treating Mycoplasma genitalium

Mycoplasma genitalium (M. genitalium), is thought to affect up to 400,000 Australians. It causes urethritis in men, and in women it can lead to pelvic inflammatory disease, cervicitis and preterm labour. It is also a recognised cause of anorectal proctitis along with other infections including Chlamydia trachomatis (including the LGV strains), gonorrhoea, syphilis, HSV and shigellosis. Asymptomatic infection is also common. Who to test Only test those with symptoms and their contacts. Screening asymptomatic people for M. genitalium is not currently recommended. Diagnosis Females: PCR on endocervical or vaginal swab, first pass urine (FPU), ThinPrep -collected by cervical brush/swab. Males: PCR on urethral swab (in preference to FPU), anorectal swabs. Throat swabs are not recommended as pharyngeal infection is uncommon. Transport: Ambient temperature; if there is any delay from collection to transport to the laboratory, the sample must be refrigerated Current treatment recommendations Preliminary data from the patient populations suggests resistance rates to macrolides may be as high as 64 per cent. The highest rates are likely to be in the men who have sex with men (MSM) population. Although information regarding fluoroquinolone resistance (moxifloxacin) is not available with this test, some studies suggest resistance to fluoroquinolones is present in 10–15% of infections. Doxycycline alone is ineffective in two-thirds of infections but will lower bacterial load in most cases, increasing the likelihood of cure with a subsequent antibiotic. Pretreating M. genitalium infections with doxycycline for one week and then treating susceptible infections with azithromycin and macrolide-resistant infections with a fluoroquinolone eradicates >90% of infections. Current treatment regimens Macrolide sensitive Doxycycline 100mg bd for seven days followed by azithromycin 1g stat then 500mg daily for three days (total 2.5g) OR Doxycycline 100mg bd for seven days followed by azithromycin 1g single dose. It is not known to what extent the improved outcomes resulting from the use of doxycycline followed by 2.5g azithromycin are due to this dose of azithromycin, rather than simply the pre-treatment with doxycycline. The higher dose of azithromycin requires a private prescription. Macrolide resistant Doxycycline 100mg bd for seven days followed by moxifloxacin 400mg daily for seven days. A longer course of moxifloxacin may be required in women with pelvic inflammatory disease. Moxifloxacin requires a private prescription, cannot be used in pregnancy and is expensive. It is associated with diarrhoea, occasional tendinopathy and rare neurological and cardiac events. Treatment failures following appropriate fluoroquinolone treatment may require specialist advice. Additional actions Advise no sex without condoms until tested for cure (14 days after completion of treatment). Advise no sex with untested previous sexual partners. Test of cure Test of cure by PCR should be done at least two weeks after treatment is completed i.e. four weeks after commencing therapy. Contact tracing In heterosexuals, the risk of PID and reproductive complications suggests a greater need to trace, test and treat infected contacts. The time period for contact tracing is unknown. Asymptomatic infection and macrolide resistance are more common in MSM and there is only limited evidence that this is harmful. As moxifloxacin will probably be required for treatment, contact tracing may be best confined to continuing partners of a symptomatic person. References: Australian STI Management Guidelines for Use in Primary Care http://www.sti.guidelines.org.au/sexually-transmissible-infections/mycoplasma-genitalium#management Australian Contact Tracing Manual contacttracing.ashm.org.au/conditions/when-contact-tracing-is-recommended/mycoplasma-genitalium General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

By Dr Jenny Robson

Cardiology

Clinical Articles

Managing the cardiovascular time bomb in patients on antipsychotics

The physical health of mentally ill patients is a "massive problem and we are doing very badly at it,” psychiatrist Dr Matthew Warden told doctors at a recent Healthed evening seminar in Sydney. In particular, the prevalence of high cardiovascular risk among patients with a history of psychosis, means this population was a "ticking time bomb", said Dr Warden, who is the Director of Acute Inpatient Services for Mental Health at St Vincent’s Hospital in Melbourne. Even without antipsychotic medication, a disproportionate number of people with a history of psychosis are overweight or obese, do very little if any physical exercise and smoke. And it is well-known that the metabolic side-effects associated with antipsychotic medications increases this cardiovascular risk enormously. Consequently, there has been growing pressure on psychiatrists to assess, monitor and manage the physical health of their patients with psychosis, but Dr Warden said, realistically this needs to be also done by GPs as they will usually be managing these patients long-term and "they are better at it.” Baseline metabolic measurements need to be taken at first episode of psychosis, including weight, BMI, BP, lipid levels, fasting blood sugar and smoking status. Weight, in particular needs to be monitored carefully following the commencement of antipsychotic medication, as weight gain is extremely common, especially with olanzapine which, Australia-wide is the most commonly prescribed antipsychotic. In answer to a GP’s question following his talk, Dr Ward said it is extremely difficult to avoid or reverse this medication-induced weight gain with diet and exercise alone. In addition, weight loss pharmacotherapy such as phentermine is contraindicated in people with a history of psychosis. Key to managing the weight gain issue was to choose an antipsychotic with the least long-term side effects from the outset. Olanzapine and clozapine are associated with the greatest weight gain while lurasidone and the partial agonists, aripiprazole and ziprasidone have the least effect on weight. Alternatively, for patients who may have been started on olanzapine or similar, swap to a more weight-neutral medication at the first sign they were gaining weight or developing other metabolic side-effects. It is more likely that a person who as gained weight on olanzapine, will lose that weight if switched to another weight-neutral medication early. The longer that patient stays on olanzapine and the weight gain is sustained, the harder it will be to shift even if the medication is changed, Dr Warden said. In addition to managing weight gain in mentally ill patients, Dr Warden also encouraged GPs to offer smoking cessation advice and help. Even though this population were often considered among the most dependent and heaviest smokers, his own research had found a significant number of patients could successfully quit or at the least cut down given the right advice and assistance. While most smoking cessation pharmacotherapy could be used, Dr Warden suggested that varenicline (Champix) was probably best avoided in these patients. At St Vincent’s Hospital in Melbourne, patients receiving antipsychotic therapy have their metabolic markers assessed at admission and at regular intervals after that, including measuring their serum prolactin. “Hyperprolactinaemia is a significant problem and should be monitored every six months if it is elevated or increasing particularly if there are symptoms then either reduce the dose or change antipsychotic or add in low dose aripiprazole which will lower prolactin levels,” Dr Warden explained. Dr Matthew Warden spoke on the “Management of Metabolic Dysregulation in Patients on Antipsychotics” at the Healthed, Mental Health in General Practice Evening Seminar held in Sydney in June, 2018.

By Dr Linda Calabresi

Obstetrics and gynaecology

Clinical Articles

Fewer Caesars with earlier induction

Among low-risk, nulliparous women, inducing a pregnancy at 39 weeks will not only be at least as safe as letting nature run its course but it will reduce the risk of having a Caesarean, according to US research. According to the randomised trial involving over 6000 women, those who were assigned to ‘expectant management’ ended up having a median gestational age of 40 weeks exactly, not a huge difference from the median gestational age of the induction group which was 39.3 weeks. However, the main aim of the study was to determine if induction at 39 weeks resulted in more adverse perinatal outcomes including conditions such as perinatal death, need for respiratory support, Apgars of less than three at five minutes, intracranial haemorrhage and the like. This potential association has been the concern which has dictated what is currently common obstetric practice. “When gestation is between 39 weeks 0 days and 40 weeks 6 days, common practice has been to avoid elective labour induction because of a lack of evidence of perinatal benefit and concern about a higher frequency of Caesarean delivery and other possible adverse maternal outcomes, particularly among nulliparous women”, the study authors said in the new England Journal of Medicine. What they found in their study however, was that these adverse perinatal outcomes occurred in only 4.3% of the babies born in the induction group and in 5.4% of those born to mothers who went into labour naturally. It appears the relative risk was reduced by 20%. And even though the induction group tended to have longer labours they had quicker recovery times and shorter hospital stays. In terms of maternal outcomes, induction at 39 weeks was associated with a significant reduction in the risk of both Caesarean section and hypertensive disorders of pregnancies. The researchers estimated one Caesarean would be avoided for every 28 low-risk, first-time mothers induced at 39 weeks. The study authors suggest that these findings have the capacity to change practice, or at the very least, provide evidence to relook at current obstetric practice policies. “These results suggest that policies aimed at the avoidance of elective labour induction among low-risk nulliparous women at 39 weeks of gestation are unlikely to reduce the rate of Caesarean delivery on a population level”, they concluded. Ref: NEJM 2018; 379:513-23 DOI: 10.1056/NEJMoa1800566

By Dr Linda Calabresi

Detecting Liver Cancer Early

GPs can make a significant difference in curbing the rising rates of liver cancer deaths in Australia, experts say. According to an analysis of over 270 cases of newly diagnosed cases of hepatocellular cancer presenting at seven Melbourne tertiary hospitals over one year, researchers say survival rates could be improved with earlier diagnosis of cirrhosis and better adherence to recommended screening schedules among those known to be at high risk. “[T]he number of liver cancer-related deaths has been the most rapid for any cancer type in Australia over the past 40 years,” the study authors said in the MJA. And of all the types of liver cancer, hepatocellular carcinoma is by far the most common, accounting for 82%. Even though treatments are available, both curative and palliative survival remains very poor with the Australian 12-month survival rate estimated to be only 62%. In this particular study, conducted over 2012/2013 the mean survival was only 18 months. As one would expect, the patients who did better, who generally survived the longest were those whose tumours were detected at an earlier stage. These were usually the patients who were known to be at high risk of developing liver cancer and were participating in a surveillance program. But this was only 40% of the 272 cases, even though 89% would have qualified for surveillance based on their risk factors. Why was this? Well firstly, many of these people did not know they were at risk. And that’s where GPs fit in. In the study the most common risk factors for liver cancer were found to be hepatitis C infection (41%), alcohol-related liver disease (39%), hepatitis B infection (22%) and non-alcoholic fatty liver disease (14%). Many had more than one risk factor. Most telling was the finding that, even though the vast majority of patients (83%) had cirrhosis when they were diagnosed with hepatocellular carcinoma, for one third of them that was the first they knew of it. The study authors suggest clinicians need to be alert for risk factors for chronic liver disease such as excess alcohol use, chronic HCV and HBV infections and even non-alcoholic liver disease in certain groups. In these people, checking for cirrhosis is likely to be worthwhile. “An aspartate transaminase to platelet ratio index (APRI) value greater than 1.0 predicts cirrhosis with 76% sensitivity and 72% specificity, and the test is simple to undertake,” the researchers said. The other major barrier to the earlier detection of liver cancer identified in the study was the poor adherence to surveillance among those people identified as being at high risk. Researchers found patients with alcohol-related liver disease or decompensated liver disease were the least likely to get regular monitoring. A surveillance program for this particular cancer involves a 6-monthly liver ultrasound and serum alpha-fetoprotein assessment. The study authors are advocating a national hepatocellular cancer surveillance program for those who are at high risk of developing the disease, which would include all patients with cirrhosis, Asian men over 40, women over 50, Africans over 20 years of age, and patients with a family history of [hepatocellular carcinoma] without cirrhosis but with chronic HBV infections. A national program to screen for hepatocellular carcinoma amongst this particular group would be worthwhile, the researchers said, as the incidence of the cancer is high, the screening is non-invasive and inexpensive and, perhaps most importantly early detection has been shown to improve survival. However, until such a national program is developed, researchers are encouraging GPs to ensure that their at-risk patients are enrolled in a surveillance program in order to hopefully improve their health outcomes. Reference: Hong TP, Gow PJ, Fink M, Dev A, Roberts SK, Nicoll A, et al. Surveillance improves survival of patients with hepatocellular carcinoma: a prospective population-based study. Med J Aust [Internet]. 2018 Sep 24; 209(8): 1-7. Available from: https://www.mja.com.au/journal/2018/209/8/surveillance-improves-survival-patients-hepatocellular-carcinoma-prospective doi: 10.5694/mja18.00373

By Dr Linda Calabresi

Clinical Articles

Oncology

What Causes Fibromyalgia?

Fibromyalgia is something of a mystery. It can’t be detected with scans or blood tests, yet it causes lifelong pain for millions of people. The disease mainly affects women (about 75-90% of cases), causing pain all over the body. Because not all healthcare professionals are adept at identifying and diagnosing fibromyalgia, reported rates of the condition vary greatly from country to country. In China, it affects only 0.8% of people, in France around 1.5%, in Canada 3.3%, and in Turkey 8.8%. Estimates in the US range from 2.2% to 6.4%, and in Russia, about 2% of the population is affected. People with the condition are often diagnosed if they have longstanding muscle pain, bone or joint pain and fatigue. Fibromyalgia can also cause insomnia, “brain fog”, some symptoms of depression or anxiety, as well as a range of other complaints, including irritable bowel syndrome and headache. Many patients are also hypermobile (“double-jointed”), and there is some overlap with chronic fatigue syndrome (also known as ME). Guidelines from the American College of Rheumatology make it clear that the diagnosis should be made using defined criteria based on the “widespread pain index” (which scores the number of painful regions out of 19) coupled with a symptom severity scale. The diagnosis also takes fatigue, generalised pain, unrefreshing sleep and cognitive symptoms into account. It doesn’t matter if the patient has another rheumatic disease, they can still be diagnosed with fibromyalgia. The scoring system, recommended by the American College of Rheumatology, is often used in clinical trials, but in the clinic, most doctors rely on detecting tender points in specific places and on excluding other medical conditions, including rheumatic conditions. Unlike say, rheumatoid arthritis or lupus, the tests do not show clear evidence of inflammation or autoimmunity (when the body’s immune system attacks itself) and scans are normal. The lack of inflammation or structural abnormality in muscles or joints – aside from making diagnosis difficult – is the main reason there are no widely accepted or effective treatments. In rheumatic diseases, where we understand the mechanisms that underlie the condition, we have the most effective treatments. In rheumatoid arthritis, for example, we know that much of the inflammation is caused by a cell-signalling protein (cytokine) called tumour necrosis factor and that blocking the activity of this protein switches off the disease in most patients. A number of possible mechanisms have been proposed in fibromyalgia, including abnormal muscle metabolism, reduced levels of steroid hormones such as cortisol, or abnormal small nerve fibres. But these abnormalities aren’t found in all patients with the condition. As such, they can’t be used as part of a diagnostic test, nor can they help develop treatments. Some experts have suggested that fibromyalgia may be related to abnormalities in the autonomic nervous system – the part of the nervous system that controls bodily functions, such as heart rate and blood pressure – and how the brain responds to pain signals and reacts to external stressors (such as infections). But there is currently no hard evidence to back up this theory. Looking for clues To fill in some of the gaps in our knowledge about this devastating condition, our research team at Brighton and Sussex Medical School is investigating the potential role of the autonomic nervous system and inflammation in fibromyalgia and chronic fatigue syndrome. For our study, we have two groups of patients: one with pain as the main symptom and the other with fatigue as the main symptom. We also have matched controls – people without the disease, but otherwise similar characteristics – to make meaningful comparisons. The study is in two parts. First, we will test the patients’ autonomic nervous system using a tilt-table. This involves tilting the person head downwards to see how well their body adapts to this change in posture by changing heart rate and blood pressure (both of which are monitored during the test).Second, we will stimulate patients’ immune systems with a typhoid vaccine (the normal type used in travellers) and perform magnetic resonance brain scans to look for changes in blood flow and also measure the levels of “inflammatory mediators” (the chemicals the body produces in response to stimuli of this type), to see whether these are higher in the fibromyalgia patients. Our study should, for the first time, help us to address the question of whether there really is an abnormal brain response to inflammation or infection in these patient groups and enable us to explore the relationship between the abnormal functioning of the autonomic nervous system and fibromyalgia and chronic fatigue syndrome. Fibromyalgia rarely goes away and treatment options are limited. Only by developing a proper understanding of the disease processes underlying this condition will doctors be able to make a clear, positive diagnosis, and most importantly, offer effective therapy. Disclosure Statement Kevin Davies receives funding from AR-UK. Jessica Eccles receives funding from Academy of Medical Sciences, National Institute of Health Research, MQ Neil Harrison receives funding from the Wellcome Trust, Medical Research Council (MRC), Arthritis Research UK, and Janssen Pharmaceuticals.

By Kevin Davies, Jessica Eccles & Neil Harrison

Clinical Articles

Rheumatology

Fatty Acids of Value in Anxiety

The value of omega-3 fatty acids has come under fire lately. But now a new systematic review suggests they might have benefits beyond the previous therapeutic targets of depression, cardiac health, eye health and arthritis. Researchers have found that omega-3 polyunsaturated fatty acids (PUFA) might reduce the symptoms of clinical anxiety, particularly among those people who had a specific clinical condition be it medical (such as Parkinson disease) or psychological (premenstrual syndrome). “This systematic review…provides the first meta-analytic evidence, to our knowledge, that omega-3 PUFA treatment may be associated with anxiety reduction, which might not only be due to a potential placebo effect, but also from some associations of treatment with reduced anxiety symptoms,” the review authors said in JAMA. The finding is likely to be welcome news for patients with this condition. Be it the potential side-effects of medications or the cost and accessibility of psychological therapy, patients with anxiety, especially those with comorbid medical conditions are keen for alternative or at least supplementary safe, evidence-based treatments for their symptoms. Previous research, in both human and animal studies had found that a lack of omega-3 PUFAs could induce various behavioural and neuropsychiatric disorders. What had not been shown was whether taking this supplement was effective in reducing the specific anxiety symptoms. The review involved an extensive literature search through a wide range of databases including PubMed and Cochrane looking for trials that had assessed the anxiolytic effects of these fatty acids in humans. In the end they found 19 trials that matched their eligibility criteria, which allowed researchers to analyse the effect of supplementation in just over 1200 participants and compare it with about 1000 matched controls who didn’t take the fatty acids. Overall, they found ‘there was a significantly better association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it.’ Subgroup analysis also showed that those taking at least 2000mg or more of the omega-3 PUFA treatment were more likely to have reduced anxiety. And somewhat surprisingly, those patients receiving supplements containing less than 60% EPA did better than those taking formulations with a greater concentration of EPA. The studies in the review included very different cohorts, and because of this and the limited number of studies included, the authors understandably say the results need to be interpreted with caution. However, while bigger, better studies are still needed to prove the benefit of omega-3 PUFAs in patients with clinical anxiety, this research certainly does suggest that higher dose formulations of less than 60% concentration of EPA might have a role as at least adjunctive treatment to standard therapy. Reference: Su KP, Tseng PT, Lin PY, Okubo R, Chen TY, Chen YW, et al. Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms; A Systematic Review and Meta-analysis. JAMA Network Open [Internet]. 2018 Sep; 1(5): e182327. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701735 doi:10.1001/jamanetworkopen.2018.2327.

By Dr Linda Calabresi

Clinical Articles

Psychiatry

Five Types of Food to Increase Your Psychological Well-Being

We all know eating “healthy” food is good for our physical health and can decrease our risk of developing diabetes, cancer, obesity and heart disease. What is not as well known is that eating healthy food is also good for our mental health and can decrease our risk of depression and anxiety. Mental health disorders are increasing at an alarming rate and therapies and medications cost $US2.5 trillion dollars a year globally. There is now evidence dietary changes can decrease the development of mental health issues and alleviate this growing burden. Australia’s clinical guidelines recommend addressing diet when treating depression. Recently there have been major advances addressing the influence certain foods have on psychological well-being. Increasing these nutrients could not only increase personal well-being but could also decrease the cost of mental health issues all around the world. 1. Complex carbohydrates One way to increase psychological well-being is by fuelling brain cells correctly through the carbohydrates in our food. Complex carbohydrates are sugars made up of large molecules contained within fibre and starch. They are found in fruit, vegetables, and wholegrains and are beneficial for brain health as they release glucose slowly into our system. This helps stabilise our mood. Simple carbohydrates found in sugary snacks and drinks create sugar highs and lows that rapidly increase and decrease feelings of happiness and produce a negative effect on our psychological well-being. We often use these types of sugary foods to comfort us when we’re feeling down. But this can create an addiction-like response in the brain, similar to illicit drugs that increase mood for the short term but have negative long-term effects. Increasing intake of complex carbohydrates and decreasing sugary drinks and snacks could be the first step in increased happiness and well-being. 2. Antioxidants Oxidation is a normal process our cells carry out to function. Oxidation produces energy for our body and brain. Unfortunately, this process also creates oxidative stress and more of this happens in the brain than any other part of the body. Chemicals that promote happiness in the brain such as dopamine and serotonin are reduced due to oxidation and this can contribute to a decrease in mental health. Antioxidants found in brightly coloured foods such as fruit and vegetables act as a defence against oxidative stress and inflammation in the brain and body. Antioxidants also repair oxidative damage and scavenge free radicals that cause cell damage in the brain. Eating more antioxidant-rich foods can increase the feel-good chemicals in our brain and heighten mood. Antioxidants can help restore the happy chemicals in the brain. www.shutterstock.com.au 3. Omega 3 Omega 3 are polyunsaturated fatty acids that are involved in the process of converting food into energy. They are important for the health of the brain and the communication of its feel-good chemicals dopamine, serotonin and norepinephrine. Omega 3 fatty acids are commonly found in oily fish, nuts, seeds, leafy vegetables, eggs, and in grass fed meats. Omega 3 has been found to increase brain functioning, can slow down the progression of dementia and may improve symptoms of depression. Omega 3 are essential nutrients that are not readily produced by the body and can only be found in the foods we eat, so it’s imperative we include more foods high in omega 3 in our everyday diet. 4. B vitamins B vitamins play a large role in the production of our brain’s happiness chemicals serotonin and dopamine and can be found in green vegetables, beans, bananas, and beetroot. High amounts of vitamins B6, B12, and folate in the diet have been known to protect against depression and too low amounts to increase the severity of symptoms. Vitamin B deficiency can result in a reduced production of happiness chemicals in our brain and can lead to the onset of low mood that could lead to mental health issues over a long period. Increasing B vitamins in our diet could increase the production of the feel good chemicals in our brain which promote happiness and well-being. 5. Prebiotics and probiotics The trillions of good and bad bacteria living in our tummies also influence our mood, behaviour and brain health. Chemical messengers produced in our stomach influence our emotions, appetite and our reactions to stressful situations. Prebiotics and probiotics found in yoghurt, cheese and fermented foods such as kombucha, sauerkraut and kimchi work on the same pathways in the brain as antidepressant medications and studies have found they might have similar effects. Prebiotics and Probiotics have been found to suppress immune reactions in the body, reduce inflammation in the brain, decrease depressed and anxious states and elevate happy emotions. Incorporating these foods into our diet will not only increase our physical health but will have beneficial effects on our mental health, including reducing our risk of disorders such as depression and anxiety. Disclosure Statement Megan Lee receives funding from Southern Cross University and Santos Organics Joanne Bradbury receives funding from the Australian Traditional-Medicinal Society (ATMS), Santos Organics, and Metagenics to support academic research

By Megan Lee & Joanne Bradbury

Clinical Articles

Diet and nutrition

Predicting and Preventing Dementia

Adolescent boys who struggle to understand how basic machines work and young girls who have difficulty remembering words are at increased risk of developing dementia when they’re older, new research has found. According to the longitudinal study published in The Journal of the American Medical Association, lower mechanical reasoning in adolescence in boys was associated with a 17% higher risk of having dementia when they were 70. With girls it was a lower memory for words in adolescence that increased the odds of developing the degenerative disease. It has been known for some time that the smarter you are throughout life, even as a child the less likely it is that you will develop dementia. Not a guarantee of protection – just a general trend. It has to do with cognitive reserve, the US researchers explain. “Based on the cognitive reserve hypothesis, high levels of cognitive functioning and reserve accumulated throughout the life course may protect against brain pathology and clinical manifestations of dementia,” they wrote. This theory has been supported by a number of studies such as the Scottish Mental Health Survey that showed that lower mental ability at age 11 increased the risk of dementia down the track. But what had been less well-defined was whether there were any particular aspects of intelligence in young people that were better predictors (or protectors) of dementia than others. This study goes some way to addressing this. Researchers were able to link sociobehavioural data collected from high school children back in 1960 with Medicare claims data over 50 years later that identified those people who had been diagnosed with Alzheimer's disease and related disorders. Interestingly, poor adolescent performance in other areas of intelligence such as mathematics and visualisation were also associated with dementia but not nearly to the extent of mechanical reasoning and word memory. So why is this so? The study authors say there are a few possible explanations. Maybe the poor performance in adolescence reflected poor brain development earlier in life, a risk factor for dementia. Or maybe these adolescents are more susceptible to neuropathology as they get older? Or maybe they are the adolescents who adopt poor health behaviours such as smoking and little exercise? “Regardless of mechanism, our findings emphasise that early-life risk stretches across the life course,” they said. And what can be done about it? That’s the million-dollar question. The researchers say the hope is if we know the at-risk group we can get aggressive with preventive management early. “Efforts to promote cognitive reserve-building experiences and positive health behaviours throughout the life course may prevent or delay clinical symptoms of Alzheimer's disease and related disorder.” An accompanying editorial takes this concept a little further. Dr Tom Russ, a Scottish psychiatrist says interventional research has identified a number of factors that can potentially influence cognitive reserve. These include modifiable health factors, education, social support, positive affect, stimulating activities and/or novel experiences, and cognitive training. As Dr Russ says, you can’t necessarily change all of these risk factors, and even the ones you can change may become less modifiable later in life. But as this study demonstrates, you may be able to work on a person’s cognitive reserve at different stages throughout their life to ultimately lower their risk of dementia. Reference

Huang AR, Strombotne KL, Horner EM, Lapham SJ, Adolescent Cognitive Aptitudes and Later-in-Life Alzheimer Disease and Related Disorders. JAMA Network Open [Internet]. 2018 Sep; 1(5): e181726. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701735 doi:10.1001/jamanetworkopen.2018.1726.

Russ TC, Intelligence, Cognitive Reserve, and Dementia: Time for Intervention? JAMA Network Open [Internet]. 2018 Sep; 1(5): e181724. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701735 doi:10.1001/jamanetworkopen.2018.1724.

By Dr Linda Calabresi

Clinical Articles

Neurology

Fetal Fraction – The Essential Factor in Non-Invasive Prenatal Testing

Non-Invasive Prenatal Testing (NIPT), the cell-free DNA-based blood test that screens for fetal chromosomal abnormalities, is fast becoming a routine part of obstetric care. NIPT at a glance During pregnancy, maternal plasma contains fragments of DNA from the mother and from the placenta (fetal DNA). The proportion of DNA fragments from particular chromosomes is usually very stable throughout pregnancy. If there is an excess of fetal fragments from one chromosome, the proportion of fragments from that chromosome will be changed. Inconclusive tests A key reason that NIPTs should precisely measures the amount of fetal DNA in the sample – the fetal fraction – is if there is insufficient fetal DNA, the result may merely reflect the genetic status of the mother. NIPT assays should report a result only if there is sufficient fetal DNA to be confident of accuracy. Rarely, a test for trisomy 21,18 and 13 cannot be reported. This occurs in 3% of women tested by Sonic Genetics and is usually because there is insufficient fetal DNA compared with maternal DNA in the mother’s plasma. This low fetal fraction can be due to a relative excess of maternal DNA and this can vary over time. It is more common in women with increased body weight, and more likely in the presence of infection and inflammation, or after exercise. It also occurs if the mother or fetus has some subtle benign variations in chromosome structure (copy number variants) that make estimating the proportion of fragments from a chromosome unreliable. In some instances, the DNA in the sample has degraded during collection and shipping to the laboratory, and the quality is insufficient for a reliable result. These factors interfere with quality control of the test. Two thirds of women will get a result on re-testing. However, if the second test is inconclusive, it should not be repeated. This occurs in 1% of pregnant women screened. It is also not worth using another form of non-invasive prenatal test. Other tests do not estimate the fetal fraction accurately and may provide false reassurance. A decision about other test modalities (combined first trimester screen, second trimester serum screen, detailed ultrasonography or invasive genetic testing such as CVS/amniocentesis) should be based on assessment of all identified risk factors and may require specialist consultation. More rarely (in 0.5 –1% of women) the test reports a result for trisomy 21, 18 and 13 but not for fetal gender and sex chromosome abnormalities. It is unlikely that a repeat test will provide a result. A decision about using fetal ultrasound or invasive genetic testing to document fetal gender should be based on assessment of need and any identified risk factors. General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

By Dr James Harraway, Sullivan Nicolaides Pathology

Clinical Articles

Obstetrics and gynaecology

New Medicare-Funded BRCA Testing – Use With Caution

GPs may have to correct some patients’ misunderstanding following reports in the general media suggesting that testing for high risk cancer genes was now available to everyone free of charge. Writing in the latest issue of the MJA, Australian genetics experts say that testing for specific high- risk genetic mutations, especially BRCA1 and BRCA2 has been available to appropriate patients free of charge (but not Medicare-rebated) by genetic specialists in public clinics for over 20 years. What’s new is that these tests now attract a Medicare rebate and you don’t have to be a genetic specialist to order them, but they are still only available to selected patients. “Testing is appropriate when there is at least a 10% chance of identifying a gene mutation responsible for the personal or family history of cancer,” the authors of the article wrote. There are a number of algorithms available to help clinicians calculate whether the likelihood of having one of these cancer-causing genetic mutations is at least 10%. Usually testing is initially considered for patients who have been diagnosed with either breast or ovarian cancer, and because of their young age and/or their strong family history are considered at high possibility of having a genetic mutation that explains their condition. The new item numbers (73295,73296 and 73297) cover testing for heritable germline mutations in seven genes including BRCA1 and BRCA2. If such a mutation is found, then at risk adult relatives will be justified in also accessing testing. However, as the article authors point out there are limitations with this type of genetic testing. Firstly most breast and ovarian cancers occur in people without an identifiable underlying genetic variant. “Only 5% of female breast cancers, 15% of invasive epithelial ovarian cancers and up to 14% of male breast cancers are related to BRCA1 or BRCA2 mutations, thus, most patients with breast cancer do not need, nor will they benefit from, a genetic test,” they said. That’s not to say the absence of BRCA1 or BRCA2, or one of the other rarer high-risk mutations currently tested for, excludes the possibility that the patient has inherited a predisposition to the cancer. Families that appear to have a high prevalence of these types of cancer may indeed have an inherited genetic mutation, it is just that because of limitations of technology and knowledge it is yet to be isolated. What’s more, the sensitivity of the current testing methods, means that a number of incidental genetic mutations may be noted, but the significance of these is as yet unknown. It is critical that when testing is requested for a relative of an affected patient, the laboratory is informed of the exact genetic variation found in the original affected patient, to ensure pathologists distinguish between the disease-causing mutation and variants of undetermined significance. The authors also suggest confining testing to only the most likely variant/s rather than requesting testing for mutations in multiple genes. “[T]he testing of multiple genes may uncover unclassified variants, variants outside the usual clinical context, variants unrelated to the current cancer, or unexpected important variants for which the patient has not been well prepared,” they said. They also suggest education and counselling be given to patients considering this genetic testing, and written consent obtained. The new Medicare item numbers represent a major step forward in terms of genetic and genomic testing becoming mainstream, but, as the current incorrect media headlines demonstrate, this transition is going to require information and education. Clinicians who order these tests are likely to benefit from establishing close ties with genetic services and specialists to ensure best and appropriate practice in this ever-expanding area of medicine. Ref: Med J Aust 2018; 209 (5): 193-196. || doi: 10.5694/mja17.01124

By Dr Linda Calabresi

Clinical Articles

Genetics

Health Check: How Long are You Contagious with Gastro?

There’s no way you’d want to go to work when you’ve got the telltale signs of gastro: nausea, abdominal cramps, vomiting and diarrhoea. But what about when you’re feeling a bit better? When is it safe to be around colleagues, or send your kids to school or daycare? The health department recommends staying home from work or school for a minimum of 24 hours after you last vomited or had diarrhoea. But the question of how long someone is contagious after recovering from gastro is a very different question. What causes gastro? To better understand how long you can be contagious with gastro, we need to look at the various causes. Viruses are the most common causes of gastro. Rotavirus is the leading cause in infants and young children, whereas norovirus is the leading cause of gastro in adults. There are around 1.8 million cases of norovirus infection in Australia each year. This accounts for almost 40% of the total cases of gastro. Bacterial gastroenteritis is also common and accounts for around 1.6 million cases a year. Of those cases, 1.1 million come from E. coli infections. Other bacteria that commonly cause gastro include salmonella, shigella and campylobacter. These bacteria are often found in raw or undercooked meat, seafood, and unpasteurised milk. Parasites such as giardia lamblia, entamoeba histolytica and cryptosporidium account for around 700,000 cases of gastro per year. Most of the time people recover from parasitic gastroenteritis without incident, but it can cause problems for people with weaker immune systems. Read more: Health Check: I feel a bit sick, should I stay home or go to work? Identifying the bug Most cases of diarrhoea are mild, and resolve themselves with no need for medical attention. But some warrant further investigation, particularly among returned travellers, people who have had diarrhoea for four or five days (or more than one day with a fever), patients with bloody stools, those who have recently used antibiotics, and patients whose immune systems are compromised. The most common test is the stool culture which is used to identify microbes grown from loose or unformed stools. The bacterial yield of stool cultures is generally low. But if it does come back with a positive result, it can be potentially important for the patient. Some organisms that are isolated in stool cultures are notifiable to public health authorities. This is because of their potential to cause serious harm in vulnerable groups such as the elderly, young children, pregnant women and those with weakened immune systems. The health department must be notified of gastro cases caused by campylobacter, cryptosporidium, listeria, salmonella, shigella and certain types of E.coli infection. This can help pinpoint outbreaks when they arise and allow for appropriate control measures. You might feel better but your poo isn’t Gastro bugs are spread via the the faecal-oral route, which means faeces needs to come into contact with the mouth for transmission to occur. Sometimes this can happen if contaminated faecal material gets into drinking water, or during food preparation. But more commonly, tiny particles of poo might remain on the hands after going to the toilet. Using toilet paper to wipe when you go to the toilet doesn’t completely prevent the contamination of hands, and even more so when the person has diarrhoea. The particles then make their way to another person’s mouth during food preparation or touching a variety of contaminated surfaces and then putting your fingers in your mouth. After completely recovering from the symptoms of gastro, infectious organisms can still be shed into stools. Faecal shedding of campylobacter, the E. coli O157 strain, salmonella, shigella, cryptosporidium, entamoeba, and giardia can last for many days to weeks. In fact, some people who have recovered from salmonella have shed the bacteria into their stools 102 days later. Parasites can remain alive in the bowel for a long period of time after diarrhoea finishes. Infectious cryptosporidium oocysts can be shed into stools for up to 50 days. Giardia oocysts can take even longer to be excreted. So, how long should you stay away? Much of the current advice on when people can return to work, school or child care after gastro is based on the most common viral gastroenteritis, norovirus, even though few patients will discover the cause of their bug. For norovirus, the highest rate of viral shedding into stools occurs 24 to 48 hours after all symptoms have stopped. The viral shedding rate then starts to quickly decrease. So people can return to work 48 hours after symptoms have stopped. Yes, viral shedding into stools can occur for longer than 48 hours. But because norovirus infection is so common and recovery is rapid, it’s not considered practical to demand patients’ stools be clear of the virus before returning to work. While 24 hours may be appropriate for many people, a specific 48-hour exclusion rule is considered necessary for those in a higher-risk category for spreading gastro to others. These include food handlers, health care workers and children under the age of five at child care or play group. If you have a positive stool culture for a notifiable organism, that may change the situation. Food handlers, childcare workers and health-care workers affected by verotoxin E.coli, for example, are not permitted to work until symptoms have stopped and two consecutive faecal specimens taken at least 24 hours apart have tested negative for verotoxin E. coli. This may lead to a lengthy exclusion period from work, possibly several days. How to stop the spread Diligently washing your hands often with soap and water is the most effective way to stop the spread of these gastro bugs to others. Consider this: when 10,000 giardia cysts were placed in the palm of a hand, handwashing with soap eliminated 99% of them. To prevent others from becoming sick, disinfect contaminated surfaces thoroughly immediately after someone vomits or has diarrhoea. While wearing disposable gloves, wash surfaces with hot water and a neutral detergent, then use household bleach containing 0.1% hypochlorite solution as a disinfectant.

By Healthed

Clinical Articles

Infectious diseases

Inpatient Rehab After Knee Surgery – a Rort?

Why are Australians having rehabilitation as an inpatient after their total knee replacements rather than as an outpatient at a rate higher than any other country in the world? And why are our rates of inpatient rehabilitation as opposed to community or home-based rehab increasing? That’s what researchers were investigating in a study just published in the MJA. Could it be inpatient rehab was associated with better health outcomes for the patient than the other options? Or were patients too complex, lived too far away or needed greater supervision to allow them to have their rehab off-site? As it turns out, the reason inpatient rehabilitation rates are increasing has much more to do with private hospitals being able to access funding than any patient factors. According to the study authors, more than 50,000 total knee replacement operations were performed in Australia in 2016, about 70% of which took place in a private hospital. In that year, 2016, 45% of patients underwent inpatient rehabilitation following surgery. This represents a substantial increase from the 31% who had the same inpatient service back in 2009. This bucks an international trend. “Inpatient rehabilitation rates in the United States decreased from a peak of 35% in 2003 to 11% in 2009, with a mean rate during 2009-2014 of 15%,” the researchers said. Randomised controlled trials have failed to show the functional improvements achieved through inpatient rehabilitation are superior to those achieved with home- or community-based rehabilitation. However, the cost was significantly more. A recent analysis including almost 260 privately insured patients at 12 Australian hospitals put the cost differential at an average of $9500. And even though the mean age for patients undergoing inpatient rehab was slightly higher than for those who did not (71.0 vs 67.3 years), and they were more likely to have comorbidities and live alone, the study authors said the differences didn’t explain the wide variation in admission rates from hospital to hospital. “Patients in hospitals with high rates of inpatient rehabilitation were similar to those in hospitals with low rates, eliminating patient complexity as the reason,” they said. It seems the greatest determinant of whether a person had inpatient rehabilitation was the hospital in which the total knee replacement took place. “This factor was substantially more important than the clinical profile of the patient,” the study authors said. They suggested some private hospitals were encouraging inpatient rehabilitation because they were able to access funding on a per day basis for the rehab, in addition to the payment received for the knee surgery. The study authors concede it is an attractive business model, but while these hospitals may be offering excellent rehab in terms of services and facilities, it all comes at a cost ‘that, for many patients, is not justified by better outcomes.’ They suggest the proportion of patients receiving inpatient rehabilitation after a total knee replacement could be reduced, improving health care efficiency without harming health outcomes. “Reducing low value care will require system-level changes to guidelines and incentives for hospitals, as hospital-related factors are the major driver of variation in inpatient rehabilitation practices,” they concluded. Reference: Schilling C, Keating C, Barker A, Wilson SF, Petrie D, Predictors of inpatient rehabilitation after total knee replacement: an analysis of private hospital claims data. Med J Aust. 2018 August 27. 209(5): 222-7. Available from: https://www.mja.com.au/journal/2018/209/5/predictors-inpatient-rehabilitation-after-total-knee-replacement-analysis doi:10.5694/mja17.01231

By Dr Linda Calabresi

Clinical Articles

Orthopaedic and sports medicine

Detecting and treating Mycoplasma genitalium

Mycoplasma genitalium (M. genitalium), is thought to affect up to 400,000 Australians. It causes urethritis in men, and in women it can lead to pelvic inflammatory disease, cervicitis and preterm labour. It is also a recognised cause of anorectal proctitis along with other infections including Chlamydia trachomatis (including the LGV strains), gonorrhoea, syphilis, HSV and shigellosis. Asymptomatic infection is also common. Who to test Only test those with symptoms and their contacts. Screening asymptomatic people for M. genitalium is not currently recommended. Diagnosis Females: PCR on endocervical or vaginal swab, first pass urine (FPU), ThinPrep -collected by cervical brush/swab. Males: PCR on urethral swab (in preference to FPU), anorectal swabs. Throat swabs are not recommended as pharyngeal infection is uncommon. Transport: Ambient temperature; if there is any delay from collection to transport to the laboratory, the sample must be refrigerated Current treatment recommendations Preliminary data from the patient populations suggests resistance rates to macrolides may be as high as 64 per cent. The highest rates are likely to be in the men who have sex with men (MSM) population. Although information regarding fluoroquinolone resistance (moxifloxacin) is not available with this test, some studies suggest resistance to fluoroquinolones is present in 10–15% of infections. Doxycycline alone is ineffective in two-thirds of infections but will lower bacterial load in most cases, increasing the likelihood of cure with a subsequent antibiotic. Pretreating M. genitalium infections with doxycycline for one week and then treating susceptible infections with azithromycin and macrolide-resistant infections with a fluoroquinolone eradicates >90% of infections. Current treatment regimens Macrolide sensitive Doxycycline 100mg bd for seven days followed by azithromycin 1g stat then 500mg daily for three days (total 2.5g) OR Doxycycline 100mg bd for seven days followed by azithromycin 1g single dose. It is not known to what extent the improved outcomes resulting from the use of doxycycline followed by 2.5g azithromycin are due to this dose of azithromycin, rather than simply the pre-treatment with doxycycline. The higher dose of azithromycin requires a private prescription. Macrolide resistant Doxycycline 100mg bd for seven days followed by moxifloxacin 400mg daily for seven days. A longer course of moxifloxacin may be required in women with pelvic inflammatory disease. Moxifloxacin requires a private prescription, cannot be used in pregnancy and is expensive. It is associated with diarrhoea, occasional tendinopathy and rare neurological and cardiac events. Treatment failures following appropriate fluoroquinolone treatment may require specialist advice. Additional actions Advise no sex without condoms until tested for cure (14 days after completion of treatment). Advise no sex with untested previous sexual partners. Test of cure Test of cure by PCR should be done at least two weeks after treatment is completed i.e. four weeks after commencing therapy. Contact tracing In heterosexuals, the risk of PID and reproductive complications suggests a greater need to trace, test and treat infected contacts. The time period for contact tracing is unknown. Asymptomatic infection and macrolide resistance are more common in MSM and there is only limited evidence that this is harmful. As moxifloxacin will probably be required for treatment, contact tracing may be best confined to continuing partners of a symptomatic person. References: Australian STI Management Guidelines for Use in Primary Care http://www.sti.guidelines.org.au/sexually-transmissible-infections/mycoplasma-genitalium#management Australian Contact Tracing Manual contacttracing.ashm.org.au/conditions/when-contact-tracing-is-recommended/mycoplasma-genitalium General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

By Dr Jenny Robson

Clinical Articles

Sexual health

Managing the cardiovascular time bomb in patients on antipsychotics

The physical health of mentally ill patients is a "massive problem and we are doing very badly at it,” psychiatrist Dr Matthew Warden told doctors at a recent Healthed evening seminar in Sydney. In particular, the prevalence of high cardiovascular risk among patients with a history of psychosis, means this population was a "ticking time bomb", said Dr Warden, who is the Director of Acute Inpatient Services for Mental Health at St Vincent’s Hospital in Melbourne. Even without antipsychotic medication, a disproportionate number of people with a history of psychosis are overweight or obese, do very little if any physical exercise and smoke. And it is well-known that the metabolic side-effects associated with antipsychotic medications increases this cardiovascular risk enormously. Consequently, there has been growing pressure on psychiatrists to assess, monitor and manage the physical health of their patients with psychosis, but Dr Warden said, realistically this needs to be also done by GPs as they will usually be managing these patients long-term and "they are better at it.” Baseline metabolic measurements need to be taken at first episode of psychosis, including weight, BMI, BP, lipid levels, fasting blood sugar and smoking status. Weight, in particular needs to be monitored carefully following the commencement of antipsychotic medication, as weight gain is extremely common, especially with olanzapine which, Australia-wide is the most commonly prescribed antipsychotic. In answer to a GP’s question following his talk, Dr Ward said it is extremely difficult to avoid or reverse this medication-induced weight gain with diet and exercise alone. In addition, weight loss pharmacotherapy such as phentermine is contraindicated in people with a history of psychosis. Key to managing the weight gain issue was to choose an antipsychotic with the least long-term side effects from the outset. Olanzapine and clozapine are associated with the greatest weight gain while lurasidone and the partial agonists, aripiprazole and ziprasidone have the least effect on weight. Alternatively, for patients who may have been started on olanzapine or similar, swap to a more weight-neutral medication at the first sign they were gaining weight or developing other metabolic side-effects. It is more likely that a person who as gained weight on olanzapine, will lose that weight if switched to another weight-neutral medication early. The longer that patient stays on olanzapine and the weight gain is sustained, the harder it will be to shift even if the medication is changed, Dr Warden said. In addition to managing weight gain in mentally ill patients, Dr Warden also encouraged GPs to offer smoking cessation advice and help. Even though this population were often considered among the most dependent and heaviest smokers, his own research had found a significant number of patients could successfully quit or at the least cut down given the right advice and assistance. While most smoking cessation pharmacotherapy could be used, Dr Warden suggested that varenicline (Champix) was probably best avoided in these patients. At St Vincent’s Hospital in Melbourne, patients receiving antipsychotic therapy have their metabolic markers assessed at admission and at regular intervals after that, including measuring their serum prolactin. “Hyperprolactinaemia is a significant problem and should be monitored every six months if it is elevated or increasing particularly if there are symptoms then either reduce the dose or change antipsychotic or add in low dose aripiprazole which will lower prolactin levels,” Dr Warden explained. Dr Matthew Warden spoke on the “Management of Metabolic Dysregulation in Patients on Antipsychotics” at the Healthed, Mental Health in General Practice Evening Seminar held in Sydney in June, 2018.

By Dr Linda Calabresi

Clinical Articles

Cardiology

Fewer Caesars with earlier induction

Among low-risk, nulliparous women, inducing a pregnancy at 39 weeks will not only be at least as safe as letting nature run its course but it will reduce the risk of having a Caesarean, according to US research. According to the randomised trial involving over 6000 women, those who were assigned to ‘expectant management’ ended up having a median gestational age of 40 weeks exactly, not a huge difference from the median gestational age of the induction group which was 39.3 weeks. However, the main aim of the study was to determine if induction at 39 weeks resulted in more adverse perinatal outcomes including conditions such as perinatal death, need for respiratory support, Apgars of less than three at five minutes, intracranial haemorrhage and the like. This potential association has been the concern which has dictated what is currently common obstetric practice. “When gestation is between 39 weeks 0 days and 40 weeks 6 days, common practice has been to avoid elective labour induction because of a lack of evidence of perinatal benefit and concern about a higher frequency of Caesarean delivery and other possible adverse maternal outcomes, particularly among nulliparous women”, the study authors said in the new England Journal of Medicine. What they found in their study however, was that these adverse perinatal outcomes occurred in only 4.3% of the babies born in the induction group and in 5.4% of those born to mothers who went into labour naturally. It appears the relative risk was reduced by 20%. And even though the induction group tended to have longer labours they had quicker recovery times and shorter hospital stays. In terms of maternal outcomes, induction at 39 weeks was associated with a significant reduction in the risk of both Caesarean section and hypertensive disorders of pregnancies. The researchers estimated one Caesarean would be avoided for every 28 low-risk, first-time mothers induced at 39 weeks. The study authors suggest that these findings have the capacity to change practice, or at the very least, provide evidence to relook at current obstetric practice policies. “These results suggest that policies aimed at the avoidance of elective labour induction among low-risk nulliparous women at 39 weeks of gestation are unlikely to reduce the rate of Caesarean delivery on a population level”, they concluded. Ref: NEJM 2018; 379:513-23 DOI: 10.1056/NEJMoa1800566

By Dr Linda Calabresi

Clinical Articles

Obstetrics and gynaecology

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Detecting Liver Cancer Early

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Five Types of Food to Increase Your Psychological Well-Being

Predicting and Preventing Dementia

Fetal Fraction – The Essential Factor in Non-Invasive Prenatal Testing

New Medicare-Funded BRCA Testing – Use With Caution

Health Check: How Long are You Contagious with Gastro?

Inpatient Rehab After Knee Surgery – a Rort?

Detecting and treating Mycoplasma genitalium

Managing the cardiovascular time bomb in patients on antipsychotics

Fewer Caesars with earlier induction

Detecting Liver Cancer Early

What Causes Fibromyalgia?

Fatty Acids of Value in Anxiety

Five Types of Food to Increase Your Psychological Well-Being

Predicting and Preventing Dementia

Fetal Fraction – The Essential Factor in Non-Invasive Prenatal Testing

New Medicare-Funded BRCA Testing – Use With Caution

Health Check: How Long are You Contagious with Gastro?

Inpatient Rehab After Knee Surgery – a Rort?

Detecting and treating Mycoplasma genitalium

Managing the cardiovascular time bomb in patients on antipsychotics

Fewer Caesars with earlier induction

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