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Lynnette Hoffman

Driving a car is so crucial to employment, socialisation, and self-esteem that people with epilepsy list it as one of their main concerns, ahead of seizures and even sudden death.

Prof Gabrielle Belz

Men and women respond differently to diseases and treatments for biological, social and psychological reasons. In this series on Gender Medicine, experts explore these differences and the importance of approaching treatment and diagnosis through a gender lens.
We know that sex hormones drive characteristic male and female traits such as breast enlargement and hip widening in women, or increased muscle mass and growth of facial hair in men. But now we also recognise they have a major impact on the immune system - our body’s inbuilt mechanism that helps fight and protect us against disease. Research suggests this has an evolutionary basis: survival of the species may mean men are harder hit by viruses, but a woman’s reactive immune system leaves her more susceptible to autoimmune diseases and allergies.

Viruses see men as weaker

Men die significantly more often from infectious diseases than women. For instance, men are 1.5 times more likely to die from tuberculosis, and twice as likely to develop Hodgkin’s lymphoma following Epstein–Barr virus (EBV) infection. Men are also five times more likely to develop cancer after infection with human papillomavirus (HPV), than women. This is because women’s immune systems mount a stronger response against foreign invaders, particularly viruses. While the male hormone testosterone tends to dampen immune responses, the female hormone oestrogen increases the number of immune cells and the intensity of their response. So women are able to recover more quickly from an infection. All this may reflect a sneaky evolutionary trick used by viruses to enable their survival. Women have developed multiple mechanisms to transmit infections; mainly through passing bugs from mother to child during gestation or birth, or through breastfeeding. So women are better vessels for viruses. Meanwhile, viruses have singled men out as the weaker sex. While popular culture has come up with the term “man flu”, suggesting men are over-dramatising flu symptoms, evidence suggests they may in reality be suffering more due to this dampening down of their immune responses.
Read more - Health Check: is man flu real?
However, this increased susceptibility of men to infection may not be an advantage for the long-term (over tens of thousands of years) survival of a disease-causing organism (pathogen), if it induces such severe disease that it results in the death of the host. Pathogens modify themselves so they can be transmitted by women during pregnancy, birth or breast feeding. Because of this, many have adapted to be less aggressive in women allowing wider infection, generally across a population. However, this feature alone is not likely to be sufficient to ensure the ongoing survival of a virus. The fitness of both sexes is necessary to reproduce long-term and thus provide new hosts for invading pathogens. Thus, the hit to the male sex must somehow be balanced by other advantages to their immune system.

Autoimmune diseases

Autoimmune diseases occur when the immune system turns on and attacks the body’s own cells or tissues, initiating a chronic cycle that results in damage or destruction of specific organs. These diseases include type 1 diabetes, lupus, rheumatoid arthritis, multiple sclerosis, and up to 80 different diseases that affect systems such as the intestine, bones, joints and nervous systems.The most striking sex differences in the immune system are seen in autoimmune diseases. Autoimmune disease affects about 8% of the population, but 78% of those affected are women. Women are three times more likely than men to develop these types of disease.
Read more - Explainer: what are autoimmune diseases?
In the case of lupus, the immune system mistakenly attacks the person’s own DNA (the structure that carries a person’s genetic code) causing damage to multiple organs that will lead to weight loss, anemia and eventually heart and kidney failure. Nine out of ten patients with lupus are women and clinical observations suggest that, again, hormones are the culprits. These differences of susceptibility between males and females tend to appear after puberty, and flare-ups increase during pregnancy. On the contrary, menopause is associated with a lower disease severity. Studies have linked oestrogen levels with the exacerbation of lupus. Oestrogens directly act on a particular immune cell (called the plasmacytoid dendritic cell) to promote their capacity to secrete inflammatory signals, which exacerbate lupus symptoms. Although these dendritic cells are generally important for fighting viral infections, in the context of lupus and multiple sclerosis, they cause significant harm.

Hormones and allergies

One in nine Australians (more than 2.5 million in total) suffer from asthma – a disease that causes swelling and narrowing of the airways. This makes it difficult to breathe when we encounter environmental allergens such as pollen. Twice as many women develop asthma compared to men. Interestingly, males are more susceptible to asthma before to the onset of puberty but, after puberty, females are more affected and develop more severe asthma than men. Until now, the reasons for this were not obvious, but hormones were speculated to play a role. In a recent study, we showed that high levels of testosterone in males protect them against the development of allergic asthma. During puberty, the level of testosterone increases. Testosterone acts as a potent inhibitor of a recently discovered immune cell called an innate lymphoid cell (ILC2), which accumulates in the lungs and initiates asthma. ILC2 cells release inflammatory signals that drive the swelling and airway narrowing characteristic of asthma when people are exposed to pollen, dust mites, grass or other common allergens. Testosterone reduces the numbers of ILC2 in the lungs of males, while female hormones provide no protective effect.
Read more: Do kids grow out of childhood asthma?
Immunity and sex are far more intricately linked than we had previously appreciated. More research needs to be done to better understand the triggers involved in the different responses of males and females. But the recent discoveries open the door for tactics to potentially target hormonal pathways or receptors that are preferentially expressed on male or female immune cells.
The ConversationRead the first article in our Gender Medicine series - Medicine’s gender revolution: how women stopped being treated as ‘small men’ Gabrielle Belz, Professor, Molecular Immunology, Walter and Eliza Hall Institute and Cyril Seillet, Senior research scientist, Walter and Eliza Hall Institute This article was originally published on The Conversation. Read the original article.
Dr Linda Calabresi

Effectively treating depression in patients who have just experienced a heart attack will not only improve their quality of life, it could well improve their mortality, new research from Korea suggests. Among 300 patients who had recently experienced acute coronary syndrome and had depression as a comorbidity, those randomised to a 24-week course of escitalopram were 30% less likely to have a major adverse cardiac event over a median of eight years compared with those given placebo. In actual numbers, 40.9% (61)of the 149 patients given escitalopram had a major adverse event (including cardiac death, MI or PCI) over the period of follow-up compared with 53.6% (81) of the placebo group (151 patients), according to the study findings published in JAMA. It has long been known that depression is a common morbidity associated with acute coronary syndrome. It is also known that patients who have this comorbidity tend to have worse long-term cardiac outcomes than those who are depression-free. But what has yet to be proven is the benefit of treating this depression, at least in terms of mitigating this increased risk of a poor cardiac outcome. To date studies on the topic have yet to prove a significant benefit, with research providing conflicting results. According to the study authors, in this trial there was a significant correlation between improvement in the depression and better protection against major cardiac events. Even when they excluded those people who were still taking the antidepressant one year after the acute coronary syndrome, the protective effect was still present. Consequently, they hypothesised that the protection was more a reflection of the successfully treatment of the depression rather than the particular medication. This was consistent with a trend seen in previous research using different medications and treatments. However, the better result could be because escitalopram is more effective in treating acute coronary syndrome depression than other agents that were studied previously, the authors suggested. “Escitalopram may have modifying effects on disease prognosis in ACS-associated depressive disorder through reduction of depressive symptoms,” the study authors suggested. There were a number of caveats with regard this study that the authors said needed to be considered. These included the fact the cohort was entirely Korean which may have caused an ethnic bias, the depressive symptoms were less severe than in previous studies (though this was more likely to lead to the effect being an under-estimate) and also the severity of the underlying heart disease (namely heart failure) was relatively low. Nonetheless the researchers were able to conclude that among patients with depression who had had a recent acute coronary event, 24 weeks of treatment of escitalopram significantly reduced the risk of dying or having a further adverse cardiac event after a median of 8.1 years. How generalisable these findings are, will need to be the subject of further research. Ref: JAMA 2018;320 (4): 350-357. Doi: 10.1001/jama.2018.9422

Prof Linda-Gail Bekker

HIV remains a global challenge. Between 36.7 million and 38.8 million people live with the disease worldwide. And more than 35 million have died of AIDS related causes since the start of the epidemic in the mid-1980s. Two years ago the International Aids Society and The Lancet put together a commission made up of a panel of experts to take stock and identify what the future response to HIV should be. The report is being released to coincide with the 22nd International Aids Conference in Amsterdam. The Conversation Africa’s Health and Medicine Editor Candice Bailey spoke to Head of the International AIDS Society Professor Linda-Gail Bekker, who also led the commission, about its report. What have we learnt about the global HIV response in the last 30 years? The world had an emergency on its hands 30 years ago with the arrival of HIV. A huge amount of effort was put into trying to find solutions. And there were some incredible breakthroughs. First was the miracle of lifesaving antiretroviral treatment, the biggest game changer over the last three decades. Great strides have been made in rolling out the treatment. UNAIDS tells us that 22 million people are currently on treatment. That’s truly remarkable. But we’ve also learnt that relying on the current pace is insufficient. That’s clear from the figures. In some countries the incidence is rising, and in many parts of the world the incidence rate has stalled or plateaued. We are not seeing the downturn that we need to be able to reach the global goal of ending the HIV pandemic by 2030. The biggest lesson we’ve learnt is that we need to reinvigorate the prevention message especially since we have new tools to combat HIV transmission in many different settings. This includes Pre-exposure prophylaxis (PrEP) – a daily antiretroviral that’s given to people who have a high risk of contracting HIV to lower their chances of getting infected – as well as treatment as prevention, which involves giving people living with HIV antiretrovirals to suppress their viral loads. For a sustainable response and looking forward to the next era, it will be important to position our responses to HIV within the broader health agenda. Patients don’t only have HIV, they have other issues. There are mental health needs and there are sexual and reproductive health needs, so HIV treatment and care must fit into that broader agenda. This will enable a more sustainable response. This is a challenge in many parts of the world where HIV is in a siloed response and people are only treated by HIV specific services. There needs to be a service delivery model that considers the broader health agenda. This goes beyond integration. We need to think about where can we take the lessons from HIV into other diseases. In the case of HIV, person centred and community-based care has become critical to ensure people get access to treatment. The message is simple: the epidemic is far from over and it’s not time to disengage. We’re here for the long haul. To ensure we have a sustainable approach we need to recalibrate. The commission is calling for a new way of doing business that will seek common cause with other global health issues. We understand that the HIV response will need resources. This will be a great way to get a double bang for the buck. What’s still going wrong? In many regions we have left whole sectors of the population behind. These include men who have sex with men, women who trade sex and people who inject drugs. They aren’t getting proper services because of policy, prejudice and stigma. And different regional pockets need particular attention. One is in Eastern Europe and Central Asia where there has been a 30% increase in new infections since 2010. This is particularly concerning. Its clear that whole regions are being left behind because of politics, denial and stigma. Here the administrations are not doing the evidence based thing – they are failing their people and the response. Another pocket is West and Central Africa. These are countries that are not reducing rates of infection as quickly as we had hoped, often due to limited resources. Nigeria, for example, needs help with the reduction of mother to child transmission. These are areas that are going to need attention, help and encouragement. But we don’t want to put out the notion that we are in trouble across the world. In East and South Africa, for example, we have made significant gains. There is still a lot to be done but the trends are going in the right direction. In many ways South Africa really is a good news story because its administration and politics favour an enthusiastic response to do the right thing. Domestic funding around HIV has increased. South Africa still has the biggest number of people in the world living with HIV – 7.9 million according to the latest HSRC report. But the country is beginning to turn the ship around. That’s something we can be incredibly proud of. There are, nevertheless, still pockets that need attention. For example, adolescent girls and young women under the age of 25 in KwaZulu-Natal are roughly three times more likely than men younger than 25 to be living with HIV. We have had them in our sights but we now need a concentrated effort to tackle HIV in this cohort otherwise we will miss the target. We need to look at the evidence and where can we make an impact with integrated care. This would be through HIV programmes that are part of sexual and reproductive health along with economic empowerment initiatives such as getting girls to stay in school and making sure they have opportunities to make autonomous decisions about sexual and reproductive health. Doing everything for everyone is a waste of money and time. We need to sharpen the tip of our response. We must put our responses where we get the biggest bang for buck and call on those resources that offer prevention and treatment. What are the biggest challenges between now and 2030? Resources are the constant challenge globally. We live in a world where politics is unpredictable. We need to constantly advocate for funding while diversifying funding opportunities. The second challenge is stigma and discrimination. Policy and ideology that is counter productive also feeds into stigma and discrimination. We need to do to something about laws that criminalise behaviour, like sex work, and stigmas towards intravenous drug users, gay people and men who have sex with men. Decriminalising sex work in South Africa, for example, would go a long way to reduce stigma, enable services and help the public health approach. Continuing to understand how to reach young women and girls and protect them socially and medically; those are also big challenges. The ConversationFinally, in South Africa there is a challenge to find men who are not in the health services and get them into care and onto treatment. We know that a suppressed viral load means no HIV transmission and so this should be on its agenda. Linda-Gail Bekker, Professor of medicine and deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town This article was originally published on The Conversation. Read the original article.

Healthed

For farmers, drought is a major source of stress. Their livelihoods and communities depend on the weather. To better support farmers and their families we need to better understand the impact of drought on them and their communities. Our research, published today in the Medical Journal of Australia, found young farmers who live and work on farms in isolated areas and are in financial hardship are the most likely to experience personal drought-related psychological stress. Read more: The lessons we need to learn to deal with the 'creeping disaster' of drought

What our study found

To examine farmers’ mental health during droughts, we examined data from the Australian Rural Mental Health Study and rainfall conditions in the months before farmers completed the survey. Importantly, the study covered the period of the Millennium Drought, which had devastating environmental, social and economic impacts on much of southeast Australia from 1997 to 2010. The study captured both drought and wet conditions, which enables comparisons between farmers’ mental health under different climate conditions. The study included 664 farmers from inner and outer regional, remote and very remote New South Wales. Farmers were defined as: (i) people who lived on a farm; (ii) people who worked on a farm; and (iii) people who lived and worked on a farm. The gender distribution of the participants was equal and the majority were 55-64 years old. Of the three groups investigated, farmers who both lived and worked on a farm reported more drought-related impacts and concerns. Moderately dry conditions were related to the highest scores for drought-related concerns and general psychological distress. Interestingly, higher levels of drought-related concerns were also reported following mild to moderate wet conditions. This is possibly related to much of the study area receiving very high spring rainfall during 2010 and suggests drought-related mental health impacts persist beyond the end of the drought. Read more: Farmer suicide isn't just a mental health issue
A range of social, demographic and community factors influenced the personal impact of drought for farmers:
  • Isolation plays a large role in the rural context. Farmers in outer regional, remote and very remote NSW experienced higher levels of concern about drought. Remoteness can mean people aren’t able to engage as much in social networks, which are essential for building resilience.
  • Financial hardship is increasing in rural areas but many people don’t seek financial assistance due to stigma and ingrained stoicism. Younger farmers may also be particularly impacted by less financial security than older farmers.
  • Age matters too. Farmers under the age of 35 experienced higher personal drought-related stress.

What can we do about it?

Protracted drought is a rare but recurring element of the Australian climate. Whatever the cause, future drought is inevitable. Read more: Hairdressers in rural Australia end up being counsellors too
Drought impacts are different from “rapid” climate extremes such as bushfires, floods or cyclones. So drought planning and preparedness needs to consider the impacts of drought on mental health and well-being differently to the way in which we prepare for and respond to “rapid” climate extremes. We know “rapid” climate extremes can have devastating impacts through loss of life, injury and other threats to communities. The effects can be acute or long-term. While many people cope and adapt to rapid climate extremes, we know a substantial proportion will go on to develop mental health problems as a result. Much less is known about chronic, slow-onset climate extremes such as protracted drought. The unfamiliarity, unpredictability and longevity of drought have substantial personal and social consequences over time. The mechanisms for such impacts are not as well known as for “rapid” climate extremes. Our findings suggest the disruption to community viability, the financial strain, loss of property and stock, and impact on future personal hopes are likely to play a role. Supporting rural communities, and especially farmers, to cope with droughts can have benefits for their well-being and mental health. Strengthening personal, financial and social support for farmers may help in adapting to droughts when drought-related stress is affecting their mental health. General practitioners are uniquely placed to support farmers experiencing persistent worry that is affecting their day-to-day functioning. But it’s often trusted people who engage with farmers regularly, such as rural financial counsellors and vets, who occupy first responder roles. Insights from our study are useful for informing the practical steps required to improve farmers’ mental health. These include:
  • reducing stigma about mental health problems to overcome barriers to seeking professional help and advice early
  • professional help to be more readily available and easier to access in rural and remote areas (such as e-health programs)
  • professional education for all health services, including general practitioners, so they can look out for and address the effects of drought-related stress – they need a good understanding of the pressures facing farmers and farming communities and the ways they can be more alert to their needs
  • community education and public health campaigns so farmers and rural residents can identify the effects of drought-related stress and take appropriate action
  • education and training for non-medical agricultural support services, such as rural financial counsellors, who need to be able to confidently identify early signs of drought-related stress and provide appropriate support
  • continued funding of Rural Adversity Mental Health Program coordinators who link rural and remote residents to services and provide community education and support
  • better opportunities and encouragement to maintain and develop community connections and social networks
  • reasonably priced and reliable internet access to enable increased use of e-health and relieve isolation
  • The Conversationtransparent and consistent information about the processes farmers need to follow to access grants and loans. Farmers should be able to apply for financial support when it’s needed rather than having to fit in with government budget cycles and deadlines. Efficient processing of grant and loan applications is needed to minimise the period of uncertainty and stress while waiting for the outcome.
Emma Austin, PhD Researcher, University of Newcastle; Anthony Kiem, Associate Professor – Hydroclimatology, University of Newcastle; Brian Kelly, , University of Newcastle; David Perkins, Director, Centre for Rural and Remote Mental Health and Professor of Rural Health Research, University of Newcastle; Jane Rich, Research Associate, University of Newcastle, and Tonelle Handley, Research fellow, University of Newcastle This article was originally published on The Conversation. Read the original article.
Dr Jenny Robson

The microbiology laboratory has made great strides in introducing clinically useful diagnostics over the past couple of decades, particularly in recent years with the development of molecular assays that ‘narrow the gap’ and provide early diagnoses. While introducing new tests, it has also been important to evaluate and discard old tests that may not contribute greatly to patient outcomes. One such test that has come under the spotlight is the classic Widal agglutination test in the diagnosis of typhoid. The Widal test, developed by George Fernand Widal in 1896, uses a suspension of killed Salmonella typhi as antigen to detect agglutinating antibodies to somatic O antigens and flagellar H antigens present in serum of typhoid patients. There are many reasons for its lack of clinical utility. Antibodies are not present in the acute illness and take time to develop. Significant cross reactivity can occur with other infectious agents that mimic typhoid including malaria, dengue, endocarditis, tuberculosis and chronic liver disease. Other limitations are of a technical nature and include non-standardisation of the antigen preparation used in the assay, interference with serological responses following typhoid vaccination commonly provided to travellers, and prior exposure and antibodies in patients most susceptible to typhoid, especially those from endemic areas visiting friends and relatives (VFRs). Unless multiple antigens are included, it generally does not detect the other causes of enteric fever, S. Paratyphi A, B and C. It is now time to discontinue this simple agglutination test for typhoid in modern medicine and consider more appropriate diagnostic tests. Typhoid fever Typhoid fever is a life-threatening illness caused by the bacterium Salmonella Typhi. Whereas Salmonellae which cause gastroenteritis are zoonoses, humans are the only reservoir for S.Typhi and S. Paratyphi which cause enteric fever. Typhoid fever is still common in the developing world where it affects about 21.5 million people each year but is much less common in the Lucky Country such as ours where good sanitation prevails. About 100 cases are notified each year in Australia. In 2014, 92% of cases were acquired overseas. India continues to be the most common country of acquisition and in 2014 accounted for more than half of cases. Most transmission occurs through contaminated drinking water or food. Large epidemics are most often related to faecal contamination of water supplies or street-vended foods. A chronic carrier state – excretion of the organism for more than one year – occurs in about 5% of infected persons. Where no travel history is present, the likely source of infection is contaminated food or water from a human carrier akin to ‘Typhoid Mary’. Such an outbreak was reported in Auckland, New Zealand, this year where 20 local cases and one death occurred when a carrier from Samoa helped prepare food at a church community gathering. The incubation period is typically eight to 14 days but may be much longer. Without therapy, the illness may last for three to four weeks and death rates range between 12% and 30%. Increasing resistance to available antimicrobial agents, including fluoroquinolones, has occurred in recent years. Resistance to antimicrobials including amoxycillin, and trimethoprim+sulfamethoxazole has limited the options for treatment; reduced susceptibility to quinolones is common in infections acquired on the Indian subcontinent and in Southeast Asia. While awaiting the results of susceptibility testing, azithromycin or ceftriaxone should be used for initial therapy for infections acquired in these regions. Diagnosis of enteric fevers Two sets of blood cultures are the single most useful diagnostic procedure for diagnosis of enteric fever. Other bodily fluids and tissues may yield positive cultures including faeces, urine, and if seeded, bones and joints, liver and gall bladder. Food handlers, healthcare workers, carers of children, and carers of the elderly, and others who are not able to maintain their own personal hygiene, should further be excluded from working with food or caring for people until two consecutive stool specimens – collected at least 48 hours apart and the first specimen collected not sooner than 48 hours post-cessation of antibiotics – are culture negative. Prevention Both an oral live attenuated multi-dose vaccine and a killed vaccine are available. Booster doses after 3-5 years are generally required if continued exposure occurs. Vaccine efficacy is of the order of only 80%. What to order Blood culture x 2 (Salmonella Typhi and Salmonella Paratyphi) Faeces for Bacterial PCR and MCS; Urine MCS Collection Centres: Faeces and urine samples are accepted at all collection centres. Blood cultures are collected only at designated collection centres. Sample Blood (use blood culture bottles), faeces, urine Transportation Ambient Costs Medicare rebate applies Typhoid Mary Mary Mallon, better known as Typhoid Mary, was an Irish immigrant to New York and the first person in the United States identified as an asymptomatic carrier of the pathogen associated with typhoid fever. Over the course of her career as a cook, she was presumed to have infected 51 people, three of whom died. She was twice forcibly isolated by public health authorities and died after a total of nearly three decades in isolation.   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.

Dr Linda Calabresi

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  

Healthed

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.

Dr Linda Calabresi

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

Dr Linda Calabresi

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

Dr Linda Calabresi

It wasn’t that long ago that vitamin D appeared to be the panacea for everything from preventing MS to reducing the risk of diabetes. But the one area where we thought the benefit of this vitamin was not up for debate was bone health. It has been proven - lack of vitamin D causes rickets. It has been proven that vitamin D is important in bone metabolism and turnover. And it has been proven the people with low bone density are more likely to experience fractures. Therefore add vitamin D and improve bones, right? Wrong! The latest meta-analysis of more than 80 randomised controlled trials shows that vitamin D supplementation does not prevent fractures or falls, and does not have any consistently clinically relevant effects on bone mineral density. This comes as a bit of a surprise, to say the least. According to the systematic review, vitamin D had no effect on total fractures, hip fractures, or falls among the 53,000 participants in the pooled analysis. And it didn’t matter if higher or lower doses of vitamin D were used, the New Zealand researchers reported in The Lancet. In looking for a reason for the lack of an effect from supplementation, previous explanations such as baseline 25OHD of trial participants being too high, or the supplement dose being too low, or the trial being done in the wrong population just don’t hold water. The sheer number and variety of trials included in this meta-analysis has meant all of these possible confounders have been accounted for. “The trials we included have a broad range of study designs and populations, but there are consistently neutral results for all endpoints, including the surrogate endpoint of bone mineral density,” they said. Consequently, the researchers said future trials were unlikely to alter these conclusions. “There is little justification to use Vitamin D supplements to maintain or improve musculoskeletal health,” they stated. And while they acknowledge the clear exception to this is in the case of the prevention or treatment of rickets and osteomalacia, in general clinical guidelines should not be recommending vitamin D supplementation for bone health. The conclusion appears quite emphatic and definitive, and it is supported in an accompanying commentary by a leading US endocrinologist. “The authors should be complimented on an important updated analysis on musculoskeletal health,” said Dr Chris Gallagher from Creighton University Medical Centre, Omaha in the US. But he suggests many Vitamin D supporters will still be flying the flag for supplementation, pointing to the multiple potential non-bony benefits. “Within three years, we might have that answer because there are approximately 100,000 participants currently enrolled in randomised, placebo-controlled trials of vitamin D supplementation,” he said. “I look forward to those studies giving us the last word on vitamin D.”  

References

Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol. 2018 Oct 4. Available from: http://dx.doi.org/10.1016/S2213-8587(18)30265-1 [epub ahead of print] Gallagher JC. Vitamin D and bone density, fractures, and falls: the end of the story? Lancet Diabetes Endocrinol. 2018 Oct 4. Available from: http://dx.doi.org/10.1016/S2213-8587(18)30269-9 [epub ahead of print]
Dr Kym Mina

A genetic test is now available to assist in the diagnosis of lactose intolerance in both children and adults.

Key points

  • Lactose intolerance affects approximately 75% of the population.
  • Genetic testing can confirm lactose tolerance (also referred to as lactase persistence).
  • The test differentiates between primary lactose intolerance, due to lactase deficiency, and secondary causes of lactose intolerance, due to other more serious conditions that affect the small bowel.
  • The test is not affected by intercurrent illness and can be performed non-invasively on patients of all ages.
The test only needs to be performed once during a person’s lifetime.

How does the test work?

Testing is now available to detect the genetic variant (LCT-13910C>T) that accounts for close to 100% of lactase persistence in Europeans. Three other genetic variants that have a similar effect and are more common in non-European populations are also detected. These variants are thought to act as enhancers of the lactase gene that in turn stimulates lactase production. When one of these variants is found, a diagnosis of primary lactose intolerance can be excluded. Lactose intolerance can be secondary to other conditions that affect the small bowel, such as gastroenteritis, inflammatory bowel disease and coeliac disease. Genotyping can help to distinguish these causes of intolerance.

What causes lactose intolerance?

Lactose is the major carbohydrate in mammalian milk. Lactose intolerance is caused by deficiency of lactase, the enzyme required for digestion of lactose. Symptoms include abdominal pain, diarrhoea, nausea, flatulence and/or bloating, following the consumption of lactose-containing foods.

Who is affected by lactose intolerance?

After infancy, approximately 75% of the population lose the ability to digest lactose, due to a deficiency in lactase, referred to as primary lactose intolerance. The remainder of people maintain their tolerance for lactose-containing foods because of genetic variants that enable continued production of lactase, referred to as lactase persistence. The prevalence of primary lactose intolerance varies significantly with ethnic background. Lactose intolerance is uncommon in populations that consume large amounts of dairy, for example, northern Europeans (as low as 10%), but is frequent in other populations (as high as 100% in Asiatic countries). It is hypothesised that this is the result of selective genetic advantage; populations that have historically been dependent on dairy food sources for nutrition have survived by having genetic variants that allow tolerance for lactose.

Other testing alternatives

Currently, testing for lactose intolerance can also be performed by a hydrogen breath test with lactose load, or by measurement of intestinal lactase enzyme activity in a biopsy obtained during endoscopy. These tests may give a false-positive result when lactase levels have been affected by a recent viral illness or coeliac disease. These procedures are also not suitable for testing children younger than seven years old. Genotyping is not affected by intercurrent illness and can be performed non-invasively on patients of all ages.

Genetic testing limitations

Please note that genotyping will not identify very rare genetic variants associated with persisting lactase activity, and therefore the absence of a variant can only be used to support a diagnosis of lactose intolerance along with other clinical and laboratory findings.

Arranging a test

  1. Complete a standard pathology request form to refer the patient for ‘lactase persistence’ or ‘lactose intolerance genetic testing’.
  2. Collect or send the patient to a pathology collection centre for a blood test or buccal swab. No special preparation or booking is necessary.
  3. The result is reported back to the doctor, usually within five business days of the laboratory receiving the patient’s sample.

Cost

Medicare does not cover the cost of this test and the patient will receive an invoice for $75.*

References

  • Bayless T, Brown E, Paige DM. Lactase non-persistence and lactose intolerance. Curr Gastroenterol Rep. 2017 May; 19(5): 23. DOI: 10.1007/s11894-017-0558-9
  • Mattar R, de Campos Mazo DF, Carrilho FJ. Lactose intolerance: diagnosis, genetic, and clinical factors. Clin Exp Gastroenterol. 2012; 5: 113-21. DOI: 10.2147/CEG.S32368
  • Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS, et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet. 2007 Jan; 39(1): 31-40. DOI: 10.1038/ng1946
  • Heyman MB, Committee on Nutrition. Lactose intolerance in infants, children, and adolescents. Pediatrics. 2006 Sep; 118(3): 1279-86. DOI: 10.1542/peds.2006-1721
*Correct at time of printing. Please to refer to the Sonic Genetics website, www.sonicgenetics.com.au, for current pricing. General Practice Pathology is a 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.