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Read the latest articles relevant to your clinical practice, including exclusive insights from Healthed surveys and polls.

By reading selected clinical articles, you earn CPD in the Educational Activities (EA) category whenever you click the “Claim CPD” button and follow the prompts. 

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Prof Mariano Barbacid
  • Clinical Articles

New research gives hope in the fight against pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the third most common cause of death from cancer in the United States and the fifth most common in the United Kingdom. Deaths from PDAC outnumber those from breast cancer despite the significant difference in incidence rates. Late diagnosis and ineffective treatments are the most important reasons for these bleak statistics. PDAC is an aggressive and difficult malignancy to treat. Until now, the only chance for cure is the complete surgical removing of the tumor. Unfortunately, because PDAC is usually asymptomatic, by the time it is diagnosed 80% to 90% of patients have disease that is surgically incurable. PDAC thus remains one of the main biomedical challenges today due to its low survival rate – just 5% of patients are still alive five years after diagnosis. However, in recent decades a number of studies have shed light on the molecular mechanisms responsible for the initiation and progression of PDAC. Our recent research has shown that progress toward a cure is possible.

Ineffective treatments

The molecular mechanisms responsible for pancreatic cancer are complex. This is why recent advances in personalized medicine and immunotherapy (which helps the immune system fight cancer) have failed to improve the treatment of pancreatic cancer. This is mainly due to two characteristics:
  • 95% of these tumors are caused by mutations in KRAS oncogenes. Oncogenes are genes that, once mutated, are capable of inducing the transformation of a normal cell into a cancerous cell. KRAS is a gene that acts as an on/off switch. Normally, KRAS controls cell proliferation. When it is mutated, however, the cells start to grow uncontrollably and proliferate – a hallmark of cancer cells. So far, KRAS oncogenes have not been able to be targeted by drugs.
  • PDACs are surrounded by abundant fibrous connective tissue that grows around some tumor types. In the case of PDAC, this tissue forms a barrier that prevents cells that recognize and attack tumor cells, called cytotoxic T lymphocytes, from reaching the inside of the tumor mass and killing its cells. This renders immunotherapy treatments useless.
For these reasons, PDAC continues to be treated with drugs that destroy cancerous cells but can also destroy healthy ones. Options include Demcitabine, approved in 1997, and Nab-paclitaxel, a new paclitaxel-based formulation. Even if such a treatment is an option, it typically only extends the patients’ lives a few weeks, a marginal improvement at best. In recent years, however, a number of studies have shed light regarding the molecular mechanisms responsible for the initiation and progression of PDAC. Today we know that most of these tumors are caused by mutations in the KRAS oncogene. They lead to benign alterations that cause additional mutations in a range of tumor-suppressor genes, which usually repair DNA mistakes, slow down cellular division or tell cells when to die. Mutated cells can grow out of control, and in this context progress to malignant PDAC. While this process is relatively well known, it has not had an immediate impact on the development of new and more effective treatments.

In search of new strategies

Multiple strategies are currently being studied in an attempt to inhibit the growth of these tumors by blocking the growth of either the tumor cells or their surrounding “shielding” connective tissue. In our laboratory, we focused on blocking the signaling pathways that mediate the oncogenic activity of the initiating KRAS oncogenes. A decade ago, our lab decided to use genetically engineered mouse-tumor models capable of reproducing the natural history of human PDAC. We did this in order to analyze the therapeutic potential of the main components of the KRAS signaling pathways. These studies have unveiled the reason why the drugs tested so far have intolerable toxic effects, with mice dying within several weeks: they target some proteins that are essential for the dynamic state of equilibrium that is the condition of optimal functioning of the cells. This is called normal homeostasis. These crucial proteins are mainly kinases, enzymes that are able to modify how other molecules function. They play a critical and complex role in regulating cellular signaling and orchestrate processes such as hormone response and cell division. These results might explain why the KRAS-signaling inhibitors tested so far have failed in clinical trials. On the other hand, the removal of other signaling kinases did not have toxic side effects, but also had no impact on tumor development. Of the more than 15 kinases involved in the transmission of signals from the KRAS oncogene, only three displayed significant therapeutic benefits without causing unacceptable side effects. These are: RAF1, the epidermal growth factor receptor (EGFR) and CDK4.

It works! (in mice)

In initial studies, we observed that the elimination (via genetic manipulation) of the expression of some of these three kinases prevented the onset of PDAC caused by the KRAS oncogene. However, its elimination in animals with advanced tumors had no significant therapeutic effects. These results caused us to question whether it would be possible to eliminate more than one kinase simultaneously without increasing the toxic effects. As described in our recent work published in the journal Cancer Cell, the elimination of RAF1 and EGFR expression induced the complete regression of advanced PDACs in 50% of the mice. We are currently studying whether we can increase this by also eliminating CDK4. The analysis of the pancreas of animals in which we were no longer able to observe tumors by imaging techniques revealed the complete absence of lesions in two of them. Two mice showed some abnormal ducts, probably residual scarring from the tumor. The others had tumor micro-masses of one-thousandth the size of the original tumor. The study of these revealed the presence of tumor cells, in which the expression of the two targets, EGFR and RAF1, had not been completely eliminated, a common technical problem in this type of study. It is significant that these results were observed not only in mice. The inhibition of the expression of these two proteins in cells derived from nine out of ten human PDACs were also capable of blocking their proliferation in vivo when transplanted into immunosuppressed mice as well as in vitro cultures.

What now?

While these results have only been observed in a subset of mice for now, their importance lies in the fact that it is the first time that it has been possible to completely eliminate advanced PDAC tumors by eliminating a pharmacologically directed target. These observations are clearly important for the development of treatments based on the inhibition of RAF1 and EGFR, but they only represent a first step on a long, hard road ahead. First, it is important to identify the differences between the PDACs that respond to the combined elimination of RAF1 and EGFR and those that are resistant. As described in our work, the analysis of these two tumor types revealed that they are not active in the same way – more than 2,000 genes are expressed differently. Identifying additional targets in resistant tumors that do not increase treatment toxicity is not going to be an easy task. To continue our tests with genetically engineered mice, the immediate but no less difficult task is the development of specific RAF1 inhibitors. Indeed, we only currently have potent drugs against the second target, EGFR. In principle, there are four possible approaches:
  • Generate selective inhibitors for its kinase activity.
  • Generate inhibitors for its binding to the KRAS oncogene.
  • Generate inhibitors for its interaction with effector targets that transmit oncogenic signaling mediated by RAF1.
  • Degrade the RAF1 protein with drugs.
Designing inhibitors of the RAF1 kinase activity would seem to be the most affordable option, given the experience of the pharmaceutical industry in designing this molecule type. The problem resides in the fact that there are two other kinases of the same family, ARAF and BRAF, whose catalytic centers (the “active core” of the enzymes) are nearly identical. RAF1 kinase inhibitors are also targeting these other kinases, which causes collateral damage. The ones tested to date have caused high toxicities and the clinical trials had to be stopped. Continuing to develop effective molecules that are capable of blocking RAF1 activity in patients with PDAC will not be easy. It will surely take more time than we hope, but at least a road map has already been outlined that shows us how to keep moving forward. Created in 2007 to help accelerate and share scientific knowledge on key societal issues, the AXA Research Fund has been supporting nearly 600 projects around the world conducted by researchers from 54 countries. To learn more about this AXA Research Fund project, please visit the dedicated page. This article was translated from the original Spanish by Sara Crespo, Calamo & Cran.The Conversation Mariano Barbacid, profesor e investigador AXA-CNIO de Oncología Molecular, Centro Nacional de Investigaciones Oncológicas CNIO This article is republished from The Conversation under a Creative Commons license. Read the original article.
By Prof Mariano Barbacid
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Dr Linda Calabresi
  • Clinical Articles

Mental health first aid

Managing patients with mental health issues is a common recognised challenge for Australian GPs. Managing families and carers is a common often unrecognised challenge for Australian GPs. Knowing someone with a mental health issue, living with them, working with them or caring for them can be extremely difficult and exhausting, never knowing what the right thing is to say or do. Mental Health First Aid is a perfect resource that you can recommend in just these circumstances. The not-for-profit organisation behind this charity is on a mission to train all Australians in the best evidenced-based approach to helping people with a psychological problem. So on the website, people can find authoritative and practical advice on topics such as when should you suspect someone is psychotic and what should you do if you fear someone is contemplating suicide. In addition there are courses that anybody can undertake that actually train you in mental health first aid. How empowering that must be for all those friends and carers who are struggling to help someone they care about who is ill. The information is also available in a range of languages, and also has specific resources for some of the unique issues experienced by Aboriginal and Torres Strait Islander people. This excellent resource is likely to prove valuable not only for patients, but health professionals as well.   >> Access the resource here Recommended at the Sydney Annual Women’s and Children’s Health Update in February, 2019 by Dr Claire Kelly, Director of Curriculum at Mental Health First Aid Australia.

By Dr Linda Calabresi
teething baby
Dr Mihiri Silva
  • Clinical Articles

Beware teething remedies

If you imagine a teething child, what do you see? An irritable tot with a fever, in pain, and generally unwell? Teething’s a normal developmental process that people have long associated with illness. However, the evidence says otherwise. How strong is this evidence? Is there anything you can do to help a teething child? What about teething gels and teething necklaces? Teething is when new teeth emerge through the gums, and usually starts at about six months of age. A review of 16 studies found that although teething was linked with signs and symptoms, these were usually mild involving gum irritation, irritability, and drooling. Although body temperature may be slightly raised, the review found poor evidence to suggest teething caused fever. Many symptoms linked to teething, like irritability, sleep disturbance and drooling, are difficult to measure objectively and are based on what parents report, which is subjective and may be inaccurate. And, as teething comes and goes, and its timing is relatively unpredictable, recording even measurable symptoms like temperature changes in a reproducible, reliable way is virtually impossible. So teething problems seem to be over-reported in the types of studies that rely on people remembering what happened.

What else could cause the symptoms?

Other biological triggers may in fact explain the symptoms traditionally linked to teething. Teething coincides with normal changes in children’s immunity; the mother’s antibodies are transferred to babies in pregnancy and help protect the baby in the first 6-12 months of life, but start to wane at about the same time as teething. This, together with behavioural changes as infants start to explore their surroundings, increases the chances of catching viral infections with symptoms like those reported for teething. Separation anxiety and normal changes in sleep patterns may also account for irritability and sleep disturbances, which may be mistakenly attributed to teething. As teething symptoms are generally likely to be mild and focused on the mouth, parents are warned against presuming that signs of illness in other parts of the body are due to teething. That’s because this may delay the detection of potentially serious infections that may need medical attention. It may also delay parents getting help settling their child to sleep.

How about teething gels?

The search for solutions to the perceived problem of teething may lead parents to pin their hopes on gels, toys and other products, none of which have been scientifically assessed to alleviate teething symptoms. Nevertheless, teething gels usually contain a variety of ingredients that help relieve supposed teething-related symptoms. Some, such as the recently discontinued Adelaide Women’s and Children’s Hospital Teething Gel, contain the anaesthetic lidocaine. Very little lidocaine is absorbed into the body when applied to the gums, and only minor complications like vomiting have been reported in Australia. However, accidental swallowing and applying too much can lead to poisoning, resulting in seizures, brain injury, and heart problems. The decision to discontinue the gel follows a 2014 warning issued by the US Food and Drug Administration against using teething gels with topical anaesthetics, after reports of infant and child hospitalisation and death. There have also been warnings about teething gels containing benzocaine. This is another anaesthetic applied to the gums that can lead to a dangerous and fatal blood condition called methaemoglobinaemia, which affects the blood’s ability to carry oxygen. Another common ingredient in popular teething gels is choline salicylate, an anti-inflammatory similar to aspirin. This increases the risk of liver disease and brain injury if the child eats too much. This may also carry the risk of Reye syndrome, a rare but serious condition that can lead to seizures, loss of consciousness and death. Reye syndrome has been linked to the use of aspirin in children, particularly during viral infections. A case of suspected teething gel-induced Reye syndrome in 2008 led to the products being contraindicated (warned against) in children in the UK. A number of young Australian children who used too much salicylate-containing teething gel have also reportedly been hospitalised with side-effects. But the products are still available in Australia.

How about ‘natural’ products?

Although a range of “natural” and homeopathic teething solutions are heavily marketed to parents of young children, these too have risks. A manufacturer recently recalled a range of natural teething gels after cases of reported poisoning. And US regulatory authorities found the same range contained higher than reported levels of belladonna, a poisonous plant that despite its dangers is used as a homeopathic pain killer and sedative. In searching for “natural” therapies, parents are also turning to amber teething necklaces that supposedly relieve teething symptoms. Amber is a fossilised tree resin that has historically been suggested to have anti-inflammatory properties. However, several widely reported cases of strangulation have led to warnings from both US and Australian regulatory authorities. There is currently no scientific evidence these necklaces work. The Australian Competition and Consumer Commission (ACCC) says amber and other “teething” necklaces, even when mothers wear them, are:
…colourful and playful in design, and may be confused with toys.
All toys for children aged 36 months and below, including teething toys, are strictly regulated by Australian standards. As the ACCC warns, teething necklaces are unlikely to fulfil this requirement.

What to do?

So what are the best options to relieve teething symptoms? With a lack of any good-quality evidence to recommend any specific therapy, experts suggest the best remedy is affection and attention. Rubbing a clean finger on the gum, or applying gentle, firm pressure with a cooled (but not frozen), clean washcloth or teething ring may provide some relief. Although it’s hard to know exactly how these work, they are unlikely to lead to serious problems. Teething can be a difficult time, but it will eventually pass. In the meantime, it is important that parents avoid falling prey to supposed cures that are not only unproven, but are also potentially dangerous. Mihiri Silva, Paediatric dentist, Senior Lecturer and Post-doctoral Research Fellow, Murdoch Children's Research Institute This article is republished from The Conversation under a Creative Commons license. Read the original article.
By Dr Mihiri Silva
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Dr Linda Calabresi
  • Clinical Articles

Meat no more

Bad news for steak lovers. The latest findings from two very large, well-known prospective cohort studies show that increasing your intake of red meat, even if it’s only by half a serving a day, significantly increases your risk of death. And the increased mortality risk is independent of how much red meat you were eating to start with, what other lifestyle factors you make at the same time you increase your red meat intake or whether the meat is processed or unprocessed, although the association was stronger for processed meat, according to the research recently published in The BMJ. The researchers were analysing data from Nurses’ Health Study (over 53,000 women) and the Health Professionals Follow-up study (involving almost 28,000 men). Both US studies included repeated measures of diet and lifestyle factors, so the study authors were able to determine that increases in red meat consumption of at least half a serving a day over eight years was associated with a 10% higher mortality risk over the next eight years. The increase in deaths was generally related to cardiovascular or neurodegenerative disease. It’s been known for some time that eating lots of red meat is not good for you, increasing your risk of chronic diseases and premature death. What we haven’t known (until now) is what difference changing your consumption of red meat over time does to this increased health risk. Interestingly the analysis also found a decrease in red meat consumption was not associated with mortality. But if the meat intake was replaced by a healthy alternative then your risk of dying prematurely is lowered. “A decrease in total red meat consumption and a simultaneous increase in the consumption of nuts, fish, poultry without skin, dairy, eggs, whole grains, or vegetables over eight years was associated with a lower risk of death in the subsequent eight years,” they said. So it really is yet another nail in the coffin for the traditional Aussie high meat diet. “Our analysis provides further evidence to support the replacement of red and processed meat consumption with healthy alternative food choices,” they concluded.  

Reference:

Zheng Y, Li Y, Satija A, Pan A, Sotos-Prieto M, Rimm E, et al. Association of changes in red meat consumption with total and cause specific mortality among US women and men: two prospective cohort studies. BMJ. 2019 Jun 12; 365: I2110. DOI: 10.1136/bmj.l2110
By Dr Linda Calabresi
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Dr Evangeline Mantzioris
  • Clinical Articles

How to get the nutrients you need without eating as much red meat

If you’re a red meat-eater, there’s a good chance you’re eating more of it than you should. At last count, Australians ate an average of 81 grams of red meat per day. The planetary health diet was developed by researchers to meet the nutritional needs of people around the world, while reducing food production’s environmental impact. It recommends reducing our red meat intake to around 14g a day. That’s around 100g of red meat a week. Australia’s dietary guidelines are more conservative and recommend limiting red meat intake to a maximum of 455g a week, or 65g a day, to reduce the additional cancer risk that comes from eating large quantities of red meat. So, what should you eat instead? And how can you ensure you’re getting enough protein, iron, zinc and vitamin B12?

Protein

Animal sources of protein provide essential amino acids, which the body uses to make muscle, tissue, hormones, neurotransmitters and the different cells and antibodies in our immune system. The planetary health diet offers a good blueprint for gaining enough protein from a variety of other animal sources. It recommends eating, on average:
  • 25g of chicken per day
  • 28g of fish per day day
  • 1.5 eggs per week
  • 200g of milk per day day
  • 50g of cheese per day.
In addition to the 14g of red meat in the planetary health diet, these foods would provide a total of 45g of protein per day, which is around 80% of our daily protein needs from animal sources. The remaining protein required (11g) is easily met with plant foods, including nuts, legumes, beans and wholegrains.

Iron

Iron is essential for many of the body’s functions, including transporting oxygen to the blood. Iron deficiency can lead to anaemia, a condition in which you feel tired and lethargic. Pre-menopausal women need around 18 milligrams a day, while men only need 8mg. Pre-menopausal women need more iron because of the blood they lose during menstruation. So, how can you get enough iron? Beef, of course, is a rich source of iron, containing 3.3mg for every 100g. The same amount of chicken breast contains 0.4mg, while the chicken thigh (the darker meat) contains slightly higher levels, at 0.9mg. Pork is similarly low in iron at 0.7mg. But kangaroo will provide you with 4.1mg of iron for every 100g. Yes, kangaroo is a red meat but it produces lower methane emissions and has one-third the levels of saturated fat than beef, making it a healthier and more environmentally friendly alternative. Plant protein sources are also high in iron: cooked kidney beans have 1.7mg and brown lentils have 2.37mg per 100g. If you wanted to cut your red meat intake from the 81g average to the recommended 14g per day while still getting the same amount of iron, you would need to consume the equivalent of either 50g of kangaroo, 100g of brown lentils or 150g of red kidney beans per day.

Zinc

Zinc is an essential mineral that helps the body function optimally. It affects everything from our ability to fight bugs, to our sense of smell and taste. Zinc requirements are higher for men (14mg a day) than women (8mg a day) due to zinc’s role in the production and development of sperm. Of all meat sources, beef provides the most zinc, at 8.2mg per 100g. Chicken breast provides just 0.68mg, while the chicken thigh has 2mg. In kangaroo meat, the levels of zinc are lower than beef, at 3.05mg. The richest source of zinc is oysters (48.3mg). Beans such lentils, red kidney beans and chickpeas all provide about 1.0mg per 100g. To meet the shortfall of zinc from reducing your red meat intake, you could eat 12 oysters a day, which is unlikely. Or you could eat a combination of foods such as 150g of red kidney beans, one serve (30g) of zinc-supplemented cereals like Weet-bix, three slices of wholegrain bread, and a handful of mixed nuts (30g).

Vitamin B12

Vitamin B12 is important for healthy blood and nerve function. It’s the nutrient of most concern for people cutting out meat products as it’s only found in animal sources. Requirements of vitamin B12 are the same for both women and men at 2.4 micrograms (mcg) a day. Beef and kangaroo provide 2.5mcg per 100g serve, while chicken and turkey provide about 0.6mcg. Dairy products also contain vitamin B12. One glass of milk would give you half your daily requirement requirement (1.24mcg) and one slice of cheese (20g) would provide one-fifth (0.4mcg). Vitamin B12 can be found in trace amounts in spinach and fermented foods, but these levels aren’t high enough to meet your nutritional needs. Mushrooms, however, have consistently higher levels, with shiitake mushrooms containing 5mcg per 100g. To meet the shortfall of vitamin B12 from reducing red meat intake, you would need to eat 75g kangaroo per day or have a glass of milk (200ml) plus a slice of cheese (20g). Alternatively, a handful of dried shiitake mushrooms in your salad or stir-fry would fulfil your requirements.

Don’t forget about fibre

A recent study found fibre intakes of around 25 to 29g a day were linked to lower rates of many chronic diseases such as coronary heart disease, type 2 diabetes, stroke and bowel cancer. Yet most Australian adults currently have low dietary fibre levels of around 20g a day. By making some of the changes above and increasing your intake of meat alternatives such as legumes, you’ll also be boosting your levels of dietary fibre. Substituting 100g of lentils will give you an extra 5g of fibre per day. With some forward planning, it’s easy to swap red meat for other animal products and non-meat alternatives that are healthier and more environmentally sustainable.The Conversation Evangeline Mantzioris, Program Director of Nutrition and Food Sciences, University of South Australia This article is republished from The Conversation under a Creative Commons license. Read the original article.
By Dr Evangeline Mantzioris
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Dr Linda Calabresi
  • Clinical Articles

Quality improvement in aged care

If you look after patients in an aged care facility you should really have a look at this resource. It’s from the Australian Government’s Department of Health and it basically gives you all you need to know about the most recent initiative to ensure high standard of care in these facilities. From July 1, all aged care facilities that receive government subsidies for the services they provide will need to collect and provide data on three specific adverse outcomes that residents might experience. Specifically the government is asking these facilities to record information on pressure injuries, use of physical restraint and unplanned weight loss because these are indicators of clinical quality, or more exactly indicators of poor clinical quality. Every three months residential facilities will need to submit this Quality Indicator (QI) data to the Department of Health which will generate a report. So where do GPs fit in? According to the resource information, GPs will need to get involved in making sure facilities proactively respond to this QI information. The actions GPs are being asked to take are mainly about getting engaged in the programme – ask questions, ask to see the 3-monthly QI reports and help with the interpretation of the information from these reports. It will also be important that GPs contribute ideas on how to improve care. Even though this new initiative is only looking at three indicators, and there are many more that could be considered such as pain and falls, these three were chosen because they each have a broad impact across a number of other care areas – these are the canaries in the mine so to speak. Improve these and a whole lot of other areas of care improve as well. It’s not our usual type of recommended resource but if you’re a GP looking after patients in aged care you will recognise how this initiative could be very important to the health of our elderly patients. Check it out.   >> Access the resource here

By Dr Linda Calabresi
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Dr Linda Calabresi
  • Clinical Articles

Anorexia and cancer risk

You’d think having anorexia nervosa was bad enough. But among all the negative effects it can have on your body, could it also increase your risk of cancer? Or does the condition perversely mimic the caloric restriction and fasting that have been demonstrated to benefit the prevention of some malignancies - meaning could it protect against cancer? That's what European oncology researchers wanted to find out through their systematic review and meta-analysis of a series of studies involving more than 42,000 people with the eating disorder. The result was both encouraging and intriguing. It appears that overall there was no association of anorexia nervosa with risk of cancer. But that’s not the whole story. On further analysis it appears anorexia nervosa was associated with some cancers and not others. In some cases the condition increased the risk and in others it appeared protective, hence the balancing out effect of no association overall. “Findings from our meta-analysis suggest that anorexia nervosa was associated with decreased breast cancer incidence compared with the general female population, with high confidence,” said the study authors in JAMA Network Open. And on the down side, the researchers found anorexia nervosa appeared to be associated with an increased risk of developing lung and oesophageal cancer, although the evidence was less compelling than that for breast cancer. As the authors point out, the breast cancer protection makes sense in terms of physiology. Anorexia notoriously interferes with a woman’s hormones, reducing her levels of oestradiol as well as insulin-like growth factor 1. Women with anorexia often have delayed puberty, early menopause and an overall decreased lifetime exposure to oestrogen so it stands to reason that a hormone-sensitive cancer, such as breast cancer is less likely to develop. But the increased risk of lung and oesophageal cancer is harder to explain. One might think, given the types of cancer we’re talking about that perhaps there was a greater prevalence of smoking among people with anorexia nervosa. But no. “[T]he increased risk of developing lung or oesophageal cancer does not seem to be attributable to a higher prevalence of smoking among women with anorexia nervosa,” they said. Interestingly the authors refer to a 2016 meta-analysis that determined smoking prevalence was much higher among people with bulimia nervosa than the general population, but not anorexia nervosa. The researchers offer no explanation for the association between anorexia and lung and oesophageal cancer, conceding the evidence isn’t strong. However they do warn that the findings suggest perhaps a need for greater vigilance in investigating symptoms suggestive of cancers of either the respiratory tract or the GIT in anorexia nervosa patients. As with most studies, the study authors call for further research to confirm or refute these associations, suggesting that the findings have possibly important implications. “Understanding the mechanisms underlying these associations could have important preventive potential,” they concluded.  

Reference:

Catalá-López F1, Forés-Martos J, Driver JA, Page MJ, Hutton B, Ridao M, et al. Association of Anorexia Nervosa With Risk of Cancer: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019; 2(6): e195313. DOI: 10:1001/jamanetworkopen.2019.5313
By Dr Linda Calabresi
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Dr Linda Calabresi
  • Clinical Articles

Help for women with vulval issues

Female patients who present with vulval pain or itch have usually put up with symptoms for some time before coming to the doctor. When it comes to this area of the female anatomy there is still a lot of ignorance and embarrassment in the world outside our surgeries. And while it is true you can find the answer to almost any question on the net, for these particular problems there’s a lot of dodgy information out there. So here’s an information source you can trust and recommend. Care down there (www.caredownthere.com.au) is a consumer-directed website written by respected health professionals that provides accurate, up-to-date and practical information and advice about all things vulval. From herpes to vulval sclerosis, the site covers the broad range of conditions that can affect women as well as providing some fundamental education about how to distinguish between normal anatomy and physiology and something going awry. The site was founded by Dr Gayle Fischer and Dr Jennifer Bradford who are well-known, well-respected members of the Australasian College of Dermatologists and the Royal Australian and the New Zealand College of Obstetricians and Gynaecologists. The content has been developed by a group of Australian health professionals with an interest and experience in vulval problems including dermatologists, gynaecologists, a pain management specialist, a sexual health physician, a psychologist and a pelvic floor physiotherapist. It is sponsored by Epiderm but exists as an independent resource. If you’re wanting to direct your female patients to a resource that is both comprehensive and authoritative, this really does fit the bill.   >> Access the resource here

By Dr Linda Calabresi
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Dr Linda Calabresi
  • Clinical Articles

Are you burnt out at work? Ask yourself these 4 questions

It’s normal to feel stressed at work from time to time. But for some people, the stress becomes all-consuming, leading to exhaustion, cynicism and hatred towards your job. This is known as burnout. Burnout used to be classified as a problem related to life management, but last week the World Health Organisation re-labelled the syndrome as an “occupational phenomenon” to better reflect that burnout is a work-based syndrome caused by chronic stress. The newly listed dimensions of burnout are:
  • feelings of energy depletion or exhaustion
  • increased mental distance from one’s job, or feelings of negativism or cynicism related to one’s job
  • reduced professional efficacy (work performance).
In the era of smartphones and 24-7 emails, it’s becoming increasingly difficult to switch off from the workplace and from those who have power over us. The new definition of burnout should be a wake-up call for employers to treat chronic stress that has not been successfully managed as a work health and safety issue.

How do you know if you’re burnt out?

If you think you might be suffering burnout, ask yourself the following questions:
  1. has anyone close to you asked you to cut down on your work?
  2. in recent months have you become angry or resentful about your work or about colleagues, clients or patients?
  3. do you feel guilty that you are not spending enough time with your friends, family or even yourself?
  4. do you find yourself becoming increasingly emotional, for example crying, getting angry, shouting, or feeling tense for no obvious reason?
If you answered yes to any of these questions, it might be time for change. These questions were devised for the United Kingdom Practitioner Health Programme and are a good starting point for all workers to identify if you are at risk of burning out. (You can also complete the British Medical Association’s online burnout questionnaire, although it’s tailored for doctors so the drop-down menu will ask you to select a medical specialty). If you think you’re suffering burnout, the first step is to talk to your line manager or workplace counsellor. Many workplaces now also have confidential external psychologists as part of their employee assistance programme.
Wes Mountain/The Conversation, CC BY-ND

What causes burnout?

We all have different levels of capacity to cope with emotional and physical strains. When we exceed our ability to cope, something has to give; the body becomes stressed if you push yourself either mentally or physically beyond your capacity. People who burn out often feel a sense of emotional exhaustion or indifference, and may treat colleagues, clients or patients in a detached or dehumanised way. They become distant from their job and lose the zeal for their chosen career. They might become cynical, less effective at work, and lack the desire for personal achievement. In the long term, this is not helpful for the person or the organisation. While burnout isn’t a mental health disorder, it can lead to more serious issues such as family breakdowns, chronic fatigue syndrome, anxiety, depression, insomnia, and alcohol and drug abuse.

Who is most at risk?

Any worker who deals with people has the potential to suffer from burnout. This might include teachers, care workers, prison officers or retail staff. Emergency service workers – such as police, paramedics, nurses and doctors – are at even higher risk because they continually work in high-stress conditions. A recent survey of 15,000 US doctors found 44% were experiencing symptoms of burnout. As one neurologist explained:
I dread coming to work. I find myself being short when dealing with staff and patients.
French research on hospital emergency department staff found one in three (34%) were burnt out because of excessive workloads and high demands for care. Lawyers are another profession vulnerable to burnout. In a survey of 1,000 employees of a renowned London law firm, 73% of lawyers expressed feelings of burnout and 58% put this down to the need for a better work-life balance. No matter what job you do, if you are pushed beyond your ability to cope for long periods of time, you’re likely to suffer burnout.

It’s OK to say no to more work

Employers have an organisational obligation to promote staff well-being and ensure staff aren’t overworked, overstressed, and headed towards burnout. There are things we can all do to reduce our own risk of burnout. One is to boost our levels of resilience. This means we’re able to respond to stress in a healthy way and can bounce back after challenges and grow stronger in the process. You can build your resilience by learning to switch off, setting boundaries for your work, and thinking more about play. As much as you can, inoculate yourself against job interference and prevent it from ebbing into your personal life. No matter what your profession, don’t let your job become the only way you define yourself as a person. And if your job is making you miserable, consider moving jobs or at least have a look at what else is out there. You may surprise yourself. If you or anyone you know needs help or support, you can call Lifeline on 13 11 14.The Conversation Michael Musker, Senior Research Fellow, South Australian Health & Medical Research Institute This article is republished from The Conversation under a Creative Commons license. Read the original article.
By Dr Linda Calabresi
vcacinations in pregnancy
Dr Linda Calabresi
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Improving vaccination rates in pregnancy

Increasingly, pregnant women are heeding the warnings about the dangers of pertussis and getting vaccinated but the same does not appear to be happening with influenza protection. According to an Australian retrospective analysis, pertussis vaccination of pregnant women in Victoria increased from 38% in 2015 to 82% two years later. However, when they looked at rates of influenza vaccination the prevalence fluctuated according to the season but even so, the overall rate was only 39%. Looking first at the factors that appeared to influence whether a woman got vaccinated at all, the researchers found women who were older, who were having their first child, attended antenatal care earlier in the pregnancy and who were receiving GP-led care were more likely to receive immunisation (thumbs up for the GPs). On the negative side, the likelihood of vaccination was significantly lower in women born overseas, those who smoked during pregnancy and among Aboriginal and Torres Strait Islander women. Overall it appeared the more contact a pregnant woman had with the health system, especially if that contact was with health professionals who are well-versed in all things immunisation, ie GPs, the more likely it was that vaccination would be offered, accepted and delivered. The variation in coverage rates across different hospital-led organisations reflects the fact that immunisation for flu and pertussis has not yet become part of standard, best practice guidelines for routine antenatal care. “Fewer than half the respondents indicated that vaccines were always or usually administered during routine antenatal care,” they wrote. Following on from these general observations, researchers tried to determine why it was that vaccination coverage for pertussis rose so dramatically between 2015 and 2017, and why coverage for influenza prevention didn’t. “This may reflect continued promotion by state and national bodies of the importance of maternal pertussis vaccination, and increased awareness among pregnant women of the seriousness of pertussis in infants,” they said. By contrast, the researchers suggest that influenza is often believed to pose a greater health risk to the mother as opposed to the infant, and this along with concerns about the safety of the flu vaccine itself may, at least in part, explain the poor uptake of this vaccine. To improve this situation and increase rates of protection for Australian pregnant women and their children, the study authors had a number of recommendations. Most importantly they suggest we need to build vaccination against pertussis and influenza into the standard of care for all antenatal practices – be they hospital based, midwife-led or part of the GP antenatal shared care program. Basically we need to bring vaccination up and centre into our consciousness, so women get offered the vaccine and then ensure our systems have the capacity to be able to provide this vaccination as the opportunity arises. “Maternal vaccination should be embedded in all antenatal care pathways, and systems should be improved to increase the uptake of vaccination by pregnant women,” they conclude. Other recommendations included highlighting the benefits of vaccination to those groups of women most at risk such as women who smoke and Aboriginal and Torres Strait Islander women. But key to all the recommendations is making vaccination just part of routine care. As an accompanying editorial points out, “Embedding vaccination into standard pregnancy care, whether delivered by GPs, midwives or obstetricians, normalises the process, improves access to vaccination and reduces the risk of missing opportunities for vaccination.”  

References:

Rowe SL, Perrett KP, Morey R, Stephens N, Cowie BC, Nolan TM, et al. Influenza and pertussis vaccination of women during pregnancy in Victoria, 2015-2017. Med J Aust 2019 Jun 3; 210(10): 454-62. DOI: 10.5694/mja2.50125 Marshall HS, Amirthalingam G. Protecting pregnant women and their newborn from life-threatening infections. Med J Aust 2019 Jun 3; 210(10): 445-6. DOI: 10.5694/mja2.50174
By Dr Linda Calabresi
Simple blood test a mortality predictor
Dr Linda Calabresi
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Smartvax

It’s only been around a few years, but this little bit of technology has already received world wide acclaim for its ability to improve the safety of vaccines in the real-world setting. In simple terms, Smartvax is a program practices install into their software system that sends an SMS directly to patients three days after they receive a vaccination. Patients are asked if they experienced an adverse reaction to the vaccine. A straightforward Yes (Y) or No (N) is all that is required. A No reply ends the conversation, but a Yes will trigger a brief questionnaire that examines the nature of the adverse reaction. If the reaction resulted in the need to seek medical attention this is then flagged in the GP’s software inbox as well as with the local health authority. In practical terms this means adverse reactions are tracked in real time and act as an early warning signal that something could be amiss with a vaccine. Smartvax was developed by Perth GP, Dr Alan Leeb and Ian Peters, following a spate of serious and unexpected adverse reactions among young children who received one brand of flu vaccine back in 2010. It was apparent that a better, more time-sensitive system of monitoring side effects to vaccines was needed to ensure the safety of patients. With the widespread use of mobile phones, the day three post vax text has proven a very effective means of tracking reactions, with a high level of acceptance by patients. In a study from one NSW general practice, the response rate to the SMS  text was 85% post-childhood vaccination, and even in the over 65 year age range the response rate was 74%. Smartvax has now been adopted by more than 280 practices around Australia. The technology can also be used as a reminder system to prompt patients when their next vaccine is due. This is such a clever idea and as general practice becomes more and more tech savvy one can envisage a day when Smartvax is a basic requirement for all clinics that provide vaccinations.   >> Access the resource here

By Dr Linda Calabresi
shutterstock_1467369743
Dr Linda Calabresi
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Gene-directed prescribing coming to general practice

It’s been around for some time now. The idea of checking a person’s genes to guide appropriate prescribing is not new. It is pretty much standard practice when treating many if not most cancers. But pharmacogenomics in general practice? Looking at an individual’s genetic variants to work out the best treatment for their depression, high cholesterol or gout? Yes – it’s coming. As authors of a recently published review in the Australian Journal of General Practice say, all practising clinicians will have had the experience of patients responding differently to medications despite every indication the medication should be effective, based on all the evidence from randomised controlled trials. It is known that certain genes that regulate the absorption, distribution, metabolism and excretion (ADME) of medications are commonly responsible for this difference in response, as these genes can vary between individuals. Researchers have also identified another group of genes that can influence medication responses directly, which, while less common can have important implications for prescribing. “For example, carbamazepine should not be prescribed to patients with certain human leucocyte antigen (HLA) genotypes because of an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis,” the Australian review authors said. Overall, there have been at least 15 genes identified for which testing can be useful and clinically beneficial in guiding prescribing of 30 different medications. How important will this be in general practice? According to this review at least, very. Firstly the likelihood of having a genetic variation that will influence how a person responds to a common medication is incredibly high. “A recent study of 5400 Australians who underwent testing of just four ADME genes showed that 96% had at least one clinically actionable pharmacogenomic variant,” the review authors said. And then the likelihood that a person will be prescribed one of the drugs that we can now predict the response based on genetic testing is also incredibly high. On analysis of PBS data from 2017, the researchers determined that in that year approximately 1.7 million Australians had filled a prescription for at least one the drugs that has the highest level of evidence of clinically relevant gene-medication association. In their review the authors present a number of case studies which demonstrate the usefulness of genetic testing in clinical practice. These include a patient with anxiety and depression who fails to respond to standard treatment leading to a significant deterioration of her condition. Genetic testing of CYP enzymes found the patient had a genetic variation that meant they rapidly metabolised certain antidepressants, but could be prescribed an alternative medication that wasn’t as dependent on the affected enzyme. Another example involved an older Han Chinese man who needed to be prescribed allopurinol for gout. Because this particular ethnicity has a 20% chance of carrying a gene that puts them at risk of developing severe cutaneous adverse reaction to allopurinol, gene testing was done to help ensure this risk was minimised. Similarly, a genetic variation that gives a higher than normal risk of muscle toxicity when taking simvastatin or atorvastatin can be tested for prior to patients being prescribed these medications, and a safer alternative statin offered. Fundamentally this type of testing will lead to more effective, safer prescribing. The problem is of course, pharmacogenomic testing does not attract a Medicare rebate in Australia and the cost is prohibitive for most patients, even though, according to the review authors the costs are decreasing all the time. A panel of common CYP enzymes now costs between $150 and $200. But the authors suggest this situation will have to change. Even on the basis of economics alone, the government needs to consider allowing rebates for at least some pharmacogenomic tests. “A report in 2008 estimated that the widespread implementation of such testing in Australia could yield savings in excess of $1 billion annually by the avoidance of adverse medication reactions alone,” they said. And imagine how much time, money and angst could be saved if doctors could ensure the first antidepressant a patient is prescribed had a high likelihood of having an effect, rather than the current trial and error approach. However while we wait for better reimbursement for this testing, the authors suggest the doctors consider using the tests where appropriate in patients who are prepared to pay. “Responsible doctors can use the tests and evidence that are already available to improve prescribing decisions for their patients,” they conclude.

Reference

Polasek TM, Mina K, Suthers G. Pharmacogenomics in general practice: The time has come. AJGP. 2019 March; 48(3): 100-5. Available from: https://www1.racgp.org.au/ajgp/2019/march/pharmacogenomics-in-general-practice
By Dr Linda Calabresi

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