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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 Linda Calabresi

Children who persistently or frequently experience high anxiety need help, says psychologist Jennie Hudson, Professor and Director of the Centre for Emotional Health, at Sydney’s Macquarie University. “There has been a tendency to believe kids are going to grow out of [their anxiety]”, she said. In the past, anxiety in children was believed to be normal part of growing up. In fact, in the first Australian Child and Adolescent Mental Health survey in 1998, the question of anxiety disorders in children was not included at all. But the reality is, anxious children grow into anxious teenagers and then into anxious adults, and by then it is not only harder to treat it is also too late to reverse much of the negative impact this condition has had on these people’s lives, she explained in an interview following her presentation on the subject at HealthEd’s Mental Health in General Practice evening seminar held recently in Sydney. “Children need strategies to manage their anxiety now,” she said. “We, as health professionals need to be encouraging parents to seek help if they feel their child’s anxiety is interfering with their life.” For GPs who are wondering about the most appropriate advice to give parents of anxious children, a key principle is to encourage children not to avoid tasks or situations they fear. Parents need to support their child in facing the situations that make them afraid, even if it is ‘bit by bit’, and celebrate each time they manage to accomplish even part of a feared task be it at school, sport or socially. “There is a natural tendency for a parent to protect their child from feeling anxious – they will answer for the child who gets worried about replying or say they don’t need to give the speech in class that is making them nervous for example” but this tends to fuel the anxiety. By enabling the child to practise avoidance, the parent is inadvertently endorsing the child’s belief that this is something to be feared. Another important principle in managing anxiety in children is to try and get the child to identify their worried thoughts, what it is that they fear is going to happen. Commonly a child will catastrophise the consequences of a situation for example “failing this maths test means my life will be ruined”. Once the fear is described the parent and child can discuss, logically why this feared consequence is unlikely to happen. “We call it ‘detective thinking’ – encouraging the child to develop strategies to undertake a realistic appraisal of the situation,” Professor Hudson explained. In terms of resources available for parents, there are a number Professor Hudson recommends. “Helping Your Anxious Child: A Step-by-Step Guide for Parents,” written by Australian psychologists Ronald Rapee, Ann Wignall, Susan Spence, Vanessa Cobham, and Heidi Lyneham is practical, relevant and up-to-date. Another good option is “Helping Your Child with Fears and Worries 2nd Edition: A self-help guide for parents” written by UK experts in anxiety, Cathy Creswell and Lucy Willetts. As well as written material, there are some online programs and resources available, Professor  Hudson said. Macquarie University, Sydney has developed a couple of online programs, one called Cool Kids for 7-16-year-olds (https://www.mq.edu.au/about/campus-services-and-facilities/hospital-and-clinics/centre-for-emotional-health-clinic/programs-for-children-and-teenagers#Online) and another called Cool Little Kids (https://coollittlekids.org.au/ ) for children aged seven and under. Another good, evidence-based, online program is Brave (http://www.brave-online.com/) designed for 7-16-year-olds, and developed by researchers at the University of Queensland. Useful fact sheets for parents are available from the Macquarie University’s,  Centre for Emotional Health website (https://www.mq.edu.au/research/research-centres-groups-and-facilities/healthy-people/centres/centre-for-emotional-health-ceh/resources) as well as the Raising Children: The Australian parenting website (www.raisingchildren.net.au) For children with anxiety, CBT is recommended as the first line of treatment. As the risk of adverse effects with CBT is negligible it is recommended that treatment in children be commenced early on the basis of concern of the parent, carer or health professional. There are a number of reliable screening measures for anxiety in children, including the Spence Children’s Anxiety Scale (www.scaswebsite.com). The SCAS has a parent, child and teacher report along with Australian norms for 6-18-year-olds. The DASS21 is a reliable screening and monitoring tool for older adolescents. Currently in Australia only two of the SSRIs, fluvoxamine and sertraline, are approved for use in children and adolescents with obsessive compulsive disorder, Professor Hudson said. “There have been trials in Australia and the US combining CBT and sertraline. In our study, combining CBT and sertraline did not improve outcomes over and above CBT and placebo for children and adolescents with anxiety,” she added.

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.

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

Dr Linda Calabresi

Teenagers who are constantly checking their phones are more likely to develop ADHD symptoms than their less social-media-engaged peers, US researchers say. In what the study authors say is the first longitudinal study investigating the issue, researchers found that the frequency of digital media use among over 2500 non-ADHD 15-and 16-year-olds was significantly associated with the subsequent development of ADHD symptoms over a two-year period of follow up. A high frequency of media activity – most commonly checking their smart phone was associated with an 10% increased likelihood of developing inattentive and hyperactive-impulsive symptoms in this teenage cohort. Associations were significantly stronger in boys and participants with more mental health symptoms, such as depressive symptoms and delinquent behaviours. But while the association was statistically significant, further research was needed to determine if the digital media use was the cause of problem, the US authors said in JAMA. “The possibility that reverse causality or undetected baseline ADHD symptoms influenced the association cannot be ruled out”, they said. To date, the potential risks of intense engagement in social media is largely an evidence-free zone, they said. Prior longitudinal studies on this topic have most commonly involved computers, televisions and video-game consoles. But the engagement associated with these devices is markedly different to that seen with modern media platforms especially in terms of accessibility, operating speed, level of stimulation and potential for high-frequency exposure. And as an accompanying editorial points out, television and gaming are sporadic activities whereas the current widespread use of smartphones means social media is now close at hand. “In 2018, 95% of adolescents reported having access to a smartphone (a 22-percentage-point increase from 2014-2015), and 45% said they were online ‘almost constantly’”, the US editorial author explained. This instant access to highly engaging content is designed to be habit-forming. Also the effect of current social media engagement not only involves exposure to violence in games and displacement of other activities that were the major issues in the past. Social media today has been designed to engage the user for longer periods and reward repeated users. New behaviours to consider include frequent attention shifts and the constant media multitasking, which might interfere with a person’s ability to focus on a single task, especially a non-preferred task. It is also hypothesised that the ready availability of desired information may affect impulse control (no waiting is required). And the ‘always-on’ mentality may be depriving young brains of ‘down time’, allowing the mind to rest, tolerate boredom and even practise mindfulness. The study researchers were keen to emphasise their research findings are a long way from proving digital media increases the risk of ADHD symptoms, and even if they did, the public health and clinical implications of this are uncertain. However, the editorial was more enthusiastic about the study’s implications. “With more timely digital media research, parents may feel more confident in the evidence underlying recommendations for how to manage the onslaught of media in their households,” it said. The editorial author suggested the findings support American Academy of Pediatrics guidelines that recommend adolescents focus on activities that have been proven to promote ‘executive functioning’ such as sleep, physical activity, distraction-free homework and positive interactions with family and friends – with the implication being – ‘switch the phone off’. Ref: JAMA 2018; 320(3): 255-263 doi:10.1001/jama.2018.8931 JAMA 2018; 320(3): 237-239

Dr Linda Calabresi

All newly-diagnosed hypertensive patients should be screened for primary aldosteronism before they are started on treatment, Australian experts suggest in the latest issue of the MJA. “Primary aldosteronism is common, specifically treatable, and associated with significant cardiovascular morbidity and mortality,” say researchers Dr Jun Yang, Professor Peter Fuller and Professor Michael Stowasser. They refer to a recent systematic review of over 30 studies, that found among a cohort of people with severe or resistant hypertension (systolic BP >180mmHg and diastolic BP >110), 16.4% were found to have primary aldosteronism. Admittedly these studies were carried out in tertiary centres. There been far fewer studies on the issue conducted in primary care with somewhat mixed results, with one small Australian study suggesting 11.5% of people with significant hypertension in the general practice setting had primary aldosteronism. But its not only the patients with severe hypertension that need to be considered for primary aldosteronism screening, the authors suggest. They point to an Italian study including over 1600 GP patients selected randomly who were screened for primary aldosteronism and found a prevalence of 5.9%.  Importantly 45% of these had mild hypertension (BP 140-159/90-99mmHg). According to the article authors, these patients, because would have most likely remained undiagnosed if not for the study. And the effect of the untreated aldosterone excess would have most likely led to poor blood pressure control and increased cardiovascular, renal and metabolic morbidity long-term. In other words, identifying these patients early in the course of the disease could allow more appropriate treatment and ultimately avoid the end-organ damage that is more likely to occur if diagnosis is delayed until after the development of severe hypertension. “Targeted treatment of [primary aldosteronism] using surgery or mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, rather than non-specific antihypertensive medications, can reverse the underlying cardiovascular pathology,” they said. The recommended biochemical screening tool for primary aldosteronism is the aldosterone to renin ratio which is elevated in this condition because plasma aldosterone is normal or elevated while renin is suppressed. The experts suggest screening prior to commencing antihypertensive therapy as many of these drugs, including beta blockers, calcium channel blockers, ACE inhibitors, ARBs and diuretics usually interfere with this aldosterone to renin ratio. The test isn’t perfect, they admit, as it can be influenced by a number of confounders including salt intake and age, but as a screening tool it has been proven, in trials both in Australia and internationally to be very useful, resulting in significantly increased numbers of patients diagnosed. Current Australian hypertension guidelines recommend clinicians consider primary aldosteronism in patients with hypertension particularly those with moderate to severe or treatment-resistant hypertension. But, as the article authors point out, given the prevalence of primary aldosteronism and the health burden associated with this cardiovascular risk factor both to the Australian population and the economy, maybe it is time to consider screening all newly-diagnosed hypertensive patients for this condition, before the commencement of non-specific antihypertensive therapy. “This diagnostic strategy should lead to significant individual and population health and economic impacts as a result of many patients with hypertension being offered the chance of curative or simpler treatment at an early stage of their disease.” Ref: MJA doi:10.5694/mja17.00783

Healthed

New research from South Australian scientists has shown that vitamin D (also commonly known as the sunshine vitamin) is unlikely to protect individuals from multiple sclerosis, Parkinson's disease, Alzheimer's disease or other brain-related disorders. The findings, released today in the science journal 'Nutritional Neuroscience' reported that researchers had failed to find solid clinical evidence for vitamin D as a protective neurological agent. "Our work counters an emerging belief held in some quarters suggesting that higher levels of vitamin D can impact positively on brain health," says lead author Krystal Iacopetta, PhD candidate at the University of Adelaide. Based on a systematic review of over 70 pre-clinical and clinical studies, Ms Iacopetta investigated the role of vitamin D across a wide range of neurodegenerative diseases. "Past studies had found that patients with a neurodegenerative disease tended to have lower levels of vitamin D compared to healthy members of the population," she says. "This led to the hypothesis that increasing vitamin D levels, either through more UV and sun exposure or by taking vitamin D supplements, could potentially have a positive impact. A widely held community belief is that these supplements could reduce the risk of developing brain-related disorders or limit their progression." "The results of our in-depth review and an analysis of all the scientific literature however, indicates that this is not the case and that there is no convincing evidence supporting vitamin D as a protective agent for the brain," she says. >> Read more   Source: News Medical Net

Dr Esther Myint

A case report A 56-year-old patient presents with a smooth, round, slightly scaly lump on the forehead, 2mm in maximum dimension. The clinical diagnosis was query basal cell carcinoma and it was excised. Microscopic findings were of sebaceoma and following immunohistochemistry staining shows loss of nuclear positivity of the DNA mismatch repair enzymes MSH2 and MSH6, which is usually associated with high-degree microsatellite instability (MSI), and raises the possibility of Muir Torre syndrome associated tumour. The patient underwent investigations, including colonoscopy, and was found to have a fungating lesion in the sigmoid colon. The patient had a left-sided hemicolectomy and the microscopic findings were of a moderately differentiated adenocarcinoma. It also has the same loss of nuclear positivity of the DNA mismatch repair enzymes MSH2 and MSH6, which further raises the possibility of Muir Torre syndrome associated tumour. Discussion Not all skin cancers are straight-forward and some can be associated with internal malignancies or visceral cancers. Skin cancers can be syndromic; they can occur together and characterise a particular abnormality or condition and Muir Torre syndrome (MTS) is a good example. Syndromes are mostly inherited as autosomal dominant traits. MTS is characterised by the development of sebaceous tumours, often multiple, in association with visceral neoplasms, usually gastrointestinal carcinomas. MTS is found as a variant of the autosomal dominant disorder, hereditary non-polyposis colorectal cancer (HNPCC), with tumours demonstrating microsatellite instability (MSI) and germline mutations in the DNA mismatch repair genes MutS homolog MSH2 and MLH1. Muir Torre syndrome This syndrome was first noted by Muir et al in 1967 and Torre in 1968 and is defined by the occurrence of a sebaceous neoplasm and internal malignancy in the absence of other predisposing factors. Cancers of the gastrointestinal and genitourinary tracts are the most common, with colorectal cancers often occurring at or proximal to the splenic flexure, contrary to most sporadic colorectal cancers. The skin lesions which develop in MTS include sebaceous adenoma, sebaceoma and sebaceous carcinoma. Multiple keratoacanthomas (with or without areas of sebaceous differentiation) are seen in some cases and reticulated acanthoma with sebaceous differentiation. Multiple sebaceous tumours and sebaceous tumours occurring before the age of 50 years are strong indicators of the syndrome. The cutaneous tumours may precede or follow the direct manifestation of the visceral cancer and may occur sporadically in family members. The visceral tumours behave less aggressively than would be expected from the histologic findings and this is particularly true for tumours with MSI. Detection of MSI in cutaneous neoplasms may form the basis of a non-invasive screening technique for hereditary non-polyposis colon syndrome (also known as Lynch syndrome), of which the Muir Torre syndrome is regarded as an allelic variant and represents 1-2% of cases with Lynch syndrome. MTS is inherited as an autosomal dominant trait. Mutations in one of the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 have been found in these patients. Recommendations in Muir Torre syndrome - Consider MTS in patients presenting with a sebaceous neoplasm. Immunohistochemistry examination of tumours for MLH1 and MSH2 protein can be used as a screening test to identify patients. -Individuals with or at risk of MTS or HNPCC should have: 1) Colonoscopy every 1-2 years, beginning at age 20–25, or 10 years younger than the youngest age at diagnosis in the family is strongly recommended. 2) Annual history and physical examination, including a complete skin examination and urinalysis, as well as periodic endometrial sampling and/or transvaginal ultrasound for women.
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

New study findings confirm what many parents already believe, introducing solids early helps babies sleep through the night. The UK randomised trial, published in JAMA Pediatrics showed the early introduction of solids into an infant’s diet (from three months of age) was associated with longer sleep duration, less frequent waking at night and a reduction in parents reporting major sleep problems in their child. Researchers analysed data collected as part of the Enquiring About Tolerance study, which included on-going parent-reported assessments on over 1300 infants from England and Wales who were exclusively breastfed to three months of age. At baseline, there were no significant differences in sleeping patterns between those infants who were then introduced to solids early and those who remained exclusively breastfed to six months, as per the World Health Organisation recommendation. However, at six months the difference between was significant. “At age six months,..[those babies who had started solids] were sleeping 17 minutes longer at night, equating to two hours of extra sleep per week, and were waking two fewer times at night per week,” the study authors said. “Most significantly, at this point, [early introduction group] families were reporting half the rate of very serious sleep problems,” they added, saying the results confirm the link between poor infant sleep and parental quality of life. And the findings contradict previous claims that a baby’s poor sleep habits and frequent waking has nothing to do with hunger. The study found that those babies with the highest weight gain between birth and three months (when they were enrolled in the study) were the most likely to be waking at night. “This is consistent with the idea that their rapid weight gain was leading to an enhanced caloric and nutritional requirement, resulting in hunger and disrupted sleep,” they said. Overall, it seems that the study has simply proved what many parents had already suspected. The study authors referred to previous research that showed that, despite WHO and British guidelines recommending babies be exclusively breastfed to six months, three quarters of British mothers introduce solids before five months and 26% report night waking as influencing this decision. Interestingly, recent evidence with regard reducing the risk of allergy and atopy has seen some organisations including our own Australian Society of Clinical Immunology and Allergy, recommending infants be introduced to solids earlier than six months. The authors of this study suggest that parents following these newer guidelines might find they get the added benefit of more sleep. “With recent guidelines advocating introducing solids from age four to six months in some or all infants, our results suggest that improved sleep may be a concomitant benefit,” they concluded. Ref: JAMA Pediatr. doi:10.1001/jamapediatrics.2018.0739

Dr Linda Calabresi

Findings from a newly published study are likely to silence those who suggest doctors need to return to wearing white coats to improve patient respect. According to US researchers, patient perception in terms of a doctor’s capability, trustworthiness and reliability is not affected by the presence of visible tattoos and non-traditional piercings (on the doctor not the patient). “Physician tattoos and facial piercings were not factors in patients’ evaluations of physician competence, professionalism or approachability,” the study authors said. This interesting study, published in the Emergency Medicine Journal involved surveying over 900 patients who had attended the emergency department of a large teaching hospital in the US. The patients were not told the purpose of the survey, they were simply asked to rate their experience, including the care they received from their attending doctor across a range of domains including competence, professionalism, caring, approachability, trustworthiness and reliability. The doctors provided their own controls meaning that some shifts they worked without any ‘exposed body art’, other shifts they were ‘pierced’ (hoop earrings for men or fake nasal studs for women) and other shifts they were ‘tattooed’ (with a temporary standardised black tribal tattoo around the arm). Sometimes the doctors were both pierced and tattooed. Nurses asked the patients to complete the survey and they did provide prompts to remind the patient of the doctor who had attended them, but the prompt was along the line of ‘the young male doctor with red hair’ rather than drawing attention to the tattoo or piercing. More than 75% of the time the patient gave the attending doctor the top rating across all the domains surveyed regardless of appearance. The findings appear to be in contrast with previous research which has found patients prefer their physicians to be traditionally dressed. However, the authors of this study suggest that the evidence to date has been limited by a lack of patient blinding to the study purpose. What’s more, they suggest that existing policies regarding visible body art on doctors are likely to be driven by administrator preferences rather than data on patient satisfaction. There were a number of limitations to the study in particular the small number of doctors involved (seven) and because the patients weren’t specifically asked about the body art we don’t know whether they actually didn’t care about it or whether they were able to overcome their disapproval of it. Given the trial took place in an emergency department, the results cannot necessarily be extrapolated to the community setting as in general practice. Nonetheless, the results will be of interest given the increasing popularity of body art, especially tattoos with the study authors citing research showing, in 2006, 24% of young and middle adult persons had at least one tattoo. Concerns that a doctor’s visible body art has a negative impact on a patient’s perception of their professionalism or a patient’s satisfaction do not appear founded, the researchers concluded. Ref: Doi: 10.1136/emermed-2017-206887

Dr Jo Marchant

Is there real science in the spiritualism of meditation? Jo Marchant meets a Nobel Prize-winner who thinks so. It’s seven in the morning on the beach in Santa Monica, California. The low sun glints off the waves and the clouds are still golden from the dawn. The view stretches out over thousands of miles of Pacific Ocean. In the distance, white villas of wealthy Los Angeles residents dot the Hollywood hills. Here by the shore, curlews and sandpipers cluster on the damp sand. A few metres back from the water’s edge, a handful of people sit cross-legged: members of a local Buddhist centre about to begin an hour-long silent meditation. Such spiritual practices may seem a world away from biomedical research, with its focus on molecular processes and repeatable results. Yet just up the coast, at the University of California, San Francisco (UCSF), a team led by a Nobel Prize-winning biochemist is charging into territory where few mainstream scientists would dare to tread. Whereas Western biomedicine has traditionally shunned the study of personal experiences and emotions in relation to physical health, these scientists are placing state of mind at the centre of their work. They are engaged in serious studies hinting that meditation might – as Eastern traditions have long claimed – slow ageing and lengthen life.

§

Elizabeth Blackburn has always been fascinated by how life works. Born in 1948, she grew up by the sea in a remote town in Tasmania, Australia, collecting ants from her garden and jellyfish from the beach. When she began her scientific career, she moved on to dissecting living systems molecule by molecule. She was drawn to biochemistry, she says, because it offered a thorough and precise understanding “in the form of deep knowledge of the smallest possible subunit of a process”. Working with biologist Joe Gall at Yale in the 1970s, Blackburn sequenced the chromosome tips of a single-celled freshwater creature called Tetrahymena (“pond scum”, as she describes it) and discovered a repeating DNA motif that acts as a protective cap. The caps, dubbed telomeres, were subsequently found on human chromosomes too. They shield the ends of our chromosomes each time our cells divide and the DNA is copied, but they wear down with each division. In the 1980s, working with graduate student Carol Greider at the University of California, Berkeley, Blackburn discovered an enzyme called telomerase that can protect and rebuild telomeres. Even so, our telomeres dwindle over time. And when they get too short, our cells start to malfunction and lose their ability to divide – a phenomenon that is now recognised as a key process in ageing. This work ultimately won Blackburn the 2009 Nobel Prize in Physiology or Medicine. In 2000, she received a visit that changed the course of her research. The caller was Elissa Epel, a postdoc from UCSF’s psychiatry department. Psychiatrists and biochemists don’t usually have much to talk about, but Epel was interested in the damage done to the body by chronic stress, and she had a radical proposal. Epel, now director of the Aging, Metabolism and Emotion Center at UCSF, has a long-standing interest in how the mind and body relate. She cites as influences both the holistic health guru Deepak Chopra and the pioneering biologist Hans Selye, who first described in the 1930s how rats subjected to long-term stress become chronically ill. “Every stress leaves an indelible scar, and the organism pays for its survival after a stressful situation by becoming a little older,” Selye said. Back in 2000, Epel wanted to find that scar. “I was interested in the idea that if we look deep within cells we might be able to measure the wear and tear of stress and daily life,” she says. After reading about Blackburn’s work on ageing, she wondered if telomeres might fit the bill. With some trepidation at approaching such a senior scientist, the then postdoc asked Blackburn for help with a study of mothers going through one of the most stressful situations that she could think of – caring for a chronically ill child. Epel’s plan was to ask the women how stressed they felt, then look for a relationship between their state of mind and the state of their telomeres. Collaborators at the University of Utah would measure telomere length, while Blackburn’s team would measure levels of telomerase. Blackburn’s research until this point had involved elegant, precisely controlled experiments in the lab. Epel’s work, on the other hand, was on real, complicated people living real, complicated lives. “It was another world as far as I was concerned,” says Blackburn. At first, she was doubtful that it would be possible to see any meaningful connection between stress and telomeres. Genes were seen as by far the most important factor determining telomere length, and the idea that it would be possible to measure environmental influences, let alone psychological ones, was highly controversial. But as a mother herself, Blackburn was drawn to the idea of studying the plight of these stressed women. “I just thought, how interesting,” she says. “You can’t help but empathise.” It took four years before they were finally ready to collect blood samples from 58 women. This was to be a small pilot study. To give the highest chance of a meaningful result, the women in the two groups – stressed mothers and controls – had to match as closely as possible, with similar ages, lifestyles and backgrounds. Epel recruited her subjects with meticulous care. Still, Blackburn says, she saw the trial as nothing more than a feasibility exercise. Right up until Epel called her and said, “You won’t believe it.” The results were crystal clear. The more stressed the mothers said they were, the shorter their telomeres and the lower their levels of telomerase. The most frazzled women in the study had telomeres that translated into an extra decade or so of ageing compared to those who were least stressed, while their telomerase levels were halved. “I was thrilled,” says Blackburn. She and Epel had connected real lives and experiences to the molecular mechanics inside cells. It was the first indication that feeling stressed doesn’t just damage our health – it literally ages us.

§

Unexpected discoveries naturally meet scepticism. Blackburn and Epel struggled initially to publish their boundary-crossing paper. “Science [one of the world’s leading scientific journals] couldn’t bounce it back fast enough!” chuckles Blackburn. When the paper finally was published, in the Proceedings of the National Academy of Sciences in December 2004, it sparked widespread press coverage as well as praise. Robert Sapolsky, a pioneering stress researcher at Stanford University and author of the bestselling Why Zebras Don’t Get Ulcers, described the collaboration as “a leap across a vast interdisciplinary canyon”. Mike Irwin, director of the Cousins Center for Psychoneuroimmunology at the University of California, Los Angeles, says it took a lot of courage for Epel to seek out Blackburn. “And a lot of courage for Liz [Blackburn] to say yes.” Many telomere researchers were wary at first. They pointed out that the study was small, and questioned the accuracy of the telomere length test used. “This was a risky idea back then, and in some people’s eyes unlikely,” explains Epel. “Everyone is born with very different telomere lengths and to think that we can measure something psychological or behavioural, not genetic, and have that predict the length of our telomeres? This is really not where this field was ten years ago.” The paper triggered an explosion of research. Researchers have since linked perceived stress to shorter telomeres in healthy women as well as in Alzheimer’s caregivers, victims of domestic abuse and early life trauma, and people with major depression and post-traumatic stress disorder. “Ten years on, there’s no question in my mind that the environment has some consequence on telomere length,” says Mary Armanios, a clinician and geneticist at Johns Hopkins School of Medicine who studies telomere disorders. There is also progress towards a mechanism. Lab studies show that the stress hormone cortisol reduces the activity of telomerase, while oxidative stress and inflammation – the physiological fallout of psychological stress – appear to erode telomeres directly. This seems to have devastating consequences for our health. Age-related conditions from osteoarthritis, diabetes and obesity to heart disease, Alzheimer’s and stroke have all been linked to short telomeres. The big question for researchers now is whether telomeres are simply a harmless marker of age-related damage (like grey hair, say) or themselves play a role in causing the health problems that plague us as we age. People with genetic mutations affecting the enzyme telomerase, who have much shorter telomeres than normal, suffer from accelerated-ageing syndromes and their organs progressively fail. But Armanios questions whether the smaller reductions in telomere length caused by stress are relevant for health, especially as telomere lengths are so variable in the first place. Blackburn, however, says she is increasingly convinced that the effects of stress do matter. Although the genetic mutations affecting the maintenance of telomeres have a smaller effect than the extreme syndromes Armanios studies, Blackburn points out that they do increase the risk of chronic disease later in life. And several studies have shown that our telomeres predict future health. One showed that elderly men whose telomeres shortened over two-and-a-half years were three times as likely to die from cardiovascular disease in the subsequent nine years as those whose telomeres stayed the same length or got longer. In another study, looking at over 2,000 healthy Native Americans, those with the shortest telomeres were more than twice as likely to develop diabetes over the next five-and-a-half years, even taking into account conventional risk factors such as body mass index and fasting glucose. Blackburn is now moving into even bigger studies, including a collaboration with healthcare giant Kaiser Permanente of Northern California that has involved measuring the telomeres of 100,000 people. The hope is that combining telomere length with data from the volunteers’ genomes and electronic medical records will reveal additional links between telomere length and disease, as well as more genetic mutations that affect telomere length. The results aren’t published yet, but Blackburn is excited about what the data already shows about longevity. She traces the curve with her finger: as the population ages, average telomere length goes down. This much we know; telomeres tend to shorten over time. But at age 75–80, the curve swings back up as people with shorter telomeres die off – proof that those with longer telomeres really do live longer. “It’s lovely,” she says. “No one has ever seen that.” In the decade since Blackburn and Epel’s original study, the idea that stress ages us by eroding our telomeres has also permeated popular culture. In addition to Blackburn’s many scientific accolades, she was named one of Time magazine’s “100 most influential people in the world” in 2007, and received a Good Housekeeping achievement award in 2011. A workaholic character played by Cameron Diaz even described the concept in the 2006 Hollywood film The Holiday. “It resonates,” says Blackburn. But as evidence of the damage caused by dwindling telomeres piles up, she is embarking on a new question: how to protect them.

§

At first, the beach seems busy. Waves splash and splash and splash. Sanderlings wheel along the shoreline. Joggers and dog walkers amble across, while groups of pelicans hang out on the water before taking wing or floating out of sight. A surfer, silhouetted black against the sky, bobs about for 20 minutes or so, catching the odd ripple towards shore before he, too, is gone. The unchanging perspective gives a curious sense of detachment. You can imagine that the birds and joggers and surfers are like thoughts: they inhabit different forms and timescales but in the end, they all pass. There are hundreds of ways to meditate but this morning I’m trying a form of Buddhist mindfulness meditation called open monitoring, which involves paying attention to your experience in the present moment. Sit upright and still, and simply notice any thoughts that arise – without judging or reacting to them – before letting them go. For Buddhists this is a spiritual quest; by letting trivial thoughts and external influences fall away, they hope to get closer to the true nature of reality. Blackburn too is interested in the nature of reality, but after a career spent focusing on the measurable and quantifiable, such navel-gazing initially held little personal appeal and certainly no professional interest. “Ten years ago, if you’d told me that I would be seriously thinking about meditation, I would have said one of us is loco,” she told the New York Times in 2007. Yet that is where her work on telomeres has brought her. Since her initial study with Epel, the pair have become involved in collaborations with teams around the world – as many as 50 or 60, Blackburn estimates, spinning in “wonderful directions”. Many of these focus on ways to protect telomeres from the effects of stress; trials suggest that exercise, eating healthily and social support all help. But one of the most effective interventions, apparently capable of slowing the erosion of telomeres – and perhaps even lengthening them again – is meditation. So far the studies are small, but they all tentatively point in the same direction. In one ambitious project, Blackburn and her colleagues sent participants to meditate at the Shambhala mountain retreat in northern Colorado. Those who completed a three-month course had 30 per cent higher levels of telomerase than a similar group on a waiting list. A pilot study of dementia caregivers, carried out with UCLA’s Irwin and published in 2013, found that volunteers who did an ancient chanting meditation called Kirtan Kriya, 12 minutes a day for eight weeks, had significantly higher telomerase activity than a control group who listened to relaxing music. And a collaboration with UCSF physician and self-help guru Dean Ornish, also published in 2013, found that men with low-risk prostate cancer who undertook comprehensive lifestyle changes, including meditation, kept their telomerase activity higher than similar men in a control group and had slightly longer telomeres after five years. In their latest study, Epel and Blackburn are following 180 mothers, half of whom have a child with autism. The trial involves measuring the women’s stress levels and telomere length over two years, then testing the effects of a short course of mindfulness training, delivered with the help of a mobile app. Theories differ as to how meditation might boost telomeres and telomerase, but most likely it reduces stress. The practice involves slow, regular breathing, which may relax us physically by calming the fight-or-flight response. It probably has a psychological stress-busting effect too. Being able to step back from negative or stressful thoughts may allow us to realise that these are not necessarily accurate reflections of reality but passing, ephemeral events. It also helps us to appreciate the present instead of continually worrying about the past or planning for the future. “Being present in your activities and in your interactions is precious, and it’s rare these days with all of the multitasking we do,” says Epel. “I do think that in general we’ve got a society with scattered attention, particularly when people are highly stressed and don’t have the resources to just be present wherever they are.”

§

Inevitably, when a Nobel Prize-winner starts talking about meditation, it ruffles a few feathers. In general, Blackburn’s methodical approach to the topic has earned a grudging admiration, even among those who have expressed concern about the health claims made for alternative medicine. “She goes about her business in a cautious and systematic fashion,” says Edzard Ernst of the University of Exeter, UK, who specialises in testing complementary therapies in rigorous controlled trials. Oncologist James Coyne of the University of Pennsylvania, Philadelphia, who is sceptical of this field in general and describes some of the research on positive psychology and health as “morally offensive” and “tooth fairy science”, concedes that some of Blackburn’s data is “promising”. Others aren’t so impressed. Surgeon-oncologist David Gorski is a well-known critic of alternative medicine and pseudoscience who blogs under the name of Orac – he’s previously described Dean Ornish as “one of the four horsemen of the Woo-pocalypse”. Gorski stops short of pronouncing meditation as off-limits for scientific inquiry, but expresses concern that the preliminary results of these studies are being oversold. How can the researchers be sure they’re investigating it rigorously? “It’s really hard to do with these things,” he says. “It is easy to be led astray. Nobel Prize-winners are not infallible.” Blackburn’s own biochemistry community also seems ambivalent about her interest in meditation. Three senior telomere researchers I contacted declined to discuss this aspect of her work, with one explaining that he didn’t want to comment “on such a controversial issue”. “People are very uncomfortable with the concept of meditation,” notes Blackburn. She attributes this to its unfamiliarity and its association with spiritual and religious practices. “We’re always trying to say it as carefully as we can… always saying ‘look, it’s preliminary, it’s a pilot’. But people won’t even read those words. They’ll see the newspaper headings and panic.” Any connotation of religious or paranormal beliefs makes many scientists uneasy, says Chris French, a psychologist at Goldsmiths, University of London, who studies anomalous experiences including altered states of consciousness. “There are a lot of raised eyebrows, even though I’ve got the word sceptic virtually tattooed across my forehead,” he says. “It smacks of new-age woolly ideas for some people. There’s a kneejerk dismissive response of ‘we all know it’s nonsense, why are you wasting your time?’” "When meditation first came to the West in the 1960s it was tied to the drug culture, the hippie culture,” adds Sara Lazar, a neuroscientist at Harvard who studies how meditation changes the structure of the brain. “People think it’s just a bunch of crystals or something, they roll their eyes.” She describes her own decision to study meditation, made 15 years ago, as “brave or crazy”, and says that she only plucked up the courage because at around the same time, the US National Institutes of Health (NIH) created the National Center for Complementary and Alternative Medicine. “That gave me the confidence that I could do this and I would get funding.” The tide is now turning. Helped in part by that NIH money, researchers have developed secularised – or non-religious – practices such as mindfulness-based stress reduction and mindfulness-based cognitive therapy, and reported a range of health effects from lowering blood pressure and boosting immune responses to warding off depression. And the past few years have seen a spurt of neuroscience studies, like Lazar’s, showing that even short courses of meditation can forge structural changes in the brain. “Now that the brain data and all this clinical data are coming out, that is starting to change. People are a lot more accepting [of meditation],” says Lazar. “But there are still some people who will never believe that it has any benefit whatsoever." Blackburn’s view is that meditation is a fair topic to study, as long as robust methods are used. So when her research first pointed in this direction, she was undaunted by concerns about what such studies might do to her reputation. Instead, she tried it out for herself, on an intensive six-day retreat in Santa Barbara. “I loved it,” she says. She still uses short bursts of meditation, which she says sharpen her mind and help her to avoid a busy, distracted mode. She even began one recent paper with a quote from the Buddha: “The secret of health for both mind and body is not to mourn for the past, worry about the future, or anticipate troubles but to live in the present moment wisely and earnestly.” That study, of 239 healthy women, found that those whose minds wandered less – the main aim of mindfulness meditation – had significantly longer telomeres than those whose thoughts ran amok. “Although we report merely an association here, it is possible that greater presence of mind promotes a healthy biochemical milieu and, in turn, cell longevity,” the researchers concluded. Contemplative traditions from Buddhism to Taoism believe that presence of mind promotes health and longevity; Blackburn and her colleagues now suggest that the ancient wisdom might be right.

§

I meet with Blackburn in Paris. We’re at an Art Nouveau-themed bistro just down the road from the Curie Institute, where she is on a short sabbatical, arranging seminars between groups of scientists who don’t usually talk to one another. In a low, melodious voice that I strain to hear through the background clatter, the 65-year-old tells me of her first major brush with Buddhist thinking. In September 2006, she attended a conference held at the Menla Mountain Buddhist centre, a remote retreat in New York’s Catskill mountains, at which Western scientists met with Tibetan-trained scholars including the Dalai Lama to discuss longevity, regeneration and health. During the meeting, the spiritual leader honoured Blackburn’s scientific achievements by inducting her as a “Medicine Buddha”. If Epel’s psychiatry research had been another world, the scholars’ Eastern philosophy seemed to Blackburn more alien still. Over dinner one evening, while explaining to the other delegates how errors in the gene for telomerase can cause health problems, she described genetic mutation as a random, chance event. That’s dogma for Western scientists but not for those trained in the Tibetan worldview. “They said ‘oh no, we don’t regard this as chance’,” says Blackburn. For these holistic scholars, even the smallest events were infused with meaning. “I suddenly thought, whoa, this is a very different world from the one I’m on.” But instead of dismissing her Eastern counterparts, she was impressed, finding the Dalai Lama to have “a very good brain”, for example. “They’re scholarly in a very different way, but it is still good-quality thinking,” she explains. “It wasn’t ‘God told me this’, it was more ‘let’s see what actually happens in the brain’. So there are certain elements of the approach that I am quite comfortable with as a scientist.” Blackburn isn’t tempted to embrace the spiritual approach herself. “I’m rooted in the physical world,” she says. But she combines that grounding with an open mind towards new ideas and connections, and she seems to love breaking out of established paradigms. For example, she and Epel have shown that the effects of stress on telomeres can be passed on to the next generation. If women experience stress while pregnant, their children have shorter telomeres, as newborns and as adults – in direct contradiction of the standard view that traits can only be passed on via our genes. In the future, information from telomeres may help doctors decide when to prescribe particular drugs. For example, telomerase activity predicts who will respond to treatment for major depression, while telomere length influences the effects of statins. In general, however, Blackburn is more interested in how telomeres might help people directly, by encouraging them to live in a way that reduces their disease risk. “This is not a familiar model for the medical world,” she says. Conventional medical tests give us our risk of particular conditions – high cholesterol warns of impending heart disease, for example, while high blood sugar predicts diabetes. Telomere length, by contrast, gives an overall reading of how healthy we are: our biological age. And although we already know that we should exercise, eat well and reduce stress, many of us fall short of these goals. Blackburn believes that putting a concrete number on how we are doing could provide a powerful incentive to change our behaviour. In fact, she and Epel have just completed a study (as yet unpublished) showing that simply being told their telomere length caused volunteers to live more healthily over the next year than a similar group who weren’t told. Ultimately, however, the pair want entire countries and governments to start paying attention to telomeres. A growing body of work now shows that the stress from social adversity and inequality is a major force eroding these protective caps. People who didn’t finish high school or are in an abusive relationship have shorter telomeres, for example, while studies have also shown links with low socioeconomic status, shift work, lousy neighbourhoods and environmental pollution. Children are particularly at risk: being abused or experiencing adversity early in life leaves people with shorter telomeres for the rest of their lives. And through telomeres, the stress that women experience during pregnancy affects the health of the next generation too, causing hardship and economic costs for decades to come. In 2012, Blackburn and Epel wrote a commentary in the journal Nature, listing some of these results and calling on politicians to prioritise “societal stress reduction”. In particular, they argued, improving the education and health of women of child-bearing age could be “a highly effective way to prevent poor health filtering down through generations”. Meditation retreats or yoga classes might help those who can afford the time and expense, they pointed out. “But we are talking about broad socioeconomic policies to buffer the chronic stressors faced by so many.” Where many scientists refrain from discussing the political implications of their work, Blackburn says she wanted to speak out on behalf of women who lack support, and say “You’d better take their situations seriously.” While arguments for tackling social inequality are hardly new, Blackburn says that telomeres allow us to quantify for the first time the health impact of stress and inequality and therefore the resulting economic costs. We can also now pinpoint pregnancy and early childhood as “imprinting periods” when telomere length is particularly susceptible to stress. Together, she says, this evidence makes a stronger case than ever before for governments to act. But it seems that most scientists and politicians still aren’t ready to leap across the interdisciplinary canyon that Blackburn and Epel bridged a decade ago. The Nature article has engendered little response, according to a frustrated Epel. “It’s a strong statement so I would have thought that people would have criticised it or supported it,” she says. “Either way!” “It’s now a consistent story that the ageing machinery is shaped at the earliest stages of life,” she insists. “If we ignore that and we just keep trying to put band-aids on later, we’re never going to get at prevention and we’re only going to fail at cure.” Simply responding to the physical symptoms of disease might make sense for treating an acute infection or fixing a broken leg, but to beat chronic age-related conditions such as diabetes, heart disease and dementia, we will need to embrace the fuzzy, subjective domain of the mind. This article first appeared on Mosaic and is republished here under a Creative Commons licence.

Dr Joyce Wu

Glycated haemoglobin (HbA1c) has been used for monitoring patients with established diabetes for many years but its diagnostic application is a more recent development. This article provides some background to the test, explains dual reporting of results and discusses the use of HbA1c in the diagnosis and monitoring of diabetes.

What is HbA1c?

Adult haemoglobin is predominantly (97% of total) HbA. HbA1c is formed when a glucose molecule non-enzymatically attaches to the N-terminal valine of the β-chain of HbA. The amount of HbA1c formed is directly proportional to the average plasma glucose concentration during the 120-day life span of the erythrocyte, with recent plasma glucose contributing more than earlier concentrations. HbA1c is therefore a reflection of the average glycaemia over roughly the preceding 6–8 weeks and has a vital role in assessing the risk of an individual developing the complications of diabetes.1

HbA1c for the diagnosis of diabetes mellitus

A 2012 position statement of the Australian Diabetes Society, the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB)2 contains the following:
  • HbA1c levels ≥6.5% (≥48 mmol/mol) are acceptable for diagnosing diabetes so long as the test is done in a laboratory and no conditions exist which preclude its accuracy.
  • In an asymptomatic patient with a positive result, the test should be repeated to confirm the diagnosis.
  • The existing criteria based on fasting and random glucose levels and on the oral glucose tolerance test remain valid and are the diagnostic tests of choice for gestational diabetes, type 1 diabetes and in the presence of conditions that interfere with HbA1c measurement.
The use of HbA1c simplifies the diagnostic process and may facilitate the detection of diabetes diagnosis. The test can be performed at any time of the day, does not require special pre-test preparation, such as a diet or fasting, and is stable when collected in the appropriate specimen tube. Testing should be restricted to patients at high risk of undiagnosed diabetes and who are asymptomatic.3 If one or more symptoms suggestive of diabetes are present in a low-risk patient, blood glucose tests should be used, because patients with rapidly evolving diabetes can have normal HbA1c. HbA1c <6.5% (<48mmol/mol) indicates that diabetes is unlikely but (since the patient is high-risk) the test should be repeated in 12 months. Patients should be given appropriate lifestyle advice and other modifiable cardiovascular risk factors should be assessed.3 There is uncertainty about the use of HbA1c to diagnose prediabetes. While patients with HbA1c above normal but below 6.5% (48 mmol/mol) are more likely to develop diabetes than is suggested by their AUSDRISK score alone, they have minimal risk of developing microvascular complications. Management is the same as for those at high risk of type 2 diabetes with HbA1c within the normal range.3 HbA1c ≥6.5% (≥48 mmol/mol) should be confirmed by another test (glucose or repeat HbA1c). Repeat HbA1c should be performed on a different day but as soon as possible, before any lifestyle or pharmacological interventions are initiated.3 It is important that clinicians state clearly the indication for the test when requesting HbA1c testing, with wording such as ‘diabetes monitoring’ or ‘diabetes screening’. This will allow the correct Medicare item number and interpretative comments to be used.

Individualisation of HbA1c treatment targets

In monitoring patients with established diabetes, the general target is ≤7.0% (≤53 mmol/mol). Individualisation of target HbA1c, taking into account patient-specific factors, such as type of diabetes and its duration, pregnancy, diabetes medication used, existing cardiovascular disease, risk of hypoglycaemia and comorbidities, may modify the target range from ≤6.0% (≤42 mmol/mol) to ≤8.0%(≤64 mmol/mol).4

Dual reporting of HbA1c

There are many assays for measuring HbA1c. For many years, the NGSP in the US and other national and regional programs harmonised HbA1c methods. This allowed valid, interlaboratory comparison of results. The NGSP uses percentage (%) units. The IFCC standardised glycated haemoglobin measurement by making it traceable to an international standard.5 The IFCC uses mmol/mol (mmol HbA1c per mol total Hb). The improved specificity of IFCC-HbA1c is reflected in results which are consistently 1.5%–2.0% lower than NGSP values.1 A 2007 consensus statement from the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), IFCC and International Diabetes Federation (IDF) was adopted and implemented by Australasian laboratories.5 It recommended that HbA1c results be reported in both IFCC units (mmol/mol) and derived NGSP units (%) to allow clinicians to become familiar with IFCC results before reporting of NGSP % units is withdrawn. Currently, there is no agreement on when dual reporting will cease and hence HbA1c results are still reported with two units.

Conditions affecting HbA1c results

As HbA1c is simply haemoglobin with the addition of a glucose molecule, conditions that affect red blood cells or their survival time, such as haemoglobinopathies or anaemia, will affect the HbA1c result.3 Patients with abnormal haemoglobins may form other glycated products which may form at different rates to that of normal haemoglobin. Haemolytic anaemia can reduce HbA1c by decreasing red cell survival, leading to reduction in the availability of haemoglobin for glycation. This occurs with autoimmune haemolytic anaemia, haemoglobinopathies and chronic renal failure. Any drugs that give rise to haemolytic anaemia will have the same effect. Red cell survival time is also reduced in severe liver disease, anaemia of chronic disease, vitamin B12 and folic acid deficiencies, and regular phlebotomy. Interestingly, iron deficiency anaemia can increase HbA1c by up to 2%.1 There are alternative ways of monitoring diabetes treatment in these patients, including the use of closer glucose monitoring and fructosamine testing. Any discordance between glucose and HbA1c levels should alert the clinician so that other testing options should be considered.

Key points

When requesting HbA1c it is vital that the clinician specify clearly the indication for the test, for example, ‘diabetes monitoring’ or ‘diabetes screening’.
  • HbA1c ≥6.5% (≥48 mmol/mol) can be used to diagnose diabetes in asymptomatic, high-risk patients. HbA1c ≥6.5% should be confirmed with glucose or another HbA1c performed on a different day but as soon as possible, before any intervention has commenced.
  • The recommended treatment target is HbA1c ≤7.0% (≤53 mmol/mol). Treatment targets may need to be individualised to between ≤6.0% (≤42 mmol/mol) to ≤8.0% (≤64 mmol/ mol), depending on patient-specific factors, such as type and duration of diabetes and risk of hypoglycaemia.
  • Currently, HbA1c is reported in both National Glycohemoglobin Standardization Program (NGSP) units (%) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) units (mmol/mol), with the aim of eventually reporting in IFCC units only.
  • A number of medical conditions affect HbA1c results and preclude its use in both monitoring and diagnosis of diabetes mellitus.

References

  1. Kilpatrick ES. Haemoglobin A1c in the diagnosis and monitoring of diabetes mellitus. J Clin Pathol 2008;61(9):977-982
  2. d’Emdem MC. et al. The role of HbA1c in the diagnosis of diabetes mellitus in Australia. MJA 2012;197(4):1-3
  3. d’Emdem MC. et al. Guidance concerning the use of glycated haemoglobin (HbA1c) for the diagnosis of diabetes mellitus – A position statement of the Australian Diabetes Society. MJA 2015;203(2):89-91
  4. Cheung NW. et al. Position statement of the Australian Diabetes Society: individualisation of glycated haemoglobin targets for adults with diabetes mellitus. MJA 2009;191(6):339-344
  5. Jones G. et al. Consensus Statement on the Worldwide Standardisation of the Haemoglobin A1c Measurement – An Australasian Update. The Clinical Biochemist Newsletter 2008;14-18. Available online: https://www.aacb.asn.au/documents/item/1213

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.