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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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Dr Linda Calabresi
  • Clinical Articles

All benzos risky in pregnancy

Benzos increase the risk of having a miscarriage in early pregnancy, regardless of whether you’re taking a short-acting one for insomnia or a longer-acting one for anxiety, Canadian researchers say. According to their large case-controlled study involving almost 450,000 pregnancies, benzodiazepine exposure in early pregnancy was associated with an 85% higher risk of spontaneous abortion compared to pregnancies where that class of drugs were not taken. And this increased risk remained the same, after a whole range of possible confounders had been adjusted for, including maternal mood and anxiety disorders. But this isn’t the new bit. Previous research, including both a UK population-based study and an Israeli prospective study had confirmed the link between benzos and spontaneous abortion. In Australia, benzodiazepines have been given a Category C rating in terms of safety in pregnancy. (Drugs owing to their pharmacological effects have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations.) “Benzodiazepines cross the placental barrier and accumulate in the fetal circulation at levels that are one to three times higher than the maternal serum levels”, the researchers explained. What hasn’t been known, to date, is whether this is a class effect or are some benzos worse than others. Well – according to this study published in JAMA Psychiatry – ‘the risk was similar among pregnancies exposed to short-acting …and long-acting benzodiazepines during early pregnancy.’ So it didn’t matter if you were prescribed long-acting clonazepam or short-acting lorazepam (interestingly the two most frequently prescribed benzos), the risk was more or less the same. “All benzodiazepine agents were independently associated with an increased risk of [spontaneous abortion],” the study authors said. In addition the study found the risk increased as the daily dose of benzodiazepines increased, suggesting a dose-response effect. So basically the more doses of benzos a pregnant woman takes, either in terms of strength or duration, the greater the risk she will miscarry. Overall, the researchers concluded that pregnant women should avoid taking benzodiazepines, and if they have to take them only take the lowest dose possible for shortest duration possible. “Alternative nonpharmacologic treatments exist and are recommended, but if benzodiazepines are needed, they should be prescribed for short durations,” they concluded.  

Reference

Sheehy O, Zhao JP, Bérard A. Association Between Incident Exposure to Benzodiazepines in Early Pregnancy and Risk of Spontaneous Abortion. JAMA Psychiatry. 2019 May 15. DOI: 10.1001/jamapsychiatry.2019.0963 [Epub ahead of print]  
By Dr Linda Calabresi
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Dr Patty Thille
  • Clinical Articles

How anti-fat bias in health care endangers lives

When Ellen Maud Bennett died a year ago, her obituary published in the local newspaper gained national media attention in Canada, though she wasn’t a celebrity. Bennett’s obituary revealed she died from cancer days after finally being diagnosed — after years of seeking help. Her diagnosis came so late, beyond the point where treatments were possible, because the 64-year-old woman was repeatedly told her health problems were caused by her weight — or more specifically, by the amount of fat on her body. She died because of bad assumptions that caused poor quality care. And she used her own obituary to share her dying wish:
“Ellen’s dying wish was that women of size make her death matter by advocating strongly for their health and not accepting that fat is the only relevant health issue.”
How to know if this might be happening to you? When do you need to advocate for yourself? I studied the phenomenon of anti-fat stigma in Canadian primary care clinics for my PhD. Knowing how it happens might help.

Fatness as a sign of inferiority

Bodily fatness is a stigmatized body characteristic in Canada and other wealthy countries. Within any given culture, some characteristics or histories are assumed to reflect a character flaw. The characteristic is treated as a sign of inferiority. The result is loss of social status and widespread societal discrimination. With bodily fatness, the assumed character flaws are laziness, ignorance or weak willpower. In a comprehensive review published 10 years ago, there was strong evidence of fatness-related discrimination in employment, while other sectors were less researched. Studies carried out since that time confirm the pattern — including within health care.

‘Just eat more salads’

Poor quality clinical care due to anti-fat stigma occurs when doctors or nurses assume the stereotype holds true. One common way this happens: a clinician simply tells you to “lose weight,” as Bennett heard many times when seeking help. That’s like telling patients to “lose blood sugar.” Telling people to produce an outcome is not good quality clinical care. This is especially awful when weight is not related to the topic at hand — an ear infection, for example. Sometimes, clinicians do this as “opportunistic counselling.” It’s done assuming the benefits outweigh harms — except we know that doing this for weight reduces trust in health-care providers. And reduced trust can lead to avoidance, for obvious reasons — needs aren’t met. Unfortunately, some clinicians give very simplistic weight loss advice, such as “eat more salads,” without any assessment of what the patient already knows, does, has tried or can afford and fit into their lives. Simplistic advice is patronizing at best; it assumes patients are ignorant, as per the stereotype. This approach vastly underestimates the knowledge of a patient, gained in part through repeated past attempts to change body composition. One Canadian study found that half of those classified as overweight, and 71 per cent of those categorized as obese, had attempted to reduce their body weight in the last year. Simplistic messages — “lose weight” or “exercise more” — assume thinness is easy and simply involves some lifestyle tweaks. When such advice is given without assessment of health concerns — for instance, headaches — anti-fat biases can endanger lives.

Bias trumps science, sometimes

Clinicians should, at minimum, recommend actions that have a chance at producing an outcome. Lifestyle changes only produce modest effects for most, yet many clinicians assume much bigger impacts. Obesity Canada, an organization that uses evidence-based action to better prevent and manage obesity, reminds health-care providers that the typical body weight reduction from sustained lifestyle changes is five per cent of body weight. Dramatic life changes, such as those of participants on the TV show The Biggest Loser, can slow the body’s resting metabolic rate, triggering weight regain. Science also tells us that factors beyond lifestyle are influencing population shifts around body weight and fatness. But these scientific findings are still not routinely integrated into health-care professionals’ understandings of weight. As a result, many still emphasize poor willpower as the core problem. You shouldn’t have to advocate for yourself to get adequate health care. You should be able to trust your health-care professionals.

How to advocate for yourself

There are many people working to ensure access to good quality health care. But tackling discrimination is complex. You can help. When clinicians make one of these common mistakes or in some other way block you being diagnosed or treated, you are on good grounds to challenge them. Say something like: “What would you do if someone with a thin body had this problem?” Then encourage them to treat you in the same way. Send them this or other articles. Write your story and give it to them. Find a Health-At-Every-Size® practitioner, and check for local resources (such as the Good Fat Care website in Winnipeg). After receiving poor quality care, register a complaint with the provider’s professional licensing body. They may not investigate your individual complaint but do track trends. Patient advocates are also available in some hospitals to help you get the care you need. News stories come and go. But the issues Ellen Maud Bennett raised in her obituary should not disappear from our consciousness so quickly. You deserve good care, just as she did. This article is written in memory of Ellen Maud Bennett, with the permission of her sister.The Conversation Patty Thille, Assistant Professor in Physical Therapy, University of Manitoba This article is republished from The Conversation under a Creative Commons license. Read the original article.
By Dr Patty Thille
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Dr Linda Calabresi
  • Clinical Articles

Surprise benefit of glucosamine

Glucosamine’s effectiveness in treating arthritis remains controversial, however a study suggesting that the supplement, when taken regularly, will help prevent heart attacks certainly adds to its appeal. According to findings from a large prospective study just published in The BMJ, habitual glucosamine use is associated with a 15% lower risk of cardiovascular events. Breaking that down a bit further, it appears regular glucosamine lowered the risk of dying from a cardiovascular event by 22%, lowered the risk of coronary heart disease by 18% and lowered the risk of stroke by 9%. All statistically significant results. The research involved over 440,000 people from the UK biobank who didn’t have cardiovascular disease at the outset. Courtesy of an initial questionnaire, researchers knew who was taking glucosamine and how often. Interestingly about 20% of the cohort, reported they took the non-vitamin, non-mineral supplement daily – a figure the researchers said was representative in other adult populations around the world – including Australia. The cohort was then followed for a median of seven years. Over this time there were over 10,000 CVD events including heart attacks and strokes, with over 3,000 of these resulting in death. Even though the study was basically observational, the size of the sample strengthens its value. As does the fact that the researchers obtained a wealth of information about the patient’s diet, medical history and lifestyle at the initial questionnaire, which was all utilised in the final analysis. Consequently the 15% lower risk of a cardiovascular event associated with taking glucosamine can’t be easily written off as caused by another confounder. The researchers were able to conclude the association was “independent of traditional risk factors, including sex, age, income, body mass index, physical activity, healthy diet, alcohol intake, smoking status, diabetes, hypertension, high cholesterol, arthritis, drug use, and other supplement use.” So how does it work? How does glucosamine positively affect the cardiovascular system? According to the study authors, there are a number of plausible mechanisms that could explain the link. One relates to the anti-inflammatory properties of glucosamine. There already exists evidence that regular glucosamine reduces CRP levels, a marker of systemic inflammation. Another theory relates to how glucosamine affects metabolism. “[A] previous study found that glucosamine could mimic a low carbohydrate diet by decreasing glycolysis and increasing amino acid catabolism in mice; therefore, glucosamine has been treated as an energy restriction mimetic agent,” they said. But while the study findings appear very exciting, the study authors themselves suggest caution, claiming their study had some limitations. Among these limitations was the fact that details about the dose, duration of use, type of glucosamine supplement was not recorded. Obviously further research is needed to test this association. Nonetheless, the trial is destined to fuel on-going interest in the supplement, albeit for a totally different condition from the one we’re used to.  

References:

Ma H, Li X, Sun D, Zhou T, Ley SH, Gustat J, et al. Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank. BMJ. 2019 May 14; 365: l1628. DOI: 10.1136/bmj.l1628
By Dr Linda Calabresi
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Dr Linda Calabresi
  • Clinical Articles

Pancreatic cancer support

It’s still probably one of medicine’s most devastating diagnoses – pancreatic cancer. Despite all the scientific advances that have been made in treating so many malignancies, the prognosis for pancreatic cancer is most often pretty bleak. Consequently, patients presented with this diagnosis are most likely to be in need of significant support. PanSupport (pansupport.org.au) is a newly-developed site, produced by the University of Melbourne that is likely to prove incredibly valuable to patients battling this condition, and their families. This resource not only provides valuable information about pancreatic cancer and its treatment, but it also gives practical advice with regard aspects of management such as diet and exercise. Importantly it also directs patients to any potential clinical trials for which they may be eligible. In keeping with the very practical and realistic approach of the entire site, Pansupport also includes information about palliative care and Advanced Care directives, allowing patients to access what they need to know in their own time frame. The PanSupport website has been developed in collaboration with the Pancare Foundation, RMIT University and the Peter MacCallum Cancer Centre. It has been funded with a Cancer Grant Initiative funded by the Australian Government. >> Find out more about PanSuport here 

By Dr Linda Calabresi
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Dr Edmond Chan
  • Clinical Articles

Peanut Allergies: Research Shows ‘Oral Immunotherapy’ is Safe for Preschoolers

  “We don’t have to live in fear anymore.” That’s the common refrain from hundreds of parents of preschoolers with peanut allergy that my colleagues and I have successfully treated with peanut “oral immunotherapy” over the past two years. Oral immunotherapy (OIT) is a treatment in which a patient consumes small amounts of an allergenic food, such as peanut, with the dose gradually increased to a target maximum (or maintenance) amount. The goal for most parents is to achieve desensitization — so their child can ingest more of the food without triggering a dangerous reaction, protecting them against accidental exposure. A recent study published in The Lancet has suggested that this treatment may make things worse for children with peanut allergies. The researchers behind the meta-analysis argue that children with peanut allergies should avoid peanuts. This study has limitations however. It did not include a single child under the age of five years old. And it runs the risk of confusing parents. My colleagues and I have seen firsthand that oral immunotherapy is not only safe, but is well tolerated in a large group of preschool children. We published data demonstrating this recently in the Journal of Allergy and Clinical Immunology: In Practice.  

Safe for preschoolers

For any parent of a child with severe allergy, the idea of giving them even a small amount of the allergenic food might give them pause. I don’t blame them — giving a child a known allergen is a daunting thought. Some allergists share this fear and do not offer OIT to patients in their clinics due to safety concerns. To assess the safety of oral immunotherapy, we followed 270 children across Canada between the ages of nine months and five years who were diagnosed with peanut allergy by an allergist. The children were fed a peanut dose, in a hospital or clinic, that gradually increased at every visit. Parents also gave children the same daily dose at home, between clinic visits, until they reached the maintenance dose. We found that 243 children (90 per cent) reached the maintenance stage successfully. Only 0.4 per cent of children experienced a severe allergic reaction. Out of over 40,000 peanut doses, only 12 went on to receive epinephrine (0.03 per cent). Our research provides the first real-world data that OIT is safe for preschool-aged children with peanut allergy when offered as routine treatment in a hospital or clinic, rather than within a clinical trial.  

The Lancet study was of older children

So why does the meta-analysis published in The Lancet show that peanut OIT increases allergic reactions, compared with avoidance or placebo? The researchers behind this study argue that avoidance of peanut is best for children with peanut allergy. They describe that in older children, the risk of anaphylaxis is 22.2 per cent and the risk of serious adverse events is 11.9 per cent. It is important for parents to note that The Lancet study only assessed children aged five and older participating in clinical trials (average age nine years old), and the researchers don’t even mention this as a limitation of their analysis. Our study, on the other hand, assessed preschool children (average age just under two years old) in the real world outside of research. While I agree that there are certainly more safety concerns in older children, and more research is needed to see which of them would most benefit, our results demonstrate with real-world data that, in preschoolers, OIT is a game-changer.  

For many patients, benefits outweigh risks

It isn’t rocket science that avoiding what one is allergic to will be safer than eating it. An analogy is knee replacement surgery. Of course, not having knee replacement surgery would be “safer” than having the surgery. But not having knee replacement surgery doesn’t provide any potential of benefits and also provides little hope for families. Likewise, telling parents of children with peanut allergy that avoidance is the only option outside research fails to take into account the negative long-term consequences of avoidance — such as poor quality of life, social isolation and anxiety. Allergists and the medical community as a whole must stop confusing parents with endless mixed messages about OIT both within and outside of research. The fact is, many allergists are already offering OIT outside of research. In our current era of basing medical treatment decisions on a comparison of risks versus benefits, there is simply no one-size-fits-all approach. Rather than concluding that all children with peanut allergy should be managed with avoidance, we should be concluding that there are some patients, such as preschoolers, for whom the benefits of offering this treatment outweigh the risks. OIT has proven to be effective in many studies, and we will similarly follow the progress of our patients long term to track effectiveness. The bottom line is this: OIT is safe for preschool children and should be considered for families of those very young children with peanut allergy who ask for it.The Conversation  

- Edmond Chan, Pediatric Allergist; Head & Clinical Associate Professor, Division of Allergy & Immunology, Department of Pediatrics, Faculty of Medicine; Investigator, BC Children's Hospital Research Institute, University of British Columbia

This article is republished from The Conversation under a Creative Commons license. Read the original article.
By Dr Edmond Chan
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Dr Linda Calabresi
  • Clinical Articles

Dysplastic naevi: the controversy continues

The entity ‘mildly dysplastic naevus’ has been removed from the World Health Organisation’s classification of dysplastic naevi. Dysplastic naevi are now to be graded as ‘low grade dysplastic naevus’ (previous moderately dysplastic naevus) or ‘high grade dysplastic naevus’ (previous severely dysplastic naevus).
  • Current data suggest no further treatment is necessary for lentiginous junctional/compound naevi and dysplastic naevus with low grade dysplasia (previous mildly dysplastic and moderately dysplastic naevi) with clear histologic margins and no pigment evident clinically, unless there was a high level of prebiopsy clinical concern.
  • Re-excision with a 2-5mm clinical clearance is recommended for high grade dysplastic naevi (previous severely dysplastic naevi) with involved histologic margins.
  • There is growing evidence that observation may be reasonable for low grade dysplastic naevi (previous moderately dysplastic naevus) if they were excised with clinically clear margins/ no residual clinical pigment is observed, despite histologically involved margins. More data may be required before this is accepted into clinical practice.
  • There does not appear to be a clear consensus regarding whether high grade dysplastic (previous severely dysplastic) naevi require re-excision, if initially excised with clear margins, albeit less than 2mm.
    •  

    Dysplastic naevus: the controversy since the 1970s

    The entity of dysplastic naevus has been shrouded in controversy since first described in the 1970s.1 This appears to be due to:
    1. Interobserver differences between histopathologists in applying the previous three tier grading system for dysplasia
    2. Perceived risk of progression to melanoma, and
    3. The possibility of benign entities simulating melanoma, all of which contribute to uncertainty and variability in management.2,3
    Dysplastic naevi are benign neoplasms of melanocytes.3 Dysplasia in melanocytes may occur de novo or in association with either congenital dermal naevi or common dermal naevi. It is probable that dysplasia arising in pre-existing naevi results from successive acquisition of genetic abnormalities.3 Both common naevi and dysplastic naevi demonstrate BRAF or NRAS mutations.3 It was at one time proposed that there is a step-wise model of tumour progression from dysplastic naevi through mild, to moderate, then severe dysplasia, and finally melanoma.4 However, there is no evidence that dysplastic naevi are, in fact, common precursors of melanoma.4 In actuality, the most common naevus remnant found in association with melanoma is the common acquired naevus.4 Given the large number of dysplastic naevi, compared with the comparatively small number of melanomas arising in association with dysplastic naevi, it seems that the rate of progression from dysplastic naevus to melanoma is extremely low.4 Dysplastic naevi seen associated with melanomas have an increased incidence of TERT promoter mutations, a common early genetic event in the evolution of melanoma in situ.3 This suggests that some dysplastic naevi are an intermediate entity between benign naevus and melanoma.3 There is a lack of data examining the frequency of similar genetic alterations in non-melanoma associated dysplastic naevi; thus, although the risk of progression is very low, it is suggested that naevi with high grade dysplasia or added genetic events (e.g. TERT promoter mutation) are considered for complete excision.3 It has been suggested that dysplastic naevi represent a marker of increased risk for an individual developing melanoma.5 It is difficult to establish the risk of melanoma at a separate site in patients with dysplastic naevi, as the reported incidence of dysplastic naevi in fair-skinned individuals varies widely (between 2% and 50%).4 One study has demonstrated that only the diameter of the dysplastic naevus had a significant association with a personal history of melanoma,6 whilst another study has shown that individuals with many naevi, whether common or dysplastic, have an increased risk of developing melanoma.7 Thus it would seem that two factors are associated with an individual’s risk of developing melanoma: a large number of common or dysplastic naevi (>100) and the larger size of the naevi (>4.4mm).6 It is generally agreed that there is low interobserver agreement between pathologists when grading dysplastic naevi, particularly in those lesions exhibiting moderate atypia to early in situ melanoma.8,9 This leads to uncertainty with regard to management of these lesions, especially if there is margin involvement. In 2017, Wall et al.2 conducted a survey investigating the management of dysplastic naevi by Australian dermatologists. This survey demonstrated that, similarly to comparable studies reported within the USA and Canada, most dermatologists would re-excise a moderately or severely dysplastic naevus with involved margins.2 There is, however, variability in Australian dermatologists’ approaches to severely dysplastic naevi (clinically concerning for melanoma) which are completely excised on biopsy, with 44% re-excising with a 5mm margin, and the remainder considering no further treatment necessary.2 In addition, whilst between 5-12% of US and Canadian dermatologists re-excise mildly dysplastic naevi involving margins, that rate in Australian dermatologists is 49%.2 A consensus statement released by Kim et al.10 in 2015 identified a critical gap in knowledge with regard to management of dysplastic naevi with involved margins. This consensus statement recommended that mildly to moderately dysplastic naevi with clear histologic margins need no re-excision. If a biopsy report reveals severe dysplasia with positive margins, re-excision to achieve a 2-5mm clinical margin is recommended. The statement suggested that mildly dysplastic naevi with positive histologic margins after biopsy (and no residual pigment) may be observed, and while observation may be a reasonable option for moderately dysplastic naevi with positive histologic margins (and no clinical pigment), more data are required to make a definitive recommendation.10 A further multi-centre retrospective cohort study in 2018 by Kim et al.11 suggests that close observation is a reasonable management approach for moderately dysplastic naevi with positive histologic margins. No specific recommendations are made regarding a severely dysplastic naevus with clear margins on biopsy.  

    WHO redefines melanocytic naevi

    The World Health Organisation (WHO) released their new Classification of Skin Tumours in 2018.3 They define dysplastic naevus as ‘a subset of melanocytic naevi that are clinically atypical and characterized histologically by architectural disorder and cytological atypia, always involving their junctional component.10 Diagnostic criteria for dysplastic naevi traditionally include a division of cytoarchitectural atypia into mild, moderate and severe categories.3 Pathologists often further subdivide these categories into ‘mild to moderate’ and ‘moderate to severe’ to reflect the histological field effect often perceived in these lesions. Lentiginous junctional or compound naevi (previously labelled mildly dysplastic naevi) are not associated with increased melanoma risk/progression to melanoma, and are also common within the population.3 The WHO consensus meeting working group recommends against the continued use of the term ‘mildly dysplastic naevus’ and instead recommends the use of low grade and high grade dysplasia. So, where are we now with these new recommendations regarding the grading of dysplastic naevi, and what are the management implications? It seems that the new WHO recommendations support the view that biopsies of the previously known mildly dysplastic naevi need no further treatment, having removed the entity from their classification. It would appear that there is agreement that dysplastic naevi with high grade dysplasia (previous severely dysplastic naevi) with involved margins requires re-excision to achieve a 2-5mm clinical margin of clearance. However, there appears to be no recommendations or clear consensus regarding whether these high grade dysplastic (previous severely dysplastic) naevi require re-excision, if initially excised with clear margins, albeit less than 2mm. With regard to dysplastic naevi with low grade dysplasia (previous moderately dysplastic naevi), there is a slowly growing body of evidence to suggest that it may be reasonable for these cases to be observed if they were excised with clinically clear margins/no residual clinical pigment is observed, despite histologically involved margins. Given the current variation in clinical management of these lesions, as well as the continued lack of interobserver agreement between histopathologists when diagnosing these lesions, more data may be required before this recommendation is accepted. In conclusion, as the consensus statement by Kim et al.10 recommends, the decision to re-excise dysplastic naevi should be based on both the clinical and histologic findings. If the prebiopsy level of clinical concern is high, re-excision should be considered if the biopsy reveals positive margins, even if the level of histopathological dysplasia is low. In addition, there may be clinical scenarios warranting re-excision of a mildly, mildly-moderately/moderately dysplastic lesion (now known as lentiginous junctional/compound naevi and dysplastic naevus with low grade dysplasia respectively), including patient preference.10  

    References:

    1. Duffy K, Grossman D. The dysplastic nevus: from historical perspective to management in the modern era. J Am Acad Dermatol. 2012;67 (1): 1. E1-18. DOI: 10.1016/j.jaad.2012.03.013
    2. Wall N, De’Ambrosis B, Muir J. The management of dysplastic naevi: a survey of Australian dermatologists. Australasian Journal of Dermatology. 2017;58:304-307. DOI: 10.1111/ajd.12720
    3. Elder DE, Massi D, Scolyer RA, Willemze R, editors (2018). WHO classification of skin tumours. 4th Ed. Lyon: IARC.
    4. Busam KJ, Gerami P, Scolyer RA (2019). Pathology of Melanocytic Tumors. 1st Ed. Philadelphia: Elsevier.
    5. Elder DE. Dysplastic naevi: an update. Pathology. 2010;56(1):112-120.
    6. Xiong M, Rabkin M, Piepkorn M, Barnhill R, Argenyi Z, et al. Diameter of dysplastic naevi is a more robust bio marker of increased melanoma risk than degree of histologic dysplasia: a case-controlled study. J Am Acad Dermatol. 2014;71(6):12578.e4. DOI: https://doi.org/10.1016/j.jaad.2014.07.030
    7. Holly EA, Kelly JW, et al. Number of melanocytic nevi as a major risk factor for malignant melanoma. J Am Acad Dermatol. 1987;17:459-468. DOI: https://doi.org/10.1016/S0190-9622(87)70230-8
    8. Hiscox B, Hardin MR, Orengo IF, Rosen T, Mir M, Diwan AH: Recurrence of moderately dysplastic nevi with positive histological margins. J Am Acad Dermatol . 2017;76:527530.  DOI: 10.1016/j.jaad.2016.09.009
    9. Stefanato C. The “Dysplastic Nevus” Conundrum: A look back, a peek forward. Dermatopathology. 2018;5:53-57. DOl: https://doi.org/10.1159/000487924 
    10. Kim C, Swetter S, Curiel-Lewandrowski C, Grichnik J, Grossman D, et al. Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi. JAMA Dermatol. 2015;151(2):212218. DOI: 10.1001/jamadermatol.2014.2694
    11. Kim C, Berry E, Marchetti M, Swetter S, Liam G, et al. Risk of subsequent cutaneous melanoma in moderately dysplastic nevi excisional biopsies but with positive histologic margins. JAMA Dermatology. 2018;154(12):1401-1408 DOI: 10.1001/jamadermatol.2018.3359
      - General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.  
    By Dr Linda Calabresi
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    Prof Clare Collins
    • Clinical Articles

    Have you gone vegan? Keep an eye on these 4 nutrients

    There are many reasons people go vegan, from wanting to be healthier, to reducing their environmental footprint, to concerns about animal welfare. No matter what the reason, many people find it difficult to meet the nutrient intake targets for specific vitamins and minerals while on a vegan diet. These include vitamin B12, iron, calcium, and iodine. Here’s how to make sure you’re getting enough of these vitamins and minerals while following a vegan diet.

    1. Vitamin B12

    Vitamin B12, or cobalamin, is essential for making red blood cells, DNA (your genetic code), fatty acids located in myelin (which insulate nerves), and some neurotransmitters needed for brain function. Vitamin B12 is stored in the liver, so a deficiency probably won’t happen in adults in the short term.
    Symptoms of B12 deficiency
    Symptoms of vitamin B12 deficiency include tiredness, lethargy, low exercise tolerance, light-headedness, rapid heart rate or palpitations, bruising and bleeding easily, weight loss, impotence, bowel or bladder changes, a sore tongue, and bleeding gums. Other symptoms related to the nervous system include a loss of sensation in the hands or feet, problems related to movement, brain changes ranging from memory loss to mood changes or dementia, visual disturbances, and impaired bowel and bladder control.
    Testing for B12 deficiency
    Your doctor may request a blood test to check your vitamin B12 status and determine whether indicators are in the healthy range.
    Vegan food sources of B12
    Vitamin B12 is abundant in animal foods including meat, milk and dairy products. For vegans, plant sources of vitamin B12 include some algae and plants exposed to bacterial action or contaminated by soil or insects. While traces of vitamin B12 analogues can be found in some mushrooms, nori or fermented soy beans, more reliable sources include vitamin B12-supplemented soy or nut “milks”, or meat substitutes. Check the nutrition information panel on the label for the the B12 content. Crystalline vitamin B12 added to these products can boost the B12’s absorption rate to a level similar to that from animal products.

    2. Calcium

    Calcium is needed to develop and maintain the skeleton bones, and is stored in the teeth and bones. It is also essential for heart, muscle and nerve function.
    Testing for calcium deficiency
    Low calcium intakes are associated with osteoporosis or “brittle bones” and a higher risk of bone fractures. A bone scan is used to measure bone density, with osteoporosis diagnosed when bone density is low. Both low calcium intakes and low vitamin D levels increase the risk of osteoporosis. Check your bone health using the Know Your Bones online quiz.
    Vegan food sources of calcium
    Although the richest sources of calcium are milk and milk-based foods, vegans can get calcium from tofu or bean curd, some fortified soy or nut beverages, nuts, seeds, legumes, and breakfast cereals. Calcium needs can be higher for vegans and vegetarians due to the relatively high oxalic acid content of foods such as spinach, rhubarb, beans, and the high phytic acid content of seeds, nuts, grains, some raw beans, and soy products. These specific acids can lower the calcium absorption from these foods by 10-50%. In a study of calcium intakes of 1,475 adults , vegans were below national recommendations and had lower calcium intakes compared with vegetarians, semi-vegetarians, pesco-vegetarians, and omnivores.

    3. Iodine

    Iodine is needed to make thyroxine, a thyroid hormone used in normal growth, regulation of metabolic rate, and development of the central nervous system. Iodine is concentrated in the thyroid gland.
    Symptoms of iodine deficiency
    Iodine deficiency can lead to the enlargement of the thyroid gland, a goitre, or hypothyroidism. Symptoms of hypothyroidism include lethargy, tiredness, muscular weakness, feeling cold, difficulty concentrating, poor memory, weight gain, depression, facial puffiness, hair loss, dry skin, constipation, and slower heartbeat. In women, iodine deficiency can increase risk of miscarriage and stillbirth, and congenital anomalies, including mental retardation and cretinism.
    Testing for iodine deficiency
    Your iodine status can be assessed by a range of tests, including thyroid hormones in your blood, the size of your thyroid gland, or the presence of a goitre. Talk to your doctor about these tests.
    Vegan food sources of iodine
    The iodine content of food depends on the iodine content of plants, which in turn depends on soil iodine content. When soil content is low, iodine may need to be supplemented. Major sources of iodine are seafood, dairy products, and eggs. For vegans, iodised salt, commercial bread made using iodised salt, fortified soy or nut milks (check the product label) and seaweed are important. Substances called goitrogens, which are found in brassica vegetables – including cabbage, broccoli and Brussels sprouts, sweet potato and maize – can interfere with the production of thyroid hormones.

    4. Iron

    Iron is needed to make haemoglobin in red blood cells, which carries oxygen around your body. Iron is also needed for the production of energy in your muscles, and for concentration and a healthy immune system.
    Symptoms and testing for iron deficiency and anaemia
    Not having enough iron leads to iron deficiency, and is associated with reduced work capacity, impaired brain function, lower immunity, and delayed development in infants. The first stage of iron deficiency is referred to as low iron stores and your doctor may refer you for a blood test to check your iron status.
    Vegan food sources of iron
    In Australia and New Zealand, the biggest contributors to iron intake are wholegrain cereals, meats, chicken, and fish. The amount of iron absorbed from food depends on a person’s iron status (with those who are iron-deficient absorbing more), as well as the iron content of the entire meal, and whether iron is haem (from animal foods) or non-haem iron from plant sources such as grains and vegetables. Although iron from plant sources is less able to enter the body, you can boost your absorption by adding lemon or lime juice (citric acid) or other vitamin C-rich vegetables and fruits, which convert non-haem iron to a form than is better absorbed. Take care with food components that inhibit absorption of both haem and non-haem iron, including calcium, zinc and phytates in legumes, rice and other grains, and polyphenols and vegetable proteins that can inhibit absorption of non-haem iron. Long-term vegans will also need to keep an eye on levels of vitamin D, omega-3 fat and protein. A good strategy is to check in with your GP periodically to review your health and well-being, and an accredited practising dietitian can check whether you’re getting all the nutrients you need.The Conversation This article is republished from The Conversation under a Creative Commons license. Read the original article.
    By Prof Clare Collins
    shutterstock_577395964
    Dr Linda Calabresi
    • Clinical Articles

    Reproductive carrier screening

    Have you seen this? This little print-out could save you a good 30 minutes in valuable consulting time. It’s the information from Sonic for couples who are planning a family about the potential value for testing their carrier status for conditions such as cystic fibrosis and fragile X. Even though the information is coming from an organisation with a vested interest in promoting the testing, there is not even a suggestion of bias. It is all straight down the line – here are the risks – this is what is available for testing should you choose to pursue it. There’s no denying it is worth considering. RANZCOG recommends that information about reproductive carrier screening be offered to every woman either prior to conception (preferred) or in early pregnancy. Having this site bookmarked and ready to print off ensures your advice when advising women pre-conception is in keeping with best practice. >> Click here for resource

    By Dr Linda Calabresi
    shutterstock_305164379
    Dr Linda Calabresi
    • Clinical Articles

    Fluoroquinolones and neuropathy, is that a thing?

    How big is the risk of peripheral neuropathy with fluoroquinolones? That’s the question UK researchers were looking to answer with their large case-controlled study recently published in JAMA Neurology. And – cutting to the chase – what’s the answer? Well, the risk isn’t huge but there is certainly a risk. And the association is worth bearing in mind if a patient develops peripheral neuropathy because the timing of this side-effect can be unpredictable, making the link less obvious. According to the study which analysed details from a large UK primary care population database involving almost 1.4 million patients over seven years, taking oral fluoroquinolone increased the relative risk of developing peripheral neuropathy by 47% compared to not taking the drug. “The absolute risk with current oral fluoroquinolone exposure was 2.4 per 10,000 patients per year of current use,” the study authors wrote. And just to be sure the association wasn’t simply related to having an infection that needed antibiotics, the researchers also looked at all those patients who had received a different antibiotic, namely amoxicillin-clavulanate, to see if there was a similar association with this particular side-effect. But no – the problem just seemed to occur with the fluoroquinolones. “No significant increased risk was observed with observed with oral amoxicillin-clavulanate exposure,” they found. Aside from quantifying the risk of peripheral neuropathy with fluoroquinolones, which was the main aim of the study, researchers also found that the relative risk remained significantly increased up to 180 days after taking the drug. So, if a doctor is investigating the cause of a patient’s newly-developed peripheral neuropathy, they need to ask about fluoroquinolone use in the previous six months. The study findings also suggested certain patients might be more at risk of developing this adverse effect than others. The risk appeared to be greater among men and those aged older than 60 years. The risk also seemed to increase the longer a person took the drug. The findings seem to suggest increased caution needs to be taken when prescribing fluoroquinolones, especially given that they have other known potential side-effects such as tendon rupture and aortic aneurysm. “Health care professionals should consider these potential risks when prescribing fluoroquinolone antibiotic,” the study authors concluded. But, an accompanying editorial warns against getting the risk out of perspective. The editorial authors from the Mayo Clinic in the US point out that when a side-effect is very rare, it can be challenging to determine predisposing factors or potential confounders. There is also a lack of a strong hypothesis on the mechanism underlying fluoroquinolone-induced neuropathy. “It is clearly a rare event in a sea of fluoroquinolone use, and no clear pattern has been defined that differentiates it from other causes of peripheral neuropathies,” they wrote. However, they support the findings of the original study that there is an association, but suggest further research is needed before doctors start avoiding using these drugs.

    Reference

    Morales D, Pacurariu A, Slattery J, Pinheiro L, McGettigan P, Kurz X. Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy. JAMA Neurol. Published online April 29, 2019. doi:10.1001/jamaneurol.2019.0887 Staff NP, Dyck PJB. On the Association Between Fluoroquinolones and Neuropathy. JAMA Neurol. Published online April 29, 2019. doi:10.1001/jamaneurol.2019.0886    
    By Dr Linda Calabresi
    shutterstock_1535946863 (1)
    Emmanuel Stamatakis
    • Clinical Articles

    How much do sedentary people really need to move? It’s less than you think

    As little as 20 minutes of exercise a day can offset a sedentary lifestyle. And that exercise can include walking the dog. People who spend much of their day sitting may need to move around less than we thought to counteract their sedentary lifestyle, new research shows. Our research, published today in the Journal of the American College of Cardiology, found about 20-40 minutes of physical activity a day seems to eliminate most health risks associated with sitting. That’s substantially lower than the one hour a day a previous study has found. We spend almost all our waking day sitting, standing, or moving. The health impact of each one of these can be complex. For example, too much standing can lead to lower back problems and even a higher risk of heart disease. But sitting for too long and not moving enough can harm our health. Then there are people who sit for many hours and also get in reasonable amounts of physical activity. For example, someone who has an office job but walks to and from work for 20 minutes each way and runs two to three times a week easily meets the recommended level of physical activity. While we know moving is better than sitting, what is far less clear is how much of a good thing (moving) can offset the harms of a bad thing (sitting). That’s what we wanted to find out in our study of almost 150,000 Australian middle-aged and older adults. We followed people enrolled in the 45 and Up Study for nearly nine years. We looked at links between sitting and physical activity with deaths from any cause, and deaths from cardiovascular disease such as heart disease and stroke, over that time. We then estimated what level of moderate-to-vigorous physical activity might offset the health risks of sitting. This kind of activity is strenuous enough to get you at least slightly out of breath if sustained for a few minutes. It includes brisk walking, cycling, playing sports or running.

    What we found

    People who did no physical activity and sat for more than eight hours a day had more than twice (107%) the risk of dying from cardiovascular disease compared to people who did at least one hour of physical activity and sat less than four hours a day (the “optimal group”). But it wasn’t enough just to sit less. People who did less than 150 minutes of physical activity a week and sat less than four hours a day still had a 44-60% higher risk of dying from cardiovascular disease than the optimal group. We also calculated the effect of replacing one hour of sitting with standing, walking, and moderate and vigorous physical activity. Among people who sit a lot (more than six hours a day) replacing one hour of sitting with equal amounts of moderate physical activity like strenuous gardening and housework, but not standing, was associated with a 20% reduction in dying from cardiovascular disease. Replacing one hour of sitting with one hour of vigorous activity such as swimming, aerobics and tennis, the benefits were much greater, with a 64% reduction in the risk of dying from cardiovascular disease.

    What does it all mean?

    The great news for people who sit a lot, including sedentary office workers, is that the amount of physical activity needed to offset the health risks of sitting risks was substantially lower than the one hour a day a previous study found. Even around 20-40 minutes of physical activity a day - the equivalent of meeting the physical activity guidelines of 150 to 300 minutes a week – seemed to eliminate most risks associated with sitting. For people who sat a lot, replacing sitting with vigorous physical activity was better than replacing it with moderate activity; and replacing sitting with moderate activity or walking was better than replacing it with standing.

    What’s the take-home message?

    Our study supports the idea that sitting and exercise are two sides of the same health “coin”. In other words, enough physical activity can offset the health risks of sitting. Should we worry about sitting too much? Yes, because sitting takes up valuable time we could spend moving. So too much sitting is an important part of the physical inactivity problem. We also know only a minority of adults get enough physical activity to offset the risks of sitting. For those who sit a lot, finding ways to reduce sitting would be a good start but it is not enough. The most important lifestyle change would be to look for or create opportunities to include physical activity into our daily routine whenever possible.

    How to widen our activity ‘menu’

    Not everyone has a supportive environment and the capacity to create opportunities to be active. For example, lack of time and physical activity being low on people’s list of priorities are the main reasons why inactive adults don’t exercise. Also, many do not have the motivation to power through a strenuous workout when they are juggling many other life challenges. There are no known remedies to a lack of time or low motivation. So, perhaps we need to add new approaches, beyond exercising and playing sport for leisure, to the “menu” of physical activity options. Incidental physical activity like active transportation – think walking fast or cycling part or all of the way to work – or taking stairs are great ways to become or stay active without taking much extra time.The Conversation Emmanuel Stamatakis, Professor of Physical Activity, Lifestyle, and Population Health, University of Sydney; Joanne Gale, Research Fellow Biostatistician, University of Sydney, and Melody Ding, Senior Research Fellow of Public Health, University of Sydney This article is republished from The Conversation under a Creative Commons license. Read the original article.
    By Emmanuel Stamatakis, Joanne Gale, Melody Ding
    shutterstock_1682411368
    Dr Linda Calabresi
    • Clinical Articles

    Proof – food is medicine

    A decent eating program can keep you out of hospital, according to US research into the value of providing ready-to-consume meals to a select adult population. The retrospective cohort study involved just over 1000 participants, average age 53, almost 500 of whom were allocated to receive 10 meals a week, tailored to a recipient’s specific medical needs, for a period of just over two years. This group was then compared to a control group who had been matched for age and area of residence etc. Overall the study found the medically tailored meal delivery program was associated with approximately half the number of inpatient admissions over the duration of the study. Similarly, receiving the set meals was associated with significantly fewer admissions to skilled nursing facilities and a substantial reduction in health care costs. A pretty impressive result, yes? But before we go demanding an MBS item number for Meals on Wheels, even the researchers themselves advise caution in interpreting these results. Firstly, the study was not randomised. People who were allocated to receive the meal delivery intervention were generally more ill than the control patients – they were significantly more likely to have HIV, cancer and diabetes. “It is unlikely that similar results would be seen were the intervention applied to a healthier population, as the risk of admission or high health care costs, even in the absence of intervention would be substantially lower,” the study authors said in The Journal of the American Medical Association (JAMA) Internal Medicine.  And we don’t know whether it was the actual healthy food that made the difference, or whether it was the fact that they were getting their food for free thereby enabling the recipients to have more money for other things such as medications (remembering we are talking about the US health system here). Nonetheless, the study raises some valuable points. It is well-recognised that ‘following an appropriate diet is a cornerstone of maintaining health and managing illness.’ But this is often difficult for patients with complex medical conditions, especially if they are socioeconomically disadvantaged. As an accompanying editorial points out, much of the more recent focus has been on diet-related diseases and the health and economic burden they increasingly represent. Diseases such as diabetes, cardiovascular disease and obesity-related cancers have claimed much of the spotlight. But nutrition as a solution, and how we can use specific nutritional interventions to effectively manage a patient’s health care has been less well defined. “One obstacle has been demonstrating the efficacy and cost implications of specific nutritional interventions,” the editorial authors said. This JAMA study does that. Specifically, the researchers have shown that the provision of free, medically tailored meals at home is associated with reduced health care use and net cost savings. More importantly for Australians, the study supports the incorporation of nutrition into health care to improve patient health outcomes and keep vulnerable patients out of tertiary care. “Given their potential for significant health benefits and cost-savings, [medically tailored meals] may represent the tip of the spear for a national evolution toward such food-is-medicine approaches,” the editorial concludes.

    Reference

    Berkowitz SA, Terranova J, Randall L, Cranston K, Waters DB, Hsu J. Association Between Receipt of a Medically Tailored Meal Program and Health Care Use. JAMA Intern Med. Published online April 22, 2019. doi:10.1001/jamainternmed.2019.0198 Mozaffarian D, Mande J, Micha R. Food Is Medicine—The Promise and Challenges of Integrating Food and Nutrition Into Health Care. JAMA Intern Med. Published online April 22, 2019. doi:10.1001/jamainternmed.2019.0184
    By Dr Linda Calabresi
    measles
    Dr Linda Calabresi
    • Clinical Articles

    Diagnosing Measles

    The Department of Health requires suspected cases of measles to be notified immediately without waiting for laboratory confirmation. Measles is an urgent, highly contagious, notifiable disease. Secondary infections occur in 75-90% of susceptible household contacts Transmission of the measles virus is by respiratory droplets and direct contact with respiratory secretions
  • Serological testing and PCR are the mainstays of laboratory diagnosis

    • Background

    Measles is a highly contagious disease with secondary infections occurring in 75 – 90% of susceptible household contacts.1 With suboptimal vaccination coverage in some areas, measles outbreaks remain an unfortunate reality in Australia.2 A single case therefore has significant public health implications.

    Clinical features

    Transmission of measles virus is by respiratory droplets and direct contact with respiratory secretions. The virus can also survive on inanimate objects in the patient’s environment for at least 30 minutes. After an incubation period of 10 days (range 7 – 18 days) patients develop a prodrome consisting of fever, malaise, cough, coryza and non-purulent conjunctivitis. Koplik’s spots may develop during this time. These are whitish spots on an erythematous background on the buccal mucosa classically arising opposite the molar teeth. After about four days, a morbilliform rash appears, initially on the face and head, then extending to the trunk and limbs (Figure 1). The rash lasts 3 – 7 days. Patients usually make a full recovery, but complications including otitis media, pneumonia, seizures, and rarely encephalitis (subacute sclerosing panencephalitis) can occur. The case fatality rate in stable populations is estimated at around 2%, but rates up to 32% have been seen in refugee and displaced populations.4

    Laboratory testing

    Serological testing and PCR are the mainstays of laboratory diagnosis. In the early stages of infection, a single serology result demonstrating negative measles IgG and positive IgM in the context of the clinical picture outlined above provides strong evidence for a case of measles. It is important to note that serology can be negative in the early stages of infection. In a minority of patients, IgM may not be detected up to four days after the rash onset.5 Definitive serological diagnosis can be established with acute and convalescent sera, usually taken 10 – 14 days apart. A diagnostic rise in measles-specific IgG is a reliable indicator of recent infection. In early infection, PCR is performed on nose and throat swabs. Nose and throat swabs are usually pooled and analysed together in the testing laboratory. Swabs sent in viral or universal transport media are acceptable for testing, as are ‘dry’ swabs (no transport media). Swabs using bacterial transport media should be avoided as rates of viral detection may be lower. Other specimens that can be used for PCR are first pass urine and anticoagulated blood. When positive, PCR provides rapid confirmation of the clinical picture.

    Case definition for measles

    Initial investigation of suspected Measles
     
    ▪ Generalised maculopapular rash usually lasting three or more days and ▪ Fever (at least 38° if measured) present at the time of rash onset and ▪ Cough, coryza, conjunctivitis and Koplik’s spots
    Notify immediately.
    Laboratory Testing – Serology (IgG & IgM) and PCR.
     

    Treatment and prevention

    Treatment of measles remains supportive only. Infection control measures are important in order to avoid secondary cases. In the clinic;
    • The receptionist receiving patients should be alert to possible measles cases.
    • Those presenting with fever and rash should be given a single use mask and isolated from other patients
    • Consultation rooms used for assessment of suspected measles cases should be left vacant for at least 30 minutes after the consultation.3
    Measles vaccination as part of the routine immunisation schedule for clinic patients is of the utmost importance. It is also important is ensuring that clinic staff vaccinations are kept up-to-date.

    Notification

    Due to its public health importance, the Department of Health requires all suspected cases of measles to be notified immediately without waiting for laboratory confirmation. This will help facilitate timely follow-up of the contacts, vaccination where required and will help prevent further transmission of the virus.

    References

    1. Perry RT, Halsey NA. The Clinical Significance of Measles: A Review. J Infect Dis. 2004 May 1; 189(S1): S4-16. DOI: 10.1086/377712
    2. Victorian Department of Health, Blue Book, Infectious Diseases Epidemiology and Surveillance, Measles. [Accessed 8.9.2014] Available at: https://www2.health.vic.gov.au/public-health/infectious-diseases/disease-information-advice/measles
    3. Kouadio IK, Kamigaki T, Oshitani H. Measles outbreaks in displaced populations: a review of transmission, morbidity and mortality associated factors. BMC Int Health Hum Rights. 2010 Mar 19; 10: 5 [Accessed 8.9.2014]. DOI: 10.1186/1472-698X-10-5
    - General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
    By Dr Linda Calabresi

    Education by clinicians, for clinicians

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