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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

Cheapest Option Just as Good for Vaginal Atrophy

Post-menopausal women experiencing vulvovaginal symptoms will benefit just as much from using the cheapest over-the-counter lubricant or moisturiser as using topical oestrogen, a new study suggests. The 12-week randomised clinical trial, published in JAMA Internal Medicine, compared the efficacy of a low-dose vaginal oestradiol tablet and a vaginal moisturiser, each versus placebo among a group of over 300 post-menopausal women with moderate to severe vulvovaginal symptoms. To determine the effectiveness of the treatment women were asked to report on the severity of their ‘most bothersome symptom’ which included pain with vaginal penetration (60%), dryness (21%), itching (7%), irritation (6%) and pain (5%). Across the board, regardless of which treatment was used, most women had a decrease of at least 50% in symptom severity over the course of the study. This was significant in light of the fact that most women said they ‘frequently’ or ‘always’ distressed about their sex life at enrolment, whereas after the 12-week study nearly half said they were ‘rarely’ or ‘never’ distressed. “No treatment group differences in symptom reduction were observed for vaginal oestradiol tablet plus placebo gel vs dual placebo, or vaginal moisturiser plus placebo tablet vs dual placebo”, the US researchers reported. And it didn’t matter if the most bothersome symptom was dyspareunia or itching, it appeared the hormone treatment or the specific vaginal moisturiser (Replens) had no advantage over the placebo combination. According to the study authors, the placebo gel used in the study had a similar pH and viscosity as the vaginal moisturiser (Replens) but was less mucoadhesive. The fact that both formulations were equally effective in reducing symptoms suggests that the mucoadhesive properties are less important than previously thought. Similarly, markers of vaginal oestrogenisation such as the vaginal maturation index, did, naturally improve more with the topical oestrogen but this did not translate into a greater benefit in terms of symptoms over placebo. As an accompanying editorial points out, “ultimately, it is improvement in symptoms rather than surrogates such as tissue markers that should define the goal of care.” And while the study authors conclude that treatment choice for women with troublesome postmenopausal vulvovaginal symptoms should be ‘based on individual patient preferences regarding cost and formulation’ the editorial authors go in much stronger. “[P]ostmenopausal women experiencing vulvovaginal symptoms should choose the cheapest moisturiser or lubricant available over the counter – at least until new evidence arises to suggest there is any benefit to doing otherwise.” Ref: JAMA Intern Med. doi:10.1001/jamainternmed.2018.0116 JAMA Intern Med. doi:10.1001/jamainternmed.2018.0094

By Dr Linda Calabresi
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Dr Vivienne Miller
  • Clinical Articles

There is no perfect contraception…

Let us imagine that there has been a significant side-effect from a contraceptive choice occurs and a patient suffers harm. It is a known but very rare side-effect. How much legal and ethical responsibility lies with the doctor who prescribes the contraceptive, how much lies with the medical experts advocating this form of contraception as reasonable and safe, and how much lies with the pharmaceutical company who researched this product? Should this contraceptive be withdrawn from use, and if so, why would it be still available and advised for use in other countries around the world? A reasonable response to this question would include an assessment of the incidence of this particular complication among all users of this contraceptive, the incidence of any other significant complications, and the outcome for the patients of these complications. However, let us imagine the media finds this story and runs with it, giving widespread coverage of this single case and highlighting the contraceptive as the cause. This is the situation at present with the progestogen IUD, Mirena® in the United States. It is also the case with oral contraceptive pills that contain cyproterone acetate (such as Diane-35®) in Australia. Contraceptive pills like Diane-35® are more oestrogenic in their balance and this could potentially increase their risk of venous-thromboembolism (VTE), although this still remains somewhat controversial. It was temporarily banned in France because of this in 2013. However, the risks need to be put in perspective. Even if the worst case-scenario is accepted, the actual increased risk of VTE for these newer pills over older types is an extra four to six VTEs per 10,000 Pill users per year.1 “The risk of death from a VTE induced by a combined oral contraceptive is approximately one in 100,000, significantly less than the risk during pregnancy,” said Dr Foran. It is known that oral contraceptive pills containing 35ug ethinyl oestradiol and cyproterone acetate are being prescribed in Australia for indications beyond contraception, namely androgenising signs in women.  It is also known, that for some women these pills provide the best control of their symptoms. In Europe, the regulatory authorities decided that the benefits outweighed the rare risks for properly selected patients and this OCP was quickly reintroduced to the market after only six months. However, in Australia there have recently been calls for the banning or restriction of this product in Australia following the diagnosis of a VTE in a young woman. How reasonable is it in our society to allow the traumatic stories of individuals to override medical opinion and determine regulation? The public needs to be made to realise that not only are these products very safe for the overwhelming majority of women, when prescribed appropriately, but they are also so much safer for women than an unplanned pregnancy would be. It might be valid to argue that there are other combined oral contraceptives that are ‘safer’ than those containing 35ug ethinyl oestradiol and cyproterone acetate, or that cyproterone acetate is available separately for use. However, what happens when one of these other oral contraceptive choices causes a major medical event in a different woman? In the UK, doctors have been advised to warn patients that there is an increased risk of VTE with Femodene®, Marvelon® and Yasmin® named as some examples. The Daily Mail UK1 had a massive heading to this effect: “Deadly risk of pill used by one million women: Every GP in Britain told to warn about threat from popular contraceptive” If media and legal pressure is allowed to result in the withdrawal of these medications, at some stage, there will be no oral contraceptive choices left. The seriousness of the situation is highlighted in the case of the Mirena® IUD, since there is no similar alternative to this product in Australia. In the United States, this contraceptive device has been under a cloud of bad publicity since 2009, due to US Food and Drug Administration warnings relating to migration and perforation. Since then, the Mirena® IUD has been scrutinised by patients with side-effects and, of course, lawyers. “The real question here is whether hysterectomy or endometrial ablation is a safer option than the Mirena® IUD for women with heavy menstrual bleeding.” Dr Foran. The maintenance of a range of choices is important and women should have the right to make these decisions for themselves in consultation with their doctors. The Mirena IUD is also a safe form of contraception, especially for women who have thrombophilias and for older premenopausal women, most of whose other choices are less safe. Is it still enough for doctors to fully inform women of the side-effects and complications of their contraceptive options and to let them decide, or is modern contraception becoming a very personal, public and legal battlefield, the main casualties of this being expert medical advice and a woman’s choice?  …and in the end, who is left holding the baby?  
  1. Bitzer J et al. Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate and the associated risk of thromboembolism. J Fam Plann Reprod Health Care. doi: 10. 1136/ jfprhc-2013-100624 http://srh.bmj.com/content/familyplanning/early/2013/04/10/jfprhc-2013-100624.full.pdf
  2. Daily Mail, UK, 22nd Feb 2018 http://www.dailymail.co.uk/news/article-2550216/Deadly-risk-pill-used-1m-women-Every-GP-Britain-told-warn-threat-popular-contraceptive.html
  This article is based on an interview with Dr Terri Foran, Sexual Health Physician, Lecturer with the UNSW’s School of Women’s and Children’s Health and Director of Master Women’s Health Medicine on Saturday 17th February 2018 at the Annual Women’s and Children’s Health Update, Sydney

By Dr Vivienne Miller
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Dr Linda Calabresi
  • Clinical Articles

Don’t pickle old brains

Want to preserve your brain function into old age? Cut down on the booze. That’s the conclusion of a large, longitudinal study just published in JAMA Psychiatry. After comparing more than 200 alcohol dependent adults with a similar number of healthy adults, over a 14 year period, the US researchers concluded alcohol-dependence accelerated the cortical ageing process even if the alcohol habit developed later in life. They found, through a series of MRIs that alcohol dependence (as per the DSM-IV criteria) resulted in more rapid frontal lobe deterioration than that which just occurred with age, regardless of gender. As part of the study the researchers also looked at whether comorbidities such as drug use or hepatitis C infection made a difference to the decline in cognitive function. And while they found they compounded the shrinkage of the frontal lobe, the actual deficits in the frontal cortex seemed to be associated chiefly with the alcohol. “We observed a selectivity of frontal cortex to age-alcoholism interaction beyond normal aging effects and independent of deficits related to drug dependence,” they said. Also, the researchers found that the deterioration was more associated with current drinking habits  than the cumulative effect of many years of alcohol abuse. People who had become alcohol dependent later in life were just as vulnerable as people whose alcohol use disorder started when they were younger. “The accelerated volume deficits in the older alcohol-dependent participants could not readily be attributed to more years of heavy drinking, given that many had a late onset of their disorder and lower lifetime alcohol consumption estimates than their early-onset counterparts,” the study authors said. So, it appears the frontal cortex, which is that part of brain that helps people plan, reason, modify behaviours and problem solve is the most vulnerable to damage in people with alcohol use disorder. Add this to the fact the frontal cortex deterioration associated with aging, is fundamentally responsible for the deterioration in executive function that limits an elderly person’s ability to function and live independently, and you have a recipe for disaster for those older people who drink to excess. What does this all mean? An accompanying editorial makes the take home message quite clear. “Given the rapidly growing aging population… it is critical that we improve and implement strategies to address alcohol misuse among older drinkers. As Yoda might say, “Protect their brains, we must.” Ref: JAMA Psychiatry. Published online March 14, 2018. doi:10.1001/jamapsychiatry.2018.002 JAMA Psychiatry. Published online March 14, 2018. doi:10.1001/jamapsychiatry.2018.0009

By Dr Linda Calabresi
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Dr Jenny Robson
  • Clinical Articles

Know your fungi

In Australia the commonest encounter with fungi in a medical sense is with superficial and cutaneous fungal infections such as those infecting the skin, scalp or nails.

Tinea or ringworm of the scalp, skin and nails

Fungal infection of the scalp (tinea capitus), skin (tinea) and nails (tinea unguium, onychomycosis) is usually caused by dermatophytes which have a unique ability to utilise keratin as a nutrient source due to the presence of the enzyme keratinase allowing colonisation of the stratum corneum. The presence of the fungus and its metabolic products can occasionally induce an allergic or inflammatory response in the host. The type and severity of the host response is often related to the species and strain of dermatophyte causing the infection. Following is a list of the dermatophytes that have been identified in our laboratories:
SPECIES NATURAL HABITAT INCIDENCE
Epidermophyton floccosum Humans Common
Trichophyton rubrum [worldwide] Humans Very common
Trichophyton interdigitale [anthropophilic] Humans Very common
Trichophyton tonsurans Humans Common
Trichophyton violaceum Humans Less common
Trichophyton concentricum Humans Rare
Trichophyton schoenleinii Humans Rare
Trichophyton soudanense Humans Rare
Trichophyton rubrum [African] Humans Rare
Microsporum audouinii Humans Less common
 
SPECIES NATURAL HABITAT INCIDENCE
Trichophyton interdigitale [zoophilic] Mice, rodents Common
Trichophyton erinacei Hedgehogs Rare
Microsporum canis Cats Common
 
SPECIES NATURAL HABITAT INCIDENCE
Microsporum gypseum Soil Common
Microsporum nanum Soil/pigs Rare
Microsporum cookei Soil Rare

Mycotic infections

Despite the majority of work done by mycology laboratories being concerned with superficial and cutaneous fungal infections, in recent years there has been an increase in fungal subcutaneous and systemic disease. Mycotic infections are usually classified according to the level of tissue involvement in the patient. The following table includes examples of such mycotic infections, their classification and an indication of their incidence.
LEVEL OF INFECTION MYCOSIS CAUSATIVE ORGANISM INCIDENCE
Superficial Pityriasis versicolor Seborrhoeic dermatitis including dandruff and follicular pityriasis Malassezia furfur (a lipophilic yeast) Common
Tinea nigra Hortaea werneckii Rare
White Piedra Trichosporon sp Common
Black Piedra Piedraia hortaea Rare
Cutaneous Dermatophytosis Trichophyton, Epidermophyton, Microsporum
Dermatomycosis Fungi other than dermatophytes
Candidiasis Candida species
Other yeasts Geotrichum, Trichosporon
Subcutaneous Sporotrichosis Sporothrix schenckii Rare
Chromoblastomycosis Fonsecaea, Phialophora, Cladophialophora etc Rare
Phaeohyphomycosis Cladophialophora, Exophiala, Bipolaris, Exserohilum, Curvularia Rare
Dimorphic Systemic Mycoses Histoplasmosis Histoplasma capsulatum Rare
Opportunistic Systemic Mycoses Candidiasis Candida albicans and related species Common
Cryptococcosis Cryptococcus neoformans Rare/Common
Aspergillosis Aspergillus fumigatus etc Rare

Specimen Collection

Laboratory diagnosis requires collection of an adequate amount of material for both microscopy and culture. The site needs to be cleaned with an alcohol wipe, which helps lower the contamination rate from bacteria, saprophytic moulds and yeasts that may overgrow a dermatophyte. As a health and safety precaution, scalpel blades should not be enclosed with specimen.

Scalp

In general, zoophilic fungi e.g. M.canis tend to cause ectothrix or involvement of the outside of the hair shaft and the lesions tend to be inflammatory, while anthropophilic fungi e.g. T.tonsurans result in endothrix or involvement of the hair shaft itself. The lesions are less inflammatory. Lustreless, broken, infected hairs should be sampled from the edge of a lesion. It is important to collect hair roots, as this is where fungal elements are detected. A scalpel blade may be used to dislodge crusts or scales in which hair stumps may be embedded.

Skin

Skin scrapings should be obtained by scraping the active border of the infection which usually is typically scaly, red and elevated and where the hyphae are present. In cases of kerion, swabs of the exudates should be collected. Separate specimens should be taken from the representative lesions on various parts of the body. When scraping feet, the site of most common involvement is between the fourth and fifth toes.

Nails

Scrape under the nail plate until the crumbling white degenerative portion is reached. All the keratin debris from under the nail should be collected directly onto a black collection card. The distal portion of the nail may need to be trimmed with nail clippers. Fungal elements remain viable for weeks at room temperature. Nail scrapings showing hyaline septate hyphae are diagnostic for a dermatophyte.

Transportation

Glass or plastic bottles with screw tops are not recommended since high relative humidity encourages proliferation of bacteria and reduces the chances of isolating fungi. Specimens for mycological studies are best submitted within the special black fungal scrapings cards provided by the laboratory or, if these are not available, within a folded paper (preferably dark) packet. Although delays are to be avoided, fungi are generally resistant to drying and survive transportation well at room temperature.

Negative Laboratory Report

The reasons for negative microscopy and/or culture include: • Incorrect clinical diagnosis • Sampling variation associated with an inadequate specimen • Splitting the sample to perform microscopy and culture • Presence of non-viable hyphae in the distal portion of nails • Uneven fungal colonisation of nails • Overgrowth by contaminant saprophytic fungi Careful recollection obtaining sufficient material may be necessary to confirm results. Adequate/Inadequate collection
General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
By Dr Jenny Robson
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Dr Vivienne Miller
  • Clinical Articles

New privacy laws affect all GPs

From February this year, changes to privacy laws have been put in place that are likely to significantly affect doctors and their practice. Many doctors will not be aware of their new obligations leaving them vulnerable to inadvertently breaching the Privacy Amendment Act, 2017. “Ignorance is no excuse as a legal argument,” Dr Peter Walker, GP and senior risk manager at Avant explained. This latest amendment to the privacy laws demands that doctors must have an updated protocol on how breaches of a patient’s privacy should be handled. Both the patient and the relevant authority must be notified if a breach occurs that is thought to potentially cause the patient harm. If something goes wrong and the patient’s privacy is breached, doctors must now conduct a risk assessment, including an assessment of the risk of harm resulting from the breach. If harm is possible (physical, emotional, psychological, financial, or harm to reputation), the doctor is then obliged to alert the patient/s concerned and write a statement for the Office of the Australian Information Commission via their online form. Fines may be incurred if the action to reduce the risk of possible breaches has not been made, or if it is insufficient, especially if serious harm results. Fines are also possible for doctors who fail to comply with the amended Privacy Act (for example, if they do not notify the Australian Information Commission of a breach or if they do not have an updated privacy plan). The obligation to notify a patient of a privacy breach does enable that patient to take further action if they perceive they have been harmed. They may then escalate the issue themselves, perhaps in Court. In serious circumstances, the Commission will also refer to other entities, such as the Australian Health Practitioner Regulation Agency or if the matter is criminal, to the Police. If no harm is likely to result, doctors do not have to notify the patient or the Commission, but this is likely to be difficult for a clinician to assess without legal advice. “Prevention really is better than cure, but many doctors are unaware of this new legislation.” Dr Walker said. The following examples are given to illustrate to GPs considerations about privacy in the light of the amended Act. “Sorry, Mr B, I need your consent before I fax that referral letter to the specialist for you because this is not a form of communication that is absolutely safe regarding your privacy. For example, a wrong number may be typed in by accident or the specialist may not receive the fax. For your interest, the fax has a hard drive that will store information and so for this reason we remove this before we dispose of the fax machine. If any of this is of concern to you regarding your privacy you can pass the letter over yourself on the day of your consultation…” “Sorry, Mr B, we don’t email information either to you or the specialist, as email may be hacked; this is less likely to happen to medical email systems, but it is still possible and our practice policy has decided not to use email…” “Mr B, I can text the information from the referral letter to the specialist’s mobile phone with your permission to do so. However, please understand that someone who is holding his phone for him may see the message. This is quite possible, as he is operating now…” “Sorry, Mr B, I understand your concern about needing an urgent appointment, and that the post is slow and the referral may not get to the specialist in time, but this is considered to be a legally safe way of sending correspondence if you don’t take the referral with you now. I know the specialist wants to see the referral before offering you an urgent appointment …” Other possible scenarios in which privacy breaches may occur include the theft of documents (e.g. laptop, briefcase), conversations about a patient’s condition being overheard where the patient can be identified, the incorrect disposal of paperwork that identifies a patient, and discussions about a patient with a third party (who is not part of the health team managing them) without that patient’s consent. The Privacy Amendment Act 2017 builds upon the Privacy Act, amended in March 2014, that instructed all medical practices to have a Privacy Policy. The Australian Information Commission is able to audit any medical practice regarding this to see if that practice complies. This legislation is aimed at promoting the security of a patient’s personal details in all communications between themselves and health professionals, and among health professionals generally. To this end, doctors will need to look carefully for any potential breaches of these new privacy laws resulting from their current means of communication with colleagues and the patients themselves. Reference Office of the Australian Information Commissioner. Notifiable Data Breaches. Available at: oaic.gov.au/engage-with-us/consultations/notifiable-data-breaches This article is based on Dr Peter Walker’s video interview conducted at the Sydney Women’s and Children’s Health Update on Saturday February 17th 2018.

By Dr Vivienne Miller
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Dr Linda Calabresi
  • Clinical Articles

Advice for shift workers

We know night shift work is not good for your health. Evidence shows night shift work is associated with an increased risk of sleep loss, occupational accidents, obesity and weight gain, type 2 diabetes, coronary heart disease, and breast, prostate and colorectal cancers, according to a review in the BMJ by two intensive care specialists. But what of strategies to help night shift workers mitigate these risks? What does the research say we should be advising these patients to do to optimise their health, remembering that many health professionals will be involved in this type of shift work? According to the review, there is a ‘paucity of adequately powered, well designed, randomised controlled trials’ on the subject however from what there was and with the addition of expert opinion the review authors recommended the following.
  • Try and make sure you’re not sleep-deprived before a night shift. Try and wake the morning before naturally (without an alarm) and, if possible have a daytime nap maybe taking advantage of that ‘circadian dip’ between 2 and 6pm the afternoon before you front up for night duty.
  • If you get the opportunity to nap during the night shift, try to limit the duration of these to less than 30 minutes, “to avoid slow wave sleep followed by grogginess on waking, known as ‘sleep inertia’”, the authors advise.
  • Caffeine reduces sleepiness and improves performance 20-45 minutes after taking it, with the effect lasting up to five hours.
  • There is evidence that drugs such as modafinil are effective in reducing sleepiness in night shift workers compared with placebo but these drugs have been associated with skin reactions and their long-term safety is yet to be established. Similarly, exposure to bright light has been proposed as a possible means of inhibiting melatonin, reducing sleepiness and perhaps reducing the cancer risk associated with shift work but neither these drugs nor bright light exposure is supported by sufficient evidence to be conclusively recommended.
  • Hunger and digestion are both affected by circadian rhythm. There is some evidence to suggest if you don’t eat you’ll perform better over the duration of the night shift than if you eat, however it is likely you will experience hunger and will be more likely to get GI symptoms leading the authors to recommend a main meal immediately before the shift and then small snacks as required to stave off hunger overnight.
  • And the big one. How to optimise sleep between night shifts? Well- the recommendations are fairly predictable – avoid bright light on the way home (wear sunglasses), employ blue screens on your computer and phone, use eye masks and ear plugs and develop a predictable pre-bed routine. Avoid caffeine for at least six hours before sleep time and perhaps consider taking melatonin the morning after a night shift –some evidence suggests that this increases sleep duration by up to 24 minutes.
“A meta-analysis of 66 studies concluded that regular exercise leads to improvement in sleep quantity and quality, but the optimum timing, duration, and type of exercise for sleep promotion have yet to be determined,” they said. In addition, the review authors didn’t recommend any other sleeping tablets due to a lack of quality evidence of their effectiveness and the risk of dependency. Finally, the researchers advised night shift workers to be aware their performance is likely to be reduced especially in that particularly vulnerable time between 3 and 5am and therefore they should seek support when required to do critical tasks at this time. They also warned workers to be aware of their vulnerability when driving home after night shift and referred to a patient, the inspiration for this review, who experienced the life-changing consequences of being involved in a road traffic accident while on a set of night shifts in 2005. Ref: BMJ 2018; 360:j5637 doi: 10.1136/bmj.j5637

By Dr Linda Calabresi
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Dr Linda Calabresi
  • Clinical Articles

Opioids offer little over NSAIDs for chronic severe pain

Opioids have really fallen out of favour as a chronic pain relief option. Even for patients with severe chronic back pain, or severe pain from their osteoarthritis in their hip or knee, opioids will not offer any better relief in terms of pain-restricted function that non-opioid medication, a recent study published in JAMA has shown. The US clinical trial involved 240 US adults with moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic.  Researchers compared whether treatment with opioids such as morphine, oxycodone or hydrocodone/paracetamol improved pain-related function over a 12-month period over treatment with nonopioid such as paracetamol or an NSAID. Surprisingly, the results showed no significant difference in terms of pain related function over the course of the study. In fact, the pain intensity was significantly better in the nonopioid group over the 12-month period, however the study authors said the clinical importance of this finding was unclear. As was perhaps more expected, the group that took opioids had more side effects. “Overall, opioids did not demonstrate any advantage over nonopioid medication that could potentially outweigh their greater risk of harms,” the researchers said. When looking at all the results – even including secondary outcomes,  the only area where opioids were found to be superior to nonopioids in this study of chronic pain patients was in the area of anxiety. The opioid group had fewer anxiety symptoms – so they had just as little function, and even more intense pain but they worried about it less. The study authors said their findings added to the growing body of evidence that opioids offer little benefit over other medications and even placebo in the management of chronic pain conditions, especially when their side effect profile is taken into consideration. “Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain”, they concluded. Ref: JAMA 2018;319(9) 872-882. doi:10.1001/jama.2018.0899

By Dr Linda Calabresi
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Dr Janet Cheung
  • Clinical Articles

Phenibut – the Russian anti-anxiety drug linked to Gold Coast teens’ overdoses

Phenibut was initially developed in the 1960s in Russia as an anti-anxiety (anxiolytic) drug with cognitive enhancing properties. It has since attracted a strong following of users in the “smart drug” market, with claims of boosting memory recall and exam performance. Originally given to Soviet cosmonauts to combat anxiety and insomnia, the powdered drug is suspected to have played a role in the recent overdose of seven teenagers at a Queensland private school.

How it works

Phenibut – also known as pbut, noofen, party powder (or its scientific name β-phenyl-γ-aminobutyric acid and brand name Bifren) – is a psychotropic drug, which means it affects the user’s mental state. The drug is similar in structure to a type of neurotransmitter known as neurotransmitter γ-aminobutyric acid (GABA), which plays a role in reducing excitability and anxiety, as well as enhancing euphoria and cognitive function. Phenibut binds to a specific subtype of the GABA receptor, activating a similar reaction as GABA. Animal studies have shown that phenibut is able to penetrate the blood brain barrier. The blood-brain barrier is is an important mechanism that stops harmful toxins and bugs travelling through the blood stream and entering the brain.
Read more: Explainer: what is the blood-brain barrier and how can we overcome it?
Once phenibut reaches the brain the result is reduced anxiety and social inhibition. Because it depresses the central nervous system (like GABA), it is also used as a mood elevator and tranquiliser. Phenibut is structurally similar to the widely prescribed drug baclofen (Lioresal), which is available in Australia. Baclofen is prescribed as a muscle relaxant for patients with conditions such as multiple sclerosis.

What is it used for?

Phenibut can be used to treat anxiety, post-traumatic stress disorder, alcohol withdrawal syndrome and vestibular (balance) disorders such as vertigo. It is also used recreationally in many countries including the United States, United Kingdom and Australia to reduce social anxiety and induce feelings of euphoria. Animal studies also show it has potential to improve brain function after a stroke. Phenibut is not licenced for use in the European Union, Australia or the United States due to safety concerns. In Australia specifically, the drug regulator, the Therapeutic Goods Administration (TGA) has rejected 11 public submissions for registration and states that phenibut “represents a significant risk of harm, including overdose”. Although phenibut is commercially available in few countries around the world, aside from Russia, a recent study showed that 48 unrelated internet suppliers sold phenibut from the United Kingdom, United States, China, Australia and Canada. In Russia and the Ukraine, it is commercially available as БИФРЕН® (Bifren) and daily doses range from 500 to 2000 mg. Phenibut was available as a powder in amounts ranging from 5 g to 1,000  kg and as capsules containing 200–500 mg in packs of between six and 360.

How was was it developed?

Phenibut was first synthesised in Russia in the 1960s by Vsevolod Vasilievich Perekalin and his associates at the Department of Organic Chemistry of the Herzen Pedagogical Institute in St Petersburg, Russia. In initial publications, phenibut was known as phenigamma. The drug used to be included in medical kits for cosmonauts on Russian space flights due to the reports of enhanced cognition and high tranquilising properties.

Side effects

Side effects of phenibut are generally linked to its central nervous system depressant effects, such as sedation and problems with breathing. There is currently limited information about phenibut. But because it has similar pharmacological properties to baclofen it’s likely to have similar side effects.
Read more: Explainer: how do drugs work?
These include gastrointesinal symptoms (nausea, vomiting, diarrhoea), central nervous system symptoms (insomnia, confusion, euphoria, depression, hallucinations), and visual disturbances and musculoskeletal symptoms (such as tremors). Users of phenibut can also develop tolerance within days, needing more of the drug to feel the same effects. This can increase the risk of adverse effects. Users may develop withdrawal effects, such as severe rebound anxiety and insomnia, when they stop taking the drug. Despite phenibut not being registered or legally available in Australia, the TGA has received three reports of problems related to phenibut use in the past five years. These cases range from isolated symptoms of headaches, to a cluster of symptoms such as visual impairment, muscle spasms, palpitations and nausea/vomiting. Signs of overdose include: shallow irregular breathing; drowsiness and lethargy; increased sweating; decreasing blood pressure; nausea and vomiting; and lowering body temperature. The ConversationThe reported adverse events of phenibut are just scratching surface of a largely unregulated online drug market with no standards of quality assurance. So for those students seeking the competitive edge, it looks like those extra marks are not worth it after all. Janet Cheung, Lecturer in Pharmacology, University of Sydney and Jonathan Penm, Lecturer (Pharmacy), University of Sydney This article was originally published on The Conversation. Read the original article.
By Dr Janet Cheung, Dr Jonathan Penm
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Dr Daman Langguth
  • Clinical Articles

Investigation of Paraproteinaemia

Paraproteins are abnormal monoclonal immunoglobulins produced in plasma cell disorders (eg multiple myeloma), lymphoproliferative disorders (eg CLL, Waldenstrom’s macroglobulinaemia) and in some infections (hepatitis C). The introduction of the assay, serum free light chains (FLC) has meant the initial investigation of paraproteinaemia has become much simpler. Previously, serum tests had great difficulty in detecting immunoglobulin light chains for two reasons: 1. Light chains are rapidly cleared by the kidneys, up until a certain point where they ‘spilled’ over into the blood. 2. Assays had poor sensitivity in detecting ‘free’ light chains ie light chains not bound to heavy chains as in normal immunoglobulin. The FLC assay (a propriety product) when combined with serum protein electrophoresis (EPP) and immunofixation allows detection of the vast majority (>99%) of paraproteins, virtually eliminating the need for urine collection and analysis, thus giving a greater degree of patient satisfaction. With nearly all very sensitive assays, there are some costs to specificity. In renal failure and in polyclonal gammopathy (such as in chronic inflammation, liver disease or infection), the FLC assay may suggest the presence of a monoclonal light chain when non is present, in up to 10% in some series. Tis also occurs in chronic renal failure with EPP and immunofixation testing. This must be kept in mind when investigating patients for paraproteins. The FLC assay only detects free (unbound) immunoglobulin light chains, so traditional serum EPP plus immunofixation must also be done on initial investigation. It has been shown that the vast majority of ‘non-secretory’ myelomas actually produce free light chains, detectable by this new assay. The serum FLC assay can be used to guide chemotherapy in myeloma, and has already been incorporated into some international response criteria for myeloma. Summary The FLC assay, when combined with serum EPP and immunofixation, allows the detection and evaluation of paraproteins.
General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

By Dr Daman Langguth
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Dr Linda Calabresi
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Change in advice for abscess drainage

Skin abscesses are best treated with incision and drainage plus antibiotics, rather than just incision and drainage alone, recommends an international guideline panel in the BMJ. After critically appraising all the current evidence, the panel found adjuvant antibiotic therapy in addition to incision and drainage of uncomplicated skin abscesses reduced the risk of treatment failure and abscess recurrence by approximately 13% compared to treatment without additional antibiotics. In particular the randomised controlled trials included in the review, were evaluating the use of clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) in addition to incision and drainage. “TMP-SMX or clindamycin modestly reduces pain and treatment failure and probably reduces abscess recurrence, but increases the risk of adverse effects including nausea and diarrhoea,” they said. TMP-SMX is the more preferable option over clindamycin as it is less likely to cause diarrhoea, they added. The recommendation is in contrast to most of the current guidelines that generally advise uncomplicated skin abscesses be treated with incision and drainage alone except in cases where there is systemic illness, extensive tissue damage, immunocompromising conditions, an artificial joint or a high risk of endocarditis. And while the panel concedes that the benefit of adjuvant antibiotic therapy is modest, they anticipate that most fully informed patients would consider it large enough to choose it over incision and drainage alone. Of course, the major counter argument against increasing antibiotic use would be the possible increased risk of antimicrobial resistance. “From a societal perspective, it is possible that the modest benefits from adjuvant antibiotics in this scenario would not outweigh the risk of antimicrobial resistance in the community,” they said. However, the impact of a single course of antibiotics on this public health problem remains unknown, so any conclusion about net benefit versus net harm can only be speculative, they concluded, even though the issues are worth considering as part of the shared decision making. The panel also considered evidence for using cephalosporins for adjuvant treatment of skin abscesses, however they concluded that this class of antibiotics was unlikely to provide any benefit over incision and drainage in the majority of cases of skin abscesses, and therefore could not be recommended. Ref: BMJ 2018; 360: k243 doi.org/10.1136/bmj.k243

By Dr Linda Calabresi
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Prof Allen Cheng
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Here’s what you need to know about the new flu vaccines for over-65s

In an attempt to avoid a repeat of last year’s horror flu season, Health Minister Greg Hunt yesterday announced the government would fund two new flu vaccines in 2018 to try to better protect the elderly. While influenza affects people of all ages, infections among the elderly are more likely to require hospitalisation or cause serious complications such as pneumonia and heart attacks. Of the 1,100 Australians who died last year from flu-related causes, 90% were aged 65 and over. The two free vaccines for over-65s work in different ways: FluZone High Dose is a high-dose version; Fluad adds an additional ingredient to boost its effectiveness. Both are recommended for use only in people aged 65 and over. But neither is perfect. And it’s important to remember flu vaccines are, at best, only partially protective.

Why do we need new vaccines for flu?

Australia’s National Immunisation Program provides free influenza vaccine for the elderly, as well as other high-risk groups including pregnant women, those with chronic diseases and Indigenous Australians.
Read more: Flu vaccine won't definitely stop you from getting the flu, but it's more important than you think
Older people’s immune systems don’t respond to flu vaccines as well as younger people’s. Recent studies have also shown that flu vaccines don’t appear to be as effective in the elderly at protecting against flu and its complications. Compounding this problem is that the flu subtype that tends to affect older people (A/H3N2) is different to that which affects younger people (A/H1N1). Although the seasonal flu vaccine now contains four strains to cover all the relevant subtypes present, the protection against H3N2 infection appears to be poorer than against other strains. Two strategies are attempting to improve the effectiveness of flu vaccines. One is to increase the dose of the flu strains in the vaccine. This is the basis for Sanofi’s High Dose FluZone vaccine, which contains four times the amount of flu antigen than the standard dose. Another way is to add a substance that improves the immune response, known as an adjuvant, in combination with the flu strains. This is the basis for Seqirus’ (CSL) Fluad vaccine, which contains the adjuvant MF59. This vaccine has been used overseas for many years, but has only been become available in Australia this year.

How much better are these vaccines than the current vaccine?

Compared to the standard flu vaccine, the high-dose version has been shown to better stimulate the immune system of older users to make protective antibodies. It has been shown to better reduce rates of flu infection in over-65s than the standard vaccine. And, interestingly, it also seems to protect against pneumonia. One common criticism of clinical trials is that they don’t include the types of people who are found in the “real world”. But population based observational studies suggest that the high-dose vaccine is more protective than the standard-dose vaccine where H3N2 is the predominant circulating strain – as it was last year.
Read more: Here's why the 2017 flu season was so bad
What about the Fluad (adjuvanated) vaccine? Compared to the standard vaccine, adjuvanted flu vaccine has been shown to better stimulate the immune system of older users to make protective antibodies. Unlike the high-dose vaccine, there have not been clinical trials that show a difference in infection rates compared with the standard vaccine. But observational data suggests the adjuvanted vaccine is more protective against hospitalisation with influenza or pneumonia – to a similar degree as the high-dose vaccine. One problem with both these vaccines is that they only contain three strains, rather than the four strains in the current vaccine. The strain missing from the new vaccines is an influenza B type. But the benefits of better protection against the most common three strains in the new vaccine appear to outweigh the potential loss of protection against the missing B strain.

Are the new vaccines safe?

Both vaccines are safe, but commonly cause mild side effects, and very rarely can cause serious side effects. However, these risks from the vaccine are less than from getting influenza infection. The main side effect of vaccines relates to their effect in stimulating the immune system. In many people they cause a sore arm and, less commonly, a fever. The side effects of these new flu vaccines are slightly more common than with standard vaccines. Generally, these side effects are mild and don’t last long. None of the flu vaccines used in Australia contains live virus and therefore can’t cause flu infection. However, the vaccination season (April to June) usually occurs around the same time as when another respiratory virus (RSV) circulates, so this respiratory infection is commonly misattributed to vaccination.
Read more: Health Check: when is 'the flu' really a cold?
Rare but serious side effects, such as Guillain Barre Syndrome (where the immune system attacks nerves), have been described after flu vaccination. Studies suggest that the risk of these side effects are less common after the flu vaccine than after flu infection. People with allergies should discuss flu vaccines with their doctor. In the past, there has been concern that the flu vaccines, which are manufactured in eggs, may elicit allergic reactions in people with egg allergy. However, it is now thought that people with egg allergies can receive flu vaccines safely under appropriate supervision. In 2009, an adjuvanted vaccine (Pandemrix) was thought to be implicated in cases of narcolepsy (a disease associated with excessive sleepiness) in Europe. However, this primarily occurred in children (rather than the elderly), and with a different adjuvant (ASO3) than is being used in Fluad (MF59)

Which vaccine should I get?

The two vaccines have not been compared head to head, so it isn’t known which one is better. The available data suggest they are similar to each other. In practice, what vaccine you’ll receive will depend on what’s available at your GP or pharmacy. It is important to note that these vaccines are only recommended for use in people 65 years of age or older, and are not recommended for use in people under this age. The standard vaccine will still be available for younger people. There are no data to support the use of multiple doses of vaccines of the same or different types.
Read more: Flu is a tragic illness. How can we get more people to vaccinate?
Neither of the new vaccines is perfect – they simply reduce your risk of getting flu to a slightly greater effect than the standard vaccine. Like other flu vaccines, there is still the chance that the vaccine strains don’t match what’s circulating. The ConversationDespite the common perception that the flu is mild illness, it causes a significant number of deaths worldwide. To make an impact on this, we need better vaccines, better access to vaccines worldwide and new strategies, such as increasing the rate of vaccination in childhood. Allen Cheng, Professor in Infectious Diseases Epidemiology, Monash University This article was originally published on The Conversation. Read the original article.
By Prof Allen Cheng
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Dr Jenny Robson
  • Clinical Articles

Focus on dermatophytes

Once specimens are received in the laboratory, microscopy is performed. An interim report is then released. Specimens are then set up on specialised agar containing antibiotics and cycloheximide to inhibit the growth of bacteria and saprophytic fungi. Cultures are incubated at 28°C for three weeks. If microscopy is positive (M+) and no pathogen (C-) has grown in the interim, specimens are held an extra week. Infrequently, where microscopy and culture of nail scrapings is negative and the diagnosis is still suspected, nails can be examined for fungal elements using special stains.

Results:

Specimen types have been subdivided into three anatomical categories (nails, hair and skin) based broadly on the three clinical presentations of onychomycosis, tinea capitis, and tinea corporis/ cruris/pedis. Onychomycosis refers to fungal infections of the nails and includes tinea unguium caused by dermatophytes but also non-dermatophyte fungi and yeasts, predominantly Candida spp.

Negative laboratory report:

A common reason for negative microscopy and /or culture is an incorrect clinical diagnosis. More than 50% of dystrophic nails do not have a fungal cause, so it is important to establish a correct laboratory diagnosis before treating a patient with an antifungal agent. Other reasons for false negative results include sampling variation associated with an inadequate specimen and/or splitting the sample to perform microscopy and culture; the presence of nonviable hyphae in the distal portion of the nail; uneven colonisation of the nail by fungus; and overgrowth by contaminant saprophytic fungi. Careful re-collection to obtain sufficient material may be necessary to confirm negative results.

Nails:

The analysis of nail specimens from the hands and feet. Fingernails: Of 1202 specimens processed, 59% were negative by both microscopy and culture; 11% had hyphae seen on microscopy but were negative by culture; 27% of all finger and thumbnail cultures grew a yeast, predominantly Candida albicans (88% of all positive nail/hand cultures). Only 3% of all fingernail specimens grew a dermatophyte.

Toenails:

57% of 5097 toenail cultures were negative by both microscopy and culture. 22% were positive by microscopy but culture negative for reasons stated previously. As the literature would suggest, yeast infection of toenails is rare. Dermatophytes (20%) predominate as the main cause of onychomycosis of the lower limbs. Transmission of these dermatophytes is usually via the feet and toe web spaces, which are the major reservoir on the human body. Onychomycosis can be regarded as the end stage of tinea pedis. Desquamated skin scales containing hyphae are shed and survive for months to years on floors and carpets. Infrequently non-dermatophyte moulds are implicated in toenail infections such as Aspergillus. There is some uncertainty as to the significance of these cultures, and repeat culture may be indicated.

Treatment options:

With tinea unguium, topical treatment is successful only with surgical removal of the nail combined with oral therapy. First-line treatment for all types of nail tinea consists of: 1. terbinafine (child < 20 kg: 62.5 mg; 20 to 40 kg: 125 mg) 250 mg orally, daily for six weeks for fingernails and 12 weeks for toenails or (if terbinafine is not tolerated) 2. itraconazole 200 mg orally, twice daily for seven days every month for 2-4 months or 3. fluconazole 150 to 450 mg orally, once weekly for 12 to 52 weeks. Successful management of candidiasis of the nail requires removal of risk factors e.g. water immersion.

Tinea capitis:

Of 414 hair samples submitted over this period, 329 (80%) were negative by both microscopy and culture. Dermatophytes isolated include M. canis (46%); T. tonsurans (42%); M. gypseum (5%); T. mentagrophytes (5%) and T. rubrum (2.5%). This condition afflicts predominantly prepubertal children. Clinically it can present as alopecia or a more inflammatory lesion (kerion). It is noteworthy that T. tonsurans, an anthropophilic fungus, is emerging as a common cause of tinea capitis in children and spreads easily from child to child.

Treatment options:

Tinea capitis often requires oral therapy to eradicate the infection. Treatment options include 1. griseofulvin fine particle (child: 20 mg/kg up to) 500 mg orally, daily for 4-8 weeks, or 2. terbinafine (child< 20 kg: 62.5 mg; 20 to 40 kg: 125 mg) 250 mg orally, daily for four weeks.

Tinea corporis/cruris/pedis:

Of the 7406 specimens received from skin sites, 73% were both microscopy and culture negative; 5% were positive only by microscopy. Of the 22% culture positive specimens, 19% grew a dermatophyte and 3% a yeast.

Treatment options:

When topical treatments have failed, recommended oral therapy includes: 1. griseofulvin fine particle (child: 10 to 20 mg/kg up to) 500 mg orally, daily for at least four weeks or 2. terbinafine (child <20 kg: 62.5 mg; 20 to 40 kg: 125mg) 250 mg orally, daily for at least two weeks, depending on the response or 3. itraconazole capsules 200 mg orally, twice daily for one week for tinea of the feet or hands or 4. itraconazole capsules 200 mg orally, once daily for one week for tinea elsewhere.
General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
By Dr Jenny Robson

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