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Recognise this scenario? You prescribe an inhaler for the patient. You educate the patient on why they need the inhaler. You draw diagrams. You demonstrate the technique on the placebo inhaler. You write the script. And then… you cross your fingers.

Expert/s: Dr Linda Calabresi

Drugs and devices

Clinical Articles

While the ‘opioid epidemic’ might be grabbing all the headlines at the moment, Australian toxicologists are reminding us that paracetamol is the most common drug used in overdoses in this country. What’s more the numbers of both paracetamol-related hospital admissions and liver injury have been increasing over the past decade at a rate that far exceeds the rate of population increase. According to a retrospective study recently published in The Medical Journal of Australia, there has been an average 3.8% annual increase in the number of paracetamol-related hospital admissions since 2007, and a mean 7.7% annual increase in paracetamol-related liver injury cases, whereas the population has been increasing at a rate of only 1.6% annually.

Expert/s: Dr Linda Calabresi

Drugs and devices

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

Expert/s: Dr Linda Calabresi

Drugs and devices

Clinical Articles

Efudix wins over other AK treatments

Got a patient with multiple sun spots on their head that need treatment? Well it looks like the old, tried and true 5FU cream is still the way to go, according to a randomised trial just published in the New England Journal of Medicine. Among more than 600 randomly assigned patients, Dutch researchers compared the effectiveness of four topical treatments commonly used to treat multiple actinic keratoses as part of a ‘field treatment’. In addition to the 5% fluorouracil cream (Efudix), the study looked at the effectiveness of 5% imiquimod cream (Aldara), methyl aminolevulinate photodynamic therapy (MAL PDT or Metvix PDT) and 0.015% ingenol mebutate gel (Picato gel). After 12 months, the study showed that the Efudix was the most effective in terms of maintaining a reduction of at least 75% of actinic keratoses from the baseline. In other words, this cream was the best of the four therapies, at getting rid of these sun spots completely. “And the differences between fluorouracil cream and imiquimod, PDT and ingenol mebutate were significant,” the study authors said. They found the likelihood of success for those patients using fluorouracil was almost 75%, compared with only 54% for imiquimod, 38% for PDT and 29% for those using ingenol mebutate. And this independent study didn’t do anything tricky with the dosing regimen either. “In our trial, we used the most commonly prescribed dosing regimens of the therapies studied,” they said. In terms of sticking to the dosing regimen, patients were much better adhering to the schedule when they were taking ingenol mubutate (99% adherence) or PDT (97%) rather than the fluorouracil (89%) or the imiquimod (88%), but this appeared to directly correlate with how often they had to take the therapy and for how long. Overall, however this adherence rate did not reflect treatment satisfaction rate. “Satisfaction with treatment and improvement in health-related quality of life at 12 months after the end of treatment were highest in the fluorouracil,” the study authors reported. Nothing like a treatment actually working to make a patient feel happy about having had it. A bonus of this study, according to the researchers was the inclusion of patients with the more severe actinic keratosis lesions (Grade III lesions), patients who have been commonly excluded from previous similar trials of topical treatments. “[Including these patients] is more representative of patients seen in daily practice,” they said. In addition to effectiveness, cost is another appealing factor for fluorouracil over the other treatments. This study has the capacity to change practice. The study authors quote the prevalence actinic keratoses among whites aged 50 and over as being at 37.5%. While cryotherapy remains the treatment of choice for single lesions, where there are multiple lesions present field treatment should be considered. Currently the guidelines for this field treatment don’t advocate one treatment over any other, more or less suggesting all four of the treatments in this study as being efficacious. However, as these Dutch researchers say “our results could affect treatment choices in both dermatology and primary care.”

Reference

Jansen MHE, Kessels JPHM, Nelemans PJ, Kouloubis N, Arits AHMM, van Pelt HPA, et al. Randomized Trial of Four Treatment Approaches for Actinic Keratosis. N Engl J Med. 2019 Mar 7; 380(10): 935-46. DOI: 10.1056/NEJMoa1811850

Expert/s: Dr Linda Calabresi

Drugs and devices

Clinical Articles

Challenging the Penicillin Allergy Label

It would be a brave doctor who would ignore the warning ‘allergic to penicillin’ when deciding which antibiotic to prescribe for a patient. But according to a new review published recently in JAMA, despite up to 10% of the population reporting allergies to penicillin, few have clinically significant reactions. “Although many patients report they are allergic to penicillin, clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon (<5%),” the US review authors said. And the issue is an important one. As the authors point out, not only will patients, labelled as having a penicillin allergy be given alternative antibiotics that are more likely to fail and cause side-effects but the use of these alternatives increase the risk of antimicrobial resistance developing. So for all these reasons, the researchers propose that is worthwhile that all patients labelled as having an allergy to penicillins be re-evaluated. As a starting point, a comprehensive history should be taken. And while the reviewers acknowledge that, to date no allergy questionnaires have been validated in terms of defining risk levels, there are plenty of features in a history that can give a clue as to whether a person could safely be offered skin prick testing or a drug challenge. Broadly speaking, patients with a history of a minor rash, that was not significantly itchy that developed over the course of days into the course of the antibiotic are considered low-risk. This is opposed to people who have a history of developing a very pruritic rash within minutes to hours of taking the drug (which tends to indicate an IgE-mediated reaction) or people who experienced significant blistering and/or skin desquamation after taking penicillin (which generally represents a severe T-cell-mediated reaction). Among those patients whose rash-history suggests they are at low-risk, other factors should be considered before attempting a challenge. “Even in the context of low-risk allergy history, patients with unstable or compromised haemodynamic or respiratory status and pregnant patients should be considered as having at least a moderate-risk history,” they said. However, patients whose penicillin allergy history included non-allergic-type symptoms such gastrointestinal symptoms or patients who only have a family history of penicillin allergy should be considered at low-risk. Once the patient has been assessed as being at low-risk of having an acute allergic reaction, the study authors suggest they be given amoxicillin under medical observation. “For penicillin allergy, administration of 250mg of amoxicillin with one hour of observation demonstrates penicillin tolerance,” they said. Should the patient tolerate this dose of amoxicillin, it can be concluded that all beta-lactams can be administered safely, and the issue of cross-reactivity (between penicillin and cephalosporin which occurs in about 2% of truly penicillin-allergic people) is rendered irrelevant. Patients who are considered at moderate-risk of having an allergic reaction to penicillin, namely those patients with a history of urticaria or mild pruritic rashes but no anaphylaxis should be considered for skin-prick testing. Only those with a negative skin prick test should be considered for an oral drug challenge. People with a history of high-risk reactions – usually anaphylaxis should not be skin-prick tested or challenged. They might be considered for desensitisation programs but only in select circumstances and only under the close supervision of a specialist. All in all, the authors advocate health professionals not simply take the label of ‘allergic to penicillin’ as gospel. “Evaluation of penicillin allergy has substantial benefits for patients by allowing improved antimicrobial choice for treatment and prophylaxis,” they concluded.

Reference

Shenoy ES, Macy E, Rowe T, Blumenthal KT. Evaluation and Management of Penicillin Allergy: A Review. JAMA 2019 Jan 15; 321(2): 188-99. DOI: 10.1001/jama.2018.19283

Expert/s: Dr Linda Calabresi

Drugs and devices

Clinical Articles

Safety Data on Ondansetron in Pregnancy

Finally, we’ve got some robust evidence to answer the question - is ondansetron safe to take for morning sickness. Published in JAMA, a very large retrospective study involving over 1.8 million pregnancies, almost 90,000 of which included exposure to ondansetron in the first trimester has found that taking the drug did not increase the risk of cardiac malformations or congenital malformations overall. However, first trimester ondansetron was associated with a very small increased risk of oral clefts (three additional cases per 10,000 women treated). Interestingly the increased risk for oral clefts was confined to cleft palate, there was no evidence for an increased risk of cleft lip. The information will be eagerly received by the thousands of pregnant women who experience severe nausea and vomiting, and the clinicians who care for them many of whom have been prescribing ondansetron because of its effectiveness, despite the lack of detailed safety data. “Although not formally approved for the treatment of nausea and vomiting during pregnancy, ondansetron, a 5-HT receptor antagonist, has rapidly become the most frequently prescribed drug for nausea and vomiting during pregnancy in the United States because of its perceived superior antiemetic effects and improved adverse effect profile compared with treatment alternatives,” the study authors said. “In 2014, an estimated 22% of pregnant women used ondansetron in the United States,” they said. The major strengths of this study lie in the size of the cohort and the fact that the information on ondansetron exposure was based on filled prescriptions, thereby negating any possible recall bias. Both these factors are particularly important given how rare these abnormalities are and how many possible confounders there could be. As for limitations of the study, of course just because a prescription has been filled doesn’t always mean the medication has been taken, but even if the exposure wasn’t as great as calculated, the risk would be only lessened rather than raised. There is also the possibility that there might have been some other unrecognised factor involved especially since all the women in the study were uninsured and treated under Medicaid insurance and therefore included a higher percentage of women from disadvantaged communities. However, given the detailed information collected on these women and their pregnancies, and the multiple analyses conducted on this data, the likelihood of unmeasured confounders affecting the findings was thought to be low. Overall the results of this study should provide reassurance for clinicians and pregnant women, according to an accompanying editorial, written by a US obstetrician and gynaecologist. “As clinicians and pregnant women engage in informed, shared decision-making surrounding treatment for nausea and vomiting, the current information is important for contextualising risks in light of the potential benefits,” he concluded.

References

Huybrechts KF, Hernández-Díaz S, Straub L, Gray KJ, Zhu Y, Patorno E, et al. Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA. 2018 Dec 18; 320(23): 2429-37. DOI: [10/1001/jama.2018.18307] Haas DM. Helping Pregnant Women and Clinicians Understand the Risk of Ondansetron for Nausea and Vomiting During Pregnancy. JAMA. 2018 Dec 18; 320(23): 2425-6. DOI: [10.1001/jama.2018.19328]

Expert/s: Dr Linda Calabresi

Drugs and devices

Clinical Articles

Antidepressants in Pregnancy

“Be patient with yourself… nothing in Nature blooms all year.” One of my favourite quotes regarding perinatal depression and anxiety which affects 10-16% of all new parents. The importance of perinatal mental health cannot be overstated. Research has shown that an untreated perinatal mental health condition can lead to substance misuse, poor antenatal attendance as well as poor self-care. There is also a risk of poor attachment to the infant, and a long-term risk of poor child development outcomes through neglect. Suicide is the final risk. The government have recently supported our concerns regarding this important topic by changing the MBS item numbers (16590, 16591, 16407) to include a mental health assessment. We have a duty of care to our patients to know what is safe to prescribe or continue to use in pregnancy- remembering that pregnancy is not protective against mental illness. Did you know that more than half of all women abruptly discontinue antidepressant medication upon confirming a pregnancy? Almost 70% of these women suffer a relapse of depression. Currently the recommendations for a woman on an antidepressant who has been euthymic for at least 12 months include cease the medication in pregnancy, continue the current medication, change to an alternative, safer medication or cease the medication and then reintroduce it if a relapse occurs. Antidepressant medications can cross the placenta, meaning the fetus is exposed. There are also potential pregnancy complications, but the risks to the fetus and the pregnancy are very low. Congenital malformation may occur from exposure to some antidepressants in the first trimester. Growth restriction and neurobehavioural problems may result from exposure in the second trimester. And congenital cardiac defects have been associated with paroxetine use in pregnancy. Postpartum haemorrhage is the only significant potential obstetric complication associated with SSRI and SNRI use. There is also a small increased risk of persistent pulmonary hypertension of the newborn associated with SSRI, SNRI and TCA use in late pregnancy. Antidepressants taken in late pregnancy, may also cause poor neonatal adaptation syndrome (PNAS). This manifests as hypotonia, respiratory distress, hypoglycaemia, seizures and most commonly ‘jittery-ness’ in the infant. Paroxetine has the highest risk of PNAS. Despite this, it is NOT recommended that the dose of medication be reduced in late pregnancy. Because the fetus may not clear the medication in the same way the mother does, lowering the dose might simply risk a relapse of depression in the mother while gaining little or no benefit to the infant. RANZCOG states that SSRIs are generally considered low risk and safe to prescribe in pregnancy and breastfeeding. It is important to know that sertraline has the lowest placental exposure and the lowest excretion into breastmilk. Other medications are listed in the table below as a quick reference guide:

Table 1. ANTIDEPRESSANT CATEGORIES FOR PREGNANCY AND BREASTFEEDING:

Medication	Pregnancy Category	Breastfeeding
TCAs * avoid doxepin during breastfeeding	C	Compatible
Citalopram	C	Compatible
Escitalopram *preferred to citalopram in breastfeeding	C	Compatible
Fluoxetine	C	Compatible
Mirtazapine	C	Compatible
Paroxetine *can cause cardiac defects with high dose first trimester but safest for breastfeeding along with sertraline	D	Compatible
Sertraline	B	Compatible
Venlafaxine	C	Compatible

Compatible- an acceptably low relative infant dose or no significant plasma concentrations or no adverse effects in breastfed infants. When managing perinatal depression is it important to consider potential risk against the known benefits of the medications and the potential detrimental effects of mental illness on the development of the infant and other children in the home.

Key References:

The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Perinatal Depression and Anxiety: C-Obs 48. East Melbourne (AU): RANZCOG; Mar 2015. 16 p. RANZCOG Cat. No.: C-Obs 48. Available from: https://www.ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Mental-health-care-in-the-perinatal-period-(C-Obs-48).pdf?ext=.pdf
White L. Antidepressants in Pregnancy. O&G Magazine. 2018; 20(3): 24-25. Available from: https://www.ogmagazine.org.au/20/3-20/antidepressants-in-pregnancy/
Galbally M, Lewis AJ, Snellen M. Introduction Pharmacological management of major depression in pregnancy. In: Gabally M, Snellen M, Lewis AJ, editors. Psychopharmacology and Pregnancy. Berlin: Springer; 2014. p. 67-85.

Dr Julia Marcello works at Bentley Maternity Unit which provides maternity services to low risk women in WA. The unit is staffed by GP obstetricians, specialist obstetricians and gynaecologists and midwives and offers the option of private care within a public setting. The midwife service is available to low risk women and includes antenatal care, birthing services and postnatal care through the visiting midwifery service and lactation consultant support. GP shared care services are also available. The Unit also provides a gynaecology service led by Dr Aseel Alkiaat and specialists from King Edward Hospital. For further information go to www.bhs.health.wa.gov.auFor-health-professionals

Expert/s: Dr Julia Marcello

Drugs and devices

Clinical Articles

The Vit D Story Now a Fairytale

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

References

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

Expert/s: Dr Linda Calabresi

Drugs and devices

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 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.

Expert/s: Dr Janet Cheung, Dr Jonathan Penm

Drugs and devices

Clinical Articles

Green light for ginkgo

Ischaemic stroke patients are less likely to deteriorate mentally if they take ginkgo biloba extract in addition to low-dose aspirin in the acute phase, a new study suggests. “Cognitive decline after stroke can result in vascular cognitive impairment and Alzheimer’s disease,” the study authors wrote. Importantly then, this randomised controlled trial showed stroke patients who took ginkgo as well as aspirin had better memory function, executive functions, neurological function and daily life in the six months after experiencing their stroke than those patients who took aspirin alone. The Chinese study also showed that taking ginkgo was not associated with an increased incidence of adverse events. The results of the study, published in the journal, Stroke and Vascular Neurology support the long-held hypothesis that ginkgo protects against neuronal death caused by ischaemia, which had been demonstrated in animal stroke models. It has been suggested that the possible mechanism of ginkgo’s effectiveness may include anti-apoptosis and increasing cerebral blood flow. In the study, researchers randomised over 340 patients, from five hospitals who had had an ischaemic stroke in the previous seven days to receive either 450mg of ginkgo biloba extract with 100mg aspirin daily or only the 100mg of aspirin daily. Both groups were treated for six months and were various intervals over that period. From the very early assessments (at 12 days) and through until 180 days, the difference in the assessments of cognitive and executive function was statistically significant. Similarly neurological and global function was significantly better in the group that took ginkgo. “These data suggest that [ginkgo biloba extract] is effective and could be recommended in the treatment of acute ischaemic stroke,” the study authors concluded. Ref: Li S, et al. Stroke and Vascular Neurology 2017; 0:000104. doi:10.1136 /svn-2017-000104

Expert/s: Dr Linda Calabresi

Drugs and devices

Clinical Articles

Assassination by pacemaker: Australia needs to do more to regulate internet-connected medical devices

In the future, people are going to be just a little bit cyborg. We’ve accepted hearing aids, nicotine patches and spectacles, but implanted medical devices that are internet-connected present new safety challenges. Are Australian regulators keeping up? A global recall of pacemakers has sparked new fears and splashy headlines about hacked medical devices. But the next 20 years of medicine will normalise the use of intelligent implants to control pain, provide data for diagnostic purposes and supplement ailing organs, which means we need proper security as well as access in case of emergency.
Read More: Three reasons why pacemakers are vulnerable to hacking
Pharmaceuticals and medical devices in Australia are regulated by the Therapeutic Goods Administration (TGA), an arm of the national Health Department. Can we rely on Australia’s medical devices regime? Recurrent criticisms by parliamentary committees and government inquiries suggest the regulator may be struggling.

The job of the TGA

The TGA regulates medical devices such as stents, pacemakers, joint implants, breast implants, and the controversial vaginal mesh that has featured recently in the media (and a Senate inquiry) over claims it seriously injured patients. The role of the TGA is vital, because defective devices can result in injury or death. They have a major cost for the public health system and affect patient quality of life. They often result in litigation, sometimes with billion-dollar settlements. In undertaking its mission, the TGA looks to information from manufacturers and distributors, from overseas regulators and its own staff. Like counterparts such as the US Food and Drug Administration, TGA staff are under pressure to get products into the marketplace and reduce “red tape”.

The TGA and cybersecurity

Wireless medical devices need greater security than, say, an internet-connected fridge. It is axiomatic that they must work. We need to ensure that information provided by the devices is safeguarded and that control of the devices – implantable or otherwise – is not compromised. To do that, we can use existing tools such as robust passwords, encryption and systems design. It also requires product vendors and practitioners to avoid negligence. Regulators must proactively foster and enforce standards. Put simply, bodies like the TGA need to deal with software rather than simply bits of metal and plastic. It is unclear whether the TGA has the expertise or means to do so.

Solutions, not panic

The past decade has seen a succession of inquiries into the TGA, including the 2015 Sansom Review and 2012 Senate PIP Inquiry. Each has demonstrated that the TGA is not always keeping up with its task. Problems are ongoing: think defective joint implants, breast implants and vaginal mesh. But there are some potential paths towards improvement. Accountability One solution is to ensure the TGA is more accountable. Currently, if someone wishes to bring a claim alleging a device was improperly permitted, the TGA has immunity from civil litigation about regulatory failure. Removal of immunity will force it to focus on outcomes. That can be reinforced by giving it independence from the Department of Health, making it report direct to Parliament and ensuring the openness emphasised by the Pearce Inquiry. Regulatory capture Medical products regulation in Australia has been a matter of penny wise, pound poor. The TGA is funded by fees from the manufacturers and distributors that it regulates, in addition to some government funding. It needs a discrete budget that recoups costs but is not dependent on companies that complain regulation is expensive. It needs enough resources to do its job well in the emerging age of the internet of things, including access to independent expertise regarding cybersecurity and devices. A device register How many devices have been implanted and how many removed? The lack of data about medical devices is a problem. The government has so far not embraced recommendations for a comprehensive device register, one allowing timely identification of what was implanted and by whom.

Read More: Vaginal mesh controversy shows collective failure of the TGA and Australia’s specialists

Such a register would provide a means for determining problems with devices or medical practice. We need timely, consistent reporting of problems on a mandatory basis, as well as recall and transparent investigation of what went wrong. Disclosure of interests The inquiry into vaginal mesh revealed the WA Branch of Australian Medical Association had a financial interest in a device that may have seriously affected numerous women. There must be full disclosure of such interests, with meaningful sanctions where disclosure has not been made. This requires action by the TGA, professional bodies and the government.

So, what about assassination by wireless pacemaker?

The cybersecurity of medical devices is a matter for everyone. We need the TGA to work with manufacturers, distributors and health professionals to mandate best practice. Should, for example, manufacturers and practitioners ensure that implants do not rely on default passwords that are easily crackable? What about access by emergency services? There is a fundamental need to develop and enforce a national safety standard regarding all wireless implants. For that we need thoughtful policy, not just headlines. Bruce Baer Arnold, Assistant Professor, School of Law, University of Canberra This article was originally published on The Conversation. Read the original article.

Expert/s: Dr Bruce Baer Arnold

Drugs and devices, Infectious diseases, Vaccination

Videos

New pneumococcal 15-valent conjugate vaccine that includes coverage against serotype 3

In this Product Explainer, Public Health Physician and Infectious Diseases Epidemiologist Prof Paul Van Buynder explains the burden of pneumococcal disease in both children and adult population. He explains why PCV 15 has increased serotype coverage and why improved immunogenicity against serotype 3 is important both from a clinical and public health perspective (5 mins).

Expert/s: Prof Paul Van Buynder