2019

DPP-4 Inhibition: Playing the Long Game in Type 2 Diabetes

Melanoma in pregnancy

Did you know that melanoma is the most common malignancy in pregnancy? It accounts for one third of pregnancy-associated malignancies in Australia. Terrifying stuff isn’t it?

Fortunately, melanoma occurring in a pregnant woman remains a very rare occurrence. But no one wants to be the doctor that misses it, especially as we all know picking it up early can, quite literally, be the difference between life and death.

The really tricky part is that pregnancy does add an extra dimension to detecting and managing melanoma. For a start melanocytic naevi darken during pregnancy in one in ten women.

NOACs – surgery and everything else

If you work in a truly general general practice you will no doubt be familiar with this scenario. The patient on a NOAC who is going for a dental procedure, cataract operation or arthroscopy.

Do they need to stop their NOAC? And if so, when and for how long?

Often there are more than a couple of opinions out there, with a lot of different considerations to take into account.

Pharmacogenomics in general practice

Despite potential savings of more than $1 billion annually, awareness of pharmacogenomic tests among Australian prescribers is low and national guidelines for their use have not been developed. This void contributes directly to the continued prescribing of ineffective medications, unacceptably high rates of adverse drug reactions and associated personal and economic costs.

Pharmacogenomics (PGx) is the study of how the genome of an individual patient influences their response to a medication.

Listeria protection

These days the first question most GPs get asked, after confirming a wanted first pregnancy is what does the woman need to take or eat, and, importantly what should she avoid.

It gets tricky doesn’t it? If you avoided  everything that is said to potentially cause harm (according to the world wide web and social media) the pregnant woman will run a serious risk of malnutrition!  Much of the fear stems from the risk of contracting listeria – that surreptitious bacteria that can cause – very occasionally, severe infection in affected adults – but more importantly for the pregnant women can cause miscarriage, premature birth or stillbirth. You need some authoritative, credible information sources to fall back on when giving these vulnerable patients advice.

Enter the Food Standards Australia and New Zealand website. On their website they have this fantastic resource: an information page entitled Listeria and food.

Quite simply, it’s a precis of what women should and should not eat to keep them safe from this infection. To be fair this resource doesn’t help women keep the problem in perspective, as it doesn’t mention how rarely this condition affects pregnant women. But it gives very definitive advice – eat this – don’t eat that. The reality is, this could save the GP at least 15 minutes discussion time, and provide a ready reckoner for the woman negotiating the local café menu or shopping centre food halls.

There is no debate, the pregnant woman, especially the first-time pregnant woman represents a very vulnerable, information-hungry demographic. Keep this site bookmarked and you won’t be sorry.

>> Access the resource here

An uncommon fungal infection from farm animals

Introduction

Trichophyton verrucosum is a cosmopolitan zoophilic dermatophyte. The normal host for this organism is cattle and occasionally horses. Human infection is acquired through direct contact with these animals or contaminated fomites, usually following minor trauma to the skin.

Figure 1. Case 4 developed lesion after contact with beef cattle

Aim

To review cases of T. verrucosum infection diagnosed over a five year period.

Method

The Sullivan Nicolaides Pathology data base from 2009 – 2014 was searched for isolates of T. verrucosum.

The laboratory services Queensland and extends into New South Wales as far south as Coffs Harbour.

Results

Seven cases of T. verrucosum over a five year period time frame that identified more than 12,500 dermatophyte infections in total.

The most recent case (7) was a 54-year-old retired meat worker who owns a small property with one beef and three dairy calves all of which suffered from fungal infection. After clearing lantana and sustaining multiple scratches he developed a non-healing inflammatory lesion on his forearm which healed after three weeks of oral griseofulvin with some residual scarring.

Biopsy, bacterial and fungal cultures all demonstrated fungal infection and cultures grew T. verrucosum. Scrapings collected from his infected cattle also demonstrated large spore ectothrix infection and grew this dermatophyte.

Cases included six males and one female (Table 1). The age ranged from 27–71, mean 45 years.

All except one (Case 5) had association with cattle with one also with horses. The site of infection was the forearm (5) (figure 1), leg (1) and face (1). Case 6 developed her leg lesion after birdwatching and camping on a cattle property although did not have direct contact with cattle.

Three patients underwent skin biopsy and histology and in only one was hyphae seen on tissue sections.

Four of five bacterial cultures also grew T. verrucosum on bacterial agar. Unlike other dermatophytes growth is enhanced at 37^OC. The cases were concentrated in SE Queensland and Northern NSW.

Four of the cases required systemic antifungal therapy to clear and a number were treated with several courses of antibiotics prior to the diagnosis being established.

Table 1: Culture positive cases T. verrucosum infection SNP 2009-2014

Conclusion

1. verrucosum is an unusual zoonotic infection of the skin causing a highly inflammatory response involving the scalp, beard or exposed areas of the body in contact with cattle and horses.

Fluorescence under Wood’s ultra-violet light has been noted in cattle but not in humans.

Unlike other dermatophytes, growth is enhanced at 37^OC.

Systemic therapy is usually required to clear the infection which is frequently mistaken for an inflammatory bacterial infection, initially being treated with antibiotics.

Advice on clearing the infection from animals was seen as important.

To read more or view the original summary click here 

– General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

Closing the Immunisation Gap in Older Australians

This article discusses how GPs can improve the vaccination coverage among older Australians which is currently poor despite the ready availability, safety and effectiveness of these vaccines.

Written by A/Prof Michael Woodward AM, MB, BS, MD, FRACP, and A/Prof John Litt MB, BS, DRACOG, MSc(Epid), FRACP, FAFPHM, PhD

Cardiovascular Risk and Testosterone Supplementation

This article examines the evidence for the cardiovascular safety of testosterone replacement therapy in older men with non-specific symptoms and unexplained low testosterone levels.

Improving vaccination rates in pregnancy

Increasingly, pregnant women are heeding the warnings about the dangers of pertussis and getting vaccinated but the same does not appear to be happening with influenza protection.

According to an Australian retrospective analysis, pertussis vaccination of pregnant women in Victoria increased from 38% in 2015 to 82% two years later. However, when they looked at rates of influenza vaccination the prevalence fluctuated according to the season but even so, the overall rate was only 39%.

Looking first at the factors that appeared to influence whether a woman got vaccinated at all, the researchers found women who were older, who were having their first child, attended antenatal care earlier in the pregnancy and who were receiving GP-led care were more likely to receive immunisation (thumbs up for the GPs).

On the negative side, the likelihood of vaccination was significantly lower in women born overseas, those who smoked during pregnancy and among Aboriginal and Torres Strait Islander women.

Overall it appeared the more contact a pregnant woman had with the health system, especially if that contact was with health professionals who are well-versed in all things immunisation, ie GPs, the more likely it was that vaccination would be offered, accepted and delivered.

The variation in coverage rates across different hospital-led organisations reflects the fact that immunisation for flu and pertussis has not yet become part of standard, best practice guidelines for routine antenatal care.

“Fewer than half the respondents indicated that vaccines were always or usually administered during routine antenatal care,” they wrote.

Following on from these general observations, researchers tried to determine why it was that vaccination coverage for pertussis rose so dramatically between 2015 and 2017, and why coverage for influenza prevention didn’t.

“This may reflect continued promotion by state and national bodies of the importance of maternal pertussis vaccination, and increased awareness among pregnant women of the seriousness of pertussis in infants,” they said.

By contrast, the researchers suggest that influenza is often believed to pose a greater health risk to the mother as opposed to the infant, and this along with concerns about the safety of the flu vaccine itself may, at least in part, explain the poor uptake of this vaccine.

To improve this situation and increase rates of protection for Australian pregnant women and their children, the study authors had a number of recommendations.

Most importantly they suggest we need to build vaccination against pertussis and influenza into the standard of care for all antenatal practices – be they hospital based, midwife-led or part of the GP antenatal shared care program. Basically we need to bring vaccination up and centre into our consciousness, so women get offered the vaccine and then ensure our systems have the capacity to be able to provide this vaccination as the opportunity arises.

“Maternal vaccination should be embedded in all antenatal care pathways, and systems should be improved to increase the uptake of vaccination by pregnant women,” they conclude.

Other recommendations included highlighting the benefits of vaccination to those groups of women most at risk such as women who smoke and Aboriginal and Torres Strait Islander women. But key to all the recommendations is making vaccination just part of routine care.

As an accompanying editorial points out, “Embedding vaccination into standard pregnancy care, whether delivered by GPs, midwives or obstetricians, normalises the process, improves access to vaccination and reduces the risk of missing opportunities for vaccination.”

References:

Rowe SL, Perrett KP, Morey R, Stephens N, Cowie BC, Nolan TM, et al. Influenza and pertussis vaccination of women during pregnancy in Victoria, 2015-2017. Med J Aust 2019 Jun 3; 210(10): 454-62. DOI: 10.5694/mja2.50125

Marshall HS, Amirthalingam G. Protecting pregnant women and their newborn from life-threatening infections. Med J Aust 2019 Jun 3; 210(10): 445-6. DOI: 10.5694/mja2.50174

Smartvax

It’s only been around a few years, but this little bit of technology has already received world wide acclaim for its ability to improve the safety of vaccines in the real-world setting.

In simple terms, Smartvax is a program practices install into their software system that sends an SMS directly to patients three days after they receive a vaccination. Patients are asked if they experienced an adverse reaction to the vaccine. A straightforward Yes (Y) or No (N) is all that is required. A No reply ends the conversation, but a Yes will trigger a brief questionnaire that examines the nature of the adverse reaction.

If the reaction resulted in the need to seek medical attention this is then flagged in the GP’s software inbox as well as with the local health authority.

In practical terms this means adverse reactions are tracked in real time and act as an early warning signal that something could be amiss with a vaccine. Smartvax was developed by Perth GP, Dr Alan Leeb and Ian Peters, following a spate of serious and unexpected adverse reactions among young children who received one brand of flu vaccine back in 2010. It was apparent that a better, more time-sensitive system of monitoring side effects to vaccines was needed to ensure the safety of patients.

With the widespread use of mobile phones, the day three post vax text has proven a very effective means of tracking reactions, with a high level of acceptance by patients. In a study from one NSW general practice, the response rate to the SMS  text was 85% post-childhood vaccination, and even in the over 65 year age range the response rate was 74%.

Smartvax has now been adopted by more than 280 practices around Australia. The technology can also be used as a reminder system to prompt patients when their next vaccine is due.

This is such a clever idea and as general practice becomes more and more tech savvy one can envisage a day when Smartvax is a basic requirement for all clinics that provide vaccinations.

>> Access the resource here

All benzos risky in pregnancy

Benzos increase the risk of having a miscarriage in early pregnancy, regardless of whether you’re taking a short-acting one for insomnia or a longer-acting one for anxiety, Canadian researchers say.

According to their large case-controlled study involving almost 450,000 pregnancies, benzodiazepine exposure in early pregnancy was associated with an 85% higher risk of spontaneous abortion compared to pregnancies where that class of drugs were not taken. And this increased risk remained the same, after a whole range of possible confounders had been adjusted for, including maternal mood and anxiety disorders.

But this isn’t the new bit. Previous research, including both a UK population-based study and an Israeli prospective study had confirmed the link between benzos and spontaneous abortion. In Australia, benzodiazepines have been given a Category C rating in terms of safety in pregnancy. (Drugs owing to their pharmacological effects have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations.)

“Benzodiazepines cross the placental barrier and accumulate in the fetal circulation at levels that are one to three times higher than the maternal serum levels”, the researchers explained.

What hasn’t been known, to date, is whether this is a class effect or are some benzos worse than others.

Well – according to this study published in JAMA Psychiatry – ‘the risk was similar among pregnancies exposed to short-acting …and long-acting benzodiazepines during early pregnancy.’

So it didn’t matter if you were prescribed long-acting clonazepam or short-acting lorazepam (interestingly the two most frequently prescribed benzos), the risk was more or less the same.

“All benzodiazepine agents were independently associated with an increased risk of [spontaneous abortion],” the study authors said.

In addition the study found the risk increased as the daily dose of benzodiazepines increased, suggesting a dose-response effect. So basically the more doses of benzos a pregnant woman takes, either in terms of strength or duration, the greater the risk she will miscarry.

Overall, the researchers concluded that pregnant women should avoid taking benzodiazepines, and if they have to take them only take the lowest dose possible for shortest duration possible.

“Alternative nonpharmacologic treatments exist and are recommended, but if benzodiazepines are needed, they should be prescribed for short durations,” they concluded.

Reference

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

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