{"id":46684,"date":"2020-02-20T05:10:45","date_gmt":"2020-02-20T04:10:45","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=46684"},"modified":"2020-02-20T05:10:45","modified_gmt":"2020-02-20T04:10:45","slug":"alex-nowbars-journal-reviews-20-february-2020","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2020\/02\/20\/alex-nowbars-journal-reviews-20-february-2020\/","title":{"rendered":"Alex Nowbar’s journal reviews\u201420 February 2020"},"content":{"rendered":"

Alex Nowbar reviews the latest research from the top medical journals.<\/p>\n

\"\"<\/b><\/p>\n

Annals of Internal Medicine<\/b><\/em><\/p>\n

Treatment in advanced HIV infection<\/b><\/span><\/p>\n

Levy et al<\/a> performed a multinational randomised controlled trial in people with advanced HIV infection who had never taken anti retrovirals. This was an important study because of the large numbers of people diagnosed with HIV at a late stage. These French researchers compared addition of maraviroc to combined anti-retroviral therapy with the addition of placebo in a double blind fashion. Maraviroc blocks entry of HIV into cells but is also thought to have additional immunologic effects which the researchers thought might help in untreated people. The primary endpoint was first occurrence of a severe morbidity including serious infections, immune reconstitution syndrome and death. There was no difference between the two groups. Strengths of this study\u2019s design include adequate length of follow-up (72 weeks) and the use of clinically relevant endpoints (not just biomarkers).<\/span><\/p>\n

CMV vaccine victory<\/b><\/span><\/p>\n

The Triplex vaccine is designed for people who have received an allogeneic haematopoietic stem cell transplant and have latent cytomegalovirus because of the great challenges in keeping cytomegalovirus\u00a0at bay in this context. The name Triplex is generated by the presence of three small pieces of cytomegalovirus\u00a0DNA inserted into the weakened modified vaccinia Ankara virus (this virus is used in a number of other vaccines). In this double-blind US trial<\/a>, 102 people were randomised to the vaccine or placebo. At 100 days, there was cytomegalovirus\u00a0reactivation in 10% of people in the vaccine group compared with 20% of those in the placebo group. This result is encouraging. As this was a phase 2 study, one of the most important outcomes is that no safety concerns were identified. There is a slight niggle about the dosing schedule. All participants received a dose 28 days after transplant and most again at 56 days. More doses may be needed but caution was required for giving a new vaccine to immunocompromised people.<\/span><\/p>\n

JAMA<\/b><\/em><\/p>\n

Comparing devices <\/b>in\u00a0patients with\u00a0myocardial infarction<\/strong><\/span><\/p>\n

People having a myocardial infarction can get into real trouble. Cardiogenic shock is a serious complication, but there are a few methods for haemodynamic support. One method is an intra-aortic balloon pump. Another is an intravascular microaxial left ventricular assist device (LVAD). The focus in Dhruva et al\u2019s<\/a> retrospective US cohort study is on rates of in-hospital mortality and in-hospital major bleeding rates for the intravascular microaxial LVAD. The weakness of this study is the observational design. It is difficult to draw conclusions about clinical outcomes when confounders cannot be eliminated (propensity matching mitigates this but it\u2019s still not ideal). But I will try to dispassionately report the figures. The death rate in the intravascular microaxial LVAD group was 45% and 34% in the balloon pump group. The major bleeding rates were 31% in the LVAD group and 16% in the balloon pump group. It is important that registry work like this is done but this contentious and life-on-the-line area still needs work (ideally in randomised form).<\/span><\/p>\n

JAMA Internal Medicine<\/b><\/em><\/p>\n

Reducing low value laboratory tests<\/b><\/span><\/p>\n

It is delightful to see these American researchers examine changes in use of two low-value laboratory tests covering over 50 million people after a policy change (the Choosing Wisely recommendations of 2010). And what is low value stuff? The examples in this study<\/a> are quite apt: vitamin D deficiency screening and T3 level testing. The lack of value in these strategies is still unbeknownst to many. The truth is that vitamin D deficiency treatment across the population doesn\u2019t improve outcomes and that thyroid stimulating hormone is sufficient for monitoring hypothyroidism. The reductions in testing rates in 2013 and 2014 were very modest most of the assessed jurisdictions. One jurisdiction did have a 93% relative reduction in vitamin D screening though. That was associated with elimination of reimbursement for this in Ontario, Canada. This suggests that recommendations alone had little impact, but changes in payment structure were more effective. However this is circumstantial evidence, and not a comprehensive analysis of the impact of policy changes in all regions. I suspect that the data that were used were accessible and detailed enough for the purpose, rather than comprehensive prospective data.<\/span><\/p>\n

Lancet<\/b><\/em><\/p>\n

Accelerated hip surgery vs. standard care<\/b><\/span><\/p>\n

The eye-twitchingly named HIP-ATTACK trial<\/a> randomised almost 3000 people with a hip fracture requiring surgery to either accelerated hip surgery (i.e. within 6 hours) or standard care. This international 69 centre study is impressive. Death rates were similar in both groups. The other primary endpoint was a composite of major complications including myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia and major bleeding). There was also no difference in rates of these outcomes. These are good endpoints, by which I mean, relevant and largely objective. And adjudication of the outcomes was done in the optimal fashion, by investigators masked to the randomisation arm. This is not to say that timing of surgery isn\u2019t important anymore. The authors also report \u201cAccelerated surgery was associated with lower risk of delirium, faster mobilisation, and a shorter length of hospital stay.\u201d They also conclude that the accelerated pathway is safe and feasible, but I\u2019m not sure how strong an argument that is for implementation when this strategy was not effective for the primary endpoints.<\/span><\/p>\n

Covid-19 in late pregnancy<\/u><\/b><\/span><\/p>\n

I hesitate to say there is any good news about coronavirus at the moment, but in this very small sample<\/a> of pregnant infected women (9 of them), the virus was not passed onto the offspring. Six of the nine had amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples tested. They were all negative. The major caveat is that the virus was likely contracted in late pregnancy so these results may not apply if the virus is acquired earlier in gestation. The second caveat is that all of the women had C-section deliveries. Therefore we are none the wiser about transmission risk with vaginal delivery. The third caveat is that none of the women had severe covid-19 so again these results may not apply to pregnant women who contract severe covid-19.<\/span><\/p>\n

NEJM<\/b><\/em><\/p>\n

Bold breast cancer drug findings<\/b><\/span><\/p>\n

This study about CDK4\/6 inhibitors, the<\/span> MONALEESA-3 trial, is quite exciting. Slamon et al<\/a> randomised women with hormone-receptor\u2013positive, HER2-negative advanced breast cancer to either ribociclib plus fulvestrant or fulvestrant alone. In 2018 this pharma-sponsored Phase 3 trial indicated a reduction in progression-free survival with the combination therapy. This report looks at overall survival in an interim analysis and found criteria were met for stopping the study. At this point there was a 34.5% death rate in the combination group and 44.6% death rate in the placebo group. This difference is statistically significant. There were of course more adverse events in the treatment group, particularly neutropenia and hepatobiliary toxicity. But dare I say it, this is a positive study showing great promise for prolonging life in advanced breast cancer.<\/span><\/p>\n

Alex Nowbar<\/strong> is a clinical research fellow at Imperial College London<\/span><\/i><\/p>\n

Competing interests:<\/strong> None declared<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Alex Nowbar reviews the latest research from the top medical journals. […]<\/p>\n

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