Richard Lehman’s journal review—26 June 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM  22 Jun 2017  Vol 376

A better, faster flu vaccine?

At present, influenza vaccines are made by growing viruses in eggs. Recombinant techniques produce vaccines much more quickly (within 6 to 8 weeks instead of 6 months) with haemagglutinins that are identical with those of the target viruses, and without any extraneous material. In the future it may even be possible to add additional protective antigens to these vaccines. That’s the sales pitch here, from Protein Sciences: how did the trial of their flu vaccine go in real life Americans aged over 50? Their quadrivalent, recombinant influenza vaccine (RIV4) was about 30% better than egg-derived vaccine: 2.2% of participants got PCR-confirmed influenza, compared with 3.2% in the egg-based vaccine group. Personally I’d be rather blasé about such a risk difference in an ordinary flu season, but come the next lethal pandemic, I might feel differently. A tailored flu vaccine that could go into scaled production within 8 weeks has to be a comforting thought.

Positioning after stroke

Here is a trial of liedownumab versus propupizumab for the management of acute stroke. Billions of dollars hang on the efficacy of these new agents. Actually, this is not true: they cost absolutely nothing. It was just a trial of positioning the patients in bed: lie them down or prop them up. In this Australian cluster-randomised trial, 11,093 patients with acute stroke (85% of the strokes were ischaemic) received care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees for 24 hours. There was no difference between groups in death, disability, or rates of pneumonia. How good to see a simple well-powered trial that puts a clinical question to bed. Flat out or propped up. Fair dinkum.

JAMA 20 Jun 2017  Vol 317

BRCA1 and BRCA2 mutations and cancer risk

An analysis of several databases from the UK, Netherlands, and France provides new quantification of the risk of breast or ovarian cancer in nearly 10,000 women with BRCA1 and BRCA2 mutations. The cumulative breast cancer risk to age 80 years was 72% for BRCA1 and 69% for BRCA2 carriers, and the figures for ovarian cancer were 44% and 17% respectively. But the great value of this study lies in the detail on the time course of these risks and their relation to family history and mutation location. It’s a step towards being able to offer the individualized advice that these women badly need.

High dose vitamin D use in US adults

While academics and guideline writers argue about the optimal dose of vitamin D, the great American public has taken matters into its own hands. The National Health and Nutrition Study for 1999-2000 showed that 0.3% of the population sample were taking vitamin D at doses above 1000iu per day. This had risen to 18% overall by 2013-14. In fact over a quarter of American women and 38.5% of over-70 year olds now take high dose vitamin D. The US populace doesn’t have gun control, and they soon won’t have healthcare, but they will go to their graves well saturated with calciferols.

JAMA Intern Med  Jun 2017  Vol 177

Faecal immunochemical testing in high risk patients

Always beware of a conclusion in a systematic review where the “quality of evidence (trustworthiness) for all results was very low.” Reviewers who have put an immense amount of work searching through rather rubbishy trials and collating the figures are bound to want a message to give to the world at the end, and here it is that faecal immunochemical testing has “high overall accuracy” for colorectal cancer but moderate accuracy for advanced neoplasia when screening asymptomatic adults at high risk. But the caveat is the important bit: “Heterogeneity and wide confidence intervals limit the trustworthiness of our findings.” Like so many systematic reviews of diagnostic strategies, this one is bedevilled by confusing terminology and the problems of aggregating data from different contexts. In the end, we just need a huge well-designed new trial of faecal immunological testing as a first-stage screen in people with a family history of colon cancer or previous adenomas.

Ann Intern Med  20 Jun 2017 

Yoga or physio for chronic back pain?

Think yoga. What do you see? Middle-class, young-to-middle-aged thin white people sitting with their eyes closed, their legs crossed, their backs straight and their arms held in front of them. But think again: this trial of yoga versus physiotherapy for chronic back pain went out of its way to recruit 320 predominantly low-income, racially diverse adults with nonspecific chronic low back pain. They received an awful lot of yoga: 12 weekly sessions. Or even more physio: 15 visits. Both interventions had minimal effect on self-reported pain or function at 12 weeks, compared with an educational book and newsletters; though both were associated with 21-22% reduction in pain medication compared with the education-only group.

The Lancet  24 Jun 2017  Vol 389

Women with AAA fare badly

Although abdominal aortic aneurysms are four times commoner in men than women, that’s not a sufficient excuse for the relative paucity of information about the management of female compared to male AAA. This systematic review helps to make up for that. It’s a painstaking analysis of the trials that contain enough information about the characteristics of the unruptured aneurysms to make meaningful comparisons between outcomes in women and men. They are much worse. Fewer women have aneurysms that are morphologically suitable for endovascular repair, and those who are suitable have a 30-day post-operative mortality of 2.3% compared with 1.4% in men. The overall estimate for open repair also was higher in women (5·4%) than in men (2·8%). In observational studies, the difference tends to be even greater.

Onlay mesh to prevent incisional hernia

The aim of the PRIMA trial was to evaluate the effectiveness of mesh reinforcement in high-risk patients, to prevent incisional hernia.” Next look at the funding source: Baxter; B Braun Surgical SA. The trial used a lightweight polypropylene mesh (Optilene mesh LP, 6 × 35 cm; B Braun Surgical SA) used with a fibrin sealant (Tisseel; Baxter Healthcare). But it wasn’t just a trial of these products: it had three arms to compare onlay mesh reinforcement, sublay mesh reinforcement, and primary suture. And it found that onlay mesh reinforcement had a stronger and more significant effect on prevention of incisional hernia than did sublay mesh reinforcement. I would make an abominable abdominal surgeon, but I think this is useful knowledge for the tribe.

The BMJ  24 Jun 2017  Vol 357

Deaths from cancer fall far less than CVD

The words “burden” and “toll” always crop up in articles about cardiovascular disease and cancer. Oddly I quite like to read “you’ve got to die of something” articles, even though I can feel my turn coming up soon. The bell will toll and I will no longer be a burden: there’s a certain comfort in the thought. Here is an almost Lancet-style paper called “Benchmarking life expectancy and cancer mortality: global comparison with cardiovascular disease 1981-2010.” There are some dainty mobile infographics to be enjoyed on the website. As everybody gets fatter and less active, rates of cardiovascular disease are falling rapidly. Cancer, however, is falling less fast. I don’t understand the authors’ conclusion, which seems to assert that it is all a matter of control, and that women, who are offered HPV vaccine and cervical and breast cancer screening, are neglected compared with men.” The control of CVD has led to substantial gains in life expectancy (ages 40-84) worldwide. The inequality in improvement in longevity attributed to declining cancer mortality rates reflects inequities in implementation of cancer control, particularly in less resourced populations and in women.”

Physical activity does not stave off dementia

On a personal level, I believe physical activity is a good thing and would gladly do more of it given the time. Whatever it staves off on a population level I will leave for others to determine. Dementia is not one of them, as this 27-year (28 in the title) follow-up of the Whitehall II cohort demonstrates. To stave off dementia you have to spend your weekends sitting at a PC writing reviews of the medical literature. Though even now I am having doubts.

Plant of the Week: Abutilon “Nabob”

This week in June usually marks the very height of garden glory in England. Ours looks lovely, though just a touch too blue. The problem is that if we see something with clear blue flowers on it in a nursery we buy it and think later. All our scarce horizontal space is already taken up.

Abutilon “Nabob” is a darkish but very hot red, which we hope will provide an antidote to excessive blue coolness. Moreover it will take little space as it is as much vertical as horizontal.

Like most abutilons, it should flower throughout the year, if it survives our rural climate. My London son has one which flourishes on a protected wall in Dulwich, while ours will have to take its chances on a nippier Cotswold surface. In an ideal world, I would take cuttings and protect them in a frame, but so far I have failed to get a frame. So we will probably buy another abutilon next year.


  • kidmugsy

    “As everybody gets fatter and less active, rates of cardiovascular disease are falling rapidly.” Or, as immune systems get better at fighting the causative micro-organisms (whatever they may be) the epidemic dwindles away.