Richard Lehman’s journal review—19 September 2016

richard_lehmanNEJM  15 Sep 2016  Vol 375

Preherpetic vaccines in the old
For most people who get shingles, the rash and discomfort last for a couple of weeks and then gradually remit. The point of a shingles vaccine is to prevent post-herpetic neuralgia, an uncommon, unremitting condition which can blight people’s lives. Age increases both your chances of getting shingles and the risk of it causing postherpetic neuralgia. The title of this paper is “Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older” and “Medical writing was provided by 4Clinics, France, with funding support from GlaxoSmithKline Biologicals.” So let’s see what effect this vaccine had on rates of postherpetic neuralgia. “In the pooled modified vaccinated cohort that included all participants 50 years of age or older, postherpetic neuralgia developed in 4 of 32 HZ/su recipients and in 46 of 477 placebo recipients with herpes zoster, during a mean follow-up period of 3.8 years.” By slipping in the word “pooled,” the writers from 4Clinics, France have merged two trials and are no longer reporting on ZOE-70 alone, as they did up to this point, but adding in the over-70 subset from ZOE-50. And in so doing they also reveal that in the over-50s trial, there were no cases at all of postherpetic neuralgia under the age of 70. By that token, I can’t see any point in giving the GSK vaccine to people under the age of 70, especially as it causes a local reaction and/or fatigue in the majority of recipients. But maybe that is not the message that we are meant to take away. **See note below**

Waiting versus intervention for PSA-detected cancers

Everyone will by now be aware of this massively important British trial which did PSA tests on 82,429 men 50 to 69 years of age, and randomised 1643 to active monitoring (545 men), surgery (553), or radiotherapy (545). “There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group, 5 in the surgery group and 4 in the radiotherapy group; the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups).” So in the second week of September 2016, every urologist in the world knows that PSA screening detects very few cancers that are ever going to kill men, and that they will be equally alive at ten years whether you watch them or operate or give them radiotherapy. This is an ethnographer’s dream. Imagine that you were studying cargo cults on three Melanesian islands and that after many years, cargo boats arrived at all three in the same week. None of them contained anything more than a few rats and the odd bag of tea. What would the believers do? Sacrifice the rats and wait for another boat? Worship the bags of tea? Give up the whole idea and become cargo atheists? Please somebody—go out there and study urologists’ behaviour from henceforth and for five years.

JAMA  13 Sep 2016  Vol 316

Cardiac MRI to reduce angiography?

This week’s JAMA features two articles about cardiac care in the UK. This first one describes how a group of British investigators went about testing the hypothesis that among patients with suspected CHD, cardiovascular magnetic resonance (CMR)–guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines–directed care and myocardial perfusion scintigraphy–guided care in reducing unnecessary angiography. To me, the most interesting thing is that it was a publicly funded trial which explicitly sets patient importance above public health importance, though it ended up informing both. “It remains a point of debate as to whether all of protocol-defined unnecessary angiograms in this study were clinically unnecessary; some would argue that negative tests are the “price to pay” for not missing important disease in others. This assumes a population perspective, and our trial primary end point was derived after close consultation with patient and public representatives: from an individual patient perspective, an angiogram that does not change their treatment or their clinical outcome is considered by patients to have been unnecessary.” Bravo. The pre-test probability of the participants having occlusive coronary disease was nearly 50%. Having CMR resulted in fewer angiograms than following NICE guidance. The number of major adverse cardiovascular events was the same in all groups. I really like the way this trial was done and written up. It leaves lots of questions unanswered but it helpfully lists them all, and shows impressive thought and honesty throughout.

NSTEMI management in England & Wales

The Journal of the American Medical Association is also the place to find out about the management of non-ST myocardial infarction in England and Wales between 2003 and 2013. This report is based on data on patients with NSTEMI in 247 hospitals in England and Wales obtained from the Myocardial Ischaemia National Audit Project. It’s great that we had this audit going across so many centres, but I think the Scandinavians did even better when they set up the randomised FRISC trial at the same time, as I reported last week. Anyway, we are doing something right: “Among patients hospitalized with NSTEMI in England and Wales, improvements in all-cause mortality were observed between 2003 and 2013. This was significantly associated with use of an invasive coronary strategy and not entirely related to a decline in baseline clinical risk or increased use of pharmacological therapies.”

JAMA Intern Med  Sep 2016

Sugar industry tricks

As I get older, I become more of a defeatist about good and evil. That’s illogical, because I was born only five years after the end of Hitler’s war. Until I reached the age of 40, the world was threatened by nuclear annihilation. The world is now a far better, healthier, and happier place. But this year we seem to be unlearning all the lessons that lead to peace and prosperity, and it could still get much worse. What really bugs me is that there seem to be so many people who don’t mind distorting the truth even though they know it will harm millions. I suppose it was ever thus, as this paper about the sugar lobby of the 1960s and 70s demonstrates. “Together with other recent analyses of sugar industry documents, our findings suggest the industry sponsored a research program in the 1960s and 1970s that successfully cast doubt about the hazards of sucrose while promoting fat as the dietary culprit in CHD.” Checking Amazon, I see that contrary to urban myth, John Yudkin’s prophetic 1972 book about the sugar lobby, Pure White & Deadly, is currently available as a cheap paperback. Non-DOI: the living John S Yudkin is a friend of mine but will gain no royalties from this book, which was written by his deceased uncle.

Sex differences in MI

A sudden drop in temperatures reminds me that England is generally too cold, meaning that Norway must be basically uninhabitable. No wonder Norsemen plundered and settled every warm place they could find, from Sicily to North America. People in Norway get heart attacks, like people everywhere. And Norwegian women get fewer than Norwegian men, like women everywhere. Nobody knows why, and after this population-based prospective study from Tromsø, Norway, we still don’t. “The observed sex contrast in risk of MI cannot be explained by differences in established CHD risk factors. The gender gap persisted throughout life but declined with age as a result of a more pronounced flattening of risk level changes in middle-aged men.”

Lancet  17 Sep 2016  Vol 388

Malaria & mosquito trapping

Sometimes it is nice when a trial fails, even a malaria trial. Actually this one didn’t exactly fail, but the investigators thought they had the right power for a definitive cluster-randomised trial, and in that they were disappointed, because the incidence of malaria was so low during their study. The intervention was a solar-powered odour-baited mosquito trapping system. It doesn’t sound all that effective to me: overall, 2660 trap-nights of mosquito monitoring recorded 651 female Anopheles mosquitoes during the 100-week intervention period. Perhaps they should try a different fragrance. Still, the clusters with perfume  machines installed had significantly lower malaria prevalence than did those without them during the entire intervention period of 24 months. The authors conclude that, “The unexpectedly low clinical incidence of malaria during roll-out led to an imprecise estimate of effectiveness from the clinical incidence data. The substantial effect on malaria prevalence is explained by reduction in densities of Anopheles funestus.” It doesn’t quite add up to me. I’m sure I’ve been in holiday rooms with at least 651 female mosquitoes in them.

BMJ  17 Sep 2016  Vol 354

AF and patient outcomes

Let this be a week of peace and harmony between The BMJ and The Lancet. In the print edition of the latter journal is an article on atrial fibrillation across the world, which I reported on a couple of weeks ago. On the website of The BMJ is a systematic review of AF outcomes, led by a doctoral student. Both convey the same message: AF confers a much higher relative risk for heart failure than for stroke, and is associated with a wide range of cardiovascular modes of death. These include renal failure if, like me, you regard the kidneys mainly as clearing stations for the cardiovascular system.

Hyperglycaemia in pregnancy

“What is gestational diabetes and how would you treat it?”, I was asked as a medical student in 1974. How certain everything was then. Last week I suggested arrogance as a motive for those who would have us announce simple solutions for complex questions. But maybe it is just nostalgia. “This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes.”

E-cigarettes & quitting

I was glad to see this study in The BMJ because I feared the journal was “taking a stance” against e-cigarettes. I am always troubled when scientific journals take stances, especially when they seem to contradict the evidence, but also when they over-egg it. It’s been clear for some time that e-cigarettes are used extensively and successfully as quitting aids. And that is the main message from this series of cross-sectional studies. May they have harms if used long-term? Possibly. Are they made by tobacco companies? Certainly. Can they induce nicotine addiction? Yes. But overall they are so effective an answer to the blight of combustible tobacco that we could reasonably use them to end its sale, if any government so wished.

Fungus of the Week: Calvatia gigantea 

It’s giant puffball week again. Each of these amazing fungi is designed to grow beyond the size of a soccer ball and then to burst in a great black cloud containing more spores than it would take to cover the entire planet, if they all germinated. It is your duty, therefore, to hunt these fungi and remove them before their spores have had time to mature. The future of the Earth hangs in the balance.

Take your giant puffball and treat it thus. Cut it in half with a long sharp knife. If it shows signs of going yellow or brown or grey within, put it in the compost bin. If it is pure white and of a firm consistency, telephone your friends and announce a Puffball Feast. Bring out a heavy iron pan or skillet. Into this place a good quantity of the fattiest bacon you can find, and melt it until the meat is dark brown and floating in half a centimetre of fat, with a blue haze above. Into this pan place sections of puffball, to fry until brown on each side. Since the middle section of a proper sized puffball is the size of a large frying pan, you will need to keep doing this for a good while. Meanwhile your guests need to be furnished with glasses of a good white wine—Gavi is ideal—and a heap of finely chopped chives & parsley and the means to grind salt and pepper, to garnish for themselves the slices of puffball. They will go “ooh” and “aah” while you continue to work in a cloud of fatty smoke. Continue at the pan until the puffball is finished, drinking Gavi di Gavi the while. Your final slice will be covered with black bacon residue and the herbs will all have gone, but you will have done your duty by your friends, and that is what counts.

**note about Preherpetic vaccines in the old. A reader pointed out on Twitter that there was no PHN in the vaccine group but there were 12 cases in placebo group for NNT 491 at 4 yrs. **