Richard Lehman’s journal review—18 July 2016

richard_lehmanNEJM 14 July 2016 Vol 375
Olanzapine stops chemo vomiting
134 For about five thousand years, doctors sought out plants that would make their patients vomit, believing that this would expel noxious humours. In this week’s NEJM there’s a good example of this in an interesting short piece about early clinical trials featuring Adrien Helvétius (1662–1727) who introduced ground ipecacuanha root (ipecac) from Brazil. It was still given to children who had taken accidental overdoses when I was a junior doctor. But the true benefactors of mankind today are those who discover powerful anti-emetics to help people taking cancer chemotherapy. Many anti-emetics have been discovered by chance, and the latest of them is olanzapine. We’re used to seeing it used as an antipsychotic which causes somnolence, weight gain, and type 2 diabetes. But over the last two or three years it’s been increasingly used short-term as an anti-emetic for cancer patients. This trial shows that it is highly effective even at the extreme end of the vomiting spectrum. It was compared with placebo in combination with dexamethasone, aprepitant, or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. I think I shall start taking olanzapine half an hour before switching on the news. It might prevent that strange feeling of nausea and being about to go mad.

Anything worth watching on the telehealth?
154 A couple of weeks ago I warned readers that I am keeping a special vat of boiling oil in readiness for anyone who uses the word “telehealth.” Here’s a review article on the “State of Telehealth” but I will spare its authors the deep-fry treatment because they include a nice long section on its limitations and are thoughtful and realistic about what it can and can’t do. Most trials in developed countries have tried to use it as a substitute for face-to-face contact in people with chronic conditions, in the hubristic belief that we know enough to micromanage them and keep them out of hospital. Not surprisingly, nearly all of these have failed and some have shown harm and increased service use. But it’s in the developing world that the real potential lies. Here there are more mobile devices than lavatories. I love it that the authors have spotted how children can use i-phones as vectors of knowledge and progress within their communities: it’s a theme that Andy Oxman, Iain Chalmers, and Trudie Lang are already exploring in different ways, and I’m hoping that the Gates Foundation will back it too.

Vom++ Rx??
177 To coincide with the olanzapine study, here’s an open-access interactive discussion piece about chemotherapy-induced nausea and vomiting. The question is how you apply trial-based evidence ahead of time to individual patients. If you know the answer, then please step forward. We shall make you the new God of Medicine.

Beta-lactam antibiotics for TB
OL The most interesting unpublished item on the NEJM website currently is a letter with the subtitle “New Trick for an Old Dog.” Within each tuberculosis bacterium lies a beta-lactamase gene which has managed to outwit attempts to block it using clavulanic acid in the past. But in a pilot trial in South Africa, patients with highly resistant TB showed a very good initial response when IV meropenem was added to clavulanic acid with amoxicillin. Even if it just works as initial rescue therapy, this sounds like a good trick using cheap old drugs.

JAMA 12 July 2016 Vol 316
@POTUS & affordable care
OL He hasn’t gone yet, but for me Barack Obama already inspires a kind of nostalgia. He has goodness. This was thwarted by malign opposition at every point of his presidency, but by some miracle the Affordable Care Act made it onto the statute book. Obama takes pages to describe its achievements. It is not a single-payer, universal system; it is full of misaligned incentives; and the USA continues to have the world’s least cost-effective health care delivery system. But for Americans, the ACA represents a step forward. “As this progress with health care reform in the United States demonstrates, faith in responsibility, belief in opportunity, and ability to unite around common values are what makes this nation great.” Please let the US continue this way under its next president. These are the values of the world and not of any one nation, and if we do not unite around them we are stuffed.

Progress with HIV
While the JAMA website has lots of commentary pieces reflecting on its presidential scoop, the print version is taken up with articles about human immunodeficiency virus. When I started writing these reviews in 1998, HIV infection had just made the transition from being a death sentence to being a containable condition. People were still arguing about the best antiretroviral drug regimens and CD-4 counts, as they still do. But GPs like myself had long been cut out of the loop, and I wisely decided that I would not cover articles about HIV and its treatment, since they were the exclusive province of specialists. I do wish I had done the same for coronary stents and most aspects of nephrology. There are few worse places to learn about such things than from my weekly emissions. Yet still I persevere, though the escape clause on HIV remains. If you want to read the articles, all of this week’s are free on the JAMA website.

JAMA Intern Med July 2016
OL Over the last ten years of my time as a GP partner, we came under increasing pressure to cut down on prescribing benzodiazepines to help people sleep. Observational evidence (since contested) blamed them for falls in the elderly. Their prescription still awakens moral displeasure. Consequently, elderly people are given other drugs with really serious adverse effects: tricyclic antidepressants and trazodone which commonly cause serotoninergic poisoning when combined with SSRIs and/or tramadol, and antipsychotics like risperidone and quetiapine which cause daytime somnolence, parkinsonism, diabetes and weight gain. A survey of admissions to a clinical teaching unit in Canada confirms the popularity of quetiapine in particular (it’s the sound of its name I suppose). About 45% of the admitted patients aged 65 or over were on 10 or more drugs and about 12.5% were on quetiapine. Many others were given it for sleep during admission. This misuse of quetiapine is quite disquieting I opine.

Talking badly about serious illness
OL Doctors are supposed to have communication skills, and this narrative review looks for evidence of their existence. It finds that “Timely and effective communication about serious illness in primary care is hampered by key clinician barriers, which include deficits in knowledge, skills, and attitudes; discomfort with prognostication; and lack of clarity about the appropriate timing and initiation of conversations. Finally, system failures in coordination, documentation, feedback, and quality improvement contribute to lack of conversations.” If I have counted right, that makes nine major domains of need: enough to challenge the whole of medical education from pre-clinical to the highest grade of specialism. The training that doctors get, the evidence tools they are given, and the systems they surround themselves with are no good when tested against the needs of people with serious or complex illness. Much of the current discourse about “shared decision making” is an attempt to address this. But it needs to go wider and deeper than that. It will take decades of listening to patients, reforming professional training, acquiring new skills and designing new systems of minimally burdensome care to meet this challenge.

Lancet 16 July 2016 Vol 388

The Lancet is using the summer to print off the large backlog of articles it had acquired on its website, leaving me with nothing new to comment on from this week’s paper copy. On the website there is another global survey of body mass index in relation to health.

How global is your BMI?
OL I guess how you read a paper like this depends on where you are, how old you are, and how fat you are. You’ll skip the text and try to find yourself on one of the figures matching your BMI with your mortality risk. The take home message for me is that the older you are, the less it matters whether you are fat. This is what I want to hear. It’s quite another matter for the under-40s. Much as it pains an anti-puritan like me to admit it, obesity really is a massive population health problem for developed countries. It was quite different when I grew up in England. Food was generally so horrible that you ate as little of it as you could. Now that it is nice, I eat as much of it as possible. It’s a race between the menu and the funeral. The strength of this new survey is that it draws data from the group you probably belong to, limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up. It’s a wonderful example of the classic Lancet global health article, based on studies of over 10 million people across four continents. What it really cries out for though is a link to some interactive infographics to play with à la David Spiegelhalter or Hans Rosling.

BMJ 16 July 2016 Vol 354
The hidden death of
On Brexit vote day, I was going to chair a discussion at Evidence Live about how NHS patient data might best be made available for research, perhaps via a modified, safeguarded version of Then I heard that the key report by Dame Fiona Caldicott, which was supposed to appear in February, was not going to appear until after the EU referendum vote. So the session was cancelled, and on the Friday morning we woke up to hear that due to a cock-up fuelled by internal Tory party politics, the UK was taking a massive step backwards. Instead of leading the world in making population health data from the NHS available with adequate safeguards, was to be wound up with nothing to replace it. I guess that in the general dismay and political chaos that followed that morning, most of us haven’t given this the thought we otherwise might have. So full marks to The BMJ for making it the lead story this week, with thoughtful editorials by Fiona Godlee and Nicola Perrin, and a good analysis piece. I particularly like the idea of patients holding their own data, though the devil will be in the detail. Whatever happens, Britain will have missed an opportunity to lead the world in data sharing for common benefit. And so much else.

OL Julia Hippisley-Cox was one of the first to appreciate the potential of electronic GP records for observational research, and her QResearch database continues to provide key insights and generate patient-important hypotheses. Due to the historic failures of interventional research in type 2 diabetes, we have a very inadequate knowledge of the effects of many commonly used glucose-lowering drugs. This study looked at the records of 469 688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015. For anyone who prescribes drugs to such patients, this is a must-read. We are doing them some good: for example, compared with non-use, gliptins were significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart failure, and no significant change in risk of cardiovascular disease; corresponding values for glitazones were significantly decreased risks of 23% for all cause mortality, 26% for heart failure, and 25% for cardiovascular disease. But alas, this kind of data analysis cannot substitute for randomised trials. As Ben Goldacre and others have repeatedly pointed out, it should be very simple to set up a system of instant randomisation where there is equipoise in treatment choices within primary care. The NHS is ideally placed to lead in this. But I suspect that it is not on Jeremy Hunt’s list of priorities, if indeed he has one for the continued existence of the NHS.

Plant of the Week: Trifolium ochroleucon

Summer holiday time brings childhood memories of playing in fields and parks, of dust or sand or mud, and tumbling among plants and grasses gone rank or sweetly fragrant. I hope most English children still now and again pick the brown and yellow flowers of meadow clover which smell of honey and grass. We used to hunt for the four-leaved stems which bring luck: trifoliums are obviously only meant to have three.

The larger trifoliums are a bit hard to place in a small, well-ordered garden. They really need the semi-wildness of a bank that is left to look after itself most of the time. We have adopted just such a bank beyond the fence of our proper garden. So when we saw a big yellow-flowered clover at Coton Manor, we had to buy it. It is a lovely sprawly thing with a smell more lemony than that of field clover, but just as sweet. It will be hard to leave it to the mercies of our council owned bank but that is clearly where it belongs. Maybe it will naturalise there, as we hoped a dozen previous victims might. Now and again, one actually manages.