Richard Lehman’s journal review—9 December 2013

Richard LehmanNEJM  5 Dec 2013  Vol 369
2183   Respect: this trial collected nearly a thousand patients who survived out-of-hospital cardiac arrest and ended up in one of 36 intensive care units spread across Europe and Australia. They were then randomised to treatment involving hypothermia to 33 deg celsius—as recommended by current guidelines—or without hypothermia. This logistic feat proved worthwhile, because it shows that hypothermia achieves nothing. This futile procedure can be dropped at once. Cooling is not cool.

2207   Although I try to report advances in the management of myocardial infarction for you every week, if I had a heart attack myself I would have only the faintest idea what my options really were and what their relative harms and merits might be. Perhaps as I was sucking on my aspirin tablet, I might ask the paramedic to leave the blood pressure cuff inflated for about five minutes to achieve a bit of ischaemic preconditioning. I might call for a tot of cardioprotective brandy: they say it goes well with diamorphine. Has anyone done a trial of oral alcohol for acute MI? I suppose I would let the ambulance take me to the nearest catheter lab for PCI, although more than an hour might elapse before I even reached the hospital door. What should I accept on the way there? The Medicines Company hope that I would say bivalirudin. In the EUROMAX trial that they funded, 2218 people with AMI were randomised to either receive bivalirudin on the way to a PCI centre, or else a “optional receipt of a glycoprotein IIb/IIIa inhibitor.” A rather odd study design, made even odder by a change in the composite primary end-point after the trial had started. So compared with optional receipt of a glycoprotein IIb/IIIa inhibitor, and using the post-commencement composite end-point of death or major bleeding not associated with coronary-artery bypass grafting (CABG), “Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis.” Is that clear to everybody? Would you ask for bivalirudin in the ambulance?

2226    Amidst all the “what’s the world coming to” gloom around us, there are some very good things happening. In the last 25 years, we have seen the end of the Cold War, Mandela bringing peace to South Africa, mobile telephones for everybody, the internet, effective treatment for HIV, a steep decline in cardiovascular disease, and a massive fall in death rates among mothers, newborn babies, and children in the poor world. What a nice planet we could live on if only we were ruled by Mandelas and not bankers. People with their basic needs taken care of might feel free to enjoy being good rather than greedy. On the down side, this might breed a sense of entitlement in people who had not taken the trouble to be born into rich families. Further reduction of global maternal and child mortality is well within our grasp, according to this review article. See also “Global health 2035: a world converging within a generation” in this week’s Lancet. And in the BMJ, take a look at “Global determinants of mortality in under 5s: 10 year worldwide longitudinal study.

2236   And British GPs, wondering whatever will become of their patients and the NHS under a regime of perpetual Old Etonian austerity, should take comfort in the endless scientific fascination offered by medicine, as well as our unique ability to help people despite everything. If you find yourself gently sobbing about the effects of the Lansley Act, cuts to local services leaving your patients helpless, some new idiotic directive about what you must or mustn’t prescribe, the impossibility of recruiting a new partner, or some other little burden of the day, just read this review of mitochondrial diseases. It has a strangely soothing effect.

JAMA  4 Dec 2013  Vol 310
2262   This week’s issue of JAMA is allegedly devoted to medical education, though it takes a pretty broad view of its brief. The first paper is not about education at all but about “handoff bundles” for American paediatric residents. “Implementation of a handoff bundle was associated with a significant reduction in medical errors and preventable adverse events among hospitalized children. Improvements in verbal and written handoff processes occurred, and resident workflow did not change adversely.” Sounds good, but this was just a before-and-after study.

2271   The next paper is an important reminder that communication with patients is a serious medical intervention. In situations of maximal vulnerability, health professionals need to deploy the greatest skill in balancing honesty with reassurance and hope. Nobody can honestly reflect on a career in medicine and claim to have got this right every time. One way to help young professionals to hone their communication skills without risking harm to patients would be to use simulation-based training, and of course this is done in a wide variety of contexts. But the results of this randomised trial carried out over several years in two American centres are not reassuring. “Among internal medicine and nurse practitioner trainees, simulation-based communication training compared with usual education did not improve quality of communication about end-of-life care or quality of end-of-life care, but was associated with a small increase in patients’ depressive symptoms. These findings raise questions about skills transfer from simulation training to actual patient care and the adequacy of communication skills assessment.”

Lancet   7 Dec 2013  Vol 382
1879   The Lancet is a very odd journal, in case you hadn’t noticed. Some weeks it contains pharma-funded phase 2 trials of astounding clinical irrelevance; occasionally it contains important papers heralding major breakthroughs, or reporting massive RCTs; then there are some issues entirely devoted to health in a particular part of the globe you are unlikely to visit; last week the journal was all about sex and the British, in case you are thinking of having sex in Britain; and this week the entire research section is taken up with this analysis the safety and efficacy of drug-eluting stents in women, based on patient-level results from 26 randomised trials; plus a paper on risk stratification at diagnosis for children with hypertrophic cardiomyopathy. We seem to have wandered into the pages of Circulation rather than The Lancet. Anyway, the message from the stents-for-women analysis is that drug-eluting stents are safer than bare metal stents, and that second-generation drug-eluters are better than first generation. This is very much what pharma would like you to believe, so I am inclined to disbelieve it. But then neither I nor you, dear reader, are in a position to re-interrogate the data and the methods of 26 major trials. We must believe what we read, and buy the latest products.

BMJ   7 Dec 2013  Vol 347
For me, the best thing in this week’s BMJ is an editorial by Harlan Krumholz about the new cholesterol-lowering guidelines from the American College of Cardiology and the American Heart Association. Those who read this column regularly will realise that I am quite a fan of Harlan’s work, and in this case he can take some credit for a major change in policy by these organisations. For many years he has pointed out the fact that statins alone among LDL-cholesterol lowering drugs reduce cardiovascular risk, and that using them should depend on the level of risk, not the level of cholesterol. When he and Rod Hayward wrote an open letter to the guideline committee two years ago in Circulation: Cardiovascular Quality and Outcomes, there were dark mutterings about undermining public confidence in medical practice. But now the same people have looked at the evidence and come up with a guideline that embodies a model based on risk, and that acknowledges that cheap generic statins have a solid evidence base that other lipid-lowering drugs lack. Harlan generously acknowledges this change of heart. Nothing is more difficult for authority figures than to change their minds in public: look at the diabetes community, still wriggling around the issue of targets in type 2 diabetes. I think Harlan’s commentary is not only the best written, but also the most persuasive, of all the many that have appeared in the last two weeks. Several others have been excellent, including one by Ioannidis available free on the JAMA website.

This paper says that its objective was, “To examine the association between physical activity and risk of ulcerative colitis and Crohn’s disease.” Well, that may have been their objective, but it was not a pre-stated objective of the Nurses’ Health Study and Nurses’ Health Study II from which they took their data. These 194 711 women provide an almost unlimited playground for data dredging and hypothesis generating. Put this in fancy dress and you can come up with paragraphs like this: “In two large prospective cohorts of US women, increased physical activity was associated with a lower risk of Crohn’s disease, but not of ulcerative colitis. Whether these associations with disease incidence may imply a benefit of physical activity on disease activity in patients with existing Crohn’s disease is unclear and merits further study. In addition, further studies on the effect of physical activity on risk and progression of Crohn’s disease in the context of known genetic risk factors in autophagy and innate immunity pathways will help elucidate the mechanism underlying this association. Ultimately, this may lead to lifestyle interventions among subgroups with known genetic risk factors for Crohn’s disease to modify the risk of disease or among patients with established disease to limit its progression.” The whole thing reads to me like a bad case of autophagy.

Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis“—a usefully negative paper. The trouble is that probiotics may be “good germs” in some situations, but what you need to prevent wheeze in kids is bad germs. Poo. From pets, or other kids. Or both. Call it microbiome enrichment if you prefer. But start early and keep a nice dirty farmhouse if you want to avoid atopy in your offspring.

Plant of the Week: Levisticum officinale

“Levisticum officinale, is a tall perennial plant, the sole species in the genus Levisticum in the family Apiaceae, subfamily Apioideae, tribe Apieae.” This makes it sound more like something from Leviticus than plain old Levisticum, which is better known as lovage.

I knew nothing of lovage until my sixtieth birthday, which we decided to spend in a hotel right next to Lincoln Cathedral, close to where I was born. We had tracked down a nice sounding restaurant nearby called The Old Bakery, and put in a special request for oysters followed by crab, as these are my favourites. The nice young Italian chef sat us down and asked how we would like them served, and in an act of instant and well-merited trust, we left the decision to him. Both the molluscs and the crustaceans came with a light dusting of herbs, carrying a subtle taste I could not identify. This was lovage.

It took us a long time to acquire our own lovage plant, and when we did we didn’t really know what to do with it. Keeping the best things of life for old age, I did not eat my first ceviche until I went to Lima three years later. I have no idea what Peruvians usually put in these exquisite dishes, apart from fish, onion, and lime juice: even the fish is not usually named, though it is always fresh and good. But on coming home I was determined to try making my own ceviche and including lovage. It worked. Now we can’t bear the thought of ceviche without lovage, or for that matter going a week without ceviche.

The trouble is that when the first frosts came, the foliage of the lovage plant died instantly. So I had to go out and divide the roots (which can be eaten as a vegetable, by the way) and make many new plants by diving them and potting them up. I brought the biggest of the divisions inside to live on the kitchen windowsill and awaited events. Within two weeks it has sprouted an enormous leading stem with the promise of abundant leaf throughout the winter.

In the meantime we have experimented with a mixture of fennel leaf, celery leaf, coriander and parsley in our ceviche: most pleasant, but we are looking forward to an imminent reacquaintance with lovage.

  • deebles

    Speculation: if a patient, having an MI, possesses the fortitude to request a brandy, is it best to accede to their request (time and help allowing)?

    I’m tempted to say yes, not so much because of its ambivalent effects on fibrinolysis/coagulation, but more to keep them happy and, given that their request may indicate alcohol dependence, postpone the moment they go into withdrawal…