6 May, 14 | by BMJ
NEJM 1 May 2014 Vol 370
1702 Britons, mourn. Our biggest drug company, GlaxoSmithKline, had a potential blockbuster on its hands. Darapladib would stabilise unstable plaque, everybody would want to take it, and GSK would make billions. But, although darapladib is a selective oral inhibitor of lipoprotein associated phospholipase A2, which is an enzyme associated with plaque instability, 8000 people with stable coronary artery disease took it for three years with outcomes no different from the 8000 people who took placebo. Britons rejoice. The NHS will not have to pay for millions of prescriptions for darapladib. We have enough wonderfully effective substances already for the secondary prevention of cardiovascular events: fruit, fish, alcohol, aspirin and statins. And nuts.
1724 In the lush undergrowth encouraged by a mild wet winter, ticks that feed on animals will abound, says the BBC News website. Beware Lyme disease, my fellow countrymen. Its traditional home is in Connecticut, where the winters are never mild, but ticks still abound. The NEJM features an excellent review of this condition to coincide with the start of the annual season. I hope they will forgive me for excerpting a chunk summarising what every doctor should know:
• Erythema migrans lesions often do not have central clearing; the majority either are uniformly erythematous or have enhanced central erythema.
• Antibody testing of patients with erythema migrans is not indicated routinely because of poor sensitivity in detecting early infection.
• Treatment with doxycycline, amoxicillin, or cefuroxime is safe and highly efficacious for early Lyme disease.
• A single 200 mg dose of doxycycline reduces the risk of Lyme disease in persons bitten by Ixodes scapularis ticks; however, it is not indicated routinely (given the low risk of transmission from a tick bite even in areas where the disease is endemic) and is contraindicated for pregnant women and for children younger than eight years of age.
• There is no evidence that patients treated for Lyme disease who have persistent, non-specific symptoms (e.g. arthralgia and fatigue) have persistent infection; the risks of prolonged treatment with antimicrobial agents far outweigh the benefits, if any.
JAMA Intern Med May 2014
OL A big US database study confirms what we had already been told in systematic reviews of serotonin reuptake inhibitors for children and adolescents. High doses of SSRIs double the risk of deliberate self harm compared with “modal” doses: there was approximately one additional event for every 150 such patients treated with high dose (instead of modal dose) therapy. Just don’t use these doses: there is no logic in increasing risk when there is no evidence that higher doses confer any benefit.
JAMA Vol 311
OL There is no printed JAMA this week. But to make our loss easier to bear, they have put online a short viewpoint called “Reducing the Trauma of Hospitalization.” In January last year, you may remember, the NEJM printed a piece by Harlan Krumholz on Post-Hospital Syndrome—An Acquired, Transient Condition of Generalized Risk. This described the dysfunctional features of hospital care, which render some patients so vulnerable that they get readmitted within a week or two of discharge, often with a different principal diagnosis from the first admission. Here Harlan is joined by Allan Detsky in proposing some solutions. These are:
• Promote personalisation
• Ensure that patients receive enough rest and nourishment
• Eliminate unnecessary tests and procedures
• Decrease random medication alterations
• Encourage activity
• Provide a post-discharge safety net
Download this piece: it is free, and covers two pages. Send it to the manager of your local hospital. Send it to the patient user group. Ask how these issues are going to be addressed. One day it may be your turn to road test the system.
Lancet 3 May 2014 Vol 383
1549 Smoking is an unfortunate addiction with many harmful effects, but I’ve never been very convinced about the effect of tobacco smoke on other people. The evidence always seems to be of a lower standard than we have a right to expect. Banning smoking in public places was a good measure for reasons of courtesy rather than health, but there is some evidence that it may have had some health benefits too. It all depends on how well you believe that broad-brush before and after data can be freed from confounding. I’m inclined to let you decide for yourselves. “Five North American studies described local bans and six European studies described national bans. Risk of bias was high for one study, moderate for six studies, and low for four studies. Smoke-free legislation was associated with reductions in preterm birth (four studies, 1 366 862 individuals; −10•4% [95% CI −18•8 to −2•0]; p=0•016) and hospital attendances for asthma (three studies, 225 753 events: −10•1% [95% CI −15•2 to −5•0]; p=0•0001).”
1561 When I read meta analyses I look for something to guide the way I discuss treatments with patients. I may not be an oncologist, but I do occasionally see people with early stage non-small cell lung cancer, and I would like to be able at least to help them understand what treatments others may be planning for them. It is a great anomaly that multi-disciplinary cancer teams seldom involve patients themselves in these decisions. This meta analysis tells me that “preoperative chemotherapy significantly improves overall survival, time to distant recurrence, and recurrence-free survival in resectable NSCLC. The findings suggest this is a valid treatment option for most of these patients.” OK, so it’s valid. And what about the down side? “Toxic effects could not be assessed.” That won’t do: for sharing decisions with patients, you need both the number needed to treat and the number needed to harm, plus an understanding of the weighting that each individual gives to each benefit and each harm.
1593 “Preschool wheeze is . . . highly prevalent; about a third of children aged 1—6 years in Europe and the USA have wheezed in the preceding 6 months, and almost 50% of children report at least one episode of wheeze in the first 6 years of life.” Now that I do mainly out of hours acute primary care, I see more of it than ever. There still seems to be a widespread habit in UK general practice to pin the label “asthma” to children, even in the first year of life. I much prefer the term “preschool wheeze,” which is the subject of this review, but the authors are not ideally clear about the distinction—probably because one can’t be. Hidden away in the depths of the text is what I think is the most important message: “pre-emptive medium doses of inhaled corticosteroids at the first and subsequent wheezing episodes in infancy do not prevent progression from episodic to persistent wheezing, and convey no statistically significant symptom relief.” Almost all the brown inhalers given to young children are useless. And yet not so long ago, the ratio of “preventer” to “reliever” inhalers given out was regarded as a quality measure.
BMJ 3 May 2014 Vol 348
Studies conducted in the USA now abound in The BMJ, which hopes to extend its transatlantic readership. This article begins: “Disability is a leading driver of healthcare costs, accounting for more than one in four dollars spent on healthcare.” Well, I suppose if they had said one in four of our quaint British pounds, the message would have been the same. And the fact that lots of low intensity activity slows the progression of disability in people with early knee arthritis no doubt applies equally to the aging denizens of Wigan, Ipswich, and Yeovil as to those of Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island, USA.
Those who peered into the living rooms of middle aged British doctors this weekend would have seen some strange sights. Persons of both sexes with greying hair would solemnly sit in a chair and then get in and out of it repeatedly as fast as they could. They would then close their eyes and stand on one leg until they toppled over. They would then consult their watches and either smile or frown. Many of the frowners would then have a second go. Such is our desire to know how long we are likely to live: and by now you have probably already read this paper, which tells us you can do just this at the age of 53 by performing the above mentioned tricks and by measuring grip strength. When I was little I used to think 53 was impossibly old, now I think it is impossibly young. I think that age marked the transition between my being a pessimist carping from the sides to being a pessimist wanting to achieve something before I die. If you take that attitude, you won’t really mind when you die. On the one hand, you won’t have achieved everything you wanted; but on the other, you will have achieved something, and can look forward to having a rest.
A while back I suggested in these reviews that the major journals should refuse any further papers about stem cells for regenerating myocardium until one of them showed some positive effects on patient important outcomes. Ten years ago, this concept was exciting and it was reasonable for hope to triumph over cold reality; but, as the reality has stayed cold, the converse now applies. Yet, as a recent Cochrane review update suggested, there are some studies that have faintly positive outcomes, though with a high risk of bias. Darrel Francis and the DAMASCENE team went further and performed the exacting task of looking at all the trials to discover whether their sums add up. The results of this brilliant analysis are quite damning: there was a direct relationship between figures that contradicted each other and alleged increases in ejection fraction following autologous bone marrow cell administration:
People who go out of their way to eat cereal fibre (The BMJ actually spells it “fiber” here) are not typical. They are “health conscious” and are likely to wear sandals, ride bicycles, grow their own vegetables, and all sorts of other things that I might do myself were I ever to acquire the skill and inclination. They have a low risk of myocardial infarction and a higher chance of surviving it if they do experience an event. This is not surprising. What is surprising is that anyone supposes you can isolate this component of behavior (sic) while adjusting for all the rest.
Book of the Week: The Science of the Art of Medicine by John Brush
Like all of you, I rarely read a medical book at all, let alone from cover to cover. It’s become a truism that all medical texts are out of date before they are printed. This book is a rare exception, and I would even go so far as to say that it will be read in a hundred years’ time and still have valuable things to say. Moreover it does not have covers and it is not printed.
You were among the brightest of your class at school. When you got a place at medical school, you realised that you only had to persevere for five or six years, well within the limits of your abilities, and you would have a job for life. You were taught innumerable facts and skills, and then you were cast into the real world of hospital medicine. You were often tired, you sometimes wished for patients to die so that you could get some sleep, you made mistakes and they did die, and you lay awake and wondered what you should have done differently. Gradually you learnt your own coping skills: things first done arduously became instinctive, and you also learned through the camaraderie of those who shared your stresses, mistakes, and triumphs.
That is how you learned the “Art of Medicine.” Do you feel it was the right way? Do you feel you now know how to do it better than anyone else? If so, there is absolutely no need to read John Brush’s book. You should instead write one of your own. But I bet it won’t be as good.
Here is a fuller account of what I think about it. It is free, it is beautiful, and it is short. I defy any clinician to read it and not benefit.