Richard Lehman’s journal review – 24 October 2011

Richard LehmanJAMA  19 Oct 2011  Vol 306
There are definite green shoots of recovery in this week’s JAMA. Howard Bauchner hasn’t yet made the sweeping changes he’s promised, but there’s a nice mix of papers and the poetry remains as thrillingly bad as ever.

1659   A few weeks ago, The Lancet ran a couple of papers about desperate remedies for Shiga-toxin producing E coli, indicating that plasma exchange might be a life saving treatment. Here is the equivalent observational study for severe acute respiratory distress syndrome caused by H1N1 influenza. Patients whose blood gas levels could not be maintained in a local intensive care unit were either kept there or sent to one of four hospitals in the UK which offer extracorporeal membrane oxygenation (ECMO). This was not randomization, and only afterwards were their characteristics matched using software called GenMatch. But for all the obvious limitations of this study, the result is pretty convincing: similar patients stood twice the chance of survival if they received ECMO.

1669   I first started following the epidemiology of heart failure in the mid-1990s, and kept coming across the name Harlan Krumholz on all the best papers from the USA. And still they keep coming: here is a painstaking study of the patterns of heart failure mortality and hospital admission in all 50 states of the USA, plus DC and Puerto Rico, between 1998 and 2008. Deaths have hardly declined but hospital admission rates are down by 29%. The work that went into this classic analysis of Medicare data by Jersey Chen is mind-boggling. Now I myself am working in Harlan’s unit, so I have the privilege of attending their fortnightly publications-in-progress meetings; and I can assure you that this river of good studies is not going to dry up any time soon.

1679    And next a nice little piece of Canadian detective work. Manufacturers of haemodialysis membranes had taken to sterilizing them using electron beam radiation. Coincidentally, a few haemodialysis patients had their blood counts done post dialysis and were found to be short on platelets. This isn’t all that unusual, but gradually a pattern began to emerge. Patients dialyzed on the new machines in British Columbia, with electron-beam sterilised membranes, were getting thrombocytopenia, whereas those on older machines weren’t. Was this a specific manufacturer problem or did it apply to membranes supplied by a different manufacturer, also using electron-beam sterilization, in Alberta? Indeed it did. I rest my case, m’lud: the electron beam is guilty as charged. And the charge is −1.602×10−19 coulomb per electron.

1688    Hospital readmission is a complex phenomenon, governed by a wide range of factors, as every GP knows. The nature of the disease, the availability of supportive care in the community, social circumstances, patient anxiety, adequacy of follow-up, compliance with therapy etc etc. – how can you put all these and a hundred more into a risk prediction model? Very inadequately, is the conclusion of this systematic review. Still, that’s not going to stop the UK government using readmission data as a stick to beat GPs; or is it hospitals? Or both, perhaps. Someone should make the Coalition cabinet sit down for a day listening to the limitations of multiple regression analysis. If nothing else, it would be a dreadful punishment for their crimes.

NEJM  20 Oct 2011  Vol 365
Almost the whole of this issue of the New England Journal is free, because it is about tuberculosis in people with HIV infection. Try to put yourself in the position of a health worker trying to save the lives of hundreds of such patients in the conditions of an under-resourced clinic in Cambodia or India or Botswana. You have no diagnostic facilities to speak of, though perhaps you can do chest X-rays and even CD4+T- cell counts if a generous donor has been your way. Each of these patients will need three antiretroviral drugs, three anti-TB drugs and probably antibiotic and antifungal cover too. Depending on what you do, the patient may make a full recovery or else die of galloping TB if you give the antiretroviral therapy (ART) before the anti-TB drugs, or AIDS if you give ART too late, or immune reconstitution inflammatory syndrome (IRIS) if you start treating the TB too early or in the wrong patients.

Three trials here reach similar conclusions. Treat the TB first for two weeks, then start ART. Don’t worry too much about IRIS except in people with generalised TB or TB meningitis.

1520   Panretinal Photocoagulation for Proliferative Diabetic Retinopathy is a common treatment which we leave to clever ophthalmologists with clever machinery. It is amazingly successful for the most part, and it works by burning away hypoxic pigment cells in the peripheral retina which soak up oxygen and produce vascular endothelial growth factor, both of which are very bad things for the viable cells in the macula. Early treatment has been shown to give the best results, though the absolute benefit is small. Read all about it here.

1541    The film Contagion gets a four-star rating in this week’s BMJ, confirming the views of my wife and a friend who came away impressed and scared. Given that influenza viruses can mutate and mingle so dangerously, how can we ensure the survival of civilization as we know it? Step forward Corti et al. who screened 104,000 plasma cells from donors who had antibodies to three diverse influenza types, and discovered just four cells which carried a universal anti-influenza antibody. They then performed an exact characterization of the antibody. So the Holy Grail has been found! Now we need to fashion the Holy Spear which will defeat the hordes of Satan, in the shape of a universal influenza vaccine.

Lancet  22 Oct 2011  Vol 378
1461   There’s nothing that Richard Horton likes better than to sound off about issues of global health, and the best thing about The Lancet under his editorship has been the endless stream of papers delineating various aspects of global epidemiology. This latest effort is concerned with breast and cervical cancer in 187 countries between 1980 and 2010. Skim through the text and pore over the multi-coloured world maps and incidence charts if you have a subscription to this strange publication. How much more useful these prodigious compilations of data would be if they were posted free on  – the most interesting website in the world if you are interested in global issues.

1485    But of course The Lancet is also the standard bearer of rigorous British standards of medical research and publishing. Here is a trial paid for by Weight Watchers International. Participants with BMI between 25 and 35 were randomised to Weight Watchers or standard care. The overall dropout rate was around 43%. According to Figure 2, those completing the WW programme ended up with a mean weight of 80kg as compared with 84kg in the standard care group, which is the biggest difference the data can bear. This figure is a classic example of how to make small differences look big by chopping off the bottom end of a scale. Two different intention-to-treat analyses show that WW was about 2.3-2.8kg superior at 12 months. So those of us who advise our patients to try Weight Watchers are vindicated; they may lose an extra 5-7 pounds in a year, provided they are not seriously obese to start with. The authors naturally conclude that with such an effective intervention already available on everyone’s doorstep, there is no need for health systems to indulge in expensive provision of their own. We have no way of watching the weight of reprints that The Lancet now sells to Weight Watchers.

BMJ  22 Oct 2011  Vol 343
How can you tell when someone is genuinely close to suicide? This is not an easy subject to investigate and I was impressed by this qualitative study of those close to 14 people aged between 18 and 34 who had killed themselves. There is way to summarise the findings of as complex a study as this, but I agree wholeheartedly with the Conclusion: “Efforts to strengthen the capacity of lay people to play a role in preventing suicide are urgently needed and should be informed by a thorough understanding of these difficulties. They should highlight the ambiguous nature of
warning signs and should focus on helping people to acknowledge and
overcome their fears about intervening.”

Polycystic ovary syndrome is an endocrine disorder with ill-determined boundaries and uncertain treatment, but the label definitely means something in terms of fertility, diabetes risk, and birth outcomes. This Swedish cohort study sheds some light on the obstetric risks, by comparing outcomes in 3787 births in women with the label of PCOS with over a million other births. PCOS confers a 25-69% added risk of pre-eclampsia, and more than doubles the risk of gestational diabetes and very premature birth. Babies born to such mothers tend to be large-for-dates, to have lower Apgar scores, and are more liable to meconium aspiration.

“Estimating treatment effects for individual patients based on the results of randomised clinical trials” – how about that for a bold title? It’s just what we’d like to do for everybody all the time. But when we come to look at the randomised trials, for example of glucose lowering in diabetes, we find that the trials of the last 40 years tell us exactly nothing useful about the treatment effects for individual patients using any agent. This paper is an academic exercise based on the JUPITER trial of rosuvastatin. It introduces the new concept of NWT – number willing to treat. I in turn suggest a new measurement for articles of this kind – the NWR – number willing to read. I am afraid that I am not of this number. It is true that we can extract some extra information for clinical decision-making by better modelling using existing data. But until human experimentation using drugs and devices is taken entirely out of the hands of people with an interest in marketing them, and is designed by consensus to reach end-points that matter to patients, we shall merely be trying to produce better filters for muddied water which mostly remains undrinkable.

“Non-responding” presumed lower respiratory tract infection in primary care is the stuff of general practice: no winter week will pass without us seeing a few cases. This article is about a 49 year old lady who is not satisfied by her improvement after a week’s course of antibiotics. It is written by a clinical research fellow and a hospital chest physician: it is very unlikely that they ever see such ladies, except socially. But they trundle through the pros and cons of various investigations and then conclude that the general practitioner may wish to point out that acute cough can take two or three weeks to resolve and may not need a further antibiotic. Gosh. It’s uncanny how these people have learnt our skills.

Ann Intern Med  18 Oct 2011  Vol 155
481    In the USA, mammography is a belief system and is to be approached with the respect which polite people accord to the irrational. If people here are ever going to be weaned from the belief that it is in their interests to have their breasts squashed and irradiated every year, and biopsied for lesions that may never do anything, then it must be done very slowly. This paper makes a beginning by showing that outcomes are just the same if you do mammography every two years instead of every year. The same authors proceed to show that digital image capture has no clear advantage over conventional breast radiology.

520   Hospital readmission is a complex phenomenon, governed by a wide range of factors, as every GP knows. The nature of the disease, the availability of supportive care in the community, social circumstances, patient anxiety, adequacy of follow-up, compliance with therapy etc etc. Oops, am I repeating myself? We’ve already read about this in JAMA – there it was about risk scores for readmission, here it’s about interventions to reduce 30-day readmission. And would you believe it – if you do a systematic review, none of these interventions can be shown to work consistently. It’s almost as if this is not a simple problem with a simplistic answer.

Plant of the Week: Acer saccharum

This is the Sugar Maple, a great source of income to the peoples of northern North America both from the syrup it produces and from the spectacular beauty of its autumn leaf colour, which fills the guest houses of Vermont and Maine and Canada with troops of “leaf-peepers” at this time of the year.

Syrup tapping is a spring activity, as the sap rises in the trees when the sun gets stronger. Maple syrup is still collected entirely in the wild from vessels placed under pipes hammered into this species of maple and the closely related Black Maple, A nigrum. Vermonters rise at frosty dawn for several weeks of the early year to identify these trees and collect their sap as it is squeezed out by the alternate action of frost and sun. They sell postcards depicting visitors who knock their tapping pipes into telegraph poles.

The Sugar Maple also has hard wood which is valuable as timber. Do not confuse it with Acer saccharinum, the White Maple, which has brittle, useless wood and no sugar. It is only useful for bringing down power cables in windy weather, and lifting up paving slabs with its shallow roots.