Richard Lehman’s journal review – 20 June 2011

Richard LehmanJAMA  15 June 2011  Vol 305
2419    Here is a study which may have major resource implications for you and your commissioning group, because it seems to show that there is no mortality benefit over 6.7 years in men who undergo bariatric surgery. You can relax: there will be no need to find money to pay Barry the surgeon after all. But this appears to conflict with previous observational evidence, and there are plenty of unanswered questions about high-risk subgroups, particularly diabetic patients. So you had better pay close attention to this paper, and that is no easy task: essentially you are being asked to examine various methods of matching and comparison. Simply eyeballing the characteristics of the 850 surgical cases and the 41 244 controls, there are major differences in age and BMI, but these were then eliminated by one-to-one propensity matching. Let me direct you to the summary: “In unadjusted Cox regression, bariatric surgery was associated with reduced mortality (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.51-0.80). After covariate adjustment, bariatric surgery remained associated with reduced mortality (HR, 0.80; 95% CI, 0.63-0.995). In analysis of 1694 propensity-matched patients, bariatric surgery was no longer significantly associated with reduced mortality in unadjusted (HR, 0.83; 95% CI, 0.61-1.14) and time-adjusted (HR,0.94; 95% CI, 0.64-1.39) Cox regressions.” Go on – after reading it a few times, you will understand. At least I think you will, but you can imagine how terrifying it is for a superannuated Brit GP to try and look savvy in a room full of super-bright young Americans who get this sort of stuff immediately and then move straight on to Bonferroni corrections and chi-squared testing.

2440    Now here is the kind of outcomes research even I can understand: patient has myocardial infarction, local emergency department is on divert so ambulance is diverted, twelve hours are lost. This is in California, a big state, but it’s still hard to credit a 12-hour delay – and does it matter? It sure does. These MI patients are more likely to be dead at 30 days, 90 days, 9-months and one year.

NEJM  16 June 2011  Vol 364
2282    The chief conceptual triumphs of preventive medicine date back to the nineteenth century, the age of public sanitation and vaccination. Both are still needed in the twenty-first century if the mortality from rotavirus gastroenteritis in infants and children is going to be reduced in developing countries. The countries in question here are Mexico and Brazil, which have introduced a policy of universal vaccination with the monovalent vaccine RV1. The aim of the study was to determine whether this vaccine carries a significant risk of causing intussusception and how this might compare with the mortality reduction from rotavirus infection. As expected, the temporal association of the new vaccine with intussusception is much smaller than with its predecessor Rotashield, and the arithmetic approximates to one death from the complications of intussusception for every 250 rotavirus deaths prevented.

2293    Every 10-12 years, a belt of Africa from Ethiopia to Senegal is struck by an epidemic of group A meningococcal disease – one of those oddities that bacteriologists like to tell us about, and which we ought by now to have brought under control. If all goes to plan, that may be what this vaccine study presages. A new MenA conjugate vaccine PSa-TT was tested on babies and on individuals between 2-29 years of age, and showed better immunogenicity than a previous quadrivalent polysaccharide vaccine. There is good reason to believe that the new vaccine, unlike the old, will produce a durable response and will reduce carriage – if given on a whole-population scale, as envisaged by Bill and Melinda Gates.

Lancet  18 June 2011  Vol 377
There isn’t much to engage the generalist in the research published in The Lancet this week – not even much occasion for scorn or indignation. A rather weak Australian study finds a 38% reduction in CIN-1 cervical lesions following a HPV vaccine programme, which the Abstract announces as a 0.38% reduction. A global survey of health in adolescence and young adulthood provides a mass of largely unsurprising data. A trial of novel chemotherapy for colorectal cancer proves negative.

But The Lancet announces that it will be running a new kind of Clinical Series from this week onwards, promising to explain the latest findings from basic research and at the same time provide a practical guide for the clinician. We begin with Arthritis:

2115   Osteoarthritis: an update with relevance for clinical practice delivers what it promises. The problem is that our knowledge of osteoarthritis hasn’t advanced greatly, and I was hard put to find any new learning points in this review, worthy and comprehensive though it is.

2127   The next article also combines French and Dutch authorship but is a very different beast. The purported subject is Spondyloarthritis, described as “a group of several related but phenotypically distinct disorders: psoriatic arthritis, arthritis related to inflammatory bowel disease, reactive arthritis, a subgroup of juvenile idiopathic arthritis, and ankylosing spondylitis (the prototypic and best studied subtype).” I was looking forward to enlightenment about this perplexing group of related diseases associated with theHLA-B27 tissue type, but practically the whole of the article refers exclusively to AS. The cellular mechanisms section settles on interleukin-23 as a potential therapeutic target, beyond tumour necrosis factor α. In fact I’ve now read so many of these papers that I can almost understand when they say that “TNF would simultaneously drive destruction and inhibit remodelling by the Wnt pathway by upregulating Dickkopf-related protein 1.” You too can reach this level of enlightenment if you read this article, but I don’t think you will find much here to help you identify and treat spondyloarthritis amidst the endless procession of joint aches you see every day.

2138   And so to the third article, dealing with juvenile idiopathic arthritis. There is a big overlap with the subject of the previous paper, because as the authors remark, “enthesitis-related arthritis is a form of undifferentiated spondyloarthropathy.” I have no idea what that might mean, but most of the sufferers are HLA-B27 positive and many go on to develop sacro-iliitis. However, the emphases in this account are quite different: the interleukins of interest are 1,6 and 18, and the disease marker of promise is ANA for diagnosis, and myeloid-related proteins 8 and 14 for disease response. If you really want to swank in rheumatological company you can also slip in the odd reference to FOXP3-positive Tregs.

BMJ  18 June 2011  Vol 342
Here is the latest study to make one wonder whether we aren’t doing more harm than good for many of our patients with chronic obstructive pulmonary disease. It’s a meta-analysis of the randomised controlled trials of a tiotropium mist inhaler which shows a 52% increase in mortality from the use of this anticholinergic in this form. Admittedly the absolute NNK (number needed to kill) for one year is 124; but given such clear evidence of harm, how did this stuff get licensed? By showing symptomatic benefit and a reduction of exacerbations, it seems. And how do bronchodilators kill people with COPD? The editorial speculates that it’s by helping cigarette smoke to penetrate the small airways more effectively – a hypothesis which should be testable.

For many years, I tried to ban discussion of wart treatment at our regular practice nurse/doctor meetings, but invariably someone would whisper “I know we’re not supposed to discuss warts, but…” and it would all start again. People like me who recommended salicylic acid application or no treatment would argue with others who felt we owed our patients a duty of wart care involving a supply chain for liquid nitrogen on certain days of the month. Now here should be an end to the debate. In this randomised trial, one is no better than the other. But even now, from my former practice, I can hear a soft murmur of dissent. As Henry Kissinger once said of academe, “The arguments are so fierce because the stakes are so low.”

I am completely baffled as to why anyone would want to carry out a case-control study of the association between (recollected) maternal sleep practices and late stillbirth, still more why any journal should want it to see the light of day. Is somebody proposing that high-risk women should sleep in a particular way? Or that mothers bereft in this way should feel to blame for lying awake on their left sides? Or that people can recollect their position while asleep? Bizarre.

However, just to drive home my point about the general quality of the BMJ’s Clinical Reviews, here’s an excellent practical account of the diagnosis and management of ectopic pregnancy.

Arch Intern Med  13 Jun 2011  Vol 171
977    Non-invasive cardiovascular imaging sounds good. This meta-analysis tries to determine whether it has any place in the primary prevention of CV disease. To my mind, the review casts the net much too wide. Coronary CT angiography, coronary calcium scoring, and radionuclide angiography all involve large doses of ionizing radiation: even if they had any demonstrable benefit in asymptomatic individuals, their advertisement to the general public would seem inadvisable. Nobody should have more than a couple of these tests in a lifetime if they can avoid it. As they have no demonstrable benefit, I think their promotion is unethical. The direct harm of exercise ECG and arterial ultrasonography, however, lies more in the inaccuracy of the tests and their likelihood of generating nothing but anxiety or false reassurance. And yet people love these awful screening procedures and attribute nothing but good to them, even when the harm in unnecessary intervention is extreme, as Lisa Schwartz and Steve Woloshin have nicely demonstrated.

998   Now one form of overdiagnosis that has become very popular is osteopenia leading to the prescription of bisphosphonates. These drugs in turn often cause oesophagitis or gastric irritation, and so countless old ladies dutifully take proton pump inhibitors every morning and a long-acting bisphosphonate on Sundays. Here is a Danish database study looking at how the use of a PPI might affect the rate of hip fracture in patients taking alendronate. It seems to show a dose-related decrease in the protection afforded by the alendronate: this needs confirmation from say the UK GPRD, but if true will need a whole new approach to bisphosphonate prescribing – yearly IV zolendronate for everyone, perhaps?

Plant of the Week: Taxodium distichum “Falling Waters”

The swamp cedar comes from the southwest USA but flourishes throughout the temperate world. The standard form grows to 30m and more and is widely planted in botanical gardens next to Metasequoia glyptostroboides, the dawn redwood, as a test for would-be tree experts. The taxodium has slightly finer, paler leaf-needles.

If you have a grand garden with a lake you should plant your mighty taxodium by the waterside or even in the water, as at the botanical garden of Cracow university. There it may reward you by forming large “knees” of root rising above the water. But if you possess merely a humble, dry little garden you may still grow this excellent tree and enjoy its autumn colour and ferny spring awakening. In the USA, and perhaps in the UK too, there is now a weeping form which won’t grow much above 5m. In the botanic garden at Smith College, Mass, they have a couple of these grown into a pergola – very nice too.