JAMA 20 July 2011 Vol 306
277 As I try to write, much of America lies torpid in a heat wave approaching 40 degrees centigrade. This issue of JAMA, like last week’s, seems to suffer from a sort of anticipatory heat stroke – not one of the research papers belongs in a generalist journal, and some of the commentary pieces really don’t belong anywhere. Perhaps it’s just me being irritable from the heat, as I sit lightly clad under a ceiling fan, sipping iced water. Takotsubo cardiomyopathy is a clinical curiosity which you are never likely to encounter unless you are a cardiologist in a tertiary centre, so the real achievement of this study was to collect 256 cases from Europe and North America. This is a form of acute heart failure in the absence of established heart disease, characterised by apical ballooning in most cases and complete recovery in all. The great majority of sufferers are postmenopausal women who have been subjected to some form of major stress, either physical or emotional. They managed to get all these patients into a magnet while they were still symptomatic and took some very nice pictures of ventricles looking like squeezed balloons and then going back to normal.
302 Here’s a commentary piece with the intriguing title, Prevention of Melanoma With Regular Sunscreen Use. Is melanoma caused by sun exposure? I don’t think anyone really knows. Previous papers have suggested that regular sunscreen use might even cause melanoma; whereas the two American authors here cite an Australian study as convincing evidence that using sunscreen will prevent melanoma. This was a ten-year follow up study of a four year intervention (lots of free sunscreen, applied to the head, neck and extremities) which demonstrated a “reduction of the observed rate of melanoma in those randomly assigned to daily
sunscreen use (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.24-1.02; P=.051).” In other words, the result did not reach significance. In fact the Journal of Oncology subsequently published a letter convincingly criticizing the methodology of this study and noting that the results could equally be interpreted as showing that sunscreen increases melanoma on the treated areas. But our earnest commentators nonetheless go on to advise the liberal use of sunscreen on large areas of the body which were specifically excluded in this study, and conclude their piece with the categorical claim that “Regular use of sunscreen can effectively reduce the risk of developing melanoma for at-risk individuals”. Enough: if you are interested, you can make up your own mind, as the Journal of Oncology has an open access policy. You can even write a letter to JAMA if you so wish. I am too hot and bored.
NEJM 21 July 2011 Vol 365
213 Collectors of choice studies from Framingham must add this classic to their collection. You couldn’t wish for a better teaching paper for advanced students of surrogate outcome measures and predictive scoring systems plus the statistical data interrogation methods you need for each. But there are some lessons for the ordinary clinician here too. Carotid intima-media thickness is often touted as an important tool in cardiovascular risk assessment that’s easily measured by ultrasound. Here nearly 3,000 members of the Framingham Offspring cohort underwent measurement of their carotid arteries and were followed up for just over 7 years, during which there were 296 events. The upshot is that maximal CI-MT adds little to conventional Framingham scoring except at the extreme upper values. It matters a lot how carefully you do the measurement as well. Far from being a cheap, quick way of improving CV risk measurement, CIMT remains a research tool; and even then, like all surrogates, is only useful for hypothesis generating, not for clinical decision-making.
231 Has it ever struck you that although eczema and psoriasis are very common, you hardly ever see them both together in the same person? Or indeed that eczema frequently gets infected while psoriasis does not? Perhaps these observations are so commonplace that no dermatologist ever bothers to mention them, while I was too dim to notice till quite late in my career. Anyway, the answer may well lie in T-cell function. Atopic eczema arises from a systemic Th2-cell–dominated immune shift characterized by frequent elevations of total and allergen-specific IgE levels. In psoriasis, by contrast, Th1 and Th17 T-lymphocytes drive a process which is mediated by interferons and interleukins. That’s the easy bit. If you want to know how these lymphocytes fight it out in those rare patients who have both conditions at the same time, go to this paper which examines three cases from Germany and Italy in minute immunochemical and histological detail.
239 Here is a good Italian-British-Australian update on Febrile Urinary Tract Infections in Children: “the most common serious bacterial infection in childhood,” as the opening sentence announces. So everybody who deals with febrile kids should read this piece: but I know that not many of you will. If you’re a jobbing clinician in the developed world, that would mean either subscribing to the NEJM or ordering a copy of the article from your local medical library: if you work in a part of the world where these infections create the highest morbidity, your chances of being able to afford this are close to zero. Sadly this applies to clinical reviews in all the journals I regularly review here, even the BMJ, which made a retrogressive commercial decision some years ago. If you want to do something about it, join HIFA2015, and write or edit your own review for Wikipedia, the most accessible and most accessed source of medical information in the world. And if you don’t think a Wikipedia article is very good, that’s your fault: get in there and make it better.
266 Now here is how it should be done: a case-based discussion of the Treatment of a 6-Year-Old Girl with Vesicoureteral Reflux – educative, interactive, web-based, and free. Three treatment options are presented: watchful waiting, prophylactic antibiotics, and reflux surgery. Persuasive cases are made for each and then debated on-line. Yet the review article (above) which would inform debate is for subscribers only.
Lancet 23 July 2011 Vol 378
319 It was a neat idea; it worked in a mouse model of type 1 diabetes; unfortunately it didn’t work in people. Good double-blind randomized trials with clear results are always a triumph for clinical science, however disappointing they may be for investigators and patients. The auto-immune process which causes catastrophic beta-cell loss in type 1 DM is heavily targeted towards glutamic acid decarboxylase (GAD), and animal experiments suggested that introducing exogenous GAD with adjuvant (alum) would modify this response. So 145 human subjects with recent onset T1DM were randomized to receive “immunization” with GAD alone, GAD with alum, or alum alone. Nothing happened: so we can move on, either to different experiments with the GAD pathway or with other approaches.
328 Early stage prostate cancer can be cured with radical prostatectomy, performed as an open retropubic procedure. Early stage prostate cancer can also be treated by external beam radiotherapy. Early stage prostate cancer can also be left undetected and untreated, and only a small proportion of it will ever progress to end-stage disease. All of which makes it very difficult to discuss with a patient who has just been given this “cancer” diagnosis. Should he wait and take his chances? Or should he go for surgery, knowing from this British study that 75% of men will be incontinent after radical prostatectomy and that pelvic floor exercises will not improve the situation, even if they are carefully supervised? If it’s a choice between a 15% chance of dying from the cancer and a 75% chance of being incontinent for the rest of your life, which do you prefer? Ah, how sweet are the joys of being an elderly male.
This paper also reports a parallel study of men rendered incontinent by transurethral prostatectomy for benign disease. They too did not benefit from supervised pelvic floor exercises.
348 If you went into medicine to do the most good to the greatest number of people, then why aren’t you in vaccine research? The Lancet is running a short series on vaccine development, singling out Edward Jenner and Richard Moxon for special praise, and inviting the latter to co-author an overview of what the next decade might hold. Vaccines for HIV and malaria? Multivalent vaccines for every type of meningococcus and pneumococcus and influenza virus? Just imagine if you could claim credit for one of those. You really would deserve a bronze statue and a blue plaque on your house.
BMJ 23 July 2011 Vol 343
Nursing homes full of dementia patients are the inevitable price we pay for the advances in medicine which permit longevity, and they are places where doctors should be encouraged to spend more time (I mean prior to retirement, not after). I am sorry to reflect on how un-proactive I often was in the care of these patients – salving my conscience with the thought that in the institutions I served, the nursing staff were generally reliable and – importantly – kind. This cluster-randomized Norwegian trial looked at the effect of a graded analgesic protocol on agitated patients who could not report pain. This was at least as successful as treatment with psychoactive drugs, and probably both safer and kinder. There can never be certainty in studies of this sort, but this at least reminds us that it in an agitated demented patient, one should always look for a source of pain – and also for infection.
Had I been responsible for this Canadian retrospective cohort study of pre-operative echocardiography, I think I would have submitted it to the Archives series called “Less is More.” Maybe they did, and got the BMJ as second prize. No matter: the message is that medical fashions often run riot before anyone stops to say, “Do we really know why we are doing this?” Apparently pre-op echo for major non-cardiac procedures has become a standard procedure, almost a hallmark of quality, in many North American hospitals. For all I know, it may be catching on in the UK too. From the evidence of this study, it has zero effect on patient outcomes. Probably the quickest way to stop it being done would be for North American insurers to stop paying for it.
Ann Intern Med 19 July 2011 Vol 155
87 Steven Woloshin and Lisa Schwarz have been researching better ways of discussing the benefits and harms of treatment with patients for many years: their little book, Know Your Chances (2008) is a must for every practice library. Here they present a randomized trial which overturns the widely stated dogma that people understand risk best when it is expressed as natural frequencies i.e. number per 1,000. In the trial, randomly selected US adults were tested on their comprehension of figures given per 1,000, vs. whatever gave a numerator above 1, vs a percentage. Plus two combinations. It seems that people understand percentage data best, but a third failed the test outright. So here is another “rule of thirds” in medicine: a third of patients understand what you tell them perfectly; a third understand it a bit; and a third don’t understand however hard you try. The last group are nowadays said to have “poor health literacy” and if you like this classification you can find out how it affects health outcomes in a systematic review on p.97. No prizes for guessing.
108 Out-of-hours primary care is an important domain of clinical practice which largely lacks its own literature. Just yesterday I addressed a mixed audience of doctors and researchers from the USA, Brazil, Iran, India and China on the subject of “How Do Our Health Systems Really Work?” and it was interesting to note that out-of-hours care is provided in a similar way in most health systems – by a mixture of primary care centres and hospital emergency departments, with a lot of overlap in case-mix. Judging from this narrative review of OOH primary care in the Netherlands, they are the world leaders in quality and speed of response – an average of 30 min for a non-urgent home visit, for example! Of course it helps that you can practically cross the whole country on a bicycle in that time. But the thing they haven’t quite solved is how to integrate the working of their primary care centres with their hospital emergency departments. Time for a collaborative British-Dutch study I think.
Plant of the Week: Aesculus parviflora
As July turns towards August, there are so few interesting large plants in flower that longstanding readers must forgive me a bit of repetition. I’ve praised this shrubby horse chestnut in previous years, and even commanded you to plant it if you have a large open garden that I might visit in August. It needs lots of space, because it is broader than it is high and suckers freely. There is a lovely specimen in the Botanical Gardens of Sheffield, covered in tall white candles of flower for a fortnight during the summer holidays.
Now there are a few good examples of this plant here in New Haven, and I was looking forward to seeing them in flower. One is on my bus route to work and was quite resplendent for a day. The next day the flower spikes were brown, and now they are just curly remnants, thinking of producing conkers of their kind. The summer heat must be to blame, you would think: but in fact the “Bottlebrush Buckeye” comes from much further south in the USA, in Carolina, Georgia and Florida. From there it was brought to Britain by John Fraser in 1785, from which time it was distributed so successfully that by 1820 it was “to be met with in most of our nurseries.”
I think that this is a rare instance of a plant that might look better outside its natural habitat. In the USA, it just behaves like an impatient organ of reproduction: wham, bang, here are my conkers. But on the cloudy Pennine slopes of Sheffield, 20 degrees north of its natural latitude, it takes it slow and provides joy for weeks.