Richard Lehman’s journal review – 16 August 2010

Richard Lehman JAMA  11 Aug 2010  Vol 304
641    All this week the media has (sic) been proclaiming the end of the antibiotic era, on the basis of data which shows (sic) that new multi-resistant plasmids can cross from one bacteria (sic) to another in Indian hospitals. Give or take a few plurals, you get my gist. Rather like language(s), bacteria (plural) constantly mutate and leave angry pedants behind. Staphylococci are supposed to be killed by meticillin and when they survive this and the usual alternatives, they become killer plague superbugs or MRSA. When they first emerged, the media (plural) of the time declared that all staphylococci would soon become MRSA(s) and the world would end. But New Labour declared war on MRSA in British hospitals and rates of invasive MRSA in hospital declined by 9.4% per year between 2005 and 2009 and community-acquired MRSA declined by 5.7% per year. Except that I’m cheating: these (sic recte) data about the bacterium (sic recte) come from the USA; so it happened without any help from New Labour.

649    Prevalence of diabetic retinopathy in the United States, 2005-2008. That seems a rather short comparison period, and when you get to the meat of the text, you realise why: this isn’t a comparative study at all, but a cross-sectional study of prevalence done as part of NHANES 2005-8. About 60% of type 2 diabetics develop some degree of retinopathy within 20 years, and it’s an important outcome measure in trials of treatment for diabetes. But also a rather slippery one: the important category is sight-threatening and within this the most important is sight-threatening despite optimal treatment. I find it difficult to tease out this end-point from this observational study; still more so in the interventional studies which are supposed to guide our management of T2DM.

657    Cancer of the oesophagus is getting commoner, and so is the prescription of regular bisphosphonates, which frequently cause oesophagitis: are the two by any chance linked? The reassuring message of this study of data from the UK General Practice Research Database is a firm negative: bisphosphonate intake for any length of time is not associated with a higher risk of cancer either of the oesophagus or the stomach.

NEJM  12 Aug 2010  Vol 363
609    A patient of mine has been going to the renal clinic for several years now, ever since her creatinine went above 200 for no apparent reason. It is now 500, but she continues to feel perfectly well and is reluctant to enter renal dialysis. At what point, in an IDEAL world, should she be persuaded to start? This antipodean study (IDEAL) suggest that the answer is: when she feels like starting renal dialysis. They attempted to randomise patients with a falling glomerular filtration rate to start as soon as it fell between 10 and 15 ml per minute or to wait until the GFR had fallen below 7. There was no difference in outcomes, though there was a big cross-over to dialysis in the latter group, driven by symptomatic deterioration.

620 Every time I open my Spam file I am accosted by people who offer me sildenafil at reduced prices, often accompanied by derisive hints that I cannot  achieve vasodilatation in circumstances where this is desirable. What do they know. One such circumstance is when people with idiopathic pulmonary fibrosis try to breathe; their pulmonary vasculature does not produce enough nitric oxide to open up properly. This can in some measure be relieved by phosphodiesterase-5 inhibitors like sildenafil, but unfortunately this has no effect on the fibrosis itself. So this short-term study was able to detect a few physiological improvements in the treated group, but nothing that is likely to be clinically useful.

640  Occasionally we have to break the diagnosis of early Hodgkin’s lymphoma to a young and previously fit patient: it’s an awful shock, the treatment will be a bit unpleasant, but they will almost certainly be cured. The study here is aimed at finding out how the treatment could be made less unpleasant without affecting cure rates, and it finds that you can halve the chemo and reduce the radiotherapy by a third without affecting outcomes in stages I and II. The article which follows (p.653) reviews the whole field of treatment for early Hodgkin’s, while the Case Study on p.664 describes the demise of a 56-year-old lady with:
“Acute myocardial infarction due to coronary artery disease, cardiac valvular disease, chronic pulmonary fibrosis, ductal carcinoma in situ of the breast, soft-tissue sarcoma, cervicoscapular muscle atrophy, and oesophageal dysmotility, all probably resulting from radiation therapy for Hodgkin’s lymphoma.”

“It is important to note that this patient had 40 productive years after she was cured of Hodgkin’s lymphoma with what was then state-of-the-art treatment… Although we can do better now, it doesn’t mean that we did not do well by this patient.” Nicely observed.

Lancet  14 Aug 2010  Vol 376
If you reduce a person’s weight, you will reduce their insulin resistance and ultimately their cardiovascular risk: so ran the logic of the CRESCENDO trial. The intervention was the cannabinoid-1 receptor antagonist  rimonabant, which was going to make a fortune for Sanofi-Aventis, funders of the trial. But when after about 14 months the intervention group showed a significant excess of suicide and severe psychiatric adverse effects, the trial was terminated and rimonabant lost its licence. “The premature termination of this trial has important lessons for drug development”, say the investigators. Yes indeed: drugs which help weight reduction should not cause death.

524  My favourite approach to the heart is via an armchair and a journal, rather than through a sternotomy with lots of tubes and blood. In fact I am such a stranger to the business end of cardiac surgery that I was quite unaware that there are two ways of replacing the aortic valve without a mechanical device – an autograft or a homograft. This trial assesses the long-term merits of the two approaches, as done by Magdi Yacoub ten years ago. To get an autograft you have to remove the patient’s own pulmonary valve with its root, and then swing it over to fill the gap you have created by removing the aortic valve and root. You then replace the pulmonary valve with an homograft. Or you can opt to replace the aortic valve itself directly with homograft. This is as big a series as you’re likely to get (n=228), and it shows that the more complex procedure, done by the great man, gives you a normal life expectancy, whereas an aortic homograft carried 3-4 times the mortality in the first 10 years. (Christmas cracker joke – Q: When you met Sir Magdi Yacoub, did you get his signature? A: No, but I got his autograft.)

540  I love marine omega-3 fatty acids and will eat anything that contains them, except capsules. Others in the household, however, take a dimmer view of the pervasive scent of grilled or fried herring or mackerel, and even decline to be associated with the delicious but threatened common eel. Salmon has grown boring: so turbot it must be. Grilled with its skin on, it absolutely oozes with these esteemed omega-3s, and at a local supermarket fresh young specimens can be had for less than £5 per pound, on Fridays only. If you are a food faddist, you may wish to read this review all about the alleged cardiovascular benefits of these fish oils; if you eat for enjoyment, though, you will make sure you put plenty of salt and butter on your turbot before you grill it, and then cover it in some delicious egg-and-butter sauce such as bearnaise or hollandaise; or a sauce based on wine, leeks, oyster jus and boiled double cream. Heaven for the stomach, if unproven for the heart.

BMJ  14 Aug 2010  Vol 341
We all beat ourselves up about the allegedly terrible UK cancer survival statistics, because some of the blame must attach to general practice. But in fact our breast cancer mortality statistics show a marked decline since 1990 and now are on a level with those of the rest of Europe. But this is marshy ground: for what appears to be a clear analysis, see the editorial on p.309; but for the truer picture of all the bogs that analysts can fall in, see the Rapid Response by David Brewster et al.

336 Here’s a prospective cohort study of modifiable risk factors for dementia from Montpellier in the south of France. If you want more on this subject, there’s a meta-analysis and US guidelines in the current issue of Ann Intern Med, but so lengthy and inconclusive that I didn’t comment on them last week. This article is more interesting but I was a bit thrown by its casual mention of crystallized intelligence. Apparently those of us who are wise and diligent develop these crystals as we get older. Not literally, but better than tangles and plaques, I guess. Anyway, eat fruit and veg, exercise, don’t drink too much, stop smoking, read plenty etc.: all the usual ways to avoid everything avoidable.

Arch Intern Med  9/23 Aug 2010  Vol 170
Yet another study showing that waist circumference is an independent predictor of mortality beyond the body mass index. It’s based on a cohort of more than 100,000 Americans aged 50 and over followed up for ten years, and it shows particularly large mortality effects at the extreme end of the belt size range.

1302  What wrong with you, what medicines are you taking, why are you taking them and who’s your doctor? In a community hospital affiliated to Yale, a great many patients couldn’t answer most of these questions. Most of the physicians believed that they could, of course; though the surprising exception was in information about drug therapy, where the physicians judged themselves much more harshly than the patients.

1358 There’s been a recent upsurge in interest in allopurinol as a drug with cardiac benefits, especially in heart failure. We need some big randomised controlled trials, but in the mean time a Canadian study intriguingly shows that while gout is an adverse prognostic factor in HF, people who have gout and heart failure but take allopurinol fare as well as HF patients without gout. So always give patients with gout and HF some allopurinol with colchicine cover but on no account give them NSAIDs ever ever.

Plant of the Week: Crocosmia x crocosmiiflora

While touring Anglesey last week, we were struck by the abundance of these “montbretias” providing splashes of orange in hedgerows and wild places throughout the island. It’s the same on the North Island of New Zealand, except there they grow to twice the size. These are all the progeny of garden escapes following the creation of this hybrid in 1882 by the great French nurseryman Emile Lemoine and his sons from two species found in the Cape of South Africa. In their native grassland these are hardly invasive at all, but on the wet islands inhabited by Britons, their child goes wild, literally.

Our own garden is a test bed of Darwinian survival. Our crocosmias were put under a protrusion of the house which is north-facing and dry. They were then covered in a mixture of stone, rubble and compacted clay. This was not malice, just forgetfulness. But the following year they started putting out leaves, and now a large clump is flowering happily. A tough plant, then, and a worthy addition to the Welsh and Kiwi landscapes, whatever purists may say.