Richard Lehman’s journal blog 27 July 2010

Richard Lehman JAMA  21 July 2010  Vol 235
This issue of JAMA is devoted to human immunodeficiency virus infection in resource-poor countries and as usual I won’t attempt to comment on issues such as preventing mother-to-child transmission in Africa and the benefits and limitations of using generic antiviral drugs in resource-poor settings. We’re talking here about individuals who are HIV positive of course: but when might it be a good thing to be HIV positive? Answer: when it is an indicator of successful vaccination against HIV. We don’t yet have a vaccine of proven efficacy, but several large field trials are going on and inevitably they depend on inducing the very antibodies that we normally use to diagnose HIV infection. Fortunately there are ways around this: in the unlikely event of your being faced with the problem, see Figure 1on on p.277 in the print journal.

NEJM  22 July 2010  Vol 363
    Insulin pumps have been around for a long time, and so has the idea that they could one day be linked with continuous sensor measurements of blood glucose, creating an automated feedback system for treating type 1 diabetes. This study doesn’t go quite that far: although the implanted sensor measures blood sugar every five minutes, the patient has to adjust the insulin pump accordingly. The results are also beamed off to the patient’s physician. The trial (STAR 3) was a modest success in that the children and adults randomised to the device achieved a reduction in glycated haemoglobin (7.5 v 8.3%) compared to those randomised to multiple daily insulin injections, without any increase in hypoglycaemia. However, we are still some way from a high-tech fix for type 1 diabetes using a closed feedback system, for reasons set out in the thoughtful editorial (on p.383 for print readers).

331    “The optimal management of a torn anterior cruciate ligament (ACL) of the knee is unknown,” is the mince-no-words first sentence of this paper. You might have thought it was obvious that early ACL reconstruction was bound to prove superior to a policy of rehabilitation plus optional delayed reconstruction, but not so. This admirable Swedish study pushes the boundaries of evidence-based orthopaedics to prove that fit young adults do equally well with either approach. Operative treatment will only be needed in a third of patients if you first wait to see how much rehabilitation improves the situation.

365    Functional hypothalamic amenorrhea is the rather grand name given to stoppage of periods due to stress, weight loss, or exercise. Stress doesn’t get much mention in this single-author review, which is also keen to avoid discussing anorexia nervosa. That mostly leaves girls who are keen athletes and/or excessive slimmers, and these will generally recover with less exercise and more food. Except that most of them would rather not go those routes, and so end up oestrogen deficient. We don’t really know if bisphosphonates are safe in this age group. Most interventions are laughably under-researched (16 subjects in a CBT trial, 12 in a hypnotherapy study, 3 and 12 in two trials of naltrexone). For me this review was most useful just for its list of hormone tests to rule out other disorders.

Lancet  24 July 2010  Vol 376
235    Two studies seek to prove that a new drug called olaparib can have a targeted effect on cancers associated with BRCA1 and BRCA2 mutations. These mutations were amongst the first to cancer predisposition genes to be identified and they remain the most important, even though they only account for 5-10% per cent of breast and ovarian cancers. The thing about olaparib that excites investigators is that it specifically targets the repair mechanisms of BRCA mutated cancer cells by inhibiting poly(ADP)-ribose polymerase (PARP). The thing that will appeal to patients is that olaparib is orally available and has little severe toxicity. In these observational studies it was used as a last-ditch treatment for BRCA-related cancers that had recurred after several rounds of standard chemotherapy. The median progression-free survival for both breast and ovarian cancers was about 6 months. I think we shall hear more about this drug for earlier treatment in this subgroup of patients.

BMJ  24 July 2010  Vol 341
185    I am too much of a coward to think of jumping off a viaduct, though perhaps under extreme circumstances I might jump off a river bridge: less of a splat factor for all concerned. I have little idea why the BMJ decided to publish this study of “jump rates” in Toronto following the erection of a protective barrier at Bloor Street Viaduct: I suppose it’s the sort of thing that gets it cited in newspapers. The barrier prevented Bloor St splats but had no effect on the overall jump rate in Toronto.

186   The Swedish study which follows is a great deal more interesting, though the data are pretty ancient – people who attempted suicide between 1973-82 followed up to 2003. In the 70s Sweden was famous for sex and suicide; and it remains a very violent and fairly sexy place if Wallander is to be believed, quite the equal of St Mary Mead, the fabled county of Midsomer, or Morse’s Oxford, and a great deal gloomier. The hazard ratios for a repeat suicide attempt range from 1 for self-poisoning or cutting to 6.5 for hanging or strangulation, with shooting, jumping and drowning half way between. Except that in Kurt Wallander’s Ystad, such happenings are always the result of a drug gang or a religious cult. Watch it every Saturday and learn Swedish the easy way. Helvete!

188   I’ve spent a lot of years musing on the assessment of diagnostic tests, and have reached the conclusion that for all practical purposes the predictive value of a test depends on just two things – what it actually measures, and its prevalence in the population you are looking at. Faecal calprotectin is a good teaching example, or would be if we had enough studies in different presenting populations. Calprotectin is a complex of two proteins that is released from the inflamed bowel lining as part of the initial innate response, and it is distributed throughout the stool, or skit as it is known in Sweden. It can be detected by a standard enzyme linked immunoabsorbent assay (ELISA). So, readers, what does a faecal calprotectin ELISA measure? That’s right, inflammation of the bowel. And what causes the bowel to become inflamed? Miscellaneous infections which usually resolve quickly, and inflammatory bowel disease, which does not. So which population would we use this test for? Yes, people with persistent bowel symptoms. In this study, it was used in people referred for such symptoms to secondary care in the Netherlands, and it had a sensitivity of 93% and a specificity of 96% for the diagnosis of IBD. So how should we use it in primary care? Answer: in a study setting which replicates as nearly as possible the way it would be used by GPs to sort out their patients, most of whom will not have IBD. That’s the only way we will know how useful this test may be in the patients we actually deal with.

190    The area of diagnostic research I was particularly interested in 15 years ago was chronic heart failure, the subject here of a good review under the older adjective “congestive”. I was the first to investigate the correlation between primary care diagnoses of “heart failure” and levels of BNP – and found that there wasn’t much. Gradually it dawned on me that the certainties that were being proclaimed about the condition were all wrong – half of people with heart failure have a normal systolic ejection fraction, and even in those with a low EF, titrating up ACE inhibitors is of little benefit, as shown by three negative trials and two that produced a minimal reduction in hospital admission for an 8-fold increase in dose. BNP is great for proving there is something straining the heart, and if it’s normal then the heart is not being strained. It’s also great for estimating prognosis, whereas the EF is nearly useless. And so on. Some of this revisionism – but not all – is reflected in this review, which also scores marks for knowing the literature about end-of-life care for HF.

Plant of the Week: Kniphofia “Timothy”

The issue of red-hot pokers in the garden once divided opinion in this household, but I am glad to say that over the years a solid appreciation of their merits has replaced the deprecation which was once sadly observable in certain quarters. Much of the credit for this belongs to Bob Brown – the flamboyant owner of the almost unfindable Cotswold Garden Flowers nursery in Badsey, near Evesham. He keeps an unrivalled stock which he claims can provide a poker for almost every month of the year, and while he hymns the beauties of many in his quirky catalogue (“Like a blue octopus after rigor mortis has set in” he quotes of one poker, approvingly), he is not afraid to fulminate against others , e.g. “Kniphofia “Tuckii :” Coarse plant. (Destroyed – not good enough). Bobs Score=2.0.

Of “Timothy” Bob writes: “Soft salmon-peach flowers lined with deeper colour from dark buds, bronze stems Jul-Sep, 70cm. Easy and a most beautiful and unusual colour. Selected by Carlisles. (Plant thriving). Bobs Score=8.5.'”

To get Timothy, you may only need to visit your local garden centre. However, to ensure a succession of good pokers, you need to make the pilgrimage to Badsey. I would suggest “Wol’s Red Seedling” to precede Timothy (Bobs score 8.0) and “Bitter Chocolate” to succeed him (no Bobs score yet). There are scores of others, and some even have a maximum Bobs score of 10; but these are generally sold out. You can’t beat a good poker.