Richard Lehman’s journal review – 28 December 2011

Richard LehmanJAMA  21 Dec 2011  Vol 306
2567   Amongst all the awful things that can befall human beings, poor sleep seems but a trivial inconvenience. Well, maybe: it merely doubles one’s risk of cardiovascular events and depression, and leads to undesirable effects on everyone around. In this survey of nearly 5,000 US police officers, 40% were found to have to have some form of sleep disorder, and 30% had evidence of sleep apnoea. There was an unsurprising correlation between this and falling asleep at meetings and at the wheel of a car; also with complaints from the public and administrative errors. I think the biggest improvement in medicine during my career has been the diminution in levels of sleep deprivation among doctors: at least you get the chance to sleep these days, even if you are a bad sleeper.

2588   Thiazide diuretics have been around for longer than most doctors can remember, and the thiazide-like chlortalidone received FDA approval in 1960, which is before most doctors now practising were even born. At least one large trial (ALLHAT) has shown that chlortalidone is better at reducing cardiovascular events than other blood pressure lowering drugs, though whether it is better than other thiazides we do not really know. It is certainly the logical choice for first-line treatment of elevated blood pressure, as confirmed by the long-term data from the SHEP trial which are published here. Older people with isolated systolic hypertension will on average be spared cardiovascular death by one day for each month they take chlort(h)alidone.

2608   Something terribly wrong is going on in the field of drug development. The commercial model which generated new drugs throughout the second half of the twentieth century is increasingly incapable of meeting the needs of the twenty-first. This is especially true of new drugs for cancer, the subject of this commentary piece. Spectacular advances in basic science and the genomics of cancer cell lines have produced a vast range of tempting targets for cancer therapeutics, but the net benefit to most cancer patients so far has been negligible. The current process of patenting and secretive testing, followed by years of phase 2 and phase 3 human trials, is enormously time-consuming and expensive and does not guarantee either a return for the drug manufacturer (the article quotes a figure of 0.3%) or a useful drug for the public – as illustrated by the case of trastuzumab (Herceptin). There must be a better way, involving open data-sharing from the outset rather than a scramble for intellectual property rights and patents, and Jay Bradner at Harvard has shown how it can be done.

(I wrote this before reading Robert Schwartz’s perspective piece in the NEJM. He says exactly the same, and cites a book by Philip Mirowski called Science-Mart: Privatizing American Science, Harvard 2011. Spread Christmas gloom.)

2610   Ten years ago, my GP partner Harold Hin and I got interested in the measurement of B12 levels and the whole question of what homocysteine levels really mean in the population. Harold concluded that methylmalonic acid was probably the best test of the overall metabolic effect of folic acid and B12, and did an excellent community study which never got the attention it deserved. His views are echoed in this commentary by David Spence and Meir Stampfer: it could well be that although homocysteine-lowering trials failed to lower cardiovascular events in the populations tested, there may be subgroups who benefit and these might best be identified by measuring methylmalonic acid in serum or urine. Worth re-exploring.

2612   Howard Brody and Franklin Miller write a lovely essay on the placebo effect and its essential, humane role in the medical encounter. Much of what they write about is the art of communication, empathy, and simple kindness. All the more important for that: don’t forget that these things work for patients, and help you become a better human being too. This has nothing to do with deliberately deceiving patients with hocus-pocus, but much to do with using the consultation as a therapeutic act in itself.

NEJM  22 Dec 2011  Vol 365
2357    The year ends with a milestone in medical history: successful gene therapy for haemophilia B (Christmas disease). Six patients with less than 1% of normal factor IX (FIX) activity were infused with a single dose of a serotype-8–pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein. They all began to produce their own FIX and four were able to stop prophylactic treatment and remained free of haemorrhagic episodes over 12 months. The other two needed fewer FIX injections. Had this treatment been developed a century ago, the Russian royal family would have given the discoverers ten million gold roubles and most of Poland. As it is, it would surely be right if the Nobel Prize went to a team of clinical researchers for the first time in decades.

2366   I rather struggled with this report of long-term outcomes from the Diabetes Control and Complications Trial (DCCT) and the observational study that followed it, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. The original interventional study (n=1441) aimed at reducing the HbA1c in patients with type 1 diabetes in the interventional group to little more than 6% over a mean of 6.5 years: in fact the level achieved was 7.3%, whereas in the control group it averaged 9%. This paper describes renal outcomes at a median follow-up of 22 years. Unfortunately the authors concentrate on the glomerular filtration rate rather than hard outcomes, but hidden in the text you can discover that in the tight control group, 29 subjects died and 8 developed end-stage renal failure; in the usual care group, 34 patients died and 16 developed end-stage renal failure. So in this population of young people with type 1 diabetes, there is definitely some benefit to the kidneys from tight control, but in absolute terms it is not large. 

2389    Primary hyperparathyroidism is a topic I considered for the Easily Missed series, especially since a family member was diagnosed with it and I was forced to consider whether I might have it myself. Subtle features of asymptomatic hyperparathyroidism include weakness, easy fatigability, anxiety, and cognitive impairment: just like the symptoms of being alive, really. Perhaps I should have my calcium and PTH checked; but then, on reading this review, I can’t really find much evidence that parathyroid surgery makes a lot of difference. Which is why we decided against including it in Easily Missed, and I still haven’t had my blood tests.

2398    Make your Christmas experience complete: read an update on focal segmental glomerulosclerosis.

Ann Intern Med  20 Dec 2011  Vol 155
820   I have tried to keep up with the large and confusing literature about vitamin D over recent years, and I was attracted by the title of this review: New Insights About Vitamin D and Cardiovascular Disease. The authors plod through the evidence and explain the mechanistic possibilities by which vitamin D deficiency or insufficiency might play a part in hypertension and atherosclerosis. On the other hand, vitamin D deficiency may just be a marker for not getting out much and not being able to afford the right food. More studies are needed, they conclude: and I concur, but this is not a “new insight.”

Lancet  24 Dec 2011  Vol 378
This does not seem to exist, though the last issue was said to cover only the week Dec 17-23. Perhaps the Universe now faces a Lancet gap, with unforeseeable consequences for the fabric of space-time.

BMJ  24 Dec 2011  Vol 343
A good Christmas issue but not a classic. The favourite with rapid responders seems to be the study showing that orthopaedic surgeons are both stronger and more intelligent than anaesthetists. In fact it seems to show that anaesthetists are of below average intelligence (IQ 98.4): most unfair.

Plant of the Week: The Christmas Tree

Christmas trees are best made out of plastic. Happy Christmas.