Richard Lehman’s journal review, 10 January 2011

Richard Lehman

JAMA 5 Jan 2011 Vol 305
43 Implantable cardioverter-defibrillators are a good intervention for those who have bad systolic heart failure with a risk of ventricular arrhythmia, and would rather die slowly than suddenly. The “utility” of the device is that it can have a statistically significant effect on mortality in younger, properly selected patients; the “dysutility” includes everything that can go wrong with the machines and the possibility that dying from pump failure may be accompanied by multiple painful electric shocks. As you’ll gather, I’m not a great fan of these devices, but most cardiologists are. In the USA, their use by Medicare and Medicaid was approved in 2005, since when a registry has been kept, and this study examines it to find out how many ICD implantations were not evidence-based. Using agreed criteria, the answer is about 22.5%, meaning that between a fifth and a quarter of all ICDs cannot be expected to do any good to the patient, while the potential for harm is considerable. I wonder what kind of informed, shared decision-making goes on before these things are inserted into people?

50 Old people slow down before they die. Before they shuffle off this mortal coil, they just shuffle. In case you hadn’t noticed, here is a 19-author study of 9 cohorts of elderly people showing that reduced gait speed predicts shorter survival. Why do things like this get published?

78 Chronic Prostatitis/Chronic Pelvic Pain Syndrome is described here as a “diagnosis of exclusion”: in other words, you put the man with the pain through all sorts of tests and anxieties and then pronounce that you don’t know what’s causing it, but he can try this that or the other. The best you can hope for is a friendly stalemate of mutual frustration. At least, that was the message of a recent clinical review in the BMJ, but this systematic review of treatments is a bit more optimistic, particularly about the benefits of a-blockers and antibiotics. Most of the trials are of poor quality, and there is no mention of the classic Chinese remedy, Three Penis Wine. Maybe that’s because there is considerable variation in the cost and content of this fine potation, according to the creatures used in its preparation: for the rich and desperate, there is even Five Penis Wine.

NEJM 6 Jan 2011 Vol 364
11 Here’s a classic pharma-funded trial of eplerenone in systolic heart failure with mild symptoms: EMPHASIS-HF. Pfizer paid for patients to be recruited in 278 centres in 29 countries, with fewer than 10 patients per centre; their mean age was 69, with none reaching 76, the mean age of heart failure patients in the community; and 78% of them were male. The trial was stopped prematurely when the eplerenone group showed a large reduction in the composite end-point of death and readmission. So we know that the drug works for this group of patients, though the effect size and long term effects cannot be known accurately due to early termination. We have no idea what the drug does for symptoms, since these weren’t considered. We don’t know what its effects will be on older patients with comorbidities, or on patients with heart failure and a normal ejection fraction. It will probably cause much more serious hyperkalaemia in the community than in the trial, as was the case with spironolactone following the RALES study. Sales of eplerenone will soar in its last few years on patent, and the heart failure community will be happy that its academic centres and conferences will have been paid for until the next bonanza comes along. Meanwhile, clinicians will struggle to know what best to do for their patients, especially as a quarter of the patients in this trial had QRS prolongation and should have had biventricular pacing.

22 Rifamixin is an antibiotic derived from rifamycin which is very poorly absorbed from the gut. In the USA and some parts of Europe where it is available, it is widely used to treat travellers’ diarrhoea, Clostridium difficile (pronounced however you like), bacterial overgrowth in the gut, and even hepatic encephalopathy. In the UK, it doesn’t have a licence, and this study of its effect on irritable bowel syndrome doesn’t help to bias me in its favour. We tend to be desperate to treat these patients with anything that might possibly work, and the trial shows that in about 10% of those with bloating, rifamixin has some benefit over placebo. For the sake of a marginal benefit in a few individuals, maintained for a few weeks, we might be giving an expensive antibiotic to hundreds of thousands of people and pushing our much-abused bowel flora in yet another unwelcome direction.

51 Bipolar disorder is deeply unenjoyable for most of its sufferers, as depressive swings tend to outnumber highs. Patients like this tend to be psychiatrist-averse, and also they swing around in general practice rather than at times which suit CPNs and mental health outpatient clinics. The temptation is to use antidepressants, and I often have, but you have to be ready to look out for signs of suicidality and/or rebound mania, and this is hard and dangerous work. Moreover there is no trial evidence to back this strategy, so that this excellent clinical practice article warns against it. The trouble is that there is so little evidence that backs any strategy at all. The psychiatrists’ current favourites, olanzapine and quetiapine, are suggested; lithium of course; and possibly lamotrigine, though any benefit is very marginal.

Lancet 8 Jan 2011 Vol 377
127 Comparing cancer survival in different countries is fiendishly difficult, whereas making up “British Cancer Deaths Scandal” type headlines is fiendishly easy. The press duly had a fiend day when this study first appeared, seeming to show that the UK lags behind Australia, Canada, Sweden and Norway in cancer survival. However, a brilliant French editorial on p.99 gives a list of 30 factors which may confound or at least affect such statistics. Here is my nakedly political take on the situation. Britain’s cancer registries tend to fall 10-15% short of the completeness of Scandinavian registries, so there is probably a tendency to lose cases of more favourable prognosis. The figures from 1995-2007 given in this paper also reflect the baleful effect of GP fundholding in the 1990s, which actively discouraged early imaging and specialist referral. If GPs now become the agents of global rationing, British cancer survival statistics are bound to get worse.

153 I live about as far from the sea as it’s possible to get on this island, and my only reason to go near it is in the hope of dining on fresh fish and seafood. We leave it to others to plunge into its briny depths and risk decompression illness, hopefully with a view to finding the best scallops and giant crayfish for our modest table. If I were younger, that would be my one incentive to risk the bends, which are described in great detail in this comprehensive seminar with 145 references. The standard treatment consists of recompression in 100% oxygen, followed by slow decompression, and a meal of oysters and turbot (optional).

165 “Uricase was lost to man and some non-human primates via a missense mutation in the gene encoding the enzyme. In other species, uricase converts urate to allantoin, which is five to ten times more water-soluble and more readily eliminated than urate.” Hence gout in man (and sometimes woman). The last section of this paper on new therapeutic agents for gout deals with some experimental ways of reintroducing uricase into human beings, though most of it is taken up with new agents which reduce uric acid. But the main problem is that we do not use the existing agent, allopurinol, with sufficient care to reach serum uric acid levels of around 350 µmol/L. Trials of a new agent, febuxostat, cheat openly by using an inadequate fixed dose of allopurinol 200mg as the comparator. Other new agents are equally dubious: don’t wait for therapeutic improvements but use existing agents with more careful monitoring, however tiresome that may be for you and the patients.

BMJ 8 Jan 2011 Vol 342
93 These days I spend half my time as a semi-detached academic, but I am not sure I am cut out for it. It’s too much of a shock to move from 40 daily encounters with problems of immediate relevance that need an answer within ten minutes, to broad questions of dubious relevance that might get answered within 3-5 years. In day-to-day general practice, we occasionally use QRISK or similar scores because they’re on the computer and they can be of some help in borderline situations. Meanwhile under fluorescent lights in Nottingham University, aided by endless cups of strong coffee, Julia Hippisley-Cox and her team number-crunch their way from one version of QRISK to the next. The latest is a model for estimating lifetime risk of cardiovascular disease. “Is this useful?” asks a fellow-dweeb from New Zealand, Rod Jackson, with two colleagues. “No, but forecasting short-term risk throughout life is”, he argues, somewhat impenetrably.

95 Last week’s Clinical Review in the BMJ was about adult rheumatoid, and I compared it to a dull workmanlike Dutch winter landscape. I can be a bit kinder about this week’s account of juvenile idiopathic arthritis, a longer, livelier affair which tells you all you need to know about the modern management of Still’s disease. A sort of Dutch Still’s life, with exciting half-eaten pomegranates and lobsters, so to speak. But time to shut up with the metaphors, I think.

Ann Intern Med 4 Jan 2011 Vol 154
1 The main hope that warfarin will be replaced by fixed dose oral drugs lies in the pricing policies of manufacturers for direct thrombin inhibitors and factor Xa antagonists. The system costs of INR monitoring are enormous; but there is a danger that in the new world of anticoagulation, we will be held to ransom by price fixing: “In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS2 score =1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States.” Unfortunately, that is the conclusion of this modelling study, not the question. How do we get these profit-driven drug companies into enough competition to benefit the world, not just the USA?

22 When you’ve had a colonoscopy and polypectomy you don’t particularly want another, if personal experience is anything to go by. But the plus side is a greatly reduced risk of bowel cancer over the subsequent ten years, confirmed by this population case-control study from the lofty hills and vineyards of the Rhine-Neckar region of Germany.

31 I can’t remember when I last reviewed a case series. Today’s general medical journals resemble ruminants with five stomachs, churning, predigesting and redigesting data; but you rarely get a mouthful of fresh grass, like this paper. Good news: a combination of tapered prednisone and mycofenolate mofetil can reverse the progression of retroperitoneal fibrosis. This treatment rendered all 28 patients in the series asymptomatic, though disease recurred in two. The authors suggest the need for confirmation in randomised trials, but if I had this nasty, progressive condition I wouldn’t want a placebo.

Plant of the Week: Daphne “Eternal Fragrance”

Last week I bemoaned the near-destruction by frost of our best and biggest daphne, called Jacqueline Postill. I have much better news to bring of this smaller, tougher daphne which is nearly living up to its corny name. A few of its leaves show frosting, and all of the flowers that were out in the hard frost have perished, but there are pink-purple shows of promise in the remaining flower buds. In the next mild spell, I think we may catch wind of that Eternal Fragrance.

Growing daphnes used to be a game for plantsmen, who did it for the interest of seeing how soon they would die. With the coming of these tough, free-flowering new hybrids, all that is changing. They are low, well-mannered plants, perfect for small gardens. The only problem is that you have to get on your hands and knees to enjoy their wonderful scent.