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Richard Lehman’s journal review – 19 December 2011

19 Dec, 11 | by BMJ Group

Richard LehmanJAMA  14 Dec 2011  Vol 306
2459   The topic of stillbirth got a thorough airing in The Lancet last April, when the British press seized on the fact that our figures were as bad as Estonia and therefore a disgrace to the civilized world. In fact they are much better than those in the USA, as cited in two reports here from The Stillbirth Collaborative Research Network, and the reasons become clear as you read their findings: stillbirth rates are chiefly a function of ethnicity and hardly at all a marker of the quality of antenatal care. The stillbirth rate in this very carefully studied cohort was 14% higher in Hispanic women compared with “white women,” and 250% higher in black women. But when you ascertain the cause of fetal death by post-mortem examination, as with most of the cases described here, the causes are very similar throughout groups, and none of them are easily avoidable.

2469   A second report from the study looks at the association between stillbirth and risk factors known at pregnancy confirmation. The great majority of stillbirths are not associated with any such risk factors. No doubt a gradual increase in understanding will bring about a continued slow fall in the stillbirth rate, but there are no simple answers.

2487   For many centuries, the concept of rescue cabbage was unknown to the English-speaking world, though it was well recognized by the inhabitants of Central Europe, who would keep a barrel or two of fermented Sauerkraut or kapusta to see the household through the hungry days of late winter. Nowadays we do not use this term to refer to such elemental foodstuffs of the Northern races, but to emergency coronary artery bypass grafting (CABG) following dissection or perforation during angioplasty (PCI). This used to be quite a common event, but now happens in less than 0.5% of PCIs, so in the USA many hospitals without the capacity for CABG have begun to offer PCI. This study shows that their outcomes are as good as hospitals that can offer both.

NEJM  15 Dec 2011  Vol 365
2255   The great success of statins in improving cardiovascular outcomes was well illustrated in the long-term Heart Protection Study figures published last week, though if you look at the main figure you will see that the absolute benefit for most people is not huge. For some drug companies the patent life of these drugs meant annual profits of billions of dollars, and the last decade has seen a scramble for the next lipid-lowering blockbuster, based on the idea that the more you lower LDL-C and the more you raise HDL-C, the more you will reduce cardiovascular risk and the more you will be able to pay your executives and shareholders in years to come. But this stubbornly refuses to happen. Even if it did, the absolute benefit to most people already on cardioprotective drugs would be marginal. Niacin is a fairly unpalatable vitamin which does the right things to lipid levels and showed slight promise in earlier trials. Here in the AIM-HIGH trial it was given in a long-acting preparation alongside simvastatin (up to 80mg daily) and sometimes ezetimibe plus whatever other drugs were being prescribed to the 3414 recruited subjects with established cardiovascular disease. The trial was stopped at 3 years for lack of efficacy: in fact the rate of ischaemic stroke was higher in the niacin group. Facts are stubborn things, as John Adams said: and the fact is that statins have been shown to work, and other lipid-lowering drugs have not.

2268    Dronedarone is a drug we all wanted to succeed when it first appeared as a potential benign successor to amiodarone, the iodine-bearing anti-arrhythmic much hated by patients, endocrinologists, and dermatologists. Given to patients with intermittent atrial fibrillation in hospital, dronedarone restored sinus rhythm and reduced death or rehospitalization. The PALLAS trial was carried out under the aegis of dronedarone’s manufacturer Sanofi Aventis (rather than the goddess Athene), but far from proving that all patients with AF should take the drug, it showed that dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Perhaps Sanofi Aventis (now deprived of potential tens of billions in sales) should reread their Homer, and pay more attention to performing the correct sacrifices before naming a trial after this fickle goddess.

2287   When Jack Wennberg first started examining the irrational patterns of variation in care use in the USA, no medical journal would publish his results, which eventually appeared in the journal Science in 1973 to huge acclaim. Jack’s motto (taken from Napoleon) is that Geography is Destiny, and that what happens to you medically is determined by the facilities around you. If a hospital near you needs to keep its beds full in order to stay in profit, its beds will mysteriously fill up to the level required. Same with your physician’s appointment book. This study of Medicare admissions shows that rates of admission and readmission for heart failure and pneumonia are far more related to the characteristics of the hospitals than to any clinical characteristics of the patients. This happens when you have an oversupply of hospital beds and incentives to fill them. Researchers wishing to study the opposite phenomenon have a wide choice of locations in the UK to choose from.

2296   Catheter ablation for atrial fibrillation remains a technically challenging procedure and results depend both on operator skill and the careful selection of patients. When last seen, my only patient to undergo the procedure had had his fourth attempt. He was dramatically better whenever he was restored to sinus rhythm and he did not respond to any drug treatment that he could tolerate. These are the patients to consider – and this is the account to read if you want to learn about the procedure.

Lancet  17 Dec 2011 Vol 378
2095   Human parturition is a dangerous and ungainly affair, and we must be grateful that there are still a number of doctors who wish to be involved with it. If you want to see all that can go wrong with childbirth, there is no better place to go than the obstetrical gallery of the university museum in Bologna, full of beautiful waxworks of abnormalities which would have meant a painful death for mother and baby when they were created in the eighteenth century. Modern obstetrics is still not entirely risk-free: for example, there was one uterine rupture in this large Dutch trial of induction of labour comparing a mechanical method – inflation of the 30ml balloon of a Foley catheter in the cervical canal – with a chemical method, using vaginal prostaglandin E gel. The paper also contains a useful systematic review of all such trials, which tend to show better results with the Foley catheter method. It’s a very long time since I entered a birthing room, so I don’t know what modern practice is like, but it seems to me that the Foley method is the one of choice if you have to induce a woman with an unfavourable cervix near term.

2104   Last week we learnt that androgen deprivation therapy improves survival in locally advanced prostate cancer without increasing cardiovascular events. This study tells us that localized radiotherapy produces some additional survival benefit, though at the cost of local adverse effects. The absolute survival difference is 10% over a median of 6 years’ follow-up. The paper suggests that bowel symptoms are rarely severe, but the editorial points out that the wrong instrument was used to ascertain them. I think this is really important for shared decision-making, and needs to be looked at in the next analysis of this cohort and all future studies of prostate radiotherapy.

2112   Four authors clearly enjoy the opportunity to expatiate on the subject of allergic rhinitis in the pages The Lancet. I can’t say that I learnt a huge amount from reading this review, but it is well written and thorough and not to be sneezed at. Poorly controlled allergic rhinitis is a marker for a much increased risk of unstable asthma, which is only to be expected as it is a strong marker for atopy, though the review makes it sound as if that makes the treatment of allergic rhinitis per se a matter of some importance. The paper also introduces the concept of entopy, a local form of mucosal reactivity not linked to IgE. This must not be confused with entropy, the disturbing physical principle proclaimed in the Second Law of Thermodynamics. If you want to learn about entropy as opposed to entopy, the octogenarian genius Roger Penrose has written a book on the cosmic conservation of entropy called Cycles of Time (2010) – which has convinced me that not even Penrose really knows what it actually is.

BMJ  17 Dec 2011  Vol 343
1242   The statins were developed to reduce cholesterol synthesis in the liver by inhibiting 3-hydroxy-3- methyl-glutaryl co-enzyme A reductase. Whether this is their main mode of action in reducing cardiovascular events is still hotly debated, but it is clear that they work in other ways which have been bundled up into the obscure Greek word “pleiotropic.” For a while it was believed that statins were extraordinarily “pleiotropic” in a variety of beneficial ways. They were supposed to prevent osteoporosis and dementia and infections: but the evidence for prevention of infections is examined and dismissed in this meta-analysis of data from large randomized controlled trials. For a discussion of possible modes of pleiotropic action, see the Circulation paper by Liao on the link.

1243   Having been drawn into debate about targets in type 2 diabetes over the last three years, I’ve become aware of how pitifully little evidence we have for shared decision making with patients who bear this label. This is not for lack of effort: this paper identifies 145 risk models and scores for diabetes but muses on why so few clinicians use them. The basic problem is that they cannot overcome the deficiencies in the evidence we use to determine treatment choices.

1245   Among all the disease-mongering of the present age, nothing baffles me more than the promotion of “non-alcoholic fatty liver disease.” This is an ultrasound finding in up to a third of the population, and here a prospective cohort study from the USA determines its prognostic significance. “Non-alcoholic fatty liver disease was not associated with an increased risk of death from all causes, cardiovascular disease, cancer or liver disease.” In other words, it is not a disease at all. As a friend has said, it is of the same importance as fatty elbow disease.

Arch Intern Med  12/26 Dec 2011  Vol 171
1990   Have you got the faintest idea what advice your patients with diabetes receive from other health professionals? The chances are that these HPs have been indoctrinated by believers in tight glycaemic control and low fat diets and other forms of mythology dear to the devisers of guidelines and sellers of drugs. But this trial shows that however much of such advice is given, little of it is heeded. In this study, patients with long-standing poorly controlled diabetes (i.e. HbA1c around 9), three interventions achieved nearly the same lack of effect: a structured behavioural intervention of five 2-hour sessions; an educator-led attention control group education program, whatever that was; and unlimited individual nurse and dietitian education sessions for 6 months. The first worked faintly more than the other two.

2001   More alarmingly, the next study strove to achieve levels of HbA1c below 7% through the use of educational interventions. Fortunately it did not succeed. The authors acknowledge that the evidence for this target changed during the period of the study, and in fact they may have done more good than harm because most of the reductions were from above 8 to the mid-7s. They found that individual education sessions worked better than group education using the US Diabetes Conversation Map program.

2011   Finally, a group of low-income patients with poorly controlled type 2 diabetes was randomized to receive an educational intervention by video, workbook, and five telephone sessions. This achieved nothing at all.

2043   Scepticism about the benefits of screening mammography has been slow to catch on in America. The Dartmouth team of Gilbert Welch, Steven Woloshin, and Lisa Schwartz set out the case against in their excellent book Overdiagnosed, and here Welch and another colleague calculate the true chance that a woman with screen-detected breast cancer will have had her “life saved” by such screening. The likelihood they calculate from long-term US data is between 3% and 13%. They conclude that “Most women with screen-detected breast cancer have not had their life saved by screening. They are instead either diagnosed early (with no effect on their mortality) or overdiagnosed.”

Plant of the Week: Nandina domestica
Mid-December is a stern test of garden-worthiness, but coming back to our small plots in England we were struck by how much more there is to look at than in Connecticut at this time of year. Perhaps the champion plant is the Chinese sacred bamboo, a small upright shrub standing exposed to wind and frost on our front bank. It is too tender to survive in New England but seems pretty imperturbable here.

It is no bamboo at all but a relative of mahonia and berberis. Ours is even trying to produce spikes of white flower at the moment, something which should only happen in July. At some point these flowers turn into bright red berries. But this is not a plant you really grow for its flowers or fruits, but for its dainty habit and elegant sprays of evergreen leaf. As Graham Stuart Thomas says, “There is nothing like it.”

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