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Richard Lehman’s journal review—17 September 2012

17 Sep, 12 | by BMJ

Richard LehmanJAMA  12 Sep 2012  Vol 308
981    “Considering the cost, invasiveness, inpatient requirement, and morbidity of bariatric surgery, a truly intensive nonsurgical comparison group is not only justifiable but also necessary to avoid scientific bias. A suitably intensive lifestyle intervention should include multiple components, such as residential treatment for several weeks to initiate rapid weight loss under medical supervision and development of a personalised treatment plan; home-based treatment for several months, with provision of prepared meals consistent with dietary goals, weekly sessions with a nutritionist and personal trainer, behavioural counseling, cooking classes, and membership to a sports or fitness club; and follow-up for several years, involving monthly sessions with nutrition and behavioral experts, group classes, and Internet and social media support. The financial costs of such an intervention would likely not exceed those of bariatric surgery.” This welter of wild surmise comes in the middle of a piece called surgical vs lifestyle treatment for type 2 diabetes. One of the authors is a deputy editor of JAMA, and the others work at the New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital. It may be “necessary to avoid scientific bias” but I’ve never seen it done quite so comprehensively.

987    The management of mild-to-moderate chronic asthma in adults has remained essentially unchanged for about 40 years: low-dose inhaled corticosteroids for prevention, and inhaled beta-adrenergics for symptomatic flare-ups (“rescue therapy,” here used as a surrogate for “treatment failure”). Over the decades, various attempts have been made to bring science to bear on this area: there was once a vogue for daily peak flow measurements, and currently there is a fashion for measuring exhaled nitric oxide. The BASALT trial sought to find a difference in asthma control guided by patient symptoms, physician assessment, or measurement of NO: there was none. Basically, the prediction of asthma exacerbations remains a highly inexact science, and adjusting the dose of inhaled corticosteroids is a highly ineffective way of preventing them.

1024   The pleasures of oily fish are a matter of contention; but the benefit of fish oil in preventing cardiovascular disease events has been pretty definitely refuted in this widely publicized meta-analysis of 20 major studies of omega-3 supplementation by diet or supplements. My favourite fishy treat is a large, very fresh herring fried in butter; and could somebody please now do a meta-analysis proving that dairy fat has no association with heart disease? Not that I care in the least. Health is a subject that should never be mentioned at the table.

NEJM   13 Sep 2012  Vol 367
991   Fame is the spur that the clear spirit doth raise
(That last Infirmity of Noble mind)
To scorn delights, and live laborious dayes
as Milton observed in his great elegy Lycidas (1637). FAME-2 is the reason I am living a laborious day instead of enjoying late summer sunshine in the garden. This is quite a tough trial for a non-cardiologist to unpack, but potentially practice-changing. When the COURAGE trial was reported 5 years ago, the pendulum swung away from percutaneous intervention for stable angina towards optimal medical therapy: usually aspirin, statin and beta-blocker. Because outcomes were identical, there now seemed little point in even performing coronary angiography on most of these patients. But for better or worse, FAME-2 looks like pushing the pendulum back towards invasive investigation, because it demonstrates a huge reduction in the need for urgent revascularization in patients who show functionally significant stenoses. And in order to demonstrate a functionally significant stenosis you have to go into the coronary artery with a wire sensor which measures the fractional flow reserve. If this is below 0.8, patients will benefit from a drug-eluting stent, to such an extent that the trial was stopped early. Cardiac catheter labs will fill up again, at least in the USA. And many will spend laborious days arguing about this trial, but I shall be elsewhere. Read the accompanying editorial, nicely entitled, “Which Is More Enduring—FAME or COURAGE?”

1012   Pertussis is a very common cause of persisting paroxysmal cough in older children and adults. Before the advent of whole-cell pertussis vaccine, it used to kill a lot of babies (perhaps 10,000 annually in the USA), but by 1976 it had almost vanished in some parts of the USA. Since the whole-cell vaccine was replaced by acellular pertussis vaccine, however, there have been cyclical epidemics of whooping cough every 3-5 years, one of the worst being in California in 2010. This painstaking study of B pertussis infection detected by PCR during this epidemic demonstrates that immunity quickly wanes following the final vaccine dose (there commonly given at 6). The authors conclude that “Our findings highlight the need to develop new pertussis-containing vaccines that will provide long-lasting immunity.”

Other recondite delights which show that the great NEJM tradition is not dead include: Outbreak of Mycobacterium chelonae Infection Associated with Tattoo Ink, a clinical review of Melioidiosis (a potential agent of biological warfare) and an essay by Hartzband and Groopman which does not quite live up to its wonderful title,There Is More to Life Than Death.

Lancet  15 Sep 2012  Vol 380
977    The Lancet too has all its idiosyncracies on display this week, including this phase 2 trial of spray-applied cell therapy for chronic venous ulcers, run by Healthpoint Biotherapeutics in 28 centres across North America. The company had a major part in writing the paper and their “Interpretation” is that “Venous leg ulcers can be healed with a spray formulation of allogeneic neonatal keratinocytes and fibroblasts without the need for tissue engineering, at an optimum dose of 0•5×106 cells per mL every 14 days.” They demonstrated this to a p value of 0.045 in a subgroup of 43 patients, whose ulcers were “15.89%” smaller than those who had not received this treatment. Clinicians were free to apply sharp debridement at will. It is hard to decipher the time frame, and there is no mention of likely cost. I’m not even convinced this deserves a phase 3 trial.

986    By contrast, a potentially momentous breakthrough in the treatment of tuberculosis gets a wonderfully measured write-up from the Global Alliance for TB Drug Development. “PA-824-moxifloxacin-pyrazinamide is potentially suitable for treating drug-sensitive and multidrug-resistant tuberculosis. Multiagent EBA studies can contribute to reducing the time needed to develop new antituberculosis regimens.” This was a 14-day preliminary study: the accompanying editorial is worth reading to put it into context. These are exciting times: we may be on the verge of outsmarting this lazy old killer, but that will require cunning and patience as well as new drugs.

1011   Europe is in a political mess just now. The poor will suffer most, as always, and this grand Marmot survey of inequalities and health in 53 European countries shows that they already are. There is at least an afternoon’s worth of reading in this paper and its numerous fascinating tables. Whether its rhetoric will ever reach the ears of Angela Merkel and those who hold the future of Europe in their hands is another matter. Where there is no vision, the people perish.

BMJ   15 Sep 2012  Vol 345
Objective: To determine the effectiveness of interventions designed to improve outcomes in patients with multimorbidity in primary care and community settings.” Suggestion: you can’t do this. Complexity x complexity = too much complexity. “Conclusions: Interventions to date have had mixed effects, although are likely to be more effective if targeted at risk factors or specific functional difficulties. A need exists to clearly identify patients with multimorbidity and to develop cost effective and specifically targeted interventions that can improve health outcomes.” Well, kinda: perhaps try and move beyond the dustbin term “multimorbidity” and look at achieving patient goals and preferences when—wonder of wonders—they have more than one thing wrong with them.

A record linkage study from the UK tries to quantify the risk of preterm birth following treatment for intraepithelial cervical neoplasia. It comes out with an estimate of 2.3 additional preterm births per 100, considerably below that of previous, mainly Nordic, studies.

Last week I mentioned the renown that the town of Framingham (Mass.) has earned both from the Framingham Heart Study and the New England Wildflower Society Woodland Garden. We must also remember the knee. A separate cohort of Framinghamites over the age of 50—neither heart people nor their offspring, and probably not members of the Wildflower Society—underwent MRI scanning of their knees in this study. Those with knee pain in the previous month (29%) showed a 90-97% prevalence of MRI abnormalities. Those without knee pain in the previous month showed an 86-88% prevalence of MRI abnormalities. Conclusion: over the age of 50, having a normal knee is highly abnormal.

However you remunerate doctors, there will be perverse incentives—to do too little, or too much, or the wrong things. If you can get behind the BMJ paywall, you can enjoy a brilliant letter by Martin Roland which puts them all into a table.

Arch Intern Med  10 Sep 2012  Vol 172
1211   Cardiac troponin testing for myocardial infarction is a surprisingly recent phenomenon: I know it must be, because I can remember calling for its rapid adoption in one of these reviews in the early 2000s, when only 4 hospitals in England had the test available. Within a year they all had, and since then troponin measurement has changed both the definition and the management of MI throughout the world. But there is still that tedious wait of 6-12 hours to rule out MI in borderline patients with chest pain. Now that we have high sensitivity cardiac troponin T (hs-cTnT) tests, a lot of this may be avoided, according to this interesting European study which derived an algorithm for ruling out MI by two hs-cTnT measurements within the first hour of presentation at hospital with chest pain. When confirmed, this could lead to further major changes in practice and three-quarters of such patients walking home after just a couple of hours on the trolley.

1229   Scarcely a week goes by without some new gene locus or biomarker being heralded as a new risk factor for myocardial infarction on the basis of a hazard ratio of 1.27 or similar. Show me a hazard ratio of 25 or 30 and I’ll sit up and take notice. But then I am not an orthopaedic surgeon, and could never be mistaken for one; I drive an 11-year-old hatchback and wear a distracted, bookish air; I could never spring with annoying vigour from a brand-new Porsche left rakishly across two spaces in the private hospital car park. Someone needs to go over and tell these guys that total hip replacement is dangerous to the heart, and total knee replacement even more so. Above all, somebody needs to do an urgent trial of prophylactic aspirin and statins in these patients.

Plant of the Week: Rosa “Sombreuil” climbing

This lovely old rose is classed as a Tea Noisette and was introduced in France in 1850. It has scented flowers with tightly clustered petals of ivory-white, and with us it seems to keep its best display for September. It is moderately vigorous and seems to be able to handle a high degree of neglect—as shown by ours surviving for many years. We planted it right next to a particularly good vigorous form of shrubby hibiscus called “Blue Bird” (properly Hibiscus syriacus “Oiseau Bleu”) and the combination of the exotic deep mauve-blue hibiscus flowers and these aristocratic white blooms is irresistible. It would also look wonderful with any deep-coloured viticella clematis.

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