Richard Lehman’s journal review—16 March 2015

richard_lehmanNEJM 12 March 2015 Vol 372
1009 Stroke is a wonderfully straightforward word. When used in a medical context, everybody thinks of a sudden blow. It is something that needs swift action. But actually “stroke” isn’t a straightforward word: ask the cat that has just jumped on to my lap. Now it means a slow and pleasurable process in which she purrs while I pass my hand along her back. That’s the problem with words with deep Indo-European roots: the *streig root is well preserved in several languages, but over thousands of years it has come to mean almost opposite things. And brain strokes can vary between anything from a hammer stroke, which obliterates life, to a brush stroke, which causes some local weakness for a few days. The problem lies between the two ends, and in the need for investigations and treatment to be done at great speed. Two trials of endovascular therapy for ischaemic stroke with perfusion imaging selection in this week’s NEJM present a major advance in stroke treatment, but also illustrate these difficulties. The interventions compared in the first trial (mainly Australian and publicly funded) were intravenous alteplase within 4.5 hours with or without endovascular thrombectomy using the Solitaire FR (Flow Restoration) stent retriever. The patient groups had a mean age of 68 and 70 (the groups were not perfectly matched), and had occlusion of the internal carotid or middle cerebral artery, and evidence of salvageable brain tissue and ischaemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The trial was stopped prematurely because the thrombectomy group showed markedly better neurological improvement at three days and 90 days.

1019 The second trial was broadly similar and had a similar outcome: it was stopped early for efficacy. It was funded by Covidien, the manufacturers of the Solitaire FR device, but unlike the publicly funded trial it did not insist on the exclusive use of their product—strange! Anyway, the message is clear. If you have the means to select these patients, by CT angiography and CT perfusion imaging, then they will have a 2.6 fold better chance of a good neurological outcome if treated first with IV alteplase and then with a reperfusion procedure within 60-90 minutes. But pause a minute to consider what this might mean for stroke service provision. Time is of the essence: previous trials of reperfusion, like MR CLEAN, failed because their time frames and selection procedures were looser. So you need very rapid means of transfer and cutting edge CT technology with a team able to interpret it. The team must then discuss their recommendation with the patient or relatives, and proceed at once to perform a quite sophisticated procedure with its own hazards and learning curve. Adoption will not happen at a stroke.

JAMA 10 March 2015 Vol 313
1007 “The TAVR [transcatheter aortic valve replacement ] story is a wonderful example of a transformative technology that began with an idea many dismissed, gained momentum through iterative device modifications pioneered by industry, earned an increasing sense of feasibility with animal research and early human studies, achieved US Food and Drug Administration approval after reporting of findings from a pivotal randomized clinical trial, and expanded to additional clinical sites that met quality standards.” In their Viewpoint on Innovation and Implementation in Cardiovascular Medicine, the president of the American College of Cardiology and his colleague cite this “wonderful example” of the American Dream come true, but go on to lament the paucity of other examples. The answer? America needs more young heroes. “Established researchers and institutions need to support and mentor the next generation of innovators. If the courageous pioneers of cardiac surgery did not have the freedom to experiment or the strength to fail 50 or 60 years ago, where would cardiovascular care be today?” I see their point, but cardiovascular care today all too often consists of doing the interventions; plonking in the drugs (regardless of individualised preferences and likelihood of benefit); and a spiral of cost, futility, and repeated admission as the inevitable end approaches. The true heroes, young and old, will be the physicians and researchers who help to meet the difficult and exhausting needs of real people on the way to cardiac death.

1011 Last year, the statins debate took some strange and personal turns in the UK. The issues were complex and entangled in unhelpful ways, but one fundamental question is that of statin intolerance: why do the findings of clinical trials and clinical experience appear to differ so much? The best way to determine the true prevalence of statin related muscle pains would be through a large series of n-of-one trials with complete blinding and adequate washout periods; but this is never going to be practical. The worst would be to depend on GP record entries and patient discontinuation. There are some in-between possibilities and I look forward to Ben Goldacre’s coming short book on the topic. In the meantime, if you are interested in the issue, look up this quite useful Viewpoint.

1019 So just how wonderful an example of a transformative technology is TAVR (transcatheter aortic valve replacement )? This study looks at 12 182 procedures performed from November 2011 to the end of June 2013 in 299 American hospitals. The sex ratio was equal and the median age was 85. Most of these people would have been expected to die within a year or two, as TAVR is still mostly a last ditch procedure for people too frail to have open replacement. Among the patients who had TAVR, overall mortality was 23.7%, the stroke rate was 4.1% at one year follow-up. So at present we know that TAVR buys time in the very elderly: the other uses mentioned in the Viewpoint still need fuller evaluation. This is not yet the full American Dream.

JAMA Intern Med March 2015

OL The study of shared decision aids using a full information package for patients began at Dartmouth College about 25 years ago, and the pilot topic was benign prostatic hypertrophy. It was costly and labour intensive for clinicians and patients. Although the Dartmouth team covered a huge amount of conceptual ground and made a real difference in practice, the adoption of shared decision making has nonetheless been slow and patchy, even in relatively simple situations where there is a clear choice between options of similar efficacy. Here is a scoping study of how urologists and radiologists use decision aids when discussing treatment options with men who have localised prostate cancer. About two thirds of respondents in both groups don’t use decision aids at all. Those who do prefer those from their own specialist society. They all, presumably, have some financial interest in the treatment they recommend. This is not where we need to be.

OL I was born to Polish Seventh-Day Adventist parents. Because they frowned upon Ellen G White, who was the vegetarian founding prophetess of American Adventism, they were keen meat eaters, although too poor to afford meat more than a few times a year for a good part of my childhood. I mention these oddities because American Seventh-Day Adventists feature prominently in epidemiology: the Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96 354 Seventh-Day Adventist men and women recruited between 1 January 2002, and 31 December 2007. In this part of the study, they are segmented by diet: vegan, lacto-ovo vegetarian, pescovegetarian, semivegetarian, or nonvegetarian. During a mean follow-up of 7.3 years, vegetarian diets were associated with an overall lower incidence of colorectal cancers. Pescovegetarians (those who include fish in their diet) in particular had a much lower risk compared with nonvegetarians. But beware of extrapolating these results to the general population. The few Adventists who eat meat don’t eat pork or shellfish. They do not smoke and don’t drink alcohol. Most avoid caffeine. They keep a day a week (the seventh day) for rest and religious activity. They are close knit among themselves but semi-detached from the wider world, which they are bound to believe must end soon (adventism). For the same reason, they should not care about longevity, but nevertheless they pride themselves on it.

The Lancet 14 March 2015 Vol 385
966 Once I had broken free of Adventism, I was very keen to make up for lost time in the consumption of seafood, pork products, and alcohol, but never tobacco. In a way I regret that, because it means that I have no personal experience of nicotine addiction and therefore remain a mere preacher from the outside. Approaching 65, and happier than I have ever been, I don’t set a huge value on longevity, but I do hate the various horrible ways by which smoking kills people—heart failure, cancer, respiratory failure—or renders old age miserable with peripheral vascular disease, dementia, and macular degeneration. Yet the international commerce in death and misery has yet to peak among the poorest in the world, according to this analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control. If only Jesus would come with clouds descending and smite the people responsible. But since he won’t, we need to do it ourselves. There are three good pieces on the subject in this week’s Lancet:
A tobacco-free world: a call to action to phase out the sale of tobacco products by 2040
The road to effective tobacco control in China
Exposing and addressing tobacco industry conduct in low-income and middle-income countries

977 I am writing on a cold grey Sunday afternoon while getting over a combination of minor illnesses, and this would be an ideal opportunity to go to bed and mull over this classic Lancet survey of cancer survival between 1995 and 2009. It’s an immense and painstaking piece of work, and as usual the UK figures look pretty ordinary. So according to my fluctuating point of view, I could start thinking of reasons why all the others are skewed or how UK cancer detection and treatment need improving. But hey, it’s Sunday afternoon, I’m not very well, and that isn’t as much fun as carrying on rereading Don Quixote. (Few things are.)

The BMJ 14 March 2015 Vol 350
B-type natriuretic peptide (BNP) is the voice of the ventricles. When things are fine, it is heard as a low hum of content, but put the heart under strain and the murmur becomes a growl, and then a shout. All this happens within a few minutes, and dies down within half an hour. If you remember this, you will see why plasma BNP (or NTproBNP) has the diagnostic characteristics that it has. Below a certain level, it rules out “heart failure.” Above a certain level, it indicates that there is a problem, but it doesn’t tell you what it is or how long it has been going on. You can’t tell which ventricle is shouting or why. Used to monitor treatment, BNP fails because there is too much random variability or background noise. This systematic review sets itself the poorly defined task of “assessing the diagnostic accuracy of the natriuretic peptides in heart failure.” This turns out to mean acute heart failure, and sure enough the review concludes that a heart which is not shouting out BNP is not a heart that is failing. Beyond that, don’t trust it. If your patient has chest crackles and a high BNP, that could be heart failure; or it could be a chest infection with a degree of right ventricular overload. I have had quite a long relationship with this peptide, and it’s been a bit of a disappointment.

The National Joint Registry for England and Wales tells us that for the five main types of total hip replacement, 10 year revision rate estimates were all less than 5%, and in some instances considerably less. That’s very useful knowledge, which the authors of the study call a benchmark. I guess that means a quality standard, and therefore something to be monitored at the level of the hospital and the individual surgeon. But only with careful thought to avoid unintended consequences.

“In this review of NICE clinical guidelines, potentially serious drug-drug interactions were relatively common among recommendations for each of three index conditions (type 2 diabetes, heart failure, and depression) and 11 other common conditions.” This is massively important. We are poisoning far too many patients with guideline driven medicine and thoughtless polypharmacy, not helped by computer systems, which cry wolf so often about drug interactions that we have ceased to take any notice.

Plant of the Week: Clematis fasciculiflora

This large evergreen clematis was collected some years ago by Roy Lancaster on the slopes of the great Buddhist mountain Emei Shan in Sichuan province, China. The bunches of flower, which give it its name, appear in mid-March. They are creamy straw yellow, bell shaped, and sweetly scented. A real treasure then, and little known.

Ours was planted last autumn in a sunny sheltered position and it is just starting to flower, near the base of its stem. The leaves show no winter damage.

For years we had a huge specimen of Clematis armandii, which gave us lovely almond scented flowers at this time of year. But then it died of the wilt, and so has every replacement we have attempted. But most clematis species from the wild are wilt resistant, and we are praying that this also applies to those from the slopes of sacred Mt Emei Shan.