JAMA 10 July 2013 Vol 310
149 Fifteen years ago, JAMA was my favourite journal. Its covers were always beautiful, thanks to M Therese Southgate’s choice of paintings and works of art, and her short essays on each were unpretentious and delightful. The contents then were more clinically relevant than those of the Lancet or NEJM. Subsequently the journal went into gradual decline, which some hoped might be arrested by the arrival of Howard Bauchner as editor two years ago. But this week marks a low point. Howie B has got rid of the art. He has made all the other JAMA journals uniform and subservient to his, which is not the best of them. He has done away with independent statistical analysis for industry-funded research. Fifteen years later, JAMA is by no means my favourite journal, and it seems determined to press on in the wrong direction.
151 Still, it has the best piece in all the journals this week, which is an editorial by Harlan Krumholz on variation in healthcare—a trumpet call to wake up and start sharing decisions with patients. Just do as this guy says and healthcare will be sorted for the rest of the century.
155 There are two Medicare schemes in the USA, one which incentivises physicians to do more (Medicare FFS) and another that doesn’t (Medicare Advantage). So guess how this affects the number of patients having invasive cardiac procedures? Yes, there are more under FFS; but there are colossal variations in angiography rates under both payment systems, as this Denver study discovers. Nor is this anything new: in 2007 the rate of coronary angiography varied nearly 6-fold from 6.8 per 1000 Medicare fee-for-service beneficiaries in Honolulu, Hawaii, to 39.8 per 1000 in Gulfport, Mississippi. If a hurricane didn’t get you in Gulfport, a cardiologist would. It would be good to know what the pattern is in the UK: regions, plus private v NHS.
163 A clinical review in the NEJM a couple of months ago told us to change our whole conception about coronary atheroma: the really “critical” plaques may not be the ones that cause the obvious stenoses. On the contrary, the true villains are probably the deep soft fatty plaques that may not even disturb the lumen until they crack open and cause a thrombotic cascade. This thinking has yet to permeate the research literature, if it ever does: the “blocked” pipe analogy of CAD is so convenient for both patients and interventional cardiologists. And existing plaque is probably a good surrogate for hidden plaque, and should serve as a warning to use clot stabilising medications. I digress, led on by the fact that in New York State, nearly 70% of people subjected to coronary angiography have no obstructive atheroma, whereas in Ontario not far north, the figure is 55%.
189 I’m not a cardiologist, and I don’t get time to read all the specialist journals, but has there been any further work since COURAGE on stenting compared with various antithrombotic regimens for stable coronary disease? I’m led to wonder because there seem to be an awful lot of trials comparing agents after stenting—this review covers them—but not a lot about simply giving the drugs and omitting the stent. It seems to me that whenever a cardiologist does an angiogram on a person without unstable symptoms, all stents should be removed from the building, but maybe I’m missing something.
NEJM 11July 2013 Vol 369
111 In this remarkable trial, a group of Italian researchers were acting in breach of an ancient Roman law, the Lex Cornelia, enacted by Lucius Cornelius Sulla in 82 BC for the suppression of arsenic poisoning. The Borgias too, of course, tended to ignore this law: but they were not so intent on saving life as the triallists here, who were aiming to push up cure rates for promyelocytic leukaemia from 80% to 100%. And they succeeded, by using arsenic trioxide instead of conventional chemotherapy to augment all-trans retinoic acid. For this, they deserve at least a dukedom, if not the papacy: and may all their enemies fall sick and perish.
122 There are many reasons for not wanting to be a patient with advanced malignant melanoma: being on the brink of death, probably young, watching dark tumours appear around your body, and knowing that within a few years of your death, the condition may have become curable. In fact the cure may be here now, but nobody knows exactly what combination of monoclonal antibodies to use. This week’s NEJM shows them trying hard: in this first trial, Bristol Myers Squibb contributes ipilimumab and Ono Pharmaceutical contributes nivolumab. Ipilimumab blocks cytotoxic T-lymphocyte–associated antigen 4, and the other blocks the programmed death 1 (PD-1) receptor: in current clinical use they would probably cost more than $200K for a course of treatment. “53% of patients had an objective response, all with tumor reduction of 80% or more. Grade 3 or 4 adverse events related to therapy occurred in 53% of patients in the concurrent-regimen group, but were qualitatively similar to previous experience with monotherapy and were generally reversible.” So it works for about half of patients, and about half of these get severe adverse effects, which only go away if they stop it.
134 Nextonthelistomab sounds a bit nicer. It’s actually called lambrolizumab (and was previously known as MK-3475) and it also acts on the programmed death pathway. Again, it works to a promising extent in half of patients with disseminated MM: “responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013.” Adverse effects were fewer than with the previous agents. Those who’ve read Mukherjee’s The Emperor of Maladies will be reminded of similar tantalizing periods preceding breakthrough with other cancers such as Hodgkin’s disease in previous decades. But did cancer survival ever before come with such a daunting price tag? Write to email@example.com who is organizing a group of oncologists and other health professionals to do something about unaffordable drugs for cancer.
145 What can we do about type 2 diabetes? At present we achieve most benefit by controlling blood pressure and prescribing statins, and a bit of good by keeping glycated Hb under 9%. But surely we would achieve the greatest reductions in cardiovascular events through an intensive lifestyle intervention to increase exercise and reduce weight? The Look AHEAD trial hoped to prove this within the pre-specified thirteen years, but instead it was abandoned for futility at 9.6 years. The patients in the intervention arm did well at keeping their weight down and having better levels of fitness; they even had lower sugar levels; but they did not score better on a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina. This is a truly disappointing result from a well-designed non-drug trial which worked hard to achieve its desired surrogate end-points, but failed to achieve the end-points that mattered. Everybody would like to see a positive result from a trial in diabetes; but so far only bariatric surgery seems to deliver any goods, and that’s a message not one of us really likes to hear.
Lancet 13 July 2013 Vol 382
The main articles of interest in this week’s Lancet once again come from China and deal with the threat of H7N9 influenza, which currently seems to be receding due to the closure of live poultry markets. Remember that when it was first reported in 2009, H5N1 influenza seemed to have a high mortality rate and affected younger people. In the end it turned out to have a lower mortality than ordinary annual flu. The same might turn out to be true of H7N9, if it ever becomes pandemic, but we simply don’t know. As the editorial states, “the symptomatic case fatality risk could be between 160 (95% CI 63—460) and 2800 (1000—9400) per 100 000 symptomatic cases. This estimate is highly sensitive to assumptions about testing propensity, surveillance coverage, and health-care seeking behaviour.” Add to that the uncertainties of viral mutation and you’d be hard put to say anything meaningful.
The most praiseworthy aspect of this journal is its emphasis on improving health in poor countries through specific interventions: this week it is the use of external facilitators to introduce audit and better practices to hospitals in Senegal.
The least praiseworthy aspect of this journal—apart from some truly awful pharma studies—is its encouragement of sentences like “Collaboration across general and specialised healthcare professionals is needed to fully address the challenge of prevention of acute and chronic kidney disease and improve outcomes.” Poor authors are almost forced to come up with stuff like this when they are given titles like “Evolving importance of kidney disease: from subspecialty to global health burden.” And though I agree that kidney disease is a subspecialty that has grown disproportionately, I don’t think that renal physicians really count as a global health burden, however hard some of them try. Moreover I am baffled by the term “Global Kidney Disease,” under which this article appears. I had not heard of it before. Are global kidneys a subtype of polycystic kidneys, or are they born global?
BMJ 13 July 2013 Vol 347
More evidence that we don’t know anything substantive about the natural history of H7N9 flu. China has set up a system of sentinel hospitals to chart the spread of this epidemic by contact tracing, but this report can only describe five individuals in the community who were detected by this method. They ranged in age between 2 and 26 (compared with a mean of 60 in the published hospital series) and they all had a mild illness and made an uneventful recovery.
At the moment I am reading Chris Dowrick’s Beyond Depression (OUP 2009), which I’m finding one of the best written and best argued books ever to come out of UK academic primary care. I haven’t got to the drugs bit yet: I suspect I shall disagree with some of it, but then when don’t I? However, I cannot see “lithium” in the index. You will recollect that lithium is as old as our Universe, having formed in the first second of the Big Bang together with hydrogen and helium. Cosmologists puzzle over why there is so little of it about. Psychiatrists puzzle over when to use it and how often to monitor blood levels of it. But there seems no doubt at all that it reduces the risk of suicide in mood disorder: the odds ratio given in this meta-analysis is 0.13 (95% CI 0.03-0.66) and it even seems to have an all-cause mortality benefit in these trials. “Lithium may exert its antisuicidal effects by reducing relapse of mood disorder, but additional mechanisms should also be considered because there is some evidence that lithium decreases aggression and possibly impulsivity, which might be another mechanism mediating the antisuicidal effect.”
The clinical review this week is shared with the Drugs and Therapeutics Bulletin and struggles to make sense of infantile colic and its management. The passage of time has deprived us of all useful remedies: laudanum, gin, gripe-water, even dicyclomine. Referral to the health visitor is our remaining last resort. Anything to make the weeks go by.
The head to head this week pits John Castellani, president and chief executive officer, Pharmaceutical Research and Manufacturers of America (PhRMA) against our own Ben Goldacre. Castellani argues that clinical trial data shouldn’t be disclosed any more than they are already for fear of breaching the intellectual property rights of companies and reducing pharma’s financial incentive to produce new drugs. Ben… well, Ben does not agree. It’s as if there are more important things than just producing new drugs, like finding out if they work and whether they harm people.
JAMA Intern Med 8 July 2013 Vol 173
1175 People with chronic obstructive pulmonary disease have irreversible airways damage which is usually caused by smoking. Inhaled long-acting beta-adrenergic drugs or anticholinergic drugs seldom make more than a small difference to their symptoms, but can do bad things to their hearts. This is confirmed in a large Canadian case-control study: new use of these inhalers is associated with an increase in cardiovascular hospital admissions of around 30% in COPD patients aged 66 or older. “Close monitoring of COPD patients requiring long-acting bronchodilators is needed regardless of drug class.” Nonsense: the close monitoring should be of physicians, to stop them using these drugs.
1195 I always wriggle uneasily when I hear people trying to argue that shared decision making will decrease health costs. It may, or it may not. It will certainly take up more medical time, and increase patient knowledge, and this may lead to greater demand where there is underprovision, and less demand where there is overprovision. It’s no use generalising from one health system or one clinical condition to another. This study shows that patient preference to participate in decision making concerning their care may be associated with increased resource utilization among hospitalized patients in the University of Chicago Medical Center. No matter: you either believe in SDM as a human right, or you don’t. In the end, doing things better never saves costs in healthcare.
Plant of the Week: Rosa “Absolutely Fabulous”
I have had a strange relationship with roses. I started by affecting a snobbish dislike of the entire tribe, but then decided that climbing roses were a good thing, provided that they were of sufficiently distinguished pedigree. The only bush rose permitted into the garden was the very ancient Coptic monastic rose Rosa richardii, for obvious reasons. It still flowers abundantly and has a wonderful scent of hymn books.
I am afraid that with the depravity and abandon of age, I can fall for any nice looking and nice smelling rose these days. To plant by the garden bench were we hope to sit and crumble slowly in summers to come, my wife chose “Indian Summer” and I chose “Absolutely Fabulous.” Mine starts deep yellow with a hint of orange, and then unfurls to give out a wonderful scent of sweet liquorice, before the flowers fade and are replaced with a dozen others all season long. It was not named after the television series, but after an exclamation from a rose grower. Yet this is not its true name in the strict sense, as it was raised in America and originally named after Julia Childs, the food writer.