JAMA 27 June 2012 Vol 307
2595 Of all the things that made me glad to retire from general practice two years ago, pay for performance must top the list. Here’s a Viewpoint piece from the USA which explains why: “Focusing on specific outcomes does not reward skills or result in managing complexity, solving problems, or creativity. Indeed, Pink suggests such reward systems will undermine these desirable attributes.” Good old Pink: I like the cut of his jib. “Translating the ideas of Trisolini and Pink into a clinical medicine context leads to several recommendations: pay physicians a rewarding yet reasonable salary rather than piecework rewards, provide a direct ability to influence patient outcomes, and offer a continual sense of accomplishment and recognition. These would represent a more effective approach to motivating performance than specifically paying for production functions.” Good old Trisolini, too: nice jib. And here is the last paragraph of this excellent piece by Christine Cassell and Sachin Jain: “Efforts to assess physician performance are here to stay. The current system of care has invested a great deal in these measures, both financially and intellectually, and the goals they seek to achieve are critical to a high-functioning healthcare system. To reach sustainable quality goals, however, close attention must be given to whether and how these initiatives motivate physicians and not turn physicians into pawns working only toward specific measurable outcomes, losing the complex problem-solving and diagnostic capabilities essential to their role in quality of patient care, and diminish their sense of professional responsibility by making it a market commodity. Rewards should reinforce, not undermine, intrinsic motivation to pursue needed improvement in health system quality.” Amen.
2597 And now from the man who has worked harder than anybody to improve health service quality—Donald Berwick’s address to Harvard medical graduates as they set out: “You will soon learn a lovely lesson about doctoring; I guarantee it. You will learn that in a professional life that will fly by fast and hard, a hectic life in which thousands of people will honor you by bringing to you their pain and confusion, a few of them will stand out.” The one who stands out for him is called Isaiah. He was a black child, addicted to cannabis at 5, crack at 14, by which time he had already done his first armed robbery. Berwick saved him from acute lymphoblastic leukaemia. He was found dead in the street 18 years later. “Society gives you rights and license it gives to no one else, in return for which you promise to put the interests of those for whom you care ahead of your own. That promise and that obligation give you voice in public discourse simply because of the oath you have sworn. Use that voice. If you do not speak, who will?”
2600 And now back to the kind of medicine that gets published in journals. A lot of people who get ischaemic stroke are taking warfarin, usually for atrial fibrillation. Is it safe to give these people intravenous tissue plasminogen activator (tPA) if they get an ischaemic stroke? The bottom line seems to be yes: “Conclusion: Among patients with ischemic stroke, the use of intravenous tPA among warfarin-treated patients (INR ≤1.7) was not associated with increased symptomatic intracranial haemorrhage risk compared with non–warfarin-treated patients.” But read that again. These patients were not being meaningfully anticoagulated with warfarin: their INRs were all 1.7 or less. Had their warfarin been properly monitored, they would probably never have had their stroke in the first place.
2609 Another study supports the idea that children who show an excellent response to chemotherapy for Hodgkin’s disease do not need to undergo the rigours of involved-field radiotherapy, with all its potential for long-term harm.
NEJM 28 June 2012 Vol 366
2443 “The programmed death 1 (PD-1) receptor is another inhibitory T-cell receptor that is engaged by its two known ligands, PD-L1 (also known as B7-H1 or CD274) and PD-L2 (also known as B7-DC or CD273), primarily within the tumor microenvironment.” They don’t make it easy for us, do they? But rather than complain, let us here praise cancer immunologists, who work with endless diligence on all these strangely numbered ligands and obscure pathways, so that eventually we may have drugs which produce lasting cures in patients with advanced metastatic cancer. Two studies in this week’s NEJM report on the anti-tumour activity and safety of antibodies that specifically block PD-1. In a range of end-stage cancers, anti-PD-1 antibody can produce a response which is usually durable for over a year. Patients with metastatic melanoma, non-small-cell lung cancer, renal cancer and a few other hitherto untreatable advanced malignancies may experience large improvements in survival: but four-fifths do not. The editorial on these trials offers the prospect that cancers may be testable for PD-1 expression in the future, so this treatment can be targeted. “The durability of the tumor response to anti–PD-1 and anti–PD-L1 antibodies in a great majority of patients who had objective tumor regressions in the studies by Topalian et al. and Brahmer et al. predicts that these antibodies unleash a memory immune response to cancer. The use of PD-1 blockade—with its reduced rate of toxic effects and potential ability to further select patients who have an increased likelihood of tumor response—may well have a major effect on cancer treatment.”
2466 Infective endocarditis is a pleasing diagnosis to make, but not a good one to receive. Ever since I first read it at the age of 18, I’ve been haunted by this scene from the memoirs of Alma Mahler: “Chantemesse, who was a celebrated bacteriologist, now made a culture from Mahler’s blood and after a few days he came to us in great delight with a microscope in his hand. I thought a miracle had happened. He placed the microscope on the table. “Now, Madame Mahler, come and look. Even I—myself—have never seen streptococci in such a marvellous state of development.” But I could not listen. Dumb with horror, I turned and left him.” In the trial reported here, patients with left-sided infective endocarditis, severe valve disease, and large vegetations were randomly assigned to early surgery (37 patients) or conventional treatment (39). The primary end point was a composite of in-hospital death and embolic events that occurred within 6 weeks after randomization. It was a small trial, but an easy win for surgery done within 48 hours.
2483 A quarter of a million American women sought assisted reproduction between 2004 and 2009, and this resulted in over 140,000 live births. This is pretty amazing: “live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favourable patient and embryo characteristics.” In older women, donated oocytes perform better than autologous oocytes.
Lancet 30 June 2012 Vol 379
2412 Appalled by the prospect of the Supreme Court declaring Obama’s health act unconstitutional, Richard Horton is moved to fill the whole of Offline this week with an eloquent, coherent, historically informed view of America’s strange relationship with its health providers, and how this distorts the whole of global health provision. I never thought to write such praise of Offline; but I still prefer Victor Montori on Twitter: “Health care is a human right. Societies must protect and promote it. Debate how, not whether.”
2459 I don’t know how far down the line the NHS may be in ensuring pulse oximetry for every newborn baby, but it’s time we got on and did it. The trials have accumulated and now this meta-analysis shows a specificity for congenital heart disease of 99.9% in asymptomatic babies, with a sensitivity of 76%. It’s simple, cheap and has no harms that I can think of.
2466 Cholera causes diarrhoea of such severity that the mean time from onset of symptoms to death in the Haiti outbreak was 12 hours. It’s really a very simple disease, as this review shows: it is preventable by vaccines and by a reliable supply of clean water, and it is easily treated with fluid replacement and with antibiotics in more severe cases. I guess that Vibrio cholerae is never going to disappear completely, but as a threat to human health will disappear as soon as we have a decent global system.
BMJ 30 June 2012 Vol 344
An excellent editorial by Trish Groves and Fiona Godlee praises the new Royal Society report Science as an Open Enterprise: Open Data for Open Science and the government policy report by Jane Finch which recommends open access publication for all government-funded research. Things have moved at a terrific pace in the last six months: in November I set up a Google group called PATH (Publish All Trials on Humans), in the hope that it would bring together leading advocates of open data sharing in clinical research. I little thought that within six months, thanks to the Royal Society and others (including the BMJ), it would become the accepted norm. There is plenty yet to be done, so do look up the discussions and join if you are interested. And do read the Royal Society report: it’s a cracker.
Those of us who are interested in the full disclosure of all data from clinical trials are not all paranoid geeks by nature. It has taken me the best part of fifteen years to realise how biased and incomplete the evidence base for common interventions can be, despite the efforts of the regulatory agencies. A classic case was rosiglitazone (Avandia) where cardiovascular harms were suspected from the start, but were supposedly laid to rest in the open-label RECORD trial, sponsored by the manufacturers; in fact there is clear evidence of biased adjudication in this study, presented to the FDA two years ago and never explained since. I was therefore stunned to see the RECORD study appear in this meta-analysis of new oral anticoagulants following hip and knee replacement, again in the context of a seemingly biased adjudication. To quote in full: “However, major bleeding rates reported in the four pivotal RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes) studies with rivaroxaban were 7-8 times lower than those in the enoxaparin groups of the remaining studies, which was attributed to the exclusion of most wound bleedings from the definition of major bleeding, as previously reported. This issue prevented the pooling of data on major bleeding reported in the publications of the RECORD studies. However, the major bleeding rates in the RECORD studies without excluding major wound bleedings were reported in an FDA review, and were similar to the major bleeding rates of the remaining studies.” Hmm. I thought there was only one RECORD study, which was nothing to do with rivaroxaban. In fact there are four others, sponsored by Bayer and Johnson and Johnson, in which the acronym stands for Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism. It is time for the BMJ to set the RECORD straight. As for the meta-analysis, it proves that it’s swings and roundabouts with dabigatran, rivaroxaban, and apixaban for preventing VTE: the new oral agents may be slightly more protective than enoxaparin, but at the cost of slightly more bleeds.
Plant of the Week: Philadelphus “Belle Étoile”
I once used to devote this section to rarities, but this mock orange is far from rare, except in the Elizabethan sense of wonderful. “Most rare in scent upon the summer air” as Shakespeare (or Drayton, more likely) might have put it. As far as I am concerned, it cannot be common enough.
At this time of the year, I yearn to have every species and hybrid of philadelphus, except for the few wretches without fragrance. All of them flower abundantly and take no notice of the wind and rain of English high summer. It doesn’t even have to be warm for them to fill the whole garden with intoxicating perfume.
I have no idea why they carry the Greek name for brother-loving. The word philadelphos is a rather late coinage, since in early Greek myth, brothers were quite likely to try and kill each other. Later still the term became very popular in Christian theology as another expression for agape or non-sexual love; and maybe the pure white flowers of some philadelphus species reminded some botanist of chastity. But a summer garden filled with the evening scent of mock orange is not, in my opinion, conducive to chastity. Happily, quite the opposite.