Richard Lehman’s journal review—13 October 2014

richard_lehmanNEJM 9 October 2014 Vol 371
1381  With blood transfusion, it seems that less is usually better. This has been shown in renal patients and palliative care, and is now reconfirmed in septic shock. Fifteen years ago, the Canadian Critical Care Trial Group study showed that transfusing critically ill patients at threshold of 10 G/dl of haemoglobin produced worse outcomes than using a threshold of 7. Now Scandinavian triallists have gathered and randomised 1000 patients with septic shock in 32 general ICUs in Denmark, Sweden, Norway, and Finland: a logistic feat to be wondered at. They have shown that a threshold of 7 is as good as a threshold of 9, saving gallons of blood. In fact, it halves the amount of blood used.

1369  I’m struggling to find anything else to report on from the NEJM this week, partly because I have exhausted most of the generalist items on the website. Most of the remaining pieces are about Ebola virus, a subject on which I don’t feel qualified to comment, though no doubt I shall be driven to before long. So instead I offer for your delectation the opening sentence of a perspective piece on deep brain stimulation for Parkinson’s disease: “Scribonius Largus, the court physician for the Roman emperor Claudius, used an electrical torpedo fish in 50 A.D. to treat headaches and gout.”

JAMA 8 October 2014 Vol 312
1409  Paper JAMA and its website are full of stuff about infectious diseases this week. Where to begin? Well, the journal starts with two immunogenicity trials of avian flu vaccines, so we might as well get them out of the way. Should human beings need protection against avian influenza A/H7N9, they now probably can have it, since: “Point-of-use mixing and administration of 2 doses of H7N9 vaccine at the lowest tested antigen dose with MF59 adjuvant produced seroconversion in 59% of participants. Although these findings indicate potential value in this approach, the study is limited by the absence of antibody data beyond 42 days and the absence of clinical outcomes.”

1420  We’re further ahead with H5N1. “Previous receipt of a single dose of influenza A(H5N1) Vietnam vaccine was associated with sufficient immunologic priming to facilitate antibody response to a different H5N1 antigen using low-dose Anhui (booster) vaccine.” So we really have this one taped.

1438  OK, and now for antibiotics. Great Britain is an island and we have managed to keep our rates of antibiotic resistance in the community nice and low. And, in fact, you don’t have to be an island to do this: resistant strains of bacteria won’t travel far unless they have handy vectors and susceptible hosts. Hospitals everywhere, however, provide ideal microenvironments for breeding resistance, with a wonderful wealth of vectors and bed after bed containing susceptible hosts. And, because of this, hospital doctors tend to spurn the common antibiotics that still work so well in the community and go straight to the big guns. Half of all patients in this large survey of American hospitals received antibiotics during their stay. The commonest was intravenous vancomycin, followed by ceftriaxone, piperacillin-tazobactam, and levofloxacin. I don’t know what the answer is. When I am very sick, I hope I get the antibiotic most likely to work first time. Call me a selfish member of the herd, but I have no inclination to be a martyr in the cause of better stewardship.

OL  Equally, I don’t want to leave hospital with Clostridium difficile owing to antibiotic overuse. But a very effective way of treating C. diff has already been found. You can go to websites with pictures of kitchen blenders containing brown material and tubes by which you can administer it to yourself. I think I could find a willing stool donor too. Now researchers at Massachusetts General Hospital have tried out oral capsules containing frozen donor microbiome. In a phase 1 trial on 20 patients, it worked for 70% of the patients with treatment-resistant C diff. Some have objected to JAMA publishing such a small unblinded study, but to me this sounds like hot shit. Sorry, very cold faeces.

Ann Intern Med Vol 161
OL  Lurking on the Annals website since 9 September is a very useful updated systematic review of the Comparative Effectiveness of Pharmacologic Treatments to Prevent Fractures. You can download it free of charge, and it’s worth doing that because this is a topic which comes up every week in general practice, and the treatments used are continued for years. They work and most have been around for a long time, but we still lack information to support informed choices: “Few studies have directly compared drugs used to treat osteoporosis. Data in men are very sparse. Costs were not assessed . . . Side effects vary among drugs, and the comparative effectiveness of the drugs is unclear.” The usual story—so much research, so little to guide patients and clinicians.

Lancet 11 October 2014 Vol 384
1349  If I were Oscar Wilde, I would stretch my legs and declare, “My dear, if I have to read another of these trials I shall simply die of tedium.” The object of despair is called: “Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial.” Spending on type 2 diabetes in the UK is rising disproportionately, driven by incretin mimetic drugs with unknown long term effects. So here is a single blinded trial run by Eli Lilly to test its me-too contender. The language used is rather strange. “An independent external committee adjudicated deaths and non-fatal cardiovascular adverse events in a masked manner, with prespecified event criteria based on the preponderance of the evidence and clinical knowledge and experience.” What does that actually mean? And if that is obscure, look at the conclusion, presented in statistic-wonkese: “Once-weekly dulaglutide is non-inferior to once-daily liraglutide for least-squares mean reduction in HbA1c, with a similar safety and tolerability profile.” Delve deeper those who will: for my part I shall yawn and send for a good cigar, a glass of hock and seltzer, and a green carnation for my buttonhole.

OL  Here is a trial with the acronym SARAH, which is to do with hand exercises for rheumatoid arthritis. Oh, and the principal investigator is called Sarah Lamb. “We have shown that a tailored hand exercise programme is a worthwhile, low-cost intervention to provide as an adjunct to various drug regimens.” Congratulations Sarah/SARAH. You don’t often see a trial of a non-drug, non-device, non-surgical intervention in the Lancet.

OL  Here is the other end of the spectrum: the transplanted womb report. If you can access the PDF, you can see the uterus in question sitting on the surgeon’s glove, look at the ultrasound pictures, scan the tocograph, and ooh, see the tiny new baby itself. What I hadn’t realised is that: “Uterus transplantation is the first ephemeral type of transplantation that has been introduced in which the graft is not intended for lifelong use. The uterus can be removed after one or two babies have been born, which would reduce the long-term side-effects caused by the immunosuppressive drugs.”

The BMJ 11 October 2014 Vol 349
Talking rationally about antibiotic use in primary care seems unusually difficult, if the editorial in this week’s The BMJ is anything to go by. It is a good piece—far better than anything I have seen in the media or indeed from the Department of Health. But it lumps all prescribing together and then concentrates on prescribing for respiratory tract infections, which we all know are mostly viral. Doctors’ behaviours are criticised, but after 40 years I still have difficulty telling a viral set of chest crackles from a bacterial one. And, fortunately in the UK, the leading antibiotics for respiratory infections have shown no drift towards resistance. Soft tissue and skin infections are generally easy to recognise (except when they overlap with insect stings) and, with the still uncommon exception of MRSA, are easy to treat. Urinary tract infections are a separate category, and it’s here alone that problems of true bacterial resistance are a common cause for patients to return. It’s rare to do an out-of-hours shift in the Thames Valley (which, by the way, has the UK’s lowest rate of antibiotic prescribing in primary care) and not have someone turn up with ascending urinary tract symptoms because the trimethoprim she was given has not worked. But we know that a general shift towards cefalexin or ciprofloxacin as first line treatment would produce a general loss of effectiveness. Anyway, it’s time for me to shut up now: I was only taking my chance while the chief medical officer’s back is turned towards Ebola.

Long term survival with thoracoscopic versus open lobectomy: propensity matched comparative analysis using SEER-Medicare database” may not be a title to catch the weekend interest of most GPs. I read this because of late I’ve got somewhat interested in shared decision making before surgical procedures. What sort of information do patients need to make informed choices? This is a database study of 6008 patients undergoing some form of lobectomy for lung cancer. So it depends on “propensity matching” to balance out clinical characteristics between comparison groups. One step down from a randomised controlled trial then, and often quite a big step down. And in all surgery much depends on operator skill, volume, and experience. So not even a RCT can ever fully inform choice, but this analysis usefully tells us that patients undergoing thoracoscopic lobectomy had similar overall, cancer specific, and disease-free survival compared with patients undergoing thoracotomy lobectomy.

Speaking of informed choice before procedures, how many patients accurately perceive the benefits of elective percutaneous coronary intervention in stable coronary artery disease? I don’t know the answer for British patients, but John Spertus and his team have tried to find out about Americans. The answer, of course, is not very many: 90% thought that the procedure would extend life and 88% thought it would prevent a future heart attack. So much for the public understanding of evidence based medicine versus the vested interests of interventional cardiologists.