Richard Lehman’s journal review—12 August 2013

Richard LehmanNEJM  8 Aug 2013  Vol 369
507   A phase 1 study of a drug for an arcane cancer gets first place in the NEJM this week, and I think it deserves it, because ibrutinib seems to be a major breakthrough in the treatment of mantle-cell lymphoma. The name for once means something: this drug inhibits (hence “inib”) Bruton’s (hence “brut”) tyrosine kinase, which is a mediator of the B-cell–receptor signalling pathway implicated in the pathogenesis of B-cell cancers. This is clever pharmacology at its best, and resulted in a complete response rate of 21% and a partial response rate of 44%, whether or not the patients had received prior treatment with bortezomib. Expect further trials in other B-cell cancers.

517   Well if that was arcane, how about Sequence-Based Discovery of Bradyrhizobium enterica in Cord Colitis Syndrome? Ever heard of these things? Me neither, but if you delve into the paper you will learn that people with haematological malignancies who are treated with allogeneic hematopoietic stem-cell transplantation quite frequently get colitis. This can be caused by ordinary pathogens or by graft-versus-host disease, but there seemed to be something else going on when 11 out of 104 patients at Brigham and Women’s Hospital developed a syndrome of frequent non-bloody stool passage 3-11 months after receiving an umbilical stem cell transplant. In came the clever bacteriologists of Boston with their nucleic acid analyzers, and joy of joys, they discovered and named a gut pathogen hitherto unknown to science: Bradyrhizobium enterica. So they got a paper in the New England Journal, and all the patients got better with metronidazole or ciprofloxacin.

540   We’ve read a lot recently about the doubling of dementia risk in diabetic patients who experience severe hypoglycaemia: this paper by contrast is about the increased risk of dementia according to blood sugar levels below or above the threshold for diabetes. It’s a complex analysis of data from the 2067 participants in the Adult Changes in Thought cohort who had a mean age of 76 at enrolment and were followed up for a median of 6.8 years. The curves in Fig.1 for non-diabetic and diabetic subjects are fascinating. Below the threshold for diabetes, the curve goes consistently upwards, so that even small increments in blood sugar are associated with a small increase in dementia risk—just as they are with cardiovascular risk. But in treated diabetics, the curve is U-shaped, probably because of treatment effects. The best sugar level to avoid dementia if you are an elderly treated diabetic is 165mg/dl, i.e. about 9 mmol/L.

JAMA  7 Aug 2013  Vol 310
This week’s JAMA is themed around the consequences of violence and disaster. It seems to me that the doctor’s role in helping people who have been the subjects or the witnesses of violence is threefold: firstly, a simple human role of listening and empathy; secondly, an advisory and enabling role in helping people to find the psychological therapies that work best for them; and lastly and least, a prescribing role.

488   The prescribing role is the easiest to investigate. This study looks at the place of naltrexone in the treatment of people with “comorbid alcohol dependence and post traumatic stress disorder.” The two, of course, are frequently associated. This trial randomised subjects to four different combinations of naltrexone and/or prolonged exposure therapy, with supportive counselling thrown in. Alcohol use fell sharply in all groups, but most in those receiving naltrexone. In the UK, where neither supportive counselling nor prolonged exposure therapy are easy to access, it may be tempting for GPs to prescribe naltrexone to such patients for want of anything better: I suspect this is not a good idea.

Lancet  10 Aug 2013  Vol 382
507   “Small subcortical brain infarcts, commonly known as lacunar strokes, comprise about 25% of ischaemic strokes. Most result from disease of the small penetrating arteries.” The SP3 trial looked at the effect of blood pressure lowering to a systolic blood pressure target above or below 130 in this specific type of stroke. There was no significant difference in outcomes. Nonetheless, the authors hold to the principle “the lower the better” because for recurrent stroke and cardiovascular death the trend was towards reduction, and “treatment-related serious adverse events were infrequent.” I can go with this so far, but when you are talking about giving stroke patients lifelong medication on the basis of numbers-needed-to-treat which are incalculably large, even non-serious adverse effects such as tiredness, cough, polyuria and dizziness on getting up are hard to justify. Treat the patient, not the target.

516   CLOTS 3 is the acronym of a trial of intermittent pneumatic compression to reduce DVT on patients immobilized by stroke. If you try really hard you can extract these letters from “Clots in Legs Or sTockings after Stroke.” Going by initials, that should really be CILOSAS; but enough of acronyms, which provide innocent fun for researchers in the hope that they will help readers remember the trial. Preventing DVT after severe stroke is probably worthwhile, and these inflating stockings do reduce venous clots by about a third. The median age of the patients was 76, and a lot of them died: 33 fewer in the intervention group, which was not statistically significant given the large size of this UK trial.

BMJ  10 Aug 2013  Vol 347
The BMJ scoops what is perhaps the first case report of human-to-human transmission of H7N9 influenza. Does this spell doom to the human race? Not yet: the current virus has great difficulty spreading from person to person and could only become epidemic or pandemic if it shared its genes with a human influenza virus. But that could happen, because there may be a lot of subclinical H7N9 around, mostly in birds, but also in people. The editorial warns that “the threat posed by H7N9 has by no means passed.”

Helicobacter pylori is a moving target. Until the coming of antibiotics, it was probably carried by 90% of the human race, just as most mammals carry their own pet helicobactres. As we have sought increasingly to eradicate it, so it has sought to elude standard triple therapy. This global meta-analysis shows that on the whole, “sequential therapy is superior to seven day triple therapy and similar to regimens of longer duration and those including more than two antimicrobial agents.” But there are wide regional differences. Be guided by the friendly microbiologists who live harmlessly in the lining of your local hospital.

“2698 patients (were) recruited from local general practices before 2009 with heart failure, coronary heart disease, diabetes, or chronic obstructive pulmonary disease; and a history of inpatient or outpatient hospital use.” They were then individually randomized to usual care or “telephone health coaching (which) involved a personalised care plan and a series of outbound calls usually scheduled monthly.” The aim was to reduce hospital admissions. The result was to increase them. Since then, the most popular research idea seems to be to hand out iPads for education and monitoring to reduce admissions for chronic disease. Will this have any effect? Yes, I think it will increase disease awareness, anxiety, and iPad ownership.

The indefatigable Margaret McCartney takes a look at patient information leaflets: “a stupid system,” to quote the no less indefatigable fellow-Glaswegian Muir Gray. Different trusts pay different agencies to produce patient information with differing levels of inaccuracy, bias, and incompleteness. Apparently this is all going to change within the NHS over the coming years. It needs to change everywhere.

Patient information in the NHS may be hit-or-miss, but the quality of information in the BMJ’s Clinical Reviews is consistently superb. This week we have Frontotemporal dementia. Forgetting things, behaving inappropriately, failing to understand what people say, buying stuff you don’t need: recognize a pattern? Get your lobes into an MRI scanner at once.

Anns Intern Med  6 Aug 2013  Vol 159
161    Most doctors have a strong urge to save people from themselves. Deliberately or otherwise, we instil guilt into people about behaviours they find difficult to alter, in the hope of prolonging their healthy lives. This is often accompanied by an unpardonable sense of moral superiority, and success is measured in our terms, not the patient’s, because we can seldom quantify the likely benefit for most individuals. Fortunately this may be changing thanks to work by the U.S. Preventive Services Task Force (USPSTF). Here’s a proof of concept modelling study to give you a taste of what may be to come: “For an obese man aged 62 years who smoked and had hypercholesterolemia, hypertension, and a family history of colorectal cancer, the model’s top 3 recommendations (from most to least gain in life expectancy) were tobacco cessation (adding 2.8 life-years), weight loss (adding 1.6 life-years), and blood pressure control (adding 0.8 life-year). Lower-ranked recommendations were a healthier diet, aspirin use, cholesterol reduction, colonoscopy, screening for abdominal aortic aneurysm, and HIV testing (each adding 0.1 to 0.3 life-years). For a person with the same characteristics plus uncontrolled type 2 diabetes mellitus, the model’s top 3 recommendations were diabetes control, tobacco cessation, and weight loss (each adding 1.4 to 1.8 life-years).” I find some of this surprising, but I wouldn’t mind having a programme like this on my practice computer, updated quarterly.

Plant of the Week: Echinacea purpurea

The echinaceas are biggish plants of the daisy family, native to Eastern and Central parts of the USA, where they get a summer scorching and a deep freeze in the winter. They can just about take English summers, but tend to rot in the warmth of English winters.

The best varieties are worth taking a chance with, though don’t be surprised if they only last a year. They have scented leaves and flowers, and the latter can be spectacular. We like the greenish whites and the deepest brown-purples. It’s hardly worth giving you their names, even if we knew them. Just go to a nursery with a good selection in July or August, and pick the ones you fancy. You will love them while they last, and if the winter proves hard, you can take comfort in the chance that they may reappear to liven your garden next summer.