21 Oct, 13 | by BMJ
NEJM 17 Oct 2013 Vol 369
1491 “Tiotropium (Spiriva, Boehringer Ingelheim), a long-acting inhaled anticholinergic bronchodilator, improves lung function, quality of life, and exercise endurance and reduces exacerbations in patients with chronic obstructive pulmonary disease (COPD).” I quote not from an advertisement for Spiriva, but from the start of a paper comparing one delivery method of tiotropium with another, showing that they have the same safety and effectiveness. The ringing claims of this sentence are supported by citations from four previous trials, all funded by Boehringer-Ingelheim, which makes profits of more than $4 billion annually from the sale of this drug. If it can prolong its patent life by changing the delivery method, that means another few years of blockbuster sales. This Handihaler vs Respimat trial wins extravagant praise from the editorialist, who discloses that she has accepted speaker’s payments from the manufacturer. Just one small problem: “it is important to note that the absence of a placebo group in this study has implications for its interpretation and that it cannot be concluded from these results that tiotropium reduces mortality in patients with COPD.” Well, indeed. A Cochrane review found that continuous tiotropium use in COPD patients has a NNT of 16 to prevent one exacerbation and has no effect on mortality. And even these modest conclusions are based largely on industry-run trials with no independent replication studies. Health systems spend billions of dollars uncomplainingly on drugs of marginal effectiveness, while bridling at the thought of giving a few extra millions for impartial comparative effectiveness research. It’s mad.
1512 The miseries of self-conscious pubescence often include the wearing of a brace, ensuring that the young person’s dentition will appear repulsive to the opposite sex. But imagine the misery of a brace worn not in your mouth, but down your entire back. Such was the fate of 143 participants aged 10 to 15 in this trial of bracing vs observation for adolescent idiopathic scoliosis. Wearing of the spinal brace for at least 15 hours a day was measured using a temperature sensor in the brace. Those who persevered were rewarded by a very significant reduction in spinal curvature: this old-fashioned treatment actually works.
1522 A few weeks ago, I was surprised to find colchicums flowering early in the alpine meadows of the Haute-Savoie. They looked lovely, though I would not particularly recommend them for most gardens because (a) they seem to flop over too readily and (b) they are very poisonous. But many of our best drugs come from plant poisons, and colchicine has been used for at least three and a half thousand years. The Egyptians used it for rheumatism, others used it as an emetic and/or laxative, and of course all of us still use it from time to time for gout. In this Italian double-blinded randomized trial it was used for acute pericarditis, and taken continuously in combination with anti-inflammatory painkillers it reduced persistence or recurrence of pericarditis. But the most surprising aspect of this trial was the lack of diarrhoea: “Gastrointestinal disturbance was the main side effect and was reported with similar frequency in the two groups (9.2% in the colchicine group and 8.3% in the placebo group, P=0.67).”
JAMA Intern Med 14 Oct 2013 Vol 173
1672 Vitamin D is a most annoying vitamin. Observational studies link it to all sorts of things, like cognitive function, cardiovascular health, muscular strength, and pretty well everything else you want to hang on to. There are vitamin D receptors all over the body, with lots in the brain and arteries. But if you give extra vitamin D to people, it generally doesn’t do anything measurable. I suspect that this is because you need to have had enough early in life, perhaps even prenatally. By the time you are old and have systolic hypertension, meaning your arteries are stiff, it is a tall order to expect vitamin D to bring back their bounce. And indeed this trial of cholecalciferol to improve isolated systolic hypertension in the over-70s achieved nothing.
1682 Eat meat, eat fruit, eat salt, drink wine! Try stopping me. But is this the dietary advice that your practice nurse gives to your patients with high-risk type 2 diabetes patients with microalbuminuria? It jolly well should be, according to this follow-up study of the ONTARGET trial, which focussed on chronic kidney disease progression. “Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95% CI, 0.65-0.87) and mortality (OR, 0.69; 95% CI, 0.53-0.89).”
1725 Michael O’Donnell has spent a lifetime trying to make doctors kinder, less pompous, and more conscious of the words they use. It is forever a losing battle, but forever one that must be fought; and the fun it brings along the way is its main reward. I loved the use of the term “Outreach Colonoscopy” in the title of this paper, which describes a project to bring colon cancer screening to the uninsured poor of a county in Texas. The project was entirely worthy and had some success. But it also conjures up a charming image of eager colonoscopists on the streets of Texas, chasing nervous citizens with their outstretched instruments of inspection.
JAMA 16 Oct 2013 Vol 310
1571 “Objective: To assess whether wearing gloves and gowns for all patient contact in the ICU decreases acquisition of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) compared with usual care.” Result: it made no difference.
1581 The FREEDOM trial showed that in patients with type 2 diabetes and multi-vessel coronary disease, coronary artery bypass graft (CABG) surgery resulted in lower rates of death and myocardial infarction, but a higher risk of stroke when compared with percutaneous coronary intervention (PCI) using drug-eluting stents. There is complete equipoise between the options, so the patient should be the one to decide. And thanks to the use of the Seattle Angina Questionnaire throughout the follow-up period, we have a very good idea of how the two procedures affected the way patients felt and functioned after the two procedures. For the first two years, there was a slight advantage in the CABG group, but after that it was no longer discernible. There’s a crying need for a decision aid to be used by all patients and doctors facing these alternatives.
1601 In 2000, the NEJM published the first large observational study showing that the use of metoclopramide in the first trimester of pregnancy was not associated with any increase in fetal abnormalities. That came as a great relief to me because I then had a safe option for treating morning sickness in a large number of pregnant women in subsequent years. Now a massive Danish registry study confirms the safety of metoclopramide for pregnancy-related nausea and vomiting. Looking at a million and a quarter pregnancies, metoclopramide-exposed and unexposed women were matched (1:4 ratio) on the basis of age, calendar year, and propensity scores and no differences were found. Confirmation on this scale is always nice to have.
Lancet 19 Oct 2013 Vol 382
1341 The Greeks gave the name pessos to an oval stone which was used for board games. But by the time the word reached Latin as pessarium, it was used to denote something pushed into the vagina; and this seems to be the sole meaning of the English word “pessary.” Word for Windows still refuses to acknowledge the existence of such indelicate objects. In this study of twin pregnancy, the pessaries were devices designed to be inserted at 16 to 20 weeks’ gestation in the hope of preventing preterm birth. I don’t know what shape they took, because the paper provides no illustrations. Anyway, they were about as much use as an oval stone.
1350 Zoroastrianism seems to me the most admirable of religions, but after its first thousand years it had developed some really odd practices, such as the persecution of cats and owls as creatures of Ahriman (Satan), and strong approval of consanguineous marriage, including what we would class as incest. This greatly outraged the fifth-century Christian Bishop of Caesarea, Basil the Great, who led the attack on the ancient religion of the Persians, though in fact a great deal of what is best in Christianity has its roots there. Nowadays there are only a few hundred thousand Zoroastrians in the world, but consanguineous marriage remains popular in the regions around Pakistan and Afghanistan where Mazda-worship once flourished, until replaced by Islam over a thousand years ago. Muslims from Pakistan form a large community in Bradford, England (or rather Yorkshire, which is really another country). The Born in Bradford study looks at risk factors for congenital anomalies in a multi-ethnic birth cohort, and finds that “Consanguinity is a major risk factor for congenital anomaly. The risk remains even after adjustment for deprivation, and accounts for almost a third of anomalies in babies of Pakistani origin.” Strange are the effects of religious tradition in remote areas of the East over three thousand years.
1360 Asthma is a bad term for a variety of conditions—and the same applies to a lot of the commonest medical labels. Here’s a good update piece from Arizona which starts off with the authors describing it as “a heterogeneous group of conditions that result in recurrent, reversible bronchial obstruction.” I’m not convinced that there have been any advances in the treatment of asthma over the 38 years that I have been a doctor, though there has been a patchy increase in understanding of some causes of recurrent wheezing, particularly in children. Genomics, as usual, has yielded few insights of any clinical value. Raising children in faecally rich environments seems to be a promising approach to reducing the prevalence of allergic asthma, though it doesn’t seem to have caught on much. Come on, big pharma: there is gold in them thar dog-poo bins.
BMJ 19 Oct 2013 Vol 347
Britain in 2013 lies depopulated: twitching decerebrate ghouls stagger among the corpses and the rats, soon to join the dead. This was the vision conjured up by a Leeds bacteriologist when new variant Creutzfeld-Jacob disease appeared on these shores in the late 1980s: only vegetarians would be spared. In fact the death toll stopped at 177, and I still find the whole thing a mystery, though most people seem to believe that vCJD is caused by misfolded proteins called prions. Yet almost nobody with these prions ever gets vCJD: from a study of 32 441 archived appendix samples, it seems that there are about 30,000 people in the UK carrying the guilty protein without suffering any harm.
What is the best blood pressure treatment for lowering cardiovascular risk in people with mildly lowered renal function and raised BP? An ACE inhibitor? An angiotensin blocking agent? Not according to this meta-analysis of individual patient data from 23 randomized trials, with summary data from another three. “The results were similar irrespective of whether blood pressure was reduced by regimens based on angiotensin converting enzyme inhibitors, calcium antagonists, or diuretics/β blockers. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different eGFR.”
A big look at a miserable problem: surgical adhesions. Small bowel obstruction, difficulties at reoperation, infertility, and chronic pain are common problems following abdominal surgery, even in the twenty-first century. It would be interesting to examine the time trends, which this paper does not attempt to do. I am old enough to remember the time when all surgical gloves were covered in talc, and no general surgeon knew what a laparoscope looked like. The incidence of adhesions must certainly have fallen since then, because talc certainly causes adhesions, and laparoscopic surgery carries a lower risk than open surgery.
Ivabradine, nicorandil, ranolazine, trimetazidine: do you ever prescribe these? If you are a British GP, the chances are that you have only ever prescribed the first three after your patient has seen a cardiologist, and you can’t have prescribed trimetazidine because you can’t in the UK. These are the relatively new drugs for angina discussed in this review. Although I rail against expensive new drugs of doubtful utility every week in these blogs, I’m quite a sucker for reading about new treatments, and this is a good account. Just don’t go prescribing them as first-line treatment. And by the way, it’s very embarrassing when a Brit has to talk about anj-EYE-na in the States: over here you have to call it AN-jyna, which sounds a bit like Angela.
Ann Intern Med 15 Oct 2013 Vol 159
514 You can read this paper in Chinese translation if you prefer. It reports on the prevalence of unruptured cerebral aneurysms in the adult population of Shanghai, as determined by random MRI scanning. This comes in at an astonishing 7%, proving that nobody should have a brain MRI without very good reason, for fear of finding out something that will worry them for the rest of their lives.
Plant of the Week: Cucurbita pepo
This is the commonest kind of pumpkin, a plant of extreme popularity in New England at this time of the year. I helped to carry a 32 pound example of its fruit back to the home of Joe Ross, only one of five huge examples that will contribute to the extraordinary splendour of his Halloween Party. His cellar of ghouls has to be seen to be believed.
Hollowing out pumpkins and cleaning their seeds is a wonderful way to spend a warm sunny autumn afternoon in Connecticut. It is a pity that there are so few decent pumpkin recipes, though from time to time I have eaten good pumpkin soup. And the seeds are delicious when roasted with salt. I have mixed feelings about Halloween as an imported phenomenon in England: but here it feels just right, and the only place to celebrate it is at Joe’s. Sadly we can’t stay for the party this year.