Liraglutide for weight loss
A paper in the Lancet assesses liraglutide, a glucagon-like peptide-1 agonist with an extended half-life, in 564 non-diabetic obese patients. Over 20 weeks, patients treated with liraglutide plus calorie restriction and exercise lost a mean of 4.8 kg at the lowest dose, rising to 7.2 kg at the highest. By comparison, those substituting liraglutide with placebo lost only 2.8 kg, and those receiving orlistat, 4.1 kg. An accompanying Comment observes that the orlistat figure is surprisingly low, and warns that while liraglutide looks promising, an injected drug that can cause nausea may not be popular outside a trial setting.
Off-pump CABG?
There have been hopes in recent years that performing cardiovascular bypass surgery without the traditional heart–lung machine ("off-pump CABG") might reduce the rate of complications, but studies have typically been small. The ROOBY trial, a large multicentre study published in the NEJM, is not encouraging: among 2203 patients randomly assigned to on -or off- pump CABG, outcomes were worse at one year in the off-pump group, with no differences in neuropsychological outcomes or short-term resource use. However, an accompanying Editorial points out that these younger, fitter male patients are not the ones expected to benefit from the off-pump approach, and that questions about surgical expertise remain.
Epo antibodies
Recombinant human erythropoietin has proved highly effective in treating the anaemia associated with chronic kidney disease, but occasionally provokes the production of neutralising antibodies that also block the patient’s endogenous erythropoietin. This causes red cell aplasia, which may be so severe that repeated transfusion is the only way to maintain a viable red cell count. A trial in the NEJM tests a peptide erythropoietin receptor agonist that has a structure unrelated to erythropoietin but binds to and directly stimulates the erythropoietin receptor. Although 13 of the 14 patients given this ingenious treatment were able to stop blood transfusions, its long-term safety remains to be established.
Adverse effects of azathioprine
Azathioprine is often used to treat autoimmune and inflammatory diseases and has a good safety profile, except in people with unusual genetic polymorphisms of thiopurine methyltransferase, in whom it can cause severe myelotoxicity. There is, however, concern that prolonged use increases the risk of lymphoma. The Lancet reports a large long-term follow-up study of a group of patients with inflammatory bowel disease, showing that this anxiety is entirely justified: taking azathioprine was associated with a five-fold increase in the risk of non-Hodgkin’s lymphoma. Although the absolute risk is low, at around one case per 1000 person-years of exposure, it can’t be ignored.
Severe H1N1 flu
A paper in JAMA reports a large series (n = 1088) of hospitalised and fatal H1N1 influenza from California. It confirms clear differences from seasonal flu, with a lower median age (27 years), more frequent gastrointestinal involvement, > 30% requiring intensive care, and an 11% mortality rate. It also warns against excluding this diagnosis on molecular grounds, as 34% were falsely negative on rapid antigen tests. Lastly, it observes a link with obesity, which has not previously been reported: of adults with BMI data available, 58% were obese and 25% morbidly obese. The authors think this may be due to associations with comorbidities such as diabetes, cardiovascular disease, and obstructive sleep apnoea.
Face masks vs respirators
Staying on the subject of influenza, a second paper in JAMA assesses face masks versus N95 respirators as preventive measures for nurses treating patients with febrile respiratory illnesses, with laboratory-confirmed influenza as the primary outcome. Despite being recommended by a variety of guidelines, the respirators fared no better than the masks in preventing influenza, with infection rates of 22.9% and 23.6% (p = 0.86) respectively. A control arm using neither method would have been informative, but perhaps that’s too much to ask in a flu epidemic. An accompanying Editorial bemoans the lack of randomised trials in this area, and emphasises the importance of healthcare workers staying home when sick.
Much cheaper but almost as good
You’re probably familiar with the incremental cost effectiveness ratio. It’s the cost per additional unit of benefit, a QALY say, from a healthcare intervention. An article in Annals of Internal Medicine turns the idea on its head, asking what we know about decremental cost effectiveness ratios – interventions that are only slightly less effective than the best available option, but that save a lot of money. Two examples are percutaneous coronary intervention for multivessel disease instead of CABG, and watchful waiting for inguinal hernia instead of surgical repair. From a utilitarian point of view, cost-saving interventions can improve outcomes overall because they allow better distribution of limited resources.
National dementia strategy
Talking of saving money, another good way is not to spend it on expensive initiatives until you are sure that they will be effective. An editorial in JRSM questions the national dementia strategy, which was published earlier this year, and its plans to improve early diagnosis and treatment by setting up a nationwide network of multidisciplinary memory clinics. Although there is evidence on the effectiveness of some of the individual elements of memory clinics, there’s little evidence about the benefits of the package as a whole. Although doubts have been raised over the strategy before, there has been rather little criticism generally, perhaps because nobody wants to be branded a therapeutic nihilist.