Hope in refractory hypertension
A paper in the Lancet reports encouraging results for a new treatment for refractory hypertension. In 370 patients whose systolic blood pressure exceeded 140 mmHg despite at least three antihypertensive agents, the selective endothelin antagonist darusentan produced mean reductions of 17–18 mmHg, depending on dose, vs only 9 mmHg with placebo. The main adverse effect was fluid retention and/or peripheral oedema, so it’s not suitable for patients with heart failure. As an accompanying Comment says, clarifying darusentan’s role in managing hypertension will need further research, but it appears to be an effective approach in some patients.
Benign acute childhood myositis
A previously healthy 6-year-old boy gets a fever and a runny nose. Four days later, he complains of sore legs and the next morning, although his coryza is better, he won’t get out of bed. When his mother attempts to stand him up, he is unable to bear weight on his legs. Neurological examination is normal, but creatine kinase is strikingly elevated. This is benign acute myositis of childhood, first described in 1957, a rare sequel to a viral illness. It occurs sporadically in northern latitudes, in winter months, in school-aged children, particularly boys. This patient recovered completely within a week. The condition and its differential diagnosis are briefly reviewed in the CMAJ.
Omega 3 fatty acids in depression
There’s some evidence linking low levels of omega-3 fatty acids with both depression and increased risk of cardiac mortality. There’s also a hint that supplements of these fatty acids may enhance the efficacy of antidepressants. So perhaps it makes sense to try adding supplements of eicosapentaenoic and docosahexaenoic acids to sertraline when treating patients suffering from both major depression and coronary heart disease. Unfortunately, it doesn’t work in practice. In an RCT in JAMA, the combination of sertraline and omega-3 fatty acids produced no improvement in depression outcomes at 10 weeks over sertraline and placebo.
Breaking hips and failing hearts
Cardiovascular disease and osteoporosis have been suspected to share aetiological factors for some time, but the strength of the connection is difficult to assess. A study published in JAMA interviews ~25,000 Swedish twins to investigate the degree of correlation and the influence of genetics and early environmental factors, as opposed to later lifestyle. All major cardiovascular events were a risk factor for subsequent hip fracture in individual patients (hazard ratios from 2.32 to 6.6, depending on the event). Although not all such events correlated with hip fracture in a co-twin without cardiovascular disease, heart failure (HR 3.74) and stroke (HR 2.29) did so, suggesting some role for shared genetics.
Mystery genes of osteoporosis
Although osteoporosis undoubtedly has a large heritable component, attempts to identify the genes involved have so far been disappointing. A study in Annals of Internal Medicine analyses 36,000 polymorphisms in 150 candidate genes in five large European populations, but finds only nine associated with bone mineral density, and only five with risk of fracture, all with rather unimpressive odds ratios. Some of these genes do at least have biologically plausible roles, such as involvement in RANKL and Wnt signalling pathways. An accompanying Editorial thinks this is the ‘tip of the iceberg’ in terms of understanding osteoporosis, but it remains unclear what may lie beneath the surface.
Steroids for COPD
A trial in Annals of Internal Medicine examines long-term effects on lung function of fluticasone and salmeterol in moderate to severe chronic obstructive pulmonary disease. Patients (n=114) were randomised to four arms: 30 months fluticasone, 6 months fluticasone plus 24 months placebo, 30 months fluticasone plus salmeterol, and 30 months placebo. All were steroid-naive. Patients appeared to benefit from the steroid, with reduced inflammation and slower decline in lung function, these effects being reversed in the discontinuation group. However, addition of salmeterol slightly improved lung function, but did not slow its decline or reduce inflammation further. Larger numbers will be needed to assess long-term safety effectively.
Thoracic kidney
When a 74-year-old man had a chest X-ray, a large mass was seen in the lower left hemithorax. He had no pulmonary symptoms, no history of chest trauma, and physical examination was normal. CT eventually identified the mass as a thoracic kidney – a rare congenital anomaly that occurs in conjunction with defective fusion of the posteromedial part of the diaphragm. The pictures in the NEJM are dramatic, but the condition requires no treatment.
Rethinking screening
The introduction of effective screening for cancer should first produce an increase in numbers diagnosed with early disease, then later a decrease in numbers with advanced disease. Overall, detection rates should remain more or less constant. A thoughtful essay in JAMA considers how well breast and prostate cancer screening programmes in the US meet these criteria. Although rates of detection of early disease have increased substantially, the incidence of diagnosis of more advanced disease has declined far less than hoped. Most probably, screening has increased detection of indolent cancers while missing the most aggressive tumours. In other words, tumour biology is far more important than time of diagnosis, so the basic assumption of screening programs – that finding and treating early-stage disease will prevent advanced and metastatic disease – may be wrong.
