Combined BRAF and MEK inhibition in melanoma
N Engl J Med 2012; 367: 1694-1703
Cases of melanoma have risen by about 70% in the past 20 years. The impact on the health economy over the next 20 years is likely to be huge.
Many treatment strategies involve the use of biologics. This fascinating study looked at patients with metastatic disease with the BRAF v600 mutation. It aimed to understand the advantage of combining the BRAF kinase inhibitor dabrafenib with the mitogen-activated protein kinase inhibitor trametinib compared with dabrafenib monotherapy.
Several endpoints were evaluated, including time without progression of disease and overall survival. Side-effects were also considered.
Combined therapy produced a 9.4 month progression-free survival compared with 5.8 months for monotherapy. Partial or complete response to combined therapy was 76%, against 54% for monotherapy, although this was not statistically significant.
There may be an argument for further trials. Clearly, we need to increase efforts to prevent patients developing melanoma in the first place.
Premature death after self-harm
Lancet 2012; 380: 1568-74
Self-harm is a risk factor for premature death. This study aimed to look at premature death in self-harmers in England, considering factors such as deprivation and physical health.
More than 30,000 people who self-harmed were followed up for six years on average. Of these, 6.1% died before the end of the evaluation period. There was an increased risk of death with males.
This is not surprising, but there was also a 2-7.5 times additional risk of death by natural causes. All-cause mortality increased with decreasing socioeconomic status.
Alcohol was associated with death from conditions relating to mental health and drug disorders and the GI system. Cardiovascular disease also featured significantly. Physical health was far poorer in this group.
Clearly, we as GPs need to consider physical as well as psychological care when managing patients who self-harm or who are at risk of self-harm.
Gabapentin for refractory chronic cough
Lancet 2012; 380: 1583-9
Patients often present with chronic cough. We try our best to exclude sinister causes, drug reactions, asthma, post-nasal drip and reflux, yet, despite our efforts, the cough remains. Patients lose faith and doctors become despondent. Refractory cough, however, has parallels to neuropathic pain models and this provided the basis for trying gabapentin in patients with chronic cough.
In this small RCT, gabapentin was compared with placebo. A total of 62 patients were randomised and 10 did not complete the study period. Perhaps surprisingly, patients randomised to the gabapentin group had a significantly favourable cough-specific quality of life compared with those taking placebo.
The NNT was also impressive, at 3.58. Although some patients experienced side-effects, this study offers evidence for the use of gabapentin in the cough treatment repertoire.
Multivitamins for the prevention of cardiovascular disease in men
JAMA 2012; 308: 1751-60
Cardiovascular disease (CVD) remains the number one killer in the UK. Prevention is critical. It is not unusual for patients to ask if multivitamins would reduce their cardiovascular risk.
This RCT involved nearly 15,000 US doctors over the age of 50, some of whom had CVD. They were randomised to multivitamin or placebo.
They were followed up for an average 11.2 years. The results were fairly straightforward. Multivitamins did not reduce cardiovascular risk or all-cause mortality.
Data are needed across different demographics, but this is strong evidence to support the view that multivitamins should not be routinely used in the prevention of CVD.
Topical treatment for head lice
N Engl J Med 2012; 367: 1687-93
Head lice may have significant consequences for family, school and social life, as well as psychological wellbeing. Treatment failure may be secondary to poor adherence, or due to treatment resistance.
This multisite RCT looked at the efficacy of 0.5% ivermectin as a topical lousicide. It was applied and left for 10 minutes before rinsing.
Of 765 patients, 94.9% in the treatment group were lice-free on day two, against 31.3% of the control group. Figures for days eight and 15 were 85.2% versus 20.8% and 73.8% versus 17.6% respectively. The results against placebo are obvious; it would be interesting to see how ivermectin performs against its competitors.
- Dr Thakkar is a GP in Wooburn Green, Buckinghamshire, and a member of our team who regularly review the journals
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