On The Pulse - 6th July 2012

HPV infection
It has been known for decades that having multiple sexual partners is a risk factor for cervical cancer so the report in the BMJ that this is also a risk factor for infection with human papilloma virus doesn’t come as a surprise. Rather more interestingly, the study, which involved 2000 sexually active female students at universities and colleges in London, found that about half the infections were with carcinogenic HPV types that aren’t targeted by the current immunisation programme. It sounds as if the need for cervical cytology will continue in both vaccinated and unvaccinated women.

Progress in psoriasis?
There are many treatments for psoriasis, but long-term efficacy is often lacking. A study in the Lancet randomises 352 patients with moderate to severe psoriasis to one of four doses of apremilast, an oral treatment that targets cAMP, or placebo. At week 16, a 75% reduction from baseline psoriasis area was seen in only 6% of the placebo group, but increasingly with dose in the apremilast groups, up to 41% at the highest dosage, albeit with some incidence of nausea and vomiting. An accompanying Comment finds the results convincing, but cautions that at least a year of follow-up is needed for a proper evaluation.

Cardiovascular risk scores
Only last month, this column lamented the lack of head-to-head comparisons between the various risk scores used to predict cardiovascular events. As if in response, a paper in the BMJ evaluates QRISK2-2011 against the NICE version of the Framingham equation, using data from the Health Improvement Network (THIN) database. It assesses performance in terms of calibration (how closely the predicted risk agrees with the observed risk) and discrimination (how well the score differentiates between people who do and do not have a cardiovascular event) and declares QRISK2-2011 the clear winner on both counts.

Dermatological signs of diabetes
A 52-year-old man with type 2 diabetes presents with a persistent rash on both shins. He says that the rash bleeds sometimes, but it’s not painful and doesn’t itch. When you examine him, you find yellow–brown plaques with ulceration and telangiectasia in a thinned epidermis – see a photograph in Image Challenge in the NEJM. This is necrobiosis lipoidica, a chronic dermatitis of unknown cause characterised by a granuloma formation, collagen degeneration and fat deposition. It’s fairly rare and, although often associated with diabetes, it may precede it. There’s no very effective treatment.

tPA, warfarin and stroke
Intravenous tissue plasminogen activator (tPA) improves outcomes in ischaemic stroke if given early, but increases the risk of intracranial haemorrhage. Although you might expect this risk to be higher in people taking warfarin, a large registry-based study from the US in JAMA finds this isn’t so. Patients taking warfarin were older, had more comorbid conditions and had more severe strokes, but after adjustment for these baseline differences, their rate of symptomatic intracranial haemorrhage after tPA was not significantly higher than that of patients not taking warfarin but also treated with tPA, and nor were rates of systemic haemorrhage, other tPA-related complications and in-hospital mortality.

Linagliptin for type 2 diabetes
The gliptins, inhibitors of dipeptidyl peptidase-4, are a relatively new class of drug for treating type 2 diabetes, that both increase postprandial insulin secretion and reduce glucagon secretion. A trial in the Lancet compares linagliptin with the sulphonylurea glimepiride in 200 patients with HbA_1c ≥6.5 on metformin. At 2 years, the two produced similar changes in HbA_1c, but hypoglycaemia and cardiovascular events were substantially less common in the linagliptin group, although numbers of the latter were small. An accompanying Comment thinks the lower rate of hypoglycaemia might justify the expense of linagliptin for patients in whom this is a particular concern.

Fluid replacement in severe sepsis
Hydroxyethyl starch (HES) fluids are widely used to treat hypovolaemia due to severe sepsis, but data on their use are lacking, particularly on HES 130/0.4, partly because 90 papers by a single investigator were retracted in 2010–11 amid ethical concerns. A blinded study in the NEJM suggests that clinical practice may need to change. Among ~800 ICU patients with severe sepsis randomised to either HES 130/0.4 or Ringer’s acetate, mortality was higher at 90 days with HES 130/0.4 (51% vs 43%, p < 0.03) as was the need for dialysis (22% vs 16%, p=0.04).

Cardiac surgery without transfusion
An observational study in Archives of Internal Medicine casts an interesting light on arguments for more conservative use of transfusions. It compares complications, morbidity and long-term survival after cardiac surgery in Jehovah’s Witnesses, most of whom have theological objections to at least some forms of transfusion, and a matched set of non-Witnesses. Intriguingly, the Witnesses had fewer acute complications, shorter hospital stays, slightly better 1-year survival and unchanged 20-year survival compared to non-Witnesses. An accompanying Commentary thinks surgeons may select healthier Witnesses for operation, knowing that transfusion is unavailable, but agrees that it bolsters the case for reducing use of transfusions.