All you need to read in the other general journalsBMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e76 (Published 11 January 2012) Cite this as: BMJ 2012;344:e76
Setback for vaccine against genital herpes
Efforts to develop a vaccine against genital herpes suffered a recent setback when GlaxoSmithKline’s candidate failed to protect women from genital disease caused by the herpes simplex virus (HSV). Overall efficacy was not significantly different from a control vaccine against hepatitis A in a trial of more than 8000 women (efficacy against clinical disease 20%, 95% CI −29% to 50%)⇑.
The authors and sponsors were disappointed and puzzled. The same vaccine had worked in previous trials in serodiscordant couples, and they were hoping for better. The latest trial recruited a broader selection of young women from the US and Canada. None had antibodies to HSV types 1 or 2 (HSV-1 or HSV-2) at the start of the trial. After 20 months of follow-up, 0.9% of women given the herpes simplex vaccine (35/3798) and 1.1% of women given the hepatitis A vaccine (35/3076) had developed genital herpes.
In secondary analyses, GlaxoSmithKline’s vaccine seemed to work better against HSV-1 (genital disease confirmed in 0.3% v 0.7% of women, efficacy 58%, 12% to 80%) than HSV-2 (0.6% v 0.5%, efficacy −38%, −167% to 29%), which is another puzzle, because the vaccine is derived from a glycoprotein in HSV-2. Although HSV-1 is an important cause of clinical disease, say the authors, a vaccine that protects against only one of the two genital herpes viruses is unlikely to be approved for general use.
Poor countries need effective strategies against group B streptococcus
Invasive group B streptococcal infections are a leading cause of neonatal sepsis and death. A meta-analysis covering the past decade reports an incidence of 0.53 per 1000 live births (95% CI 0.44 to 0.62) worldwide, and a mean case fatality rate of 9.6% (7.5% to 11.8%) for infants under 3 months of age. The authors were particularly interested in epidemiological data from developing countries, where most neonatal deaths occur. They found little to go on, and they make a plea for more work on this lethal pathogen in countries with the most to lose. Just five of the 74 studies in the meta-analysis were from low income countries, such as Malawi, Mozambique, and Bangladesh. With the limited data available, the incidence of invasive infections looked highest in Africa⇑.
Between 10% and 20% of women carry group B streptococci in the genital tract and can pass it on to infants during birth. The use of prophylactic antibiotics coupled with screening for colonisation is already standard practice in developed countries, says a linked comment (doi:10.1016/S0140-6736(11)61881-3). The provision of intrapartum antibiotics to all women with risk factors is also effective, and this approach may be easier to scale up in countries without the resources to manage screening. Major risk factors for vertical transmission include premature labour, premature rupture of membranes, and maternal fever.
Serotype III was the most common group B streptococcus identified globally, and the same handful of serotypes dominated in all regions with available data. Vaccines are already in the final stages of development and trials are scheduled to start soon in Africa, say the authors.
Prescription drugs are the worst of many options for adults with neck pain
Most adults report non-specific neck pain at some point in their lives, and possible treatments include drugs, spinal manipulation, mobilisation, and unsupervised exercises. A pragmatic trial comparing these options found little to choose between 12 weeks of spinal manipulation and two teaching sessions to help people mobilise plus exercise at home. Both physical treatments worked significantly better than a doctor’s choice of prescription drugs.
All groups improved during the 52 week trial, but participants treated by chiropractors (spinal manipulation or home exercises and mobilisation) reported greater reductions in pain scores than those given prescription drugs, including non-steroidal anti-inflammatory agents, muscle relaxants, and opioids. The difference between drugs and home exercises was significant at 26 weeks only. All significant differences between treatment groups measured less than one point on a 10 point pain scale.
So adults with acute or subacute neck pain should be given a choice, says a linked editorial (p 52). And many will choose to go home and treat themselves. Previous trials and reviews have repeatedly reported marginal differences between treatments for neck pain, possibly because so far we have failed to define important clinical subgroups that may benefit from one treatment or another. Non-specific neck pain is a heterogeneous disorder, says the editorial. It is time to stop doing trials that lump all cases together.
Diabetes guidelines lack rigour and independence
Can we trust guidelines on oral antidiabetic drugs for adults with type 2 diabetes? After a systematic search, researchers found and rated 11 of these guidelines from the US, Canada, and the UK. In general, the guidelines’ recommendations agreed with a systematic review of evidence published by the same researchers in 2007. Seven of the guidelines correctly recommended metformin first and 10 correctly identified the potential for heart failure and oedema associated with thiazolidinediones⇑.
Mismatches between guidelines and the systematic review were mostly confined to guidelines with a narrow focus, including one on treatment options during Ramadan. The researchers found that recommendations were either correct or missing, and never simply wrong. But they did find serious deficiencies in the way the guidelines were developed. Eight scored less than 50% (often far less) on a measure of rigour, which included the presence or absence of external peer review, and an explicit link between evidence and recommendations. Five of the same guidelines also scored less than 50% on a measure of editorial independence.
Guidelines produced by health providers and clinics looked substantially less rigorous and independent than those produced by bigger developers such as the Canadian Diabetes Association and the International Diabetes Foundation. Only one guideline, produced by the National Institute for Clinical Excellence (NICE), which covers England and Wales, scored 100% for both rigour and independence.
Antiviral drugs aren’t good enough to control epidemic of HSV-2
Antiviral drugs aciclovir and valaciclovir aren’t effective enough to eliminate viral shedding in people with genital herpes, even at high doses, say researchers. Three crossover trials found that adults with confirmed herpes simplex virus type 2 (HSV-2) shed the virus, usually without symptoms, once or twice a month even when taking six times the usual dose of valaciclovir (16.5 v 14.9 episodes per person-year for adults taking a standard dose; P=0.34).
A standard dose of aciclovir worked significantly better than no treatment. And higher doses of both antivirals did reduce the proportion of genital swabs containing HSV-2 when compared with lower doses. But higher doses did not prevent bursts of shedding, which were short (less than 12 hours) but could be intense.
Perhaps that’s why antiviral drugs that help prevent symptomatic lesions on the genitals have a limited effect on transmission to uninfected partners, say the researchers. We need new, better treatments. Genital herpes is an important risk factor for HIV.
About a fifth of all adults in the US and Europe have HSV-2, says a linked comment. (doi:10.1016/S0140-6736(11)61614-0). Most have no symptoms and don’t need drugs, so it will be hard to control this epidemic with antiviral agents alone, however effective they are. Vaccines look like a better solution, it says. Drug companies and the public sector should be encouraged to take a keener interest.
Occasional use of marijuana does not seem to impair lung function
Light social use of marijuana does no discernible harm to users’ lungs, according to a large cohort study from the US. More than 5000 young adults joined the study in 1985 and answered regular questions about use of tobacco and marijuana for the next 20 years. They also had five sets of pulmonary function tests. If anything, light smoking of marijuana was associated with improved lung function, particularly a higher forced vital capacity (FVC). The link with FVC has been noticed before, say the authors, who suspect some kind of training effect from repeated deep inhalations.
The authors used “joint years” to measure lifetime exposure, where one joint year means one joint a day for one year or 365 joints. Among adults with low lifetime exposure (two joint years), each joint year was associated with an extra 13 mL (95% CI 6.4 to 20) of forced expiratory volume in one second (FEV1) and an extra 20 mL of FVC (12 to 27). These positive associations disappeared in heavier users. But only the very small number of adults who currently smoked marijuana at least 20 times a month had a significantly reduced FEV1. The 1860 marijuana smokers in this study reported an average of just two or three sessions a month.
Lung function behaved much more predictably in tobacco smokers—a steady linear decline in both measures with increasing exposure to cigarettes.
High risk of hospital admission for adults with dementia
We know that adults with dementia have more hospital admissions than other adults of the same age. A new study suggests that many of these extra admissions are potentially preventable. In a cohort of older adults, those who developed new dementia were significantly more likely than the rest to be admitted for a condition commonly managed outside hospital, such as urinary tract infection (fully adjusted ratio of admission rates 3.38, 95% CI 1.93 to 5.93), heart failure (1.73, 1.15 to 2.60), pneumonia (1.88, 1.25 to 2.82), and duodenal ulcer (4.39, 1.66 to 11.50). The link between dementia and potentially preventable admissions remained significant through extensive adjustments for confounding factors, including comorbidities and ability to perform activities of daily living.
We should step up efforts to keep this vulnerable group of adults out of hospital, says a linked editorial (p 197), starting with a more proactive approach to dementia. Early diagnosis gives everyone more time to build support networks and to make sure common health problems are managed as tightly as possible. For someone with dementia, a single admission to hospital can mean serious and sometimes irreversible decline.
Absolute rates of all potentially preventable admissions were 116 per 1000 people per year for adults with dementia and 37 per 1000 people per year for those without.
Cite this as: BMJ 2012;344:e76