All you need to read in the other general journals

China confirms likely transmission of avian flu H5N1 between humans

Lancet 2008 online April 8; doi: 10.1016/S0140-6736(08)60493-6

• Download figure
• Open in new tab
• Download powerpoint

Infection control authorities in China have reported the likely transmission of the avian influenza virus H5N1 from a young man to his father⇑. The 24 year old salesman became ill six days after visiting a local poultry market and was eventually diagnosed in hospital only 24 hours before he died. His father, a 52 year old engineer, cared for him at home and in hospital. He became ill the day after his son’s funeral, but he survived after prompt treatment with oseltamivir, rimantidine, and a transfusion of plasma from a woman who had been vaccinated against the virus in a preliminary trial.

Genome sequencing of viral isolates confirmed that both patients were infected with an almost identical strain. The team of specialists that investigated the outbreak says the most likely explanation is that the son infected his father. But it is unclear exactly when or how transmission occurred. The investigators are unable to rule out the possibility that both cases were infected by contact with local poultry. The father had visited a market eight days before he became ill, but he says he went nowhere near the stalls selling chickens.

The investigators tested another 91 close contacts including friends, family, and healthcare workers. None had evidence of infection with H5N1.

Acyclovir won’t prevent HIV in women with HSV-2

N Engl J Med 2008;358:1560-71OpenUrlCrossRefPubMedWeb of Science

HIV has no cure. While many scientists continue to look for one, others are equally busy searching for ways to prevent infection. The journey has been littered with disappointments and setbacks, says one comment article (p 1543). Vaccines are decades away, and barriers such as vaginal microbicidal gels and diaphragms don’t protect against HIV. Even interventions that change risky behaviour have more effect on other sexually transmitted diseases than on HIV.

Against this backdrop, an international team recently published their anxiously awaited trial testing a strategy to reduce the incidence of HIV by suppressing herpes simplex virus type 2 (HSV-2) with acyclovir. It didn’t work. Tanzanian women who received acyclovir were no less likely to become infected with HIV than similar young women who received placebo (4.4 v 4.12 infections/100 person years). All participants were seropositive for HSV-2, a known risk factor for HIV. They were also working in bars, hotels, and restaurants, where an estimated 63% of new HIV infections are attributable to HSV-2.

Research into HIV prevention still faces enormous challenges, says the comment. But they can and must be overcome. In the time it could take to develop a vaccine, 20-60 million people worldwide will become infected with HIV.

Vaccinated college students dominated 2006 mumps outbreak in the US

N Engl J Med 2008;358:1580-9OpenUrlCrossRefPubMedWeb of Science

• Download figure
• Open in new tab
• Download powerpoint

Plans by the US authorities to eliminate mumps by 2010 were set back in 2006 when eight Midwestern states had their largest outbreak for 20 years⇑. More than 6500 cases of mumps were reported that year, mostly from the contiguous states of Illinois, Iowa, Kansas, Minnesota, Missouri, Nebraska, South Dakota, and Wisconsin (5586/6584, 85%). An analysis of the outbreak reported that the highest incidence was in people aged 18-24 (31.1 v 8.4/100 000 for all other age groups combined, P<0.001). Around three quarters of these adults were at college. More than four fifths had had the recommended two doses of mumps vaccine, probably as children.

The authors blame a combination of factors for the outbreak—waning immunity; low exposure to natural mumps, which almost disappeared during the 1990s; and congregation in crowded college dormitories. Mumps could possibly have spread from the UK, where a larger outbreak was peaking at around the same time. Both outbreaks were caused by the same strain of virus.

The US outbreak was over by the end of summer 2006. No one died, and only 85 patients needed hospital treatment. For now, the national policy on vaccination remains unchanged.

Urgently needed: good trials of specialised palliative care services

JAMA 2008;299:1698-709OpenUrlCrossRefPubMedWeb of Science

Despite decades of research, it is still hard to know exactly how specialised palliative care services benefit dying patients and their carers. The evidence is patchy, heterogeneous, and inconclusive, say researchers who systematically reviewed 22 randomised trials published since 1984. The only consistent evidence they found suggested that specialised services based in the home, outpatient clinic, or hospital probably improve satisfaction reported by care givers. They found no good evidence that these services reduced symptoms or improved quality of life for terminally ill patients. But many of the trials were too small to rule out important benefits. Other common problems included high dropout rates, poor presentation, and the use of quality of life measures not developed or validated for patients with terminal illnesses.

More and more people are being offered specialist palliative care in the final months of their lives, say the researchers. Evaluating these services properly won’t be easy, but careful planning, standardised interventions, and outcomes tailored to the special needs of dying people and their carers should help.

Telmisartan and ramipril work equally well in patients with vascular disease

N Engl J Med 2008;358:1547-59OpenUrlCrossRefPubMedWeb of Science

A randomised trial in over 25 000 patients shows convincingly that the angiotensin converting enzyme (ACE) inhibitor ramipril and the angiotensin receptor blocker telmisartan give the same cardiovascular protection to patients with vascular disease or high risk diabetes. Rates of the combined end point—death from cardiovascular causes, heart attack, stroke, or hospital admission for heart failure—were 16.5% (1412/8576) in participants who took ramipril and 16.7% (1423/8542) in those who took telmisartan. Both groups took their assigned drug for a median of 56 months. The drugs’ benefits were statistically indistinguishable, but telmisartan was associated with a lower risk of cough (1.1% v 4.2%, P<0.001), a lower risk of angio-oedema (0.1% v 0.3%, P=0.01), and a higher risk of hypotensive symptoms excluding syncope (2.6% v 1.7%, P<0.001).

In a third group, the combination of ramipril and telmisartan did not have a greater effect on cardiovascular events, but participants who took both drugs had significantly more side effects, including renal dysfunction (13.5% v 10.2%, P<0.001), than those who took ramipril alone.

This trial’s participants had diseased coronary, cerebral, or peripheral arteries. More than a third had diabetes with end organ damage. None had heart failure. Most people with this profile can be safely and effectively treated with cheaper ACE inhibitors, says a linked editorial (p 1615). Angiotensin receptor blockers should be reserved for those who develop side effects such as cough.

Aggressive control of blood pressure and LDL cholesterol slows atherosclerosis in high risk Americans

JAMA 2008;299:1678-89OpenUrlCrossRefPubMedWeb of Science

• Download figure
• Open in new tab
• Download powerpoint

Native Americans with type 2 diabetes have a high risk of atherosclerosis. Aggressive control of low density lipoprotein (LDL) cholesterol and blood pressure reduced the appearance of early signs of the disease in a randomised trial. The authors used intima medial thickness of the common carotid artery as a marker for atherosclerosis and compared two sets of treatment targets—an LDL cholesterol concentration no more than 70 mg/dl (1.81 mmol/l) and systolic blood pressure no more than 115 mm Hg versus LDL cholesterol no more than 100 mg/dl and systolic blood pressure no more than 130 mm Hg. Intima medial thickness regressed in participants treated aggressively and progressed in those treated to standard blood pressure and cholesterol targets. The difference was significant⇑.

Aggressive treatment didn’t help prevent cardiovascular events over three years, but this trial wasn’t powerful enough to exclude an effect. So for a final answer to the question of how low to go, doctors will have to wait for bigger, longer, and much more costly primary prevention trials, says an editorial (p 1718). In this trial, aggressive treatment caused significantly more side effects (38.5% (97/252) v 26.7% (66/247), P=0.005), particularly from antihypertensive drugs.

International progress on maternal and child deaths is “strikingly inadequate”

Lancet 2008;371:1247-58OpenUrlCrossRefPubMedWeb of Science

International agencies tracking maternal and child deaths in 68 developing countries say less than a quarter are improving fast enough to meet millennium development goals set for 2015. Only 16 countries are likely to hit millennium goal 4—to reduce mortality in children younger than 5 years by two thirds between 1990 and 2015. None is in sub-Saharan Africa, where 12 countries are actually getting worse, not better.

Maternal mortality remains high or very high in 56 of the 68 countries. International investigators say it is impossible to know how maternal deaths are changing over time because surveillance data are so poor. The lifetime risk of dying as a result of pregnancy or childbirth is one in seven for women in Niger, according to the latest estimates. For women in Sierra Leone and Afghanistan, the risks are one in eight. Serious shortfalls in contraceptive services and antenatal, perinatal, and postnatal care are responsible. There are no quick fixes, and interventions to save these women are falling behind the relatively cheaper and easier interventions for children, such as immunisations and bed nets treated with insecticide.

One commentator describes progress towards both millennium development goals as strikingly inadequate (p 1217). The indifferent response so far from politicians, policy makers, donors, research funders, and civil society betrays a “pervasive disrespect for human life.” Health professionals must not accept it, he says.

Omega 3 free fatty acids don’t prevent relapses of Crohn’s disease

JAMA 2008;299:1690-7OpenUrlCrossRefPubMedWeb of Science

Omega 3 free fatty acids are a popular alternative treatment in patients with inflammatory bowel disease, possibly because at least one small trial reported that the supplements helped prevent relapse. Two larger trials recently failed to confirm these results in patients with Crohn’s disease. Both trials, done in parallel by the same investigators, found that omega 3 fatty acids worked no better than placebo for people in remission. In one trial, around a third of both groups relapsed during one year of follow-up (hazard ratio 0.82, 95% CI 0.51 to 1.19). In the other, just over half of both groups relapsed (0.90, 0.67 to 1.21). The manufacturers Tillotts Pharma AG funded both studies, which were conducted for regulatory purposes. The authors say their studies are unlikely to have missed a clinically meaningful effect and conclude that omega 3 free fatty acids don’t prevent relapses of Crohn’s disease.