Research news: June 2009
Governments need two drugs, not one
PLoS Medicine 2009, doi:10.1371/journal.pmed.1000085
Most countries are currently stockpiling a single antiviral, oseltamivir, to use against potentially pandemic influenza viruses including swine flu. Governments will also need a smaller supply of an alternative antiviral to help prevent the spread of drug resistance, say researchers.
In their mathematical model, using a “spare” drug at the start of a pandemic curbed the spread of resistance to the primary drug (oseltamivir), reduced the overall attack rate of the virus, and reduced the proportion of the population infected by resistant strains. Two strategies seemed to work equally well—using the spare drug and the primary drug in combination until the spare drug ran out; and using up the spare drug first before distributing the primary drug. A small stockpile of zanamivir or even amantadine might be enough to prevent resistance to oseltamivir emerging early and spreading further, the researchers conclude. Early use of a spare antiviral agent seemed to work both for the source population and for other populations infected later by travellers, so long as the source population used the spare agent first.
No mathematical model is completely watertight, but the researchers say their findings justify further work to find out which drug would be the best spare and which of the two strategies (combined or sequential) would have the greatest impact on the morbidity and mortality associated with drug resistant pandemic influenza. (From the BMJ, 2009;338:b1895.)
Link to maternal height in India
A national survey of Indian children has found a clear link between mortality in under 5s and maternal height . The absolute risk of death for children with mothers measuring at least 160 cm was 0.05 (95% confidence interval 0.04 to 0.07) compared with 0.09 (0.07 to 0.12) for children born to mothers measuring less than 145 cm, a significant increase of 70% (relative risk 1.71, 1.37 to 2.14). 1
The authors also found a significant association between shorter stature in women and stunting, wasting, and underweight in their children. All three indicators of poor health were common. Nearly a half (17 428/40 089) of surviving children were stunted, 42.2% (14 791) were underweight, and nearly a fifth (7236) had wasting. The survey was nationally representative, and included between 40 000 and 50 000 children under 5 from all 29 states in India. The analysis was fully adjusted for demographic and social factors that influence childhood mortality.
The relative risks associated with each 1 cm decrease in maternal height were small but discernible, and the large numbers allowed the authors to calculate risks with some precision. They are fairly certain the link is real, and it shows how poor health in childhood, which determines growth, is passed from generation to generation. (From the BMJ, 2009;338:b1712.)
Many unsuspected, undetected heart attacks
PLoS Med 2009, doi:10.1371/journal.pmed.1000057
Magnetic resonance imaging of the heart looking for late gadolinium enhancement is a relatively new way to find previously unsuspected myocardial infarction. When US researchers did the test in 185 patients with recently suspected coronary artery disease, a third had myocardial damage consistent with previous infarction (65/185). Most of these patients had no Q waves on their electrocardiogram. Their infarctions had caused no symptoms and had been undetectable by conventional methods.
The 50 silent infarctions that caused no Q waves tended to be small, but they were associated with extensive coronary artery disease and a high mortality. Thirteen of the 50 patients with these lesions died during 2.2 years of follow-up (adjusted hazard ratio 11.4, 95% confidence interval 2.5 to 51.1 relative to patients with no evidence of infarction). The high mortality was independent of left ventricular function, which was largely preserved. Patients with non-Q wave infarction had a mean left ventricular ejection fraction of 52%.
The authors and a linked comment (doi:10.1371/journal.pmed.1000060) agree that this is a small cohort and it is too early to recommend expensive scans for everyone with suspected coronary artery disease. First we need to know if the scans alter management and ultimately improve outcome. The patients in this study had their scans immediately before scheduled coronary angiography. (From the BMJ, 2009;338:b1895.)
Association with intense antiplatelet therapy
Arch Intern Med 2009;169:788-96
A retrospective look at 1677 patients who had coronary artery bypass surgery at one US hospital found a significant association between dual antiplatelet therapy before surgery and an increased risk of infections after surgery. People taking both aspirin and clopidogrel had significantly more postoperative infections than those taking just aspirin (23.1% v 16.1%; adjusted hazard ratio 1.42, 95% confidence interval 1.01 to 2.00). The difference was not explained by any social, demographic, or clinical differences between the two groups.
People taking both drugs also needed more transfusions in the perioperative period (68% v 60.4%, P=0.04) than people taking just aspirin. But mortality was no different at 30 days.
Dual antiplatelet therapy is now the standard of care for many people with heart disease—and for anyone with a drug eluting stent. It is still unclear how best to manage these drugs before, during, and after major surgery, say the authors. This retrospective observational study hints at infectious complications with dual therapy and exposes a gap in our knowledge of the risks and benefits associated with continuing or interrupting clopidogrel treatment in the perioperative period. Platelets have a supporting role in the immune system, they write. A link between infections and intense inhibition of platelet activity is biologically plausible and deserves further study. (From the BMJ, 2009;338:b1895.)
Cite this as: BMJ 2009;339:b2086