Short Cuts

All you need to read in the other general journals

BMJ 2009; 338 doi: (Published 17 February 2009) Cite this as: BMJ 2009;338:b627

Inhaled steroids linked to pneumonia in people with COPD

Inhaled corticosteroids are associated with an increased risk of pneumonia in people with chronic obstructive pulmonary disease (COPD), according to a meta-analysis. The extra episodes of pneumonia don’t seem to threaten survival, however. In a pooled analysis of 18 randomised trials, people using inhaled steroids were 60% more likely to get pneumonia than controls (relative risk 1.6, 95% CI 1.33 to 1.92) and 71% more likely to get serious pneumonia (1.71, 1.46 to 1.99), but they were no more likely to die of pneumonia or anything else. Combined treatment with inhaled steroids and the long acting β agonist salmeterol was also associated with significantly more pneumonia than treatment with salmeterol alone (1.68, 1.2 to 2.34).

The 16 996 patients in these trials took their assigned treatment for at least 24 weeks. Most trials tested fluticasone propionate alone or combined with salmeterol. Two trials tested inhaled budesonide. The authors estimated one extra episode of serious pneumonia would occur for every 47 (34 to 73) patients treated long term with inhaled steroids.

This isn’t the first analysis to find a clinically important link between inhaled steroids and pneumonia in this patient group, say the authors. Local immunosuppression within the lung is one biologically plausible explanation.

Extra payments help employees to stop smoking

Experts estimate that employees who stop smoking save their employers around $3400 (£2380; €2600) a year in reduced time off sick and increased productivity. So paying employees to stop smoking might save money, if it works. Small trials have reported inconsistent results. In a recent large trial, however, financial incentives of up to $750 helped one US corporation’s smokers to quit for up to 18 months. Employees given the extra payments were more likely to attend and complete a smoking cessation programme, more likely to quit short term (20.9% (91/436) v 11.8% (52/442); P<0.001), and then more likely to quit long term (9.4% (41/436) v 3.6% (16/442); P<0.001) than controls who had nothing to gain financially from giving up smoking. The authors checked salivary cotinine concentrations to confirm self reported smoking (or lack of it).

Participants in the incentive group were given the money in stages—$100 for completing a cessation programme, $250 for giving up within six months, and a final $400 for staying off cigarettes for a further six months. Controls were told where to go for help but were given no money.

Most of these participants were well educated and affluent. They smoked around 20 cigarettes a day, and more than four fifths were thinking about or actually planning to give up when they joined the trial.

Stem cell transplant for leukaemia controls one patient’s HIV

HIV infects CD4 positive cells by attaching to essential coreceptors on the cell. One of them, known as CCR5, is absent in 1-3% of Western populations because of a deletion affecting its gene. People with two copies of the deletion are highly resistant to HIV, and researchers have been hoping to exploit this phenomenon to develop new treatments.

Stem cells from a bone marrow donor homozygous for the CCR5 gene deletion seemed to control long standing HIV infection in one German patient. He needed a bone marrow transplant for acute myeloid leukaemia and his doctors chose a donor whose stem cells might also help treat his HIV. After two stem cell transplants and 548 days without antiretroviral drugs, the patient is in remission with no signs of active HIV in his bloodstream. His CD4 positive T cells returned to within the normal range, and a biopsy found no HIV in his rectal mucosa.

A linked editorial (p 724) says this is a good sign but bone marrow transplantation, which requires ablation of host immune cells, is probably too risky for people with just HIV. It is also unlikely to cure anyone with a mixed infection of HIV subtypes. Although R5 HIV types need CCR5 to enter CD4 positive cells, the X4 types do not. Patients often have both HIV types at the same time. A very low amount of the X4 type was present in this patient’s plasma before his transplants.

Obese pregnant women have a higher risk of fetal abnormalities

Obesity is bad for everyone, but it is particularly bad for pregnant women, who have higher rates of gestational diabetes, hypertension, thromboembolism, and caesarean section. A new study adds congenital abnormalities to the list of possible adverse outcomes.

Researchers carefully reviewed 39 observational studies and pooled data from 18. They found a significant association between maternal obesity and a raft of different fetal abnormalities including neural tube defects (odds ratio 1.87, 95% CI 1.62 to 2.15), cardiovascular defects (1.30, 1.12 to 1.51), cleft lip and palate (1.20, 1.03 to 1.40), and limb reduction anomalies (1.34, 1.03 to 1.73). The significant associations survived various sensitivity analyses and the authors are fairly confident that the link is real. They suggest it could be caused by undiagnosed hyperglycaemia or nutritional deficiencies in obese women. Fetal abnormalities might also be easier to miss in obese women because ultrasound scanning is technically more demanding. Missed abnormalities could mean fewer terminations.

The absolute risk of a congenital abnormality remains small—in this study obesity was associated with an extra 0.47 neural tube defects per 1000 births and an extra 0.67 serious heart defects per 1000 births. The effect of being overweight, rather than obese, was weak and inconsistent.

New survey techniques expose gaps in measles vaccination in Zambia

Three years after a supplemental vaccination programme, population immunity is still too low to stop the transmission of measles in Lasaka, Zambia, say researchers. They used satellite technology to sample households for a cross sectional survey. Only 67% (679/1015) of children surveyed were immune to measles—not enough to prevent outbreaks. Mapping of vaccination coverage and immunity showed clear clustering of unprotected children in the townships surveyed.

The researchers used satellite images of three densely populated urban townships to choose a random sample of households for study. Six hundred and ninety one of 1194 households agreed to take part, and 1015 children aged 9 months to 5 years gave oral fluid samples for antibody testing. Their carers gave details of vaccination history and clinical measles.

Although 84% (853/1015) of the children had a reported history of measles vaccination, fewer than half of them had documentary evidence. Six per cent (64/1015) of all children had antibodies to HIV but they were not particularly susceptible to measles.

Although a serum antibody sample remains the gold standard, oral samples are easier to collect and can be a useful alternative in resource poor settings, says a linked comment (doi:10.1016/S0140-6736(09)60143-4). The technique, especially when combined with satellite photography, deserves further study for monitoring and planning future vaccination campaigns.

Zolidronic acid slows progression of some early breast cancers

Evidence is emerging that the bisphosphonate zoledronic acid has antitumour properties that extend beyond bone. The latest evidence comes from a large trial in women with early breast cancer. Adding zoledronic acid to standard endocrine therapy prolonged disease-free survival during an average follow-up of four years (94% (845/899) v 90.8% (821/904); hazard ratio 0.64, 95% CI 0.46 to 0.91). All the women were premenopausal and had endocrine responsive cancers treated with surgery followed by goserelin. None had postoperative chemotherapy.

The four armed trial was designed to test two potential new treatments for these women—the aromatase inhibitor anastrozole and zoledronic acid.

In head to head analyses, women given anastrozole did no better than controls given tamoxifen, a surprise result because anastrozole has been shown to prolong survival in postmenopausal women with endocrine responsive cancers. Adding zoledronic acid to either treatment improved both disease-free and recurrence-free survival. The authors estimate that disease progression would be prevented in one woman for every 31 women treated. The zoledronic acid infusions—initially monthly then reduced to once every six months—had no effect on overall mortality (hazard ratio 0.6, 0.32 to 1.11). Women given the drug reported more arthralgia (24% v 18%), bone pain (35% v 25%), and transient fever (9% v 2%) than women treated with endocrine therapy alone.

Postpartum psychosis peaks during the first weeks after delivery

Postpartum psychosis is rare but can be devastating for both mother and infant. Although having a previous psychiatric history increases a woman’s risk, postpartum psychosis can occur out of the blue. In one large Swedish cohort, half the 892 women admitted to hospital because of psychosis within 90 days of their first delivery had no previous history of mental illness.

The authors studied nearly three quarters of a million women who became first time mothers between 1983 and 2000. The overall incidence of psychosis in the first 90 days was 1.2 per 1000 births. Incidence peaked in the first month then tailed off fairly rapidly—285 of the 892 women (32%) were admitted to hospital during the first week after childbirth, and 523 (59%) were admitted within the first two weeks. Among those with no previous history, incidence was 10 times higher in the first 90 days than in the second 90 days after childbirth.

These trends suggest that the birth itself triggers psychosis in some women, say the authors. Plunging oestrogen concentrations are one possible factor. Exploratory analyses looking for other risk factors suggested women over 35 were at higher risk of a first postpartum psychosis than women under 19, and that diabetes and a big baby were protective.

Severe ankle sprains recover quicker with plaster casts

In patients with a severe ankle sprain, a below knee cast for 10 days improved ankle function by a mean difference of 9% (95% CI 2.4 to 15.0) in a recent trial that compared three mechanical supports with tubular compression. A brief spell in a plaster cast was also slightly better for pain, symptoms, activities of daily living, and ability to do sport at three months. The Aircast brace, which allows limited movement, improved ankle function at three months (mean difference of 8%, 1.8 to 14.2) compared with Tubigrip, but it had no effect on secondary outcomes. The Bledsoe boot worked no better than Tubigrip.

A linked comment (p 524) says the findings are controversial because current practice for sprained ankles favours an early return to weight bearing and normal movement. A change of approach would bring management of ankle sprain in line with management of ligament injuries in the knee and shoulder. Both are usually immobilised.

In this trial, all management options were comparable at nine months, so a £16.45 (€18.29; $23.35) below knee cast is only advantageous in speeding recovery.

Sprained ankles can have serious consequences, says the commentary. Recurrences are common, and around 30% of patients have chronic instability of the ankle. It is probably time to re-evaluate treatment.


Cite this as: BMJ 2009;338:b627

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