Short Cuts

All you need to read in the other general journals

BMJ 2009; 339 doi: (Published 12 August 2009) Cite this as: BMJ 2009;339:b3257

Africans with HIV should start taking antiretrovirals earlier

The World Health Organization recommends that people with HIV start antiretroviral treatment when they reach stage 3 or 4 of the disease or when the CD4 count decreases to fewer than 200 × 106 cells/l. However, starting treatment earlier may reduce the rates of opportunistic infections, prolong life, and be cost effective. Modelling studies done in developed countries have found that starting treatment when the CD4 count drops below 350 × 106 cells/l, or even below 500 × 106 cells/l, may be beneficial. A study now confirms that this may be true for South Africa too.

A computer simulation model that used data from randomised trials and observational cohorts in South Africa estimated that if treatment was started when the CD4 count is 350 × 106 cells/l rather than when the CD4 count is 250 × 106 cells/l then over the next five years 25 000 deaths could be saved if 10% of people infected with HIV are identified and linked to care. If all HIV positive people were identified, 253 000 deaths would be averted. The incremental cost effectiveness ratio was estimated to be $1100 (£660; €770) per year of life saved for starting treatment at 250 × 106 cells/l compared with no treatment, and $1200 for starting treatment at 350 × 106 cells/l compared with 250 × 106 cells/l.

Trials are under way to determine the optimal time to start antiretroviral treatment in people with HIV, but the results will not be available for five to 10 years. Until then, argue the authors, treatment guidelines should be liberalised to allow antiretroviral treatment to start at a CD4 count of <350 × 106 cells/l; they say, however, that this should only be implemented in settings with adequate capacity to treat all people who are eligible and at highest risk.

Induction of labour is advisable for women with mild hypertensive disease beyond 37 weeks’ gestation

In a multicentre trial, 756 women with a singleton pregnancy and a fetus in cephalic presentation who were at 36-41 weeks’ gestation and had gestational hypertension or mild pre-eclampsia were randomised to receive induction of labour or expectant monitoring. Less than a third (117/377, 31%) of the women randomised to induction and nearly half (166/379, 44%) of the women randomised to watchful waiting experienced at least one component of the composite primary outcome (maternal mortality, eclampsia, HELLP (Haemolytic anaemia, Elevated Liver enzymes, and Low Platelet count) syndrome, pulmonary oedema, thromboembolic disease, placental abruption, progression to severe hypertension or proteinuria, or major post-partum haemorrhage, defined as blood loss >1000 ml (relative risk 0.71, 95% CI 0.59 to 0.86).

Progression to severe disease was less frequent among the women who were randomised to induction (23% v 36%; relative risk 0.64 (0.51 to 0.80)), and fewer caesarean sections were needed in the induction group, although the difference wasn’t significant (14% v 19%). No deaths or cases of eclampsia were recorded, and adverse outcomes in newborns did not differ significantly between the two groups.

Of 1153 eligible women, only 756 consented to participate in the trial. Most of the women who chose not to participate opted for watchful waiting (82%). Among these women, a poor maternal composite outcome was present in 31 (43%) women who underwent induction and 123 (38%) women who received expectant monitoring.

The commentator confirms (doi:10.1016/S0140-6736(09)61380-5) the authors’ conclusion that induction of labour should be advised for women with gestational hypertension and a diastolic blood pressure of ≥95 mm Hg or mild pre-eclampsia at 37 weeks’ gestation and beyond.

Add infliximab when people with early rheumatoid arthritis don’t respond to methotrexate alone

How best to treat early rheumatoid arthritis in people who have failed to respond to methotrexate? According to a multicentre randomised trial, a tumour necrosis factor antagonist such as infliximab should be added to methotrexate, rather than the conventional disease modifying antirheumatic drugs sulfasalazine and hydroxychloroquine.

The 487 participants had symptoms of rheumatoid arthritis that had started in the year preceding enrolment. The 258 participants who had not achieved low disease activity within three to four months of treatment with up to 20 mg a week of methotrexate were randomly allocated to receive infliximab alone or sulfasalazine and hydroxychloroquine. One year later, 50 of the 128 (39%) who had received infliximab achieved the primary outcome—achievement of a good response according to European League Against Rheumatism (EULAR) criteria—compared with 32 of the 130 (25%) participants who had received sulfasalazine and hydroxychloroquine (risk ratio 1.59, 95% CI 1.10 to 2.30).

One serious adverse event occurred in each group: a prolonged febrile episode with infliximab and an extended generalised illness with sulfasalazine and hydroxychloroquine. No malignant diseases or deaths occurred, and adverse events were in line with what could be expected based on the known adverse event profiles of the drugs: hepatic adverse events, infections, and skin or allergic reactions were most frequent with infliximab, while haematological, gastrointestinal, and central nervous system adverse events were most prevalent with sulfasalazine and hydroxychloroquine.

The trial continues towards results at two years, and an extension is planned for participants who achieve low disease activity or remission to see whether infliximab can be discontinued.

Vertebroplasty may not be better than placebo

Two multicentre, double blind randomised trials failed to show that vertebroplasty—percutaneous injection of polymethylmethacrylate into the vertebral compression fracture—is better than a sham procedure for people with painful vertebral fractures caused by osteoporosis.

One trial included 78 people with one or two painful osteoporotic vertebral fractures that were of less than 12 months’ duration and unhealed. None of the outcome measures (overall pain, pain at night and at rest, physical functioning, quality of life, perceived improvement, and use of opioids) differed between the groups at any point during a six month follow-up. Instead, most outcomes improved in both groups. Only the score for the quality of life questionnaire of the European Foundation for Osteoporosis at week 1 favoured the placebo group.

The other trial enrolled 131 patients who had one to three painful osteoporotic vertebral compression fractures. Both groups experienced marked improvement in disability and pain scores immediately after the vertebroplasty, and no differences were seen between the groups at one month in disability, pain, quality of life, use of opioids, or self perceived health. Still, a clinically meaningful improvement in pain (defined as a 30% decrease from baseline) was more common in the vertebroplasty group (64% v 48%, P=0.06), and when crossover was offered to participants at three months, more people from the control group (43% v 12%, P<0.001) wanted to switch group.

Vertebroplasty has been on the rise since several institutions and professional societies endorsed its use on the basis of unblinded and quasi-randomised studies. Patients now have better evidence to inform their choices, says the linked editorial (p 619).

Universal screening doesn’t seem to benefit women exposed to intimate partner violence

In Canada, a randomised trial done in 11 emergency departments, 12 family practices, and three obstetrics and gynaecology clinics asked 8293 women aged 18-64 years, regardless of why they were seeing a doctor, to participate in a trial of screening for intimate partner violence. Of these women, 6743 (81%) agreed and were randomised to completing the “woman abuse screening tool,” which asks about intimate partner violence in the preceding year, before or after the visit. Doctors of women who screened positive were informed of this and were free to act on the information as normal. All women received information on where to seek help in their community, and women who screened positive were interviewed at baseline and every six months until the end of the study at 18 months.

Loss to follow-up was high, both among screened and non-screened women (43% and 41%, respectively), and screening did not improve recurrence of violence, quality of life, or health outcomes such as depressive symptoms, alcohol and drug misuse, or post-traumatic stress disorder, but it didn’t cause harm either. Immediately after the visit, 44% of screened women and 8% of non-screened women reported discussing violence with their doctor during the visit.

The editorialists (p 568) warn that better approaches to prevent the recurrence of abuse for women at risk of violence need to be developed and tested without further delay.

Victims of sexual abuse have impaired physical health later in life

A systematic review of 23 observational studies with 4640 participants found that people who have been sexually abused have a higher lifetime risk of being diagnosed with functional gastrointestinal disorders, such as irritable bowel syndrome (odds ratio 2.43, 95% CI 1.36 to 4.31), non-specific chronic pain (2.20, 1.54 to 3.15), psychogenic seizures (2.96, 1.12 to 4.69), and chronic pelvic pain (2.73, 1.73 to 4.30). However, no association was found for fibromyalgia (1.61, 0.85 to 3.07), obesity (1.47, 0.88 to 2.46), or headache (1.49, 0.96 to 2.31). No studies assessed syncope.

When sexual abuse met the criteria for rape, it was associated with an increased lifetime risk of being diagnosed with fibromyalgia (3.35, 1.51 to 7.46), chronic pelvic pain (3.27, 1.02 to 10.53), and functional gastrointestinal disorders (4.01, 1.88 to 8.57).

Prolonged travel nearly triples risk of venous thromboembolism

The association between travel and venous thromboembolism is supported by a plausible pathophysiological rationale. Nearly half of the observational studies on this subject have failed to confirm the association, however, and measuring the excess risk, if any, has perplexed researchers.

On the basis of 14 observational studies with 4055 cases, a systematic review estimated the pooled relative risk for venous thromboembolism in travellers, compared with non-travellers, at 2.0 (95% CI 1.5 to 2.7), with significant heterogeneity between studies. After excluding six case-control studies in which controls had been referred for suspicion of venous thromboembolism but were found not to have the condition, heterogeneity disappeared. In addition, the pooled relative risk was 2.8 (2.2 to 3.7) for the remaining studies and 1.2 (0.9 to 1.6) for the excluded studies. Furthermore, a dose-response association was present: each two hour addition to the duration of travel was associated with an 18% (4% to 33%) or 26% (7% to 48%) increase in the risk of venous thromboembolism, for any mode of transportation or air travel, respectively.

The authors conclude that travel increases the risk for venous thromboembolism nearly threefold, and that heterogeneity in previous studies resulted from selection bias towards the null caused by the use of referred control participants. The editorialists (p 212) use the study as an example in a broader discussion of the selection of controls for case-control studies.


Cite this as: BMJ 2009;339:b3257

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