Hot off the presses! May 13 LANCET

The May 13 issue of the LANCET is now up on Pubget (About LANCET): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Reducing road dangers
  - LANCET 377(9777):1543 (2011)
  
• New guidelines for early detection of ovarian cancer
  - LANCET 377(9777):1544 (2011)
  
• Financing HPV vaccination in developing countries
  - LANCET 377(9777):1544 (2011)
  
• Appendicitis: is surgery the best option?
  - LANCET 377(9777):1545-1546 (2011)
  
• Improving treatment outcome for children with HIV
  - LANCET 377(9777):1546-1548 (2011)
  
• Isoniazid preventive therapy in HIV infection
  - LANCET 377(9777):1548-1550 (2011)
  
• Stillbirths: missing from the family and from family health
  - LANCET 377(9777):1550-1551 (2011)
  
• Value-based medicine pricing: NICE work?
  - LANCET 377(9777):1552-1553 (2011)
  
• Clinical research: time for sensible global guidelines
  - LANCET 377(9777):1553-1555 (2011)
  
• Offline: Russia pitches for global health
  - LANCET 377(9777):1556 (2011)
  
• China progresses with health reform but challenges remain
  - LANCET 377(9777):1557-1558 (2011)
  
• Burning issues: tackling indoor air pollution
  - LANCET 377(9777):1559-1560 (2011)
  
• The perils of excessive medical care
  - LANCET 377(9777):1561-1562 (2011)
  
• Remain in light
  - LANCET 377(9777):1562 (2011)
  
• Rebecca Ivers: driving down the toll of injury
  - LANCET 377(9777):1563 (2011)
  
• Gone to earth—the burial grounds of the Royal London Hospital
  - LANCET 377(9777):1564-1565 (2011)
  
• Baruch Samuel Blumberg
  - LANCET 377(9777):1566 (2011)
  
• Restricted elimination diet for ADHD
  - LANCET 377(9777):1567 (2011)
  
• Restricted elimination diet for ADHD
  - LANCET 377(9777):1567 (2011)
  
• Restricted elimination diet for ADHD
  - LANCET 377(9777):1567-1568 (2011)
  
• Restricted elimination diet for ADHD – Authors' reply
  - LANCET 377(9777):1568 (2011)
  
• Towards universal health coverage in India
  - LANCET 377(9777):1568-1569 (2011)
  
• Towards universal health coverage in India
  - LANCET 377(9777):1569 (2011)
  
• Towards universal health coverage in India
  - LANCET 377(9777):1569-1570 (2011)
  
• Towards universal health coverage in India
  - LANCET 377(9777):1570-1571 (2011)
  
• Health in southeast Asia
  - LANCET 377(9777):1571 (2011)
  
• Health in southeast Asia
  - LANCET 377(9777):1571 (2011)
  
• Making a difference to health in slums: an HIV and African perspective
  - LANCET 377(9777):1571-1572 (2011)
  
• Pricing the Advance Market Commitment
  - LANCET 377(9777):1572 (2011)
  
• Department of Error
  - LANCET 377(9777):1572 (2011)
  
• Department of Error
  - LANCET 377(9777):1572 (2011)
  
• Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial
  - LANCET 377(9777):1573-1579 (2011)
  Background Researchers have suggested that antibiotics could cure acute appendicitis. We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis. Methods In this open-label, non-inferiority, randomised trial, adult patients (aged 18–68 years) with uncomplicated acute appendicitis, as assessed by CT scan, were enrolled at six university hospitals in France. A computer-generated randomisation sequence was used to allocate patients randomly in a 1:1 ratio to receive amoxicillin plus clavulanic acid (3 g per day) for 8–15 days or emergency appendicectomy. The primary endpoint was occurrence of postintervention peritonitis within 30 days of treatment initiation. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10 percentage points. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT00135603. Findings Of 243 patients randomised, 123 were allocated to the antibiotic group and 120 to the appendicectomy group. Four were excluded from analysis because of early dropout before receiving the intervention, leaving 239 (antibiotic group, 120; appendicectomy group, 119) patients for intention-to-treat analysis. 30-day postintervention peritonitis was significantly more frequent in the antibiotic group (8%, n=9) than in the appendicectomy group (2%, n=2; treatment difference 5·8; 95% CI 0·3–12·1). In the appendicectomy group, despite CT-scan assessment, 21 (18%) of 119 patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis. In the antibiotic group, 14 (12% [7·1–18·6]) of 120 underwent an appendicectomy during the first 30 days and 30 (29% [21·4–38·9]) of 102 underwent appendicectomy between 1 month and 1 year, 26 of whom had acute appendicitis (recurrence rate 26%; 18·0–34·7). Interpretation Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis. Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment. Funding French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002.
• Risk of triple-class virological failure in children with HIV: a retrospective cohort study
  - LANCET 377(9777):1580-1587 (2011)
  Background In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children. Methods In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation. Findings Of 1007 children followed up for a median of 4·2 (IQR 2·4–6·5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12·0% (95% CI 9·4–14·6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0·02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2·2 [95% CI 1·6–3·0, p<0·0001]). Interpretation Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression. Funding UK Medical Research Council award G0700832.
• 6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial
  - LANCET 377(9777):1588-1598 (2011)
  Background In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. Methods In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per μL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTr! ials.gov, number NCT00164281. Findings Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3·4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2·0%) in 1006 allocated to the continued isoniazid group (incidence 1·26% per year vs 0·72%; hazard ratio 0·57, 95% CI 0·33–0·99, p=0·047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0·26, 0·09–0·80, p=0·02), whereas participants who were tuberculin skin test-negative received no significant benefit (0·75, 0·38–1·46, p=0·40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretrov! iral therapy (adjusted hazard ratio 0·50, 95% CI 0·26–0·97). Severe adverse events and death were much the same in the control and continued isoniazid groups. Interpretation In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. Funding US Centers for Disease Control and Prevention and US Agency for International Development.
• Nearly an eye-catcher
  - LANCET 377(9777):1599 (2011)
  
• Primary biliary cirrhosis
  - LANCET 377(9777):1600-1609 (2011)
  Primary biliary cirrhosis is a chronic liver disease characterised by intrahepatic bile-duct destruction, cholestasis, and, in some cases, cirrhosis. Evidence supporting the autoimmune nature of this disorder includes the appearance of highly specific antimitochondrial antibodies (AMAs) and autoreactive T cells. Concordance rates in monozygotic twins, familial prevalence, and genetic associations underscore the importance of genetic factors, whereas findings of epidemiological studies and murine models suggest a possible role for exogenous chemicals and infectious agents through molecular mimicry. The incidence of primary biliary cirrhosis has increased over recent decades, possibly attributable to augmented testing of liver biochemistry rather than a rise in disease incidence. AMAs remain the hallmark of diagnosis in most cases and allow detection of asymptomatic patients. Symptomatic individuals usually present with either pruritus or fatigue and, more rarely, with e! ither jaundice or complications of cirrhosis. The prognosis of primary biliary cirrhosis has improved because of early diagnosis and use of ursodeoxycholic acid, the only established medical treatment for this disorder. Although not a cure, treatment can slow disease progression and delay the need for liver transplantation. However, some patients do not respond adequately to ursodeoxycholic acid and might need alternative therapeutic approaches.
• Stillbirths: how can health systems deliver for mothers and babies?
  - LANCET 377(9777):1610-1623 (2011)
  The causes of stillbirths are inseparable from the causes of maternal and neonatal deaths. This report focuses on prevention of stillbirths by scale-up of care for mothers and babies at the health-system level, with consideration for effects and cost. In countries with high mortality rates, emergency obstetric care has the greatest effect on maternal and neonatal deaths, and on stillbirths. Syphilis detection and treatment is of moderate effect but of lower cost and is highly feasible. Advanced antenatal care, including induction for post-term pregnancies, and detection and management of hypertensive disease, fetal growth restriction, and gestational diabetes, will further reduce mortality, but at higher cost. These interventions are best packaged and provided through linked service delivery methods tailored to suit existing health-care systems. If 99% coverage is reached in 68 priority countries by 2015, up to 1·1 million (45%) third-trimester stillbirths, 201 000 (5! 4%) maternal deaths, and 1·4 million (43%) neonatal deaths could be saved per year at an additional total cost of US$10·9 billion or $2·32 per person, which is in the range of $0·96–2·32 for other ingredients-based intervention packages with only recurrent costs.
• Recurrent pneumothorax
  - LANCET 377(9777):1624 (2011)