Hot off the presses! Apr 22 LANCET

The Apr 22 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:

• Medical errors in the USA: human or systemic?
  - LANCET 377(9774):1289 (2011)
  
• Preconception genetic screening: where next?
  - LANCET 377(9774):1290 (2011)
  
• NHS reforms: Stop. Look. Listen
  - LANCET 377(9774):1290 (2011)
  
• Bringing stillbirths out of the shadows
  - LANCET 377(9774):1291-1292 (2011)
  
• Plausible estimates of stillbirth rates
  - LANCET 377(9774):1292-1294 (2011)
  
• The challenges of reducing risk factors for stillbirths
  - LANCET 377(9774):1294-1295 (2011)
  
• Combination treatment to CONQUER obesity?
  - LANCET 377(9774):1295-1297 (2011)
  
• Projections of alcohol deaths—a wake-up call
  - LANCET 377(9774):1297-1299 (2011)
  
• The indoor tanning industry's double game
  - LANCET 377(9774):1299-1301 (2011)
  
• China—a call for papers
  - LANCET 377(9774):1301 (2011)
  
• Offline: The privilege of a dubious reputation
  - LANCET 377(9774):1302 (2011)
  
• South Africa takes steps to reduce perinatal mortality
  - LANCET 377(9774):1303-1304 (2011)
  
• India–EU free-trade pact could stifle generics industry
  - LANCET 377(9774):1305-1306 (2011)
  
• A bonfire of the tape measures
  - LANCET 377(9774):1307 (2011)
  
• Breaking the silence around stillbirth
  - LANCET 377(9774):1308 (2011)
  
• Shershah Syed: improving maternal care in Pakistan
  - LANCET 377(9774):1309 (2011)
  
• The Art of Medicine: Moments held—photographing perinatal loss
  - LANCET 377(9774):1310-1311 (2011)
  
• Robert Ivor Woods
  - LANCET 377(9774):1312 (2011)
  
• The International Stillbirth Alliance: connecting for life
  - LANCET 377(9774):1313 (2011)
  
• Prediction of pre-eclampsia complications
  - LANCET 377(9774):1313 (2011)
  
• Prediction of pre-eclampsia complications – Authors' reply
  - LANCET 377(9774):1314 (2011)
  
• Heterogeneous effects on child survival in neonatal vitamin A supplementation trials
  - LANCET 377(9774):1314-1315 (2011)
  
• Heterogeneous effects on child survival in neonatal vitamin A supplementation trials – Authors' reply
  - LANCET 377(9774):1315 (2011)
  
• Improve the struggle against babies' pain
  - LANCET 377(9774):1315-1316 (2011)
  
• Improve the struggle against babies' pain – Author's reply
  - LANCET 377(9774):1316 (2011)
  
• The conviction of Binayak Sen
  - LANCET 377(9774):1316 (2011)
  
• The conviction of Binayak Sen
  - LANCET 377(9774):1316-1317 (2011)
  
• A new approach to large-scale effectiveness evaluation
  - LANCET 377(9774):1317 (2011)
  
• A new approach to large-scale effectiveness evaluation
  - LANCET 377(9774):1317-1318 (2011)
  
• Saving women's lives from cervical cancer
  - LANCET 377(9774):1318 (2011)
  
• Department of Error
  - LANCET 377(9774):1318 (2011)
  
• Department of Error
  - LANCET 377(9774):1318 (2011)
  
• National, regional, and worldwide estimates of stillbirth rates in 2009 with trends since 1995: a systematic analysis
  - LANCET 377(9774):1319-1330 (2011)
  Background Stillbirths do not count in routine worldwide data-collating systems or for the Millennium Development Goals. Two sets of national stillbirth estimates for 2000 produced similar worldwide totals of 3·2 million and 3·3 million, but rates differed substantially for some countries. We aimed to develop more reliable estimates and a time series from 1995 for 193 countries, by increasing input data, using recent data, and applying improved modelling approaches. Methods For international comparison, stillbirth is defined as fetal death in the third trimester (≥1000 g birthweight or ≥28 completed weeks of gestation). Several sources of stillbirth data were identified and assessed against prespecified inclusion criteria: vital registration data; nationally representative surveys; and published studies identified through systematic literature searches, unpublished studies, and national data identified through a WHO country consultation process. For 2009, reported rates were used for 33 countries and model-based estimates for 160 countries. A regression model of log stillbirth rate was developed and used to predict national stillbirth rates from 1995 to 2009. Uncertainty ranges were obtained with a bootstrap approach. The final model included log(neonatal mortality rate) (cubic spline), log(low birthweight rate) (cubic spline), log(gross national income purchasing power parity) (cubic spline), region, type of data source, and definition of ! stillbirth. Findings Vital registration data from 79 countries, 69 nationally representative surveys from 39 countries, and 113 studies from 42 countries met inclusion criteria. The estimated number of global stillbirths was 2·64 million (uncertainty range 2·14 million to 3·82 million) in 2009 compared with 3·03 million (uncertainty range 2·37 million to 4·19 million) in 1995. Worldwide stillbirth rate has declined by 14·5%, from 22·1 stillbirths per 1000 births in 1995 to 18·9 stillbirths per 1000 births in 2009. In 2009, 76·2% of stillbirths occurred in south Asia and sub-Saharan Africa. Interpretation This study draws attention to the dearth of reliable data in regions where most stillbirths occur. The estimated trend in stillbirth rate reduction is slower than that for maternal mortality and lags behind the increasing progress in reducing deaths in children younger than 5 years. Improved data and improved use of data are crucial to ensure that stillbirths count in global and national policy. Funding The Bill & Melinda Gates Foundation through the Global Alliance to Prevent Prematurity and Stillbirth, Saving Newborn Lives/Save the Children, and the International Stillbirth Alliance. The Department of Reproductive Health and Research, WHO, through the UN Development Programme, UN Population Fund, WHO, and World Bank Special Programme of Research, Development and Research Training in Human Reproduction.
• Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis
  - LANCET 377(9774):1331-1340 (2011)
  Background Stillbirth rates in high-income countries have shown little or no improvement over the past two decades. Prevention strategies that target risk factors could be important in rate reduction. This systematic review and meta-analysis was done to identify priority areas for stillbirth prevention relevant to those countries. Methods Population-based studies addressing risk factors for stillbirth were identified through database searches. The factors most frequently reported were identified and selected according to whether they could potentially be reduced through lifestyle or medical intervention. The numbers attributable to modifiable risk factors were calculated from data relating to the five high-income countries with the highest numbers of stillbirths and where all the data required for analysis were available. Odds ratios were calculated for selected risk factors, from which population-attributable risk (PAR) values were calculated. Findings Of 6963 studies initially identified, 96 population-based studies were included. Maternal overweight and obesity (body-mass index >25 kg/m2) was the highest ranking modifiable risk factor, with PARs of 8–18% across the five countries and contributing to around 8000 stillbirths (≥22 weeks' gestation) annually across all high-income countries. Advanced maternal age (>35 years) and maternal smoking yielded PARs of 7–11% and 4–7%, respectively, and each year contribute to more than 4200 and 2800 stillbirths, respectively, across all high-income countries. In disadvantaged populations maternal smoking could contribute to 20% of stillbirths. Primiparity contributes to around 15% of stillbirths. Of the pregnancy disorders, small size for gestational age and abruption are the highest PARs (23% and 15%, respectively), which highlights the notable role of placental pathology in stillbirth. Pre-existing diabetes and hypertension remain important contributors to stillbirth in su! ch countries. Interpretation The raising of awareness and implementation of effective interventions for modifiable risk factors, such as overweight, obesity, maternal age, and smoking, are priorities for stillbirth prevention in high-income countries. Funding The Stillbirth Foundation Australia, the Department of Health and Ageing, Canberra, Australia, and the Mater Foundation, Brisbane, Australia.
• Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial
  - LANCET 377(9774):1341-1352 (2011)
  Background Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors. Methods In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18–70 years), with a body-mass index of 27–45 kg/m2 and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787. Findings Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was −1·4 kg (least-squares mean −1·2%, 95% CI −1·8 to −0·7), −8·1 kg (−7·8%, −8·5 to −7·1; p<0·0001), and −10·2 kg (−9·8%, −10·4 to −9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·! 9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events. Interpretation The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors. Funding Vivus.
• Stillbirths: why they matter
  - LANCET 377(9774):1353-1366 (2011)
  In this first paper of The Lancet's Stillbirths Series we explore the present status of stillbirths in the world—from global health policy to a survey of community perceptions in 135 countries. Our findings highlight the need for a strong call for action. In times of global focus on motherhood, the mother's own aspiration of a liveborn baby is not recognised on the world's health agenda. Millions of deaths are not counted; stillbirths are not in the Global Burden of Disease, nor in disability-adjusted life-years lost, and they are not part of the UN Millennium Development Goals. The grief of mothers might be aggravated by social stigma, blame, and marginalisation in regions where most deaths occur. Most stillborn babies are disposed of without any recognition or ritual, such as naming, funeral rites, or the mother holding or dressing the baby. Beliefs in the mother's sins and evil spirits as causes of stillbirth are rife, and stillbirth is widely believed to be a nat! ural selection of babies never meant to live. Stillbirth prevention is closely linked with prevention of maternal and neonatal deaths. Knowledge of causes and feasible solutions for prevention is key to health professionals' priorities, to which this Stillbirths Series paper aims to contribute.
• Glaucoma
  - LANCET 377(9774):1367-1377 (2011)
  Most medical practitioners have regular contact with adults who have one of the two forms of glaucoma: open-angle glaucoma or angle-closure glaucoma. Data from population-based surveys indicate that one in 40 adults older than 40 years has glaucoma with loss of visual function, which equates to 60 million people worldwide being affected and 8·4 million being bilaterally blind. Even in developed countries, half of glaucoma cases are undiagnosed. Glaucoma is mostly asymptomatic until late in the disease when visual problems arise. Vision loss from glaucoma cannot be recovered, and improved case-detection methods for glaucoma are needed. Glaucoma is commonly treated with daily eye-drop drugs, but adherence to treatment is often unsatisfactory. As a usually asymptomatic and chronic disease, glaucoma has similar treatment challenges to chronic systemic diseases. Similarities to the pathogenesis of common CNS diseases mean that common neuroprotective strategies might exist.! Successful gene therapy, which has been used for other eye diseases might be possible for the treatment of glaucoma in the future.
• Myxoma, dyspnoea, tinnitus, scoliosis, and alopecia
  - LANCET 377(9774):1378 (2011)