Hot off the presses! May 06 LANCET

The May 06 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:

• The three stages of Alzheimer's disease
  - LANCET 377(9776):1465 (2011)
  
• Strengthening the regulation of herbal medicines in Europe
  - LANCET 377(9776):1466 (2011)
  
• Artesunate for severe malaria
  - LANCET 377(9776):1466 (2011)
  
• Improving tuberculosis diagnostics and treatment
  - LANCET 377(9776):1467-1468 (2011)
  
• Concerns about injectable naltrexone for opioid dependence
  - LANCET 377(9776):1468-1470 (2011)
  
• DISPACT trial: what do we learn from equivalency?
  - LANCET 377(9776):1470-1471 (2011)
  
• Stillbirths: the professional organisations' perspective
  - LANCET 377(9776):1471-1472 (2011)
  
• Case competitions to engage students in global health
  - LANCET 377(9776):1473-1474 (2011)
  
• Lead poisoning in China: a nightmare from industrialisation
  - LANCET 377(9776):1474-1476 (2011)
  
• HbA1c: an old friend in new clothes
  - LANCET 377(9776):1476-1477 (2011)
  
• Offline: The land of holy miracles
  - LANCET 377(9776):1478 (2011)
  
• UK moves to ensure "access to unlicensed herbal medicines"
  - LANCET 377(9776):1479-1480 (2011)
  
• Native American health left out in the cold
  - LANCET 377(9776):1481-1482 (2011)
  
• The happiness wars
  - LANCET 377(9776):1483-1484 (2011)
  
• Animating images
  - LANCET 377(9776):1484 (2011)
  
• Colin Sullivan: inventive pioneer of sleep medicine
  - LANCET 377(9776):1485 (2011)
  
• 17th-century childbirth: "exquisite torment and infinite grace"
  - LANCET 377(9776):1486-1487 (2011)
  
• Martin Avigdor Birnstingl
  - LANCET 377(9776):1488 (2011)
  
• Safety of workers at the Fukushima Daiichi nuclear power plant
  - LANCET 377(9776):1489-1490 (2011)
  
• Initial combination therapy for treatment of hypertension
  - LANCET 377(9776):1490-1491 (2011)
  
• Initial combination therapy for treatment of hypertension
  - LANCET 377(9776):1491 (2011)
  
• Initial combination therapy for treatment of hypertension
  - LANCET 377(9776):1491 (2011)
  
• Initial combination therapy for treatment of hypertension – Authors' reply
  - LANCET 377(9776):1492 (2011)
  
• The complexity of ABO in coronary heart disease
  - LANCET 377(9776):1492-1493 (2011)
  
• The complexity of ABO in coronary heart disease
  - LANCET 377(9776):1493 (2011)
  
• The complexity of ABO in coronary heart disease – Authors' reply
  - LANCET 377(9776):1493-1494 (2011)
  
• Department of Error
  - LANCET 377(9776):1494 (2011)
  
• Department of Error
  - LANCET 377(9776):1494 (2011)
  
• Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study
  - LANCET 377(9776):1495-1505 (2011)
  Background The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings. Methods We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2–3 sputum smears and 1–3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used. Findings We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0–1), compared with 1 day (0–1) for microscopy, 30 days (23–43) for solid culture, and 16 days (13–21) for liquid culture. Median time to detection of resistance was 20 days (10–26) for line-probe assay and 106 days (30–124) for conventional drug-susceptibility testing. Use of the MTB/RIF test ! reduced median time to treatment for smear-negative tuberculosis from 56 days (39–81) to 5 days (2–8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures. Interpretation The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment. Funding Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development.
• Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial
  - LANCET 377(9776):1506-1513 (2011)
  Background Opioid dependence is associated with low rates of treatment-seeking, poor adherence to treatment, frequent relapse, and major societal consequences. We aimed to assess the efficacy, safety, and patient-reported outcomes of an injectable, once monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification. Methods We did a double-blind, placebo-controlled, randomised, 24-week trial of patients with opioid dependence disorder. Patients aged 18 years or over who had 30 days or less of inpatient detoxification and 7 days or more off all opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg XR-NTX or placebo by an interactive voice response system, stratified by site and gender in a centralised, permuted-block method. Participants also received 12 biweekly counselling sessions. Participants, investigators, staff, and the sponsor were masked to treatment allocation. The primary endpoint was the response profile for confirmed abstinence during weeks 5–24, assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported opioid-free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence. Analyses were by intention to treat. This trial is registered at Clinica! lTrials.gov, NCT00678418. Findings Between July 3, 2008, and Oct 5, 2009, 250 patients were randomly assigned to XR-NTX (n=126) or placebo (n=124). The median proportion of weeks of confirmed abstinence was 90·0% (95% CI 69·9–92·4) in the XR-NTX group compared with 35·0% (11·4–63·8) in the placebo group (p=0·0002). Patients in the XR-NTX group self-reported a median of 99·2% (range 89·1–99·4) opioid-free days compared with 60·4% (46·2–94·0) for the placebo group (p=0·0004). The mean change in craving was −10·1 (95% CI −12·3 to −7·8) in the XR-NTX group compared with 0·7 (−3·1 to 4·4) in the placebo group (p<0·0001). Median retention was over 168 days in the XR-NTX group compared with 96 days (95% CI 63–165) in the placebo group (p=0·0042). Naloxone challenge confirmed relapse to physiological opioid dependence in 17 patients in the placebo group compared with one in the XR-NTX group (p<0·0001). XR-NTX was well tolerated. Two patients in each group discontinued owing to! adverse events. No XR-NTX-treated patients died, overdosed, or discontinued owing to severe adverse events. Interpretation XR-NTX represents a new treatment option that is distinct from opioid agonist maintenance treatment. XR-NTX in conjunction with psychosocial treatment might improve acceptance of opioid dependence pharmacotherapy and provide a useful treatment option for many patients. Funding Alkermes.
• Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial
  - LANCET 377(9776):1514-1522 (2011)
  Background The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. Methods This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. Findings Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53–1·33; p=0·56). One patient died within the first 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. Interpretation Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. Funding German Federal Ministry of Education and Research.
• Stillbirths: what difference can we make and at what cost?
  - LANCET 377(9776):1523-1538 (2011)
  Worldwide, 2·65 million (uncertainty range 2·08 million to 3·79 million) stillbirths occur yearly, of which 98% occur in countries of low and middle income. Despite the fact that more than 45% of the global burden of stillbirths occur intrapartum, the perception is that little is known about effective interventions, especially those that can be implemented in low-resource settings. We undertook a systematic review of randomised trials and observational studies of interventions which could reduce the burden of stillbirths, particularly in low-income and middle-income countries. We identified several interventions with sufficient evidence to recommend implementation in health systems, including periconceptional folic acid supplementation or fortification, prevention of malaria, and improved detection and management of syphilis during pregnancy in endemic areas. Basic and comprehensive emergency obstetric care were identified as key effective interventions to reduce in! trapartum stillbirths. Broad-scale implementation of intervention packages across 68 countries listed as priorities in the Countdown to 2015 report could avert up to 45% of stillbirths according to a model generated from the Lives Saved Tool. The overall costs for these interventions are within the general estimates of cost-effective interventions for maternal care, especially in view of the effects on outcomes across maternal, fetal, and neonatal health.
• Live case demonstrations: patient safety, ethics, consent, and conflicts
  - LANCET 377(9776):1539-1541 (2011)
  
• A deadly aversion to pork
  - LANCET 377(9776):1542 (2011)