Hot off the presses! Aug 12 Lancet

The Aug 12 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:

• China's major health challenge: control of chronic diseases
  - Lancet 378(9790):457 (2011)
  
• Blowing the whistle on intimidation of NHS whistleblowers
  - Lancet 378(9790):458 (2011)
  
• Health care for young offenders
  - Lancet 378(9790):458 (2011)
  
• Anti-CD3 antibodies for type 1 diabetes: beyond expectations
  - Lancet 378(9790):459-460 (2011)
  
• Autologous HSCT in systemic sclerosis: a step forward
  - Lancet 378(9790):460-462 (2011)
  
• Mass eradication of Helicobacter pylori: feasible and advisable?
  - Lancet 378(9790):462-464 (2011)
  
• What is the future of epidemiology?
  - Lancet 378(9790):464-465 (2011)
  
• Is immunisation child protection?
  - Lancet 378(9790):465-468 (2011)
  
• Public health: profession, health system, government control
  - Lancet 378(9790):468-469 (2011)
  
• Offline: Our common future
  - Lancet 378(9790):470 (2011)
  
• Donors continue to hold back support from Global Fund
  - Lancet 378(9790):471-472 (2011)
  
• USA hones in on prescription drug abuse
  - Lancet 378(9790):473-474 (2011)
  
• The Lancet Technology: August, 2011
  - Lancet 378(9790):475 (2011)
  
• Everybody's got something to hide except me and my monkey
  - Lancet 378(9790):476 (2011)
  
• Nora Volkow—challenging the myths about drug addiction
  - Lancet 378(9790):477 (2011)
  
• Galen and his patients
  - Lancet 378(9790):478-479 (2011)
  
• James Joseph Rahal
  - Lancet 378(9790):480 (2011)
  
• Xpert MTB/RIF test for tuberculosis
  - Lancet 378(9790):481 (2011)
  
• Xpert MTB/RIF test for tuberculosis
  - Lancet 378(9790):481-482 (2011)
  
• Xpert MTB/RIF test for tuberculosis
  - Lancet 378(9790):482 (2011)
  
• Xpert MTB/RIF test for tuberculosis – Authors' reply
  - Lancet 378(9790):482-483 (2011)
  
• Sharing information on adverse events
  - Lancet 378(9790):483 (2011)
  
• Blood-cell banking for workers at the Fukushima Daiichi nuclear power plant
  - Lancet 378(9790):483-484 (2011)
  
• Blood-cell banking for workers at the Fukushima Daiichi nuclear power plant – Authors' reply
  - Lancet 378(9790):484-485 (2011)
  
• Blood-cell banking for workers at the Fukushima Daiichi nuclear power plant
  - Lancet 378(9790):485 (2011)
  
• Need for close watch on children's health after Fukushima disaster
  - Lancet 378(9790):485-486 (2011)
  
• Development of drugs against chemical, biological, radiological, or nuclear agents
  - Lancet 378(9790):486 (2011)
  
• Department of Error
  - Lancet 378(9790):486 (2011)
  
• Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial
  - Lancet 378(9790):487-497 (2011)
  Background Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve β-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab. Methods In this 2-year trial, patients aged 8–35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protégé study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0·5 U/kg per day and glycated haemoglobin A1c (HbA1C) of less than 6·5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00385697. Findings 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19·8% (41/207) in the 14-day full-dose group; 13·7% (14/102) in the 14-day low-dose group; 20·8% (22/106) in the 6-day full-dose group; and 20·4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0·03). Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]). The most common clinical adve! rse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group). Interpretation Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in β-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children. Funding MacroGenics, the Juvenile Diabetes Research Foundation, and Eli Lilly.
• Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial
  - Lancet 378(9790):498-506 (2011)
  Background Non-randomised studies of haemopoietic stem-cell transplantation (HSCT) in systemic sclerosis have shown improvements in lung function and skin flexibility but high treatment-related mortality. We aimed to assess safety and efficacy of autologous non-myeloablative HSCT in a phase 2 trial compared with the standard of care, cyclophosphamide. Methods In our open-label, randomised, controlled phase 2 trial, we consecutively enrolled patients at Northwestern Memorial Hospital (Chicago, IL, USA) who were aged younger than 60 years with diffuse systemic sclerosis, modified Rodnan skin scores (mRSS) of more than 14, and internal organ involvement or restricted skin involvement (mRSS <14) but coexistent pulmonary involvement. We randomly allocated patients 1:1 by use of a computer-generated sequence with a mixed block design (blocks of ten and four) to receive HSCT, 200 mg/kg intravenous cyclophosphamide, and 6·5 mg/kg intravenous rabbit antithymocyte globulin or to receive 1·0 g/m2 intravenous cyclophosphamide once per month for 6 months. The primary outcome for all enrolled patients was improvement at 12 months' follow-up, defined as a decrease in mRSS (>25% for those with initial mRSS >14) or an increase in forced vital capacity by more than 10%. Patients in the control group with disease progression (>25% increase in mRS! S or decrease of >10% in forced vital capacity) despite treatment with cyclophosphamide could switch to HSCT 12 months after enrolment. This study is registered with ClinicalTrials.gov, number NCT00278525. Findings Between Jan 18, 2006, and Nov 10, 2009 we enrolled 19 patients. All ten patients randomly allocated to receive HSCT improved at or before 12 months' follow-up, compared with none of nine allocated to cyclophosphamide (odds ratio 110, 95% CI 14·04–∞; p=0·00001). Eight of nine controls had disease progression (without interval improvement) compared with no patients treated by HSCT (p=0·0001), and seven patients switched to HSCT. Compared with baseline, data for 11 patients with follow-up to 2 years after HSCT suggested that improvements in mRSS (p<0·0001) and forced vital capacity (p<0·03) persisted. Interpretation Non-myeloablative autologous HSCT improves skin and pulmonary function in patients with systemic sclerosis for up to 2 years and is preferable to the current standard of care, but longer follow-up is needed. Funding None
• 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial
  - Lancet 378(9790):507-514 (2011)
  Background Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy. Methods Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21–65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6–8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.g! ov, registration number NCT01061437. Findings 1463 participants aged 21–65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6–14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (–0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. Interpretation Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations. Funding Bill & Melinda Gates Foundation, US National Institutes of Health.
• Mathematical models in the evaluation of health programmes
  - Lancet 378(9790):515-525 (2011)
  Modelling is valuable in the planning and evaluation of interventions, especially when a controlled trial is ethically or logistically impossible. Models are often used to calculate the expected course of events in the absence of more formal assessments. They are also used to derive estimates of rare or future events from recorded intermediate points. When developing models, decisions are needed about the appropriate level of complexity to be represented and about model structure and assumptions. The degree of rigor in model development and assessment can vary greatly, and there is a danger that existing beliefs inappropriately influence judgments about model assumptions and results.
• Addressing the vaccine confidence gap
  - Lancet 378(9790):526-535 (2011)
  Vaccines—often lauded as one of the greatest public health interventions—are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk–benefit! ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines.
• Public health in England: an option for the way forward?
  - Lancet 378(9790):536-539 (2011)
  
• Multiple endocrine abnormalities
  - Lancet 378(9790):540 (2011)