Hot off the presses! Jul 29 Lancet

The Jul 29 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:

• Animals in research: "can they suffer?"
  - Lancet 378(9788):289 (2011)
  
• The long road to improvement of human rights in China
  - Lancet 378(9788):290 (2011)
  
• Oral health care in the USA
  - Lancet 378(9788):290 (2011)
  
• Arresting type 1 diabetes after diagnosis: GAD is not enough
  - Lancet 378(9788):291-292 (2011)
  
• Managing post-prostatectomy stress urinary incontinence
  - Lancet 378(9788):293-294 (2011)
  
• Retroperitoneal fibrosis: gaining traction on an enigma
  - Lancet 378(9788):294-296 (2011)
  
• The vaccine paradox
  - Lancet 378(9788):296-298 (2011)
  
• A call to action for the new decade of vaccines
  - Lancet 378(9788):298-302 (2011)
  
• Debt crisis strains Greece's ailing health system
  - Lancet 378(9788):303-304 (2011)
  
• Uncertainty clouds China's road-traffic fatality data
  - Lancet 378(9788):305-306 (2011)
  
• Dr Jenner's House: the birthplace of vaccination
  - Lancet 378(9788):307-308 (2011)
  
• Richard Moxon: a virtuoso of vaccinology
  - Lancet 378(9788):309 (2011)
  
• Time to mandate influenza vaccination in health-care workers
  - Lancet 378(9788):310-311 (2011)
  
• Gustavo Kourí Flores
  - Lancet 378(9788):312 (2011)
  
• Greek academic psychiatry and neurology before the firing squad?
  - Lancet 378(9788):313 (2011)
  
• Helicobacter pylori eradication
  - Lancet 378(9788):313 (2011)
  
• Helicobacter pylori eradication
  - Lancet 378(9788):314 (2011)
  
• Helicobacter pylori eradication – Author's reply
  - Lancet 378(9788):314 (2011)
  
• Male circumcision for prevention of oncogenic HPV infection
  - Lancet 378(9788):314-315 (2011)
  
• Male circumcision for prevention of oncogenic HPV infection – Author's reply
  - Lancet 378(9788):315 (2011)
  
• Human papillomavirus vaccination in Africa
  - Lancet 378(9788):315-316 (2011)
  
• Blocking out the real diagnosis
  - Lancet 378(9788):316 (2011)
  
• Blocking out the real diagnosis – Authors' reply
  - Lancet 378(9788):316 (2011)
  
• Brazilian health-service organisation: problems at a glance
  - Lancet 378(9788):316-317 (2011)
  
• Post-disaster mental health care in Japan
  - Lancet 378(9788):317 (2011)
  
• Post-disaster mental health care in Japan
  - Lancet 378(9788):317-318 (2011)
  
• Life, health, and community in a tsunami-affected town
  - Lancet 378(9788):318 (2011)
  
• Support for senior management at Great Ormond Street Hospital
  - Lancet 378(9788):318 (2011)
  
• Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial
  - Lancet 378(9788):319-327 (2011)
  Background Glutamic acid decarboxylase (GAD) is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. In animal models of autoimmunity, treatment with a target antigen can modulate aggressive autoimmunity. We aimed to assess whether immunisation with GAD formulated with aluminum hydroxide (GAD-alum) would preserve insulin production in recent-onset type 1 diabetes. Methods Patients aged 3–45 years who had been diagnosed with type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and Canada, and randomly assigned to receive one of three treatments: three injections of 20 μg GAD-alum, two injections of 20 μg GAD-alum and one of alum, or 3 injections of alum. Injections were given subcutaneously at baseline, 4 weeks later, and 8 weeks after the second injection. The randomisation sequence was computer generated at the TrialNet coordinating centre. Patients and study personnel were masked to treatment assignment. The primary outcome was the baseline-adjusted geometric mean area under the curve (AUC) of serum C-peptide during the first 2 h of a 4-h mixed meal tolerance test at 1 year. Secondary outcomes included changes in glycated haemoglobin A1c (HbA1c) and insulin dose, and safety. Analysis included all randomised patients with known measurements. This trial is registered with ClinicalTrials.gov, number NCT00529399. Findings 145 patients were enrolled and treated with GAD-alum (n=48), GAD-alum plus alum (n=49), or alum (n=48). At 1 year, the 2-h AUC of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0·412 nmol/L (95% CI 0·349–0·478) in the GAD-alum group, 0·382 nmol/L (0·322–0·446) in the GAD-alum plus alum group, and 0·413 nmol/L (0·351–0·477) in the alum group. The ratio of the population mean of the adjusted geometric mean 2-h AUC of C-peptide was 0·998 (95% CI 0·779–1·22; p=0·98) for GAD-alum versus alum, and 0·926 (0·720–1·13; p=0·50) for GAD-alum plus alum versus alum. HbA1c, insulin use, and the occurrence and severity of adverse events did not differ between groups. Interpretation Antigen-based immunotherapy therapy with two or three doses of subcutaneous GAD-alum across 4–12 weeks does not alter the course of loss of insulin secretion during 1 year in patients with recently diagnosed type 1 diabetes. Although antigen-based therapy is a highly desirable treatment and is effective in animal models, translation to human autoimmune disease remains a challenge. Funding US National Institutes of Health.
• Urinary incontinence in men after formal one-to-one pelvic-floor muscle training following radical prostatectomy or transurethral resection of the prostate (MAPS): two parallel randomised controlled trials
  - Lancet 378(9788):328-337 (2011)
  Background Urinary incontinence is common immediately after prostate surgery. Men are often advised to do pelvic-floor exercises, but evidence to support this is inconclusive. Our aim was to establish if formal one-to-one pelvic floor muscle training reduces incontinence. Methods We undertook two randomised trials in men in the UK who were incontinent 6 weeks after radical prostatectomy (trial 1) or transurethral resection of the prostate (TURP; trial 2) to compare four sessions with a therapist over 3 months with standard care and lifestyle advice only. Randomisation was by remote computer allocation. Our primary endpoints, collected via postal questionnaires, were participants' reports of urinary incontinence and incremental cost per quality-adjusted life year (QALY) after 12 months. Group assignment was masked from outcome assessors, but this masking was not possible for participants or caregivers. We used intention-to-treat analyses to compare the primary outcome at 12 months. This study is registered, number ISRCTN87696430. Findings In the intervention group in trial 1, the rate of urinary incontinence at 12 months (148 [76%] of 196) was not significantly different from the control group (151 [77%] of 195; absolute risk difference [RD] −1·9%, 95% CI −10 to 6). In trial 2, the difference in the rate of urinary incontinence at 12 months (126 [65%] of 194) from the control group was not significant (125 [62%] of 203; RD 3·4%, 95% CI −6 to 13). Adjusting for minimisation factors or doing treatment-received analyses did not change these results in either trial. No adverse effects were reported. In both trials, the intervention resulted in higher mean costs per patient (£180 and £209 respectively) but we did not identify evidence of an economically important difference in QALYs (0·002 [95% CI −0·027 to 0·023] and −0·00003 [−0·026 to 0·026]). Interpretation In settings where information about pelvic-floor exercise is widely available, one-to-one conservative physical therapy for men who are incontinent after prostate surgery is unlikely to be effective or cost effective. The high rates of persisting incontinence after 12 months suggest a substantial unrecognised and unmet need for management in these men. Funding National Institute of Health Research, Health Technology Assessment (NIHR HTA) Programme.
• Prednisone versus tamoxifen in patients with idiopathic retroperitoneal fibrosis: an open-label randomised controlled trial
  - Lancet 378(9788):338-346 (2011)
  Background Glucocorticoids are the mainstay of treatment of idiopathic retroperitoneal fibrosis, but they often have substantial toxic effects. Several reports have suggested tamoxifen as an alternative to glucocorticoids. We compared the efficacy of prednisone with that of tamoxifen in maintainance of remission in patients with idiopathic retroperitoneal fibrosis. Methods In this open-label, randomised controlled trial, we enrolled patients aged 18–85 years with newly diagnosed idiopathic retroperitoneal fibrosis at the Parma Hospital, Parma, Italy, between Oct 1, 2000, and June 30, 2006. After induction therapy with 1 mg/kg daily of prednisone for 1 month, the patients who achieved remission were randomly assigned to receive tapering prednisone (initial dose 0·5 mg/kg daily) for 8 months or tamoxifen (fixed dose 0·5 mg/kg daily) for 8 months. The sequence of randomisation (1:1), blocked in groups of two and four (with block size randomly selected), was generated by the trial statistician with a computer programme. After the end of treatment, the patients were followed up for an additional 18 months. Neither patients nor those giving interventions or analysing the data were masked to group assignment. The two radiologists who assessed CT and MRI scans were masked. The primary endpoint was the relapse rate by the end of treatment (month 8)! , which was analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00440349. Findings After induction therapy, 36 of the 40 enrolled patients achieved remission and were randomly assigned to treatment (18 per group). One patient (6%) in the prednisone group and seven patients (39%) in the tamoxifen group relapsed by the end of treatment (difference −33% [95% CI −58 to −8, p=0·0408]. The difference in relapse rate between the groups was sustained after the additional 18-month follow-up: the 26-month estimated cumulative relapse probability was 17% with prednisone and 50% with tamoxifen (difference −33% [−62 to −3, p=0·0372]). Cushingoid changes and grade 2 hypercholesterolaemia were more common in the prednisone group than in the tamoxifen group (p=0·0116 and p=0·0408, respectively). Interpretation Prednisone is more effective in prevention of relapses than is tamoxifen in patients with idiopathic retroperitoneal fibrosis. Therefore, prednisone should be considered as first-line treatment for patients with newly diagnosed idiopathic retroperitoneal fibrosis. Funding Parma University Hospital.
• Dermacentor tick attached to tympanic membrane
  - Lancet 378(9788):347 (2011)
  
• The next decade of vaccines: societal and scientific challenges
  - Lancet 378(9788):348-359 (2011)
  Vaccines against microbial diseases have improved the health of millions of people. In the next decade and beyond, many conceptual and technological scientific advances offer extraordinary opportunities to expand the portfolio of immunisations against viral and bacterial diseases and to pioneer the first vaccines against human parasitic and fungal diseases. Scientists in the public and private sectors are motivated as never before to bring about these innovations in immunisation. Many societal factors threaten to compromise realisation of the public health gains that immunisation can achieve in the next decade and beyond—understanding these factors is imperative. Vaccines are typically given to healthy individuals and safety issues loom high on the list of public concerns. The public needs to regain confidence in immunisation and trust the organisations responsible for the research, development, and implementation of vaccines. In the past, by use of a judicious amalg! am of knowledge and empiricism, successful vaccines were largely developed by microbiologists who identified antigens that induced immune responses to conserved pathogen components. In the future, vaccines need to be developed against deadly diseases for which this strategy is often not feasible because of the extensive antigenic variability of relevant pathogens. High microbial diversity means that immunity after natural infection is often ineffective for prevention of disease on subsequent exposure, for example in HIV infection and malaria. Additionally, vaccines need to be generated to protect the people who are most vulnerable because of age or underlying diseases. Thus, in the future, a much deeper understanding of the immunological challenges—including the diversifying role of host genetics and environmental factors, leading perhaps to more personalised approaches—will be the touchstone for rational design and development of adjuvants that result in novel safe and! effective vaccines.
• Vaccine discovery and translation of new vaccine technology
  - Lancet 378(9788):360-368 (2011)
  An unprecedented increase in new vaccine development has occurred over the past three decades. This activity has resulted in vaccines that protect against an increased range of vaccine-preventable diseases, vaccines that reduce the number of required injections, and vaccines with improved safety and purity. New methods of discovery, such as reverse vaccinology, structural biology, and systems biology, promise new vaccines for different diseases and efficient development pathways for these vaccines. We expect development of vaccines not only for infectious diseases in children but also for healthy adults, pregnant women, and elderly people, and for new indications such as autoimmune disease and cancer. We have witnessed a concomitant development of new technology for assessment of vaccine safety to rapidly identify potential safety issues. Success of these new approaches will depend on effective implementation of vaccination programmes, creative thinking on the part of ! manufacturers and regulators as to how best to ensure that safe and effective vaccines are available in a timely manner, and improvement of public awareness about the benefits and risks of new vaccines in a way that encourages confidence in vaccines.
• Society's failure to protect a precious resource: antibiotics
  - Lancet 378(9788):369-371 (2011)
  
• Crimean-Congo haemorrhagic fever in India
  - Lancet 378(9788):372 (2011)