Hot off the presses! Jan 21 LANCET

The Jan 21 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:

• Untangling health research governance in the UK
  - LANCET 377(9761):179 (2011)
  
• China's unhealthy relations with big tobacco
  - LANCET 377(9761):180 (2011)
  
• Health in Pakistan
  - LANCET 377(9761):180 (2011)
  
• Indian health: the path from crisis to progress
  - LANCET 377(9761):181-183 (2011)
  
• Male circumcision and HPV transmission to female partners
  - LANCET 377(9761):183-184 (2011)
  
• The PIERS trial: hope for averting deaths from pre-eclampsia
  - LANCET 377(9761):185-186 (2011)
  
• Health-care-associated infections in developing countries
  - LANCET 377(9761):186-188 (2011)
  
• Vitamin D nutrient to treat TB begs the prevention question
  - LANCET 377(9761):189-190 (2011)
  
• A new era for UK clinical research?
  - LANCET 377(9761):190-192 (2011)
  
• Offline: Nudge
  - LANCET 377(9761):192 (2011)
  
• Health warnings for people who use heroin
  - LANCET 377(9761):193-194 (2011)
  
• Seeing health care as a human right in India
  - LANCET 377(9761):195-196 (2011)
  
• Saris, camera, action
  - LANCET 377(9761):197 (2011)
  
• Talking therapy fit for a king
  - LANCET 377(9761):198 (2011)
  
• Rani and Abhay Bang—pioneers of health care in rural India
  - LANCET 377(9761):199 (2011)
  
• Learning from others
  - LANCET 377(9761):200-201 (2011)
  
• John Patrick Lee
  - LANCET 377(9761):202 (2011)
  
• Organ transplantation after cardiac death
  - LANCET 377(9761):203 (2011)
  
• Organ transplantation after cardiac death
  - LANCET 377(9761):203 (2011)
  
• Organ transplantation after cardiac death
  - LANCET 377(9761):203-204 (2011)
  
• Organ transplantation after cardiac death – Authors' reply
  - LANCET 377(9761):204-205 (2011)
  
• Rituximab-containing therapy for chronic lymphocytic leukaemia
  - LANCET 377(9761):205 (2011)
  
• Rituximab-containing therapy for chronic lymphocytic leukaemia
  - LANCET 377(9761):205 (2011)
  
• Rituximab-containing therapy for chronic lymphocytic leukaemia – Authors' reply
  - LANCET 377(9761):206 (2011)
  
• UK Public Accounts Committee report on health inequalities
  - LANCET 377(9761):206-207 (2011)
  
• UK Public Accounts Committee report on health inequalities
  - LANCET 377(9761):207 (2011)
  
• Pakistan: the final frontier for a polio-free world
  - LANCET 377(9761):207-208 (2011)
  
• Use of email to acquire information from experts
  - LANCET 377(9761):208 (2011)
  
• Trans-Pacific parallels
  - LANCET 377(9761):208 (2011)
  
• Department of Error
  - LANCET 377(9761):208 (2011)
  
• Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda
  - LANCET 377(9761):209-218 (2011)
  Background Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men. Methods In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were reg! istered, numbers NCT00425984 and NCT00124878. Findings During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60–0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63–0·93, p=0·008). Interpretation Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important. Funding The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.
• Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model
  - LANCET 377(9761):219-227 (2011)
  Background Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. Methods We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. Findings 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84–0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. Interpretation The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. Funding Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.
• Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis
  - LANCET 377(9761):228-241 (2011)
  Background Health-care-associated infection is the most frequent result of unsafe patient care worldwide, but few data are available from the developing world. We aimed to assess the epidemiology of endemic health-care-associated infection in developing countries. Methods We searched electronic databases and reference lists of relevant papers for articles published 1995–2008. Studies containing full or partial data from developing countries related to infection prevalence or incidence—including overall health-care-associated infection and major infection sites, and their microbiological cause—were selected. We classified studies as low-quality or high-quality according to predefined criteria. Data were pooled for analysis. Findings Of 271 selected articles, 220 were included in the final analysis. Limited data were retrieved from some regions and many countries were not represented. 118 (54%) studies were low quality. In general, infection frequencies reported in high-quality studies were greater than those from low-quality studies. Prevalence of health-care-associated infection (pooled prevalence in high-quality studies, 15·5 per 100 patients [95% CI 12·6–18·9]) was much higher than proportions reported from Europe and the USA. Pooled overall health-care-associated infection density in adult intensive-care units was 47·9 per 1000 patient-days (95% CI 36·7–59·1), at least three times as high as densities reported from the USA. Surgical-site infection was the leading infection in hospitals (pooled cumulative incidence 5·6 per 100 surgical procedures), strikingly higher than proportions recorded in developed countries. Gram-negative bacilli represented the most common nosocomial isolates. Apar! t from meticillin resistance, noted in 158 of 290 (54%) Staphylococcus aureus isolates (in eight studies), very few articles reported antimicrobial resistance. Interpretation The burden of health-care-associated infection in developing countries is high. Our findings indicate a need to improve surveillance and infection-control practices. Funding World Health Organization.
• High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial
  - LANCET 377(9761):242-250 (2011)
  Background Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent. Methods We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D3 or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D3. This trial is registered with ClinicalTrials.gov number NCT00419068. Findings 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90–2·16; p=0.14). TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (pinteraction=0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36–48·01; p=0·02). FokI genotype did not modify the effect of vitamin D supplementation (pinteraction=0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6–88·2; p<0·0001). Interpretation Administration of four doses of 2·5 mg vitamin D3 increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism. Funding British Lung Foundation.
• Extramedullary haemopoiesis and spinal cord compression
  - LANCET 377(9761):251 (2011)
  
• Continuing challenge of infectious diseases in India
  - LANCET 377(9761):252-269 (2011)
  In India, the range and burden of infectious diseases are enormous. The administrative responsibilities of the health system are shared between the central (federal) and state governments. Control of diseases and outbreaks is the responsibility of the central Ministry of Health, which lacks a formal public health department for this purpose. Tuberculosis, malaria, filariasis, visceral leishmaniasis, leprosy, HIV infection, and childhood cluster of vaccine-preventable diseases are given priority for control through centrally managed vertical programmes. Control of HIV infection and leprosy, but not of tuberculosis, seems to be on track. Early success of malaria control was not sustained, and visceral leishmaniasis prevalence has increased. Inadequate containment of the vector has resulted in recurrent outbreaks of dengue fever and re-emergence of Chikungunya virus disease and typhus fever. Other infectious diseases caused by faecally transmitted pathogens (enteric fever! s, cholera, hepatitis A and E viruses) and zoonoses (rabies, leptospirosis, anthrax) are not in the process of being systematically controlled. Big gaps in the surveillance and response system for infectious diseases need to be addressed. Replication of the model of vertical single-disease control for all infectious diseases will not be efficient or viable. India needs to rethink and revise its health policy to broaden the agenda of disease control. A comprehensive review and redesign of the health system is needed urgently to ensure equity and quality in health care. We recommend the creation of a functional public health infrastructure that is shared between central and state governments, with professional leadership and a formally trained public health cadre of personnel who manage an integrated control mechanism of diseases in districts that includes infectious and non-infectious diseases, and injuries.
• Volcanic knee
  - LANCET 377(9761):270 (2011)