PLOS Medicine: New Articles

Prevalence of Consensual Male–Male Sex and Sexual Violence, and Associations with HIV in South Africa: A Population-Based Cross-Sectional Study

2013-06-18T21:00:00Z

by Kristin L. Dunkle, Rachel K. Jewkes, Daniel W. Murdock, Yandisa Sikweyiya, Robert Morrell

Background

In sub-Saharan Africa the population prevalence of men who have sex with men (MSM) is unknown, as is the population prevalence of male-on-male sexual violence, and whether male-on-male sexual violence may relate to HIV risk. This paper describes lifetime prevalence of consensual male–male sexual behavior and male-on-male sexual violence (victimization and perpetration) in two South African provinces, socio-demographic factors associated with these experiences, and associations with HIV serostatus.

Methods and Findings

In a cross-sectional study conducted in 2008, men aged 18–49 y from randomly selected households in the Eastern Cape and KwaZulu-Natal provinces provided anonymous survey data and dried blood spots for HIV serostatus assessment. Interviews were completed in 1,737 of 2,298 (75.6%) of enumerated and eligible households. From these households, 1,705 men (97.1%) provided data on lifetime history of same-sex experiences, and 1,220 (70.2%) also provided dried blood spots for HIV testing. 5.4% (n = 92) of participants reported a lifetime history of any consensual sexual activity with another man; 9.6% (n = 164) reported any sexual victimization by a man, and 3.0% (n = 51) reported perpetrating sexual violence against another man. 85.0% (n = 79) of men with a history of consensual sex with men reported having a current female partner, and 27.7% (n = 26) reported having a current male partner. Of the latter, 80.6% (n = 21/26) also reported having a female partner. Men reporting a history of consensual male–male sexual behavior are more likely to have been a victim of male-on-male sexual violence (adjusted odds ratio [aOR] = 7.24; 95% CI 4.26–12.3), and to have perpetrated sexual violence against another man (aOR = 3.10; 95% CI 1.22–7.90). Men reporting consensual oral/anal sex with a man were more likely to be HIV+ than men with no such history (aOR = 3.11; 95% CI 1.24–7.80). Men who had raped a man were more likely to be HIV+ than non-perpetrators (aOR = 3.58; 95% CI 1.17–10.9).

Conclusions

In this sample, one in 20 men (5.4%) reported lifetime consensual sexual contact with a man, while about one in ten (9.6%) reported experience of male-on-male sexual violence victimization. Men who reported having had sex with men were more likely to be HIV+, as were men who reported perpetrating sexual violence towards other men. Whilst there was no direct measure of male–female concurrency (having overlapping sexual relationships with men and women), the data suggest that this may have been common. These findings suggest that HIV prevention messages regarding male–male sex in South Africa should be mainstreamed with prevention messages for the general population, and sexual health interventions and HIV prevention interventions for South African men should explicitly address male-on-male sexual violence.Please see later in the article for the Editors' Summary

Bigotry and Oppressive Laws in Africa Drive HIV in Men Who Have Sex with Men

2013-06-18T21:00:00Z

by Jerome Amir Singh

The Effect of Intermittent Antenatal Iron Supplementation on Maternal and Infant Outcomes in Rural Viet Nam: A Cluster Randomised Trial

2013-06-18T21:00:00Z

by Sarah Hanieh, Tran T. Ha, Julie A. Simpson, Gerard J. Casey, Nguyen C. Khuong, Dang D. Thoang, Tran T. Thuy, Sant-Rayn Pasricha, Thach D. Tran, Tran Tuan, Terence Dwyer, Jane Fisher, Beverley-Ann Biggs

Background

Anemia affects over 500 million women, and in pregnancy is associated with impaired maternal and infant outcomes. Intermittent antenatal iron supplementation is an attractive alternative to daily dosing; however, the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Viet Nam.

Methods and Findings

This cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258 pregnant women (<16 wk gestation) in 104 communes were assigned to daily iron–folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g (standard deviation 416). There was no difference in the birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 g; 95% CI −22 to 78), or twice weekly MMN compared to daily IFA (MD −36.8 g; 95% CI −82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56).

Conclusions

Twice weekly antenatal IFA or MMN did not produce a clinically important difference in birth weight, when compared to daily IFA supplementation. The significant improvement in infant cognitive outcomes at 6 mo of age following twice weekly antenatal IFA requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal IFA in populations with low rates of iron deficiency.

Trial registration

Australia New Zealand Clinical Trials Registry 12610000944033Please see later in the article for the Editors' Summary

Targeting Asymptomatic Malaria Infections: Active Surveillance in Control and Elimination

2013-06-18T21:00:00Z

by Hugh J. W. Sturrock, Michelle S. Hsiang, Justin M. Cohen, David L. Smith, Bryan Greenhouse, Teun Bousema, Roly D. Gosling

Malignant Neglect: The Failure to Address the Need to Prevent Premature Non-communicable Disease Morbidity and Mortality

2013-06-11T21:00:00Z

by David Stuckler, Sanjay Basu

Diet and Physical Activity for the Prevention of Noncommunicable Diseases in Low- and Middle-Income Countries: A Systematic Policy Review

2013-06-11T21:00:00Z

by Carl Lachat, Stephen Otchere, Dominique Roberfroid, Abubakari Abdulai, Florencia Maria Aguirre Seret, Jelena Milesevic, Godfrey Xuereb, Vanessa Candeias, Patrick Kolsteren

Background

Diet-related noncommunicable diseases (NCDs) are increasing rapidly in low- and middle-income countries (LMICs) and constitute a leading cause of mortality. Although a call for global action has been resonating for years, the progress in national policy development in LMICs has not been assessed. This review of strategies to prevent NCDs in LMICs provides a benchmark against which policy response can be tracked over time.

Methods and Findings

We reviewed how government policies in LMICs outline actions that address salt consumption, fat consumption, fruit and vegetable intake, or physical activity. A structured content analysis of national nutrition, NCDs, and health policies published between 1 January 2004 and 1 January 2013 by 140 LMIC members of the World Health Organization (WHO) was carried out. We assessed availability of policies in 83% (116/140) of the countries. NCD strategies were found in 47% (54/116) of LMICs reviewed, but only a minority proposed actions to promote healthier diets and physical activity. The coverage of policies that specifically targeted at least one of the risk factors reviewed was lower in Africa, Europe, the Americas, and the Eastern Mediterranean compared to the other two World Health Organization regions, South-East Asia and Western Pacific. Of the countries reviewed, only 12% (14/116) proposed a policy that addressed all four risk factors, and 25% (29/116) addressed only one of the risk factors reviewed. Strategies targeting the private sector were less frequently encountered than strategies targeting the general public or policy makers.

Conclusions

This review indicates the disconnection between the burden of NCDs and national policy responses in LMICs. Policy makers urgently need to develop comprehensive and multi-stakeholder policies to improve dietary quality and physical activity.Please see later in the article for the Editors' Summary

Why Aren't We Listening Yet? A Decade of Road Safety Begins Quietly

2013-06-11T21:00:00Z

by Tracey Pérez Koehlmoos

Modern Medicine Is Neglecting Road Traffic Crashes

2013-06-11T21:00:00Z

by Donald A. Redelmeier, Barry A. McLellan

Associations between Active Travel to Work and Overweight, Hypertension, and Diabetes in India: A Cross-Sectional Study

2013-06-11T21:00:00Z

by Christopher Millett, Sutapa Agrawal, Ruth Sullivan, Mario Vaz, Anura Kurpad, A. V. Bharathi, Dorairaj Prabhakaran, Kolli Srinath Reddy, Sanjay Kinra, George Davey Smith, Shah Ebrahim, for the Indian Migration Study group

Background

Increasing active travel (walking, bicycling, and public transport) is promoted as a key strategy to increase physical activity and reduce the growing burden of noncommunicable diseases (NCDs) globally. Little is known about patterns of active travel or associated cardiovascular health benefits in low- and middle-income countries. This study examines mode and duration of travel to work in rural and urban India and associations between active travel and overweight, hypertension, and diabetes.

Methods and Findings

Cross-sectional study of 3,902 participants (1,366 rural, 2,536 urban) in the Indian Migration Study. Associations between mode and duration of active travel and cardiovascular risk factors were assessed using random-effect logistic regression models adjusting for age, sex, caste, standard of living, occupation, factory location, leisure time physical activity, daily fat intake, smoking status, and alcohol use. Rural dwellers were significantly more likely to bicycle (68.3% versus 15.9%; p<0.001) to work than urban dwellers. The prevalence of overweight or obesity was 50.0%, 37.6%, 24.2%, 24.9%; hypertension was 17.7%, 11.8%, 6.5%, 9.8%; and diabetes was 10.8%, 7.4%, 3.8%, 7.3% in participants who travelled to work by private transport, public transport, bicycling, and walking, respectively. In the adjusted analysis, those walking (adjusted risk ratio [ARR] 0.72; 95% CI 0.58–0.88) or bicycling to work (ARR 0.66; 95% CI 0.55–0.77) were significantly less likely to be overweight or obese than those travelling by private transport. Those bicycling to work were significantly less likely to have hypertension (ARR 0.51; 95% CI 0.36–0.71) or diabetes (ARR 0.65; 95% CI 0.44–0.95). There was evidence of a dose-response relationship between duration of bicycling to work and being overweight, having hypertension or diabetes. The main limitation of the study is the cross-sectional design, which limits causal inference for the associations found.

Conclusions

Walking and bicycling to work was associated with reduced cardiovascular risk in the Indian population. Efforts to increase active travel in urban areas and halt declines in rural areas should be integral to strategies to maintain healthy weight and prevent NCDs in India.Please see later in the article for the Editors' Summary

The Health Effects of Motorization

2013-06-11T21:00:00Z

by Kavi Bhalla

Household Air Pollution in Low- and Middle-Income Countries: Health Risks and Research Priorities

2013-06-04T21:00:00Z

by William J. Martin, Roger I. Glass, Houmam Araj, John Balbus, Francis S. Collins, Siân Curtis, Gregory B. Diette, William N. Elwood, Henry Falk, Patricia L. Hibberd, Susan E. J. Keown, Sumi Mehta, Erin Patrick, Julia Rosenbaum, Amir Sapkota, H. Eser Tolunay, Nigel G. Bruce

Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study

2013-06-04T21:00:00Z

by Irene Pichler, Fabiola Del Greco M., Martin Gögele, Christina M. Lill, Lars Bertram, Chuong B. Do, Nicholas Eriksson, Tatiana Foroud, Richard H. Myers, PD GWAS Consortium , Michael Nalls, Margaux F. Keller, International Parkinson's Disease Genomics Consortium , Wellcome Trust Case Control Consortium 2 , Beben Benyamin, John B. Whitfield, Genetics of Iron Status Consortium , Peter P. Pramstaller, Andrew A. Hicks, John R. Thompson, Cosetta Minelli

Background

Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.

Methods and Findings

We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%–6%; p = 0.001) per 10 µg/dl increase in serum iron.

Conclusions

Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.Please see later in the article for the Editors' Summary

Rising Health Care Costs and Life-Cycle Management in the Pharmaceutical Market

2013-06-04T21:00:00Z

by Aaron S. Kesselheim

Patented Drug Extension Strategies on Healthcare Spending: A Cost-Evaluation Analysis

2013-06-04T21:00:00Z

by Nathalie Vernaz, Guy Haller, François Girardin, Benedikt Huttner, Christophe Combescure, Pierre Dayer, Daniel Muscionico, Jean-Luc Salomon, Pascal Bonnabry

Background

Drug manufacturers have developed “evergreening” strategies to compete with generic medication after patent termination. These include marketing of slightly modified follow-on drugs. We aimed to estimate the financial impact of these drugs on overall healthcare costs and also to examine the impact of listing these drugs in hospital restrictive drug formularies (RDFs) on the healthcare system as a whole (“spillover effect”).

Methods and Findings

We used hospital and community pharmacy invoice office data in the Swiss canton of Geneva to calculate utilisation of eight follow-on drugs in defined daily doses between 2000 and 2008. “Extra costs” were calculated for three different scenarios assuming replacement with the corresponding generic equivalent for prescriptions of (1) all brand (i.e., initially patented) drugs, (2) all follow-on drugs, or (3) brand and follow-on drugs. To examine the financial spillover effect we calculated a monthly follow-on drug market share in defined daily doses for medications prescribed by hospital physicians but dispensed in community pharmacies, in comparison to drugs prescribed by non-hospital physicians in the community.Estimated “extra costs” over the study period were €15.9 (95% CI 15.5; 16.2) million for scenario 1, €14.4 (95% CI 14.1; 14.7) million for scenario 2, and €30.3 (95% CI 29.8; 30.8) million for scenario 3. The impact of strictly switching all patients using proton-pump inhibitors to esomeprazole at admission resulted in a spillover “extra cost” of €330,300 (95% CI 276,100; 383,800), whereas strictly switching to generic cetirizine resulted in savings of €7,700 (95% CI 4,100; 11,100). Overall we estimated that the RDF resulted in “extra costs” of €503,600 (95% CI 444,500; 563,100).

Conclusions

Evergreening strategies have been successful in maintaining market share in Geneva, offsetting competition by generics and cost containment policies. Hospitals may be contributing to increased overall healthcare costs by listing follow-on drugs in their RDF. Therefore, healthcare providers and policy makers should be aware of the impact of evergreening strategies.Please see later in the article for the Editors' Summary

The Paradox of Mental Health: Over-Treatment and Under-Recognition

The PLOS Medicine Editors — 2013-05-28T21:00:00Z

by The PLOS Medicine Editors

Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis

2013-05-28T21:00:00Z

by Jürgen Barth, Thomas Munder, Heike Gerger, Eveline Nüesch, Sven Trelle, Hansjörg Znoj, Peter Jüni, Pim Cuijpers

Background

Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression.

Methods and Findings

We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d = −0.62 to d = −0.92). Relative effects of different psychotherapeutic interventions on depressive symptoms were absent to small (range d = 0.01 to d = −0.30). Interpersonal therapy was significantly more effective than supportive therapy (d = −0.30, 95% credibility interval [CrI] [−0.54 to −0.05]). Moderator analysis showed that patient characteristics had no influence on treatment effects, but identified aspects of study quality and sample size as effect modifiers. Smaller effects were found in studies of at least moderate (Δd = 0.29 [−0.01 to 0.58]; p = 0.063) and large size (Δd = 0.33 [0.08 to 0.61]; p = 0.012) and those that had adequate outcome assessment (Δd = 0.38 [−0.06 to 0.87]; p = 0.100). Stepwise restriction of analyses by sample size showed robust effects for cognitive-behavioural therapy, interpersonal therapy, and problem-solving therapy (all d>0.46) compared to waitlist. Empirical evidence from large studies was unavailable or limited for other psychotherapeutic interventions.

Conclusions

Overall our results are consistent with the notion that different psychotherapeutic interventions for depression have comparable benefits. However, the robustness of the evidence varies considerably between different psychotherapeutic treatments.Please see later in the article for the Editors' Summary

Domestic Violence and Perinatal Mental Disorders: A Systematic Review and Meta-Analysis

2013-05-28T21:00:00Z

by Louise M. Howard, Sian Oram, Helen Galley, Kylee Trevillion, Gene Feder

Background

Domestic violence in the perinatal period is associated with adverse obstetric outcomes, but evidence is limited on its association with perinatal mental disorders. We aimed to estimate the prevalence and odds of having experienced domestic violence among women with antenatal and postnatal mental disorders (depression and anxiety disorders including post-traumatic stress disorder [PTSD], eating disorders, and psychoses).

Methods and Findings

We conducted a systematic review and meta-analysis (PROSPERO reference CRD42012002048). Data sources included searches of electronic databases (to 15 February 2013), hand searches, citation tracking, update of a review on victimisation and mental disorder, and expert recommendations. Included studies were peer-reviewed experimental or observational studies that reported on women aged 16 y or older, that assessed the prevalence and/or odds of having experienced domestic violence, and that assessed symptoms of perinatal mental disorder using a validated instrument. Two reviewers screened 1,125 full-text papers, extracted data, and independently appraised study quality. Odds ratios were pooled using meta-analysis.Sixty-seven papers were included. Pooled estimates from longitudinal studies suggest a 3-fold increase in the odds of high levels of depressive symptoms in the postnatal period after having experienced partner violence during pregnancy (odds ratio 3.1, 95% CI 2.7–3.6). Increased odds of having experienced domestic violence among women with high levels of depressive, anxiety, and PTSD symptoms in the antenatal and postnatal periods were consistently reported in cross-sectional studies. No studies were identified on eating disorders or puerperal psychosis. Analyses were limited because of study heterogeneity and lack of data on baseline symptoms, preventing clear findings on causal directionality.

Conclusions

High levels of symptoms of perinatal depression, anxiety, and PTSD are significantly associated with having experienced domestic violence. High-quality evidence is now needed on how maternity and mental health services should address domestic violence and improve health outcomes for women and their infants in the perinatal period.Please see later in the article for the Editors' Summary

Irreconcilable Conflict: The Tobacco Industry and the Public Health Challenge of Tobacco Use

2013-05-28T21:00:00Z

by Thomas E. Novotny

Tobacco Company Efforts to Influence the Food and Drug Administration-Commissioned Institute of Medicine Report Clearing the Smoke: An Analysis of Documents Released through Litigation

2013-05-28T21:00:00Z

by Crystal E. Tan, Thomas Kyriss, Stanton A. Glantz

Background

Spurred by the creation of potential modified risk tobacco products, the US Food and Drug Administration (FDA) commissioned the Institute of Medicine (IOM) to assess the science base for tobacco “harm reduction,” leading to the 2001 IOM report Clearing the Smoke. The objective of this study was to determine how the tobacco industry organized to try to influence the IOM committee that prepared the report.

Methods and Findings

We analyzed previously secret tobacco industry documents in the University of California, San Francisco Legacy Tobacco Documents Library, and IOM public access files. (A limitation of this method includes the fact that the tobacco companies have withheld some possibly relevant documents.) Tobacco companies considered the IOM report to have high-stakes regulatory implications. They developed and implemented strategies with consulting and legal firms to access the IOM proceedings. When the IOM study staff invited the companies to provide information on exposure and disease markers, clinical trial design for safety and efficacy, and implications for initiation and cessation, tobacco company lawyers, consultants, and in-house regulatory staff shaped presentations from company scientists. Although the available evidence does not permit drawing cause-and-effect conclusions, and the IOM may have come to the same conclusions without the influence of the tobacco industry, the companies were pleased with the final report, particularly the recommendations for a tiered claims system (with separate tiers for exposure and risk, which they believed would ease the process of qualifying for a claim) and license to sell products comparable to existing conventional cigarettes (“substantial equivalence”) without prior regulatory approval. Some principles from the IOM report, including elements of the substantial equivalence recommendation, appear in the 2009 Family Smoking Prevention and Tobacco Control Act.

Conclusions

Tobacco companies strategically interacted with the IOM to win several favored scientific and regulatory recommendations.Please see later in the article for the Editors' Summary

Grand Challenges: Integrating Mental Health Services into Priority Health Care Platforms

2013-05-28T21:00:00Z

by Vikram Patel, Gary S. Belkin, Arun Chockalingam, Janice Cooper, Shekhar Saxena, Jürgen Unützer

Gene Expression Classification of Colon Cancer into Molecular Subtypes: Characterization, Validation, and Prognostic Value

2013-05-21T21:00:00Z

by Laetitia Marisa, Aurélien de Reyniès, Alex Duval, Janick Selves, Marie Pierre Gaub, Laure Vescovo, Marie-Christine Etienne-Grimaldi, Renaud Schiappa, Dominique Guenot, Mira Ayadi, Sylvain Kirzin, Maurice Chazal, Jean-François Fléjou, Daniel Benchimol, Anne Berger, Arnaud Lagarde, Erwan Pencreach, Françoise Piard, Dominique Elias, Yann Parc, Sylviane Olschwang, Gérard Milano, Pierre Laurent-Puig, Valérie Boige

Background

Colon cancer (CC) pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses.

Methods and Findings

Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype–like, normal-like, serrated CC phenotype–like), and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II–III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse-free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95% CI 1.1–2.1, p = 0.0097). However, a limitation of this study is that information on tumor grade and number of nodes examined was not available.

Conclusions

We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.Please see later in the article for the Editors' Summary

Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness

2013-05-21T21:00:00Z

by Sylvia Kaaya, Eddy Eustache, Ilana Lapidos-Salaiz, Seggane Musisi, Christina Psaros, Lawrence Wissow

Contribution of H. pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model

2013-05-21T21:00:00Z

by Jennifer M. Yeh, Chin Hur, Deb Schrag, Karen M. Kuntz, Majid Ezzati, Natasha Stout, Zachary Ward, Sue J. Goldie

Background

Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence.

Methods and Findings

We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%–58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%–21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%–100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men.

Conclusions

Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts.Please see later in the article for the Editors' Summary

Integrating Global and National Knowledge to Select Medicines for Children: The Ghana National Drugs Programme

2013-05-21T21:00:00Z

by David Sinclair, Martha Gyansa-Lutterodt, Brian Asare, Augustina Koduah, Edith Andrews, Paul Garner

Setting Research Priorities to Reduce Mortality and Morbidity of Childhood Diarrhoeal Disease in the Next 15 Years

2013-05-14T21:00:00Z

by Kerri Wazny, Alvin Zipursky, Robert Black, Valerie Curtis, Christopher Duggan, Richard Guerrant, Myron Levine, William A. Petri, Mathuram Santosham, Rebecca Scharf, Philip M. Sherman, Evan Simpson, Mark Young, Zulfiqar A. Bhutta

Carriage of Mycoplasma pneumoniae in the Upper Respiratory Tract of Symptomatic and Asymptomatic Children: An Observational Study

2013-05-14T21:00:00Z

by Emiel B. M. Spuesens, Pieter L. A. Fraaij, Eline G. Visser, Theo Hoogenboezem, Wim C. J. Hop, Léon N. A. van Adrichem, Frank Weber, Henriette A. Moll, Berth Broekman, Marjolein Y. Berger, Tineke van Rijsoort-Vos, Alex van Belkum, Martin Schutten, Suzan D. Pas, Albert D. M. E. Osterhaus, Nico G. Hartwig, Cornelis Vink, Annemarie M. C. van Rossum

Background

Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods.

Methods and Findings

This study was conducted at the Erasmus MC–Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%–25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%–20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo.

Conclusions

Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.Please see later in the article for the Editors' Summary

Grand Challenges: Integrating Mental Health Care into the Non-Communicable Disease Agenda

2013-05-14T21:00:00Z

by Victoria K. Ngo, Adolfo Rubinstein, Vijay Ganju, Pamela Kanellis, Nasser Loza, Cristina Rabadan-Diehl, Abdallah S. Daar

Effect of Facilitation of Local Maternal-and-Newborn Stakeholder Groups on Neonatal Mortality: Cluster-Randomized Controlled Trial

2013-05-14T21:00:00Z

by Lars Åke Persson, Nguyen T. Nga, Mats Målqvist, Dinh Thi Phuong Hoa, Leif Eriksson, Lars Wallin, Katarina Selling, Tran Q. Huy, Duong M. Duc, Tran V. Tiep, Vu Thi Thu Thuy, Uwe Ewald

Background

Facilitation of local women's groups may reportedly reduce neonatal mortality. It is not known whether facilitation of groups composed of local health care staff and politicians can improve perinatal outcomes. We hypothesised that facilitation of local stakeholder groups would reduce neonatal mortality (primary outcome) and improve maternal, delivery, and newborn care indicators (secondary outcomes) in Quang Ninh province, Vietnam.

Methods and Findings

In a cluster-randomized design 44 communes were allocated to intervention and 46 to control. Laywomen facilitated monthly meetings during 3 years in groups composed of health care staff and key persons in the communes. A problem-solving approach was employed. Births and neonatal deaths were monitored, and interviews were performed in households of neonatal deaths and of randomly selected surviving infants. A latent period before effect is expected in this type of intervention, but this timeframe was not pre-specified. Neonatal mortality rate (NMR) from July 2008 to June 2011 was 16.5/1,000 (195 deaths per 11,818 live births) in the intervention communes and 18.4/1,000 (194 per 10,559 live births) in control communes (adjusted odds ratio [OR] 0.96 [95% CI 0.73–1.25]). There was a significant downward time trend of NMR in intervention communes (p = 0.003) but not in control communes (p = 0.184). No significant difference in NMR was observed during the first two years (July 2008 to June 2010) while the third year (July 2010 to June 2011) had significantly lower NMR in intervention arm: adjusted OR 0.51 (95% CI 0.30–0.89). Women in intervention communes more frequently attended antenatal care (adjusted OR 2.27 [95% CI 1.07–4.8]).

Conclusions

A randomized facilitation intervention with local stakeholder groups composed of primary care staff and local politicians working for three years with a perinatal problem-solving approach resulted in increased attendance to antenatal care and reduced neonatal mortality after a latent period.

Trial registration

Current Controlled Trials ISRCTN44599712Please see later in the article for the Editors' Summary

Assessing Population Aging and Disability in Sub-Saharan Africa: Lessons from Malawi?

2013-05-07T21:00:00Z

by Andreas E. Stuck, Lyson Tenthani, Matthias Egger

Measuring Coverage in MNCH: Current Indicators for Measuring Coverage of Diarrhea Treatment Interventions and Opportunities for Improvement

2013-05-07T21:00:00Z

by Christa L. Fischer Walker, Olivier Fontaine, Robert E. Black

Diarrhea morbidity and mortality remain important child health problems in low- and middle-income countries. The treatment of diarrhea and accurate measurement of treatment coverage are critical if child mortality is going to continue to decline. In this review, we examine diarrhea treatment coverage indicators collected in two large-scale community-based household surveys—the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS). Current surveys do not distinguish between children with mild diarrhea episodes and those at risk for dehydration. Additional disease severity questions may improve the identification of cases of severe diarrhea but research is needed to identify indicators with the highest sensitivity and specificity. We also review the current treatment indicators in these surveys and highlight three areas for improvement and research. First, specific questions on fluids other than oral rehydration salts (ORS) should be eliminated to refocus the treatment of dehydration on ORS and to prevent confusion between prevention and treatment of dehydration. Second, consistency across surveys and throughout translations is needed for questions about the caregiver behavior of “offering" the sick child fluid and food. Third, breastfeeding should be separated from other fluid and food questions to capture the frequency and duration of nursing sessions offered during the illness. Research is also needed to assess the accuracy of the current zinc indicator to determine if caregivers are correctly recalling zinc treatment for current and recent diarrhea episodes.