Objective: To estimate the extent to which intimate partner violence (IPV), at the levels of the individual and the community, is associated with shortened interbirth intervals among women in sub-Saharan Africa.Methods:We analyzed demographic and health survey data from 11 countries in sub-Saharan Africa. Only multiparous women were included in the analysis. Interbirth interval was the primary outcome. Personal history of IPV was measured using a modified Conflict Tactics Scale. Community prevalence of IPV was measured as the proportion of women in each village reporting a personal history of IPV. We used multilevel modeling to account for the hierarchical structure of the data, allowing us to partition the variation in birth intervals to the four different levels (births, individuals, villages, and countries).Results: Among the 46,697 women in the sample, 11,730 (25.1%) reported a personal history of physical violence and 4,935 (10.6%) reported a personal history of sexual violence. In the multivariable regression model, interbirth intervals were inversely associated with personal history of physical violence (regression coefficient b=−0.60, 95% confidence interval −0.91 to −0.28) and the community prevalence of physical violence (b=−1.41, 95% confidence interval −2.41 to −0.40). Estimated associations with sexual violence were of similar statistical significance and magnitude.Conclusion: Both personal history of IPV and the community prevalence of IPV have independent and statistically significant associations with shorter interbirth intervals.

Objectives. To determine if directly observed treatment with once-weekly fluoxetine would reduce depression symptom severity and improve HIV outcomes among homeless and marginally housed HIV+ adults. Methods. This was a non-blinded, randomized controlled trial of 137 HIV+ homeless and marginally housed persons who met DSM-IV criteria for Major Depressive Disorder, Dysthymia, or Minor Depressive Disorder. The intervention was directly-observed once-weekly fluoxetine for 24 weeks, then self-administered once-weekly fluoxetine for 12 weeks. The Hamilton Depression Rating Scale was the primary outcome; response was defined as a 50% reduction from baseline, and remission was defined as a score below 8. Secondary outcome measures were: Beck Depression Inventory-II, antiretroviral uptake, antiretroviral adherence as measured by unannounced pill count, and HIV-1 RNA viral suppression to <50 copies/mL. Results. The intervention reduced depression symptom severity (b= 1.97; 95% CI, -0.85 to -3.08; P<0.001) and increased response (AOR=2.40; 95% CI, 1.86-3.10; P<0.001) and remission (AOR=2.97; 95% CI, 1.29-3.87; P<0.001). Similar results were obtained with the Beck Depression Inventory-II. No statistically significant differences in secondary HIV outcomes were observed. Conclusions. Weekly fluoxetine treatment of depression among HIV+ homeless and marginally housed adults resulted in reduced depression symptom severity, but not improved HIV outcomes, over nine months of follow-up.

Background: Understanding how food insecurity among women gives rise to differential patterning in HIV risks is critical for policy and programming in resource-limited settings. This is particularly the case in Brazil, which has undergone successive changes in the gender and socio-geographic composition of its complex epidemic over the past three decades. We used data from a national survey of Brazilian women to estimate the relationship between food insecurity and HIV risk. Methods and Findings: We used data on 12,684 sexually active women from a national survey conducted in Brazil in 2006–2007. Self-reported outcomes were (a) consistent condom use, defined as using a condom at each occasion of sexual intercourse in the previous 12 mo; (b) recent condom use, less stringently defined as using a condom with the most recent sexual partner; and (c) itchy vaginal discharge in the previous 30 d, possibly indicating presence of a sexually transmitted infection. The primary explanatory variable of interest was food insecurity, measured using the culturally adapted and validated Escala Brasiliera de Segurança Alimentar. In multivariable logistic regression models, severe food insecurity with hunger was associated with a reduced odds of consistent condom use in the past 12 mo (adjusted odds ratio [AOR] = 0.67; 95% CI, 0.48–0.92) and condom use at last sexual intercourse (AOR = 0.75; 95% CI, 0.57–0.98). Self-reported itchy vaginal discharge was associated with all categories of food insecurity (with AORs ranging from 1.46 to 1.94). In absolute terms, the effect sizes were large in magnitude across all outcomes. Underweight and/or lack of control in sexual relations did not appear to mediate the observed associations. Conclusions: Severe food insecurity with hunger was associated with reduced odds of condom use and increased odds of itchy vaginal discharge, which is potentially indicative of sexually transmitted infection, among sexually active women in Brazil. Interventions targeting food insecurity may have beneficial implications for HIV prevention in resource-limited settings.

Depression is common among people living with HIV/AIDS and contributes to a wide range of worsened HIV-related outcomes, including AIDS-related mortality. Targeting modifiable causes of depression, either through primary or secondary prevention, may reduce suffering as well as improve HIV-related outcomes. Food insecurity is a pervasive source of uncertainty for those living in resource-limited settings, and cross-sectional studies have increasingly recognized it as a critical determinant of poor mental health. Using cohort data from 456 men and women living with HIV/AIDS initiating HIV antiretroviral therapy in rural Uganda, we sought to (a) estimate the association between food insecurity and depression symptom severity, (b) assess the extent to which social support may serve as a buffer against the adverse effects of food insecurity, and (c) determine whether the buffering effects are specific to certain types of social support. Quarterly data were collected by structured interviews and blood draws. The primary outcome was depression symptom severity, measured by a modified Hopkins Symptom Checklist for Depression. The primary explanatory variables were food insecurity, measured with the Household Food Insecurity Access Scale, and social support, measured with a modified version of the Functional Social Support Questionnaire. We found that food insecurity was associated with depression symptom severity among women but not men, and that social support buffered the impacts of food insecurity on depression. We also found that instrumental support had a greater buffering influence than emotional social support. Interventions aimed at improving food security and strengthening instrumental social support may have synergistic beneficial effects on both mental health and HIV outcomes among PLWHA in resource-limited settings.

Objective: We undertook a longitudinal study in rural Uganda to understand the association of food insecurity with morbidity and patterns of healthcare utilization among HIV-infected individuals enrolled in an antiretroviral treatment program. Design: Longitudinal cohort study Methods: Participants were enrolled from the Uganda AIDS Rural Treatment Outcomes cohort, and underwent quarterly structured interviews and blood draws. The primary predictor was food insecurity measured by the validated Household Food Insecurity Access Scale. Primary outcomes included: a) Health-related quality of life measured by the validated Medical Outcome Study-HIV Physical Health Summary (PHS); b) Incident self-reported opportunistic infections; c) Number of hospitalizations; and d) Missed clinic visits. To estimate model parameters, we used the method of generalized estimating equations, adjusting for socio-demographic and clinical variables. Explanatory variables were lagged by 3 months to strengthen causal interpretations. Results: Beginning in May 2007, 458 persons were followed for a median of 2.07 years, and 40% were severely food insecure at baseline. Severe food insecurity was associated with worse PHS, opportunistic infections, and increased hospitalizations (results were similar in concurrent and lagged models). Mild/moderate food insecurity was associated with missed clinic visits in concurrent models, while in lagged models, severe food insecurity was associated with reduced odds of missed clinic visits. Conclusions: Based on the negative impact of food insecurity on morbidity and patterns of healthcare utilization among HIV-infected individuals, policies and programs that address food insecurity should be a critical component of HIV treatment programs worldwide.

Background: There is limited empirical research on the underlying gender inequity norms shaping gender-based violence, power, and HIV risks in sub-Saharan Africa, or how risk pathways may differ for men and women. This study is among the first to directly evaluate the adherence to gender inequity norms and epidemiological relationships with violence and sexual risks for HIV infection. Methods: Data were derived from population-based cross-sectional samples recruited through two-stage probability sampling from the 5 highest HIV prevalence districts in Botswana and all districts in Swaziland (2004–5). Based on evidence of established risk factors for HIV infection, we aimed 1) to estimate the mean adherence to gender inequity norms for both men and women; and 2) to model the independent effects of higher adherence to gender inequity norms on a) male sexual dominance (male-controlled sexual decision making and rape (forced sex)); b) sexual risk practices (multiple/concurrent sex partners, transactional sex, unprotected sex with non-primary partner, intergenerational sex). Findings: A total of 2049 individuals were included, n = 1255 from Botswana and n = 796 from Swaziland. In separate multivariate logistic regression analyses, higher gender inequity norms scores remained independently associated with increased male-controlled sexual decision making power (AORmen = 1.90, 95%CI:1.09–2.35; AORwomen = 2.05, 95%CI:1.32–2.49), perpetration of rape (AORmen = 2.19 95%CI:1.22–3.51), unprotected sex with a non-primary partner (AORmen = 1.90, 95%CI:1.14–2.31), intergenerational sex (AORwomen = 1.36, 95%CI:1.08–1.79), and multiple/concurrent sex partners (AORmen = 1.42, 95%CI:1.10–1.93). Interpretation: These findings support the critical evidence-based need for gender-transformative HIV prevention efforts including legislation of women's rights in two of the most HIV affected countries in the world.

Background: Ongoing conflict in the Darfur region of Sudan has resulted in a severe humanitarian crisis. We sought to characterize the nature and geographic scope of allegations of human rights violations perpetrated against civilians in Darfur and to evaluate their consistency with medical examinations documented in patients’ medical records. Methods and Findings: This was a retrospective review and analysis of medical records from all 325 patients seen for treatment from September 28, 2004, through December 31, 2006, at the Nyala-based Amel Centre for Treatment andRehabilitation of Victims of Torture, the only dedicated local provider of free clinical and legal services to civilian victims of torture and other human rights violations in Darfur during this time period. Among 325 medical records identified and examined, 292 (89.8%) patients from 12 different non-Arabic-speaking tribes disclosed in the medical notes that they had been attacked by Government of Sudan (GoS) and/or Janjaweed forces. Attacks were reported in 23 different rural council areas throughout Darfur. Nearly all attacks (321 [98.8%]) were described as having occurred in the absence of active armed conflict between Janjaweed/GoS forces and rebel groups. The most common alleged abuses were beatings (161 [49.5%]),gunshot wounds (140 [43.1%]), destruction or theft of property (121 [37.2%]), involuntary detainment (97 [29.9%]), and being bound (64 [19.7%]). Approximately one-half (36 [49.3%]) of all women disclosed that they had been sexually assaulted, and one-half of sexual assaults were described as having occurred in close proximity to a camp for internally displaced persons. Among the 198 (60.9%) medical records that contained sufficient detail to enable the forensic medical reviewers to render an informed judgment, the signs and symptoms in all of the medical records were assessed to be consistent with, highly consistent with, or virtually diagnostic of the alleged abuses. Conclusions: Allegations of widespread and sustained torture and other human rights violations by GoS and/or Janjaweed forces against non-Arabic-speaking civilians were corroborated by medical forensic review of medical records of patients seen at a local non-governmental provider of free clinical and legal services in Darfur. Limitations of this study were that patients seen in this clinic may not have been a representative sample of persons alleging abuse by Janjaweed/GoS forces, and that most delayed presenting for care. The quality of documentation was similar to that available in other conflict/post-conflict, resource-limited settings.

Traditional healer and/or spiritual counselor (TH/SC) use has been associated with delays in HIV testing. We examined HIV-infected individuals in southwestern Uganda to test the hypothesis that TH/SC use was also associated with lower CD4-counts at antiretroviral therapy (ART) initiation. Approximately 450 individuals initiating ART through an HIV/AIDS clinic at the Mbarara University of Science and Technology (MUST) were recruited to participate. Patients were predominantly female, ranged in age from 18 to 75, and had a median CD4 count of 130. TH/SC use was not associated with lower CD4 cell count, but age and quality-of-life physical health summary score were associated with CD4 cell count at initiation while asset index was negatively associated with CD4 count atART initiation. These findings suggest that TH/SC use does not delay initiation of ART.

Objective: To determine whether the proximate context of gender-unequal norms about violence against women undermines women’s ability to negotiate condom use in sexual relationships. Design: Secondary analysis of cross-sectional data pooled from 22 Demographic and Health Surveys conducted in sub-Saharan Africa. Methods: Each of the 22 surveys employed a multistage stratified design with probabilistic sampling and was designed to be nationally-representative of reproductive-age women. The outcome was self-reported condom use at last sexual intercourse. The primary explanatory variable of interest was a scale consisting of five questions about whether the respondent agreed on the appropriateness of wife beating under five different scenarios. To measure the proximate context of norms about violence against women, this scale was aggregated to the level of the primary sampling unit. We fit logistic regression models with cluster-correlated robust standard errors and adjustment for country-level fixed effects and socio-demographic characteristics. Results: Our analysis sample included data from 198 806 sexually active women living in 22 sub-Saharan African countries. The wife-beating scale was internally consistent (Cronbach’s alpha = 0.84), and factor analysis confirmed the presence of a single factor. Condom use was associated with gender-unequal contextual norms about violence against women (AOR = 0.88; 95% CI, 0.85-0.92; P<0.001). The estimated association was robust to adjustment for socio-demographic characteristics and several sensitivity analyses. Conclusions: The proximate context of gender-unequal norms about violence against women is associated with lack of condom use among women in sub-Saharan Africa.

Inequality within partner relationships is associated with HIV acquisition and gender violence, but little is known about more pervasive effects on women’s health. We performed a cross-sectional analysis of associations between sexual relationship power and nutritional status among women in Uganda. Participants completed questionnaires and anthropometric measurements. We assessed sexual relationship power using the Sexual Relationship Power Scale (SRPS). We performed logistic regression to test for associations between sexual relationship power and poor nutritional status including body mass index, body fat percentage, and mid-upper arm circumference. Women with higher sexual relationship power scores had decreased odds of low body mass index (OR 0.29, p = 0.01), low body fat percentage (OR 0.54, p = 0.04), and low mid-upper arm circumference (OR 0.22, p = 0.01). These relationships persisted in multivariable models adjusted for potential confounders. Targeted interventions to improve intimate partner relationship equality should be explored to improve health status among women living with HIV in rural Africa.

Background:: Aripiprazole, a second-generation antipsychotic medication, has been increasingly used in the maintenance treatment of bipolar disorder and received approval from the U.S. Food and Drug Administration for this indication in 2005. Given its widespread use, we sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature. Methods and Findings: We systematically searched multiple databases to identify double-blind, randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder while excluding other types of studies, such as open-label, acute, and adjunctive studies. We then used a citation search to identify articles that cited these trials and rated the quality of their citations. Our evidence search protocol identified only two publications, both describing the results of a single trial conducted by Keck et al., which met criteria for inclusion in this review. We describe four issues that limit the interpretation of that trial as supporting the use of aripiprazole for bipolar maintenance: (1) insufficient duration to demonstrate maintenance efficacy; (2) limited generalizability due to its enriched sample; (3) possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effects of treatment; and (4) a low overall completion rate. Our citation search protocol yielded 80 publications that cited the Keck et al. trial in discussing the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%) mentioned adverse events reported and four (5%) mentioned study limitations. Conclusions: A single trial by Keck et al. represents the entirety of the literature on the use of aripiprazole for the maintenance treatment of bipolar disorder. Although careful review identifies four critical limitations to the trial's interpretation and overall utility, the trial has been uncritically cited in the subsequent scientific literature.

We report here a case of priapism associated with quetiapine use, with a treatment course complicated by concomitant methamphetamine, cocaine, and marijuana abuse.

Food insecurity, which affects more than one billion people worldwide, is inextricably linked with the HIV epidemic. We present a conceptual framework of the multiple pathways through which these phenomena may be causally linked that encompasses community- and individual-level factors. While the mechanisms through which HIV/AIDS can cause food insecurity have been fairly well elucidated, the ways in which food insecurity can lead to HIV are less well understood. We argue that there are nutritional, mental health, and behavioral pathways through which food insecurity leads to HIV acquisition and disease progression. Specifically, food insecurity can lead to macronutrient and micronutrient deficiencies, which can impact both vertical and horizontal transmission of HIV, and can also contribute to immunologic decline and increased morbidity and mortality among those already infected. Food insecurity can have mental-health consequences, such as depression and increased drug abuse, which in turn contribute to HIV transmission risk as well as to incomplete HIV viral load suppression, increased probability of AIDS-defining illness, and AIDS-related mortality among HIV-infected individuals. As a result of the inability to procure food in socially or personally acceptable ways, food insecurity also contributes to risky sexual practices and enhanced HIV transmission, as well as to antiretroviral non-adherence, treatment interruptions, and missed clinic visits, which are strong determinants of worse HIV health outcomes. More research on the relative importance of each of these pathways is warranted because effective interventions to reduce food insecurity and HIV are dependent upon a rigorous understanding of these multi-faceted relationships.

In high-income countries, suboptimal dose-taking behavior by persons with different types of chronic illnesses is well-documented. In resource-limited settings, however, less is known about dose-taking execution by persons with chronic illnesses other than HIV. In this issue of the Journal, Bowry et al. provide the first systematic review and meta-analysis of dose-taking behavior in the setting of cardiovascular medication use in the emerging and developing economies of Africa, Asia, and Central and South America.

Howard Brody (2011) effectively skewers “pharmapologist” objections to his favored account of conflicts of interest with regard to the American Academy of Family Physicians’ relationship with The Coca-Cola Company. Pharmapologists have frequently appealed to the ubiquity objection to argue that policies focused on financial conflicts of interest should be deemphasized. Countering this objection, Brody cites Greenland’s (2009) approach to illustrate how financial conflicts are quantitatively different from nonfinancial conflicts, and he argues that policies focused on financial conflicts should be pursued. In my open peer commentary I would like to clarify the importance of recognizing and managing nonfinancial conflicts of interest.

Objectives. We sought to identify correlates of forced sex perpetration among men and victimization among women in Botswana and Swaziland. Methods. We surveyed a 2-stage probability sample of 2074 adults from the 5 districts of Botswana with the highest HIV prevalence rates and all 4 regions of Swaziland. We used multivariable logistic regression to identify correlates of forced sex victimization and perpetration. Results. Lifetime prevalence rates of forced sex victimization of women were 10.3% in Botswana and 11.4% in Swaziland; among men, rates of perpetration were 3.9% in Botswana and 5.0% in Swaziland. Lifetime history of forced sex victimization was the strongest predictor of forced sex perpetration by men in Botswana (adjusted odds ratio [OR]=13.70; 95% confidence interval [CI]=4.55, 41.50) and Swaziland (adjusted OR=5.98; 95% CI=1.08, 33.10). Problem or heavy drinking was the strongest predictor of forced sex victimization among women in Botswana (adjusted OR=2.55; 95% CI=1.19, 5.49) and Swaziland (OR=14.70; 95% CI=4.53, 47.60). Conclusions. Sexual violence in Botswana and Swaziland is a major public health and human rights problem. Ending codified gender discrimination can contribute to fundamentally changing gender norms and may be an important lever for gender-based violence prevention in these countries.

HIV/AIDS and food insecurity are two of the leading causes of morbidity and mortality in sub-Saharan Africa, with each heightening the vulnerability to, and worsening the severity of, the other. Less research has focused on the social determinants of food insecurity in resource-limited settings, including social support and HIV-related stigma. In this study, we analyzed data from a cohort of 456 persons from the Uganda AIDS Rural Treatment Outcomes study, an ongoing prospective cohort of persons living with HIV/AIDS (PLWHA) initiating HIV antiretroviral therapy in Mbarara, Uganda. Quarterly data were collected by structured interviews. The primary outcome, food insecurity, was measured with the Household Food Insecurity Access Scale. Key covariates of interest included social support, internalized HIV-related stigma, HIV-related enacted stigma, and disclosure of HIV serostatus. Severe food insecurity was highly prevalent overall (38%) and more prevalent among women than among men. Social support, HIV disclosure, and internalized HIV-related stigma were associated with food insecurity; these associations persisted after adjusting for household wealth, employment status, and other previously identified correlates of food insecurity. The adverse effects of internalized stigma persisted in a lagged specification, and the beneficial effect of social support further persisted after the inclusion of fixed effects. International organizations have increasingly advocated for addressing food insecurity as part of HIV/AIDS programming to improve morbidity and mortality. This study provides quantitative evidence on social determinants of food insecurity among PLWHA in resource-limited settings and suggests points of intervention. These findings also indicate that structural interventions to improve social support and/or decrease HIV-related stigma may also improve the food security of PLWHA.

The past two decades have witnessed an expansion in efforts to publicly disseminate data on hospital performance based on comparisons of risk-adjusted outcomes for the purpose of affecting reimbursement or patient choice. While much is known about which risk factors should be adjusted for, less is known about the appropriate statistical methods that should be used in deriving such quality measures. We discuss the literature on profiling and risk adjustment, with an emphasis on recent econometric and statistical methods, highlighting key assumptions involved in the various analytical techniques. Particularly problematic for the traditional methods of analysis are inadequate sample sizes and unobserved severity of illness. We illustrate how these issues affected recent public profiling initiatives and highlight how recent contributions from the econometric and statistical literature may be helpful in ameliorating these problems.

Context: Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial. Objective: To determine whether antidepressant medication treatment increases the probability of HIV viral suppression. Design: Community-based prospective cohort study with assessments conducted every 3 months. Setting: Community-based research field site in San Francisco, California. Participants: One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count <350/µL) and psychiatric (Beck Depression Inventory II score >13) inclusion criteria, observed from April 2002 through August 2007. Main Outcome Measures: Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence. Results: Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P < .001). Self-reported adherence to antiretroviral therapy increased by 25 percentage points (95% CI, 14-36; P < .001), and the odds of reporting complete adherence nearly doubled (weighted odds ratio, 1.94; 95% CI, 1.20-3.13; P = .006). Conclusions: Antidepressant medication treatment increases viral suppression among persons with HIV. This effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

I report here a case of a female patient admitted to an inpatient psychiatric ward with acute mania with psychotic features, who developed a mild isolated lingual dystonia shortly after initiating pharmacotherapy with ziprasidone.

Emergency care serves a key function within health care systems by providing an entry point to health care and by decreasing morbidity and mortality. Although primarily focused on evaluation and treatment for acute conditions, emergency care also serves as an important locus of provision for preventive care with regard to injuries and disease progression. Despite its important and increasing role, however, emergency care has been frequently overlooked in the discussion of health systems and delivery platforms, particularly in developing countries. Little research has been done in lower- and middle-income countries on the burden of disease reduction attributable to emergency care, whether through injury treatment and prevention, urgent and emergency treatment of acute conditions, or emergency treatment of complications from chronic conditions. There is a critical need for research documenting the role of emergency care services in reducing the global burden of disease. In addition to applying existing methodologies toward this aim, new methodologies should be developed to determine the cost-effectiveness of these interventions and how to effectively cover the costs of and demands for emergency care needs. These analyses could be used to emphasize the public health and clinical importance of emergency care within health systems as policymakers determine health and budgeting priorities in resource-limited settings.

World AIDS Day (Dec. 1) comes at a critical time for health care reformers in the U.S., as well as those concerned about the health of people around the world. Here in San Francisco, one of the initial epicenters of the HIV/AIDS pandemic, we provide critical psychological counseling and support for many patients living with HIV/AIDS as well as many more patients at risk for HIV. We are concerned that new legislation, under consideration as part of the health care reform package now weaving its way through Congress, threatens access to new drugs for the most vulnerable in our society.

Background: Newborn infections are responsible for approximately one-third of the estimated 4.0 million neonatal deaths that occur globally every year. Appropriately targeted research is required to guide investment in effective interventions, especially in low resource settings. Setting global priorities for research to address neonatal infections is essential and urgent. Methods: The Department of Child and Adolescent Health and Development of the World Health Organization (WHO/CAH) applied the Child Health and Nutrition Research Initiative (CHNRI) priority-setting methodology to identify and stimulate research most likely to reduce global newborn infection-related mortality by 2015. Technical experts were invited by WHO/CAH to systematically list and then use standard methods to score research questions according to their likelihood to (i) be answered in an ethical way, (ii) lead to (or improve) effective interventions, (iii) be deliverable, affordable, and sustainable, (iv) maximize death burden reduction, and (v) have an equitable effect in the population. The scores were then weighted according to the values provided by a wide group of stakeholders from the global research priority-setting network. Findings: On a 100-point scale, the final priority scores for 69 research questions ranged from 39 to 83. Most of the 15 research questions that received the highest scores were in the domain of health systems and policy research to address barriers affecting existing cost-effective interventions. The priority questions focused on promotion of home care practices to prevent newborn infections and approaches to increase coverage and quality of management of newborn infections in health facilities as well as in the community. While community-based intervention research is receiving some current investment, rigorous evaluation and cost analysis is almost entirely lacking for research on facility-based interventions and quality improvement. Interpretation: Given the lack of progress in improving newborn survival despite the existence of effective interventions, it is not surprising that of the top ranked research priorities in this article the majority are in the domain of health systems and policy research. We urge funding agencies and investigators to invest in these research priorities to accelerate reduction of neonatal deaths, particularly those due to infections.

Ample evidence documents the association between individual-level risk factors and mental health status; relatively less is known about associations between features of the context in which individuals live and their mental health. The objective of this study is to assess differences in associations between contextual characteristics of both rural and urban settings and mental health status measured by the mental health component of the SF-12. Using state-representative data, we observed significant rural/urban differences in the association of mental health status with availability of health care resources but no significant associations in other contextual domains. Lack of overlap in contextual associations suggests that contextual influence operates differently in rural and urban settings and that interventions to improve mental health may not translate across settings.

Objective: To set investment priorities in global mental health research and to propose a more rational use of funds in this under-resourced and under-investigated area. Methods: Members of the Lancet Mental Health Group systematically listed and scored research investment options on four broad classes of disorders: schizophrenia and other major psychotic disorders, major depressive disorder and other common mental disorders, alcohol abuse and other substance abuse disorders, and the broad class of child and adolescent mental disorders. Using the priority-setting approach of the Child Health and Nutrition Research Initiative, the group listed various research questions and evaluated them using the criteria of answerability, effectiveness, deliverability, equity and potential impact on persisting burden of mental health disorders. Scores were then weighted according to the system of values expressed by a larger group of stakeholders. Findings: The research questions that scored highest were related to health policy and systems research, where and how to deliver existing cost-effective interventions in a low-resource context, and epidemiological research on the broad categories of child and adolescent mental disorders or those pertaining to alcohol and drug abuse questions. The questions that scored lowest related to the development of new interventions and new drugs or pharmacological agents, vaccines or other technologies. Conclusion: In the context of global mental health and with a time frame of the next 10 years, it would be best to fill critical knowledge gaps by investing in research into health policy and systems, epidemiology and improved delivery of cost-effective interventions.

The Department of Child and Adolescent Health and Development (CAH) of the World Health Organization is currently using the CHNRI methodology to develop research priority issues on the major causes of child deaths. In this paper, we present the results of this research priority-setting process applied by CAH for childhood diarrhoea.

This study employs data from rural South Africa to determine whether there were socioeconomic differences in the profile of HIV-infected persons living in the community and HIV-infected patients presenting for hospital-based outpatient HIV/AIDS care and related services. There were 776 HIV-infected persons aged 18-35 years in Limpopo Province, South Africa who were included in the study, including 534 consecutive patients who presented for care at a hospital-based outpatient HIV clinic, and 242 persons living in the community. Persons seen in clinic had a higher overall socioeconomic profile compared to the community sample. They were more likely to have completed matric or tertiary education (P=0.04), less likely to be unemployed (P<0.001), and more likely to live in households with access to a private tap water supply (P<0.001). These differences persisted after multivariable adjustment. Our findings demonstrate that important socioeconomic differences in uptake of hospital-based HIV/AIDS care were identified among HIV-infected adults living in a rural region of South Africa. This suggests an important limitation in hospital-based HIV/AIDS care and underscores the need to monitor the equity implications of highly active antiretroviral therapy scale-up in resource-limited settings.

Background: To investigate the feasibility, the ease of implementation, and the extent to which community health workers with little experience of data collection could be trained and successfully supervised to collect data using mobile phones in a large baseline survey. Methods: A web-based system was developed to allow electronic surveys or questionnaires to be designed on a word processor, sent to, and conducted on standard entry level mobile phones. Results: The web-based interface permitted comprehensive daily real-time supervision of CHW performance, with no data loss. The system permitted the early detection of data fabrication in combination with real-time quality control and data collector supervision. Conclusions: The benefits of mobile technology, combined with the improvement that mobile phones offer over PDA's in terms of data loss and uploading difficulties, make mobile phones a feasible method of data collection that needs to be further explored.

Increasingly, there is a need for national governments, public-private partnerships, private sector and other funding agencies to set priorities in health research investments in a fair and transparent way. A process of priority setting is always an activity driven by values of wide range of stakeholders, which are often conflicting. This process always occurs in a highly specific context (eg, agreed policies and targets in terms of disease burden reduction and time limit, defined geographic space, population and specific health problems).

This paper provides detailed guidelines for implementation of systematic method for setting priorities in health research investments that was recently developed by Child Health and Nutrition Research Initiative (CHNRI). The target audience for the proposed method are primarily public donors and not-for-profit foundations and international agencies, although it can also be used by private sector. It is a process that involves the investors, technical experts and numerous other stakeholders, and results in: (i) understanding and defining the context in which investments are performed; (ii) agreeing on expected “returns” on the investments and risk preferences; (iii) defining the main criteria for priority setting; (iv) systematic listing of many competing research investment options; (v) transparent valuation of each research option against each criterion; (vi) adjustment of this valuation according to values of the society; (vii) combining this adjusted valuation with predicted cost, expected “returns” and risk preferences to decide on the optimal investment strategy. “Returns” on the investments can be defined as reduction in existing disease burden (public and not-for-profit sector) or patentable products (private sector). The CHNRI methodology is a flexible process that enables prioritising health research investments at any level: institutional, regional, national, international or global. This paper presents detailed guidelines for application of the CHNRI methodology in different contexts.

Sharp and colleagues (2008) in the target article surveyed 15 years of bioethics research, documented a diverse collection of funding sources—among them few pharmaceutical companies or other for-profit corporations—and concluded that “worries about the influence of corporate financing on bioethics research may be greatly overstated” (54). Unfortunately, their use of a sampling strategy focused on empirical bioethics studies greatly limits the scope of their study’s external validity. As a result, I am not so sure that observers who worry about the pharmaceutical industry’s increasing attempts to colonize all aspects of bioethical reflection will find their fears so easily assuaged.

Objective. To examine the effect of hospital volume on 30-day mortality for patients with congestive heart failure (CHF) using administrative and clinical data in conventional regression and instrumental variables (IV) estimation models. Data Sources. The primary data consisted of longitudinal information on comorbid conditions, vital signs, clinical status, and laboratory test results for 21,555 Medicare-insured patients aged 65 years and older hospitalized for CHF in northeast Ohio in 1991–1997. Study Design. The patient was the primary unit of analysis. We fit a linear probability model to the data to assess the effects of hospital volume on patient mortality within 30 days of admission. Both administrative and clinical data elements were included for risk adjustment. Linear distances between patients and hospitals were used to construct the instrument, which was then used to assess the endogeneity of hospital volume. Principal Findings. When only administrative data elements were included in the risk adjustment model, the estimated volume–outcome effect was statistically significant (p=.029) but small in magnitude. The estimate was markedly attenuated in magnitude and statistical significance when clinical data were added to the model as risk adjusters (p=.39). IV estimation shifted the estimate in a direction consistent with selective referral, but we were unable to reject the consistency of the linear probability estimates. Conclusions. Use of only administrative data for volume–outcomes research may generate spurious findings. The IV analysis further suggests that conventional estimates of the volume–outcome relationship may be contaminated by selective referral effects. Taken together, our results suggest that efforts to concentrate hospital-based CHF care in high-volume hospitals may not reduce mortality among elderly patients.

In the latter half of the 20th century, there was a steep increase in the prevalence of diagnosed major depressive disorder; soon, this disorder is expected to become the second-largest contributor to the global burden of disease. What accounts for this remarkable increase? Do the prevailing explanations of the disorder have implications for the care of, and perhaps the cure for, people struggling with mental illness?

The conventional telling of the story is archetypal: Nancy Olivieri, a hematologist and thalassemia researcher at Toronto’s Hospital for Sick Children, obtained financial support from Apotex Research, Inc. to study L1, an experimental drug for patients with thalassemia. She discovered that L1 was causing liver fibrosis in some of her patients, but when she tried to tell her patients about the drug’s risks, Apotex clamped down on her, cancelled the study, and threatened her with lawsuits. Alone and without support from the hospital, Olivieri courageously went public with her findings, and the legendary whistleblower was born.

Objective: To use empirical data from previously published literature to address 2 research questions: (1) Do interventions that incorporate at least 1 element of the Chronic Care Model (CCM) result in improved outcomes for specific chronic illnesses? (2) Are any elements essential for improved outcomes? Study Design: Meta-analysis. Methods: Articles were identified from narrative literature reviews and quantitative meta-analyses, each of which covered multiple bibliographic databases from inception to March 2003. We supplemented this strategy by searching the MEDLINE database (1998-2003) and by consulting experts. We included randomized and nonrandomized controlled trials of interventions that contained 1 or more elements of the CCM for asthma, congestive heart failure (CHF), depression, and diabetes. We extracted data on clinical outcomes, quality of life, and processes of care. We then used random-effects modeling to compute pooled standardized effect sizes and risk ratios. Results: Of 1345 abstracts screened, 112 studies contributed data to the meta-analysis: asthma, 27 studies; CHF, 21 studies; depression, 33 studies; and diabetes, 31 studies. Interventions with at least 1 CCM element had consistently beneficial effects on clinical outcomes and processes of care across all conditions studied. The effects on quality of life were mixed, with only the CHF and depression studies showing benefit. Publication bias was noted for the CHF studies and a subset of the asthma studies. Conclusions: Interventions that contain at least 1 CCM element improve clinical outcomes and processes of care—and to a lesser extent, quality of life—for patients with chronic illnesses.

Background: Physician decisions to discontinue prescription medications for chronic conditions are fundamental determinants of drug use but have been inadequately studied. The decision to stop growth hormone (GH) therapy is an important example because of high cost (approximately $26,000/y for a 48-kg child), complexity of treatment options, and expansion of patient populations. Aim: The aim of this study was to identify the factors that influence physician recommendations in the process of discontinuing therapy. Design: A random sample of half of U.S. pediatric endocrinologists (n = 265) was mailed a survey that included case scenarios of GH-deficient adolescents. Decision options involved a 2-stage framework to 1) initiate change in ongoing GH therapy (by discussing discontinuing GH with the family but not yet stopping treatment), and 2) take action to discontinue ongoing GH therapy (by terminating GH or reducing the dose to adult maintenance level). Main Outcome Measure: Physician recommendations. Results: The response rate was 83.8%. Physiological indices of growth potential (growth velocity, bone age) significantly influenced discontinuation decisions (both P < 0.001). However, family preference, child's height, and physician attitudes exerted independent effects (each P < 0.05). Treatment price had little influence. Together, these variables accounted for 60% to 70% of the variation in recommendations. Their relative influence differed by stage in the discontinuation process. Conclusion: The variables in our framework substantially explain discontinuation decisions. The data demonstrate the importance of both physiological and nonphysiological factors. The results suggest that physicians value even small gains as final height approaches, although an additional 20% expenditure may be needed to gain the last 1% to 3% of adult height.

A few months ago, while I was completing a month-long family medicine rotation with the U.S. Indian Health Service, the conversation between me and my preceptor turned to road trips, mountains, and motorcycles. He owned two motorcycles, one which he had purchased himself years ago during his previous life in private practice. “Guess how I was able to afford the other one?” Pausing only briefly, he continued: “Drug reps.” It was a $20,000 BMW touring motorcycle that he never would have been able to afford, he admitted, on a family physician’s salary. Apparently, however, the income he derived from participating in seeding trials (Kessler et al. 1994) was more than enough to make up the difference.

In 1992, researchers from the University of California, Los Angeles, published a study on the scientific merit and validity of pharmaceutical advertisements in medical journals. Their results led them to conclude, provocatively, that many pharmaceutical advertisements contained deficiencies in areas in which the U.S. Food and Drug Administration had established explicit standards of quality. This article provides a detailed account of third-party reactions to the study following its publication in the Annals of Internal Medicine, as well as the implications for those involved, including the authors, editors, and publisher. The increasingly diverging interests between medical journal editors and publishers are also discussed and highlighted by two recent cases of editors' departures from prominent general-interest medical journals.

Study objective: We describe recent trends in payments from different payer classes and assess their relative importance to the financial solvency of emergency departments. Methods: We used Medical Expenditure Panel Survey data from 1996 and 1998. The unit of analysis was the ED visit. Primary outcome measures were ED charges and payments. The independent variable of interest was payer class, and therefore, we limited our analysis to those either uninsured or covered by Medicare, Medicaid, or private insurance. Results: From 1996 to 1998, a declining percentage of total charges were paid, from 60.3% to 53.0% (difference −7.3%; 95% confidence interval [CI] −11.3% to −3.5%). Although the percentage of total charges paid by Medicaid, Medicare, and the uninsured remained constant, the percentage of total charges paid by the privately insured declined from 75.1% to 63.4% (difference −11.7%; 95% CI −16.6% to −6.7%). Overall, adjusted mean ED charge increased from $695 to $798 (difference $103; 95% CI $61 to $146). Two payer classes experienced statistically significant increases in adjusted mean charge: the uninsured, from $544 to $740 (difference $196; 95% CI $62 to $330), and the privately insured, from $658 to $813 (difference $151; 95% CI $103 to $199). Although the adjusted mean payment rate for the uninsured remained stable, the adjusted mean payment rate for the privately insured declined from 77.7% to 65.7% (difference −12.0%; 95% CI −13.4% to −10.7%). Conclusion: The ability of EDs to provide emergency care to all regardless of ability to pay is increasingly threatened by declining overall payment rates. Cost shifting to fund care for the uninsured is an increasingly untenable financing strategy.

In periods characterized by diminished public market financing, small biotechnology firms appear to be more likely to fund R&D through alliances with major corporations rather than with internal funds (raised through the capital markets). We consider 200 alliance agreements entered into by biotechnology firms between 1980 and 1995. Agreements signed during periods of limited external equity financing are more likely to assign the bulk of the control to the larger corporate partner, and are significantly less successful than other alliances. These agreements are also disproportionately likely to be renegotiated if financial market conditions subsequently improve.

In recent years there has been a remarkable upsurge of enthusiasm for scientifically studying the empirical relationship between spirituality and health. This project has suffered from a lack of conscientious scrutiny, perhaps because an adequate book-length treatment would require both theological literacy and clinical understanding. Heal Thyself, written by Joel Shuman (a theologian with training in physical therapy) and Keith Meador (a psychiatrist with training in theology), is a welcome contribution that aims to fill that void.

Doctors and Reformers is a remarkably detailed account of the “discussion and debate” over health insurance reform during the second quarter of the 20th century. As its title implies, this book is about the major legislative remedies introduced by reformers (“professional reformers, foundation executives, philanthropists, civil servants, academics, liberal politicians, fringe medical associations, prominent individuals, labor groups, and farmers' unions”) and the truculent rejoinders from the doctors (organized medicine and independent physicians) over a period of 25 years.

American hemodialysis patients have short lifespans, frequent hospitalizations, and aggregate Medicare inpatient expenditures of $4 billion[sol ]year. Dose of dialysis, as quantified by the parameter, Kt[sol ]V, corresponds strongly with survival and is estimated to be inadequate (Kt[sol ]V [lt ]1.2) in one fourth of patients. However, little is known about the morbidity and cost implications of inadequate dialysis. We sought to determine the independent relationship between dose of dialysis and (1) number of hospitalizations, (2) hospital days, and (3) Medicare inpatient reimbursements. We randomly selected 674 patients from all 22 hemodialysis units in northeast Ohio and examined hospitalizations, hospital days, and Medicare inpatient reimbursements for a 6-month interval following a 90-day quantification of dialysis dose. Every 0.1 decrease in Kt[sol ]V was independently associated with more hospitalizations (rate ratio, 1.11; 95[percnt] confidence interval [lsqb ]CI[rsqb ], 1.07 to 1.15), increased hospital days (rate ratio, 1.12; 95[percnt] CI, 1.03 to 1.22), and higher Medicare inpatient expenditures ($940; 95[percnt] CI, $450 to $1,440) after adjustment for patient age, sex, race, cause of renal failure, number of years on dialysis, and number of comorbid conditions. We estimate that increasing dialysis doses to a Kt[sol ]V of 1.2 for all patients nationally may decrease Medicare inpatient expenditures by $150 million annually. In conclusion, inadequate dialysis dose is independently associated with increased hospitalizations, hospital days, and Medicare inpatient expenditures. Improving dialysis adequacy may both improve patient morbidity and lessen health care costs.

While the variability of public equity financing has been long recognized, its impact on firms has attracted little empirical scrutiny. This paper examines one setting where theory suggests that variations in financing conditions should matter, alliances between small R&D firms and major corporations: Aghion and Tirole [1994] suggest that when financial markets are weak, assigning the control rights to the small firm may be sometimes desirable but not feasible. The performance of 200 agreements entered into by biotechnology firms between 1980 and 1995 suggests that financing availability does matter. Consistent with theory, agreements signed during periods with little external equity financing that assign the bulk of the control to the corporate partner are significantly less successful than other alliances. These agreements are also disproportionately likely to be renegotiated if financial market conditions improve.