Search

PLOS Medicine editors and guest editors announce a call for papers for submissions for a special issue on diabetes prevention.

Cleaton-Jones, chair of the ethics committee that approved the trial of circumcision for preventing HIV, shares with us the discussions that the committee had ahead of granting approval.

The PLoS Medicine Editors and partners from the Maternal Health Task Force at the Harvard School of Public Health announce their partnership and a call for papers on “quality of maternal health care.”

Background During the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance. Methods and findings On April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19–specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population. Conclusions In this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences., Marije J. Splinter and colleagues assess the prevalence of healthcare avoidance during the COIVD-19 pandemic and investigate related determinants, Author summary Why was this study done? ➢ During the Coronavirus Disease 2019 (COVID-19) pandemic, consultation rates in both primary and specialist care declined compared to prepandemic levels, which can partially be attributed to the postponement or cancellation of elective and nonurgent medical care. ➢ It is unclear to what extent these declines in consultation rates could be related to healthcare avoidance by patients in the general population. ➢ To evaluate the collateral health damage of the COVID-19 pandemic, it is important to not only assess the prevalence of healthcare avoidance, but also for what symptoms healthcare was avoided and which determinants are associated with this behaviour. What did the researchers do and find? ➢ We sent out a paper questionnaire to 8,732 participants of the population-based Rotterdam Study containing several COVID-19–related subjects, such as healthcare utilisation, work status, mental and physical health, and concerns about contracting COVID-19. ➢ About 6,241 participants (73%) returned the questionnaire, of whom 5,656 participants (90.6%) were included in our analyses. We found that 1,142 of them (20.2%) avoided healthcare during the COVID-19 pandemic, often for symptoms that might have needed urgent medical evaluation, such as limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). ➢ Determinants that were most strongly associated with healthcare avoidance were female sex, poor self-appreciated health, and high levels of depression and anxiety. What do these findings mean? ➢ The results of this population-based study suggest that healthcare avoidance contributed to the decline in consultation rates during the COVID-19 pandemic. Importantly, our findings suggest that this behaviour may be associated with certain vulnerable groups within the population. ➢ These findings should be interpreted in light of the limitations of this study, which include that the actual severity of the symptoms that were reported by participants is unknown, since they were not medically evaluated when they experienced these symptoms. ➢ The findings of this study can be used to develop policy interventions targeted to vulnerable individuals who may be more likely to exhibit healthcare avoiding behaviours.

Civil registration and vital statistics systems are increasingly recognized as drivers of human rights, health, and development programs—especially for women and children [1]. Vital statistics systems are weak in most low-income countries [2,3], precisely where the burden of maternal and child deaths is highest and, therefore, the need for up-to-date, high-quality estimates of levels and trends in maternal and child mortality is greatest [4]. The UN Commission on Information and Accountability for Women’s and Children’s Health identified the reporting of births and deaths as a cornerstone for vital statistics systems in low-income countries [5]. This has led to intensified efforts to support and strengthen the routine reporting of vital events [6]. In this paper, we synthesize results generated by the Real-Time Monitoring of Under-Five Mortality (RMM) project, and highlight aspects that can inform efforts to strengthen vital statistics systems in low-income countries. Table 1 provides an overview of the methods tested by the RMM project in Ethiopia, Ghana, Malawi, Mali, and Niger. Full details on the design and implementation of RMM methods, the accuracy of the mortality estimates they produce, and their running costs are reported in the papers that form the Collection. Table 1 Real-time mortality monitoring (RMM) approaches tested, by country. Community-based reporting on vital events Adjusted health facility data Rapid household survey methods Paid worker Unpaid worker Repeated Imputed Ethiopia ✓ ✓ ✓ Ghana ✓ ✓ Malawi ✓ ✓ ✓ ✓ Mali ✓ ✓ Niger ✓ ✓ Open in a separate window The RMM project produced two sets of overarching findings: 1) quantitative results on the accuracy of under-five mortality estimates produced by various methodological approaches; and 2) experiential findings on the challenges of generating vital statistics for recent periods in real-world settings.

The benefits of having a continuous, piped supply of safe drinking water delivered to household premises are widely recognised. Piped supplies on premises not only reduce the time and effort required to collect water, and thereby increase the amount of water available for personal and domestic needs but also are more likely to provide water that meets required standards for drinking water quality. A recent systematic review of drinking water quality [1] confirmed that piped water supplies are less likely to be contaminated than other types of “improved” sources, such as hand pumps, protected wells, and springs. However, continuity of piped supplies—that is, the uninterrupted supply of water—and the associated health impacts, are under-studied. Two papers in this issue of PLOS Medicine each shed light on a particular aspect of continuity and are a very welcome addition to the literature. Jeandron and colleagues [2] show that in the city of Uvira, in the Democratic Republic of the Congo, there was a significant relationship between interruptions in the piped water supply and cases of suspected cholera. This association was seen even though many in the city used piped services indirectly (that is, they did not have household connections and used water from standposts and shared connections). The interruptions in the piped water supply thus represented a lost opportunity to protect a cholera-vulnerable population. In Hubli-Dharwad, in the state of Karnataka in India, Ercumen and colleagues [3] show that while upgrading the piped supply to provide continuous service for 10% of the population was associated with a notable reduction in typhoid among the poor in the beneficiary group, they did not find the expected decrease in diarrhoeal diseases. The paper suggests a number of possible reasons, including unhygienic storage of water due to the use of yard taps rather than taps in the house; the perceived threat of supply interruptions; heavy contamination of the immediate household environment due to widespread open defecation among children; and the continuing presence of open sewers. It is notable that the research in India found a strong relationship between the continuity of the supply and quality of the water delivered. Among water samples taken from households receiving a continuous supply, less than 1% did not comply with WHO guidelines for drinking water quality, compared with over one-third of samples in households that did not benefit from improvements and still had intermittent supply. The importance of continuous piped supply to households in order to protect health is clear. This link is not surprising given the engineering reality—that maintaining continuous positive pressure in a piped network and avoiding negative pressure at all costs prevents infiltration of contaminated soil water [4]. Continuous supply also removes the need to store water and makes water readily available for hygiene, such as handwashing. From a public health policy point of view, ideally, households should have continuous water supply, treated with chlorine, piped directly into the house, with accompanying improvements in the sanitary environment. For this reason, a new benchmark has been proposed to be included in the indicators used for monitoring progress towards the Sustainable Development Goals adopted by the United Nations (UN) General Assembly in September 2015. The new term “safely managed drinking water services” is proposed as the highest level of service countries should aspire to reach, and refers to a source of drinking water that is on premises, available when needed (that is, in the case of piped supplies, continuous), and free of faecal and priority chemical contamination. This represents a significant step up from the highest level of service used in monitoring during the period of the Millennium Development Goals: “improved drinking-water source,” which did not include measures of distance to the home, quality or continuity of water supplied, and included off-premises sources such as hand pumps, dug wells, and springs. Reaching this new benchmark at a global scale is undoubtedly ambitious. However, monitoring data [5] show it is not impossible. During the last 25 years, coverage of piped water on premises increased from 44% to 58% globally, so now well over half the world’s population benefits from this level of service. In those countries designated as developing countries by the UN, the use of piped water on premises has grown even faster, from 31% in 1990 to an estimated 49% in 2015, representing an additional 1.7 billion people with piped water connections. Progress in some regions has been even faster, and in Eastern Asia the number of people with piped water on premises skyrocketed from 30% to 74%, mostly as a result of rapid increases in China. Continuous, treated, piped supply to every household should be our ambition, even though achieving it may be many years in the future, and in many settings, interim arrangements with lower levels of service are going to be the reality. However, many countries have decided providing piped supply is worth the investment, and innovations are being rolled out in many places to find robust, inexpensive ways to provide this service in an affordable way. The studies in this issue of PLOS Medicine highlight the importance of continuous piped water supply, but also the pitfalls. Interruptions in the supply can negate the possible health benefits, and installing piped water without addressing other environmental concerns may not deliver the hoped-for health benefits. It must not be forgotten that piped water supplies require more than just infrastructure; good governance and competent management are needed to ensure continuous service.

As part of the Universal Health Coverage Collection, Ties Boerma and colleagues discuss monitoring intervention coverage related to the full spectrum of UHC, including health promotion and disease prevention, treatment, rehabilitation, and palliation. Please see later in the article for the Editors' Summary, Monitoring universal health coverage (UHC) focuses on information on health intervention coverage and financial protection. This paper addresses monitoring intervention coverage, related to the full spectrum of UHC, including health promotion and disease prevention, treatment, rehabilitation, and palliation. A comprehensive core set of indicators most relevant to the country situation should be monitored on a regular basis as part of health progress and systems performance assessment for all countries. UHC monitoring should be embedded in a broad results framework for the country health system, but focus on indicators related to the coverage of interventions that most directly reflect the results of UHC investments and strategies in each country. A set of tracer coverage indicators can be selected, divided into two groups—promotion/prevention, and treatment/care—as illustrated in this paper. Disaggregation of the indicators by the main equity stratifiers is critical to monitor progress in all population groups. Targets need to be set in accordance with baselines, historical rate of progress, and measurement considerations. Critical measurement gaps also exist, especially for treatment indicators, covering issues such as mental health, injuries, chronic conditions, surgical interventions, rehabilitation, and palliation. Consequently, further research and proxy indicators need to be used in the interim. Ideally, indicators should include a quality of intervention dimension. For some interventions, use of a single indicator is feasible, such as management of hypertension; but in many areas additional indicators are needed to capture quality of service provision. The monitoring of UHC has significant implications for health information systems. Major data gaps will need to be filled. At a minimum, countries will need to administer regular household health surveys with biological and clinical data collection. Countries will also need to improve the production of reliable, comprehensive, and timely health facility data. Please see later in the article for the Editors' Summary

Leontine Alkema and Danzhen You compare and summarize differences in underlying data and modelling approaches used by two key groups who publish data on global under-5 mortality rates, Background Millennium Development Goal 4 calls for a reduction in the under-five mortality rate (U5MR) by two-thirds between 1990 and 2015. In 2011, estimates were published by the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) and the Institute for Health Metrics and Evaluation (IHME). The difference in the U5MR estimates produced by the two research groups was more than 10% and corresponded to more than ten deaths per 1,000 live births for 10% of all countries in 1990 and 20% of all countries in 2010, which can lead to conflicting conclusions with respect to countries' progress. To understand what caused the differences in estimates, we summarised differences in underlying data and modelling approaches used by the two groups, and analysed their effects. Methods and Findings UN IGME and IHME estimation approaches differ with respect to the construction of databases and the pre-processing of data, trend fitting procedures, inclusion and exclusion of data series, and additional adjustment procedures. Large differences in U5MR estimates between the UN IGME and the IHME exist in countries with conflicts or civil unrest, countries with high HIV prevalence, and countries where the underlying data used to derive the estimates were different, especially if the exclusion of data series differed between the two research groups. A decomposition of the differences showed that differences in estimates due to using different data (inclusion of data series and pre-processing of data) are on average larger than the differences due to using different trend fitting methods. Conclusions Substantial country-specific differences between UN IGME and IHME estimates for U5MR and the number of under-five deaths exist because of various differences in data and modelling assumptions used. Often differences are illustrative of the lack of reliable data and likely to decrease as more data become available. Improved transparency on methods and data used will help to improve understanding about the drivers of the differences. Please see later in the article for the Editors' Summary., Editors' Summary Background In 2010, more than seven million children died before they reached their fifth birthday, and the global under-five mortality rate (also denoted in the literature as U5MR and 5q0) was 57 deaths per 1,000 live births. Most deaths before the age of five years occur in developing countries (about half occur in just five countries—India, Nigeria, the Democratic Republic of the Congo, Pakistan, and China), and most are caused by preventable or treatable diseases such as pneumonia, diarrhea, and malaria. Faced with this largely avoidable loss of young lives, in 1990, the United Nations (UN) World Summit for Children pledged to improve the survival of children. Later, in 2000, world leaders set a target of reducing under-five mortality to one-third of its 1990 level (12 million) by 2015, as Millennium Development Goal 4 (MDG 4). This goal, together with seven others, is designed to improve the social, economic, and health conditions in the world's poorest countries. Why Was This Study Done? Although progress towards MDG 4 is accelerating, MDG 4 is unlikely to be reached. It is important, therefore, to know which countries are making poor progress towards MDG 4 so that extra resources can be concentrated in these areas. To monitor both national and global progress, accurate, up-to-date estimates of U5MR are essential. The first step in estimating U5MR is the collection of data on child deaths, usually through vital registration systems (which record all births and deaths) in developed countries and through surveys that ask women about their living and dead children in developing countries. Country-specific U5MR estimates that are comparable over time and across countries are obtained from these data using a statistical process called trend fitting. Two groups—the UN Inter-agency Group for Child Mortality Estimation (UN IGME) and the Institute for Health Metrics and Evaluation (IHME)—recently published new estimates of the levels and trends in U5MR and under-five deaths across the world. However, their estimates differ somewhat and, for some countries, disagree on the progress being made towards MDG 4. Here, the researchers examine the differences in the underlying data and the trend fitting approaches used by the UN IGME and the IHME to try to understand why their estimates are different. What Did the Researchers Do and Find? The researchers first compared the estimates produced by the two groups. From 1990 to 2010, the UN IGME's global estimates of U5MR and under-five deaths were consistently slightly higher than those of the IHME. For example, in 2010, the UN IGME and IMHE estimates of U5MR were 56.7 and 53.9 deaths per 1,000 births, respectively. However, although the global estimates from the two groups were broadly similar, there were important differences between the two sets of estimates at the country level, particularly in countries where there was conflict or civil unrest (for example, Somalia) or high HIV prevalence. The researchers then examined the data used by the two groups to estimate under-five deaths and U5MR, the method used for U5MR trend fitting, and additional adjustment procedures (for example, the UN IGME incorporates feedback from experts and country consultations in its estimates). The UN IGME and IHME estimation approaches included differences in all of these areas, but differences in the data used caused on average larger differences in the estimates than the use of different trend fitting methods did. What Do These Findings Mean? These findings show that the substantial country-specific differences between UN IGME and IHME estimates for U5MR and the number of under-five deaths are the result of several differences between the data and trend fitting methods used by the two groups. In particular, the findings indicate that the lack of reliable data in many developing countries, especially those where there is civil unrest or ongoing conflicts, is often responsible for differences in estimates. These differences should, therefore, decrease as more reliable data become available. For now, though, the differences between the UN IGME and IHME national estimates of child mortality may cause confusion about the true extent of progress towards MDG 4 and could foster policy inactivity if the reasons for the discrepancies are not made clear. The researchers call, therefore, for more transparency on the methods and data used in the estimation of U5MR and for a concerted effort by governments, UN agencies, and non-governmental organizations to improve the collection of reliable data on child deaths. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001288. This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the UN Inter-agency Group for Child Mortality Estimation and a link to its database; the 2011 UN IGME report on Levels and Trends in Child Mortality is available The Institute for Health Metrics and Evaluation website includes a summary of their 2011 analysis of U5MR and under-five deaths The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages) Further information about the Millennium Development Goals is available

Cheryl Sawyer uses new methods to generate estimates of sex differences in child mortality which can be used to pinpoint areas where these differences in mortality merit closer examination., Introduction Producing estimates of infant (under age 1 y), child (age 1–4 y), and under-five (under age 5 y) mortality rates disaggregated by sex is complicated by problems with data quality and availability. Interpretation of sex differences requires nuanced analysis: girls have a biological advantage against many causes of death that may be eroded if they are disadvantaged in access to resources. Earlier studies found that girls in some regions were not experiencing the survival advantage expected at given levels of mortality. In this paper I generate new estimates of sex differences for the 1970s to the 2000s. Methods and Findings Simple fitting methods were applied to male-to-female ratios of infant and under-five mortality rates from vital registration, surveys, and censuses. The sex ratio estimates were used to disaggregate published series of both-sexes mortality rates that were based on a larger number of sources. In many developing countries, I found that sex ratios of mortality have changed in the same direction as historically occurred in developed countries, but typically had a lower degree of female advantage for a given level of mortality. Regional average sex ratios weighted by numbers of births were found to be highly influenced by China and India, the only countries where both infant mortality and overall under-five mortality were estimated to be higher for girls than for boys in the 2000s. For the less developed regions (comprising Africa, Asia excluding Japan, Latin America/Caribbean, and Oceania excluding Australia and New Zealand), on average, boys' under-five mortality in the 2000s was about 2% higher than girls'. A number of countries were found to still experience higher mortality for girls than boys in the 1–4-y age group, with concentrations in southern Asia, northern Africa/western Asia, and western Africa. In the more developed regions (comprising Europe, northern America, Japan, Australia, and New Zealand), I found that the sex ratio of infant mortality peaked in the 1970s or 1980s and declined thereafter. Conclusions The methods developed here pinpoint regions and countries where sex differences in mortality merit closer examination to ensure that both sexes are sharing equally in access to health resources. Further study of the distribution of causes of death in different settings will aid the interpretation of differences in survival for boys and girls. Please see later in the article for the Editors' Summary., Editors' Summary Background In 2000, world leaders agreed to eradicate extreme poverty by 2015. To help track progress towards this global commitment, eight Millennium Development Goals (MDGs) were set. MDG 4, which aims to reduce child mortality, calls for a reduction in under-five mortality (the number of children who die before their fifth birthday) to a third of its 1990 level of 12 million by 2015. The under-five mortality rate is also denoted in the literature as U5MR and 5q0. Progress towards MDG 4 has been substantial, but with only three years left to reach it, efforts to strengthen child survival programs are intensifying. Reliable estimates of trends in childhood mortality are pivotal to these efforts. So, since 2004, the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) has used statistical regression models to produce estimates of trends in under-five mortality and infant mortality (death before age one year) from data about childbearing and child survival collected by vital registration systems (records of all births and deaths), household surveys, and censuses. Why Was This Study Done? In addition to estimates of overall childhood mortality trends, information about sex-specific childhood mortality trends is desirable to monitor progress towards MDG 4, although the interpretation of trends in the relative mortality of girls and boys is not straightforward. Newborn girls survive better than newborn boys because they are less vulnerable to birth complications and infections and have fewer inherited abnormalities. Thus, the ratio of infant mortality among boys to infant mortality among girls is greater than one, provided both sexes have equal access to food and medical care. Beyond early infancy, girls and boys are similarly vulnerable to infections, so the sex ratio of deaths in the 1–4-year age group is generally lower than that of infant mortality. Notably, as living conditions improve in developing countries, infectious diseases become less important as causes of death. Thus, in the absence of sex-specific differences in the treatment of children, the sex ratio of childhood mortality is expected be greater than one and to increase as overall under-five mortality rates in developing countries decrease. In this study, the researcher evaluated national and regional changes in the sex ratios of childhood mortality since the 1970s to investigate whether girls and boys have equal access to medical care and other resources. What Did the Researcher Do and Find? The researcher developed new statistical fitting methods to estimate trends in the sex ratio of mortality for infants and young children for individual countries and world regions. When considering individual countries, the researcher found that for 92 countries in less developed regions, the median sex ratio of under-five mortality increased between the 1970s and the 2000s, in line with the expected changes just described. However, the average sex ratio of under-five mortality for less developed regions, weighted according to the number of births in each country, did not increase between the 1970s and 2000s, at which time the average under-five mortality rate of boys was about 2% higher than that of girls. This discrepancy resulted from India and China—the two most populous developing countries—having sex ratios for both infant and under-five mortality that remained constant or declined over the study period and were below one in the 2000s, a result that indicates excess female mortality. In China, for example, infant mortality was found to be 12% higher for boys than for girls in the 1970s, but 24% lower for boys than for girls in the 2000s. Finally, although in the less developed regions (excluding India and China) girls went from having a slight survival disadvantage at ages 1–4 years in the 1970s, on average, to having a slight advantage in the 2000s, girls remained more likely to die than boys in this age group in several Asian and African countries. What Do These Findings Mean? Although the quality of the available data is likely to affect the accuracy of these findings, in most developing countries the ratio of male to female under-five mortality has increased since the 1970s, in parallel with the decrease in overall childhood mortality. Notably, however, in a number of developing countries—including several each in sub-Saharan Africa, northern Africa/western Asia, and southern Asia—girls have higher mortality than boys at ages 1–4 years, and in India and China girls have higher mortality in infancy. Thus, girls are benefitting less than boys from the overall decline in childhood mortality in India, China, and some other developing countries. Further studies are needed to determine the underlying reasons for this observation. Nevertheless, the methods developed here to estimate trends in sex-specific childhood mortality pinpoint countries and regions where greater efforts should be made to ensure that both sexes have equal access to health care and other important resources during early life. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001287. This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine The United Nations Childrens Fund works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages) Further information about the Millennium Development Goals is available A 2011 report by the United Nations Department of Economic and Social Affairs entitled Sex Differentials in Childhood Mortality is available

Michel Guillot and colleagues did a systematic evaluation to assess what proportion of under-five mortality occurs below age one compared with at age one and above, to determine how much observed values deviate from so called “model age patterns” of under-five mortality, Background The under-five mortality rate (the probability of dying between birth and age 5 y, also denoted in the literature as U5MR and 5 q 0) is a key indicator of child health, but it conceals important information about how this mortality is distributed by age. One important distinction is what amount of the under-five mortality occurs below age 1 y (1 q 0) versus at age 1 y and above (4 q 1). However, in many country settings, this distinction is often difficult to establish because of various types of data errors. As a result, it is common practice to resort to model age patterns to estimate 1 q 0 and 4 q 1 on the basis of an observed value of 5 q 0. The most commonly used model age patterns for this purpose are the Coale and Demeny and the United Nations systems. Since the development of these models, many additional sources of data for under-five mortality have become available, making possible a general evaluation of age patterns of infant and child mortality. In this paper, we do a systematic comparison of empirical values of 1 q 0 and 4 q 1 against model age patterns, and discuss whether observed deviations are due to data errors, or whether they reflect true epidemiological patterns not addressed in existing model life tables. Methods and Findings We used vital registration data from the Human Mortality Database, sample survey data from the World Fertility Survey and Demographic and Health Surveys programs, and data from Demographic Surveillance Systems. For each of these data sources, we compared empirical combinations of 1 q 0 and 4 q 1 against combinations provided by Coale and Demeny and United Nations model age patterns. We found that, on the whole, empirical values fall relatively well within the range provided by these models, but we also found important exceptions. Sub-Saharan African countries have a tendency to exhibit high values of 4 q 1 relative to 1 q 0, a pattern that appears to arise for the most part from true epidemiological causes. While this pattern is well known in the case of western Africa, we observed that it is more widespread than commonly thought. We also found that the emergence of HIV/AIDS, while perhaps contributing to high relative values of 4 q 1, does not appear to have substantially modified preexisting patterns. We also identified a small number of countries scattered in different parts of the world that exhibit unusually low values of 4 q 1 relative to 1 q 0, a pattern that is not likely to arise merely from data errors. Finally, we illustrate that it is relatively common for populations to experience changes in age patterns of infant and child mortality as they experience a decline in mortality. Conclusions Existing models do not appear to cover the entire range of epidemiological situations and trajectories. Therefore, model life tables should be used with caution for estimating 1 q 0 and 4 q 1 on the basis of 5 q 0. Moreover, this model-based estimation procedure assumes that the input value of 5 q 0 is correct, which may not always be warranted, especially in the case of survey data. A systematic evaluation of data errors in sample surveys and their impact on age patterns of 1 q 0 and 4 q 1 is urgently needed, along with the development of model age patterns of under-five mortality that would cover a wider range of epidemiological situations and trajectories. Please see later in the article for the Editors' Summary., Editors' Summary Background In 2000, world leaders agreed on eight Millennium Development Goals designed to end extreme poverty by 2015. The fourth of these goals—MDG 4—aims to reduce under-five mortality (the number of children who die before their fifth birthday) to a third of its 1990 level by 2015. A key indicator used to monitor progress towards this target is the under-five mortality rate (the probability of a child dying before his/her fifth birthday, also denoted as U5MR or 5 q 0). In developed countries, data collected through vital registration systems (which record all births and deaths) are used to calculate 5 q 0. However, developing countries, which are where most under-five deaths occur, rarely have vital registration systems, and 5 q 0 is estimated using data collected by programs such as the World Fertility Survey (WFS) and Demographic and Health Surveys (DHS), which conduct nationally representative surveys that ask a sample of women about their living and dead children. Why Was This Study Done? Although 5 q 0 is a key indicator of child health, it conceals important information about the age distribution of child deaths. Public health experts need to know the distribution of 5 q 0 with respect to 1 q 0 (the probability that an infant will die before age one) and 4 q 1 (the probability that a child reaching age one will die below age five) to help them reduce child mortality. At a given level of 5 q 0, high values of 1 q 0 indicate high levels of death from congenital (inherited) anomalies and conditions that occur around the time of birth; these deaths can be reduced by improving the care of women during pregnancy and childbirth and the care of newborn babies. By contrast, at a given level of 5 q 0, high values of 4 q 1 indicate high levels of death from infectious diseases; these deaths can be reduced by, for example, introducing immunization programs. 1 q 0 and 4 q 1 are usually estimated from observed (empirical) values of 5 q 0 using the Coale and Demeny or United Nations (UN) “model life tables” (mathematical models of the variation of mortality with age), which were constructed in 1966 and 1982, respectively, using the best data available. Since their construction, additional sources of data about under-five mortality have become available; in this study, the researchers systematically compare global empirical values of 1 q 0 and 4 q 1 with values obtained using model life tables. What Did the Researchers Do and Find? The researchers compared empirical combinations of 1 q 0 and 4 q 1 (estimated using vital registration data, WFS and DHS data, and data from Demographic Surveillance Sites in sub-Saharan Africa) with the combinations derived from 5 q 0 using the Coale and Demeny and UN model life tables. The empirical values mainly fell within the range provided by these tables, but there were important exceptions. For example, empirical values of 4 q 1 relative to 1 q 0 tended to be above the range provided by the model life tables for sub-Saharan African countries. This pattern was mainly because of epidemiological reasons (epidemiology is the study of disease patterns in populations), such as the occurrence of diseases such as malaria, measles, and diarrhea that generate excess mortality among children older than one year. Interestingly, the emergence of HIV does not seem to have substantially modified preexisting patterns of 1 q 0 versus 4 q 1. Importantly, the researchers also show that populations often experience changes in the age patterns of infant and child mortality as they experience an overall decline in mortality. What Do These Findings Mean? These findings suggest that the existing model life tables do not cover the entire global range of epidemiological situations and trajectories and must, therefore, be used with caution for estimating 1 q 0 and 4 q 1 on the basis of 5 q 0. The development of new model age patterns of under-five mortality that cover a wider range of epidemiological situations should improve this situation, but a systematic analysis of data errors in sample surveys and the impact of such errors on estimates of 1 q 0 and 4 q 1 is also urgently needed to ensure that public health experts have access to accurate information on child mortality. Importantly, this overview shows that a wide range of 1 q 0 and 4 q 1 combinations can occur at a given level of 5 q 0. Because the level of 4 q 1 relative to 1 q 0 provides important information about the disease processes occurring in a population, this finding highlights the importance of determining 1 q 0 and 4 q 1 as well as 5 q 0 whenever possible. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001299. This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages) Further information about the Millennium Development Goals is available Information is also available about the Human Mortality Database, which holds vital registration data; the World Fertility Survey program; the Demographic and Health Surveys program; and model life tables

In the first of two papers investigating surgical provision in eight district hospitals in Saharan African countries, Margaret Kruk and colleagues find low levels of surgical care provision suggesting unmet need for surgical services., Background Surgical conditions contribute significantly to the disease burden in sub-Saharan Africa. Yet there is an apparent neglect of surgical care as a public health intervention to counter this burden. There is increasing enthusiasm to reverse this trend, by promoting essential surgical services at the district hospital, the first point of contact for critical conditions for rural populations. This study investigated the scope of surgery conducted at district hospitals in three sub-Saharan African countries. Methods and Findings In a retrospective descriptive study, field data were collected from eight district hospitals in Uganda, Tanzania, and Mozambique using a standardized form and interviews with key informants. Overall, the scope of surgical procedures performed was narrow and included mainly essential and life-saving emergency procedures. Surgical output varied across hospitals from five to 45 major procedures/10,000 people. Obstetric operations were most common and included cesarean sections and uterine evacuations. Hernia repair and wound care accounted for 65% of general surgical procedures. The number of beds in the studied hospitals ranged from 0.2 to 1.0 per 1,000 population. Conclusion The findings of this study clearly indicate low levels of surgical care provision at the district level for the hospitals studied. The extent to which this translates into unmet need remains unknown although the very low proportions of live births in the catchment areas of these eight hospitals that are born by cesarean section suggest that there is a substantial unmet need for surgical services. The district hospital in the current health system in sub-Saharan Africa lends itself to feasible integration of essential surgery into the spectrum of comprehensive primary care services. It is therefore critical that the surgical capacity of the district hospital is significantly expanded; this will result in sustainable preventable morbidity and mortality. Please see later in the article for the Editors' Summary, Editors' Summary Background Every year, about 234 million major surgical procedures take place globally. Of these procedures, only a quarter are performed in low- and middle-income countries where nearly three-quarters of the world's population lives. Put another way, in high-income countries, 10,110 people out of every 100,000 have surgery each year on average compared to only 295 people out of every 100,000 in low- and middle-income countries. Yet conditions that need surgery (including complications of childbirth and traumatic injuries) are common in developing countries and contribute significantly to the burden of disease in these countries. Various organizations are working to reduce this burden by improving emergency and essential surgical care in developing countries. For example, the Bellagio Essential Surgery Group (BESG), which includes experts in surgery, anesthesia, obstetrics (the branch of medicine that cares for women during pregnancy and childbirth), and health policy from several African countries, the World Health Organization (WHO), and the US, aims to increase access to surgical services in sub-Saharan Africa. Why Was This Study Done? One way to improve access to surgical services in sub-Saharan Africa would be to promote the provision of essential surgical services at district hospitals. These hospitals are the first referral facilities for people living in rural areas. Traditionally, patients receive much of their primary health care at these facilities but are referred to secondary and tertiary health care facilities (regional and national referral hospitals, respectively) for more specialized care. However, many surgical conditions—in particular, obstetric emergencies—need to be treated at district hospitals if lives are to be saved. Unfortunately, very little is known about the range and volume of surgical procedures currently undertaken in district hospitals in sub-Saharan Africa and such information is needed before programs can be developed to increase access to surgical services at these facilities. In this retrospective, descriptive study, the researchers (some of whom are part of the BESG) investigate the scope of surgery undertaken in district hospitals in three sub-Saharan African countries. What Did the Researchers Do and Find? The researchers obtained recent data on the surgical procedures done at two representative district hospitals each in Tanzania and in Mozambique and four representative district hospitals in Uganda by examining hospital records and by interviewing administrators. The observed range of surgical procedures performed in these hospitals was narrow, they report, consisting mainly of essential and life-saving emergency procedures such as cesarean sections for the delivery of babies and wound-related procedures. Obstetric procedures accounted for around half of all surgical procedures in all the hospitals except one Ugandan hospital. Hernia repair and wound care accounted for nearly two-thirds of general surgical procedures. The surgical output across the hospitals varied from five to 45 major procedures per 10,000 people in the population (average 25 operations per 10,000 people). Across the hospitals, between one and 17 cesarean sections and between 0.5 and seven hernia repairs were performed per 10,000 people in the population. Finally, the researchers used their data and WHO estimates of the population need for cesarean sections to estimate that in the two Tanzanian district hospitals, between half and two-thirds of women that needed a cesarean section did not have access to this life-saving procedure. What Do These Findings Mean? These findings suggest that there are low levels of provision of surgical care in district hospitals in Tanzania, Mozambique, and Uganda. Further studies are needed to confirm that these findings are generalizable to district hospitals elsewhere in sub-Saharan Africa and to quantify the extent to which this low level of surgical care translates into unmet needs. Limitations of the study include a lack of information on outcomes, on referral of patients to higher-level facilities, and on how many of the surgical procedures undertaken at these hospitals dealt with traumatic injuries. Nevertheless, the information collected in this study, together with that in a separate paper that investigates the availability of health workers and funding for the provision of essential surgery in district hospitals in these three countries, suggests that the surgical capacity of district hospitals in sub-Saharan Africa needs to be improved. If this goal can be achieved, suggest the researchers, it should avert many illnesses and deaths in this poor region of the world. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000243. The availability of health workers and funding for surgery in the same hospitals is investigated in a PLoS Medicine Research Article by Margaret E. Kruk et al. Information on the Bellagio Essential Surgery Group is available WHO's Global initiative for Emergency and Essential Surgical Care plans to take essential emergency, basic surgery and anesthesia skills to health care staff in low- and middle-income countries around the world; WHO also has a page describing the importance of emergency and essential surgery in primary health care

In 2002, a clinical trial designed to evaluate optimal ventilation practice [1],[2] for patients with acute respiratory distress syndrome (ARDS) sparked a major controversy. Critics charged that management of ARDS in the different arms of the study did not adequately reflect usual medical care, and alleged that it was essential for scientific and ethical reasons to have a usual care comparison arm in the study. The controversy over trial design enmeshed the National Institutes of Health (NIH), the Office for Human Research Protections (OHRP) and the critical care research community. The trial was put on hold and reviewed by two independent expert panels. Experts pointed to the need for further analysis of the scientific and ethical issues involved in choosing trial designs when there is no consensus on standard of care. In November 2005, NIH and a number of other federal agencies sponsored a meeting (see Text S1) to discuss clinical trial design challenges involving selection of usual care comparison groups (Text S1). The meeting was informed by a background paper (Text S1) outlining types of challenges involved in selecting usual care arms, prepared by a working group with expertise in clinical trial design, ethics, evidence-based medicine, statistics, and science policy. We present here the background framework and case studies used in this paper (Text S1). We enumerate five factors that make consensus on these issues particularly difficult, and recommend specific criteria for assessing proposed study designs. Terminology Terms such as “standard of care,” “control arm,” “usual care,” and “community care” have all been used to describe arms reflecting conventional therapy. We use the term “usual care” to describe the care commonly given by practitioners in a community to avoid any legal or normative implications of the term “standard of care.”

Louise Howard and colleagues conduct a systematic review and meta-analysis to estimate the prevalence and odds of experience of domestic violence experience among women with antenatal and postnatal mental health disorders. Please see later in the article for the Editors' Summary, 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, Editors' Summary Background Domestic violence—physical, sexual, or emotional abuse by an intimate partner or family member—is a major public health problem and although more common in women, can also affect men. Due to the nature of the problem, it is difficult to collect accurate figures on the scale of domestic violence, but a study by the World Health Organization in ten countries found that 15%–71% of women aged 15–49 years reported physical and/or sexual violence by an intimate partner at some point in their lives. Women experiencing domestic violence have significant short- and long-term health problems, particularly regarding their mental health: experience of domestic violence can lead to a range of mental health disorders such as depression, psychosis, eating disorders, and even suicide attempts. Why Was This Study Done? As perinatal mental health disorders are among the commonest health problems in pregnancy and the postpartum period, and given the rate of domestic violence during pregnancy (previous studies have suggested a domestic violence prevalence of 4%–8% during pregnancy and the postnatal period), it is plausible that there may be a link between perinatal mental health disorders and having experienced domestic violence. Indeed, previous reviews have suggested the existence of such an association but were limited by the small number of included studies and focused on depression only, rather than the full range of antenatal and postnatal mental health disorders. So in this study the researchers systematically reviewed published studies to provide more robust estimates of the prevalence of having experienced domestic violence among women with antenatal and postnatal mental health disorders; the researchers also used a meta-analysis to estimate the odds (chance) of having experienced domestic violence among women with antenatal and postnatal mental health disorders. What Did the Researchers Do and Find? The researchers searched multiple databases and hand searched three relevant journals using key search terms to identify all types of relevant studies. Using specific criteria, the researchers retrieved and assessed over 1,000 full papers, of which 67 met the criteria for their systematic review. The researchers assessed the quality of each selected study and included only those studies that used validated diagnostic instruments and screening tools to assess mental health disorders in their calculations of the pooled (combined) odds ratio (OR) through meta-analysis. Using these methods, in cross-sectional studies (studies conducted at one point in time), the researchers found that women with probable depression in the antenatal period reported a high prevalence and increased odds of having experienced partner violence during their lifetime (OR = 3), during the past year (OR = 2.8), and during pregnancy (OR = 5). The results were similar for the postnatal period. The evidence was less robust for anxiety disorders: among women with probable anxiety in the antenatal period, the researchers found an OR of 2.9 of having experienced lifetime partner violence. The odds were less in the postnatal period (OR = 1.4) In their analysis of longitudinal studies (follow-up studies over a period of time), the researchers found an increased odds of probable postnatal depression both among women who reported having ever experienced partner violence in their lifetime (OR = 2.9) and among women who reported having experienced partner violence during pregnancy (OR = 3.1). The researchers also found a combined prevalence estimate of 12.7% for probable depression during the postnatal period following experiences of partner violence during pregnancy. Because of limited data, the researchers could not calculate an OR of the association between probable antenatal depression and later experiences of partner violence. What Do These Findings Mean? These findings suggest that women with high levels of symptoms of perinatal mental health disorders—antenatal and postnatal anxiety, depression, and post-traumatic stress disorder—have a high prevalence and increased odds of having experienced domestic violence both over their lifetime and during pregnancy. However, these findings cannot prove causality, they fail to show a two-way association (that is, perinatal mental health disorders leading to subsequent domestic violence), and no information on other perinatal mental disorders, such as eating disorders and puerperal psychosis, was available. The variation of the quality of the included studies also limits the results, highlighting the need for high-quality data to suggest how maternity and mental health services could address domestic violence and improve health outcomes for women and their infants in the future. Nevertheless, this study emphasizes the importance of identifying and responding to possible domestic violence among women attending antenatal and mental health services. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001452. The World Health Organization provides information and statistics about violence against women and also about mental health disorders during pregnancy The UK Royal College of Psychiatrists has information for professionals and patients about mental health disorders during pregnancy

Romesh Silva assesses and analyzes differences in direct and indirect methods of estimating under-five mortality rates using data collected from full and summary birth histories in Demographic and Health Surveys from West Africa, East Africa, Latin America, and South/Southeast Asia., Background Given the lack of complete vital registration data in most developing countries, for many countries it is not possible to accurately estimate under-five mortality rates from vital registration systems. Heavy reliance is often placed on direct and indirect methods for analyzing data collected from birth histories to estimate under-five mortality rates. Yet few systematic comparisons of these methods have been undertaken. This paper investigates whether analysts should use both direct and indirect estimates from full birth histories, and under what circumstances indirect estimates derived from summary birth histories should be used. Methods and Findings Usings Demographic and Health Surveys data from West Africa, East Africa, Latin America, and South/Southeast Asia, I quantify the differences between direct and indirect estimates of under-five mortality rates, analyze data quality issues, note the relative effects of these issues, and test whether these issues explain the observed differences. I find that indirect estimates are generally consistent with direct estimates, after adjustment for fertility change and birth transference, but don't add substantial additional insight beyond direct estimates. However, choice of direct or indirect method was found to be important in terms of both the adjustment for data errors and the assumptions made about fertility. Conclusions Although adjusted indirect estimates are generally consistent with adjusted direct estimates, some notable inconsistencies were observed for countries that had experienced either a political or economic crisis or stalled health transition in their recent past. This result suggests that when a population has experienced a smooth mortality decline or only short periods of excess mortality, both adjusted methods perform equally well. However, the observed inconsistencies identified suggest that the indirect method is particularly prone to bias resulting from violations of its strong assumptions about recent mortality and fertility. Hence, indirect estimates of under-five mortality rates from summary birth histories should be used only for populations that have experienced either smooth mortality declines or only short periods of excess mortality in their recent past. Please see later in the article for the Editors' Summary., Editors' Summary Background In 1990, 12 million children died before they reached their fifth birthday. Faced with this largely avoidable loss of young lives, in 2000, world leaders set a target of reducing under-five mortality (death) to one-third of its 1990 level by 2015 as Millennium Development Goal 4 (MDG 4); this goal, together with seven others, aims to eradicate extreme poverty globally. To track progress towards MDG 4, experts need accurate estimates of the global and country-specific under-five mortality rate (U5MR, the probability of a child dying before age five). The most reliable sources of data for U5MR estimation are vital registration systems—national records of all births and deaths. Unfortunately, developing countries, which are where most childhood deaths occur, rarely have such records, so full or summary birth histories provide the data for U5MR estimation instead. In full birth histories (FBHs), which are collected through household surveys such as those conducted by Demographic and Health Surveys (DHS), women are asked for the date of birth of all their children and the age at death of any children who have died. In summary birth histories (SBHs), which are collected through household surveys and censuses, women are asked how many children they have had and how many are alive at the time of the survey. Why Was This Study Done? “Direct” estimates of U5MRs can be obtained from FBHs because FBHs provide detailed information about the date of death and the exposure of children to the risk of dying. By contrast, because SBHs do not contain information on children's exposure to the risk of dying, “indirect” estimates of U5MR are obtained from SBHs using model life tables (mathematical models of the variation of mortality with age). Indirect estimates are often also derived from FBHs, but few systematic comparisons of direct and indirect methods for U5MR estimation have been undertaken. In this study, Romesh Silva investigates whether direct and indirect methods provide consistent U5MR estimates from FBHs and whether there are any circumstances under which indirect methods provide more reliable U5MR estimates than direct methods. What Did the Researcher Do and Find? The researcher used DHS data from West Africa, East Africa, Latin America, and South/Southeast Asia to quantify the differences between direct and indirect estimates of U5MR calculated from the same data and analyzed possible reasons for these differences. Estimates obtained using a version of the “Brass” indirect estimation method were uniformly higher than those obtained using direct estimation. Indirect and direct estimates generally agreed, however, after adjustment for changes in fertility—the Brass method assumes that country-specific fertility (the number of children born to a woman during her reproductive life) remains constant—and for birth transference, an important source of data error in FBHs that arises because DHS field staff can lessen their workload by recording births as occurring before a preset cutoff date rather than after that date. Notably, though, for countries that had experienced political or economic crises, periods of excess mortality due to conflicts, or periods during which the health transition had stalled (as countries become more affluent, overall mortality rates decline and noncommunicable diseases replace infectious diseases as the major causes of death), marked differences between indirect and direct estimates of U5MR remained, even after these adjustments. What Do These Findings Mean? Because the countries included in this study do not have vital registration systems, these findings provide no information about the validity of either direct or indirect estimation methods for U5MR estimation. They suggest, however, that for countries where there has been a smooth decline in mortality or only short periods of excess mortality, both direct and indirect methods of U5MR estimation work equally well, after adjustment for changes in fertility and for birth transference, and that indirect estimates add little to the insights provided into childhood mortality by direct estimates. Importantly, the inconsistencies observed between the two methods that remain after adjustment suggest that indirect U5MR estimation is more susceptible to bias (systematic errors that arise because of the assumptions used to estimate U5MR) than direct estimation. Thus, indirect estimates of U5MR from SBHs should be used only for populations that have experienced either smooth mortality declines or only short periods of excess mortality in their recent past. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001296. This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available The World Health Organization has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages) Further information about the Millennium Development Goals is available Information is available about infant and child mortality data collected by Demographic and Health Surveys

Jon Pedersen and Jing Liu examine the feasibility and potential advantages of using one-year rather than five-year time periods along with calendar year-based estimation when deriving estimates of child mortality., Background Child mortality estimates from complete birth histories from Demographic and Health Surveys (DHS) surveys and similar surveys are a chief source of data used to track Millennium Development Goal 4, which aims for a reduction of under-five mortality by two-thirds between 1990 and 2015. Based on the expected sample sizes when the DHS program commenced, the estimates are usually based on 5-y time periods. Recent surveys have had larger sample sizes than early surveys, and here we aimed to explore the benefits of using shorter time periods than 5 y for estimation. We also explore the benefit of changing the estimation procedure from being based on years before the survey, i.e., measured with reference to the date of the interview for each woman, to being based on calendar years. Methods and Findings Jackknife variance estimation was used to calculate standard errors for 207 DHS surveys in order to explore to what extent the large samples in recent surveys can be used to produce estimates based on 1-, 2-, 3-, 4-, and 5-y periods. We also recalculated the estimates for the surveys into calendar-year-based estimates. We demonstrate that estimation for 1-y periods is indeed possible for many recent surveys. Conclusions The reduction in bias achieved using 1-y periods and calendar-year-based estimation is worthwhile in some cases. In particular, it allows tracking of the effects of particular events such as droughts, epidemics, or conflict on child mortality in a way not possible with previous estimation procedures. Recommendations to use estimation for short time periods when possible and to use calendar-year-based estimation were adopted in the United Nations 2011 estimates of child mortality., Editors' Summary Background In 2000, world leaders set, as Millennium Development Goal 4 (MDG 4), a target of reducing global under-five mortality (the number of children who die before their fifth birthday to a third of its 1990 level (12 million deaths per year) by 2015. (The MDGs are designed to alleviate extreme poverty by 2015.) To track progress towards MDG 4, the under-five mortality rate (also shown as 5 q 0) needs to be estimated both “precisely” and “accurately.” A “precise” estimate has a small random error (a quality indicated by a statistical measurement called the coefficient of variance), and an “accurate” estimate is one that is close to the true value because it lacks bias (systematic errors). In an ideal world, under-five mortality estimates would be based on official records of births and deaths. However, developing countries, which are where most under-five deaths occur, rarely have such records, and under-five mortality estimation relies on “complete birth histories” provided by women via surveys. These are collected by Demographic and Health Surveys (DHS, a project that helps developing countries collect data on health and population trends) and record all the births that a surveyed woman has had and the age at death of any of her children who have died. Why Was This Study Done? Because the DHS originally surveyed samples of 5,000–6,000 women, estimates of under-five mortality are traditionally calculated using data from five-year time periods. Over shorter periods with this sample size, the random errors in under-five mortality estimates become unacceptably large. Nowadays, the average DHS survey sample size is more than 10,000 women, so it should be possible to estimate under-five mortality over shorter time periods. Such estimates should be able to track the effects on under-five mortality of events such as droughts and conflicts better than estimates made over five years. In this study, the researchers determine appropriate time periods for child mortality estimates based on full birth histories, given different sample sizes. Specifically, they ask whether, with the bigger sample sizes that are now available, details about trends in under-five mortality rates are being missed by using the estimation procedures that were developed for smaller samples. They also ask whether calendar-year-based estimates can be calculated; mortality is usually estimated in “years before the survey,” a process that blurs the reference period for the estimate. What Did the Researchers Do and Find? The researchers used a statistical method called “jackknife variance estimation” to determine coefficients of variance for child mortality estimates calculated over different time periods using complete birth histories from 207 DHS surveys. Regardless of the estimation period, half of the estimates had a coefficient of variance of less than 10%, a level of random variation that is generally considered acceptable. However, within each time period, some estimates had very high coefficients of variance. These estimates were derived from surveys where there was a small sample size, low fertility (the women surveyed had relatively few babies), or low child mortality. Other analyses show that although the five-year period estimates had lower standard errors than the one-year period estimates, the latter were affected less by bias than the five-year period estimates. Finally, estimates fixed to calendar years rather than to years before the survey were more directly comparable across surveys and brought out variations in child mortality caused by specific events such as conflicts more clearly. What Do These Findings Mean? These findings show that although under-five mortality rate estimates based on five-year periods of data have been the norm, the sample sizes currently employed in DHS surveys make it feasible to estimate mortality for shorter periods. The findings also show that using shorter periods of data in estimations of the under-five mortality rate, and using calendar-year-based estimation, reduces bias (makes the estimations more accurate) and allows the effects of events such as droughts, epidemics, or conflict on under-five mortality rates to be tracked in a way that is impossible when using five-year periods of data. Given these findings, the researchers recommend that time periods shorter than five years should be adopted for the estimation of under-five mortality and that estimations should be pegged to calendar years rather than to years before the survey. Both recommendations have already been adopted by the United Nations Inter-agency Group for Child Mortality Estimation (IGME) and were used in their 2011 analysis of under-five mortality. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001289. This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 IGME report on Levels and Trends in Child Mortality is available The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages) Further information about the Millennium Development Goals is available Information is also available about Demographic and Health Surveys of infant and child mortality

The authors do not consider these competing interests, but in the interest of full transparency declare the following: Dr. Glantz holds two research grants related to tobacco from the National Cancer Institute, an endowed chair as American Legacy Distinguished Professor in Tobacco Control, and a grant from the Robert Wood Johns Foundation to assist Ms. Eubanks, who led the US Department of Justice in its successful RICO case against the tobacco industry (United States v. Philip Morris USA, et al.) in writing a book about the case. Dr. Glantz also administers an endowment from the American Legacy Foundation, which supports the UCSF Center for Tobacco Control Research and Education, which Dr. Glantz directs, and the Legacy Tobacco Documents Library. He also has the William Cahan Endowment provided by the Flight Attendant Medical Research Institute. Mr. Barnes is an attorney in Dr. Glantz' research group, who is supported in part by Dr. Glantz' National Cancer Institute grants. Ms. Eubanks retired from the Department of Justice on December 1, 2005 and is now a lawyer in private practice in Washington, D. C. None of these organizations played any role in the preparation of this paper or the decision to submit it for publication. This paper was not prepared as part of any extramurally funded project. Provenance: Not commissioned; externally

Health (GCGH) initiative, discussed in the fi rst article in this series [3], we are exploring a range of ESC issues identifi ed by the GCGH investigators and developing world key informants, discussed in the second article in this series [4]. The investigators and key informants placed particular emphasis upon the importance of community engagement, and therefore we prepared a conceptual paper on this topic, which we distributed as a working paper to GCGH investigators and program staff at the 2nd Annual GCGH Meeting. In this article, we summarize this conceptual paper. We fi rst examine the concept of CE in research in developing countries, then we describe published models of CE, and fi nally we discuss two relevant examples of CE in research from Africa. What Is a Community?

Medecins Sans Frontieres is a respectable organisation which helps people in jeopardy and provides medical relief in difficult situations all over the world. Despite this recognition I must confess I found the last paper of G. Ooms in PLoS Medicine [1] to develop highly debatable concepts about health, development, and even sustainability. Ooms postulates that sustainable intervention creates a bias for development agencies to maintain the status quo. On the other hand, it could very easily be argued that conventional emergency “humanitarian aid” has failed to improve health on even a medium-term basis in the last four decades. Common sense indicates that populations benefit more from improvements in wealth, water supply, and agriculture than from consuming free goods from international aid. Several studies provide a basis for this conclusion [2]. On the contrary, a persistent status quo could result from an exclusive humanitarian approach, precluding the necessary changes to develop health care. International agencies say that, based on numerous studies, improving health on a medium- or long-term basis is a matter of “sustainable” programmes. But what is meant by “sustainability”? It seems that Dr. Ooms interprets sustainability as durability, a confusion which is obvious when one reads the French version of his paper. Durability is a plain matter of time; pollution, totalitarian regimes, or poverty could as well, unfortunately, meet a single durability criterion. This is the main point, if one wants to assess the criticism which Ooms aims at development agencies. Their main objective is to assess the sustainability of the health programmes which means (in French the supportabilite and not the durabilite) whether these programs exceed the economic, organisational, and ecological possibilities of the country and its population. And I recognize that I am in keeping with that! To give rice to people who usually consume rice is helpful, but next time it will be even more helpful to give them the means to grow their own! Yet the reality is far more complex, something which requires that agencies carefully assess the different programmes [3]. I must add that such an approach does not preclude an increase in annual governments outlays. But before increasing expenditure, it is wise to assess whether the programmes is working, and for whom. I don't miss the point that sustainable aid is for certain governments synonymous with conditional aid, and such difficulties must not be hidden, but every one of us is able to make the distinction between the principle and some penny-pinching, restrictive policies which can be amended and reversed. Indeed, the two approaches are complementary. When an emergency situation arises, it is obvious that some of the critical health issues of the local populations could be addressed by emergency international aid. But after a few weeks, only structural and political changes (that is, peace, convenient water supply, agriculture revival, affordable energy, information, free trade, free enterprise through microrenting...) are crucial for maintaining health and eventually improving it. As a matter of fact it could be a more dangerous illusion for these endangered populations to give credit to the ideas that Dr. Ooms develops in order to justify the spending of more public funds to extend emergency humanitarian aid indefinitely.

Background Following a reduction in global child mortality due to communicable diseases, the relative contribution of congenital anomalies to child mortality is increasing. Although infant survival of children born with congenital anomalies has improved for many anomaly types in recent decades, there is less evidence on survival beyond infancy. We aimed to systematically review, summarise, and quantify the existing population-based data on long-term survival of individuals born with specific major congenital anomalies and examine the factors associated with survival. Methods and findings Seven electronic databases (Medline, Embase, Scopus, PsycINFO, CINAHL, ProQuest Natural, and Biological Science Collections), reference lists, and citations of the included articles for studies published 1 January 1995 to 30 April 2020 were searched. Screening for eligibility, data extraction, and quality appraisal were performed in duplicate. We included original population-based studies that reported long-term survival (beyond 1 year of life) of children born with a major congenital anomaly with the follow-up starting from birth that were published in the English language as peer-reviewed papers. Studies on congenital heart defects (CHDs) were excluded because of a recent systematic review of population-based studies of CHD survival. Meta-analysis was performed to pool survival estimates, accounting for trends over time. Of 10,888 identified articles, 55 (n = 367,801 live births) met the inclusion criteria and were summarised narratively, 41 studies (n = 54,676) investigating eight congenital anomaly types (spina bifida [n = 7,422], encephalocele [n = 1,562], oesophageal atresia [n = 6,303], biliary atresia [n = 3,877], diaphragmatic hernia [n = 6,176], gastroschisis [n = 4,845], Down syndrome by presence of CHD [n = 22,317], and trisomy 18 [n = 2,174]) were included in the meta-analysis. These studies covered birth years from 1970 to 2015. Survival for children with spina bifida, oesophageal atresia, biliary atresia, diaphragmatic hernia, gastroschisis, and Down syndrome with an associated CHD has significantly improved over time, with the pooled odds ratios (ORs) of surviving per 10-year increase in birth year being OR = 1.34 (95% confidence interval [95% CI] 1.24–1.46), OR = 1.50 (95% CI 1.38–1.62), OR = 1.62 (95% CI 1.28–2.05), OR = 1.57 (95% CI 1.37–1.81), OR = 1.24 (95% CI 1.02–1.5), and OR = 1.99 (95% CI 1.67–2.37), respectively (p < 0.001 for all, except for gastroschisis [p = 0.029]). There was no observed improvement for children with encephalocele (OR = 0.98, 95% CI 0.95–1.01, p = 0.19) and children with biliary atresia surviving with native liver (OR = 0.96, 95% CI 0.88–1.03, p = 0.26). The presence of additional structural anomalies, low birth weight, and earlier year of birth were the most commonly reported predictors of reduced survival for any congenital anomaly type. The main limitation of the meta-analysis was the small number of studies and the small size of the cohorts, which limited the predictive capabilities of the models resulting in wide confidence intervals. Conclusions This systematic review and meta-analysis summarises estimates of long-term survival associated with major congenital anomalies. We report a significant improvement in survival of children with specific congenital anomalies over the last few decades and predict survival estimates up to 20 years of age for those born in 2020. This information is important for the planning and delivery of specialised medical, social, and education services and for counselling affected families. This trial was registered on the PROSPERO database (CRD42017074675)., In a systematic review and meta-analysis, Svetlana V. Glinianaia and colleagues report on temporal trends in long-term survival of children born with specific congenital anomalies., Author summary Why was this study done? Following a reduction in global child mortality due to communicable diseases, the relative contribution of congenital anomalies to child mortality under age 5 years is increasing globally. Identifying and addressing the emerging priority of congenital anomalies, including for children aged 5–9 years, is one of the strategic directions for the post-2015 child health agenda. This research aimed to summarise and quantify the existing population-based evidence on long-term survival of children born with specific major congenital anomalies that manifest in childhood. What did the researchers do and find? This systematic review included 55 international studies that estimated survival beyond 1 year of age of children born with major congenital anomalies. Our meta-analysis results of 41 studies over the birth years 1970–2015 showed a statistically significant improvement in survival over time in children with spina bifida, oesophageal atresia, biliary atresia, congenital diaphragmatic hernia, gastroschisis, and Down syndrome associated with a congenital heart defect, but there was no evidence of improvement in those with encephalocele or biliary atresia with a native liver. The commonest significant independent predictors of reduced survival for any congenital anomaly type were presence of additional structural anomalies, low birth weight, and earlier birth year period. What do these findings mean? A significant improvement in survival of children with specific congenital anomalies over the last few decades reported by individual studies and identified by the meta-analysis has important public health, medical, social, and family implications. Information on predicted survival of children with congenital anomalies up to 20 years of age is important for planning specialised medical, social, and education services for these children and for estimating costs associated with special care needs in childhood and adulthood.

Background Previous research has focused on the mortality associated with armed conflict as the primary measure of the population health effects of war. However, mortality only demonstrates part of the burden placed on a population by conflict. Injuries and resultant disabilities also have long-term effects on a population and are not accounted for in estimates that focus solely on mortality. Our aim was to demonstrate a new method to describe the effects of both lives lost, and years of disability generated by a given conflict, with data from the US-led 2003 invasion and subsequent occupation of Iraq. Methods and findings Our data come from interviews conducted in 2014 in 900 Baghdad households containing 5,148 persons. The average household size was 5.72 persons. The majority of the population (55.8%) were between the ages of 19 and 60. Household composition was evenly divided between males and females. Household sample collection was based on methodology previously designed for surveying households in war zones. Survey questions were answered by the head of household or senior adult present. The questions included year the injury occurred, the mechanism of injury, the body parts injured, whether injury resulted in disability and, if so, the length of disability. We present this modeling study to offer an innovative methodology for measuring “years lived with disability” (YLDs) and “years of life lost” (YLLs) attributable to conflict-related intentional injuries, using the Global Burden of Disease (GBD) approach. YLDs were calculated with disability weights, and YLLs were calculated by comparing the age at death to the GBD standard life table to calculate remaining life expectancy. Calculations were also performed using Iraq-specific life expectancy for comparison. We calculated a burden of injury of 5.6 million disability-adjusted life years (DALYs) lost due to conflict-related injuries in Baghdad from 2003 to 2014. The majority of DALYs lost were attributable to YLLs, rather than YLDs, 4.99 million YLLs lost (95% uncertainty interval (UI) 3.87 million to 6.13 million) versus 616,000 YLDs lost (95% UI 399,000 to 894,000). Cause-based analysis demonstrated that more DALYs were lost to due to gunshot wounds (57%) than any other cause. Our study has several limitations. Recall bias regarding the reporting and attribution of injuries is possible. Second, we have no data past the time of the interview, so we assumed individuals with ongoing disability at the end of data collection would not recover, possibly counting more disability for injuries occurring later. Additionally, incomplete data could have led to misclassification of deaths, resulting in an underestimation of the total burden of injury. Conclusions In this study, we propose a methodology to perform burden of disease calculations for conflict-related injuries (expressed in DALYs) in Baghdad from 2003 to 2014. We go beyond previous reports of simple mortality to assess long-term population health effects of conflict-related intentional injuries. Ongoing disability is, in cross section, a relatively small 10% of the total burden. Yet, this small proportion creates years of demands on the health system, persistent limitations in earning capacity, and continuing burdens of care provision on family members., In a modelling study, Guy Jensen and colleagues propose a method for calculating burden of injury in conflict using data on conflict-related intentional injuries in Baghdad, Iraq 2003-2014., Author summary Why was this study done? The Global Burden of Disease (GBD) project, based at the University of Washington, publishes the estimates of prevalence, incidence, years of life lost (YLLs), and years lived with disability (YLDs) for a comprehensive list of diseases and injuries and for all countries from 1990 to the present. The World Health Organization has also published YLL and YLD estimates. Previous researchers innovated the population-proportionate to size sampling methodology for household surveys in war zones, which we used in this study. Previous papers have attempted to calculate only Iraq War deaths, as mortality is an important population health indicator and is relatively straightforward to measure. Injuries are, along with mortality, an important factor in conflict settings; they measure a more nuanced toll on public health. Ongoing disability is important, especially when associated with demands on the health system, ongoing limitations in earning capacity, and the burdens created for family caregivers. We aim to lay out our application of the GBD methodology, along with our alteration to it for calculation of burden of injury in conflict. Additionally, we aim to describe specifically how these calculations were applied in hopes of developing a methodology for the study of conflict populations. What did the researchers do and find? This study innovates the application of GBD methodology for calculating YLLs and YLDs to data collected in a war zone. We calculated a burden of injury of 5.6 million DALYs lost due to conflict-related injuries in Baghdad from 2003 to 2014. These calculations encompass both mortality as well as the effects of injury and disability on the population of Baghdad. We performed these calculations using a variation of the GBD methodology to better reflect the dynamic nature of conflict. Media reports tend to focus heavily on the more “spectacular” aspects of conflict, such as explosions, shelling, and air strikes. By contrast, our results demonstrate gunshot wounds were the leading contributor to YLDs and YLLs. What do these findings mean? Our results demonstrate the importance of data-driven, epidemiologically sound assessment of conflicts, especially those spanning multiple years. However, it should be noted that our primary goal was to develop a methodology, demonstrated by our calculations with the city of Baghdad, to allow for its use in other conflicts. With more sophisticated methods, epidemiologists might better prevent the most harmful aspects of conflict for civilian populations, might better predict losses in advance of the onset of conflict, and might contribute to health systems in planning for care delivery. Limitations for this study include the possibility for recall bias among the survey participants as well as the possible undercounting of deaths due to injury due to classifying any injuries that did not definitively result in death as YLDs rather than YLLs. Lastly, we did not adjust for changes in the population of Baghdad over the course of the study.

Background Strengthening Evidence base on scHool-based intErventions for pRomoting adolescent health (SEHER) is a multicomponent, whole-school health promotion intervention delivered by a lay counsellor or a teacher in government-run secondary schools in Bihar, India. The objective of this study is to examine the effects of the intervention after two years of follow-up and to evaluate the consistency of the findings observed over time. Methods and findings We conducted a cluster randomised trial in which 75 schools were randomised (1:1:1) to receive the SEHER intervention delivered by a lay counsellor (SEHER Mitra [SM]) or a teacher (Teacher as SEHER Mitra [TSM]), respectively, alongside a standardised, classroom-based life skills Adolescence Education Program (AEP), compared to AEP alone (control group). The trial design was a repeat cross-sectional study. Students enrolled in grade 9 (aged 13–15 years) in the 2015–2016 academic year were exposed to the intervention for two years and the outcome assessment was conducted at three time points─at baseline in June 2015; 8-months follow-up in March 2016, when the students were still in grade 9; and endpoint at 17-months follow-up in December 2016 (when the students were in grade 10), the results of which are presented in this paper. The primary outcome, school climate, was measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Intervention effects were estimated using mixed-effects linear or logistic regression, including a random effect to adjust for within-school clustering, minimisation variables, baseline cluster-level score of the outcome, and sociodemographic characteristics. In total, 15,232 students participated in the 17-month survey. Compared with the control group, the participants in the SM intervention group reported improvements in school climate (adjusted mean difference [aMD] = 7.33; 95% CI: 6.60–8.06; p < 0.001) and most secondary outcomes (depression: aMD = −4.64; 95% CI: −5.83–3.45; p < 0.001; attitude towards gender equity: aMD = 1.02; 95% CI: 0.65–1.40; p < 0.001; frequency of bullying: aMD = −2.77; 95% CI: −3.40 to −2.14; p < 0.001; violence victimisation: odds ratio [OR] = 0.08; 95% CI: 0.04–0.14; p < 0.001; and violence perpetration: OR = 0.16; 95% CI: 0.09–0.29; p < 0.001). There was no evidence of an intervention effect in the TSM group compared with control group. The effects of the lay counsellor–delivered intervention were larger for most outcomes at 17-months follow-up compared with those at 8 months: school climate (effect size [ES; 95% CI] = 2.23 [1.97–2.50] versus 1.88 [1.44–2.32], p < 0.001); depression (ES [95% CI] = −1.19 [−1.56 to −0.82] versus −0.27 [−0.44 to −0.11], p < 0.001); attitude towards gender equity (ES [95% CI] = 0.53 [0.27–0.79] versus 0.23 [0.10–0.36], p < 0.001); bullying (ES [95% CI] = −2.22 [−2.84 to −1.60] versus −0.47 [−0.61 to −0.33], p < 0.001); violence victimisation (OR [95% CI] = 0.08 [0.04–0.14] versus 0.62 [0.46–0.84], p < 0.001); and violence perpetration (OR [95% CI] = 0.16 [0.09–0.29] versus 0.68 [0.48–0.96], p < 0.001), suggesting incremental benefits with an extended intervention. A limitation of the study is that 27% of baseline participants did not complete the 17-month outcome assessment. Conclusions The trial showed that the second-year outcomes were similar to the first-year outcomes, with no effect of the teacher-led intervention and larger benefits on school climate and adolescent health accruing from extending lay counsellor–delivered intervention. Trial registration ClinicalTrials.gov NCT02907125., In an extension of a cluster randomized trial, Sachin Shinde and colleagues investigate the effects of a second year of the SEHER school health promotion intervention on school climate and adolescent health outcomes in Bihar, India., Author summary Why was this study done? Schools are recognised as a critically important platform for promoting adolescent health literacy and healthy behaviours in India. We conducted this study to assess the effects of the SEHER multicomponent school health promotion intervention on adolescent health outcomes after two years of exposure. What did the researchers do and find? We conducted a three-arm cluster randomised controlled trial in 74 government-run secondary schools in the Nalanda district of the state of Bihar in India. The SEHER intervention was delivered either by a lay counsellor or by an existing teacher. The intervention included whole school–, class-, and individual-focused components. Students enrolled in grade 9 (aged 13–15 years) in the 2015–2016 academic year were exposed to the intervention for two years and three rounds of repeated cross-sectional surveys─at baseline in June 2015; 8-months follow-up in March 2016, when the students were still in grade 9; and at 17-months follow-up in December 2016 (when the students were in grade 10). We found that the lay counsellor–delivered intervention, compared with control group, reported improvements in school climate, depression, bullying, attitude towards gender equity, violence victimisation, and violence perpetration. The effect sizes for these outcomes at end of year 2 were larger than at the end of year 1. There was no evidence of an intervention effect of the teacher-delivered intervention at either follow-up. What do these findings mean? Our findings provide compelling evidence of the incremental benefits of a multicomponent school health promotion intervention, when delivered by lay counsellor, on school climate and a range of health and well-being outcomes of adolescents. No effects are seen when the same intervention is delivered by teachers.

Background In low-resource settings where disease burdens remain high and many health facilities lack essentials such as drugs or commodities, functional equipment, and trained personnel, poor quality of care often results and the impact can be profound. In this paper, we systematically quantify the potential gain of addressing quality of care globally using country-level data about antenatal, childbirth, and postnatal care interventions. Methods and findings In this study, we created deterministic models to project health outcomes if quality of care was addressed in a representative sample of 81 low- and middle-income countries (LMICs). First, available data from health facility surveys (e.g., Service Provision Assessment [SPA] and Service Availability and Readiness Assessment [SARA]) conducted 2007–2016 were linked to household surveys (e.g., Demographic and Health Surveys [DHS] and Multiple Indicator Cluster Surveys [MICS]) to estimate baseline coverage for a core subset of 19 maternal and newborn health interventions. Next, models were constructed with the Lives Saved Tool (LiST) using country-specific baseline levels in countries with a linked dataset (n = 17) and sample medians applied as a proxy in countries without linked data. Lastly, these 2016 starting baseline levels were raised to reach targets in 2020 as endline based upon country-specific utilization (e.g., proportion of women who attended 4+ antenatal visits, percentage of births delivered in a health facility) from the latest DHS or MICS population-based reports. Our findings indicate that if high-quality health systems could effectively deliver this subset of evidence-based interventions to mothers and their newborns who are already seeking care, there would be an estimated 28% decrease in maternal deaths, 28% decrease in neonatal deaths, and 22% fewer stillbirths compared to a scenario without any change or improvement in quality of care. Totals of 86,000 (range, 77,800–92,400) maternal and 0.67 million (range, 0.59 million–0.75 million) neonatal lives could be saved, and 0.52 million (range, 0.48 million–0.55 million) stillbirths could be prevented across the 81 countries in the calendar year 2020 when adequate quality care is provided at current levels of utilization. Limitations include the paucity of data to individually assess quality of care for each intervention in all LMICs and the necessary assumption that quality of care being provided among the subset of countries with linked datasets is comparable or representative of LMICs overall. Conclusions Our findings suggest that efforts to close the quality gap would still produce substantial benefits at current levels of access or utilization. With estimated mortality rate declines of 21%–32% on average, gains from this first step would be significant if quality was improved for selected antenatal, intrapartum, and postnatal interventions to benefit pregnant women and newborns seeking care. Interventions provided at or around the time of childbirth are most critical and accounted for 64% of the impact overall estimated in this quality improvement analysis., Victoria Chou and colleagues estimate the implications of poor-quality care for maternal and child health outcomes in low- and middle-income countries., Author summary Why was this study done? In low- and middle-income countries, health systems struggle to provide high-quality medical care to pregnant women and their newborns in need. Delivery of key health interventions is critical to save lives and prevent morbidity and mortality in high-burden settings. The impact of extant or poor quality of care at a population level is poorly understood, and quantifying the benefits of improving quality among those already seeking or accessing care would be a critical first step for prioritization. What did the researchers do and find? To examine the global impact of improvement in the quality of care, we used a linking approach, which combines health facility and population-level survey data to estimate baseline for a subset of important evidence-based interventions. Intervention coverage trends were modeled in 81 countries by setting current levels of reported utilization as the final country-specific targets for 2020. If those seeking medical attention arrived at facilities reimagined with adequate resources and receive high-quality care, our systematic tally indicates that almost one quarter of the maternal deaths, neonatal deaths, and stillbirths would be preventable during the period 2016–2020 if the gaps in quality of care were eliminated. What do these findings mean? Countries and current health systems are far from ensuring that skilled providers with adequate supplies are providing timely and appropriate healthcare to existing populations in need. Our analysis of potential gains quantifies the consequences of these missed opportunities, ranging from the prenatal to postnatal periods. Bolstering the quality of care is an essential checkpoint because efforts to increase utilization will rely on the same health systems where vulnerable populations are presently accessing care. With greater attention focused on tracking country-level progress, more data will hopefully become available to effectively monitor changes in coverage for key maternal and neonatal interventions. As these parameters or inputs are better defined, modeling can contribute to the body of knowledge by offering an informed approach to examine quality of care gaps so that better strategies can be developed to improve health among mothers and their children seeking care in this context.

Background Prospective cohort studies of incident HIV and associated factors among gay, bisexual, and other men who have sex with men (GBMSM) in the United Kingdom are lacking. We report time trends in and factors associated with HIV incidence between 2013 and 2019 among a cohort of GBMSM: the AURAH2 prospective study. Methods and findings Participants were recruited through 1 of 3 sexual health clinics in London and Brighton (July 2013 to April 2016) and self-completed a baseline paper questionnaire and subsequent 4-monthly and annual online questionnaires (March 2015 to March 2018), including information on sociodemographics, lifestyle, health and well-being, HIV status, sexual/HIV-related behaviours, and preexposure prophylaxis and postexposure prophylaxis (PrEP/PEP). Incident HIV was ascertained by linkage with national HIV surveillance data from Public Health England (PHE). We investigated the associations of HIV incidence with (1) baseline factors using mixed-effects Weibull proportional hazard models, unadjusted and adjusted for age, country of birth and ethnicity, sexuality, and education level; and (2) time-updated factors, using mixed-effects Poisson regression models. In total, 1,162 men (mean age 34 years, 82% white, 94% gay, 74% university-educated) were enrolled in the study. Thirty-three HIV seroconversions occurred over 4,618.9 person-years (PY) of follow-up: an overall HIV incidence rate (IR) of 0.71 (95% confidence interval (CI) 0.51 to 1.00) per 100 PY. Incidence declined from 1.47 (95% CI 0.48 to 4.57) per 100 PY in 2013/2014 to 0.25 (95% CI 0.08 to 0.78) per 100 PY in 2018/2019; average annual decline was 0.85-fold (p < 0.001). Baseline factors associated with HIV acquisition included the following: injection drug use (6/38 men who reported injection drug-acquired HIV; unadjusted conditional hazard ratio (HR) 27.96, 95% CI 6.99 to 111.85, p < 0.001), noninjection chemsex-related drug use (13/321; HR 6.45, 95% CI 1.84 to 22.64, p < 0.001), condomless anal sex (CLS) (26/741; HR 3.75, 95% CI 1.31 to 10·74, p = 0.014); higher number of CLS partners (HRs >10 partners [7/57]; 5 to 10 partners [5/60]; and 2 to 4 partners [11/293]: 14.04, 95% CI 4.11 to 47.98; 9.60, 95% CI 2.58 to 35.76; and 4.05, 95% CI 1.29 to 12.72, respectively, p < 0.001); CLS with HIV–positive partners (14/147; HR 6.45, 95% CI 3.15 to 13.22, p < 0.001), versatile CLS role (21/362; HR 6.35, 95% CI 2.18 to 18.51, p < 0.001), group sex (64/500; HR 8.81, 95% CI 3.07 to 25.24, p < 0.001), sex for drugs/money (4/55, HR 3.27, 95% CI 1.14 to 9.38, p = 0.027) (all in previous 3 months); previous 12-month report of a bacterial sexually transmitted infection (STI) diagnoses (21/440; HR 3.95, 95% CI 1.81 to 8.63, p < 0.001), and more than 10 new sexual partners (21/471, HRs 11 to 49, 50 to 99, and >100 new partners: 3.17, 95% CI 1.39 to 7.26; 4.40, 95% CI 1.35 to 14.29; and 4.84, 95% CI 1.05 to 22.4, respectively, p < 0.001). Results were broadly consistent for time-updated analysis (n = 622 men). The study’s main limitation is that men may not be representative of the broader GBMSM population in England. Conclusions We observed a substantial decline in HIV incidence from 2013 to 2019 among GBMSM attending sexual health clinics. Injection drug use, chemsex use, and measures of high-risk sexual behaviour were strongly associated with incident HIV. Progress towards zero new infections could be achieved if combination HIV prevention including Test and Treat strategies and routine commissioning of a PrEP programme continues across the UK and reaches all at-risk populations., Nadia Hanum and colleagues analyze trends in HIV incidence among gay, bisexual, and other Men Who Have Sex with Men attending sexual health clinics in England., Author summary Why was the study done? A decline has been observed in new HIV diagnoses among gay, bisexual, and other men who have sex with men (GBMSM) in the United Kingdom. Internationally, an overall decline in HIV diagnoses and incidence among GBMSM has also been reported in several cities in developed countries such as Australia, the United States, the Netherlands, and some other European countries between 2013 and 2019. To our knowledge, no prospectively followed cohort studies of GBMSM in England have reported trends in HIV incidence in recent years or on factors associated with incident HIV. What did the researches do and find? We estimated trends in HIV incidence between 2013 and 2019 among a cohort of GBMSM attending sexual health clinics, and we found a declining trend. We also assessed factors associated with HIV incidence, and our findings emphasise the importance of awareness of high-risk sexual behaviours and recreational drug use (particularly injection drug use and chemsex-associated drug use) as factors associated with HIV acquisition. Despite observing significant declines in HIV incidence, incidence rates (IRs) remained high among men who reported injection drugs use, chemsex drug use, condomless sex with multiple partners, and group sex. What do these findings mean? Growing evidence shows that the HIV transmission declines may potentially be attributed to the comprehensive control and HIV treatment efforts in the UK. The continuation of intensification of HIV testing, immediate antiretroviral therapy (ART) initiation, the use of condoms, and routine commissioning of a preexposure prophylaxis (PrEP) programme could potentially ensure that the decline in HIV incidence is felt across all groups impacted by the epidemic.

SUMMARY POINTS: (*) The noninferiority design is being adopted in tuberculosis treatment trials to identify regimens that may have practical advantages over current standard therapy (e.g., being shorter, easier to adhere) and thus are more efficient in real-life settings, even while accepting that they might be less effective to a certain degree. (*) This margin of acceptance is called the noninferiority margin, or delta. How narrow or wide the margin should be, and how this translates into acceptable losses and desired gains, is a matter of debate. (*) Noninferiority trials are trials of ‘trade-offs’, in which one has to decide what one can lose in terms of pure efficacy against what one expects to make up in terms of effectiveness, tolerability, deployability, affordability, or else when replacing an existing intervention with a new one. (*) This paper is about the principles behind identifying a ‘meaningful noninferiority margin’—that is, a margin that is meaningful from a statistical, ethical, clinical, and health standpoint. (*) Pragmatic approaches to expressing treatment effects using the number needed to treat (NNT), the reciprocal of the absolute risk reduction, with NNT for one patient to benefit (NNTB) and NNT for one patient to be harmed (NNTH) are useful to understand the implications of outcome definition and find a way to quantify gains and losses. (*) Applying the noninferiority design to pragmatic (effectiveness) trials in addition to efficacy/safety trials would help quantify the trade-offs in real life.

Background Empirical studies and population-level policy simulations show the importance of voluntary medical male circumcision (VMMC) in generalized epidemics. This paper complements available scenario-based studies (projecting costs and outcomes over some policy period, typically spanning decades) by adopting an incremental approach—analyzing the expected consequences of circumcising one male individual with specific characteristics in a specific year. This approach yields more precise estimates of VMMC’s cost-effectiveness and identifies the outcomes of current investments in VMMC (e.g., within a fiscal budget period) rather than of investments spread over the entire policy period. Methods/Findings The model has three components. We adapted the ASSA2008 model, a demographic and epidemiological model of the HIV epidemic in South Africa, to analyze the impact of one VMMC on HIV incidence over time and across the population. A costing module tracked the costs of VMMC and the resulting financial savings owing to reduced HIV incidence over time. Then, we used several financial indicators to assess the cost-effectiveness of and financial return on investments in VMMC. One circumcision of a young man up to age 20 prevents on average over 0.2 HIV infections, but this effect declines steeply with age, e.g., to 0.08 by age 30. Net financial savings from one VMMC at age 20 are estimated at US$617 at a discount rate of 5% and are lower for circumcisions both at younger ages (because the savings occur later and are discounted more) and at older ages (because male circumcision becomes less effective). Investments in male circumcision carry a financial rate of return of up to 14.5% (for circumcisions at age 20). The cost of a male circumcision is refinanced fastest, after 13 y, for circumcisions at ages 20 to 25. Principal limitations of the analysis arise from the long time (decades) over which the effects of VMMC unfold—the results are therefore sensitive to the discount rate applied, and more generally to the future course of the epidemic and of HIV/AIDS-related policies pursued by the government. Conclusions VMMC in South Africa is highly effective in reducing both HIV incidence and the financial costs of the HIV response. The return on investment is highest if males are circumcised between ages 20 and 25, but this return on investment declines steeply with age., Medical male circumcision reduces incidences of HIV. Gorgens and colleagues present a new model that identifies the best age for this treatment, in terms of cost efficiencies and disease incidence., Editors' Summary Background Every year, about 2 million people become infected with HIV, the virus that causes AIDS. Although antiretroviral therapy can keep HIV in check, there is no cure for AIDS. Consequently, prevention of HIV transmission is an important component of efforts to control the AIDS epidemic. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of becoming infected by abstaining from sex, by having only one or a few sexual partners, and by using male or female condoms. In addition, three trials undertaken in sub-Saharan Africa a decade ago showed that male circumcision—the surgical removal of the foreskin, a loose fold of skin that covers the head of the penis—can halve the sexual transmission of HIV from HIV-positive women to HIV-negative men. In 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that individuals living in countries with generalized HIV epidemics (countries where more than 1% of the general population is HIV positive) should be offered voluntary medical male circumcision (VMMC) to help prevent HIV transmission. Why Was This Study Done? In 2011, following several studies that assessed the population-level effectiveness and cost-effectiveness of VMMC scale-up, WHO/UNAIDS set a target of having at least 80% of all men aged 15–49 circumcised in 14 priority countries in Africa by 2015. Good progress towards this target was made, but VMMC scale-up needs further improvement. Scenario-based studies provide estimates of the overall costs and impacts of VMMC policies over the whole policy period, which can span several decades, but policy makers sometimes need to know the returns on investments in VMMC over the current financial year. Here, the researchers use an “incremental” cost-effectiveness approach (one that analyzes the expected consequences of circumcising one male with specific characteristics in a specific year) to provide estimates of the impacts of current VMMC investments and to obtain more precise estimates of VMMC’s cost-effectiveness for HIV prevention in South Africa, a country with a generalized HIV epidemic. What Did the Researchers Do and Find? The researchers developed a mathematical model consisting of three elements: a demographic and epidemiological model of the South African HIV epidemic adapted to analyze the impact of one VMMC on HIV incidence over time and across the population; a module to track the costs of VMMC and financial savings from HIV infections averted by VMMC; and several financial indicators to assess the cost-effectiveness of and financial return on investments in VMMC. Using this model, the researchers estimate that the circumcision of a young man up to age 20 prevents, on average, 0.2 HIV infections, and that the number of infections averted by VMMC declines steeply with age at circumcision. Estimated financial savings from one VMMC at age 20 are US$617 at a discount rate of 5% (discounting translates future costs and benefits into present-day values); VMMC at younger and older ages results in lower financial savings. From a purely financial perspective, circumcisions at age 20 are most effective with a financial return of 14.5% (they are equivalent to a financial investment yielding an interest of 14.5% annually). Finally, the costs of a circumcision are refinanced (covered by reductions in the costs associated with HIV infection) fastest for circumcisions at ages 20–25. What Do These Findings Mean? Because the effects of VMMC unfold over many decades, the accuracy of these findings is likely to be affected by the future course of the AIDS epidemic, by HIV/AIDS policies adopted by the South African government, and by the discount rate applied in the cost-effectiveness analysis. Moreover, some of the assumptions made by the researchers in their model may affect the accuracy of their findings. Overall, however, these findings, which provide estimates of the consequences of current VMMC policies, suggest that VMMC in South Africa (and possibly in settings where a lower proportion of the population is HIV positive) is a highly effective HIV prevention intervention that is cost-saving under many circumstances. These findings also indicate how age at circumcision affects the impacts of circumcision. Specifically, they suggest that the return on investment is highest if males are circumcised between ages 20 and 25 but declines steeply with increasing age. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1002012. Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, information on male circumcision for the prevention of HIV transmission, and personal stories about living with HIV/AIDS Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on how HIV is transmitted, on voluntary medical male circumcision for HIV prevention, and on HIV/AIDS in sub-Saharan Africa; Avert also provides personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including information on voluntary medical male circumcision for HIV prevention UNAIDS provides up-to-information about the AIDS epidemic and detailed information about HIV/AIDS in South Africa The Clearinghouse on Male Circumcision for HIV Prevention provides up-to-date information and resources on male circumcision for HIV prevention

BackgroundIndia has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world's "missing" patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The "cascade of care" is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions.Methods and findingsThe care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India's TB patients. We define the TB cascade as including the following patient populations: total prevalent active TB patients in India, TB patients who reach and undergo evaluation at RNTCP diagnostic facilities, patients successfully diagnosed with TB, patients who start treatment, patients retained to treatment completion, and patients who achieve 1-y recurrence-free survival. We estimate each step of the cascade for 2013 using data from two World Health Organization (WHO) reports (2014-2015), one WHO dataset (2015), and three RNTCP reports (2014-2016). In addition, we conduct three targeted systematic reviews of the scientific literature to identify 39 unique articles published from 2000-2015 that provide additional data on five indicators that help estimate different steps of the TB cascade. We construct separate care cascades for the overall population of patients with active TB and for patients with specific forms of TB-including new smear-positive, new smear-negative, retreatment smear-positive, and multidrug-resistant (MDR) TB. The WHO estimated that there were 2,700,000 (95%CI: 1,800,000-3,800,000) prevalent TB patients in India in 2013. Of these patients, we estimate that 1,938,027 (72%) TB patients were evaluated at RNTCP facilities; 1,629,906 (60%) were successfully diagnosed; 1,417,838 (53%) got registered for treatment; 1,221,764 (45%) completed treatment; and 1,049,237 (95%CI: 1,008,775-1,083,243), or 39%, of 2,700,000 TB patients achieved the optimal outcome of 1-y recurrence-free survival. The separate cascades for different forms of TB highlight different patterns of patient attrition. Pretreatment loss to follow-up of diagnosed patients and post-treatment TB recurrence were major points of attrition in the new smear-positive TB cascade. In the new smear-negative and MDR TB cascades, a substantial proportion of patients who were evaluated at RNTCP diagnostic facilities were not successfully diagnosed. Retreatment smear-positive and MDR TB patients had poorer treatment outcomes than the general TB population. Limitations of our analysis include the lack of available data on the cascade of care in the private sector and substantial uncertainty regarding the 1-y period prevalence of TB in India.ConclusionsIncreasing case detection is critical to improving outcomes in India's TB cascade of care, especially for smear-negative and MDR TB patients. For new smear-positive patients, pretreatment loss to follow-up and post-treatment TB recurrence are considerable points of attrition that may contribute to ongoing TB transmission. Future multisite studies providing more accurate information on key steps in the public sector TB cascade and extension of this analysis to private sector patients may help to better target interventions and resources for TB control in India.

Strengthening civil registration and vital statistics (CVRS) systems in low-income countries is a central component of emerging plans for the post-2015 development agenda [1], and a major investment area for key global health and development funders [2]. A dominant theme in the investment case for CRVS is the potential of such systems to generate valid and timely population data to support sound program planning, management, and evaluation. Can CRVS systems fulfill this promise and produce population data of adequate quality to support policy and program decisions? Few formal studies have addressed this question, and global leaders have called urgently for new evidence to inform the CRVS agenda [3,4]. The PLOS Collection on Real-Time Monitoring of Under-Five Mortality (RMM) contributes to this process by reporting on a seven-year program of work in five countries in sub-Saharan Africa that aimed to develop and test methods for generating annual estimates of under-five mortality, a key measure for health investments, for recent periods. This paper introduces readers to the origins and rationale of the RMM project, describes how it was implemented, and outlines the aims of the PLOS Collection on RMM.

This paper summarises key advances and priorities since the 2011 presentation of the Malaria Eradication Research Agenda (malERA), with a focus on the combinations of intervention tools and strategies for elimination and their evaluation using modelling approaches. With an increasing number of countries embarking on malaria elimination programmes, national and local decisions to select combinations of tools and deployment strategies directed at malaria elimination must address rapidly changing transmission patterns across diverse geographic areas. However, not all of these approaches can be systematically evaluated in the field. Thus, there is potential for modelling to investigate appropriate ‘packages’ of combined interventions that include various forms of vector control, case management, surveillance, and population-based approaches for different settings, particularly at lower transmission levels. Modelling can help prioritise which intervention packages should be tested in field studies, suggest which intervention package should be used at a particular level or stratum of transmission intensity, estimate the risk of resurgence when scaling down specific interventions after local transmission is interrupted, and evaluate the risk and impact of parasite drug resistance and vector insecticide resistance. However, modelling intervention package deployment against a heterogeneous transmission background is a challenge. Further validation of malaria models should be pursued through an iterative process, whereby field data collected with the deployment of intervention packages is used to refine models and make them progressively more relevant for assessing and predicting elimination outcomes., Richard Steketee and colleagues propose an updated research agenda for combination interventions and modelling in malaria elimination and eradication.

In a double-blind randomized controlled trial, Esther Atukunda and colleagues evaluated whether sublingual misoprostol administered to women in labor was non-inferior to intramuscular oxytocin in preventing postpartum hemorrhage and reducing blood loss. Please see later in the article for the Editors' Summary, Background Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 µg, for prevention of PPH during active management of labor. Methods and Findings We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 µg of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss ≥500 ml within 24 h of delivery. Secondary outcomes included measured blood loss ≥1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, p, Editors' Summary Background Every year, worldwide nearly 290,000 women die during pregnancy or labor or during the first six weeks after giving birth (the postpartum period). Almost all of these “maternal” deaths occur in low- or middle-income countries, and most are caused by a handful of preventable or treatable conditions—postpartum hemorrhage (severe bleeding from the uterus [womb] within 24 hours of childbirth), post-delivery infections, unsafe abortion, obstructive (difficult) labor, and blood pressure disorders during pregnancy. The leading cause of maternal deaths worldwide is postpartum hemorrhage, which is responsible for 25%–30% of all maternal deaths. Postpartum hemorrhage can be prevented by giving the mother an intramuscular injection of oxytocin, a hormone that stimulates uterine contractions and limits uterine bleeding, immediately after her child is born. Why Was This Study Done? Unfortunately, oxytocin needs to be kept cool, which limits its use in low- and middle-income countries, and, until recently, it was thought that only trained personnel could give intramuscular injections. Consequently, administration of misoprostol, a synthetic prostaglandin that has effects similar to those of oxytocin, has been proposed as an alternative way to prevent postpartum hemorrhage in resource-limited settings. Misoprostol is stable at room temperature, and because it can be given sublingually (beneath the tongue), it acts very quickly. However, the comparative efficacy of sublingual misoprostol and intramuscular oxytocin for the prevention of postpartum hemorrhage has not been established. Here, the researchers undertake a double-blinded, double-dummy randomized controlled non-inferiority trial to compare sublingual misoprostol and intramuscular oxytocin for the prevention of postpartum hemorrhage in Uganda, a country where there are more than 5,500 maternal deaths every year. A randomized controlled trial compares the outcomes of individuals assigned to different interventions through the play of chance. In a double-blinded trial, neither the researchers nor the participants know who is receiving which intervention. In this particular trial, double-blinding is achieved by giving a dummy (placebo) sublingual pill to the women assigned to the oxytocin group and a dummy injection to the women assigned to the misoprostol group, as well as their assigned treatments. A non-inferiority trial investigates whether one treatment is not worse than another treatment. What Did the Researchers Do and Find? The researchers measured blood loss over the first 24 hours after delivery in 1,140 women admitted to a regional referral hospital in Uganda. The women were given either sublingual misoprostol or intramuscular oxytocin at the currently recommended doses, along with matching placebos, immediately after the birth of their child. Postpartum hemorrhage (defined as the loss of more than 500 ml of blood within 24 hours of delivery; the trial's primary outcome) occurred in 28.6% and 17.4% of the women in the misoprostol and oxytocin groups, respectively (an absolute risk difference of 11.2%). Severe postpartum hemorrhage (loss of more than 1,000 ml of blood within 24 hours of delivery) occurred in 3.6% and 2.7% of participants in the misoprostol and oxytocin groups, respectively, but this difference was not statistically significant (it could have happened by chance). On average, women given misoprostol had lost slightly more blood by two and 24 hours after delivery than those given oxytocin. There were no significant differences between the groups in terms of death, the need for blood transfusion, or the use of additional drugs to prevent blood loss, but women given misoprostol experienced shivering and fever more often than those given oxytocin. What Do These Findings Mean? In their study protocol, the researchers specified that sublingual misoprostol would be deemed non-inferior to intramuscular oxytocin if the absolute risk difference for postpartum hemorrhage between the misoprostol and oxytocin treatment groups was less than 6% (the “non-inferiority” margin). These findings therefore indicate that sublingual misoprostol given at the recommended dose is inferior to intramuscular oxytocin for the prevention of postpartum hemorrhage in women undergoing an uncomplicated birth at a regional referral hospital in Uganda. Although several aspects of this study may affect the accuracy and generalizability of its findings (for example, women at high risk of birth complications were excluded from the study), the researchers conclude that oxytocin should remain the preferred agent for the prevention of postpartum hemorrhage where it is available. However, they note, sublingual misoprostol remains important for the prevention of postpartum hemorrhage where oxytocin is unavailable or its administration is not feasible. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001752. The United Nations Children's Fund (UNICEF) provides information on maternal mortality; “Trends in Maternal Mortality: 1990 to 2013” is a recent WHO/UNICEF/UNFPA/World Bank publication that provides up-to-date information on maternal mortality worldwide The World Health Organization provides information on maternal health (in several languages) The Postpartum Hemorrhage Prevention and Treatment Website provides a forum for information sharing and learning between organizations and individuals working on the prevention and treatment of postpartum hemorrhage in developing countries; the website includes basic information about postpartum hemorrhage and links to additional resources “Veil of Tears” contains personal stories (including stories about postpartum hemorrhage) from Afghanistan about loss in childbirth “Maternal Death: The Avoidable Crisis” is a briefing paper published by Médecins Sans Frontières in 2012 More information about this trial is available