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Background: Rotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger.Methods and Findings: From August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy.Conclusions: Rotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development.Trial Registration: ClinicalTrials.gov NCT02145000. [ABSTRACT FROM AUTHOR]

Background: The psychological health of female sex workers (FSWs) has emerged as a major public health concern in many low- and middle-income countries (LMICs). Key risk factors include poverty, low education, violence, alcohol and drug use, human immunodeficiency virus (HIV), and stigma and discrimination. This systematic review and meta-analysis aimed to quantify the prevalence of mental health problems among FSWs in LMICs, and to examine associations with common risk factors.Method and Findings: The review protocol was registered with PROSPERO, number CRD42016049179. We searched 6 electronic databases for peer-reviewed, quantitative studies from inception to 26 April 2020. Study quality was assessed with the Centre for Evidence-Based Management (CEBM) Critical Appraisal Tool. Pooled prevalence estimates were calculated for depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal behaviour. Meta-analyses examined associations between these disorders and violence, alcohol/drug use, condom use, and HIV/sexually transmitted infection (STI). A total of 1,046 studies were identified, and 68 papers reporting on 56 unique studies were eligible for inclusion. These were geographically diverse (26 countries), representing all LMIC regions, and included 24,940 participants. All studies were cross-sectional and used a range of measurement tools; none reported a mental health intervention. Of the 56 studies, 14 scored as strong quality, 34 scored as moderate, and 8 scored as weak. The average age of participants was 28.9 years (age range: 11-64 years), with just under half (46%) having up to primary education or less. The pooled prevalence rates for mental disorders among FSWs in LMICs were as follows: depression 41.8% (95% CI 35.8%-48.0%), anxiety 21.0% (95% CI: 4.8%-58.4%), PTSD 19.7% (95% CI 3.2%-64.6%), psychological distress 40.8% (95% CI 20.7%-64.4%), recent suicide ideation 22.8% (95% CI 13.2%-36.5%), and recent suicide attempt 6.3% (95% CI 3.4%-11.4%). Meta-analyses found significant associations between violence experience and depression, violence experience and recent suicidal behaviour, alcohol use and recent suicidal behaviour, illicit drug use and depression, depression and inconsistent condom use with clients, and depression and HIV infection. Key study limitations include a paucity of longitudinal studies (necessary to assess causality), non-random sampling of participants by many studies, and the use of different measurement tools and cut-off scores to measure mental health problems and other common risk factors.Conclusions: In this study, we found that mental health problems are highly prevalent among FSWs in LMICs and are strongly associated with common risk factors. Study findings support the concept of overlapping vulnerabilities and highlight the urgent need for interventions designed to improve the mental health and well-being of FSWs. [ABSTRACT FROM AUTHOR]

Olivia Oxlade and co-authors introduce a Collection on tuberculosis preventive therapy in people with HIV infection. [ABSTRACT FROM AUTHOR]

The article focuses on the regulatory pathways for dengue vaccines, which was discussed at the meetings of the Developing Countries' Vaccine Regulators Network (DCVRN) and one with several pharmaceutical companies. It mentions that regulatory agencies should address issues including interference among vaccine serotypes as dengue vaccine should be tetravalent in nature. It adds that safety assessment should be undertaken to address potential risk of the said vaccines.

Background: Scaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid-rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization's (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa.Methods and Findings: The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness-implementation randomized trial comparing 3 optimized strategies for delivering 3HP-facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid-to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (≥11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes.Conclusions: 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion.Trial Registration: ClinicalTrials.gov NCT03934931. [ABSTRACT FROM AUTHOR]

Background: We aimed to estimate multimorbidity trajectories and quantify socioeconomic inequalities based on childhood and adulthood socioeconomic position (SEP) in the risks and rates of multimorbidity accumulation across adulthood.Methods and Findings: Participants from the UK 1946 National Survey of Health and Development (NSHD) birth cohort study who attended the age 36 years assessment in 1982 and any one of the follow-up assessments at ages 43, 53, 63, and 69 years (N = 3,723, 51% males). Information on 18 health conditions was based on a combination of self-report, biomarkers, health records, and prescribed medications. We estimated multimorbidity trajectories and delineated socioeconomic inequalities (based on childhood and adulthood social class and highest education) in multimorbidity at each age and in longitudinal trajectories. Multimorbidity increased with age (0.7 conditions at 36 years to 3.7 at 69 years). Multimorbidity accumulation was nonlinear, accelerating with age at the rate of 0.08 conditions/year (95% CI 0.07 to 0.09, p < 0.001) at 36 to 43 years to 0.19 conditions/year (95% CI 0.18 to 0.20, p < 0.001) at 63 to 69 years. At all ages, the most socioeconomically disadvantaged had 1.2 to 1.4 times greater number of conditions on average compared to the most advantaged. The most disadvantaged by each socioeconomic indicator experienced an additional 0.39 conditions (childhood social class), 0.83 (adult social class), and 1.08 conditions (adult education) at age 69 years, independent of all other socioeconomic indicators. Adverse adulthood SEP was associated with more rapid accumulation of multimorbidity, resulting in 0.49 excess conditions in partly/unskilled compared to professional/intermediate individuals between 63 and 69 years. Disadvantaged childhood social class, independently of adulthood SEP, was associated with accelerated multimorbidity trajectories from age 53 years onwards. Study limitations include that the NSHD cohort is composed of individuals of white European heritage only, and findings may not be generalizable to the non-white British population of the same generation and did not account for other important dimensions of SEP such as income and wealth.Conclusions: In this study, we found that socioeconomically disadvantaged individuals have earlier onset and more rapid accumulation of multimorbidity resulting in widening inequalities into old age, with independent contributions from both childhood and adulthood SEP. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma.Methods and Findings: We conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer-in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations.Conclusions: We observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required. [ABSTRACT FROM AUTHOR]

Background: Overconsumption of energy from food is a major contributor to the high rates of overweight and obesity in many populations. There is growing evidence that interventions that target the food environment may be effective at reducing energy intake. The current study aimed to estimate the effect of decreasing the proportion of higher energy (kcal) foods, with and without reducing portion size, on energy purchased in worksite cafeterias.Methods and Findings: This stepped-wedge randomised controlled trial (RCT) evaluated 2 interventions: (i) availability: replacing higher energy products with lower energy products; and (ii) size: reducing the portion size of higher energy products. A total of 19 cafeterias were randomised to the order in which they introduced the 2 interventions. Availability was implemented first and maintained. Size was added to the availability intervention. Intervention categories included main meals, sides, cold drinks, snacks, and desserts. The study setting was worksite cafeterias located in distribution centres for a major United Kingdom supermarket and lasted for 25 weeks (May to November 2019). These cafeterias were used by 20,327 employees, mainly (96%) in manual occupations. The primary outcome was total energy (kcal) purchased from intervention categories per day. The secondary outcomes were energy (kcal) purchased from nonintervention categories per day, total energy purchased per day, and revenue. Regression models showed an overall reduction in energy purchased from intervention categories of -4.8% (95% CI -7.0% to -2.7%), p < 0.001 during the availability intervention period and a reduction of -11.5% (95% CI -13.7% to -9.3%), p < 0.001 during the availability plus size intervention period, relative to the baseline. There was a reduction in energy purchased of -6.6% (95% CI -7.9% to -5.4%), p < 0.001 during the availability plus size period, relative to availability alone. Study limitations include using energy purchased as the primary outcome (and not energy consumed) and the availability only of transaction-level sales data per site (and not individual-level data).Conclusions: Decreasing the proportion of higher energy foods in cafeterias reduced the energy purchased. Decreasing portion sizes reduced this further. These interventions, particularly in combination, may be effective as part of broader strategies to reduce overconsumption of energy from food in out-of-home settings.Trial Registration: ISRCTN registry ISRCTN87225572. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials.Methods and Findings: We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children.Conclusions: Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes.Methods and Findings: We searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] -$81 to $622, p = 0.12) and was $2,568 in HICs (-$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (-34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications.Conclusions: The body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease. [ABSTRACT FROM AUTHOR]

Background: Among people living with HIV (PLHIV), more flexible and sensitive tuberculosis (TB) screening tools capable of detecting both symptomatic and subclinical active TB are needed to (1) reduce morbidity and mortality from undiagnosed TB; (2) facilitate scale-up of tuberculosis preventive therapy (TPT) while reducing inappropriate prescription of TPT to PLHIV with subclinical active TB; and (3) allow for differentiated HIV-TB care.Methods and Findings: We used Botswana XPRES trial data for adult HIV clinic enrollees collected during 2012 to 2015 to develop a parsimonious multivariable prognostic model for active prevalent TB using both logistic regression and random forest machine learning approaches. A clinical score was derived by rescaling final model coefficients. The clinical score was developed using southern Botswana XPRES data and its accuracy validated internally, using northern Botswana data, and externally using 3 diverse cohorts of antiretroviral therapy (ART)-naive and ART-experienced PLHIV enrolled in XPHACTOR, TB Fast Track (TBFT), and Gugulethu studies from South Africa (SA). Predictive accuracy of the clinical score was compared with the World Health Organization (WHO) 4-symptom TB screen. Among 5,418 XPRES enrollees, 2,771 were included in the derivation dataset; 67% were female, median age was 34 years, median CD4 was 240 cells/μL, 189 (7%) had undiagnosed prevalent TB, and characteristics were similar between internal derivation and validation datasets. Among XPHACTOR, TBFT, and Gugulethu cohorts, median CD4 was 400, 73, and 167 cells/μL, and prevalence of TB was 5%, 10%, and 18%, respectively. Factors predictive of TB in the derivation dataset and selected for the clinical score included male sex (1 point), ≥1 WHO TB symptom (7 points), smoking history (1 point), temperature >37.5°C (6 points), body mass index (BMI) <18.5kg/m2 (2 points), and severe anemia (hemoglobin <8g/dL) (3 points). Sensitivity using WHO 4-symptom TB screen was 73%, 80%, 94%, and 94% in XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively, but increased to 88%, 87%, 97%, and 97%, when a clinical score of ≥2 was used. Negative predictive value (NPV) also increased 1%, 0.3%, 1.6%, and 1.7% in XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively, when the clinical score of ≥2 replaced WHO 4-symptom TB screen. Categorizing risk scores into low (<2), moderate (2 to 10), and high-risk categories (>10) yielded TB prevalence of 1%, 1%, 2%, and 6% in the lowest risk group and 33%, 22%, 26%, and 32% in the highest risk group for XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively. At clinical score ≥2, the number needed to screen (NNS) ranged from 5.0 in Gugulethu to 11.0 in XPHACTOR. Limitations include that the risk score has not been validated in resource-rich settings and needs further evaluation and validation in contemporary cohorts in Africa and other resource-constrained settings.Conclusions: The simple and feasible clinical score allowed for prioritization of sensitivity and NPV, which could facilitate reductions in mortality from undiagnosed TB and safer administration of TPT during proposed global scale-up efforts. Differentiation of risk by clinical score cutoff allows flexibility in designing differentiated HIV-TB care to maximize impact of available resources. [ABSTRACT FROM AUTHOR]

Background: Evidence-based guidance for starting ages of screening for first-degree relatives (FDRs) of patients with prostate cancer (PCa) to prevent stage III/IV or fatal PCa is lacking in current PCa screening guidelines. We aimed to provide evidence for risk-adapted starting age of screening for relatives of patients with PCa.Methods and Findings: In this register-based nationwide cohort study, all men (aged 0 to 96 years at baseline) residing in Sweden who were born after 1931 along with their fathers were included. During the follow-up (1958 to 2015) of 6,343,727 men, 88,999 were diagnosed with stage III/IV PCa or died of PCa. The outcomes were defined as the diagnosis of stage III/IV PCa or death due to PCa, stratified by age at diagnosis. Using 10-year cumulative risk curves, we calculated risk-adapted starting ages of screening for men with different constellations of family history of PCa. The 10-year cumulative risk of stage III/IV or fatal PCa in men at age 50 in the general population (a common recommended starting age of screening) was 0.2%. Men with ≥2 FDRs diagnosed with PCa reached this screening level at age 41 (95% confidence interval (CI): 39 to 44), i.e., 9 years earlier, when the youngest one was diagnosed before age 60; at age 43 (41 to 47), i.e., 7 years earlier, when ≥2 FDRs were diagnosed after age 59, which was similar to that of men with 1 FDR diagnosed before age 60 (41 to 45); and at age 45 (44 to 46), when 1 FDR was diagnosed at age 60 to 69 and 47 (46 to 47), when 1 FDR was diagnosed after age 69. We also calculated risk-adapted starting ages for other benchmark screening ages, such as 45, 55, and 60 years, and compared our findings with those in the guidelines. Study limitations include the lack of genetic data, information on lifestyle, and external validation.Conclusions: Our study provides practical information for risk-tailored starting ages of PCa screening based on nationwide cancer data with valid genealogical information. Our clinically relevant findings could be used for evidence-based personalized PCa screening guidance and supplement current PCa screening guidelines for relatives of patients with PCa. [ABSTRACT FROM AUTHOR]

Background: Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline.Methods and Findings: The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF.Conclusions: In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF. [ABSTRACT FROM AUTHOR]

Background: In 2017, an estimated 14 million cases of Plasmodium vivax malaria were reported from Asia, Central and South America, and the Horn of Africa. The clinical burden of vivax malaria is largely driven by its ability to form dormant liver stages (hypnozoites) that can reactivate to cause recurrent episodes of malaria. Elimination of both the blood and liver stages of the parasites ("radical cure") is required to achieve a sustained clinical response and prevent ongoing transmission of the parasite. Novel treatment options and point-of-care diagnostics are now available to ensure that radical cure can be administered safely and effectively. We quantified the global economic cost of vivax malaria and estimated the potential cost benefit of a policy of radical cure after testing patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency.Methods and Findings: Estimates of the healthcare provider and household costs due to vivax malaria were collated and combined with national case estimates for 44 endemic countries in 2017. These provider and household costs were compared with those that would be incurred under 2 scenarios for radical cure following G6PD screening: (1) complete adherence following daily supervised primaquine therapy and (2) unsupervised treatment with an assumed 40% effectiveness. A probabilistic sensitivity analysis generated credible intervals (CrIs) for the estimates. Globally, the annual cost of vivax malaria was US$359 million (95% CrI: US$222 to 563 million), attributable to 14.2 million cases of vivax malaria in 2017. From a societal perspective, adopting a policy of G6PD deficiency screening and supervision of primaquine to all eligible patients would prevent 6.1 million cases and reduce the global cost of vivax malaria to US$266 million (95% CrI: US$161 to 415 million), although healthcare provider costs would increase by US$39 million. If perfect adherence could be achieved with a single visit, then the global cost would fall further to US$225 million, equivalent to $135 million in cost savings from the baseline global costs. A policy of unsupervised primaquine reduced the cost to US$342 million (95% CrI: US$209 to 532 million) while preventing 2.1 million cases. Limitations of the study include partial availability of country-level cost data and parameter uncertainty for the proportion of patients prescribed primaquine, patient adherence to a full course of primaquine, and effectiveness of primaquine when unsupervised.Conclusions: Our modelling study highlights a substantial global economic burden of vivax malaria that could be reduced through investment in safe and effective radical cure achieved by routine screening for G6PD deficiency and supervision of treatment. Novel, low-cost interventions for improving adherence to primaquine to ensure effective radical cure and widespread access to screening for G6PD deficiency will be critical to achieving the timely global elimination of P. vivax. [ABSTRACT FROM AUTHOR]

Background: Pregnant and postpartum women living with HIV (WLWH) need support for HIV and maternal child health (MCH) care, which could be provided using short message service (SMS).Methods and Findings: We compared 2-way (interactive) and 1-way SMS messaging to no SMS in a 3-arm randomized trial in 6 MCH clinics in Kenya. Messages were developed using the Health Belief Model and Social Cognitive Theory; HIV messages were integrated into an existing MCH SMS platform. Intervention participants received visit reminders and prespecified weekly SMS on antiretroviral therapy (ART) adherence and MCH, tailored to their characteristics and timing. Two-way participants could message nurses as needed. Clinic attendance, viral load (VL), and infant HIV results were abstracted from program records. Primary outcomes were viral nonsuppression (VL ≥1,000 c/ml), on-time clinic attendance, loss to follow-up from clinical care, and infant HIV-free survival. Among 824 pregnant women randomized between November 2015 and May 2017, median age was 27 years, gestational age was 24.3 weeks, and time since initiation of ART was 1.0 year. During follow-up to 2 years postpartum, 9.8% of 3,150 VL assessments and 19.6% of women were ever nonsuppressed, with no significant difference in 1-way versus control (11.2% versus 9.6%, adjusted risk ratio (aRR) 1.02 [95% confidence interval (CI) 0.67 to 1.54], p = 0.94) or 2-way versus control (8.5% versus 9.6%, aRR 0.80 [95% CI 0.52 to 1.23], p = 0.31). Median ART adherence and incident ART resistance did not significantly differ by arm. Overall, 88.9% (95% CI 76.5 to 95.7) of visits were on time, with no significant differences between arms (88.2% in control versus 88.6% in 1-way and 88.8% in 2-way). Incidence of infant HIV or death was 3.01/100 person-years (py), with no significant difference between arms; risk of infant HIV infection was 0.94%. Time to postpartum contraception was significantly shorter in the 2-way arm than control. Study limitations include limited ability to detect improvement due to high viral suppression and visit attendance and imperfect synchronization of SMS reminders to clinic visits.Conclusions: Integrated HIV/MCH messaging did not improve HIV outcomes but was associated with improved initiation of postpartum contraception. In programs where most women are virally suppressed, targeted SMS informed by VL data may improve effectiveness. Rigorous evaluation remains important to optimize mobile health (mHealth) interventions.Trial Registration: ClinicalTrials.gov number NCT02400671. [ABSTRACT FROM AUTHOR]

Background: Glucose-6-phosphate dehydrogenase (G6PD) activity is dependent upon G6PD genotype and age of the red blood cell (RBC) population, with younger RBCs having higher activity. Peripheral parasitemia with Plasmodium spp. induces hemolysis, replacing older RBCs with younger cells with higher G6PD activity. This study aimed to assess whether G6PD activity varies between individuals with and without malaria or a history of malaria.Methods and Findings: Individuals living in the Chittagong Hill Tracts of Bangladesh were enrolled into 3 complementary studies: (i) a prospective, single-arm clinical efficacy trial of patients (n = 175) with uncomplicated malaria done between 2014 and 2015, (ii) a cross-sectional survey done between 2015 and 2016 (n = 999), and (iii) a matched case-control study of aparasitemic individuals with and without a history of malaria done in 2020 (n = 506). G6PD activity was compared between individuals with and without malaria diagnosed by microscopy, rapid diagnostic test (RDT), or polymerase chain reaction (PCR), and in aparasitemic participants with and without a history of malaria. In the cross-sectional survey and clinical trial, 15.5% (182/1,174) of participants had peripheral parasitemia detected by microscopy or RDT, 3.1% (36/1,174) were positive by PCR only, and 81.4% (956/1,174) were aparasitemic. Aparasitemic individuals had significantly lower G6PD activity (median 6.9 U/g Hb, IQR 5.2-8.6) than those with peripheral parasitemia detected by microscopy or RDT (7.9 U/g Hb, IQR 6.6-9.8, p < 0.001), but G6PD activity similar to those with parasitemia detected by PCR alone (submicroscopic parasitemia) (6.1 U/g Hb, IQR 4.8-8.6, p = 0.312). In total, 7.7% (14/182) of patients with malaria had G6PD activity < 70% compared to 25.0% (248/992) of participants with submicroscopic or no parasitemia (odds ratio [OR] 0.25, 95% CI 0.14-0.44, p < 0.001). In the case-control study, the median G6PD activity was 10.3 U/g Hb (IQR 8.8-12.2) in 253 patients with a history of malaria and 10.2 U/g Hb (IQR 8.7-11.8) in 253 individuals without a history of malaria (p = 0.323). The proportion of individuals with G6PD activity < 70% was 11.5% (29/253) in the cases and 15.4% (39/253) in the controls (OR 0.7, 95% CI 0.41-1.23, p = 0.192). Limitations of the study included the non-contemporaneous nature of the clinical trial and cross-sectional survey.Conclusions: Patients with acute malaria had significantly higher G6PD activity than individuals without malaria, and this could not be accounted for by a protective effect of G6PD deficiency. G6PD-deficient patients with malaria may have higher than expected G6PD enzyme activity and an attenuated risk of primaquine-induced hemolysis compared to the risk when not infected. [ABSTRACT FROM AUTHOR]

Background: Large-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays.Methods and Findings: For this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA2DS2-VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m2, 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p < 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p < 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation.Conclusions: Age, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF.Trial Registration: Registry IRAS ID 97753 Health Research Authority (HRA), United Kingdom. [ABSTRACT FROM AUTHOR]

Background: MB66 film is a multipurpose prevention technology (MPT) product with monoclonal antibodies (mAbs) against HIV-1 (VRC01-N) and HSV-1 and 2 (HSV8-N). The mAbs were produced by transient expression in Nicotiana benthamiana (N). We conducted a Phase I clinical trial to assess the safety, pharmacokinetics (PK), and ex vivo efficacy of single and repeated doses of MB66 when used intravaginally.Methods and Findings: The clinical trial enrolled healthy reproductive-aged, sexually abstinent women. In Segment A, 9 women received a single MB66 film which was inserted into the vaginal posterior fornix by a clinician. In Segment B, 29 women were randomly assigned to MB66 (Active) or Placebo film groups and were instructed to insert 1 film vaginally for 7 consecutive days. Visits and clinical sampling occurred predose and at various time points after single and repeated film doses. The primary endpoint was number of adverse events (AEs) Grade 2 or higher related to product use. Secondary endpoints included film dissolution rate, Nugent score (a Gram stain scoring system to diagnose bacterial vaginosis), vaginal pH, post-use survey results, cytokine concentrations in cervicovaginal lavage (CVL) specimens (assessed by Luminex assay), mAb concentrations in vaginal fluid collected from 4 sites (assessed by ELISA), and HIV and HSV neutralization activity of CVL samples ex vivo (assessed by TZM-bl and plaque reduction assay, respectively). The product was generally safe and well tolerated, with no serious AEs recorded in either segment. The AEs in this study were primarily genitourinary in nature with the most commonly reported AE being asymptomatic microscopic hematuria. There were no differences in vaginal pH or Nugent scores or significant increases in levels of proinflammatory cytokines for up to 7 days after film insertion in either segment or between Active and Placebo groups. Acceptability and willingness to use the product were judged to be high by post-use surveys. Concentrations of VRC01-N and HSV8-N in vaginal secretions were assessed over time to generate pharmacokinetic curves. Antibody levels peaked 1 hour postdosing with Active film (median: 35 μg/mL) and remained significantly elevated at 24 hours post first and seventh film (median: 1.8 μg/mL). Correcting for sample dilution (1:20), VRC01-N concentrations ranged from 36 to 700 μg/mL at the 24-hour time point, greater than 100-fold the IC50 for VRC01 (0.32 μg/mL); HSV8-N concentrations ranged from 80 to 601 μg/mL, well above the IC50 of 0.1 μg/m. CVL samples collected 24 hours after MB66 insertion significantly neutralized both HIV-1 and HSV-2 ex vivo. Study limitations include the small size of the study cohort, and the fact that no samples were collected between 24 hours and 7 days for pharmacokinetic evaluation.Conclusions: Single and repeated intravaginal applications of MB66 film were safe, well tolerated, and acceptable. Concentrations and ex vivo bioactivity of both mAbs in vaginal secretions were significantly elevated and thus could provide protection for at least 24 hours postdose. However, further research is needed to evaluate the efficacy of MB66 film in women at risk for HIV and HSV infection. Additional antibodies could be added to this platform to provide protection against other sexually transmitted infections (STIs) and contraception.Trial Registration: ClinicalTrials.gov NCT02579083. [ABSTRACT FROM AUTHOR]

Introduction: Inequalities in maternal and newborn health persist in many high-income countries, including for women of refugee background. The Bridging the Gap partnership programme in Victoria, Australia, was designed to find new ways to improve the responsiveness of universal maternity and early child health services for women and families of refugee background with the codesign and implementation of iterative quality improvement and demonstration initiatives. One goal of this 'whole-of-system' approach was to improve access to antenatal care. The objective of this paper is to report refugee women's access to hospital-based antenatal care over the period of health system reforms.Methods and Findings: The study was designed using an interrupted time series analysis using routinely collected data from two hospital networks (four maternity hospitals) at 6-month intervals during reform activity (January 2014 to December 2016). The sample included women of refugee background and a comparison group of Australian-born women giving birth over the 3 years. We describe the proportions of women of refugee background (1) attending seven or more antenatal visits and (2) attending their first hospital visit at less than 16 weeks' gestation compared over time and to Australian-born women using logistic regression analyses. In total, 10% of births at participating hospitals were to women of refugee background. Refugee women were born in over 35 countries, and at one participating hospital, 40% required an interpreter. Compared with Australian-born women, women of refugee background were of similar age at the time of birth and were more likely to be having their second or subsequent baby and have four or more children. At baseline, 60% of refugee-background women and Australian-born women attended seven or more antenatal visits. Similar trends of improvement over the 6-month time intervals were observed for both populations, increasing to 80% of women at one hospital network having seven or more visits at the final data collection period and 73% at the other network. In contrast, there was a steady decrease in the proportion of women having their first hospital visit at less than 16 weeks' gestation, which was most marked for women of refugee background. Using an interrupted time series of observational data over the period of improvement is limited compared with using a randomisation design, which was not feasible in this setting.Conclusions: Accurate ascertainment of 'harder-to-reach' populations and ongoing monitoring of quality improvement initiatives are essential to understand the impact of system reforms. Our findings suggest that improvement in total antenatal visits may have been at the expense of recommended access to public hospital antenatal care within 16 weeks of gestation. [ABSTRACT FROM AUTHOR]

Background: Hypertension, together with obesity, is a leading cause of mortality and disability. Whilst metabolic surgery offers remission of several metabolic comorbidities, the effect for patients with hypertension remains controversial. The objective of the present study was to evaluate the effect of metabolic surgery on cardiovascular events and mortality on patients with morbid obesity (body mass index [BMI] ≥ 35 kg/m2) and hypertension.Methods and Findings: We conducted a matched cohort study of 11,863 patients with morbid obesity and pharmacologically treated hypertension operated on with metabolic surgery and a matched non-operated-on control group of 26,199 subjects with hypertension (matched by age, sex, and area of residence) of varied matching ratios from 1:1 to 1:9, using data from the Scandinavian Obesity Surgery Register (SOReg), the Swedish National Patient Registers (NPR) for in-hospital and outpatient care, the Swedish Prescribed Drug Register, and Statistics Sweden. The main outcome was major adverse cardiovascular event (MACE), defined as first occurrence of acute coronary syndrome (ACS) event, cerebrovascular event, fatal cardiovascular event, or unattended sudden cardiac death. The mean age in the study group was 52.1 ± 7.46 years, with 65.8% being women (n = 7,810), and mean BMI was 41.9 ± 5.43 kg/m2. MACEs occurred in 379 operated-on patients (3.2%) and 1,125 subjects in the control group (4.5%). After adjustment for duration of hypertension, comorbidities, and education, a reduction in risk was seen in the metabolic surgery group (adjusted hazard ratio [HR] 0.73, 95% confidence intervals [CIs] 0.64-0.84, P < 0.001). The surgery group had lower risk for ACS events (adjusted HR 0.52, 95% CI 0.41-0.66, P < 0.001) and a tendency towards lower risk for cerebrovascular events (adjusted HR 0.81, 95% CI 0.63-1.01, P = 0.060) compared with controls. The main limitations with the study were the lack of information on BMI and history of smoking in the control group and the nonrandomised study design.Conclusion: Metabolic surgery on patients with morbid obesity and pharmacologically treated hypertension was associated with lower risk for MACEs and all-cause mortality compared with age- and sex-matched controls with hypertension from the general population. [ABSTRACT FROM AUTHOR]

Background: As of 16 May 2020, more than 4.5 million cases and more than 300,000 deaths from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. Reliable estimates of mortality from SARS-CoV-2 infection are essential for understanding clinical prognosis, planning healthcare capacity, and epidemic forecasting. The case-fatality ratio (CFR), calculated from total numbers of reported cases and reported deaths, is the most commonly reported metric, but it can be a misleading measure of overall mortality. The objectives of this study were to (1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data and (2) infer estimates of SARS-CoV-2 mortality adjusted for biases and examine the CFR, the symptomatic case-fatality ratio (sCFR), and the infection-fatality ratio (IFR) in different geographic locations.Method and Findings: We developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases: preferential ascertainment of severe cases and right-censoring of mortality. We fitted the transmission model to surveillance data from Hubei Province, China, and applied the same model to six regions in Europe: Austria, Bavaria (Germany), Baden-Württemberg (Germany), Lombardy (Italy), Spain, and Switzerland. In Hubei, the baseline estimates were as follows: CFR 2.4% (95% credible interval [CrI] 2.1%-2.8%), sCFR 3.7% (3.2%-4.2%), and IFR 2.9% (2.4%-3.5%). Estimated measures of mortality changed over time. Across the six locations in Europe, estimates of CFR varied widely. Estimates of sCFR and IFR, adjusted for bias, were more similar to each other but still showed some degree of heterogeneity. Estimates of IFR ranged from 0.5% (95% CrI 0.4%-0.6%) in Switzerland to 1.4% (1.1%-1.6%) in Lombardy, Italy. In all locations, mortality increased with age. Among individuals 80 years or older, estimates of the IFR suggest that the proportion of all those infected with SARS-CoV-2 who will die ranges from 20% (95% CrI 16%-26%) in Switzerland to 34% (95% CrI 28%-40%) in Spain. A limitation of the model is that count data by date of onset are required, and these are not available in all countries.Conclusions: We propose a comprehensive solution to the estimation of SARS-Cov-2 mortality from surveillance data during outbreaks. The CFR is not a good predictor of overall mortality from SARS-CoV-2 and should not be used for evaluation of policy or comparison across settings. Geographic differences in IFR suggest that a single IFR should not be applied to all settings to estimate the total size of the SARS-CoV-2 epidemic in different countries. The sCFR and IFR, adjusted for right-censoring and preferential ascertainment of severe cases, are measures that can be used to improve and monitor clinical and public health strategies to reduce the deaths from SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Yuming Guo and colleagues discuss the research by Teslya et al that highlights the importance of personal preventative measures in avoiding a second wave of the COVID-19 epidemic. [ABSTRACT FROM AUTHOR]

Background: Current models of HIV service delivery, with frequent facility visits, have led to facility congestion, patient and healthcare provider dissatisfaction, and suboptimal quality of services and retention in care. The Zambian urban adherence club (AC) is a health service innovation designed to improve on-time drug pickup and retention in HIV care through off-hours facility access and pharmacist-led group drug distribution. Similar models of differentiated service delivery (DSD) have shown promise in South Africa, but observational analyses of these models are prone to bias and confounding. We sought to evaluate the effectiveness and implementation of ACs in Zambia using a more rigorous study design.Methods and Findings: Using a matched-pair cluster randomized study design (ClinicalTrials.gov: NCT02776254), 10 clinics were randomized to intervention (5 clinics) or control (5 clinics). At each clinic, between May 19 and October 27, 2016, a systematic random sample was assessed for eligibility (HIV+, age ≥ 14 years, on ART >6 months, not acutely ill, CD4 count not <200 cells/mm3) and willingness to participate in an AC. Clinical and antiretroviral drug pickup data were obtained through the existing electronic medical record. AC meeting attendance data were collected at intervention facilities prospectively through October 28, 2017. The primary outcome was time to first late drug pickup (>7 days late). Intervention effect was estimated using unadjusted Kaplan-Meier survival curves and a Cox proportional hazards model to derive an adjusted hazard ratio (aHR). Medication possession ratio (MPR) and implementation outcomes (adoption, acceptability, appropriateness, feasibility, and fidelity) were additionally evaluated as secondary outcomes. Baseline characteristics were similar between 571 intervention and 489 control participants with respect to median age (42 versus 41 years), sex (62% versus 66% female), median time since ART initiation (4.8 versus 5.0 years), median CD4 count at study enrollment (506 versus 533 cells/mm3), and baseline retention (53% versus 55% with at least 1 late drug pickup in previous 12 months). The rate of late drug pickup was lower in intervention participants compared to control participants (aHR 0.26, 95% CI 0.15-0.45, p < 0.001). Median MPR was 100% in intervention participants compared to 96% in control participants (p < 0.001). Although 18% (683/3,734) of AC group meeting visits were missed, on-time drug pickup (within 7 days) still occurred in 51% (350/683) of these missed visits through alternate means (use of buddy pickup or early return to the facility). Qualitative evaluation suggests that the intervention was acceptable to both patients and providers. While patients embraced the convenience and patient-centeredness of the model, preference for traditional adherence counseling and need for greater human resources influenced intervention appropriateness and feasibility from the provider perspective. The main limitations of this study were the small number of clusters, lack of viral load data, and relatively short follow-up period.Conclusions: ACs were found to be an effective model of service delivery for reducing late ART drug pickup among HIV-infected adults in Zambia. Drug pickup outside of group meetings was relatively common and underscores the need for DSD models to be flexible and patient-centered if they are to be effective.Trial Registration: ClinicalTrials.gov NCT02776254. [ABSTRACT FROM AUTHOR]

Background: Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs.Methods and Findings: We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.Conclusions: We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.Trial Registration: ClinicalTrials.gov Identifier: NCT02811835, NCT01331668. [ABSTRACT FROM AUTHOR]

Background: International Sustainable Development Goals (SDGs) for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In African populations, infant immunisation has been fundamental to reducing incident infections in children, but overall population prevalence of chronic hepatitis B (CHB) infection remains high. In high-prevalence populations, adult catch-up vaccination has sometimes been deployed, but an alternative Test and Treat (T&T) approach could be used as an intervention to interrupt transmission. Universal T&T has not been previously evaluated as a population intervention for HBV infection, despite high-profile data supporting its success with human immunodeficiency virus (HIV).Methods and Findings: We set out to investigate the relationship between prevalence of HBV infection and exposure in Africa, undertaking a systematic literature review in November 2019. We identified published seroepidemiology data representing the period 1995-2019 from PubMed and Web of Science, including studies of adults that reported prevalence of both hepatitis B surface antigen (HBsAg; prevalence of HBV infection) and antibody to hepatitis B core antigen (anti-HBc; prevalence of HBV exposure). We identified 96 studies representing 39 African countries, with a median cohort size of 370 participants and a median participant age of 34 years. Using weighted linear regression analysis, we found a strong relationship between the prevalence of infection (HBsAg) and exposure (anti-HBc) (R2 = 0.45, p < 0.001). Region-specific differences were present, with estimated CHB prevalence in Northern Africa typically 30% to 40% lower (p = 0.007) than in Southern Africa for statistically similar exposure rates, demonstrating the need for intervention strategies to be tailored to individual settings. We applied a previously published mathematical model to investigate the effect of interventions in a high-prevalence setting. The most marked and sustained impact was projected with a T&T strategy, with a predicted reduction of 33% prevalence by 20 years (95% CI 30%-37%) and 62% at 50 years (95% CI 57%-68%), followed by routine neonatal vaccination and prevention of mother to child transmission (PMTCT; at 100% coverage). In contrast, the impact of catch-up vaccination in adults had a negligible and transient effect on population prevalence. The study is constrained by gaps in the published data, such that we could not model the impact of antiviral therapy based on stratification by specific clinical criteria and our model framework does not include explicit age-specific or risk-group assumptions regarding force of transmission.Conclusions: The unique data set collected in this study highlights how regional epidemiology data for HBV can provide insights into patterns of transmission, and it provides an evidence base for future quantitative research into the most effective local interventions. In combination with robust neonatal immunisation programmes, ongoing PMTCT efforts, and the vaccination of high-risk groups, diagnosing and treating HBV infection is likely to be of most impact in driving advances towards elimination targets at a population level. [ABSTRACT FROM AUTHOR]

Background: The health complications experienced by women having undergone female genital mutilation/cutting (FGM/C) are a source of growing concern to healthcare workers globally as forced displacement and migration from countries with high rates of this practice increases. In this systematic review and meta-analysis, we investigate the association between FGM/C and painful gynecologic and obstetric complications in women affected by the practice.Methods and Findings: We performed a comprehensive literature search from inception to December 19, 2019 of Ovid MEDLINE, Ovid EMBASE, The Cochrane Library (Wiley), and POPLINE (prior to its retirement) for studies mentioning FGM/C. Two reviewers independently screened studies reporting prevalences of painful gynecologic and obstetric sequelae resulting from FGM/C. Random effects models were used to estimate pooled odds ratios (ORs) for outcomes obtained from cross-sectional, cohort, and case-control designs. Subgroup analysis was performed to assess and control for effect differences introduced by study design. Validated appraisal tools were utilized to assess quality and risk of bias. Our study was registered with PROSPERO. Two reviewers independently screened 6,666 abstracts. Of 559 full-text studies assessed for eligibility, 116 met eligibility criteria, which included studies describing the incidence or prevalence of painful sequelae associated with FGM/C. Pooled analyses after adjustment for study design found that FGM/C was associated with dyspareunia (6,283 FGM/C and 3,382 non-FGM/C participants; pooled OR: 2.47; 95% confidence interval [CI]: 1.45-4.21; I2: 79%; p-value < 0.01), perineal tears (4,898 FGM/C and 4,229 non-FGM/C participants; pooled OR: 2.63; 95% CI: 1.35-5.11; I2: 67%; p-value = 0.01), dysuria (3,686 FGM/C and 3,482 non-FGM/C participants; pooled OR: 1.43; 95% CI: 1.17-1.75; I2: 0%; p-value = 0.01), episiotomy (29,341 FGM/C and 39,260 non-FGM/C participants; pooled OR: 1.89; 95% CI: 1.26-2.82; I2: 96%; p-value < 0.01), and prolonged labor (7,516 FGM/C and 8,060 non-FGM/C participants; pooled OR: 2.04; 95% CI: 1.27-3.28; I2: 90%; p-value < 0.01). There was insufficient evidence to conclude that there was an association between FGM/C and dysmenorrhea (7,349 FGM/C and 4,411 non-FGM/C participants; pooled OR: 1.66; 95% CI: 0.97-2.84; I2: 86%; p-value = 0.06), urinary tract infection (4,493 FGM/C and 3,776 non-FGM/C participants; pooled OR: 2.11; 95% CI: 0.80-5.54; I2: 90%; p-value = 0.10), instrumental delivery (5,176 FGM/C and 31,923 non-FGM/C participants; pooled OR: 1.18; 95% CI: 0.78-1.79; I2: 63%; p-value = 0.40), or cesarean delivery (34,693 FGM/C and 46,013 non-FGM/C participants; pooled OR: 1.51; 95% CI: 0.99-2.30; I2: 96%; p-value = 0.05). Studies generally met quality assurance criteria. Limitations of this study include the largely suboptimal quality of studies.Conclusions: In this study, we observed that specific painful outcomes are significantly more common in participants with FGM/C. Women who underwent FGM/C were around twice as likely as non-FGM/C women to experience dyspareunia, perineal tears, prolonged labor, and episiotomy. These data indicate that providers must familiarize themselves with the unique health consequences of FGM/C, including accurate diagnosis, pain management, and obstetric planning.Review Protocol Registration: The review protocol registration in PROSPERO is CRD42018115848. [ABSTRACT FROM AUTHOR]

Background: Adolescent girls in humanitarian settings are especially vulnerable as their support systems are often disrupted. More than 20 years of violence in the Democratic Republic of the Congo (DRC) has weakened the health system, resulting in poor sexual and reproductive health (SRH) outcomes for women. Little evidence on adolescent contraceptive use in humanitarian settings is available. CARE, International Rescue Committee (IRC), and Save the Children, in collaboration with the Reproductive Health Access, Information and Services in Emergencies (RAISE) Initiative, Columbia University, have supported the Ministry of Health (MOH) since 2011 to provide good quality contraceptive services in public health facilities in conflict-affected North and South Kivu. In this study, we analyzed contraceptive use among sexually active young women aged 15-24 in the health zones served by the partners' programs.Methods and Findings: The partners conducted cross-sectional population-based surveys in program areas of North and South Kivu using two-stage cluster sampling in six health zones in July-August 2016 and 2017. Twenty-five clusters were selected in each health zone, 22 households in each cluster, and one woman of reproductive age (15-49 years) was randomly selected in each household. This manuscript presents results from a secondary data analysis for 1,022 women aged 15-24 who reported ever having sex: 326 adolescents (15-19 years) and 696 young women (20-24 years), 31.7% (95% confidence interval [CI] 29.5-34.1), of whom were displaced at least once in the previous five years. Contraceptive knowledge was high, with over 90% of both groups able to name at least one modern contraceptive method. Despite this high knowledge, unmet need for contraception was also high: 31.7% (95%CI 27.9-35.7) among 15-19-year-olds and 40.1% (95% CI 37.1-43.1, p = 0.001) among 20-24-year-olds. Current modern contraceptive use (16.5%, 95% CI 14.7-18.4) was similar in both age groups, the majority of whom received their method from a supported health facility. Among current users, more than half of 15-19-year-olds were using a long-acting reversible contraceptive (LARC; 51.7%, 95% CI 41.1-61.9) compared to 36.5% of 20-24-year-olds (95% CI 29.6-43.9, p = 0.02). Age, younger age of sexual debut, having some secondary education, being unmarried, and having begun childbearing were associated with modern contraceptive use. The main limitations of our study are related to insecurity in three health zones that prevented access to some villages, reducing the representativeness of our data, and our defining sexually active women as those who have ever had sex.Conclusions: In this study, to our knowledge one of the first to measure contraceptive prevalence among adolescents in a humanitarian setting, we observed that adolescent and young women will use modern contraception, including long-acting methods. Meaningful engagement of adolescent and young women would likely contribute to even better outcomes. Creating an enabling environment by addressing gender and social norms, however, is key to reducing stigma and meeting the demand for contraception of young women. As we continue to build such supportive environments, we can see that they will use effective contraception when contraceptive services, including short- and long-acting methods, are available, even in protracted crisis settings. [ABSTRACT FROM AUTHOR]

Background: Information regarding the prevalence of infectious diseases (IDs) in child and adolescent refugees in Europe is scarce. Here, we evaluate a standardized ID screening protocol in a cohort of unaccompanied refugee minors (URMs) in a municipal region of southwest Germany.Methods and Findings: From January 2016 to December 2017, we employed a structured questionnaire to screen a cohort of 890 URMs. Collecting sociodemographic information and medical history, we also performed a standardized diagnostics panel, including complete blood count, urine status, microbial stool testing, tuberculosis (TB) screening, and serologies for hepatitis B virus (HBV) and human immunodeficiency virus (HIV). The mean age was 16.2 years; 94.0% were male, and 93.6% originated from an African country. The most common health complaints were dental problems (66.0%). The single most frequent ID was scabies (14.2%). Of the 776 URMs originating from high-prevalence countries, 7.7% and 0.4% tested positive for HBV and HIV, respectively. Nineteen pathogens were detected in a total of 119 stool samples (16.0% positivity), with intestinal schistosomiasis being the most frequent pathogen (6.7%). Blood eosinophilia proved to be a nonspecific criterion for the detection of parasitic infections. Active pulmonary TB was identified in 1.7% of URMs screened. Of note, clinical warning symptoms (fever, cough >2 weeks, and weight loss) were insensitive parameters for the identification of patients with active TB. Study limitations include the possibility of an incomplete eosinophilia workup (as no parasite serologies or malaria diagnostics were performed), as well as the inherent selection bias in our cohort because refugee populations differ across Europe.Conclusions: Our study found that standardized ID screening in a URM cohort was practicable and helped collection of relevant patient data in a thorough and time-effective manner. However, screening practices need to be ameliorated, especially in relation to testing for parasitic infections. Most importantly, we found that only a minority of infections were able to be detected clinically. This underscores the importance of active surveillance of IDs among refugees. [ABSTRACT FROM AUTHOR]

Background: Temporary labor migration is an increasingly important mode of migration that generates substantial remittance flows, but raises important concerns for migrant well-being. The migration and health literature has seen a growing call for longitudinal, binational surveys that compare migrants to relevant non-migrant counterfactual groups in the sending country, in order to answer the basic question "Is migration good for health?" This study compares the health of male international migrants, internal migrants, and non-migrants using a unique representative panel survey of the Matlab subdistrict of Bangladesh.Methods and Findings: A cohort of 5,072 respondents born 1958-1992 were interviewed in 1996-1997, and reinterviewed in 2012-2014. Extensive migrant follow-up yielded a 92% reinterview rate. We explored health and income outcomes for respondents who at the time of the follow-up interview were current international migrants (n = 790), returned international migrants (n = 209), internal migrants (n = 1,260), and non-migrants (n = 2,037). Compared to non-migrants, current international migrants were younger (mean 32.9 years versus 35.8 years), had more schooling (7.6 years versus 5.8 years), and were more likely to have an international migrant father (9.7% versus 4.0%) or brother (49.1% versus 30.3%). We estimated multivariate ordinary least squares and logistic regression models controlling for a wide range of control variables measured as far back as 1982. Results show that current international migrants had substantially better health status on factors that likely relate to self-selection such as grip strength and self-rated health. Current international migrants had no excess risk of injury in the past 12 months compared to non-migrants (adjusted mean risk = 6.0% versus 9.3%, p = 0.084). Compared to non-migrants, current international migrants had roughly twice the risk of overweight/obesity (adjusted mean risk = 51.7% versus 23.3%, p < 0.001), obesity (6.9% versus 3.4%, p = 0.012), and stage 1 or higher hypertension (13.0% versus 7.0%, p = 0.014). Compared to internal migrants, current international migrants had significantly higher levels of overweight/obesity (adjusted mean risk = 51.7% versus 37.7%, p < 0.001). Current international migrants showed above average levels of depressive symptoms on a 12-item standardized short-form Center for Epidemiologic Studies Depression Scale (+0.220 SD, 95% CI 0.098-0.342), significantly higher than internal migrants (-0.028 SD, 95% CI -0.111, 0.055; p < 0.001). Depressive symptoms differed significantly from those reported by non-migrants when restricting to items on negative emotions (international migrant score = 0.254 SD, non-migrant score = 0.056 SD, p = 0.004). Key limitations include the descriptive nature of the analysis, the use of both in-person and phone survey data for international migrants, the long recall period for occupational and mental health risk measures, and the coverage of a single out-migration area of origin.Conclusions: In this study, we observed that international migrants had comparable or lower injury and mortality risks compared to respondents remaining in Bangladesh, due in part to the high risks present in Bangladesh. International migrants also showed higher levels of self-rated health and physical strength, reflective of positive self-selection into migration. They had substantially higher risks of overweight/obesity, hypertension, and depression. Negative health impacts may reflect the effects of both harsh migration conditions and assimilation into host population conditions. Our results suggest the need for bilateral cooperation to improve the health of guest workers. [ABSTRACT FROM AUTHOR]

Background: This randomised controlled trial (RCT) aims to compare 6-week posttreatment outcomes of an Integrative Adapt Therapy (IAT) to a Cognitive Behavioural Therapy (CBT) on common mental health symptoms and adaptive capacity amongst refugees from Myanmar. IAT is grounded on psychotherapeutic elements specific to the refugee experience.Methods and Findings: We conducted a single-blind RCT (October 2017 -May 2019) with Chin (39.3%), Kachin (15.7%), and Rohingya (45%) refugees living in Kuala Lumpur, Malaysia. The trial included 170 participants receiving six 45-minute weekly sessions of IAT (97.6% retention, 4 lost to follow-up) and 161 receiving a multicomponent CBT also involving six 45-minute weekly sessions (96.8% retention, 5 lost to follow-up). Participants (mean age: 30.8 years, SD = 9.6) had experienced and/or witnessed an average 10.1 types (SD = 5.9, range = 1-27) of traumatic events. We applied a single-blind design in which independent assessors of pre- and posttreatment indices were masked in relation to participants' treatment allocation status. Primary outcomes were symptom scores of Post Traumatic Stress Disorder (PTSD), Complex PTSD (CPTSD), Major Depressive Disorder (MDD), the 5 scales of the Adaptive Stress Index (ASI), and a measure of resilience (the Connor-Davidson Resilience Scale [CDRS]). Compared to CBT, an intention-to-treat analysis (n = 331) at 6-week posttreatment follow-up demonstrated greater reductions in the IAT arm for all common mental disorder (CMD) symptoms and ASI domains except for ASI-3 (injustice), as well as increases in the resilience scores. Adjusted average treatment effects assessing the differences in posttreatment scores between IAT and CBT (with baseline scores as covariates) were -0.08 (95% CI: -0.14 to -0.02, p = 0.012) for PTSD, -0.07 (95% CI: -0.14 to -0.01) for CPTSD, -0.07 for MDD (95% CI: -0.13 to -0.01, p = 0.025), 0.16 for CDRS (95% CI: 0.06-0.026, p ≤ 0.001), -0.12 (95% CI: -0.20 to -0.03, p ≤ 0.001) for ASI-1 (safety/security), -0.10 for ASI-2 (traumatic losses; 95% CI: -0.18 to -0.02, p = 0.02), -0.03 for ASI-3 (injustice; (95% CI: -0.11 to 0.06, p = 0.513), -0.12 for ASI-4 (role/identity disruptions; 95% CI: -0.21 to -0.04, p ≤ 0.001), and -0.18 for ASI-5 (existential meaning; 95% CI: -0.19 to -0.05, p ≤ 0.001). Compared to CBT, the IAT group had larger effect sizes for all indices (except for resilience) including PTSD (IAT, d = 0.93 versus CBT, d = 0.87), CPTSD (d = 1.27 versus d = 1.02), MDD (d = 1.4 versus d = 1.11), ASI-1 (d = 1.1 versus d = 0.85), ASI-2 (d = 0.81 versus d = 0.66), ASI-3 (d = 0.49 versus d = 0.42), ASI-4 (d = 0.86 versus d = 0.67), and ASI-5 (d = 0.72 versus d = 0.53). No adverse events were recorded for either therapy. Limitations include a possible allegiance effect (the authors inadvertently conveying disproportionate enthusiasm for IAT in training and supervision), cross-over effects (counsellors applying elements of one therapy in delivering the other), and the brief period of follow-up.Conclusions: Compared to CBT, IAT showed superiority in improving mental health symptoms and adaptative stress from baseline to 6-week posttreatment. The differences in scores between IAT and CBT were modest and future studies conducted by independent research teams need to confirm the findings.Trial Registration: The study is registered under Australian New Zealand Clinical Trials Registry (ANZCTR) (http://www.anzctr.org.au/). The trial registration number is: ACTRN12617001452381. [ABSTRACT FROM AUTHOR]

Background: During August 2017-January 2018, more than 700,000 forcibly displaced Rohingyas crossed into Cox's Bazar, Bangladesh. In response to measles and diphtheria cases, first documented in September and November 2017, respectively, vaccination campaigns targeting children <15 years old were mobilized during September 2017-March 2018. However, in a rapidly evolving emergency situation, poor sanitation, malnutrition, overcrowding, and lack of access to safe water and healthcare can increase susceptibility to infectious diseases, particularly among children. We aimed to estimate population immunity to vaccine-preventable diseases (VPDs) after vaccination activities in the camps to identify any remaining immunity gaps among Rohingya children.Methods and Findings: We conducted a cross-sectional serologic and vaccination coverage survey in Nayapara Registered Refugee Camp ("Nayapara") and makeshift settlements (MSs) April 28, 2018 to May 31, 2018, among 930 children aged 6 months to 14 years. MSs are informal, self-settled areas with a population of more than 850,000, the majority of whom arrived after August 2017, whereas Nayapara is a registered camp and has better infrastructure than MSs, including provision of routine immunization services. Households were identified using simple random sampling (SRS) in Nayapara and multistage cluster sampling in MSs (because household lists were unavailable). Dried blood spots (DBSs) were collected to estimate seroprotection against measles, rubella, diphtheria, and tetanus, using Luminex multiplex bead assay (MBA). Caregiver interviews assessed vaccination campaign participation using vaccination card or recall. In Nayapara, 273 children aged 1 to 6 years participated; 46% were female and 88% were registered refugees. In MSs, 358 children aged 1 to 6 years and 299 children aged 7 to 14 years participated; 48% of all children in MSs were female, and none were registered refugees. In Nayapara, estimated seroprotection among 1- to 6-year-olds was high for measles, rubella, diphtheria, and tetanus (91%-98%; 95% confidence interval [CI] 87%-99%); children >6 years were not assessed. In MSs, measles seroprotection was similarly high among 1- to 6-year-olds and 7- to 14-year-olds (91% [95% CI 86%-94%] and 99% [95% CI 96%-100%], respectively, p < 0.001). Rubella and diphtheria seroprotection in MSs were significantly lower among 1- to 6-year-olds (84% [95% CI 79%-88%] and 63% [95% CI 56%-70%]) compared to 7- to 14-year-olds (96% [95% CI 90%-98%] and 77% [95% CI 69%-84%]) (p < 0.001). Tetanus seroprevalence was similar among 1- to 6-year-olds and 7- to 14-year-olds (76% [95% CI 69%-81%] and 84% [95% CI 77%-89%], respectively; p = 0.07). Vaccination campaign coverage was consistent with seroprotection in both camps. However, nonresponse, the main limitation of the study, may have biased the seroprotection and campaign coverage results.Conclusions: In this study, we observed that despite multiple vaccination campaigns, immunity gaps exist among children in MSs, particularly for diphtheria, which requires serial vaccinations to achieve maximum protection. Therefore, an additional tetanus-diphtheria campaign may be warranted in MSs to address these remaining immunity gaps. Rapid scale-up and strengthening of routine immunization services to reach children and to deliver missed doses to older children is also critically needed to close immunity gaps and prevent future outbreaks. [ABSTRACT FROM AUTHOR]

Background: We performed a cross-sectional survey in April-May 2018 among Rohingya in Cox's Bazar, Bangladesh, to assess polio immunity and inform vaccination strategies.Methods and Findings: Rohingya children aged 1-6 years (younger group) and 7-14 years (older group) were selected using multi-stage cluster sampling in makeshift settlements and simple random sampling in Nayapara registered camp. Surveyors asked parents/caregivers if the child received any oral poliovirus vaccine (OPV) in Myanmar and, for younger children, if the child received vaccine in any of the 5 campaigns delivering bivalent OPV (serotypes 1 and 3) conducted during September 2017-April 2018 in Cox's Bazar. Dried blood spot (DBS) specimens were tested for neutralizing antibodies to poliovirus types 1, 2, and 3 in 580 younger and 297 older children. Titers ≥ 1:8 were considered protective. Among 632 children (335 aged 1-6 years, 297 aged 7-14 years) enrolled in the study in makeshift settlements, 51% were male and 89% had arrived after August 9, 2017. Among 245 children (all aged 1-6 years) enrolled in the study in Nayapara, 54% were male and 10% had arrived after August 9, 2017. Among younger children, 74% in makeshift settlements and 92% in Nayapara received >3 bivalent OPV doses in campaigns. Type 1 seroprevalence was 85% (95% CI 80%-89%) among younger children and 91% (95% CI 86%-95%) among older children in makeshift settlements, and 92% (88%-95%) among younger children in Nayapara. Type 2 seroprevalence was lower among younger children than older children in makeshift settlements (74% [95% CI 68%-79%] versus 97% [95% CI 94%-99%], p < 0.001), and was 69% (95% CI 63%-74%) among younger children in Nayapara. Type 3 seroprevalence was below 75% for both age groups and areas. The limitations of this study are unknown routine immunization history and poor retention of vaccination cards.Conclusions: Younger Rohingya children had immunity gaps to all 3 polio serotypes and should be targeted by future campaigns and catch-up routine immunization. DBS collection can enhance the reliability of assessments of outbreak risk and vaccination strategy impact in emergency settings. [ABSTRACT FROM AUTHOR]

Background: The European Society of Cardiology guidelines recommend (Class IA) single-time-point screening for atrial fibrillation (AF) using pulse palpation. The role of pulse palpation for AF detection has not been validated against electrocardiogram (ECG) recordings. We aimed to study the validity of AF screening using self-pulse palpation compared with an ECG recording conducted at the same time using a handheld ECG 3 times a day for 2 weeks.Methods and Findings: In this cross-sectional screening study, patients 65 years of age and older attending 4 primary care centers (PCCs) outside Stockholm County were invited to take part in AF screening from July 2017 to December 2018. Patients were included irrespective of their reason for visiting the PCC. Handheld intermittent ECGs 3 times per day were offered to patients without AF for a period of 2 weeks, and patients were instructed in how to take their own pulse at the same time. A total of 1,010 patients (mean age 73 years, 61% female, with an average CHA2DS2-VASc score 2.9) participated in the study, and 27 (2.7%, 95% CI 1.8%-3.9%) new cases of AF were detected. Anticoagulants (ACs) could be initiated in 26 (96%, 95% CI 81%-100%) of these cases. A total of 53,782 simultaneous ECG recordings and pulse measurements were registered. AF was verified in 311 ECG recordings, of which the pulse was palpated as irregular in 77 recordings (25%, 95% CI 20%-30% sensitivity per measurement occasion). Of the 27 AF cases, 15 cases felt an irregular pulse on at least one occasion (56%, 95% CI 35%-75% sensitivity per individual). 187 individuals without AF felt an irregular pulse on at least one occasion. The specificity per measurement occasion and per individual was (98%, 95% CI 98%-98%) and (81%, 95% CI 78%-83%), respectively.Conclusions: AF screening using self-pulse palpation 3 times daily for 2 weeks has lower sensitivity compared with simultaneous intermittent ECG. Thus, it may be better to screen for AF using intermittent ECG without stepwise screening using pulse palpation. A limitation of this model could be the reduced availability of handheld ECG recorders in primary care centers. [ABSTRACT FROM AUTHOR]

Drawing on experience gained from ongoing research in Mali, this paper describes practical ethical challenges relating to the achievement of valid consent in genomic epidemiology. [ABSTRACT FROM AUTHOR]

In a Collection Review, Richard Hayes and colleagues discuss metrics for assessing progress in control of the HIV/AIDS epidemic in the context of prior disease control programmes. [ABSTRACT FROM AUTHOR]

The article describes an international collaboration program between the University of Toronto and East African surgical communities through the Ptolemy Project, a developed model of electronic access to medical literature for surgeons in developing countries. The university's Office of International Surgery has provided hand-on training on using electronic media to surgeons. Satisfaction of participants has been measured by an ongoing series of surveys. Potential barriers to use Ptolemy are given.

The article focuses on the prevention of mother-to-child-transmission (MTCT) of HIV-1. The rate of MTCT without specific intervention and with an extended time of breast feeding is given. Experiments on passive immunization have indicated that antibodies can protect against HIV-1 infection in animal models. A paper published in "PLoS Medicine"addresses the question of whether human anti-HIV monoclonal antibodies might be useful in South Africa as reagents to prevent MTCT of subtype C viruses.

Background: Quantifying the effects of climate change on the entomological and epidemiological components of vector-borne diseases is an essential part of climate change research, but evidence for such effects remains scant, and predictions rely largely on extrapolation of statistical correlations. We aimed to develop a mechanistic model to test whether recent increases in temperature in the Mana Pools National Park of the Zambezi Valley of Zimbabwe could account for the simultaneous decline of tsetse flies, the vectors of human and animal trypanosomiasis.Methods and Findings: The model we developed incorporates the effects of temperature on mortality, larviposition, and emergence rates and is fitted to a 27-year time series of tsetse caught from cattle. These catches declined from an average of c. 50 flies per animal per afternoon in 1990 to c. 0.1 in 2017. Since 1975, mean daily temperatures have risen by c. 0.9°C and temperatures in the hottest month of November by c. 2°C. Although our model provided a good fit to the data, it cannot predict whether or when extinction will occur.Conclusions: The model suggests that the increase in temperature may explain the observed collapse in tsetse abundance and provides a first step in linking temperature to trypanosomiasis risk. If the effect at Mana Pools extends across the whole of the Zambezi Valley, then transmission of trypanosomes is likely to have been greatly reduced in this warm low-lying region. Conversely, rising temperatures may have made some higher, cooler, parts of Zimbabwe more suitable for tsetse and led to the emergence of new disease foci. [ABSTRACT FROM AUTHOR]

Background: China has witnessed a rapid increase of cesarean section (CS) rates in recent years. Several non-clinical factors have been cited as contributing to this trend including maternal request and perceived convenience. We aimed to assess preferences for mode of delivery and reasons for preferences for CS in China to inform the development of future interventions to mitigate unnecessary CSs, which are those performed in the absence of medical indications.Methods and Findings: We conducted a mixed-methods systematic review and included longitudinal, cross-sectional, and qualitative studies in mainland China, Hong Kong, and Taiwan that investigated preferences for mode of delivery among women and family members and health professionals, and the reasons underlying such preferences. We searched MEDLINE/PubMed, Embase, CINAHL, POPLINE, PsycINFO, Global Health Library, and one Chinese database (CNKI) using a combination of the key terms 'caesarean section', 'preference', 'choice', 'knowledge', 'attitude', 'culture', 'non-clinical factors', and 'health professionals-patient relations' between 1990 and 2018 without language restriction. Meta-analysis of quantitative studies and meta-synthesis of qualitative studies were applied. We included 66 studies in this analysis: 47 quantitative and 19 qualitative. For the index pregnancy, the pooled proportions of preference for CS reported by women in longitudinal studies were 14% in early or middle pregnancy (95% CI 12%-17%) and 21% in late pregnancy (95% CI 15%-26%). In cross-sectional studies, the proportions were 17% in early or middle pregnancy (95% CI 14%-20%), 22% in late pregnancy (95% CI 18%-25%), and 30% postpartum (95% CI 19%-40%). Women's preferences for CS were found to rise as pregnancy progressed (preference change across longitudinal studies: mean difference 7%, 95% CI 1%-13%). One longitudinal study reported that the preference for CS among women's partners increased from 8% in late pregnancy to 17% in the immediate postpartum period. In addition, 18 quantitative studies revealed that some pregnant women, ranging from 4% to 34%, did not have a straightforward preference for a mode of delivery, even in late pregnancy. The qualitative meta-synthesis found that women's perceptions of CS as preferable were based on prioritising the baby's and woman's health and appeared to intensify through interactions with the health system. Women valued the convenience of bypassing labour because of fear of pain, antagonistic relations with providers, and beliefs of deteriorating quality of care during labour and vaginal birth, fostering the feeling that CS was the safest option. Health professionals' preference for CS was influenced by financial drivers and malpractice fears. This review has some limitations, including high heterogeneity (despite subgroup and sensitivity analysis) in the quantitative analysis, and the potential for over-reporting of women's preferences for CS in the qualitative synthesis (due to some included studies only including women who requested CS).Conclusions: Despite a minority of women expressing a preference for CS, individual, health system, and socio-cultural factors converge, contributing to a high CS rate in mainland China, Hong Kong, and Taiwan. In order to reduce unnecessary CSs, interventions need to address all these non-clinical factors and concerns.Systematic Review Registry: Prospero CRD42016036596. [ABSTRACT FROM AUTHOR]

Background: Policies to mitigate climate change by reducing greenhouse gas (GHG) emissions can yield public health benefits by also reducing emissions of hazardous co-pollutants, such as air toxics and particulate matter. Socioeconomically disadvantaged communities are typically disproportionately exposed to air pollutants, and therefore climate policy could also potentially reduce these environmental inequities. We sought to explore potential social disparities in GHG and co-pollutant emissions under an existing carbon trading program-the dominant approach to GHG regulation in the US and globally.Methods and Findings: We examined the relationship between multiple measures of neighborhood disadvantage and the location of GHG and co-pollutant emissions from facilities regulated under California's cap-and-trade program-the world's fourth largest operational carbon trading program. We examined temporal patterns in annual average emissions of GHGs, particulate matter (PM2.5), nitrogen oxides, sulfur oxides, volatile organic compounds, and air toxics before (January 1, 2011-December 31, 2012) and after (January 1, 2013-December 31, 2015) the initiation of carbon trading. We found that facilities regulated under California's cap-and-trade program are disproportionately located in economically disadvantaged neighborhoods with higher proportions of residents of color, and that the quantities of co-pollutant emissions from these facilities were correlated with GHG emissions through time. Moreover, the majority (52%) of regulated facilities reported higher annual average local (in-state) GHG emissions since the initiation of trading. Neighborhoods that experienced increases in annual average GHG and co-pollutant emissions from regulated facilities nearby after trading began had higher proportions of people of color and poor, less educated, and linguistically isolated residents, compared to neighborhoods that experienced decreases in GHGs. These study results reflect preliminary emissions and social equity patterns of the first 3 years of California's cap-and-trade program for which data are available. Due to data limitations, this analysis did not assess the emissions and equity implications of GHG reductions from transportation-related emission sources. Future emission patterns may shift, due to changes in industrial production decisions and policy initiatives that further incentivize local GHG and co-pollutant reductions in disadvantaged communities.Conclusions: To our knowledge, this is the first study to examine social disparities in GHG and co-pollutant emissions under an existing carbon trading program. Our results indicate that, thus far, California's cap-and-trade program has not yielded improvements in environmental equity with respect to health-damaging co-pollutant emissions. This could change, however, as the cap on GHG emissions is gradually lowered in the future. The incorporation of additional policy and regulatory elements that incentivize more local emission reductions in disadvantaged communities could enhance the local air quality and environmental equity benefits of California's climate change mitigation efforts. [ABSTRACT FROM AUTHOR]

Background: Air pollution damages health by promoting the onset of some non-communicable diseases (NCDs), putting additional strain on the National Health Service (NHS) and social care. This study quantifies the total health and related NHS and social care cost burden due to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) in England.Method and Findings: Air pollutant concentration surfaces from land use regression models and cost data from hospital admissions data and a literature review were fed into a microsimulation model, that was run from 2015 to 2035. Different scenarios were modelled: (1) baseline 'no change' scenario; (2) individuals' pollutant exposure is reduced to natural (non-anthropogenic) levels to compute the disease cases attributable to PM2.5 and NO2; (3) PM2.5 and NO2 concentrations reduced by 1 μg/m3; and (4) NO2 annual European Union limit values reached (40 μg/m3). For the 18 years after baseline, the total cumulative cost to the NHS and social care is estimated at £5.37 billion for PM2.5 and NO2 combined, rising to £18.57 billion when costs for diseases for which there is less robust evidence are included. These costs are due to the cumulative incidence of air-pollution-related NCDs, such as 348,878 coronary heart disease cases estimated to be attributable to PM2.5 and 573,363 diabetes cases estimated to be attributable to NO2 by 2035. Findings from modelling studies are limited by the conceptual model, assumptions, and the availability and quality of input data.Conclusions: Approximately 2.5 million cases of NCDs attributable to air pollution are predicted by 2035 if PM2.5 and NO2 stay at current levels, making air pollution an important public health priority. In future work, the modelling framework should be updated to include multi-pollutant exposure-response functions, as well as to disaggregate results by socioeconomic status. [ABSTRACT FROM AUTHOR]

Background: It has long been contested that trade rules and agreements are used to dispute regulations aimed at preventing noncommunicable diseases (NCDs). Yet most analyses of trade rules and agreements focus on trade disputes, potentially overlooking how a challenge to a regulation's consistency with trade rules may lead to 'policy or regulatory chill' effects whereby countries delay, alter, or repeal regulations in order to avoid the costs of a dispute. Systematic empirical analysis of this pathway to impact was previously prevented by a dearth of systematically coded data.Methods and Findings: Here, we analyse a newly created dataset of trade challenges about food, beverage, and tobacco regulations among 122 World Trade Organization (WTO) members from January 1, 1995 to December 31, 2016. We thematically describe the scope and frequency of trade challenges, analyse economic asymmetries between countries raising and defending them, and summarise 4 cases of their possible influence. Between 1995 and 2016, 93 food, beverage, and tobacco regulations were challenged at the WTO. 'Unnecessary' trade costs were the focus of 16.4% of the challenges. Only one (1.1%) challenge remained unresolved and escalated to a trade dispute. Thirty-nine (41.9%) challenges focussed on labelling regulations, and 18 (19.4%) focussed on quality standards and restrictions on certain products like processed meats and cigarette flavourings. High-income countries raised 77.4% (n = 72) of all challenges raised against low- and lower-middle-income countries. We further identified 4 cases in Indonesia, Chile, Colombia, and Saudi Arabia in which challenges were associated with changes to food and beverage regulations. Data limitations precluded a comprehensive evaluation of policy impact and challenge validity.Conclusions: Policy makers appear to face significant pressure to design food, beverage, and tobacco regulations that other countries will deem consistent with trade rules. Trade-related influence on public health policy is likely to be understated by analyses limited to formal trade disputes. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is the leading cause of mortality in India. Yet, evidence on the CVD risk of India's population is limited. To inform health system planning and effective targeting of interventions, this study aimed to determine how CVD risk-and the factors that determine risk-varies among states in India, by rural-urban location, and by individual-level sociodemographic characteristics.Methods and Findings: We used 2 large household surveys carried out between 2012 and 2014, which included a sample of 797,540 adults aged 30 to 74 years across India. The main outcome variable was the predicted 10-year risk of a CVD event as calculated with the Framingham risk score. The Harvard-NHANES, Globorisk, and WHO-ISH scores were used in secondary analyses. CVD risk and the prevalence of CVD risk factors were examined by state, rural-urban residence, age, sex, household wealth, and education. Mean CVD risk varied from 13.2% (95% CI: 12.7%-13.6%) in Jharkhand to 19.5% (95% CI: 19.1%-19.9%) in Kerala. CVD risk tended to be highest in North, Northeast, and South India. District-level wealth quintile (based on median household wealth in a district) and urbanization were both positively associated with CVD risk. Similarly, household wealth quintile and living in an urban area were positively associated with CVD risk among both sexes, but the associations were stronger among women than men. Smoking was more prevalent in poorer household wealth quintiles and in rural areas, whereas body mass index, high blood glucose, and systolic blood pressure were positively associated with household wealth and urban location. Men had a substantially higher (age-standardized) smoking prevalence (26.2% [95% CI: 25.7%-26.7%] versus 1.8% [95% CI: 1.7%-1.9%]) and mean systolic blood pressure (126.9 mm Hg [95% CI: 126.7-127.1] versus 124.3 mm Hg [95% CI: 124.1-124.5]) than women. Important limitations of this analysis are the high proportion of missing values (27.1%) in the main outcome variable, assessment of diabetes through a 1-time capillary blood glucose measurement, and the inability to exclude participants with a current or previous CVD event.Conclusions: This study identified substantial variation in CVD risk among states and sociodemographic groups in India-findings that can facilitate effective targeting of CVD programs to those most at risk and most in need. While the CVD risk scores used have not been validated in South Asian populations, the patterns of variation in CVD risk among the Indian population were similar across all 4 risk scoring systems. [ABSTRACT FROM AUTHOR]

Background: Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine's pharmacology and the user's biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris became the first major tobacco company to admit nicotine's addictiveness. Evolving definitions of addiction have historically affected subsequent policymaking. This article examines how Philip Morris internally conceptualized addiction immediately before and after this announcement.Methods and Findings: We analyzed previously secret, internal Philip Morris documents made available as a result of litigation against the tobacco industry. We compared these documents to public company statements and found that Philip Morris's move from public denial to public affirmation of nicotine's addictiveness coincided with pressure on the industry from poor public approval ratings, the Master Settlement Agreement (MSA), the United States government's filing of the Racketeer Influenced and Corrupt Organizations (RICO) suit, and the Institute of Medicine's (IoM's) endorsement of potentially reduced risk products. Philip Morris continued to research the causes of addiction through the 2000s in order to create successful potentially reduced exposure products (PREPs). While Philip Morris's public statements reinforce the idea that nicotine's pharmacology principally drives smoking addiction, company scientists framed addiction as the result of interconnected biological, social, psychological, and environmental determinants, with nicotine as but one component. Due to the fragmentary nature of the industry document database, we may have missed relevant information that could have affected our analysis.Conclusions: Philip Morris's research suggests that tobacco industry activity influences addiction treatment outcomes. Beyond nicotine's pharmacology, the industry's continued aggressive advertising, lobbying, and litigation against effective tobacco control policies promotes various nonpharmacological determinants of addiction. To help tobacco users quit, policy makers should increase attention on the social and environmental dimensions of addiction alongside traditional cessation efforts. [ABSTRACT FROM AUTHOR]

Background: Early childhood interventions have potential to offset the negative impact of early adversity. We evaluated the impact of a community-based parenting group intervention on child development in Zambia.Methods and Findings: We conducted a non-masked cluster-randomized controlled trial in Southern Province, Zambia. Thirty clusters of villages were matched based on population density and distance from the nearest health center, and randomly assigned to intervention (15 clusters, 268 caregiver-child dyads) or control (15 clusters, 258 caregiver-child dyads). Caregivers were eligible if they had a child 6 to 12 months old at baseline. In intervention clusters, caregivers were visited twice per month during the first year of the study by child development agents (CDAs) and were invited to attend fortnightly parenting group meetings. Parenting groups selected "head mothers" from their communities who were trained by CDAs to facilitate meetings and deliver a diverse parenting curriculum. The parenting group intervention, originally designed to run for 1 year, was extended, and households were visited for a follow-up assessment at the end of year 2. The control group did not receive any intervention. Intention-to-treat analysis was performed for primary outcomes measured at the year 2 follow-up: stunting and 5 domains of neurocognitive development measured using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). In order to show Cohen's d estimates, BSID-III composite scores were converted to z-scores by standardizing within the study population. In all, 195/268 children (73%) in the intervention group and 182/258 children (71%) in the control group were assessed at endline after 2 years. The intervention significantly reduced stunting (56/195 versus 72/182; adjusted odds ratio 0.45, 95% CI 0.22 to 0.92; p = 0.028) and had a significant positive impact on language (β 0.14, 95% CI 0.01 to 0.27; p = 0.039). The intervention did not significantly impact cognition (β 0.11, 95% CI -0.06 to 0.29; p = 0.196), motor skills (β -0.01, 95% CI -0.25 to 0.24; p = 0.964), adaptive behavior (β 0.21, 95% CI -0.03 to 0.44; p = 0.088), or social-emotional development (β 0.20, 95% CI -0.04 to 0.44; p = 0.098). Observed impacts may have been due in part to home visits by CDAs during the first year of the intervention.Conclusions: The results of this trial suggest that parenting groups hold promise for improving child development, particularly physical growth, in low-resource settings like Zambia.Trial Registration: ClinicalTrials.gov NCT02234726. [ABSTRACT FROM AUTHOR]

Background: In recent decades, there has been a shift to later childbearing in high-income countries. There is limited large-scale evidence of the relationship between maternal age and child outcomes beyond the perinatal period. The objective of this study is to quantify a child's risk of developmental vulnerability at age five, according to their mother's age at childbirth.Methods and Findings: Linkage of population-level perinatal, hospital, and birth registration datasets to data from the Australian Early Development Census (AEDC) and school enrolments in Australia's most populous state, New South Wales (NSW), enabled us to follow a cohort of 99,530 children from birth to their first year of school in 2009 or 2012. The study outcome was teacher-reported child development on five domains measured by the AEDC, including physical health and well-being, emotional maturity, social competence, language and cognitive skills, and communication skills and general knowledge. Developmental vulnerability was defined as domain scores below the 2009 AEDC 10th percentile cut point. The mean maternal age at childbirth was 29.6 years (standard deviation [SD], 5.7), with 4,382 children (4.4%) born to mothers aged <20 years and 20,026 children (20.1%) born to mothers aged ≥35 years. The proportion vulnerable on ≥1 domains was 21% overall and followed a reverse J-shaped distribution according to maternal age: it was highest in children born to mothers aged ≤15 years, at 40% (95% CI, 32-49), and was lowest in children born to mothers aged between 30 years and ≤35 years, at 17%-18%. For maternal ages 36 years to ≥45 years, the proportion vulnerable on ≥1 domains increased to 17%-24%. Adjustment for sociodemographic characteristics significantly attenuated vulnerability risk in children born to younger mothers, while adjustment for potentially modifiable factors, such as antenatal visits, had little additional impact across all ages. Although the multi-agency linkage yielded a broad range of sociodemographic, perinatal, health, and developmental variables at the child's birth and school entry, the study was necessarily limited to variables available in the source data, which were mostly recorded for administrative purposes.Conclusions: Increasing maternal age was associated with a lesser risk of developmental vulnerability for children born to mothers aged 15 years to about 30 years. In contrast, increasing maternal age beyond 35 years was generally associated with increasing vulnerability, broadly equivalent to the risk for children born to mothers in their early twenties, which is highly relevant in the international context of later childbearing. That socioeconomic disadvantage explained approximately half of the increased risk of developmental vulnerability associated with younger motherhood suggests there may be scope to improve population-level child development through policies and programs that support disadvantaged mothers and children. [ABSTRACT FROM AUTHOR]

Background: Poor early childhood development (ECD) in low- and middle-income countries is a major concern. There are calls to universalise access to ECD interventions through integrating them into existing government services but little evidence on the medium- or long-term effects of such scalable models. We previously showed that a psychosocial stimulation (PS) intervention integrated into a cash transfer programme improved Colombian children's cognition, receptive language, and home stimulation. In this follow-up study, we assessed the medium-term impacts of the intervention, 2 years after it ended, on children's cognition, language, school readiness, executive function, and behaviour.Methods and Findings: Study participants were 1,419 children aged 12-24 months at baseline from beneficiary households of the cash transfer programme, living in 96 Colombian towns. The original cluster randomised controlled trial (2009-2011) randomly allocated the towns to control (N = 24, n = 349), PS (N = 24, n = 357), multiple micronutrient (MN) supplementation (N = 24, n = 354), and combined PS and MN (N = 24, n = 359). Interventions lasted 18 months. In this study (26 September 2013 to 11 January 2014), we assessed impacts on cognition, language, school readiness, executive function, and behaviour 2 years after intervention, at ages 4.5-5.5 years. Testers, but not participants, were blinded to treatment allocation. Analysis was on an intent-to-treat basis. We reassessed 88.5% of the children in the original study (n = 1,256). Factor analysis of test scores yielded 2 factors: cognitive (cognition, language, school readiness, executive function) and behavioural. We found no effect of the interventions after 2 years on the cognitive factor (PS: -0.031 SD, 95% CI -0.229-0.167; MN: -0.042 SD, 95% CI -0.249-0.164; PS and MN: -0.111 SD, 95% CI -0.311-0.089), the behavioural factor (PS: 0.013 SD, 95% CI -0.172-0.198; MN: 0.071 SD, 95% CI -0.115-0.258; PS and MN: 0.062 SD, 95% CI -0.115-0.239), or home stimulation. Study limitations include that behavioural development was measured through maternal report and that very small effects may have been missed, despite the large sample size.Conclusions: We found no evidence that a scalable PS intervention benefited children's development 2 years after it ended. It is possible that the initial effects on child development were too small to be sustained or that the lack of continued impact on home stimulation contributed to fade out. Both are likely related to compromises in implementation when going to scale and suggest one should not extrapolate from medium-term effects of small efficacy trials to scalable interventions. Understanding the salient differences between small efficacy trials and scaled-up versions will be key to making ECD interventions effective tools for policymakers.Trial Registration: ISRCTN18991160. [ABSTRACT FROM AUTHOR]

Background: Frail elderly people experience elevated mortality. However, no consensus exists on the definition of frailty, and many frailty scores have been developed. The main aim of this study was to compare the association between 35 frailty scores and incident cardiovascular disease (CVD), incident cancer, and all-cause mortality. Also, we aimed to assess whether frailty scores added predictive value to basic and adjusted models for these outcomes.Methods and Findings: Through a structured literature search, we identified 35 frailty scores that could be calculated at wave 2 of the English Longitudinal Study of Ageing (ELSA), an observational cohort study. We analysed data from 5,294 participants, 44.9% men, aged 60 years and over. We studied the association between each of the scores and the incidence of CVD, cancer, and all-cause mortality during a 7-year follow-up using Cox proportional hazard models at progressive levels of adjustment. We also examined the added predictive performance of each score on top of basic models using Harrell's C statistic. Using age of the participant as a timescale, in sex-adjusted models, hazard ratios (HRs) (95% confidence intervals) for all-cause mortality ranged from 2.4 (95% CI: 1.7-3.3) to 26.2 (95% CI: 15.4-44.5). In further adjusted models including smoking status and alcohol consumption, HR ranged from 2.3 (95% CI: 1.6-3.1) to 20.2 (95% CI: 11.8-34.5). In fully adjusted models including lifestyle and comorbidity, HR ranged from 0.9 (95% CI: 0.5-1.7) to 8.4 (95% CI: 4.9-14.4). HRs for CVD and cancer incidence in sex-adjusted models ranged from 1.2 (95% CI: 0.5-3.2) to 16.5 (95% CI: 7.8-35.0) and from 0.7 (95% CI: 0.4-1.2) to 2.4 (95% CI: 1.0-5.7), respectively. In sex- and age-adjusted models, all frailty scores showed significant added predictive performance for all-cause mortality, increasing the C statistic by up to 3%. None of the scores significantly improved basic prediction models for CVD or cancer. A source of bias could be the differences in mortality follow-up time compared to CVD/cancer, because the existence of informative censoring cannot be excluded.Conclusion: There is high variability in the strength of the association between frailty scores and 7-year all-cause mortality, incident CVD, and cancer. With regard to all-cause mortality, some scores give a modest improvement to the predictive ability. Our results show that certain scores clearly outperform others with regard to three important health outcomes in later life. Finally, we think that despite their limitations, the use of frailty scores to identify the elderly population at risk is still a useful measure, and the choice of a frailty score should balance feasibility with performance. [ABSTRACT FROM AUTHOR]

Background: Migrant and ethnic minority groups are often assumed to have poor health relative to the majority population. Few countries have the capacity to study a key indicator, mortality, by ethnicity and country of birth. We hypothesized at least 10% differences in mortality by ethnic group in Scotland that would not be wholly attenuated by adjustment for socio-economic factors or country of birth.Methods and Findings: We linked the Scottish 2001 Census to mortality data (2001-2013) in 4.62 million people (91% of estimated population), calculating age-adjusted mortality rate ratios (RRs; multiplied by 100 as percentages) with 95% confidence intervals (CIs) for 13 ethnic groups, with the White Scottish group as reference (ethnic group classification follows the Scottish 2001 Census). The Scottish Index of Multiple Deprivation, education status, and household tenure were socio-economic status (SES) confounding variables and born in the UK or Republic of Ireland (UK/RoI) an interacting and confounding variable. Smoking and diabetes data were from a primary care sub-sample (about 53,000 people). Males and females in most minority groups had lower age-adjusted mortality RRs than the White Scottish group. The 95% CIs provided good evidence that the RR was more than 10% lower in the following ethnic groups: Other White British (72.3 [95% CI 64.2, 81.3] in males and 75.2 [68.0, 83.2] in females); Other White (80.8 [72.8, 89.8] in males and 76.2 [68.6, 84.7] in females); Indian (62.6 [51.6, 76.0] in males and 60.7 [50.4, 73.1] in females); Pakistani (66.1 [57.4, 76.2] in males and 73.8 [63.7, 85.5] in females); Bangladeshi males (50.7 [32.5, 79.1]); Caribbean females (57.5 [38.5, 85.9]); and Chinese (52.2 [43.7, 62.5] in males and 65.8 [55.3, 78.2] in females). The differences were diminished but not eliminated after adjusting for UK/RoI birth and SES variables. A mortality advantage was evident in all 12 minority groups for those born abroad, but in only 6/12 male groups and 5/12 female groups of those born in the UK/RoI. In the primary care sub-sample, after adjustment for age, UK/RoI born, SES, smoking, and diabetes, the RR was not lower in Indian males (114.7 [95% CI 78.3, 167.9]) and Pakistani females (103.9 [73.9, 145.9]) than in White Scottish males and females, respectively. The main limitations were the inability to include deaths abroad and the small number of deaths in some ethnic minority groups, especially for people born in the UK/RoI.Conclusions: There was relatively low mortality for many ethnic minority groups compared to the White Scottish majority. The mortality advantage was less clear in UK/RoI-born minority group offspring than in immigrants. These differences need explaining, and health-related behaviours seem important. Similar analyses are required internationally to fulfil agreed goals for monitoring, understanding, and improving health in ethnically diverse societies and to apply to health policy, especially on health inequalities and inequities. [ABSTRACT FROM AUTHOR]

Background: Cholera prevention and control interventions targeted to neighbors of cholera cases (case-area targeted interventions [CATIs]), including improved water, sanitation, and hygiene, oral cholera vaccine (OCV), and prophylactic antibiotics, may be able to efficiently avert cholera cases and deaths while saving scarce resources during epidemics. Efforts to quickly target interventions to neighbors of cases have been made in recent outbreaks, but little empirical evidence related to the effectiveness, efficiency, or ideal design of this approach exists. Here, we aim to provide practical guidance on how CATIs might be used by exploring key determinants of intervention impact, including the mix of interventions, "ring" size, and timing, in simulated cholera epidemics fit to data from an urban cholera epidemic in Africa.Methods and Findings: We developed a micro-simulation model and calibrated it to both the epidemic curve and the small-scale spatiotemporal clustering pattern of case households from a large 2011 cholera outbreak in N'Djamena, Chad (4,352 reported cases over 232 days), and explored the potential impact of CATIs in simulated epidemics. CATIs were implemented with realistic logistical delays after cases presented for care using different combinations of prophylactic antibiotics, OCV, and/or point-of-use water treatment (POUWT) starting at different points during the epidemics and targeting rings of various radii around incident case households. Our findings suggest that CATIs shorten the duration of epidemics and are more resource-efficient than mass campaigns. OCV was predicted to be the most effective single intervention, followed by POUWT and antibiotics. CATIs with OCV started early in an epidemic focusing on a 100-m radius around case households were estimated to shorten epidemics by 68% (IQR 62% to 72%), with an 81% (IQR 69% to 87%) reduction in cases compared to uncontrolled epidemics. These same targeted interventions with OCV led to a 44-fold (IQR 27 to 78) reduction in the number of people needed to target to avert a single case of cholera, compared to mass campaigns in high-cholera-risk neighborhoods. The optimal radius to target around incident case households differed by intervention type, with antibiotics having an optimal radius of 30 m to 45 m compared to 70 m to 100 m for OCV and POUWT. Adding POUWT or antibiotics to OCV provided only marginal impact and efficiency improvements. Starting CATIs early in an epidemic with OCV and POUWT targeting those within 100 m of an incident case household reduced epidemic durations by 70% (IQR 65% to 75%) and the number of cases by 82% (IQR 71% to 88%) compared to uncontrolled epidemics. CATIs used late in epidemics, even after the peak, were estimated to avert relatively few cases but substantially reduced the number of epidemic days (e.g., by 28% [IQR 15% to 45%] for OCV in a 100-m radius). While this study is based on a rigorous, data-driven approach, the relatively high uncertainty about the ways in which POUWT and antibiotic interventions reduce cholera risk, as well as the heterogeneity in outbreak dynamics from place to place, limits the precision and generalizability of our quantitative estimates.Conclusions: In this study, we found that CATIs using OCV, antibiotics, and water treatment interventions at an appropriate radius around cases could be an effective and efficient way to fight cholera epidemics. They can provide a complementary and efficient approach to mass intervention campaigns and may prove particularly useful during the initial phase of an outbreak, when there are few cases and few available resources, or in order to shorten the often protracted tails of cholera epidemics. [ABSTRACT FROM AUTHOR]