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Introduction Despite the progress in reducing child mortality, the rate remains high, particularly in sub-Saharan African countries. Limited data exist on child survival and other birth outcomes by sex. This study compared survival rates and birth outcomes by sex among neonates and children under 2 in Ethiopia.Methods Women who gave birth after 28 weeks of gestation and their newborns were included in the analysis. Survival probabilities were estimated for males and females in the neonatal period as well as the 2-year period following birth using Kaplan-Meier curves. HRs and 95% CIs were compared between males and females under 2. Descriptive statistics and χ2 tests were used to determine the sex-disaggregated variation in the birth outcomes of preterm birth, low birth weight (LBW), stillbirth, small for gestational age (SGA) and large for gestational age (LGA).Results The study included a total of 3904 women and child pairs. The neonatal mortality rate for males (3.4%, 95% CI 2.6% to 4.2%) was higher compared with females (1.7%, 95% CI 1.1% to 2.3%). The hazard of death during the first 28 days of life was approximately two times higher for males compared with females (HR 1.99, 95% CI 1.30 to 3.06) but was not significantly different after this period. While there was a non-significant difference between males and females in the proportion of preterm, LBW and LGA births, we found a significantly higher proportion of stillbirth (2.7% vs 1.3%, p=0.003) and SGA (20.5% vs 15.6%, p

Objectives: To examine the association between parents’ influenza vaccination and their children’s coronavirus disease 2019 (COVID-19) vaccination status. Methods: Participants included father-mother dyads from Fathers & Families, a cohort of fathers and their co-parents living in the United States. Parents’ influenza vaccination status and children’s COVID-19 vaccination status were reported from June 2022-July 2023. Logistic regression was used to examine the association between parental influenza vaccination (both parents vs. neither parent vs. mother only vs. father only vaccinated) and child COVID-19 vaccination (received at least 1 vs. 0 doses). Models were adjusted for recruitment site, income, parent education, child race/ethnicity, child age, and childcare enrollment. Inverse probability weighting was used to account for selection bias into the father-mother dyad sample. Results: Children were predominately non-Hispanic White (56 %) and aged 3–5 years (62 %). In most households, both parents (64 %) received the influenza vaccine and half (53 %) of children received the COVID-19 vaccine. One-in-four fathers (23 %) lacked knowledge about their child’s COVID-19 vaccination eligibility. Compared to children with two unvaccinated parents, having only their father (adjusted odds ratio [AOR] = 2.84, 95 % confidence interval [CI]: 1.52–5.36), only their mother (AOR = 4.04, 95 % CI: 2.16–7.68), and both parents (AOR = 10.33, 95 % CI: 6.29–17.53) vaccinated against influenza was associated with higher odds of children receiving the COVID-19 vaccine. Conclusions: Father and mother influenza vaccination is associated with child COVID-19 vaccination. Given many fathers were unaware their child was eligible for the COVID-19 vaccine, it is critical to tailor vaccine messaging for fathers.

Sexually minoritized women (SMW) may be at an increased risk of adverse perinatal mental health, though prior research is limited. We examined sexual orientation-related differences in perinatal mental health (i.e., stress and depression), and antidepressant utilization among those at different severities of clinically significant perinatal depressive symptoms.Nurses’ Health Study 3 participants with prospectively assessed pregnancies (N = 6,364) received pregnancy and postpartum questionnaires. Using weighted log-binomial generalized estimating equations, we examined differences in stress (Perceived Stress Scale 4 [PSS-4]), depression (the Edinburgh Postnatal Depression Scale [EDPS] at four cut-off scores [≥7, ≥9, ≥11, ≥13]), and patterns of antidepressant utilization across five groups: completely heterosexual with no same-sex sexual partners (reference group; n = 5,178); heterosexual with same-sex sexual partners (n = 245); mostly heterosexual (n = 770); bisexual (n = 106); and lesbian (n = 47).Compared to the completely heterosexual reference group, SMW reported increased stress during pregnancy (adjusted risk ratio [ARR]: 1.14, 95% confidence interval [1.02–1.28]). SMW reported an elevated risk of pregnancy depression at every EDPS score cutoff, with the magnitude of the disparity increasing as the score increased (ARRs: 1.09 [1.00–1.20]; 1.20 [1.05–1.36]; 1.37 [1.16–1.63]; 1.49 [1.18–1.89] for EDPS scores ≥7, ≥9, ≥11, ≥13, respectively). Disparities were highest in magnitude among the mostly heterosexual and bisexual subgroups. Utilization of postpartum antidepressants increased among the reference group with increasing symptom severity but was only associated at the highest score (≥13) among SMW subgroups.SMW have increased risks of pregnancy stress and depression and are more likely to use perinatal antidepressants; mostly heterosexual and bisexual individuals had the highest risk of antidepressant use. Postpartum symptom severity closely corresponded to antidepressant use among completely heterosexual, but not SMW—suggesting disparities in mental health treatment. Further research priorities include determining the causes of these disparities and appropriately tailored solutions.

It is estimated that billions of people around the world are affected by micronutrient deficiencies. Madagascar is considered to be particularly nutritionally vulnerable, with nearly half of the population stunted, and parts of the country facing emergency, near famine-like conditions (IPC4). Although Madagascar is generally considered among the most undernourished of countries, empirical data in the form of biological samples to validate these claims are extremely limited. Our research drew data from three studies conducted between 2013–2020 and provided comprehensive biomarker profile information for 4,710 individuals from 30 communities in five different ecological regions during at least one time-point. Estimated prevalences of nutrient deficiencies and inflammation across various regions of rural Madagascar were of concern for both sexes and across all ages, with 66.5% of the population estimated to be deficient in zinc, 15.6% depleted in vitamin B12 (3.6% deficient), 11.6% deficient in retinol, and lower levels of iron deficiency (as indicated by 11.7% deficient in ferritin and 2.3% deficient assessed by soluble transferrin receptors). Beyond nutrient status biomarkers, nearly one quarter of the population (24.0%) exhibited chronic inflammation based on high values of α-1-acid glycoprotein, and 12.3% exhibited acute inflammation based on high values of C-reactive protein. There is an 8-fold difference between the lowest and highest regional observed prevalence of vitamin B12 deficiency, a 10-fold difference in vitamin A deficiency (based on retinol), and a 2-fold difference in acute inflammation (CRP) and deficiencies of zinc and iron (based on ferritin), highlighting strong geographical variations in micronutrient deficiencies across Madagascar.

Health facility delivery is one of the critical indicators to monitor progress towards the provision of skilled delivery care and reduction in perinatal mortality. In Ethiopia, utilization of health facilities for skilled delivery care has been increasing but varies greatly by region and among specific socio-demography groups. We aimed to measure the prevalence and determinants of health facility delivery in the Amhara region in Ethiopia. From December 2018 to November 2020, we conducted a longitudinal study from a cohort of 2801 pregnant women and described the location of delivery and the association with determinants. We interviewed a subset of women who delivered in the community and analyzed responses using the three delays model to understand reasons for not using health facility services. A multivariable poisson regression model with robust error variance was used to estimate the presence and magnitude of association between location of delivery and the determinants. Of the 2,482 pregnant women followed through to birth, 73.6% (n = 1,826) gave birth in health facilities, 24.3% (n = 604) gave birth at home and 2.1% (n = 52) delivered on the way to a health facility. Determinants associated with increased likelihood of delivery at a health facility included formal maternal education, shorter travel times to health facilities, primiparity, higher wealth index and having attended at least one ANC visit. Most common reasons mothers gave for not delivering in a health facility were delays in individual/family decision to seek care. The proportion of deliveries occurring in health facilities is increasing but falls below targets. Interventions that focus on the identified social-demographic determinants and delays are warranted.

Abstract INTRODUCTION The prevalence of poor sleep quality and sleep apnea differs by race and ethnicity and may contribute to racial disparities in cognitive aging. We investigated whether sleep quality and sleep apnea risk were associated with cognitive function and decline and whether the associations differed by race/ethnicity. METHODS Participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; N = 1690; mean age: 75.7 years) study, a cohort of Asian, Black, Latino, and White participants, completed a modified Pittsburgh Sleep Quality Index assessing subjective sleep quality, latency, duration, disturbances, sleep medication use, and daytime dysfunction. Sleep apnea risk was measured by questions about snoring, tiredness, and whether apnea was observed. Executive function and verbal episodic memory were assessed at three time points over an average of 2.7 years with the Spanish and English Neuropsychological Assessment Scale. We fit linear mixed‐effect models and stratified analyses by race/ethnicity. RESULTS Higher sleep apnea risk was associated with faster declines in verbal episodic memory (β̂sleep apnea = −0.02, 95% confidence interval [CI], −0.04, −0.001) but not in executive function. Poorer sleep quality was associated with lower levels of and faster decline in executive function but not in verbal episodic memory. Race/ethnicity modified these associations: compared to estimated effects among White participants, poorer global sleep quality (β̂sleep*time = −0.02, 95% CI, −0.02, −0.01) was associated with larger effects on decline in executive function among Black participants. Estimated effects of some individual sleep quality components were also modified by race/ethnicity; for example, sleep medication use was associated with faster declines in executive function (β̂sleep*time = −0.05, 95% CI, −0.07, −0.03) and verbal episodic memory β̂sleep*time = −0.04, 95% CI, −0.07, −0.02) among Black participants compared to White participants. DISCUSSION Observational evidence indicates sleep quality is a promising target for addressing racial/ethnic disparities in cognitive aging, especially among Black older adults. Highlights Sleep apnea risk was associated with faster declines in verbal episodic memory but not executive function among all participants. Global sleep quality was associated with lower levels of and faster decline in executive function but not verbal episodic memory among all participants. Black older adults were particularly susceptible to the estimated adverse cognitive impacts of global sleep quality, particularly the use of sleep medication.

Abstract Background This study reports the outcomes of Communities for Healthy Living (CHL), a cluster randomized obesity prevention trial implemented in partnership with Head Start, a federally-funded preschool program for low-income families. Methods Using a stepped wedge design, Head Start programs (n = 16; Boston, MA, USA) were randomly assigned to one of three intervention start times. CHL involved a media campaign and enhanced nutrition support. Parents were invited to join Parents Connect for Healthy Living (PConnect), a 10-week wellness program. At the beginning and end of each school year (2017-2019), data were collected on the primary outcome of child Body Mass Index z-score (BMIz) and modified BMIz, and secondary outcomes of child weight-related behaviors (diet, physical activity, sleep, media use) and parents’ weight-related parenting practices and empowerment. Data from 2 years, rather than three, were utilized to evaluate CHL due to the COVID-19 pandemic. We used mixed effects linear regression to compare relative differences during intervention vs. control periods (n = 1274 vs. 2476 children) in (1) mean change in child BMIz and modified BMIz, (2) the odds of meeting child health behavior recommendations, (3) mean change in parenting practices, and (4) mean change in parent empowerment. We also compared outcomes among parents who chose post-randomization to participate in PConnect vs. not (n = 55 vs. 443). Results During intervention periods (vs. control), children experienced greater increases in BMIz and modified BMIz (b = 0.06, 95% CI = 0.02,0.10; b = 0.07, 95% CI = 0.03, 0.12), yet were more likely to meet recommendations related to three of eight measured behaviors: sugar-sweetened beverage consumption (i.e., rarely consume; Odds Ratio (OR) = 1.5, 95% CI = 1.2,2.3), water consumption (i.e., multiple times per day; OR = 1.6, 95% CI = 1.2,2.3), and screen time (i.e., ≤1 hour/day; OR = 1.4, 95% CI = 1.0,1.8). No statistically significant differences for intervention (vs. control) periods were observed in parent empowerment or parenting practices. However, parents who enrolled in PConnect (vs. not) demonstrated greater increases in empowerment (b = 0.17, 95% CI = 0.04,0.31). Conclusions Interventions that emphasize parent engagement may increase parental empowerment. Intervention exposure was associated with statistically, but not clinically, significant increases in BMIz and increased odds of meeting recommendations for three child behaviors; premature trial suspension may explain mixed results. Trial registration ClinicalTrials.gov, NCT03334669 , Registered October 2017.

Abstract Background Maternal and neonatal mortality remain elevated in low and middle income countries, and progress is slower than needed to achieve the Sustainable Development Goals. Existing strategies appear to be insufficient. One proposed alternative strategy, Service Delivery Redesign for Maternal and Neonatal Health (SDR), centers on strengthening higher level health facilities to provide rapid, definitive care in case of delivery and post-natal complications, and then promoting delivery in these hospitals, rather than in primary care facilities. However to date, SDR has not been piloted or evaluated. Methods We will use a prospective, non-randomized stepped-wedge design to evaluate the effectiveness and implementation of Service Delivery Redesign for Maternal and Neonatal Health in Kakamega County, Kenya. Discussion This protocol describes a hybrid effectiveness/implementation evaluation study with an adaptive design. The impact evaluation (“effectiveness”) study focuses on maternal and newborn health outcomes, and will be accompanied by an implementation evaluation focused on program reach, adoption, and fidelity.

Abstract Background Preconception pregnancy risk profiles—characterizing the likelihood that a pregnancy attempt results in a full-term birth, preterm birth, clinical pregnancy loss, or failure to conceive—can provide critical information during the early stages of a pregnancy attempt, when obstetricians are best positioned to intervene to improve the chances of successful conception and full-term live birth. Yet the task of constructing and validating risk assessment tools for this earlier intervention window is complicated by several statistical features: the final outcome of the pregnancy attempt is multinomial in nature, and it summarizes the results of two intermediate stages, conception and gestation, whose outcomes are subject to competing risks, measured on different time scales, and governed by different biological processes. In light of this complexity, existing pregnancy risk assessment tools largely focus on predicting a single adverse pregnancy outcome, and make these predictions at some later, post-conception time point. Methods We reframe the individual pregnancy attempt as a multistate model comprised of two nested multinomial prediction tasks: one corresponding to conception and the other to the subsequent outcome of that pregnancy. We discuss the estimation of this model in the presence of multiple stages of outcome missingness and then introduce an inverse-probability-weighted Hypervolume Under the Manifold statistic to validate the resulting multivariate risk scores. Finally, we use data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial to illustrate how this multistate competing risks framework might be utilized in practice to construct and validate a preconception pregnancy risk assessment tool. Results In the EAGeR study population, the resulting risk profiles are able to meaningfully discriminate between the four pregnancy attempt outcomes of interest and represent a significant improvement over classification by random chance. Conclusions As illustrated in our analysis of the EAGeR data, our proposed prediction framework expands the pregnancy risk assessment task in two key ways—by considering a broader array of pregnancy outcomes and by providing the predictions at an earlier, preconception intervention window—providing obstetricians and their patients with more information and opportunities to successfully guide pregnancy attempts.

Antenatal care (ANC) coverage estimates commonly rely on self-reported data, which may carry biases. Leveraging prospectively collected longitudinal data from the Birhan field site and its pregnancy and birth cohort, the Birhan Cohort, this study aimed to estimate the coverage of ANC, minimizing assumptions and biases due to self-reported information and describing retention patterns in ANC in rural Amhara, Ethiopia. The study population were women enrolled and followed during pregnancy between December 2018 and April 2020. ANC visits were measured by prospective facility chart abstraction and self-report at enrollment. The primary study outcomes were the total number of ANC visits attended during pregnancy and the coverage of at least one, four, or eight ANC visits. Additionally, we estimated ANC retention patterns. We included 2069 women, of which 150 (7.2%) women enrolled

Abstract Background A large multi-center survey was conducted to understand patients’ perspectives on biobank study participation with particular focus on racial and ethnic minorities. In order to enrich the study sample with racial and ethnic minorities, disproportionate stratified sampling was implemented with strata defined by electronic health records (EHR) that are known to be inaccurate. We investigate the effect of sampling strata misclassification in complex survey design. Methods Under non-differential and differential misclassification in the sampling strata, we compare the validity and precision of three simple and common analysis approaches for settings in which the primary exposure is used to define the sampling strata. We also compare the precision gains/losses observed from using a disproportionate stratified sampling scheme compared to using a simple random sample under varying degrees of strata misclassification. Results Disproportionate stratified sampling can result in more efficient parameter estimates of the rare subgroups (race/ethnic minorities) in the sampling strata compared to simple random sampling. When sampling strata misclassification is non-differential with respect to the outcome, a design-agnostic analysis was preferred over model-based and design-based analyses. All methods yielded unbiased parameter estimates but standard error estimates were lowest from the design-agnostic analysis. However, when misclassification is differential, only the design-based method produced valid parameter estimates of the variables included in the sampling strata. Conclusions In complex survey design, when the interest is in making inference on rare subgroups, we recommend implementing disproportionate stratified sampling over simple random sampling even if the sampling strata are misclassified. If the misclassification is non-differential, we recommend a design-agnostic analysis. However, if the misclassification is differential, we recommend using design-based analyses.

Objectives:. To compare hypertension remission and relapse after bariatric surgery compared with usual care. Background:. The effect of Roux-en-Y gastric bypass and sleeve gastrectomy on hypertension remission and relapse has not been studied in large, multicenter studies over long periods and using clinical blood pressure (BP) measurements. Methods:. This retrospective cohort study was set in Kaiser Permanente Washington, Northern California, and Southern California. Participants included 9432 patients with hypertension 21–65 years old who underwent bariatric surgery during 2005–2015 and 66,651 nonsurgical controls matched on an index date on study site, age, sex, race/ethnicity, body mass index, comorbidity burden, diabetes status, diastolic and systolic BP, and number of antihypertensive medications. Results:. At 5 years, the unadjusted cumulative incidence of hypertension remission was 60% (95% confidence interval [CI], 58–61%) among surgery patients and 14% (95% CI, 13–14%) among controls. At 1 year, the adjusted hazard ratio for the association of bariatric surgery with hypertension remission was 10.24 (95% CI, 9.61–10.90). At 5 years, the adjusted hazard ratio was 2.10 (95% CI, 1.57–2.80). Among those who remitted, the unadjusted cumulative incidence of relapse at 5 years after remission was 54% (95% CI, 51–56%) among surgery patients and 78% (95% CI 76–79%) among controls, although the adjusted hazard ratio was not significant (hazard ratio, 0.71; 95% CI, 0.46–1.08). Conclusions:. Bariatric surgery was associated with greater hypertension remission than usual care suggesting that bariatric surgery should be discussed with patients with severe obesity and hypertension. Surgical patients who experience remission should be monitored carefully for hypertension relapse.

Abstract Background Semi-competing risks arise when interest lies in the time-to-event for some non-terminal event, the observation of which is subject to some terminal event. One approach to assessing the impact of covariates on semi-competing risks data is through the illness-death model with shared frailty, where hazard regression models are used to model the effect of covariates on the endpoints. The shared frailty term, which can be viewed as an individual-specific random effect, acknowledges dependence between the events that is not accounted for by covariates. Although methods exist for fitting such a model to right-censored semi-competing risks data, there is currently a gap in the literature for fitting such models when a flexible baseline hazard specification is desired and the data are left-truncated, for example when time is on the age scale. We provide a modeling framework and openly available code for implementation. Methods We specified the model and the likelihood function that accounts for left-truncated data, and provided an approach to estimation and inference via maximum likelihood. Our model was fully parametric, specifying baseline hazards via Weibull or B-splines. Using simulated data we examined the operating characteristics of the implementation in terms of bias and coverage. We applied our methods to a dataset of 33,117 Kaiser Permanente Northern California members aged 65 or older examining the relationship between educational level (categorized as: high school or less; trade school, some college or college graduate; post-graduate) and incident dementia and death. Results A simulation study showed that our implementation provided regression parameter estimates with negligible bias and good coverage. In our data application, we found higher levels of education are associated with a lower risk of incident dementia, after adjusting for sex and race/ethnicity. Conclusions As illustrated by our analysis of Kaiser data, our proposed modeling framework allows the analyst to assess the impact of covariates on semi-competing risks data, such as incident dementia and death, while accounting for dependence between the outcomes when data are left-truncated, as is common in studies of aging and dementia.

Abstract Background Peer leadership can be an effective strategy for implementing health programs, benefiting both program participants and peer leaders. To realize such benefits, the peer leader role must be appropriate for the community context. Also, peer leaders must find their role acceptable (i.e., satisfactory) to ensure their successful recruitment and retention. To date, parent peer leaders have seldom been part of early childhood obesity prevention efforts. Moreover, parents at Head Start preschools have rarely been engaged as peer leaders. The aim of this study is to evaluate the appropriateness and acceptability of an innovative model for engaging parents as peer leaders for this novel content area (early childhood obesity prevention) and setting (Head Start). Methods Parents Connect for Healthy Living (PConnect) is a 10-session parent program being implemented in Head Start preschools as part of the Communities for Healthy Living early childhood obesity prevention trial. PConnect is co-led by a parent peer facilitator who is paired with a Head Start staff facilitator. In the spring of 2019, 10 PConnect facilitators participated in a semi-structured interview about their experience. Interview transcripts were analyzed by two coders using an inductive-deductive hybrid analysis. Themes were identified and member-checked with two interviewees. Results Themes identified applied equally to parent and staff facilitators. Acceptability was high because PConnect facilitators were able to learn and teach, establish meaningful relationships, and positively impact the parents participating in their groups, although facilitators did express frustration when low attendance limited their reach. Appropriateness was also high, as PConnect provided adequate structure and support without being overly rigid, and facilitators were able to overcome most challenges they encountered. Conclusions The PConnect co-facilitation model was highly acceptable and appropriate for both the parent facilitators (peer leaders) and the staff facilitators. Including parents as peer leaders aligns to Head Start’s emphasis on parent engagement, making it a strong candidate for sustained implementation in Head Start. The insights gained about the drivers of peer leadership appropriateness and acceptability in this particular context may be used to inform the design and implementation of peer-led health programs elsewhere. Trial registration clinicaltrials.gov, NCT03334669 (7–11-17).

Fathers’ engagement in infant caregiving is linked with positive social, emotional, and developmental outcomes in children; however, its relationship with fathers’ own health is largely unknown. This longitudinal study examined associations between fathers’ caregiving engagement with their 6-month-old infants and their physical activity, sugar-sweetened beverage (SSB) consumption, nighttime sleep duration, and depressive symptoms 6 months later when infants were 12 months old. Participants were 143 fathers of infants (62.7% non-Hispanic White, 82.3% with a bachelor’s degree). Fathers reported their frequency of engagement in seven caregiving activities when infants were 6 months old. Fathers’ physical activity, SSB consumption, nighttime sleep duration, and depressive symptoms were assessed when infants were 6 and 12 months old. Multivariate logistic regression analysis was used to assess if fathers who reported higher infant caregiving at 6 months had more positive health outcomes at 12 months, controlling for fathers’ age, race/ethnicity, education, employment, household income, and the outcome at 6 months. Fathers who reported higher caregiving engagement when infants were 6 months old had increased odds of being sufficiently physically active 6 months later (unadjusted odds ratio [OR] = 1.19, 95% confidence interval [CI] = [1.00, 1.41]; adjusted OR = 1.47, 95% CI = [1.11, 1.96]). No links were identified between fathers’ caregiving engagement and their SSB consumption, nighttime sleep duration, or depressive symptoms. In summary, fathers’ engagement in infant caregiving may be beneficial to their physical activity in the first year after birth. There was insufficient evidence in this study that the benefits of caregiving engagement were experienced broadly across multiple health outcomes.

Isolation guidelines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are largely derived from data collected prior to the emergence of the delta variant. We followed a cohort of ambulatory patients with postvaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole-genome sequencing, and viral culture. All delta variant infections in our cohort were symptomatic, compared with 64% of non-delta variant infections. Symptomatic delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR, greater likelihood of replication-competent virus at early stages of infection, and longer duration of culturable virus compared with non-delta variants. The duration of time since vaccination was also correlated with both duration of PCR positivity and duration of detection of replication-competent virus. Nonetheless, no individuals with symptomatic delta variant infections had replication-competent virus by day 10 after symptom onset or 24 hours after resolution of symptoms. These data support US CDC isolation guidelines as of November 2021, which recommend isolation for 10 days or until symptom resolution and reinforce the importance of prompt testing and isolation among symptomatic individuals with delta breakthrough infections. Additional data are needed to evaluate these relationships among asymptomatic and more severe delta variant breakthrough infections.

Background: Neurodevelopmental studies of childhood adversity often define threatening experiences as those involving harm or the threat of harm. Whether effects differ between experiences involving harm (“physical attack”) versus the threat of harm alone (“threatened violence”) remains underexplored. We hypothesized that while both types of experiences would be associated with smaller preadolescent global and corticolimbic brain volumes, associations with physical attack would be greater. Methods: Generation R Study researchers (the Netherlands) acquired T1-weighted scans from 2905 preadolescent children, computed brain volumes using FreeSurfer, and asked mothers whether their children ever experienced physical attack (n = 202) or threatened violence (n = 335). Using standardized global (cortical, subcortical, white matter) and corticolimbic (amygdala, hippocampus, anterior cingulate cortex, orbitofrontal cortex) volumes, we fit confounder-adjusted models. Results: Physical attack was associated with smaller global volumes (βcortical=−0.14; 95% CI: −0.26, −0.02); βwhite matter= −0.16; 95% CI: − 0.28, − 0.03) and possibly some corticolimbic volumes, e.g., βamygdala/ICV-adjusted= −0.10 (95% CI: −0.21, 0.01). We found no evidence of associations between threatened violence and smaller volumes in any outcome; instead, such estimates were small, highly uncertain, and positive in direction. Conclusions: Experiences of physical attack and threatened violence may have quantitively different neurodevelopmental effects. Thus, differences between types of threatening experiences may be neurodevelopmentally salient.

[This corrects the article DOI: 10.1371/journal.pmed.1003244.].

BackgroundSocial distancing measures to address the US coronavirus disease 2019 (COVID-19) epidemic may have notable health and social impacts.Methods and findingsWe conducted a longitudinal pretest-posttest comparison group study to estimate the change in COVID-19 case growth before versus after implementation of statewide social distancing measures in the US. The primary exposure was time before (14 days prior to, and through 3 days after) versus after (beginning 4 days after, to up to 21 days after) implementation of the first statewide social distancing measures. Statewide restrictions on internal movement were examined as a secondary exposure. The primary outcome was the COVID-19 case growth rate. The secondary outcome was the COVID-19-attributed mortality growth rate. All states initiated social distancing measures between March 10 and March 25, 2020. The mean daily COVID-19 case growth rate decreased beginning 4 days after implementation of the first statewide social distancing measures, by 0.9% per day (95% CI -1.4% to -0.4%; P < 0.001). We did not observe a statistically significant difference in the mean daily case growth rate before versus after implementation of statewide restrictions on internal movement (0.1% per day; 95% CI -0.04% to 0.3%; P = 0.14), but there is substantial difficulty in disentangling the unique associations with statewide restrictions on internal movement from the unique associations with the first social distancing measures. Beginning 7 days after social distancing, the COVID-19-attributed mortality growth rate decreased by 2.0% per day (95% CI -3.0% to -0.9%; P < 0.001). Our analysis is susceptible to potential bias resulting from the aggregate nature of the ecological data, potential confounding by contemporaneous changes (e.g., increases in testing), and potential underestimation of social distancing due to spillover effects from neighboring states.ConclusionsStatewide social distancing measures were associated with a decrease in the COVID-19 case growth rate that was statistically significant. Statewide social distancing measures were also associated with a decrease in the COVID-19-attributed mortality growth rate beginning 7 days after implementation, although this decrease was no longer statistically significant by 10 days.

Procrastination is a widespread habit that has been understudied in the realm of health behaviors, especially sleep. This study aimed to examine the cross-sectional relationships between procrastination and multiple dimensions of sleep in a large national sample of US adolescents and young adults. A random sample of 8742 students from 11 US universities provided self-reports of procrastination (measured by the General Procrastination Scale-Short Form with scores ranging from 1 to 5) and sleep behaviors including social jetlag (the absolute difference between mid-sleep times on weeknights and weekend nights), sleep duration (mean weekly, weeknight, and weekend night), insomnia symptoms (trouble falling/staying asleep), daytime sleepiness, and sleep medication use. Multiple linear regression and Poisson regression models adjusted for socio-demographic and academic characteristics as well as response propensity weights. Higher levels of procrastination were significantly associated with greater social jetlag (β = 3.34 min per unit increase in the procrastination score; 95% CI [1.86, 4.81]), shorter mean weekly sleep duration (β = −4.44 min; 95% CI [-6.36, −2.52]), and shorter weeknight sleep duration (β = −6.10 min; 95% CI [-8.37, −3.84]), but not weekend night sleep duration. Moreover, procrastination was associated with insomnia symptoms (Relative Risk (RR) = 1.27; 95% CI [1.19, 1.37]) and daytime sleepiness (RR = 1.32; 95% CI [1.27, 1.38]), but not sleep medication use. The results were robust to adjustment for anxiety and depressive symptoms. Procrastination was associated with greater social jetlag, shorter sleep duration, and worse sleep quality. If causal, the results suggest that interventions to prevent and manage procrastination might help students to improve their sleep health.

Objective: Examine the emergence of differences in sleep duration between infants from different racial/ethnic backgrounds and extent to which differences are explained by socioeconomic status (SES) and sleep continuity. Methods: Sleep duration and continuity (number of night wakings and longest nighttime stretch of sleep) were assessed for 394 infants in the Rise & Sleep Health in Infancy & Early Childhood (SHINE) birth cohort at one- and six-months using the Brief Infant Sleep Questionnaire (BISQ). Multivariable regression was used to estimate associations of race/ethnicity with sleep duration adjusting for individual-level covariates, SES, and sleep continuity. Results: The sample was 40% non-Hispanic white, 33% Hispanic, 11% Black, and 15% Asian. Mean (SD) durations for daytime, nighttime, and total sleep at one-month were 6.3 (2.0), 8.9 (1.5), and 15.2 (2.7) hours, respectively. Corresponding durations at six-months were 3.0 (1.4), 9.9 (1.3), and 13.0 (1.9) hours. At one-month, Hispanic infants had shorter nighttime sleep than white infants [β: −0.44 h (95% CI: −0.80, −0.08)]. At six-months, Hispanic [β: −0.96 h (−1.28, −0.63)] and Black [β: −0.60 h (−1.07, −0.12)] infants had shorter nighttime sleep than white infants. The near 1-h differential in night sleep among Hispanics resulted in shorter total sleep [β: −0.66 h (−1.16, −0.15)]. Associations across all racial/ethnic groups were attenuated after adjustment for SES at one- and six months. Sleep continuity attenuated associations with nighttime and total sleep duration by 20–60% for Hispanic infants at six-months. Conclusions: Differences in sleep duration emerge early in life among racial/ethnic groups and are in part explained by SES and sleep continuity.

Global health research has typically focused on single diseases, and most economic evaluation research to date has analysed technical health interventions to identify ‘best buys’. New approaches in the conduct of economic evaluations are needed to help policymakers in choosing what may be good value (ie, greater health, distribution of health, or financial risk protection) for money (ie, per budget expenditure) investments for health system strengthening (HSS) that tend to be programmatic. We posit that these economic evaluations of HSS interventions will require developing new analytic models of health systems which recognise the dynamic connections between the different components of the health system, characterise the type and interlinks of the system’s delivery platforms; and acknowledge the multiple constraints both within and outside the health sector which limit the system’s capacity to efficiently attain its objectives. We describe priority health system modelling research areas to conduct economic evaluation of HSS interventions and ultimately identify good value for money investments in HSS.

Objectives: In many low- and middle-income countries, the costs of delivering public health programs such as for HIV/AIDS, nutrition, and immunization are not routinely tracked. A number of recent studies have sought to estimate program costs on the basis of detailed information collected on a subsample of facilities. While unbiased estimates can be obtained via accurate measurement and appropriate analyses, they are subject to statistical uncertainty. Quantification of this uncertainty, for example, via standard errors and/or 95% confidence intervals, provides important contextual information for decision-makers and for the design of future costing studies. While other forms of uncertainty, such as that due to model misspecification, are considered and can be investigated through sensitivity analyses, statistical uncertainty is often not reported in studies estimating the total program costs. This may be due to a lack of awareness/understanding of (1) the technical details regarding uncertainty estimation and (2) the availability of software with which to calculate uncertainty for estimators resulting from complex surveys. We provide an overview of statistical uncertainty in the context of complex costing surveys, emphasizing the various potential specific sources that contribute to overall uncertainty. Methods: We describe how analysts can compute measures of uncertainty, either via appropriately derived formulae or through resampling techniques such as the bootstrap. We also provide an overview of calibration as a means of using additional auxiliary information that is readily available for the entire program, such as the total number of doses administered, to decrease uncertainty and thereby improve decision-making and the planning of future studies. Results: A recent study of the national program for routine immunization in Honduras shows that uncertainty can be reduced by using information available prior to the study. This method can not only be used when estimating the total cost of delivering established health programs but also to decrease uncertainty when the interest lies in assessing the incremental effect of an intervention. Conclusion: Measures of statistical uncertainty associated with survey-based estimates of program costs, such as standard errors and 95% confidence intervals, provide important contextual information for health policy decision-making and key inputs for the design of future costing studies. Such measures are often not reported, possibly because of technical challenges associated with their calculation and a lack of awareness of appropriate software. Modern statistical analysis methods for survey data, such as calibration, provide a means to exploit additional information that is readily available but was not used in the design of the study to significantly improve the estimation of total cost through the reduction of statistical uncertainty.

Background: Reduction in maternal and neonatal mortality requires women's use of high-quality facilities for childbirth. Evidence that quality influences women's selection of place of delivery suggests that an investment in quality may increase use of facilities for childbirth. We assessed the impact of a quality improvement project on facility use for childbirth among women in Tanzania. Methods: Of 24 government-managed primary care clinics in Pwani Region, Tanzania, we randomly selected 12 to receive an intervention consisting of: training, supportive supervision, infrastructure support, and peer outreach. The cluster was defined as the health clinic and the villages assigned to its catchment area by the ward. We collected household surveys of women living within the catchment area of each clinic with a birth in the past year at baseline (February–April 2012) and endline (January–April 2016). Women reported the location of birth for each of their deliveries, including the facility name. The primary outcome was report of facility use for childbirth for their most recent birth. The effect of the intervention was assessed using difference-in-difference analysis. We conducted an exploratory secondary analysis among women least likely to use the health system—ie, those whose prior delivery was a home birth. We investigated three pathways from the intervention to increased facility use: improved obstetric quality, improved antenatal care (ANC) quality, and improved links between the health system and the community. Findings: In the intervention clusters, 999 (71·7%) of 1393 women gave birth in a facility at baseline and 1165 (85·3%) of 1365 did so at endline. The corresponding figures for the control clusters were 1146 (72·3%) of 1586 at baseline and 1411 (81·1%) of 1739 at endline. The intervention thus led to an increase in facility births of 6·7 percentage points (95% CI 0·6–12·8). The intervention was substantially more successful in increasing use among women least likely to utilise the health system, giving a 18·3 percentage point increase (95% CI 10·1–26·6). Among the hypothesised mechanisms, the most likely pathway of effect was through ANC: the intervention led to an increase in ANC quality, with providers performing an additional 0·8 (95% CI 0·21–1·34) actions among the low-use population and 0·5 actions among the full population (95% CI −0·01 to 1·01). Interpretation: The quality improvement intervention led to a modest increase in facility use for childbirth and a strong increase among women whose previous delivery was at home. Our analysis provides empirical evidence that investment in quality can increase health care use. In an environment of rising use, quality may be a mechanism for encouraging remaining non-system users to engage in the health system, playing a role in achieving universal health coverage. Funding: US National Institutes of Health 1R01AI093182.

Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for a variety of hematologic malignancies and disorders. Unfortunately, acute graft-versus-host disease (GVHD) is a frequent complication of HCT. While substantial research has identified clinical, genetic and proteomic risk factors for acute GVHD, few studies have sought to develop risk prediction tools that quantify absolute risk. Such tools would be useful for: optimizing donor selection; guiding GVHD prophylaxis, post-transplant treatment and monitoring strategies; and, recruitment of patients into clinical trials. Using data on 9,651 patients who underwent first allogeneic HLA-identical sibling or unrelated donor HCT between 01/1999-12/2011 for treatment of a hematologic malignancy, we developed and evaluated a suite of risk prediction tools for: (i) acute GVHD within 100 days post-transplant and (ii) a composite endpoint of acute GVHD or death within 100 days post-transplant. We considered two sets of inputs: (i) clinical factors that are typically readily-available, included as main effects; and, (ii) main effects combined with a selection of a priori specified two-way interactions. To build the prediction tools we used the super learner, a recently developed ensemble learning statistical framework that combines results from multiple other algorithms/methods to construct a single, optimal prediction tool. Across the final super learner prediction tools, the area-under-the curve (AUC) ranged from 0.613-0.640. Improving the performance of risk prediction tools will likely require extension beyond clinical factors to include biological variables such as genetic and proteomic biomarkers, although the measurement of these factors may currently not be practical in standard clinical settings.

BACKGROUND:Although the prognosis for HIV-infected individuals has improved after antiretroviral therapy (ART) scale-up, limited data exist on the incidence of AIDS-defining opportunistic infections (ADIs) and mortality during ART in resource-limited settings. METHODS:HIV-infected adults in two large hospitals in urban Hanoi were enrolled to the prospective cohort, from October 2007 through December 2013. Those who started ART less than one year before enrollment were assigned to the survival analysis. Data on ART history and ADIs were collected retrospectively at enrollment and followed-up prospectively until April 2014. RESULTS:Of 2,070 cohort participants, 1,197 were eligible for analysis and provided 3,446 person-years (PYs) of being on ART. Overall, 161 ADIs episodes were noted at a median of 3.20 months after ART initiation (range 0.03-75.8) with an incidence 46.7/1,000 PYs (95% confidence interval [CI] 39.8-54.5). The most common ADI was tuberculosis with an incidence of 29.9/1,000 PYs. Mortality after ART initiation was 8.68/1,000 PYs and 45% (19/45) died of AIDS-related illnesses. Age over 50 years at ART initiation was significantly associated with shorter survival after controlling for baseline CD4 count, but neither having injection drug use (IDU) history nor previous ADIs were associated with poor survival. Semi-competing risks analysis in 951 patients without ADIs history prior to ART showed those who developed ADIs after starting ART were at higher risk of death in the first six months than after six months. CONCLUSION:ADIs were not rare in spite of being on effective ART. Age over 50 years, but not IDU history, was associated with shorter survival in the cohort. This study provides in-depth data on the prognosis of patients on ART in Vietnam during the first decade of ART scale-up.

The two-phase design has recently received attention in the statistical literature as an extension to the traditional case-control study for settings where a predictor of interest is rare or subject to missclassification. Despite a thorough methodological treatment and the potential for substantial efficiency gains, the two-phase design has not been widely adopted. This may be due, in part, to a lack of general-purpose, readily-available software. The osDesign package for R provides a suite of functions for analyzing data from a two-phase and/or case-control design, as well as evaluating operating characteristics, including bias, efficiency and power. The evaluation is simulation-based, permitting flexible application of the package to a broad range of scientific settings. Using lung cancer mortality data from Ohio, the package is illustrated with a detailed case-study in which two statistical goals are considered: (i) the evaluation of small-sample operating characteristics for two-phase and case-control designs and (ii) the planning and design of a future two-phase study.