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Summary Background Early childhood development (ECD) programmes can help address early disadvantages for the 43% of children younger than 5 years in low-income and middle-income countries who have compromised development. We aimed to test the effectiveness of two group-based delivery models for an integrated ECD responsive stimulation and nutrition education intervention using Kenya's network of community health volunteers. Methods We implemented a multi-arm, cluster-randomised community effectiveness trial in three rural subcounties across 60 villages (clusters) in western Kenya. Eligible participants were mothers or female primary caregivers aged 15 years or older with children aged 6–24 months at enrolment. If married or in established relationships, fathers or male caregivers aged 18 years or older were also eligible. Villages were randomly assigned (1:1:1) to one of three groups: group-only delivery with 16 fortnightly sessions; mixed delivery combining 12 group sessions with four home visits; and a comparison group. Villages in the intervention groups were randomly assigned (1:1) to invite or not invite fathers and male caregivers to participate. Households were surveyed at baseline and immediately post-intervention. Assessors were masked. Primary outcomes were child cognitive and language development (score on the Bayley Scales of Infant Development third edition), socioemotional development (score on the Wolke scale), and parental stimulation (Home Observation for Measurement of the Environment inventory). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , NCT03548558 . Findings Between Oct 1 and Nov 12, 2018, 1152 mother–child dyads were enrolled and randomly assigned (n=376 group-only intervention, n=400 mixed-delivery intervention, n=376 comparison group). At the 11-month endline survey (Aug 5–Oct 31, 2019), 1070 households were assessed for the primary outcomes (n=346 group only, n=373 mixed delivery, n=351 comparison). Children in group-only villages had higher cognitive (effect size 0·52 SD [95% CI 0·21–0·83]), receptive language (0·42 SD [0·08–0·77]), and socioemotional scores (0·23 SD [0·03–0·44]) than children in comparison villages at endline. Children in mixed-delivery villages had higher cognitive (0·34 SD [0·05–0·62]) and socioemotional scores (0·22 SD [0·05–0·38]) than children in comparison villages; there was no difference in language scores. Parental stimulation also improved for group-only (0·80 SD [0·49–1·11]) and mixed-delivery villages (0·77 SD [0·49–1·05]) compared with the villages in the comparison group. Including fathers in the intervention had no measurable effect on any of the primary outcomes. Interpretation Parenting interventions delivered by trained community health volunteers in mother–child groups can effectively promote child development in low-resource settings and have great potential for scalability. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health

Approximately 15.5 million cancer survivors were alive in the United States in 2016 with expected growth to 26.1 million by 2040 (1). Cancer survivors are living longer because of advances in early detection and treatment, but face psychosocial, cognitive, financial, and physical challenges (1,2). Physical challenges include cardiovascular complications, partly because cancer and cardiovascular disease (CVD) share some cumulative risk factors including tobacco use, physical inactivity, obesity, poor diet, hypertension, diabetes, and dyslipidemia (3). In addition, many cancer treatments damage the heart, and some cancer types increase risk for developing CVD (4). The recognition and management of heart disease in cancer survivors has given rise to the discipline of cardio-oncology, which focuses on the cardiovascular health of this population (5). CVD risk has been previously estimated using prediction models, and studies suggest that physician-patient communication using predicted heart age rather than predicted 10-year risk has led to a more accurate perception of excess heart age, encouraged actions to adopt a healthy lifestyle, and improved modifiable CVD risk factors (6,7). Using the nonlaboratory-based Framingham Risk Score (FRS) to estimate 10-year risk for developing CVD, predicted heart age is estimated from the 10-year risk of CVD (predicted by age, sex, diabetes status, smoking status, systolic blood pressure, hypertension treatment status, and body mass index); it is the age of an otherwise healthy person with the same predicted risk, with all other risk factors included in the prediction model at the normal level (systolic blood pressure of 125 mmHg, no hypertension treatment, body mass index of 22.5, nonsmoker, and nondiabetic) (6). Using data from the Behavioral Risk Factor Surveillance System (BRFSS), this study estimates predicted heart age, excess heart age (difference between predicted heart age and actual age), and racial/ethnic and sociodemographic disparities in predicted heart age among U.S. adult cancer survivors and noncancer participants aged 30-74 years using previously published methods (7). A total of 22,759 men and 46,294 women were cancer survivors with a mean age of 48.7 and 48.3 years, respectively. The predicted heart age and excess heart age among cancer survivors were 57.2 and 8.5 years, respectively, for men and 54.8 and 6.5 years, respectively, for women, and varied by age, race/ethnicity, education and income. The use of predicted heart age by physicians to encourage cancer survivors to improve modifiable risk factors and make heart healthy choices, such as tobacco cessation, regular physical activity, and a healthy diet to maintain a healthy weight, can engage survivors in informed cancer care planning after diagnosis.

In this article, we present a variety of measures that quantify equity in cancer mortality outcomes, demonstrate how the measures perform with various cancer types, and identify counties, or “bright spots,” that meet the criteria of those measures. Using county-level age-adjusted mortality rates for 2007–2016 from the National Center for Health Statistics, we identified counties that had both equitable and optimal outcomes for Black and White death rates across 5 types of cancer: cancers of the lung/bronchus, prostate, female breast, colorectum, and liver. The number of counties that met the criteria ranged from 0 to 442, depending on cancer type and measure used. Prostate cancer and male liver cancer consistently had the lowest number of “bright spots,” with a maximum of 3 counties meeting the most lenient criteria. This paper presents several ways to examine equity, using rate ratios and standard error measures, in cancer mortality outcomes. It highlights areas with positive progress toward equity and areas with a potential need for equity-focused cancer-control planning. Examining local areas of positive deviance can inform cancer-control programming and planning around health equity.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced adverse reaction, which can be fatal in up to 10% of cases. The most frequently associated medications include anticonvulsants, allopurinol, sulfasalazine, and nevirapine.1 Vemurafenib is an oral BRAF kinase inhibitor, approved by the U.S. Food and Drug Administration in 2011 for unresectable or metastatic melanoma with the BRAF V600E mutation. In 2013, the first case of DRESS syndrome due to vemurafenib was described.2 Subsequent publications demonstrate that severe cutaneous reactions to the combination of vemurafenib with cobimetinib occurs not infrequently: in a series of 68 patients receiving this combination, 16% developed DRESS.3 Herein, we report a case of DRESS syndrome in a patient receiving vemurafenib and cobimetinib for metastatic melanoma. After recovery, she was successfully switched to encorafenib and binimetinib without recurrence after 6 months.

Background Hundreds of millions of children living in poverty worldwide are not reaching their full, developmental potential. Programs to promote nurturing and responsive caregiving, such as those in which community health workers (CHWs) conduct home visits to support optimal early childhood development (ECD), have been effective in small trials, but have not achieved similar success at scale. This study will explore two approaches to scale-up: converting a home-visiting model to a group-based model; and integrating the ECD curriculum into an existing government program. The objectives of the study are to: 1) Measure how the integration of ECD activities affects time and task allocation of CHWs and CHW psychosocial wellbeing; 2) Examine how the integration of ECD activities affects caregiver-child dyad participation in standard health and nutrition activities; and 3) Explore how the availability of age-appropriate play materials at home affects caregiver-child dyad participation rates in a group-based ECD program. Methods We will randomize 75 communities in rural Madagascar into three arms: 1) [C], which is the status quo (community-based health and nutrition program); 2) [T], which is C + ECD group sessions [T]; and 3) [T +], which is T with the addition of an enhanced play materials package for home use. All children between 6–30 months old at the time of the intervention launch will be eligible to participate in group activities. The intervention will last 12 months and is comprised of fortnightly group sessions in which the CHWs provide caregiver-child dyads with information relating to ECD; CHWs will also include structured time for caregivers to practice the play and child stimulation activities they have learned. We will administer monthly surveys to measure CHW time use and task allocation, and we will leverage administrative data to measure caregiver-child dyad participation in the group sessions. Discussion The results from the trial will provide the evidence base required to implement an integrated package of nutrition, health and ECD promotion activities at scale in Madagascar, and findings may be relevant in other low-income countries. Trial registration This trial is registered on the AEA Social Science Registry (AEARCTR-0004704) on November 15, 2019 and on ClinicalTrials.gov (NCT05129696) on November 22, 2021.

While studies have speculated that immune function may play a role in how water, sanitation, hygiene, and nutritional (N+WSH) interventions may individually impact child growth and development, the combined effects of these interventions on immune system development are unknown. Here, we report on a trial in rural Bangladesh, where we cluster-randomized pregnant women into control and N+WSH arms. Among the birth cohort, we quantified plasma IL-1β, IL-6, TNF-α, IL-2, IL-12p70, IFN-γ, IL-4, IL-5, IL-13, IL-17A, IL-21, IL-10, and GM-CSF at ages 14 and 28 months. Cytokine ratios were included as prespecified outcomes to examine the net inflammatory environment. We assessed 704 children. After one year, TNF-α/IL-10, IL-12/IL-10, and IL-17A/IL-10 ratios were lower in the intervention group compared to the control group (mean difference: -0.12 to -0.19, p

Author(s): Dewey, Kathryn G; Wessells, K Ryan; Arnold, Charles D; Prado, Elizabeth L; Abbeddou, Souheila; Adu-Afarwuah, Seth; Ali, Hasmot; Arnold, Benjamin F; Ashorn, Per; Ashorn, Ulla; Ashraf, Sania; Becquey, Elodie; Bendabenda, Jaden; Brown, Kenneth H; Christian, Parul; Colford, John M; Dulience, Sherlie JL; Fernald, Lia CH; Galasso, Emanuela; Hallamaa, Lotta; Hess, Sonja Y; Humphrey, Jean H; Huybregts, Lieven; Iannotti, Lora L; Jannat, Kaniz; Lartey, Anna; Port, Agnes Le; Leroy, Jef L; Luby, Stephen P; Maleta, Kenneth; Matias, Susana L; Mbuya, Mduduzi NN; Mridha, Malay K; Nkhoma, Minyanga; Null, Clair; Paul, Rina R; Okronipa, Harriet; Ouedraogo, Jean-Bosco; Pickering, Amy J; Prendergast, Andrew J; Ruel, Marie; Shaikh, Saijuddin; Weber, Ann M; Wolff, Patricia; Zongrone, Amanda; Stewart, Christine P | Abstract: ABSTRACTBackgroundMeta-analyses have demonstrated that small-quantity lipid-based nutrient supplements (SQ-LNS) reduce stunting and wasting prevalence among infants and young children. Identification of subgroups who benefit most from SQ-LNS may facilitate program design.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child growth outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n=37,066). We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models, with random-effects models as sensitivity analyses. We used random effects meta-regression to examine study-level effect modifiers. Heterogeneity was assessed using I2 and Tau2 statistics. Sensitivity analyses were conducted to examine whether results differed depending on inclusion criteria for arms within trials and types of comparisons.ResultsSQ-LNS provision decreased stunting (length-for-age z-score l −2) by 12% (relative reduction), wasting (weight-for-length (WLZ) z-score l −2) by 14%, low mid-upper arm circumference (MUAC l 125 mm or MUACZ l −2) by 18%, acute malnutrition (WLZ l −2 or MUAC l 125 mm) by 14%, underweight (weight-for-age z-score l −2) by 13%, and small head size (head-circumference z-score l −2) by 9%. Effects of SQ-LNS on growth outcomes generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact or average reported compliance with SQ-LNS. Effects of SQ-LNS on stunting, wasting, low MUAC and small head size were greater among girls than among boys; effects on stunting, underweight and low MUAC were greater among later-born (vs. first-born) children; and effects on wasting and acute malnutrition were greater among children in households with improved (vs. unimproved) sanitation. Results were similar across sensitivity analyses.ConclusionsThe positive impact of SQ-LNS on growth is apparent across a wide variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNS in the mix of interventions to prevent both stunting and wasting. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Introduction Community health workers (CHWs) deliver services at-scale to reduce maternal and child undernutrition, but often face inadequate support from the health system to perform their job well. Supportive supervision is a promising intervention that strengthens the health system and can enable CHWs to offer quality services. Objectives We examined if greater intensity of supportive supervision as defined by monitoring visits to Anganwadi Centre, CHW-supervisor meetings, and training provided by supervisors to CHWs in the context of Integrated Child Services Development (ICDS), a national nutrition program in India, is associated with higher performance of CHWs. Per program guidelines, we develop the performance of CHWs measure by using an additive score of nutrition services delivered by CHWs. We also tested to see if supportive supervision is indirectly associated with CHW performance through CHW knowledge. Methods We used longitudinal survey data of CHWs from an impact evaluation of an at-scale technology intervention in Madhya Pradesh and Bihar. Since the inception of ICDS, CHWs have received supportive supervision from their supervisors to provide services in the communities they serve. Mixed-effects logistic regression models were used to test if higher intensity supportive supervision was associated with improved CHW performance. The model included district fixed effects and random intercepts for the sectors to which supervisors belong. Results Among 809 CHWs, the baseline proportion of better performers was 45%. Compared to CHWs who received lower intensity of supportive supervision, CHWs who received greater intensity of supportive supervision had 70% higher odds (AOR 1.70, 95% CI 1.16, 2.49) of better performance after controlling for their baseline performance, CHW characteristics such as age, education, experience, caste, timely payment of salaries, Anganwadi Centre facility index, motivation, and population served in their catchment area. A test of mediation indicated that supportive supervision is associated indirectly with CHW performance through improvement in CHW knowledge. Conclusion Higher intensity of supportive supervision is associated with improved CHW performance directly and through knowledge of CHWs. Leveraging institutional mechanisms such as supportive supervision could be important in improving service delivery to reach beneficiaries and potentially better infant and young child feeding practices and nutritional outcomes. Trial registration : Trial registration number: https://doi.org/10.1186/ISRCTN83902145

IntroductionIn low- and middle-income countries, children experience multiple risks for delayed development. We evaluated a multicomponent, group-based early child development intervention including behavioural recommendations on responsive stimulation, nutrition, water, sanitation, hygiene, mental health and lead exposure prevention.MethodsWe conducted a 9-month, parallel, multiarm, cluster-randomised controlled trial in 31 rural villages in Kishoreganj District, Bangladesh. Villages were randomly allocated to: group sessions (‘group’); alternating groups and home visits (‘combined’); or a passive control arm. Sessions were delivered fortnightly by trained community members. The primary outcome was child stimulation (Family Care Indicators); the secondary outcome was child development (Ages and Stages Questionnaire Inventory, ASQi). Other outcomes included dietary diversity, latrine status, use of a child potty, handwashing infrastructure, caregiver mental health and knowledge of lead. Analyses were intention to treat. Data collectors were independent from implementers.ResultsIn July–August 2017, 621 pregnant women and primary caregivers of childrenConclusionOur findings suggest that group-based, multicomponent interventions can be effective at improving child development outcomes in rural Bangladesh, and that they have the potential to be delivered at scale.Trial registration numberThe trial is registered in ISRCTN (ISRCTN16001234).

ObjectiveTo determine the magnitude of relationships of early life factors with child development in low/middle-income countries (LMICs).DesignMeta-analyses of standardised mean differences (SMDs) estimated from published and unpublished data.Data sourcesWe searched Medline, bibliographies of key articles and reviews, and grey literature to identify studies from LMICs that collected data on early life exposures and child development. The most recent search was done on 4 November 2014. We then invited the first authors of the publications and investigators of unpublished studies to participate in the study.Eligibility criteria for selecting studiesStudies that assessed at least one domain of child development in at least 100 children under 7 years of age and collected at least one early life factor of interest were included in the study.AnalysesLinear regression models were used to assess SMDs in child development by parental and child factors within each study. We then produced pooled estimates across studies using random effects meta-analyses.ResultsWe retrieved data from 21 studies including 20 882 children across 13 LMICs, to assess the associations of exposure to 14 major risk factors with child development. Children of mothers with secondary schooling had 0.14 SD (95% CI 0.05 to 0.25) higher cognitive scores compared with children whose mothers had primary education. Preterm birth was associated with 0.14 SD (–0.24 to –0.05) and 0.23 SD (–0.42 to –0.03) reductions in cognitive and motor scores, respectively. Maternal short stature, anaemia in infancy and lack of access to clean water and sanitation had significant negative associations with cognitive and motor development with effects ranging from −0.18 to −0.10 SDs.ConclusionsDifferential parental, environmental and nutritional factors contribute to disparities in child development across LMICs. Targeting these factors from prepregnancy through childhood may improve health and development of children.

BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) reduce child stunting and provide many of the fatty acids and micronutrients that are necessary for rapid brain development that occurs during infancy and early childhood. Positive effects of SQ-LNS on developmental outcomes have been found in some trials, but not others.ObjectivesOur objectives were to generate pooled estimates of the effect of SQ-LNS, compared to control groups that received no intervention or an intervention without any nutritional supplement, on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 intervention versus control group comparisons in 13 randomized trials of SQ-LNS provided to infants and young children age 6 to 24 months in 9 low- or middle-income countries (total n=30,024). We generated study-specific estimates of SQ-LNS vs. control groups (including main effects and subgroup estimates for individual-level effect modifiers) and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.ResultsIn 11-13 intervention versus control group comparisons (n=23,588-24,561), SQ-LNS increased mean language (mean difference: 0.07 standard deviations; 95% CI: 0.04, 0.10), social-emotional (0.08; 0.05, 0.11), and motor scores (0.08; 0.05, 0.11) and reduced the prevalence of children in the lowest decile of these scores by 17% (prevalence ratio: 0.83, 95% CI 0.76, 0.91), 19% (0.81; 0.74, 0.90), and 16% (0.84; 0.77, 0.92), respectively. SQ-LNS also increased the prevalence of children walking without support at 12 months by 9% (1.09; 1.05, 1.14). Effects of SQ-LNS on language, social-emotional, and motor outcomes were larger among study populations with a higher burden (≥ 35%) of child stunting at 18 months (mean difference 0.11-0.13 SD; 8-9 comparisons) than in populations with lower stunting burden (estimates near zero). At the individual level, greater effects of SQ-LNS were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socio-economic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).ConclusionsSQ-LNS provided daily to children in the range of 6-24 months of age can be expected to result in modest, but potentially important, developmental gains, particularly in populations with high child stunting burden. Certain groups of children who experience higher risk environments, such as those from poor households or with poor baseline nutritional status, have greater potential to benefit from SQ-LNS in developmental outcomes. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Background Over recent decades, Vietnam has experienced rapid economic growth, a nutrition transition from the traditional diet to highly-processed and calorie-dense foods and beverages, and an increasing prevalence of childhood overweight/obesity (ow/ob). The goal of this study is to describe the patterns of ow/ob in a longitudinal sample of Vietnamese children from ages 1 to 8, and the sociodemographic and behavioral factors associated with ow/ob at age 8. Methods This study is a secondary data analysis of a geographically-representative, longitudinal cohort of 1961 Vietnamese children from the Young Lives Cohort Study from 2002 to 2009. Thirty-one communities were selected with oversampling in rural communities, and children age 1 were recruited from each community using simple random sampling. Surveys of families and measurements of children were collected at child ages 1, 5, and 8. Our specified outcome measure was childhood ow/ob at age 8, defined by the World Health Organization’s thresholds for body-mass-index (BMI) for age Z-scores. Associations between early and concurrent socio-behavioral factors, childhood nutrition and physical activity variables were analyzed using STATA 15. Bivariate and multivariable analyses were completed utilizing logistic regression models. Results The prevalence of ow/ob increased from 1.1% in both sexes at age 1 to 7% in females and 13% in males at age 8. Bivariate analyses show greater likelihood of ow/ob at age 8 was significantly associated with early life sociodemographic factors (at age 1), male sex (OR = 2.2, 1.6–3.1), higher wealth (OR = 1.1–1.4), and urban residence (OR = 4.3, 3–6). In adjusted analyses, ow/ob at age 8 was associated with early nutrition practices at age 5, including frequent consumption of powdered milk (OR = 2.8, 1.6–4.6), honey/sugar (OR = 2.7, 1.8–4.1), prepared restaurant/fast foods (OR = 4.6, 2.6–8.2), and packaged sweets (OR = 3.4, 2.3–4.9). In addition, breastfeeding for 6 months or longer was protective against obesity at age 8 (OR = 0.3, 0.1–0.9). Conclusions We found that increased consumption of powdered milk, honey/sugar, packaged sweets, and prepared restaurants/fast foods are associated with childhood ow/ob. In contrast, breastfeeding for 6 months or longer was protective against childhood ow/ob. These findings suggest that public health programs and campaigns aimed to prevent childhood ow/ob in Vietnam should target early feeding practices.

Item does not contain fulltext BACKGROUND: Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin analogues might decrease rebleeding rates, but the true effect size is unknown. We therefore aimed to investigate the efficacy of somatostatin analogues on red blood cell transfusion requirements of patients with gastrointestinal angiodysplasias and to identify subgroups that might benefit the most from somatostatin analogue therapy. METHODS: We did a systematic review and individual patient data meta-analysis. We searched MEDLINE, Embase, and Cochrane on Jan 15, 2016, with an updated search on April 25, 2021. All published randomised controlled trials and cohort studies that reported on somatostatin analogue therapy in patients with gastrointestinal angiodysplasias were eligible for screening. We excluded studies without original patient data, single case reports, small case series (ie

Author(s): Wessells, K Ryan; Arnold, Charles D; Stewart, Christine P; Prado, Elizabeth L; Abbeddou, Souheila; Adu-Afarwuah, Seth; Arnold, Benjamin F; Ashorn, Per; Ashorn, Ulla; Becquey, Elodie; Brown, Kenneth H; Byrd, Kendra A; Campbell, Rebecca K; Christian, Parul; Fernald, Lia CH; Fan, Yue-Mei; Galasso, Emanuela; Hess, Sonja Y; Huybregts, Lieven; Jorgensen, Josh M; Kiprotich, Marion; Kortekangas, Emma; Lartey, Anna; Le Port, Agnes; Leroy, Jef L; Lin, Audrie; Maleta, Kenneth; Matias, Susana L; Mbuya, Mduduzi NN; Mridha, Malay K; Mutasa, Kuda; Naser, Abu Mohd; Paul, Rina R; Okronipa, Harriet; Ouedraogo, Jean-Bosco; Pickering, Amy J; Rahman, Mahbubur; Schulze, Kerry; Smith, Laura E; Weber, Ann M; Zongrone, Amanda; Dewey, Kathryn G | Abstract: ABSTRACTBackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to reduce the prevalence of anemia and iron deficiency among infants and young children, but effects on other micronutrients are less well known. Identifying subgroups who may experience greater benefits from SQ-LNS, or who are more likely to respond to the intervention, may facilitate the development of public health policies and programs.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child hematological and micronutrient status outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n = 15,946). Outcomes were hemoglobin (Hb), inflammation-adjusted plasma ferritin, soluble transferrin receptor, zinc, retinol and retinol binding protein (RBP), and erythrocyte zinc protoporphyrin, and respective dichotomous outcomes indicative of anemia and micronutrient deficiency. We generated study-specific estimates of SQ-LNS vs. control, including main effects and subgroup estimates for individual-level effect modifiers, and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.ResultsProvision of SQ-LNS decreased the prevalence of anemia (Hb l 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin l 12 µg/L) by 56% and iron deficiency anemia (IDA; Hb l 110 g/L and plasma ferritin l 12 µg/L) by 64%. We observed positive effects of SQ-LNS on hematological and iron status outcomes within all subgroups of the study-level and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNS on anemia and iron status were greater in trials that provided SQ-LNS for g 12 months and provided 9 mg/d vs. l 9 mg iron/d, and among later-born (vs. first-born) children. There was no effect of SQ-LNS on plasma zinc or retinol, but there was a 7% increase in plasma RBP and a 56% reduction in vitamin A deficiency (RBP l 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics.ConclusionsSQ-LNS provided to infants and young children 6-24 months of age can substantially reduce the prevalence of anemia, iron deficiency, and IDA across a range of individual, population and study design characteristics. Policy-makers and program planners should consider SQ-LNS within intervention packages to prevent anemia and iron deficiency. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

BackgroundAnganwadi Workers (AWWs) are a group of 1.4 million community health workers that operate throughout rural India as a part of the Integrated Child Development Services program. AWWs are responsible for disseminating key health information regarding nutrition, family planning, and immunizations to the women and children in their catchment area, while maintaining detailed registers that track key beneficiary data, updates on health status, and supply inventory beneficiaries. There is a need to understand how AWWs spend their time on all of these activities given all of their responsibilities, and the factors that are associated with their time use.MethodsThis cross-sectional study conducted in Madhya Pradesh, collected time use data from AWWs using a standard approach in which we asked participants how much time they spent on various activities. Additionally, we estimated a logistic regression model to elucidate what AWW characteristics are associated with time use.ResultsWe found that AWWs spend substantial amounts of time on administrative tasks, such as filling out their paper registers. Additionally, we explored the associations between various AWW characteristics and their likelihood of spending the expected amount of time on preschool work, filling out their registers, feeding children, and conducting home visits. We found a positive significant association between AWW education and their likelihood of filling out their registers.ConclusionsAWWs spend substantial amounts of time on administrative tasks, which could take away from their ability to spend time on providing direct care. Additionally, future research should explore why AWW characteristics matter and how such factors can be addressed to improve AWWs’ performance and should explore the associations between Anganwadi Center characteristics and AWW time use.

RESUMO : A formacao docente torna-se cada vez mais desafiadora no contexto da educacao. Em meio a uma sociedade tecnologica, focada em desempenhos e resultados, a formacao docente contempla discussoes sobre a praxis e o complexo cenario de ensinar, apoiar a aprendizagem e avaliar em meio a tantas metodologias e abordagens psicologicas. Esse mesmo cenario requer qualificacao constante, saberes e fazeres docentes e boas praticas. A formacao docente precisa encontrar novas possibilidades. O objetivo deste trabalho e analisar as interacoes sociais entre professores universitarios no projeto Sala (Virtual) dos Professores. O projeto foi baseado na perspectiva historico-cultural de Vygotsky e no potencial das tecnologias, a fim de criar um processo continuo de interacao social e formacao docente. Iniciado em 2014, o projeto acontece em um curso de Administracao de uma instituicao privada do Rio Grande do Sul. Os achados aqui apresentados foram obtidos por meio de observacao participante e fichamento das atividades de 28 docentes do curso. Mediante analise tematica, os resultados indicam que o projeto contribuiu para: aumentar a participacao dos professores nas acoes devido a sua flexibilidade espaco-temporal, para a troca de conhecimentos e experiencia devido ao atendimento das necessidades especificas dos professores, de suas areas e disciplinas. Alem disso, permitiu estabelecer conexoes pessoais, criar estrategias intencionais de forma colaborativa, qualificar as atividades docentes e avaliacoes, manter uma interacao constante, apesar de nao ter potencial para substituir a presencialidade necessaria para subsidiar a atuacao e a formacao docente . PALAVRAS - CHAVE : formacao docente; Vygotsky; interacao social; tecnologias . ABSTRACT : Teacher education is becoming increasingly challenging in the context of education on a technological society. In a technological society, focused on performance and results, teacher education includes discussions on praxis and the complex scenario of teaching, supporting learning and evaluating among so many methodologies and psychological approaches. This same scenario requires constant qualification, knowledge, teaching skills and good practices. So, teacher education needs new possibilities. The objective of this work is to analyse the social interactions among university professors in the Teachers (Virtual) Room project. The project was based on Vygotsky’s historical-cultural perspective and on the potential of technologies, in order to create a continuous process of social interaction and teacher education. This project started in 2014 and takes place in a Business Administration course at a private institution in Rio Grande do Sul. The findings were obtained through participant observation and record of the activities of 28 teachers of the course. Through thematic analysis, the results indicate that the project contributed to: increasing teacher’s participation on the activities due to its space-time flexibility, to the exchange of knowledge and experience due to meeting the specific needs of teachers, their areas and disciplines. The project also allowed us to establish personal connections, creating intentional strategies, qualifying teaching activities and evaluations, supporting a constant interaction, despite not having the potential to replace the presence needed to subsidize teaching activities and training . KEYWORDS : t eacher training; Vygotsky; social interaction; tecnhologies .

OBJECTIVES: Implementation research can support iterative program improvement, yet limited examples of such dynamic experiences exist. We conducted a multi-stage and multi-method process evaluation (PE) of a large-scale m-Health intervention in India that currently reaches 581,282 frontline workers (FLWs). The intervention (Common Application Software (CAS)) includes a smartphone application that digitizes FLW service-tracking registers and acts as a job aid and multiple dashboards for real-time monitoring. We examined factors affecting the roll-out of CAS in two Indian states. METHODS: Program impact pathways were developed with implementers to inform research questions and methods. Data were collected across many time points between 2016 and 2018 to temporally align with program roll-out. In total, we did in-person surveys with FLWs (n = 100), supervisors (n = 55), other staff (n = 18), two phone surveys with FLWs (n = 404), interviews with national and state-level stakeholders (n = 21), and routine meetings with implementers. Short phone surveys were conducted between in-person surveys to give rapid feedback to implementers. RESULTS: Impediments to roll-out included state readiness, delays in device procurement and set-up, dashboard readiness, and low data storage space. Over time, FLWs satisfaction with training remained consistent (100–99%), use of CAS (82–100%), and preference to use it (74–80%) increased. Challenges declined over time [e.g., slow internet (79– >58%), battery heating (62– >45%), and network issues (68– >52%). Most FLWs were knowledgeable of CAS but were confused with symbols/colors in certain domains of CAS. Supervisors were satisfied with training, were knowledgeable of CAS, but hardware issues precluded some from using it. Use of the dashboard, a critical feedback mechanism, was limited due to gaps in staff training and version modifications. CONCLUSIONS: A dynamic and engaged PE implemented with inputs from multiple stakeholders helped provide timely and meaningful feedback to a large-scale program, enabling corrective actions and increasing potential for impact of the program. Implementing a dynamic PE is time and resource intensive and required flexibility in timing and modalities of data collection. FUNDING SOURCES: Bill & Melinda Gates Foundation, via grants to IFPRI and UCSF.

OBJECTIVES: An mHealth job aid and real time monitoring tool currently targets over 1 million community health workers in India (Anganwadi workers – AWWs). Previous studies have shown that mHealth interventions can be effective at a small scale. In this study, we evaluate whether this at-scale mHealth intervention improved the quantity and quality of AWW home visits and counseling. We also examined whether these improvements led to better infant and young child feeding (IYCF) practices among beneficiaries. METHODS: The mHealth intervention (Common Application Software – CAS) is currently being used by 581,282 AWWs across India. We conducted a village-matched, quasi-experimental design to examine program effectiveness across 428 villages in Madhya Pradesh (MP) and Bihar (BH). Repeated cross-sectional surveys were completed 17–24 months apart with AWWs (n = 1344) and mothers of children

OBJECTIVES: Administrative Data (AD) are a key component of nutrition data systems, but little is known about how AD are used or can be reshaped for accountability and action. We studied factors influencing AD use in India's Integrated Child Development Services (ICDS), in two Indian states; and assessed how an m-Health intervention (Common Application Software (CAS)) changes it. ICDS-AD system consolidates data from 11-recording registers updated every month by ∼1.3 million frontline workers (FLW). CAS digitizes these records and creates dashboards for real-time monitoring. METHODS: We conducted semi-structured interviews (n = 82) with supervisory staff at sub-district [Lady Supervisors (LS); Child Development Project Officer (CDPO)] and district level [District Program Officer (DPO)] to understand AD use patterns, facilitators and barriers. Data were coded, summarized and analysed across levels of supervisory staff. RESULTS: LS supervise FLWs, visit villages monthly to monitor data, and collate it to the sub-district level. Due to limited time and pressures to update AD on time, LS focus on data completeness and not on quality or data use. At the next level, CDPOs review and discuss program targets for indicators with LS, and check data completeness. They create monthly reports on targets for the districts, based on LS reports. At the district, DPOs use compiled reports to review subdistrict performance and discuss any gaps with CDPOs. CAS makes the data entry, compilation and report generation easier for all users. LS can monitor data entry daily in CAS and data collation is automated. CDPOs can review the CAS dashboard and use it to discuss issues with LS and DPOs. However, program target indicators dominate use of data. In CAS areas, these include growth monitoring completion, home visits, identification of malnourished children, and their referral. Overall, data use is target-driven, with indicators for monitoring prioritized by program management. CONCLUSIONS: Focus of data use has been on reporting up on target indicators rather than on local program improvement, due to staff and time constraints. CAS can address some AD use constraints by easing data entry and data compilation but a data culture that focuses on predetermined target indicators can limit use for local program improvement. FUNDING SOURCES: Bill & Melinda Gates Foundation via grants to IFPRI and UCSF.

BackgroundIron deficiency anemia affects hundreds of millions of women and children worldwide and is associated with impaired infant outcomes. Small-quantity lipid-based nutrient supplement (LNS) have been found to reduce the prevalence of anemia and iron deficiency in some trials.ObjectivesWe evaluated the effectiveness of daily LNS supplementation on child anemia and micronutrient status in Madagascar within the context of an existing, scaled-up nutrition program.MethodsWe cluster-randomized 125 communities to (T0) a routine program with monthly growth monitoring and nutrition education; (T1) T0+home visits for intensive nutrition counselling; (T2) T1+LNS for children aged 6-18mo; (T3) T2+LNS for pregnant/lactating women; or (T4) T1+parenting messages. Pregnant women and infants aged

This article looks at both nutrition and early childhood stimulation interventions as part of an integrated life cycle approach to development. We build on recent systematic reviews of child development, which are comprehensive in regard to what is currently known about outcomes reported in key studies. We then focus particularly on implementation, scaling, and economic returns, drawing mainly on experience in low- and middle-income countries where undernutrition and poor child development remain significant public health challenges with implications across the life course.

Malaria is a leading cause of morbidity and mortality among children under five years of age, with most cases occurring in Sub-Saharan Africa. Children in this age group in Africa are at greatest risk worldwide for developmental deficits. There are research gaps in quantifying the risks of mild malaria cases, understanding the pathways linking malaria infection and poor child development, and evaluating the impact of malaria on the development of children under five years. We analyzed the association between malaria infection and gross motor, communication, and personal social development in 592 children age 24 months in rural, western Kenya as part of the WASH Benefits environmental enteric dysfunction sub-study. Eighteen percent of children had malaria, 20% were at risk for gross motor delay, 21% were at risk for communication delay, and 23% were at risk for personal social delay. Having a positive malaria test was associated with increased risk for gross motor, communication, and personal social delay while adjusting for child characteristics, household demographics, study cluster, and intervention treatment arm. Mediation analyses suggested that anemia was a significant mediator in the pathway between malaria infection and risk for gross motor, communication, and personal social development delays. The proportion of the total effect of malaria on the risk of developmental delay that is mediated by anemia across the subscales was small (ranging from 9% of the effect on gross motor development to 16% of the effect on communication development mediated by anemia). Overall, malaria may be associated with short-term developmental delays during a vulnerable period of early life. Therefore, preventative malaria measures and immediate treatment are imperative for children&rsquo, s optimal development, particularly in light of projections of continued high malaria transmission in Kenya and Africa.

Author(s): Gopalakrishnan, Lakshmi; Buback, Laura; Fernald, Lia; Walker, Dilys; Diamond-Smith, Nadia; in addition to The CAS Evaluation Consortium | Abstract: BACKGROUND:mHealth technologies are proliferating globally to address quality and timeliness of health care delivery by Community Health Workers (CHWs). This study aimed to examine CHW and beneficiaries' perceptions of a new mHealth intervention (Common Application Software [CAS] for CHWs in India. The objectives of the study were to seek perspectives of CHWs and beneficiaries on the uptake of CAS, changes in CHW-beneficiary interactions since the introduction of CAS and potential barriers faced by CHWs in use of CAS. Further, important contextual factors related to CHW-beneficiary interface and dynamics that may have a bearing on CAS have been described. METHODS:A qualitative study was conducted in two states of India (Bihar and Madhya Pradesh) from March-April 2018 with CHWs (n = 32) and beneficiaries (n = 55). All interviews were conducted and recorded in Hindi, transcribed and translated into English, and coded and thematically analysed using Dedoose. FINDINGS:The mHealth intervention was acceptable to the CHWs who felt that CAS improved their status in the communities where they worked. Beneficiaries' views were a mix of positive and negative perceptions. The divergent views between CHWs and beneficiaries surrounding the use and impact of CAS highlight an underlying mistrust, socio-cultural barriers in engagement, and technological barriers in implementation. All these contextual factors can influence the perception and uptake of CAS. CONCLUSIONS:mHealth interventions targeting CHWs and beneficiaries have the potential to improve performance of CHWs, reduce barriers to information and potentially change the behaviors of beneficiaries. While technology is an enabler for CHWs to improve their service delivery, it does not necessarily help overcome social and cultural barriers that impede CHW-beneficiary interactions to bring about improvements in knowledge and health behaviors. Future interventions for CHWs including mHealth interventions should examine contextual factors along with the acceptability, accessibility, and usability by beneficiaries and community members.

Background The Quality-Adjusted Life Year (QALY) is internationally recognized as standard metric of health outcomes in cost-effectiveness analyses (CEAs) in healthcare. The ongoing debate concerning the appropriateness of its use for decision-making in palliative care has been recently mapped in a review. The aim was to report on and draw conclusions from two expert meetings that reflected on earlier mapped issues in order to reach consensus, and to advise on the QALY’s future use in palliative care. Methods A nominal group approach was used. In order to facilitate group decision making, three statements regarding the use of the QALY in palliative care were discussed in a structured way. Two groups of international policymakers, healthcare professionals and researchers participated. Data were analysed qualitatively using inductive coding. Results 1) Most experts agreed that the recommended measurement tool for the QALYs ‘Q’ component, the EuroQol-5D (EQ-5D), is inappropriate for palliative care. A more sensitive tool, which might be based on the capabilities approach, could be used or developed. 2) Valuation of time should be incorporated in the ‘Q’ part, leaving the linear clock time in the ‘LY’ component. 3) Most experts agreed that the QALY, in its current shape, is not suitable for palliative care. Conclusions 1) Although the EQ-5D does not suffice, a generic tool is needed for the QALY. As long as no suitable alternative is available, other tools can be used besides or serve as basis for the EQ-5D because of issues in conceptual overlap. 2) Future research should further investigate the valuation of time issue, and how best to integrate it in the ‘Q’ component. 3) A generic outcome measure of effectiveness is essential to justly allocate healthcare resources. However, experts emphasized, the QALY is and should be one of multiple criteria for choices in the healthcare insurance package.

Background Human capital (the knowledge, skills, and health that accumulate over life) can be optimized by investments in early childhood to promote cognitive and language development. Parents and caregivers play a crucial role in the promotion and support of cognitive development in their children. Thus, understanding caregiver perceptions of a child’s capabilities and attributes, including intelligence, may enhance investments early in life. To explore this question, we asked caregivers to rank their child’s intelligence in comparison with other children in the community, and compared this ranking with children’s scores on an assessment of developmental abilities across multiple domains. Methods Our study examined cross-sectional data of 3361 children aged 16–42 months in rural Madagascar. Child intelligence, as perceived by their caregiver, was captured using a ladder ranking scale based on the MacArthur Scale for Subjective Social Status. Children’s developmental abilities were assessed using scores from the Ages and Stages Questionnaire: Inventory (ASQ-I), which measures cognitive, language, and socio-emotional development. Ranked percentiles of the ASQ-I were generated within communities and across the whole sample. We created categories of under-estimation, matched, and over-estimation by taking the differences in rankings between caregiver-perceived child intelligence and ASQ-I. Child nutritional status, caregiver belief of their influence on child intelligence, and sociodemographic factors were examined as potential correlates of discordance between the measures using multinomial logistic regressions. Results We found caregiver perceptions of intelligence in Madagascar did not align consistently with the ASQ-I, with approximately 8% of caregivers under-estimating and almost 50% over-estimating their children’s developmental abilities. Child nutritional status, caregiver belief of their influence on child intelligence, caregiver education, and wealth were associated with under- or over-estimation of children’s developmental abilities. Conclusions Our findings suggest parents may not always have an accurate perception of their child’s intelligence or abilities compared with other children. The results are consistent with the limited literature on parental perceptions of child nutrition, which documents a discordance between caregiver perceptions and objective measures. Further research is needed to understand the common cues caregivers that use to identify child development milestones and how these may differ from researcher-observed measures in low-income settings. Trial registration Current Controlled Trials ISRCTN14393738. Registered June 23, 2015.

Summary: Background: Evidence from efficacy trials suggests that lipid-based nutrient supplementation (LNS) and home visits can be effective approaches to preventing chronic malnutrition and promoting child development in low-income settings. We tested the integration of these approaches within an existing, large-scale, community-based nutrition programme in Madagascar. Methods: We randomly allocated 125 programme sites to five intervention groups: standard-of-care programme with monthly growth monitoring and nutrition education (T0); T0 plus home visits for intensive nutrition counselling through an added community worker (T1); T1 plus LNS for children aged 6–18 months (T2); T2 plus LNS for pregnant or lactating women (T3); or T1 plus fortnightly home visits to promote and encourage early stimulation (T4). Pregnant women (second or third trimester) and infants younger than 12 months were enrolled in the trial. Primary outcomes were child growth (length-for-age and weight-for-length Z scores) and development at age 18–30 months. Analyses were by intention to treat. The trial was registered with the ISRCTN registry, number ISRCTN14393738. Findings: The study enrolled 3738 mothers: 1248 pregnant women (250 women in each of the T0, T1, T2, and T4 intervention groups and 248 in the T3 intervention group) and 2490 children aged 0–11 months (497 children in T0, 500 in T1, 494 in T2, 499 in T3, and 500 in T4) at baseline who were assessed at 1-year and 2-year intervals. There were no main effects of any of the intervention groups on any measure of anthropometry or any of the child development outcomes in the full sample. However, compared with children in the T0 intervention group, the youngest children (

Background Brazil is the most populous country with a public, universal and free health care system. The National Program for Access and Quality Improvement in Primary Care (PMAQ) was created to improve the quality of primary health care (PHC). Objective To evaluated whether progress generally has been made within Brazil’s PHC since PMAQ implementation, and if changes occurred uniformly in the country, while also identifying municipal characteristics that may have influenced the improvement. Methods This is an observational study using data from PMAQ external evaluation (2012 and 2014), a 1200-item survey used to evaluate Brazilian PHC quality. After confirming the groupings of items using factor analysis, we created 23 composed indexes (CIs) related to infrastructure and work process. Results On average, the large majority of CIs showed improvements between 2012 and 2014. Region and city size moderated changes in the PHC indices differently. Overall, there were better improvements in infrastructure in the Northeast compared with other country regions, and in smaller cities (10 000–20 000 people). Infrastructure indices appear to have improved equitably across the country. Work process improvements varied with city size and region. Conclusion Despite similar support of PMAQ across the country, improvements are not predictable nor homogeneous. Non-uniform improvements were seen in Brazil’s PHC. Though we do not directly evaluate the effectiveness of the PMAQ (financial reward) method, these initial findings suggest that it is a potentially useful tool to improve health systems, but additional support may be needed in regions that lag behind in quality improvements.

BACKGROUND Triple-negative breast cancer (TNBC) has been associated with a more aggressive histology, poorer prognosis, and nonresponsiveness to hormone therapy. It is imperative that cancer research identify factors that drive disparities and focus on prevention. METHODS Using the United States Cancer Statistics database, the authors examined differences between TNBCs compared with all other breast cancers with regard to age, race/ethnicity, and stage at diagnosis. RESULTS A total of 1,151,724 cases of breast cancer were identified from 2010 through 2014, with the triple-negative phenotype accounting for approximately 8.4% of all cases. In unadjusted analyses, non-Hispanic black women (odds ratio [OR], 2.27; 95% CI, 2.23-2.31) and Hispanic women (OR, 1.22; 95% CI, 1.19-1.25) had higher odds of diagnosis when compared with non-Hispanic white women. Women aged

INTRODUCTION: Burden of disease is often defined by using epidemiologic measures. However, there may be latent aspects of disease burden that are not factored into these types of estimates. This study quantified environmental burden of disease by using population health indicators and exploratory factor analysis at the county level across the United States. METHODS: Ninety-nine variables drawn from public use data sets from 2010 to 2016 were used to create a multifactor index — the burden index. We applied principal components analysis with promax rotation to allow the factors to correlate. Correlation coefficients for each factor and the outcome of interest, age-adjusted cancer death rate, were calculated. We used both unadjusted and adjusted linear regression techniques. RESULTS: The final additive county-level index included 9 factors that explained 68.3% of the variance in the counties and county equivalents. The burden index had a moderate association with the age-adjusted cancer death rates (r =.48, P

Forty-three percent of children under five in low and middle-income countries (LMICs) experience compromised cognitive and psychosocial development. Early childhood development (ECD) interventions that promote parent-child psychosocial stimulation and nutrition activities can help remediate early disadvantages in child development and health outcomes, but are difficult to scale. Key questions are: 1) how to maximize the reach and cost-effectiveness of ECD interventions; 2) what pathways connect interventions to parental behavioral changes and child outcomes; and 3) how to sustain impacts long-term. Msingi Bora (“good foundation” in Swahili) is a multi-arm cluster randomized controlled trial across 60 villages and 1200 households in rural Western Kenya that tests different, potentially cost-effective and scalable models to deliver an ECD intervention in biweekly sessions lasting 7 months. The curriculum integrates child psychosocial stimulation with hygiene and nutrition education. The multi-arm study will test the cost-effectiveness of two models of delivery: a group-based model versus a mixed model combining group sessions with personalized home visits. Households in a third study arm will serve as a control group. Each arm will have 20 villages and 400 households with a child aged 6–24 months at baseline. Primary outcomes are child cognitive and socioemotional development and home stimulation practices. In a 2 × 2 design among the 40 treatment villages, we will also test the role of including fathers in the intervention. We will estimate intention-to-treat and local average treatment effects, and examine mediating pathways using Mediation Analysis. One treatment arm will receive quarterly booster visits for 6 months following the end of the sessions. A follow-up survey 2 years after the end of the main intervention period will examine sustainability of outcomes and any spillover impacts onto younger siblings. Study protocols have been approved by the Maseno Ethics Review Committee (MUERC) in Kenya (00539/18) and by RAND’s institutional review board. This study is funded by the National Institute for Child Health and Human Development (R01HD090045). Results can provide policymakers with rigorous evidence of how best to design ECD interventions in low-resource rural settings. Clinical Trial NCT03548558 registered June 7, 2018 at clinicaltrials.gov; AEA-RCT registry AEARCTR-0002913.

Background There is a projected rapid increase in cancer survivors in the US population, from 15.5 million in 2016 to 26.1 million by 2040. Improvements in treatment and detection have led to increased survival, however, there is now a risk of developing new cancers as a result of environment toxins, behavioral risk factors, genetic predisposition, and late-term effects of radiation and chemotherapeutic treatments. This study takes a geospatial approach to examining the place of occurrence of multiple cancers originating in the population of four screenable cancers-female breast, colorectal, prostate, and cervical cancers-among the US population. Methods During 2004-2014, 6,523,532 primary cancer patients with one of these four screenable cancers were examined, and subsequent primary cancers (multiple cancers of any type) were noted. Individual level analyses estimated the odds of diagnosis with multiple cancers controlling for age, sex, and race-ethnicity. Change in effects on odds of multiple cancer diagnoses with age, sex, and race-ethnicity were evaluated controlling separately for late-stage diagnosis of the primary cancer or each primary cancer diagnosis type. County-level spatial cluster analysis was employed to identify and visualize higher than average multiple cancer rates. Results Over half of the study population were female and almost 30% of the study population were diagnosed at late-stage for their first cancer. Multiple occurrences of all cancers increased during the time period for patients with initial breast or colorectal cancers. Among BC primary cancer cases, subsequent multiple cancers were mostly new breast cancers. By contrast, for CRC primary cancer cases, subsequent multiple cancers were about equally likely to be new CRC cases or other cancer types. Sex, age and race-ethnicity were all significantly associated with multiple cancers. In the model controlling for CRC as the primary type, the age and race-ethnicity effects were somewhat different than for all the other models. Thus, there was something distinctly different about the multiple cancer incidence among patients with CRC as their primary cancer as compared to patients with BC, CVC, or PC primaries. In subsequent analyses by county, there were distinct geospatial patterns in multiple cancer rates with most high-rate clusters occurring in the north- and mid-west US. Conclusions There were distinct individual level and geospatial disparities in multiple cancer diagnoses for the study population of all primary breast, colorectal, cervical, or prostate cancer patients during the decade studied. It is importance to emphasize continued screening for cancer survivors and research on personal and environmental drivers of multiple primary cancers.

The UN Sustainable Development Goals provide a historic opportunity to implement interventions, at scale, to promote early childhood development. Although the evidence base for the importance of early childhood development has grown, the research is distributed across sectors, populations, and settings, with diversity noted in both scope and focus. We provide a comprehensive updated analysis of early childhood development interventions across the five sectors of health, nutrition, education, child protection, and social protection. Our review concludes that to make interventions successful, smart, and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in nurturing care. The recommendations emphasise that intervention packages should be applied at developmentally appropriate times during the life course, target multiple risks, and build on existing delivery platforms for feasibility of scale-up. While interventions will continue to improve with the growth of developmental science, the evidence now strongly suggests that parents, caregivers, and families need to be supported in providing nurturing care and protection in order for young children to achieve their developmental potential.

Despite advances in the research on new antifungal agents, Amphotericin B (AmB) is still considered as the antifungal of choice for treating most systemic mycoses due to its potency and broad-spectrum action. However, this drug has limited use because of its toxic effects on kidneys, liver and blood. The search for new and safe formulations of AmB is essential because of the emergence of antifungal resistance to other drugs and the increased number of immunosuppressed patients. Nanoparticles are a promising alternative towards achieving lower toxicity and improved pharmacokinetic properties. This study is a literature review of the use of AmB and the toxicity of formulations. Some of the current new formulations show some advantageous characteristics as compared to AmB. However, there is still need for a continued search for an effectively improved formulation. Key words: Amphotericin B, toxicity, nanotechnology, pharmaceutical technology.

A diverse group of agricultural interventions aim to improve the nutritional status of women and children. These interventions range from the cultivation of bio-fortified crop varieties to home gardening to livestock intensification. We systematically review 42 evaluations of agricultural interventions for improved maternal and child nutrition. Using these evaluations, we identify three intervention typologies – Enhancement, Diversification, and Substitution – that reflect the differential impact of interventions on household livelihoods and patterns of food consumption. Our typologies allow for a nuanced approach to categorize and generalize about pathways of impact for agricultural interventions. In applying our typologies to existing evaluations, we summarize the evidence base and emphasize areas for further inquiry, particularly in terms of understanding these interventions amid complex environmental, political and economic local contexts.

While multiple individual level factors have been identified to play a role in the etiology of breast cancer and triple-negative breast cancer, few studies have used mixed modeling techniques to explore the role that additional levels of predictors may play in triple-negative breast cancer. Since disparities persist even when known factors are accounted for, the scope of research must be expanded to examine factors that contribute to disparate outcomes at an ecologic level. Mixed modeling can perhaps better account for the spatial heterogeneity in these cases. Random intercept mixed models can account for different effects across areas, yet they assumes higher levels are independent, thus are limited in terms of handling spatial dependence. In this study, we explored the odds of triple-negative diagnosis, given breast cancer diagnosis, at the individual level, controlling for individual, county and state level variables. The intraclass correlations for county and state were 3.8% and 0.8%, respectively. When controlling for county and state level predictors, disparities by age, race and stage persisted. Non-Hispanic black women consistently had twice the odds of diagnosis with TNBC, women age 40 and under had 1.7 times the odds of diagnosis, and women diagnosed at late stage had 1.5 times the odds of diagnosis. County-level residential segregation and educational attainment variables were significant predictors of triple-negative diagnosis, while no state level policy variables were statistically significant predictors, after controlling statistically for random state intercepts that account for other omitted state variables. Residential isolation proved to be disadvantageous to diagnosis, while residential diversity and area educational attainment were protective. Future studies should continue to explore various environmental factors, physical and social, that contribute the variation in disparate rates of diagnosis. Citation Format: Lia C. Scott. Multilevel analysis of person-, county-, and state-level contributors to triple-negative breast cancer diagnosis among women in the United States [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C007.

Triple-negative breast cancer has been associated with a more aggressive histology, poorer prognosis and nonresponsiveness to hormone therapy. Due to the lack of therapeutic options for this cancer type, it is imperative that cancer research identify factors that drive disparities and focus on prevention. This study expands upon the literature by examining the outcome in population-setting rather than a sample, which can validate previous findings, by capturing the majority of the population. Using the United States Cancer Statistics database, we identified 1,151,724 cases of breast cancer from 2010-2014, with the triple-negative phenotype accounting for approximately 8.4% of all cases. The underlying distributions of age, race, and stage were statistically significantly different when we compared triple-negative breast cancer cases to all other breast cancer cases. Unadjusted and adjusted logistic regression results found that non-Hispanic black and Hispanic women had higher odds of diagnosis when compared to non-Hispanic white women, with non-Hispanic black women having over twice the odds of diagnosis. Additionally, those less than 50 years old had higher odds of diagnosis while those over 64 had lower odds, compared to age 50 to 64. Women younger than 40 had the highest odds of diagnosis, as compared to the referent group, with an odds ratio of approximately 1.8. Diagnosis at stage III and beyond conferred higher odds of diagnosis of triple-negative breast cancer. In adjusted analyses, these disparities persisted. A subset analysis was conducted on just non-Hispanic black and non-Hispanic white cases to explore the interaction of age, race and stage. This subset accounted for approximately 86% of the breast cancer population. Adjusted logistic regressions were run with age, race and stage as predictors of triple-negative breast cancer diagnosis. Interaction effects of age and stage by race were explored. Stage and race were statistically significant moderators of the relationship between age and diagnoses of triple-negative breast cancer. As age increased the odds of triple-negative diagnosis decreased; however, those diagnosed at late stage had higher odds of triple-negative breast cancer compared to those diagnosed in early stage. Additionally, non-Hispanic black women consistently had twice the probability of triple-negative diagnosis. This study shows that there is significant burden of disease in triple-negative breast cancer for women of color, specifically non-Hispanic black women, and younger women. Additional studies need to be conducted to determine what may be driving these disparities between race, age and stage. Citation Format: Lia C. Scott. Descriptive analysis of Black/White disparities in triple-negative breast cancer for the United States—A population -based study from the United States Cancer Statistics database [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C008.

Scaling up integrated nutrition programmes from small, targeted interventions or pilot studies to large-scale government-run programmes can be challenging, with risks of changing the nature and quality of the interventions such that effectiveness is not sustained. In 1999, the Government of Madagascar introduced a nationwide, community-based, growth-monitoring and nutrition education programme, which was gradually scaled up throughout the country until 2011. Data from three nationally representative surveys, administered pre- and post-programme implementation, in participating and non-participating communities, were used to evaluate the effectiveness of the programme to reduce malnutrition in children under 5 after two phases of expansion (1999-2004 and 2004-2011). In our analyses, we compared "original" communities, who had initiated the programme during the first phase, and "new" communities, who initiated the programme during the second phase. "Original" communities demonstrated a significant effect on mean weight-for-age and on the prevalence of underweight by 2004; this effect was sustained at a reduced level through 2011. In contrast, "new" communities showed no benefits for any childhood nutritional outcomes. An explanation for these findings may be that community health workers in the "new" communities reported lower motivation and less use of key messages and materials than those in the "original" communities. Frontline workers reported increased workload and irregular pay across the board during the second phase of programme expansion. Our findings underscore the risk of losing effectiveness if programme quality is not maintained during scale-up. Key factors, such as training and motivation of frontline workers, are important to address when bringing a programme to scale.

Purpose The interpretation of genetic variants after genome-wide analysis is complex in heterogeneous disorders such as intellectual disability (ID). We investigate whether algorithms can be used to detect if a facial gestalt is present for three novel ID syndromes and if these techniques can help interpret variants of uncertain significance. Methods Facial features were extracted from photos of ID patients harboring a pathogenic variant in three novel ID genes (PACS1, PPM1D, and PHIP) using algorithms that model human facial dysmorphism, and facial recognition. The resulting features were combined into a hybrid model to compare the three cohorts against a background ID population. Results We validated our model using images from 71 individuals with Koolen–de Vries syndrome, and then show that facial gestalts are present for individuals with a pathogenic variant in PACS1 (p = 8 × 10−4), PPM1D (p = 4.65 × 10−2), and PHIP (p = 6.3 × 10−3). Moreover, two individuals with a de novo missense variant of uncertain significance in PHIP have significant similarity to the expected facial phenotype of PHIP patients (p Conclusion Our results show that analysis of facial photos can be used to detect previously unknown facial gestalts for novel ID syndromes, which will facilitate both clinical and molecular diagnosis of rare and novel syndromes.

Intensive and controversial marketing of infant formula is believed to be responsible for millions of infant deaths in low and middle-income countries (LMICs), yet to date there have been no rigorous analyses that quantify these effects. To estimate the impact of infant formula on infant mortality, we pair country-specific data from the annual corporate reports of Nestle, the largest producer of infant formula, with a sample of 2.48 million births in 46 LMICs from 1970-2011. Our key finding is that the availability of formula increased infant mortality by 9.4 per 1000 births, 95%CI [3.6, 15.6] among mothers without access to clean water, suggesting that unclean water acted as a vector for the transmission of water-borne pathogens to infants. We estimate that the availability of formula in LIMCs resulted in approximately 66,000 infant deaths in 1981 at the peak of the infant formula controversy.

Tapentadol is a centrally acting analgesic with two mechanisms of action, µ-opioid receptor agonism and noradrenaline reuptake inhibition. The objectives were to describe the pharmacokinetic behavior of tapentadol after oral administration of an extended-release (ER) formulation in healthy subjects and patients with chronic pain and to evaluate covariate effects. Data were obtained from 2276 subjects enrolled in five phase I and nine phase II and III studies. Nonlinear mixed-effects modeling was conducted using NONMEM. The population estimates of apparent oral clearance and apparent central volume of distribution were 257 L/h and 1870 L, respectively. The complex absorption was described with a transit compartment for the first input. The second input function embraces saturable “binding” in the “absorption compartment”, and a time-varying rate constant. Covariate evaluation demonstrated that age, aspartate aminotransferase, and health (painful diabetic neuropathy or not) had a statistically significant effect on apparent clearance, and bioavailability appeared to be dependent on body weight. The pcVPC indicted that the model provided a robust and unbiased fit to the data. A one-compartment disposition model with two input functions and first-order elimination adequately described the pharmacokinetics of tapentadol ER. The dose-dependency in the pharmacokinetics of tapentadol ER is adequately described by the absorption model. None of the covariates were considered as clinically relevant factors that warrant dose adjustments.

Background: It is unclear what effects a conditional cash transfer (CCT) program would have on child anthropometry, language development, or school achievement in the context of the nutrition transition experienced by many low- and middle-income countries. Objective: We estimated the association of participation in Perus Juntos CCT with anthropometry, language development, and school achievement among children aged 7–8 y. Methods: We used data from the Young Lives cohort study, a cohort born between 2001 and 2002. We estimated associations of the Juntos program with height-for-age z score (HAZ), body mass index–for–age z score (BAZ), stunting, and overweight at age 7–8 y separately for children participating in the program for $ 2y( n = 169) and children participating for

Summary Objective Computerized respiratory sound analysis (CORSA) has been validated in the assessment of wheeze in infants, but it is unknown whether automatically detected wheeze is associated with impaired lung function. This study investigated the relationship between wheeze detection and conventional lung function testing (LFT) parameters. Methods CORSA was performed using the PulmoTrack® monitor in 110 infants, of median (interquartile range) postmenstrual age 50 (46–56) weeks and median body weight 4,810 (3,980–5,900) g, recovering from neonatal intensive care. In the same session, LFT was performed, including tidal breathing measurements, occlusion tests, body plethysmography, forced expiratory flow by rapid thoracoabdominal compression, sulfur hexafluoride (SF6) multiple breath washout (MBW), and capillary blood gas analysis. Infants were classified as wheezers or non-wheezers using predefined cut-off values for the duration of inspiratory and expiratory wheeze. Results Wheezing was detected in 72 (65%) infants, with 43 (39%) having inspiratory and 53 (48%) having expiratory wheezing. Endotracheal mechanical ventilation in the neonatal period for > 24 hr was associated with inspiratory wheeze (P = 0.009). Airway resistance was increased in both inspiratory (P = 0.02) and expiratory (P = 0.004) wheezers and correlated with the duration of expiratory wheeze (r = 0.394, P

Background A positive association of socioeconomic position and health is well established in high-income countries. In poorer nations, however, higher income individuals often have more cardiovascular risk factors (including obesity) than do those with less income. Our study goal was to estimate the effects of receiving a living wage (340% higher income) on short-term changes in consumption and cardiovascular risk factors among low-wage workers in a middle-income country. Methods This cross-sectional study matched workers at an apparel factory (n=105) in the Dominican Republic with those at a similar factory (n=99) nearby, 15 months after the intervention factory introduced a substantially higher living wage. Statistical matching on non-time varying individual characteristics (childhood health, childhood living conditions, work experience, demographic factors) strengthened causal inference. Primary outcomes were blood pressure (systolic and diastolic), pulse rate, body mass index and waist circumference. Secondary outcomes were dietary consumption and spending on services, consumables and durable goods. Results Receiving the living wage was associated with increased consumption of protein, dairy, soda and juice and sugars, but not with cardiovascular risk factors. Intervention factory workers spent more on grocery items and household durable goods. Conclusions While having a higher income in a middle-income country might be expected to increase obesity and its associated health risks, the current study found no short-term negative associations. There may be possible longer-term negative health consequences of increases in consumption of soda, juice and sugars, however. It is important to consider complementary interventions to support healthy dietary intake in areas with increasing wages. Electronic supplementary material The online version of this article (10.1186/s12889-018-5052-2) contains supplementary material, which is available to authorized users.

This study examines the association between 3 dimensions of food insecurity (timing, intensity, and duration) and 3 domains of child development (gross motor, communication, and personal social). Longitudinal data from 303 households (n=309 children) visited 9 times over 2years were collected. Children in households experiencing severe food insecurity 3months prior (timing) had significantly lower gross motor (β -0.14; 95% CI [0.27, -0.0033]; p=.045), communication (β -0.16; 95% CI [-0.30, -0.023]; p=.023), and personal social (β -0.20; 95% CI [-0.33, -0.073]; p=.002) Z-scores, using lagged longitudinal linear models controlling for current food insecurity; these results were attenuated in full models, which included maternal education, household asset index, and child anthropometry. Children in households that experienced greater aggregate food insecurity over the past 2years (intensity) had significantly lower gross motor (β -0.047; 95% CI [-0.077, -0.018]; p=.002), communication (β -0.042; 95% CI [-0.076, -0.0073]; p=.018), and personal social (β -0.042; 95% CI [-0.074, -0.010]; p=.010) Z-scores; these results were also attenuated in full models. Children with more time exposed to food insecurity (duration) had significantly lower gross motor (β -0.050; 95% CI [-0.087, -0.012]; p=.010), communication (β -0.042; 95% CI [-0.086, 0.0013]; p=.057), and personal social (β -0.037; 95% CI [-0.077, 0.0039]; p=.076) Z-scores; these results were no longer significant in full models. Our findings suggest that acute and chronic food insecurity and child development are related, but that many associations are attenuated with the inclusion of relevant covariates.

This study tests whether women’s relationship power modifies the effect of a conditional cash transfer (CCT) on STI risk. We analyzed 988 women enrolled in the RESPECT study in Tanzania, a yearlong, randomized-controlled trial testing the effectiveness of a CCT to reduce STI incidence. Women were randomized at the individual level to a no-cash control group, a low-cash, or a high-cash study arm. After one year, there was no main effect of study arm on risk of having an STI among women. However, in tests of heterogeneity, the effect of the CCT varied by a woman’s relationship power (adjusted RRs of the interaction term for women with higher relationship power: RR 0.567 (95% CI 0.240–0.895) for high cash and RR 1.217 (95% CI 0.794–1.641) for low cash). Specifically, women with higher relationship power in the low cash transfer arm had an elevated risk of testing positive for an STI, whereas women with high relationship power in the high cash transfer arm had a decreased risk of testing positive for an STI.