Psychometrics of psychosocial behavior items under age 6 years: Evidence from Nebraska, USA.

Because healthy psychosocial development in the first years of life is critical to lifelong well-being, governmental, and nongovernmental organizations are increasingly interested in monitoring psychosocial behaviors among populations of children. In response, the World Health Organization is developing the Global Scales of Early Development Psychosocial Form (GSED PF) to facilitate population-level psychosocial monitoring. Once validated, the GSED PF will be an open-access, caregiver-reported measure of children's psychosocial behaviors that is appropriate for infants and young children. This study examines the psychometric validity evidence from 45 items under consideration for inclusion in the GSED PF. Using data from N = 836 Nebraskan (USA) children aged 180 days to 71 months, results indicate that scores from 44 of the 45 (98%) items exhibit positive evidence of validity and reliability. A bifactor model with one general factor and five specific factors best fit the data, exhibited strong reliability, and acceptable model fit. Criterion associations with known predictors of children's psychosocial behaviors were in the expected direction. These findings suggest that measurement of children's psychosocial behaviors may be feasible, at least in the United States. Data from more culturally and linguistically diverse settings is needed to assess these items for global monitoring.

Debido a que el desarrollo sicosocial en los primeros años de vida es crítico para el bienestar de toda la vida, las organizaciones gubernamentales y no gubernamentales están más y más interesadas en observar vigilantemente las conductas sicosociales en la población infantil. Como respuesta, la Organización Mundial de la Salud está desarrollando el Formulario Sicosocial de las Escalas Globales del Temprano Desarrollo (GSED PF) para facilitar la observación sicosocial alerta al nivel del grupo de población. Una vez que se haya convalidado, el GSED PF será una medida de acceso abierto, que reportará el cuidador, sobre las conductas sicosociales de los niños que son apropiadas para infantes y niños pequeñitos. Este estudio examina la evidencia de la validez sicométrica de 45 puntos bajo consideración para ser incluidos en el GSED PF. Usando datos de N = 836 niños de Nebraska (Estados Unidos), de edad entre 180 días y 71 meses, los resultados indican que los puntajes de 44 de los 45 (98%) puntos muestran evidencia positiva de validez y confiabilidad. Un modelo bifactorial con un factor general y cinco factores específicos, que mejor encaja con los datos, mostró una fuerte confiabilidad y un modelo aceptable que encaja. Las asociaciones de criterio con factores de predicción conocidos acerca de las conductas sicosociales de los niños se encontraban en la dirección esperada. Estos resultados sugieren que la medida de las conductas sicosociales de los niños pudiera ser posible, por lo menos en los Estados Unidos. Se necesitan datos de escenarios más diversos cultural y lingüísticamente para evaluar estos puntos para la estar alerta en la observación global.

[CF Lung Disease - a German S3 Guideline: Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal recessive genetic multisystemic disease. In Germany, it affects at least 8000 people. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the airway epithelial lining fluid which leads to reduction of the mucociliary clearance.Even if highly effective, CFTR modulator therapy has been available for some years and people with CF are getting much older than before, recurrent and chronic infections of the airways as well as pulmonary exacerbations still occur. In adult CF life, Pseudomonas aeruginosa (PA) is the most relevant pathogen in colonisation and chronic infection of the lung, leading to further loss of lung function. There are many possibilities to treat PA-infection.This is a S3-clinical guideline which implements a definition for chronic PA-infection and demonstrates evidence-based diagnostic methods and medical treatment in order to give guidance for individual treatment options.

Maternal obesity and childhood asthma risk: Exploring mediating pathways.

BACKGROUND: Growing evidence for the effect of maternal obesity on childhood asthma motivates investigation of mediating pathways. OBJECTIVE: To investigate if childhood body mass index (BMI), gestational weight gain (GWG) and preterm birth mediate the association of maternal obesity on childhood asthma risk. METHODS: We used electronic medical records from mother-child pairs enrolled in Kaiser Permanente Northern California integrated healthcare system. Children were followed from their birth (2005-2014) until at least age 4 (n = 95,723), age 6 (n = 59,230) or age 8 (n = 25,261). Childhood asthma diagnosis at each age was determined using ICD-9/10 codes and medication dispensings. Prepregnancy BMI (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese [≥30] kg/m2 ) were defined using height and weight measurements close to the last menstrual period date. Child's BMI (Centers for Disease Control and Prevention BMI-for-age percentiles: underweight [<5th], normal [5th-85th], overweight [85th-95th], obese [>95th]) were obtained using anthropometric measurements taken the year preceding each follow-up age. GWG (delivery weight-prepregnancy weight) was categorised based on Institutes of Medicine recommendations (inadequate, adequate, excessive). Implementing first causal inference test (CIT) then causal mediator models (to decompose the natural direct and indirect effects), we examined the potential mediating effect of childhood BMI, GWG, and preterm birth on the association between prepregnancy BMI (continuous and categorical) and childhood asthma. RESULTS: Overall, risk of childhood asthma increased as prepregnancy BMI increased (age 4 risk ratio: 1.07, 95% confidence interval: 1.04, 1.09, per 5 kg/m2 increase in BMI; similar for age 6 and 8). CIT identified childhood BMI and preterm birth, but not GWG as potential mediators. Causal mediation models confirmed childhood BMI, but not preterm birth, as having a partial mediating effect. Results were similar for age 6 and 8, and when continuous mediators (instead of binary) were assessed. CONCLUSIONS: Childhood overweight/obesity has a modest mediating effect on the association between prepregnancy BMI and childhood asthma.

Integrating early stimulation and play at scale: study protocol for "MAHAY Mikolo", a multi-arm cluster-randomized controlled trial.

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.

Knowledge of Congenital CMV, Risk Behaviours for CMV Acquisition, and Acceptance of an Educational Infographic Among Postpartum Women: A Pilot Study.

Congenital cytomegalovirus (cCMV) infection in the newborn can present with sensorineural hearing loss and microcephaly. The objectives of this study were to determine baseline knowledge of cCMV and the acceptability of an infographic about cCMV among a group of postpartum women. Participants completed a questionnaire assessing their perceptions of an infographic as well as their knowledge and risk behaviours for acquisition of CMV. Of all 140 respondents, 119 (85%) had no prior knowledge of cCMV, and all 12 women (8.6%) who viewed the infographic indicated that it was helpful. Our study also demonstrated that passive dissemination of an infographic in clinics results in limited viewership.

Levels and potential drivers of under-five mortality sex ratios in low- and middle-income countries.

BACKGROUND: Non-biological childhood mortality sex ratios may reflect community sex preferences and gender discrimination in health care. OBJECTIVE: We assessed the association between contextual factors and gender bias in under-five mortality rates (U5MR) in low- and middle-income countries. METHODS: Full birth histories available from Demographic and Health Surveys and Multiple Indicator Cluster Surveys (2010-2018) in 80 countries were used to estimate U5MR male-to-female sex ratios. Expected sex ratios and their residuals (difference of observed and expected) were derived from a linear regression model, adjusted for overall mortality. Negative residuals indicate more likelihood of discrimination against girls, and we refer to this as a measure of potential gender bias. Associations between residuals and national development and gender inequality indices and with survey-derived child health care indicators were tested using Spearman's correlation. RESULTS: Mortality residuals for under-five mortality were not associated with national development, education, religion, or gender inequality indices. Negative residuals were more common in countries where boys were more likely to be taken to health services than girls (rho -0.24, 95% confidence interval -0.45, -0.01). CONCLUSIONS: Countries where girls were more likely to die than boys, accounting for overall mortality levels, were also countries where boys were more likely to receive health care than girls. Further research is needed to understand which national characteristics explain the presence of gender bias, given that the analyses of development levels and gender equality did not discriminate between countries with or without excess mortality of girls. Reporting on child mortality separately by sex is required to enable such advances.

Gender equality and gender norms: framing the opportunities for health.

The Sustainable Development Goals offer the global health community a strategic opportunity to promote human rights, advance gender equality, and achieve health for all. The inability of the health sector to accelerate progress on a range of health outcomes brings into sharp focus the substantial impact of gender inequalities and restrictive gender norms on health risks and behaviours. In this paper, the fifth in a Series on gender equality, norms, and health, we draw on evidence to dispel three myths on gender and health and describe persistent barriers to progress. We propose an agenda for action to reduce gender inequality and shift gender norms for improved health outcomes, calling on leaders in national governments, global health institutions, civil society organisations, academic settings, and the corporate sector to focus on health outcomes and engage actors across sectors to achieve them; reform the workplace and workforce to be more gender-equitable; fill gaps in data and eliminate gender bias in research; fund civil-society actors and social movements; and strengthen accountability mechanisms.

Gender norms and health: insights from global survey data.

Despite global commitments to achieving gender equality and improving health and wellbeing for all, quantitative data and methods to precisely estimate the effect of gender norms on health inequities are underdeveloped. Nonetheless, existing global, national, and subnational data provide some key opportunities for testing associations between gender norms and health. Using innovative approaches to analysing proxies for gender norms, we generated evidence that gender norms impact the health of women and men across life stages, health sectors, and world regions. Six case studies showed that: (1) gender norms are complex and can intersect with other social factors to impact health over the life course; (2) early gender-normative influences by parents and peers can have multiple and differing health consequences for girls and boys; (3) non-conformity with, and transgression of, gender norms can be harmful to health, particularly when they trigger negative sanctions; and (4) the impact of gender norms on health can be context-specific, demanding care when designing effective gender-transformative health policies and programmes. Limitations of survey-based data are described that resulted in missed opportunities for investigating certain populations and domains. Recommendations for optimising and advancing research on the health impacts of gender norms are made.

Lipid-Based Nutrient Supplementation Reduces Child Anemia and Increases Micronutrient Status in Madagascar: A Multiarm Cluster-Randomized Controlled Trial.

BACKGROUND: Iron 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. OBJECTIVES: We 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. METHODS: We 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 6-18 mo; (T3) T2 + LNS for pregnant/lactating women; or (T4) T1 + parenting messages. Pregnant women and infants aged <12 mo were enrolled in 2014 and followed for 2 y. Child outcome measures included hemoglobin and anemia assessed using the HemoCue 301 system (n = 3561), and serum ferritin and soluble transferrin receptor as markers of iron status, retinol-binding protein as a marker of vitamin A status, and C-reactive protein and α-1 acid glycoprotein from a finger stick blood draw among a subsample (n = 387). We estimated mean difference using linear regression and prevalence ratios using modified Poisson regression accounting for the clustered design. All analyses were intention-to-treat. RESULTS: Children in the LNS groups (T2 and T3) had ∼40% lower prevalence of anemia and iron deficiency anemia and 25% lower prevalence of iron deficiency than children in the control group (T0) (P < 0.05 for all). There were no differences in any of the biomarkers when comparing children in the T4 group with those in T0; nor were there differences between T3 and T2. CONCLUSIONS: Our findings suggest the provision of LNS in the context of a large-scale program offers significant benefits on anemia and iron status in young children.This trial was registered at www.isrctn.com as ISRCTN14393738.

Caregiver perceptions of child development in rural Madagascar: a cross-sectional study.

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.

Perils of scaling up: Effects of expanding a nutrition programme in Madagascar.

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.

Validity of caregiver-report measures of language skill for Wolof-learning infants and toddlers living in rural African villages.

Valid indigenous language assessments are needed to further our understanding of how children learn language around the world. We assessed the psychometric properties and performance of two caregiver-report measures of Wolof language skill (language milestones achieved and vocabulary knowledge) for 500 children (ages 0;4 to 2;6) living in rural Senegal. Item response models (IRM) evaluated instrument- and item-level performance and differential function by gender. Both caregiver-report measures had good psychometric properties and displayed expected age and socioeconomic effects. Modest concurrent validity was found by comparing the caregiver-report scores to transcribed child language samples from a naturalistic play session. The caregiver-report method offers a valid alternative to more costly tools, such as direct behavioral assessments or language sampling, for measuring early language development in non-literate, rural African communities. Recommendations are made to further improve the performance of caregiver-report measures of child language skill in these settings.

Concise syntheses and HCV NS5B polymerase inhibition of (2'R)-3 and (2'S)-2'-ethynyluridine-10 and related nucleosides.

(2'R)-Ethynyl uridine 3, and its (2'S)-diastereomer 10, are synthesised in a divergent fashion from the inexpensive parent nucleoside. Both nucleoside analogues are obtained from a total of 5 simple synthetic steps and 3 trivial column chromatography purifications. To evaluate their effectiveness against HCV NS5B polymerase, the nucleosides were converted to their respective 5'-O-triphosphates. Subsequently, this lead to the discovery of the 2'-ß-ethynyl 18 and -propynyl 20 nucleotides having significantly improved potency over Sofosbuvir triphosphate 24.

When Cultural Norms Discourage Talking to Babies: Effectiveness of a Parenting Program in Rural Senegal.

In some areas of rural Africa, long-standing cultural traditions and beliefs may discourage parents from verbally engaging with their young children. This study assessed the effectiveness of a parenting program designed to encourage verbal engagement between caregivers and infants in Wolof-speaking villages in rural Senegal. Caregivers (n = 443) and their 4- to 31-month-old children were observed at baseline in 2013 and 1 year later at follow-up. Results showed that caregivers in program villages nearly doubled the amount of child-directed speech during a play session compared to baseline, whereas caregivers in matched comparison villages showed no change. After 1 year, children in program villages produced more utterances, and showed greater improvement in vocabulary and other language outcomes compared to children in comparison villages.

Discovery of benzamides as potent human ß3 adrenergic receptor agonists.

The paper will describe the synthesis and SAR studies that led to the discovery of benzamide (reverse amide) as potent and selective human ß3-adrenergic receptor agonist. Based on conformationally restricted pyrrolidine scaffold we discovered earlier, pyrrolidine benzoic acid intermediate 22 was synthesized. From library synthesis and further optimization efforts, several structurally diverse reverse amides such as 24c and 24i were found to have excellent human ß3-adrenergic potency and good selectivity over the ß1 and ß2 receptors. In addition to human ß1, ß2, ß3 and hERG data, PK of selected compounds will be described.

The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors.

Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure-activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease selectivity, and demonstrating clean ion channel and cytochrome P450 profiles while trying to achieve a pharmacokinetic profile suitable for once weekly dosing in humans.

A cluster-randomized, controlled trial of nutritional supplementation and promotion of responsive parenting in Madagascar: the MAHAY study design and rationale.

BACKGROUND: Over half of the world's children suffer from poor nutrition, and as a consequence they experience delays in physical and mental health, and cognitive development. There is little data evaluating the effects of delivery of lipid-based, nutrition supplementation on growth and development during pregnancy and early childhood within the context of a scaled-up program. Furthermore, there is limited evidence on effects of scaled-up, home-visiting programs that focus on the promotion of child development within the context of an existing, national nutrition program. METHODS/DESIGN: The MAHAY ("smart" in Malagasy) study uses a multi-arm randomized-controlled trial (RCT) to test the effects and cost-effectiveness of combined interventions to address chronic malnutrition and poor child development. The arms of the trial are: (T0) existing program with monthly growth monitoring and nutritional/hygiene education; (T1) is T0 + home visits for intensive nutrition counseling within a behavior change framework; (T2) is T1 + lipid-based supplementation (LNS) for children 6-18 months old; (T3) is T2 + LNS supplementation of pregnant/lactating women; and (T4) is T1 + intensive home visiting program to support child development. There are anticipated to be n = 25 communities in each arm (n = 1250 pregnant women, n = 1250 children 0-6 months old, and n = 1250 children 6-18 months old). Primary outcomes include growth (length/height-for-age z-scores) and child development (mental, motor and social development). Secondary outcomes include care-giver reported child morbidity, household food security and diet diversity, micro-nutrient status, maternal knowledge of child care and feeding practices, and home stimulation practices. We will estimate unadjusted and adjusted intention-to-treat effects. Study protocols have been reviewed and approved by the Malagasy Ethics Committee at the Ministry of Health in Madagascar and by the institutional review board at the University of California, Davis. This study is funded by the Strategic Impact Evaluation Fund (SIEF), the World Bank Innovation Grant, the Early Learning Partnership Grant, the Japan Scaling-up for Nutrition Trustfund, and Grand Challenges Canada. The implementation of the study is financed by Madagascar's National Nutrition Office. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14393738 . Registered June 23, 2015.

Structure-activity-relationship of amide and sulfonamide analogs of omarigliptin.

A series of novel substituted-[(3R)-amino-2-(2,5-difluorophenyl)]tetrahydro-2H-pyran analogs have been prepared and evaluated as potent, selective and orally active DPP-4 inhibitors. These efforts lead to the discovery of a long acting DPP-4 inhibitor, omarigliptin (MK-3102), which recently completed phase III clinical development and has been approved in Japan.