Estimation of COVID-19 vaccine effectiveness against infections and severe outcomes using routine surveillance data in Kosovo, July-September 2021.

BACKGROUND: COVID-19 vaccines have proven effective against severe outcomes in many settings, yet vaccine effectiveness (VE) estimates remain lacking for Kosovo. We aimed to estimate VE against COVID-19 infections, hospitalisations, and deaths for one and two vaccine doses during the fourth pandemic wave in July-September 2021, the period when vaccination initially became widely available. METHODS: We analysed routine surveillance data to define cases and vaccination status as partially (one dose) or completely (two doses) vaccinated. We used the screening method to calculate the proportion of cases with the outcomes vaccinated (PCV). The proportion of the population vaccinated (PPV) was based on numbers vaccinated and the Kosovo population estimate on 30/09/2021. RESULTS: Between July-September 2021, 51,804 COVID-19 cases were reported in Kosovo with 9.3% of cases partially and 3.4% completely vaccinated. Estimated vaccine effectiveness for one dose was 93.1% (95%CI:92.9-93.2%) for infections, 90.3% (95%CI:88.8-91.7%) for hospitalisations, and 90.3% (95%CI:88.4-92.1%) for deaths. Estimated vaccine effectiveness for two doses was 97.8% (95%CI:97.6-97.9%) for infections, 94.5% (95%CI:93.3-95.6%) for hospitalisations, and 94.2% (95%CI: 93.7-96.5%) for deaths. CONCLUSIONS: This study provides real-world evidence for COVID-19 vaccine effectiveness in Kosovo using routine administrative data sources and the screening method. COVID-19 vaccine effectiveness against infections and severe outcomes in Kosovo was higher with two vaccine doses than one dose, which is in accordance with findings from other study designs and settings. Using the screening method in our study reflects an important initial methodology for estimating vaccine effectiveness with routine surveillance that may be particularly important for low- and middle-income settings with less robust surveillance systems or fewer opportunities to conduct more robust vaccine effectiveness study designs.

Does daily activity overlap of seven mesocarnivores vary based on human development?

Many species of wildlife alter their daily activity patterns in response to co-occurring species as well as the surrounding environment. Often smaller or subordinate species alter their activity patterns to avoid being active at the same time as larger, dominant species to avoid agonistic interactions. Human development can complicate interspecies interactions, as not all wildlife respond to human activity in the same manner. While some species may change the timing of their activity to avoid being active when humans are, others may be unaffected or may benefit from being active at the same time as humans to reduce predation risk or competition. To further explore these patterns, we used data from a coordinated national camera-trapping program (Snapshot USA) to explore how the activity patterns and temporal activity overlap of a suite of seven widely co-occurring mammalian mesocarnivores varied along a gradient of human development. Our focal species ranged in size from the large and often dominant coyote (Canis latrans) to the much smaller and subordinate Virginia opossum (Didelphis virginiana). Some species changed their activity based on surrounding human development. Coyotes were most active at night in areas of high and medium human development. Red fox (Vulpes vulpes) were more active at dusk in areas of high development relative to areas of low or medium development. However, because most species were primarily nocturnal regardless of human development, temporal activity overlap was high between all species. Only opossum and raccoon (Procyon lotor) showed changes in activity overlap with high overlap in areas of low development compared to areas of moderate development. Although we found that coyotes and red fox altered their activity patterns in response to human development, our results showed that competitive and predatory pressures between these seven widespread generalist species were insufficient to cause them to substantially alter their activity patterns.

National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and is associated with long-term physical, neurodevelopmental, and socioeconomic effects. This study updated national preterm birth rates and trends, plus novel estimates by gestational age subgroups, to inform progress towards global health goals and targets, and aimed to update country, regional, and global estimates of preterm birth for 2020 in addition to trends between 2010 and 2020. METHODS: We systematically searched population-based, nationally representative data on preterm birth from Jan 1, 2010, to Dec 31, 2020 and study data (26 March-14 April, 2021) for countries and areas with no national-level data. The analysis included 679 data points (86% nationally representative administrative data [582 of 679 data points]) from 103 countries and areas (62% of countries and areas having nationally representative administrative data [64 of 103 data points]). A Bayesian hierarchical regression was used for estimating country-level preterm rates, which incoporated country-specific intercepts, low birthweight as a covariate, non-linear time trends, and bias adjustments based on a data quality categorisation, and other indicators such as method of gestational age estimation. FINDINGS: An estimated 13·4 million (95% credible interval [CrI] 12·3-15·2 million) newborn babies were born preterm (<37 weeks) in 2020 (9·9% of all births [95% CrI 9·1-11·2]) compared with 13·8 million (12·7-15·5 million) in 2010 (9·8% of all births [9·0-11·0]) worldwide. The global annual rate of reduction was estimated at -0·14% from 2010 to 2020. In total, 55·6% of total livebirths are in southern Asia (26·8% [36 099 000 of 134 767 000]) and sub-Saharan Africa (28·7% [38 819 300 of 134 767 000]), yet these two regions accounted for approximately 65% (8 692 000 of 13 376 200) of all preterm births globally in 2020. Of the 33 countries and areas in the highest data quality category, none were in southern Asia or sub-Saharan Africa compared with 94% (30 of 32 countries) in high-income countries and areas. Worldwide from 2010 to 2020, approximately 15% of all preterm births occurred at less than 32 weeks of gestation, requiring more neonatal care (<28 weeks: 4·2%, 95% CI 3·1-5·0, 567 800 [410 200-663 200 newborn babies]); 28-32 weeks: 10·4% [9·5-10·6], 1 392 500 [1 274 800-1 422 600 newborn babies]). INTERPRETATION: There has been no measurable change in preterm birth rates over the last decade at global level. Despite increasing facility birth rates and substantial focus on routine health data systems, there remain many missed opportunities to improve preterm birth data. Gaps in national routine data for preterm birth are most marked in regions of southern Asia and sub-Saharan Africa, which also have the highest estimated burden of preterm births. Countries need to prioritise programmatic investments to prevent preterm birth and to ensure evidence-based quality care when preterm birth occurs. Investments in improving data quality are crucial so that preterm birth data can be improved and used for action and accountability processes. FUNDING: The Children's Investment Fund Foundation and the UNDP, United Nations Population Fund-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Psychosocial influences on pregnancy and childbirth behaviours in north-western Nigeria: a cross-sectional analysis.

Antenatal care (ANC) and facility delivery are essential maternal health services, but uptake remains low in north-western Nigeria. This study aimed to assess the psychosocial influences on pregnancy and childbirth behaviours in Nigeria. Data were from a cross-sectional population-based survey of randomly sampled women with a child under 2 years conducted in Kebbi, Sokoto and Zamfara states of north-western Nigeria in September 2019. Women were asked about their maternal health behaviours during their last pregnancy. Psychosocial metrics were developed using the Ideation Model of Strategic Communication and Behaviour Change. Predicted probabilities for visiting ANC four or more times (ANC4+) and giving birth in a facility were derived using mixed-effects logistic regression models adjusted for ideational and socio-demographic variables. Among the 3039 sample women, 23.6% (95% CI: 18.0-30.3%) attended ANC4+ times and 15.5% (95% CI: 11.8-20.1%) gave birth in a facility. Among women who did not attend ANC4+ times or have a facility-based delivery during their last pregnancy, the most commonly cited reasons for non-use were lack of perceived need (42% and 67%, respectively) and spousal opposition (25% and 27%, respectively). Women who knew any ANC benefit or the recommended number of ANC visits were 3.2 and 2.1 times more likely to attend ANC4+ times, respectively. Women who held positive views about health facilities for childbirth had 1.2 and 2.6 times higher likelihood of attending ANC4+ times and having a facility delivery, respectively, while women who believed ANC was only for sickness or pregnancy complications had a 17% lower likelihood of attending ANC4+ times. Self-efficacy and supportive spousal influence were also significantly associated with both outcomes. To improve pregnancy and childbirth practices in north-western Nigeria, Social and Behavioural Change programmes could address a range of psychosocial factors across cognitive, emotional and social domains which have been found in this study to be significantly associated with pregnancy and childbirth behaviours: raising knowledge and dispelling myths, building women's confidence to access services, engaging spousal support in decision-making and improving perceived (and actual) maternal health services quality.

Patterns and contextual determinants of antibiotic prescribing for febrile under-five outpatients at primary and secondary healthcare facilities in Bugisu, Eastern Uganda.

Objectives: To describe patterns and contextual determinants of antibiotic prescribing for febrile under-five outpatients at primary and secondary healthcare facilities across Bugisu, Eastern Uganda. Methods: We surveyed 37 public and private-not-for-profit healthcare facilities and conducted a retrospective review of antimicrobial prescribing patterns among febrile under-five outpatients (with a focus on antibiotics) in 2019-20, based on outpatient registers. Multilevel logistic regression analysis was used to identify determinants of antibiotic prescribing at patient- and healthcare facility-levels. Results: Antibiotics were prescribed for 62.2% of 3471 febrile under-five outpatients. There were a total of 2478 antibiotic prescriptions of 22 antibiotic types: amoxicillin (52.2%), co-trimoxazole (14.7%), metronidazole (6.9%), gentamicin (5.7%), ceftriaxone (5.3%), ampicillin/cloxacillin (3.6%), penicillin (3.1%), and others (8.6%). Acute upper respiratory tract infection (AURTI) was the commonest single indication for antibiotic prescribing, with 76.3% of children having AURTI as their only documented diagnosis receiving antibiotic prescriptions. Only 9.2% of children aged 2-59 months with non-severe pneumonia received antibiotic prescriptions in line with national guidelines. Higher health centre levels, and private-not-for-profit ownership (adjusted OR, 4.30; 95% CI, 1.91-9.72) were significant contextual determinants of antibiotic prescribing. Conclusions: We demonstrated a high antibiotic prescribing prevalence among febrile under-five outpatients in Bugisu, Eastern Uganda, including prescriptions for co-trimoxazole and ampicillin/cloxacillin (which are not indicated in the management of the common causes of under-five febrile illness in Uganda). Study findings may be linked to limited diagnostic capacity and inadequate antibiotic availability, which require prioritization in interventions aimed at improving rational antibiotic prescribing among febrile under-five outpatients.

The role of maternal ideations on breastfeeding practices in northwestern Nigeria: a cross-section study.

BACKGROUND: Early initiation of breastfeeding within the first hour of birth and exclusive breastfeeding (EBF) for the first six months of life are beneficial for child survival and long-term health. Yet breastfeeding rates remain sub-optimal in Northwestern Nigeria, and such practices are often influenced by complex psychosocial factors at cognitive, social and emotional levels. To understand these influences, we developed a set of breastfeeding-related ideational factors and quantitatively examined their relationship with early initiation of breastfeeding and EBF practices. METHODS: A cross-sectional population-based survey was conducted in Kebbi, Sokoto, and Zamfara states from September-October 2019. A random sample of 3039 women with a child under-2 years was obtained. Respondents were asked about the two main outcomes, early initiation of breastfeeding and EBF, as well as breastfeeding-related ideations according to the Ideation Model of Strategic Communication and Behavior Change. Average marginal effects were estimated from mixed-effects logistic regression models adjusted for ideational and socio-demographic variables. RESULTS: Among 3039 women with a child under 2 years of age, 42.1% (95% CI 35.1%, 49.4%) practiced early initiation of breastfeeding, while 37.5% (95% CI 29.8%, 46.0%) out of 721 infants aged 0-5 months were exclusively breastfed. Women who knew early initiation of breastfeeding was protective of newborn health had 7.9 percentage points (pp) [95% CI 3.9, 11.9] higher likelihood of early initiation of breastfeeding practice than those who did not know. Women who believed colostrum was harmful had 8.4 pp lower likelihood of early initiation of breastfeeding (95% CI -12.4, -4.3) and EBF (95% CI -15.7%, -1.0%) than those without that belief. We found higher likelihood of early initiation of breastfeeding (5.1 pp, 95% CI 0.8%, 9.4%) and EBF (13.3 pp, 95% CI 5.0%, 22.0%) among women who knew at least one benefit of breastfeeding compared to those who did not know. Knowing the timing for introducing complementary foods andself-efficacy to practice EBF were also significantly associated with EBF practices. CONCLUSION: Ideational metrics provide significant insights for SBC programs aiming to change and improve health behaviors, including breastfeeding practices, Various cognitive, emotional and social domains played a significant role in women's breastfeeding decisions. Maternal knowledge about the benefits of breastfeeding to the mother (cognitive), knowledge of the appropriate time to introduce complementary foods (cognitive), beliefs on colostrum (cognitive), self-efficacy to breastfeed (emotional) and perceived social norms (social) are among the most important ideations for SBC programs to target to increase early initiation of breastfeeding and EBF rates in northwestern Nigeria.

Study protocol for WHO and UNICEF estimates of global, regional, and national preterm birth rates for 2010 to 2019.

BACKGROUND: Preterm birth is a leading cause of death among children under five years. Previous estimates indicated global preterm birth rate of 10.6% (14.8 million neonates) in 2014. We aim to update preterm birth estimates at global, regional, and national levels for the period 2010 to 2019. METHODS: Preterm birth is defined as a live birth occurring before 37 completed gestational weeks, or <259 days since a woman's last menstrual period. National administrative data sources for WHO Member States with facility birth rates of ≥80% in the most recent year for which data is available will be searched. Administrative data identified for these countries will be considered if ≥80% of UN estimated live births include gestational age information to define preterm birth. For countries without eligible administrative data, a systematic review of studies will be conducted. Research studies will be eligible if the reported outcome is derived from an observational or intervention study conducted at national or sub-national level in population- or facility-based settings. Risk of bias assessments will focus on gestational age measurement method and coverage, and inclusion of special subgroups in published estimates. Covariates for inclusion will be selected a priori based on a conceptual framework of plausible associations with preterm birth, data availability, and quality of covariate data across many countries and years. Global, regional and national preterm birth rates will be estimated using a Bayesian multilevel-mixed regression model. DISCUSSION: Accurate measurement of preterm birth is challenging in many countries given incomplete or unavailable data from national administrative sources, compounded by limited gestational age assessment during pregnancy to define preterm birth. Up-to-date modelled estimates will be an important resource to measure the global burden of preterm birth and to inform policies and programs especially in settings with a high burden of neonatal mortality. TRIAL REGISTRATION: PROSPERO registration: CRD42021237861.

Socioeconomic inequality in exclusive breastfeeding behavior and ideation factors for social behavioral change in three north-western Nigerian states: a cross-sectional study.

BACKGROUND: Socioeconomic inequalities could mitigate the impact of social and behavior change (SBC) interventions aimed at improving positive ideation towards the practice of exclusive breastfeeding. This study explores the empirical evidence of inequalities in the practice of exclusive breastfeeding (EBF) and associated ideational dimensions and domains of the theory of Strategic Communication and Behavior Change in three north-western Nigeria states. METHODS: We used cross-sectional data from 3007 randomly selected women with under-two-year-old children; the convenient regression method was applied to estimate the concentration indexes (CIxs) of exclusive breastfeeding behavior, ranked by household wealth index. Inequality was decomposed to associated ideational factors and sociodemographic determinants. Avoidable inequalities and the proportion of linear redistribution to achieve zero inequality were estimated. RESULTS: Women from wealthier households were more likely to practice exclusive breastfeeding CIx = 0.1236, p-value = 0.00). Attendance of at least four antenatal clinic visits (ANC 4+) was the most significant contributor to the inequality, contributing CIx = 0.0307 (p-value = 0.00) to the estimated inequality in exclusive breastfeeding practice. The elasticity of exclusive breastfeeding behavior with respect to partners influencing decision to breastfeed and ANC4+, were 0.1484 (p-value = 0.00) and 0.0825 (p-value = 0.00) respectively. Inequality in the regular attendance at community meetings (CIx = 0.1887, p-value =0.00); ANC 4+) (CIx = 0.3722, p-value = 0.00); and maternal age (CIx = 0.0161, p-value = 0.00) were pro-rich. A 10.7% redistribution of exclusive breastfeeding behavior from the wealthier half to the poorer half of the population could eliminate the inequality (line of zero inequality). Inequalities were mainly in the cognitive and social norms dimension and were all pro-poor. CONCLUSION: Socioeconomic inequalities exist in exclusive breastfeeding behaviors and in associated ideation factors in the three states but are mostly avoidable. A 10.7% redistribution from wealthier to the poorer half of the population will achieve elimination. Messaging for SBC communication interventions to improve breastfeeding practices could be more effective by targeting the mitigation of these inequalities.

Understanding family planning outcomes in northwestern Nigeria: analysis and modeling of social and behavior change factors.

BACKGROUND: Northwestern Nigeria faces a situation of high fertility and low contraceptive use, driven in large part by high-fertility norms, pro-natal cultural and religious beliefs, misconceptions about contraceptive methods, and gender inequalities. Social and behavior change (SBC) programs often try to shift drivers of high fertility through multiple channels including mass and social media, as well as community-level group, and interpersonal activities. This study seeks to assist SBC programs to better tailor their efforts by assessing the effects of intermediate determinants of contraceptive use/uptake and by demonstrating their potential impacts on contraceptive use, interpersonal communication with partners, and contraceptive approval. METHODS: Data for this study come from a cross-sectional household survey, conducted in the states of Kebbi, Sokoto and Zamfara in northwestern Nigeria in September 2019, involving 3000 women aged 15 to 49 years with a child under 2 years. Using an ideational framework of behavior that highlights psychosocial influences, mixed effects logistic regression analyses assess associations between ideational factors and family planning outcomes, and post-estimation simulations with regression coefficients model the magnitude of effects for these intermediate determinants. RESULTS: Knowledge, approval of family planning, and social influences, particularly from husbands, were all associated with improved family planning outcomes. Approval of family planning was critical - women who personally approve of family planning were nearly three times more likely to be currently using modern contraception and nearly six times more likely to intend to start use in the next 6 m. Husband's influence was also critical. Women who had ever talked about family planning with their husbands were three times more likely both to be currently using modern contraception and to intend to start in the next 6 m. CONCLUSION: SBC programs interested in improving family planning outcomes could potentially achieve large gains in contraceptive use-even without large-scale changes in socio-economic and health services factors-by designing and implementing effective SBC interventions that improve knowledge, encourage spousal/partner communication, and work towards increasing personal approval of family planning. Uncertainty about the time-order of influencers and outcomes however precludes inferences about the existence of causal relationships and the potential for impact from interventions.

Determinants of trends in reported antibiotic use among sick children under five years of age across low-income and middle-income countries in 2005-17: A systematic analysis of user characteristics based on 132 national surveys from 73 countries.

OBJECTIVES: This study aimed to analyze any reported antibiotic use for children aged <5 years with fever, diarrhea or cough with fast or difficult breathing (outcome) from low-income and middle-income countries (LMICs) during 2005-2017 by user characteristics: rural/urban residence, maternal education, household wealth, and healthcare source visited. METHODS: Based on 132 demographic and health surveys and multiple indicator cluster surveys from 73 LMICs, the outcome by user characteristics for all country-years was estimated using a hierarchical Bayesian linear regression model. RESULTS: Across LMICs during 2005-2017, the greatest relative increases in the outcome occurred in rural areas, poorest quintiles and least educated populations, particularly in low-income countries and South-East Asia. In low-income countries, rural areas had a 72% relative increase from 17.8% (Uncertainty Interval (UI): 5.2%-44.9%) in 2005 to 30.6% (11.7%-62.1%) in 2017, compared to a 29% relative increase in urban areas from 27.1% (8.7%-58.2%) in 2005 to 34.9% (13.3%-67.3%) in 2017. Despite these increases, the outcome was consistently highest in urban areas, wealthiest quintiles, and populations with the highest maternal education. CONCLUSION: These estimates suggest that the increasing reported antibiotic use for sick children aged <5 years in LMICs during 2005-2017 was driven by gains among groups often underserved by formal health services.

Patterns and trends in causes of child and adolescent mortality 2000-2016: setting the scene for child health redesign.

The under-5 mortality rate has declined from 93 deaths per 1000 live births in 1990 to 39 per 1000 live births in 2018. This improvement in child survival warrants an examination of age-specific trends and causes of death over time and across regions and an extension of the survival focus to older children and adolescents. We examine patterns and trends in mortality for neonates, postneonatal infants, young children, older children, young adolescents and older adolescents from 2000 to 2016. Levels and trends in causes of death for children and adolescents under 20 years of age are based on United Nations Inter-agency Group for Child Mortality Estimation for all-cause mortality, the Maternal and Child Epidemiology Estimation group for cause of death among children under-5 and WHO Global Health Estimates for 5-19 year-olds. From 2000 to 2016, the proportion of deaths in young children aged 1-4 years declined in most regions while neonatal deaths became over 25% of all deaths under 20 years in all regions and over 50% of all under-5 deaths in all regions except for sub-Saharan Africa which remains the region with the highest under-5 mortality in the world. Although these estimates have great variability at the country level, the overall regional patterns show that mortality in children under the age of 5 is increasingly concentrated in the neonatal period and in some regions, in older adolescents. The leading causes of disease for children under-5 remain preterm birth and infectious diseases, pneumonia, diarrhoea and malaria. For older children and adolescents, injuries become important causes of death as do interpersonal violence and self-harm. Causes of death vary by region.

Global and regional levels and trends of child and adolescent morbidity from 2000 to 2016: an analysis of years lost due to disability (YLDs).

INTRODUCTION: Non-fatal health loss makes a substantial contribution to the total disease burden among children and adolescents. An analysis of these morbidity patterns is essential to plan interventions that improve the health and well-being of children and adolescents. Our objective was to describe current levels and trends in the non-fatal disease burden from 2000 to 2016 among children and adolescents aged 0-19 years. METHODS: We used years lost due to disability (YLD) estimates in WHO's Global Health Estimates to describe the non-fatal disease burden from 2000 to 2016 for the age groups 0-27 days, 28 days-11 months, 1-4 years, 5-9 years, 10-14 years and 15-19 years globally and by modified WHO region. To describe causes of YLDs, we used 18 broad cause groups and 54 specific cause categories. RESULTS: In 2016, the total number of YLDs globally among those aged 0-19 years was about 130 million, or 51 per 1000 population, ranging from 30 among neonates aged 0-27 days to 67 among older adolescents aged 15-19 years. Global progress since 2000 in reducing the non-fatal disease burden has been limited (53 per 1000 in 2000 for children and adolescents aged 0-19 years). The most important causes of YLDs included iron-deficiency anaemia and skin diseases for both sexes, across age groups and regions. For young children under 5 years of age, congenital anomalies, protein-energy malnutrition and diarrhoeal diseases were important causes of YLDs, while childhood behavioural disorders, asthma, anxiety disorders and depressive disorders were important causes for older children and adolescents. We found important variations between sexes and between regions, particularly among adolescents, that need to be addressed context-specifically. CONCLUSION: The disappointingly slow progress in reducing the global non-fatal disease burden among children and adolescents contrasts starkly with the major reductions in mortality over the first 17 years of this century. More effective action is needed to reduce the non-fatal disease burden among children and adolescents, with interventions tailored for each age group, sex and world region.

Integrated community case management of childhood illness in low- and middle-income countries.

BACKGROUND: The leading causes of mortality globally in children younger than five years of age (under-fives), and particularly in the regions of sub-Saharan Africa (SSA) and Southern Asia, in 2018 were infectious diseases, including pneumonia (15%), diarrhoea (8%), malaria (5%) and newborn sepsis (7%) (UNICEF 2019). Nutrition-related factors contributed to 45% of under-five deaths (UNICEF 2019). World Health Organization (WHO) and United Nations Children's Fund (UNICEF), in collaboration with other development partners, have developed an approach - now known as integrated community case management (iCCM) - to bring treatment services for children 'closer to home'. The iCCM approach provides integrated case management services for two or more illnesses - including diarrhoea, pneumonia, malaria, severe acute malnutrition or neonatal sepsis - among under-fives at community level (i.e. outside of healthcare facilities) by lay health workers where there is limited access to health facility-based case management services (WHO/UNICEF 2012). OBJECTIVES: To assess the effects of the integrated community case management (iCCM) strategy on coverage of appropriate treatment for childhood illness by an appropriate provider, quality of care, case load or severity of illness at health facilities, mortality, adverse events and coverage of careseeking for children younger than five years of age in low- and middle-income countries. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL on 7 November 2019, Virtual Health Library on 8 November 2019, and Popline on 5 December 2018, three other databases on 22 March 2019 and two trial registers on 8 November 2019. We performed reference checking, and citation searching, and contacted study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs), cluster-RCTs, controlled before-after studies (CBAs), interrupted time series (ITS) studies and repeated measures studies comparing generic WHO/UNICEF iCCM (or local adaptation thereof) for at least two iCCM diseases with usual facility services (facility treatment services) with or without single disease community case management (CCM). We included studies reporting on coverage of appropriate treatment for childhood illness by an appropriate provider, quality of care, case load or severity of illness at health facilities, mortality, adverse events and coverage of careseeking for under-fives in low- and middle-income countries. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened abstracts, screened full texts and extracted data using a standardised data collection form adapted from the EPOC Good Practice Data Collection Form. We resolved any disagreements through discussion or, if required, we consulted a third review author not involved in the original screening. We contacted study authors for clarification or additional details when necessary. We reported risk ratios (RR) for dichotomous outcomes and hazard ratios (HR) for time to event outcomes, with 95% confidence intervals (CI), adjusted for clustering, where possible. We used estimates of effect from the primary analysis reported by the investigators, where possible. We analysed the effects of randomized trials and other study types separately. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included seven studies, of which three were cluster RCTs and four were CBAs. Six of the seven studies were in SSA and one study was in Southern Asia. The iCCM components and inputs were fairly consistent across the seven studies with notable variation for the training and deployment component (e.g. on payment of iCCM providers) and the system component (e.g. on improving information systems). When compared to usual facility services, we are uncertain of the effect of iCCM on coverage of appropriate treatment from an appropriate provider for any iCCM illness (RR 0.96, 95% CI 0.77 to 1.19; 2 CBA studies, 5898 children; very low-certainty evidence). iCCM may have little to no effect on neonatal mortality (HR 1.01, 95% 0.73 to 1.28; 2 trials, 65,209 children; low-certainty evidence). We are uncertain of the effect of iCCM on infant mortality (HR 1.02, 95% CI 0.83 to 1.26; 2 trials, 60,480 children; very low-certainty evidence) and under-five mortality (HR 1.18, 95% CI 1.01 to 1.37; 1 trial, 4729 children; very low-certainty evidence). iCCM probably increases coverage of careseeking to an appropriate provider for any iCCM illness by 68% (RR 1.68, 95% CI 1.24 to 2.27; 2 trials, 9853 children; moderate-certainty evidence). None of the studies reported quality of care, severity of illness or adverse events for this comparison. When compared to usual facility services plus CCM for malaria, we are uncertain of the effect of iCCM on coverage of appropriate treatment from an appropriate provider for any iCCM illness (very low-certainty evidence) and iCCM may have little or no effect on careseeking to an appropriate provider for any iCCM illness (RR 1.06, 95% CI 0.97 to 1.17; 1 trial, 811 children; low-certainty evidence). None of the studies reported quality of care, case load or severity of illness at health facilities, mortality or adverse events for this comparison. AUTHORS' CONCLUSIONS: iCCM probably increases coverage of careseeking to an appropriate provider for any iCCM illness. However, the evidence presented here underscores the importance of moving beyond training and deployment to valuing iCCM providers, strengthening health systems and engaging community systems.

Consequences of NMDA receptor deficiency can be rescued in the adult brain.

N-methyl-D-aspartate receptors (NMDARs) are required to shape activity-dependent connections in the developing and adult brain. Impaired NMDAR signalling through genetic or environmental insults causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, autism, or schizophrenia. It is not clear whether the developmental impacts of NMDAR dysfunction can be overcome by interventions in adulthood. This question is paramount for neurodevelopmental disorders arising from mutations that occur in the GRIN genes, which encode NMDAR subunits, and the broader set of mutations that disrupt NMDAR function. We developed a mouse model where a congenital loss-of-function allele of Grin1 can be restored to wild type by gene editing with Cre recombinase. Rescue of NMDARs in adult mice yields surprisingly robust improvements in cognitive functions, including those that are refractory to treatment with current medications. These results suggest that neurodevelopmental disorders arising from NMDAR deficiency can be effectively treated in adults.

Accessibility of basic paediatric emergency care in Malawi: analysis of a national facility census.

BACKGROUND: Emergency care is among the weakest parts of health systems in low-income countries with both quality and accessibility constraints. Previous studies estimated accessibility to surgical or emergency care based on population travel times to nearest hospital with no assessment of hospital readiness to provide such care. We analysed a Malawi national facility census with comprehensive inventory audits and geocoded facility locations to identify hospitals equipped to provide basic paediatric emergency care with estimated travel times to these hospitals from non-equipped facilities and in relation to Malawi's population distribution. METHODS: We analysed a Malawi national facility census in 2013-2014 to identify hospitals equipped to manage critically ill children according to an extended version of WHO Emergency Triage, Assessment and Treatment (ETAT) guidelines. These guidelines include 25 components including staff, transport, equipment, diagnostics, medications, fluids, feeds and consumables that defined an emergency-equipped hospital in our study. We estimated travel times to emergency-equipped hospitals from non-equipped facilities and relative to population distributions using geocoded facility locations and an established accessibility mapping approach using global road network datasets from OpenStreetMap and Google. RESULTS: Four (3.5, 95% CI: 1.3-8.9) of 116 Malawi hospitals were emergency-equipped. Least available items were nasogastric tubes in 34.5% of hospitals (95% CI: 26.4-43.6), blood typing services (40.4, 95% CI: 31.9-49.6), micro nebulizers (50.9, 95% CI: 41.9-60.0), and radiology (54.2, 95% CI: 45.1-63.0). Nationally, the median travel time from non-equipped facilities to the nearest emergency-equipped hospital was 73 min (95% CI: 67-77) ranging 1-507 min. Approximately one-quarter (27%) of Malawians lived over 120 min from an emergency-equipped hospital with significantly better accessibility in Central than North and South regions (16% vs. 38 and 35%, p < 0.001). CONCLUSIONS: There are unacceptable deficiencies in accessibility of basic paediatric emergency care in Malawi. Reliable supply chains for essential drugs and commodities are needed, particularly nasogastric tubes, asthma drugs and blood, along with improved capacity for time-sensitive referral. Further child mortality reductions will require substantial investments to expand basic paediatric emergency care into all Malawi hospitals for better managing critically ill children at highest mortality risk.

Trends in reported antibiotic use among children under 5 years of age with fever, diarrhoea, or cough with fast or difficult breathing across low-income and middle-income countries in 2005-17: a systematic analysis of 132 national surveys from 73 countries.

BACKGROUND: Global assessments of antibiotic consumption have relied on pharmaceutical sales data that do not measure individual-level use, and are often unreliable or unavailable for low-income and middle-income countries (LMICs). To help fill this evidence gap, we compiled data from national surveys in LMICs in 2005-17 reporting antibiotic use for sick children under the age of 5 years. METHODS: Based on 132 Demographic and Health Surveys and Multiple Indicator Cluster Surveys from 73 LMICs, we analysed trends in reported antibiotic use among children under 5 years of age with fever, diarrhoea, or cough with fast or difficult breathing by WHO region, World Bank income classification, and symptom complaint. A logit transformation was used to estimate the outcome using a linear Bayesian regression model. The model included country-level socioeconomic, disease incidence, and health system covariates to generate estimates for country-years with missing values. FINDINGS: Across LMICs, reported antibiotic use among sick children under 5 years of age increased from 36·8% (uncertainty interval [UI] 28·8-44·7) in 2005 to 43·1% (33·2-50·5) in 2017. Low-income countries had the greatest relative increase; in these countries, reported antibiotic use for sick children under 5 years of age rose 34% during the study period, from 29·6% (21·2-41·1) in 2005 to 39·5% (32·9-47·6) in 2017, although it remained the lowest of any income group throughout the study period. INTERPRETATION: We found a limited but steady increase in reported antibiotic use for sick children under 5 years of age across LMICs in 2005-17, although overlapping UIs complicate interpretation. The increase was largely driven by gains in low-income countries. Our study expands the evidence base from LMICs, where strengthening antibiotic consumption and resistance surveillance is a global health priority. FUNDING: Uppsala Antibiotic Centre, Uppsala University, Uppsala University Hospital, Makerere University, Gothenburg University.

Pneumonia-related ideations, care-seeking, and treatment behaviors among children under 2 years with pneumonia symptoms in northwestern Nigeria.

BACKGROUND: Prompt treatment of pediatric pneumonia symptoms is a cornerstone of child survival programs but remains a challenge in Nigeria. Psychosocial influences, or ideations, directly influence pathways to care but have not been previously measured or examined for pediatric pneumonia. METHODS: A two-stage cluster-sample cross-sectional population-based survey was conducted in Kebbi, Sokoto, and Zamfara States in September 2019. Across 108 enumeration areas, all households were enumerated to census pregnant women and randomly sample women with children under 2 years ("under-twos") for inclusion. Respondents were asked about pediatric pneumonia and other health-related behaviors and ideations developed using the Ideation Model of Strategic Communication and Behavior Change. Prevalence ratios for predictors of care-seeking from formal medical sources and antibiotic treatment for pneumonia symptoms among under-twos were calculated using mixed-effects Poisson regression models with robust error variance. RESULTS: Among 350 under-twos with pneumonia symptoms, 33.8% were taken to formal medical care and 38.0% used antibiotics. Women who positively viewed treatment efficacy and those who positively viewed health services quality had 1.35 (95% CI: 1.00-1.82; P = .050) and 2.13 (95% CI: 1.35-3.35; P = .001) times higher likelihood of attending formal medical sources, while women viewing peers as mostly attending drug shops had 29% lower likelihood. Perceived treatment efficacy and illness susceptibility were also significant predictors for antibiotic use. CONCLUSIONS: Program interventions focusing on increasing pneumonia knowledge alone may not be sufficient to improve care-seeking and treatment rates and should expand to address perceived and actual poor-quality health services and maternal beliefs about treatment efficacy, social norms, illness severity, and susceptibility.

Trends in nonresident abortion rates in New York City from 2005 to 2015: a time series analysis.

OBJECTIVES: To examine trends and utilization patterns of NYC abortion services by nonresidents since growing abortion restrictions across many states could drive women to seek care in less restrictive jurisdictions including NYC. STUDY DESIGN: We used data from Induced Termination of Pregnancy certificates filed with the NYC Department of Health and Mental Hygiene in 2005-2015. An autoregressive integrated moving average (ARIMA) model was fit to the monthly nonresident abortion rate time series. Pearson's χ2 tests determined associations between women's residence and other variables. RESULTS: During 2005-2015, 885,816 abortions were reported in NYC, with 76,990 (8.7%) among nonresidents; 50,211 (65.2%) nonresidents lived in other New York State counties. The NYC abortion rate declined from 49.4 per 1000 women 15-44 in 2005 to 32.7 in 2015, while the nonresident rate showed minimal change from 0.12 per 1000 US women 15-44 in 2005 to 0.10 in 2015. ARIMA(0,1,1)(0,0,1) [12] fit the time series indicating minimal monthly changes in nonresident rates reflecting seasonal patterns and shorter-term dependencies between successive observations. Nonresidents differed from residents in all investigated variables including terminating at 20+ weeks (9.0% vs. 2.5%, p<.001) and having procedural methods (87.2% vs. 82.2%, p<.001). CONCLUSIONS: Nonresidents constituted few abortion patients in NYC with minimal change in nonresident rates in 2005-2015. Nonresidents more often sought later-term abortions and more complicated procedures posing greater associated costs/risks. Monitoring nonresident abortion trends and utilization patterns is valuable for planning local service delivery particularly in jurisdictions committed to providing comprehensive women's healthcare where nonresidents may increasingly seek abortions. IMPLICATIONS: While we found limited change in nonresident abortion rates in NYC in 2005-2015, other jurisdictions bordering more restrictive states could show different results and should consider conducting similar research. Such analyses are important in jurisdictions committed to providing comprehensive women's healthcare where nonresidents may increasingly seek abortions in the future.

Determinants of Severe Maternal Morbidity and Its Racial/Ethnic Disparities in New York City, 2008-2012.

Objectives Severe maternal morbidity (SMM) is an important indicator for identifying and monitoring efforts to improve maternal health. Studies have identified independent risk factors, including race/ethnicity; however, there has been limited investigation of the modifying effect of socioeconomic factors. Study aims were to quantify SMM risk factors and to determine if socioeconomic status modifies the effect of race/ethnicity on SMM risk. Methods We used 2008-2012 NYC birth certificates matched with hospital discharge records for maternal deliveries. SMM was defined using an algorithm developed by the Centers for Disease Control and Prevention. Mixed-effects logistic regression models estimated SMM risk by demographic, socioeconomic, and health characteristics. The final model was stratified by Medicaid status (as a proxy for income), education, and neighborhood poverty. Results Of 588,232 matched hospital deliveries, 13,505 (229.6 per 10,000) had SMM. SMM rates varied by maternal age, birthplace, education, income, pre-existing chronic conditions, pre-pregnancy weight status, trimester of prenatal care entry, plurality, and parity. Race/ethnicity was consistently and significantly associated with SMM. While racial differences in SMM risk persisted across all socioeconomic groupings, the risk was exacerbated among Latinas and Asian-Pacific Islanders with lower income when compared to white non-Latinas. Similarly, living in the poorest neighborhoods exacerbated SMM risk among both black non-Latinas and Latinas. Conclusions for Practice SMM determinants in NYC mirror national trends, including racial/ethnic disparities. However, these disparities persisted even in the highest income and educational groups suggesting other pathways are needed to explain racial/ethnic differences.