Factors Predicting Completion of Four or More Antenatal Care Visits in Sarlahi District, Nepal.

Background: A significant number of women die from pregnancy and childbirth complications globally, particularly in low- and middle-income countries (LMICs). Receiving at least four antenatal care (ANC) visits may be important in reducing maternal and perinatal deaths. This study investigates factors associated with attending ≥ 4 ANC visits in Sarlahi district of southern Nepal. Methods: A secondary analysis was conducted on data from the Nepal Oil Massage Study (NOMS), a cluster-randomized, community-based longitudinal pregnancy cohort study encompassing 34 Village Development Committees. We quantified the association between receipt/attendance of ≥ 4 ANC visits and socioeconomic, demographic, morbidity, and pregnancy history factors using logistic regression; Generalized Estimating Equations were used to account for multiple pregnancies per woman. Results: All pregnancies resulting in a live birth (n=31,867) were included in the model and 31.4% of those pregnancies received 4+ ANC visits. Significant positive associations include socioeconomic factors such as participation in non-farming occupations for women (OR=1.52, 95% CI: 1.19, 1.93), higher education (OR=1.79, 95% CI: 1.66, 1.93) and wealth quintile OR=1.44, 95% CI: 1.31, 1.59), nutritional status such as non-short stature (OR=1.17, 95% CI: 1.07, 1.27), obstetric history such as adequate interpregnancy interval (OR=1.31, 95% CI: 1.19, 1.45) and prior pregnancy but no live birth (OR=2.14, 95% CI: 1.57, 2.92), symptoms such as vaginal bleeding (OR=1.35, 95% CI:1.11, 1.65) and awareness of the government's conditional cash transfer ANC program (OR=2.26, 95% CI: 2.01, 2.54). Conversely, belonging to the lower Shudra caste (OR=0.56, 95% CI: 0.47, 0.67), maternal age below 18 or above 35 (OR=0.81, 95% CI:0.74, 0.88; OR=0.77, 95% CI: 0.62, 0.96)), preterm birth (OR=0.41, 95% CI: 0.35, 0.49), parity ≥ 1 (OR=0.66, 95% CI: 0.61, 0.72), and the presence of hypertension during pregnancy (OR=0.79, 95% CI: 0.69, 0.90) were associated with decreased likelihood of attending ≥ 4 ANC visits. Conclusions: These findings underscore the importance of continuing and promoting the government's program and increasing awareness among women. Moreover, understanding these factors can guide interventions aimed at encouraging ANC uptake in the most vulnerable groups, subsequently reducing maternal-related adverse outcomes in LMICs. Trial registration: The clinicaltrial.gov trial registration number for NOMS was #NCT01177111. Registration date was August 6th, 2010.

Counting older women: Measuring the health and wellbeing of older women in LMICs.

Health systems globally are unprepared for responding to the needs of aging populations-the majority of whom are women. This is exacerbated by data systems that exclude older women. There is an urgent need to address this gap to ensure policies and services promote healthy aging across the life course.

Comparison of parent or caregiver-completed development screening tools with Bayley Scales of Infant Development: a systematic review and meta-analysis.

BACKGROUND: Parent/caregiver-completed developmental testing (PCDT) is integral to developmental care in children; however, there is limited information on its accuracy. In this systematic review, we compared the diagnostic accuracy of PCDT with concurrently administered Bayley Scales of Infant Development for detection of developmental delay (DD) in children below 4 years of age. METHODS: We searched databases PubMed, Embase, CINAHL, PsycINFO and Google Scholar until November 2023. Bivariate and multiple thresholds summary receiver operating characteristics were used to obtain the summary sensitivity and specificity with 95% CIs. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used for risk of bias assessment. RESULTS: A total of 38 studies (31 in the meta-analysis) were included. Ages and Stages Questionnaire (ASQ) and Parent Report of Children's Abilities-Revised (PARCA-R) were the most commonly evaluated PCDTs. ASQ score >2 SD below the mean had an overall sensitivity of 0.72 (0.6, 0.82) and 0.63 (0.50, 0.75) at a median specificity of 0.89 (0.82, 0.94) and 0.81 (0.76, 0.86) for diagnosing moderate to severe DD and severe DD, respectively. PARCA- R had an overall sensitivity of 0.69 (0.51, 0.83) at median specificity of 0.75 (0.64, 0.83) for predicting severe DD. Participant selection bias and partial verification bias were found in over 50% of the studies. The certainty of evidence was low for the studied outcomes. CONCLUSIONS: The most commonly studied parental tools, ASQ and PARCA-R, have moderate to low sensitivity and moderate specificity for detecting DD in young children. High risk of bias and heterogeneity in the available data can potentially impact the interpretation of our results. PROSPERO REGISTRATION NUMBER: CRD42021268629.

Targeting strategies for balanced energy and protein (BEP) supplementation in pregnancy: study protocol for the TARGET-BEP cluster-randomized controlled trial in rural Bangladesh.

BACKGROUND: The World Health Organization (WHO) recommends balanced energy and protein (BEP) supplementation be provided to all pregnant women living in undernourished populations, usually defined as having a prevalence > 20% of underweight women, to reduce the risk of stillbirths and small-for-gestational-age neonates. Few geographies meet this threshold, however, and a large proportion of undernourished women and those with inadequate gestational weight gain could miss benefiting from BEP. This study compares the effectiveness of individual targeting approaches for supplementation with micronutrient-fortified BEP vs. multiple micronutrient supplements (MMS) alone as control in pregnancy in improving birth outcomes. METHODS: The TARGET-BEP study is a four-arm, cluster-randomized controlled trial conducted in rural northwestern Bangladesh. Eligible participants are married women aged 15-35 years old identified early in pregnancy using a community-wide, monthly, urine-test-based pregnancy detection system. Beginning at 12-14 weeks of gestation, women in the study area comprising 240 predefined sectors are randomly assigned to one of four intervention arms, with sector serving as the unit of randomization. The interventions involving daily supplementation through end of pregnancy are as follows: (1) MMS (control); (2) BEP; (3) targeted BEP for those with pre-pregnancy body mass index (BMI) < 18.5 kg/m2 and MMS for others; (4) targeted BEP for those with pre-pregnancy BMI < 18.5 kg/m2, MMS for others, and women with inadequate gestational weight gain switched from MMS to BEP until the end of pregnancy. Primary outcomes include birth weight, low birth weight (< 2500 g), and small for gestational age, defined using the 10th percentile of the INTERGROWTH-21st reference, for live-born infants measured within 72 h of birth. Project-hired local female staff visit pregnant women monthly to deliver the assigned supplements, monitor adherence biweekly, and assess weight regularly during pregnancy. Trained data collectors conduct pregnancy outcome assessment and measure newborn anthropometry in the facility or home depending on the place of birth. DISCUSSION: This study will assess the effectiveness of targeted balanced energy and protein supplementation to improve birth outcomes among pregnant women in rural Bangladesh and similar settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576207. Registered on October 5th, 2022.

Adherence and acceptability of multiple micronutrient supplementation during pregnancy: Study protocol for a cluster-randomized non-inferiority trial in Cambodia.

BACKGROUND: Iron and folic acid (IFA) supplements are currently provided to Cambodian women during pregnancy. However, recent research has found benefits of a multiple micronutrient supplement (MMS) over just IFA alone on several outcomes of perinatal and infant health. The Ministry of Health in Cambodia has proposed a transition from IFA to MMS but to effectively guide this transition requires implementation research on the acceptability and adherence to MMS (over IFA). METHODS: This non-inferiority trial aims to assess the adherence and acceptability of IFA (60 mg elemental iron and 400 µg folic acid) compared to MMS (standard UNIMMAP formulation including 15 micronutrients) during antenatal care in Cambodia. A prospective cohort of 1545 pregnant women will be assigned to one of three trial arms: (1) IFA for 90 days [IFA-90]; (2) MMS for 180 days with two distributions of 90-count tablet bottles [MMS-90]; or (3) MMS for 180 days with one 180-count tablet bottle [MMS-180]. Each arm will enroll 515 women across 48 health centers (clusters) in Kampong Thom Province in Cambodia. The primary outcome is the non-inferiority of adherence rates of MMS-180 compared to IFA-90, as assessed by tablet counts. Mixed-effects logistic and linear regression models will be used to estimate the difference in the adherence rate between the two groups, with an 'a priori' determined non-inferiority margin of 15%. Acceptability of MMS and IFA will be measured using a quantitative survey conducted with enrolled pregnant women at 30-day, 90-day, and 180-day time-points. DISCUSSION: Findings from this study will guide an effective and feasible MMS scale-up strategy for Cambodia. Additionally, the findings will be shared globally with other stakeholders planning to scale up MMS in other countries. TRIAL REGISTRATION: NCT05867836 ( ClinicalTrials.gov , registered May 18, 2023).

Effectiveness of Capacity-Building and Quality Improvement Interventions to Improve Day-of-Birth Care in Kinshasa, Democratic Republic of the Congo.

In sub-Saharan African settings like the Democratic Republic of the Congo, high-quality care during childbirth and the immediate postpartum period is lacking in public facilities, necessitating multipronged interventions to improve care. We used a pre-post design to examine the effectiveness of a low-dose, high-frequency capacity-building and quality improvement (QI) intervention to improve care for women and newborns around the day of birth in 16 health facilities in Kinshasa, Democratic Republic of the Congo. Effectiveness was assessed based on changes in provider skills, key health indicators, and beneficiary satisfaction. To assess changes in the competency of the 188 providers participating in the intervention, we conducted objective structured clinical examinations on care for mothers and newborns on the day of birth, immediate postpartum family planning (PPFP) counseling and method provision, and postabortion care before and after implementation of training and at 6 and 12 months after training. Interrupted time series (ITS) analysis techniques were used to analyze routine health service data for changes in select maternal, newborn, and postpartum outcomes before and after the intervention. To assess changes in clients' perceptions of care, 2 rounds of telephone surveys were administered. Before the intervention, less than 2% of participating providers demonstrated competency in skills. Immediately after training, more than 80% demonstrated competency, and 70% retained competency after 12 months. ITS analyses show the risk of early neonatal death declined significantly by 9% (95% confidence interval [CI]=4%, 13%, P<.001), and likelihood of immediate PPFP uptake increased significantly by 72% (95% CI=53%, 92%, P<.001). Client satisfaction improved by 58% over the life of the project. These findings build on previous studies documenting the effectiveness of clinical capacity-building and QI approaches. If implemented at scale, this approach has the potential to substantively contribute to improving maternal and perinatal health in similar settings.

Chatbots That Deliver Contraceptive Support: Systematic Review.

BACKGROUND: A chatbot is a computer program that is designed to simulate conversation with humans. Chatbots may offer rapid, responsive, and private contraceptive information; counseling; and linkages to products and services, which could improve contraceptive knowledge, attitudes, and behaviors. OBJECTIVE: This review aimed to systematically collate and interpret evidence to determine whether and how chatbots improve contraceptive knowledge, attitudes, and behaviors. Contraceptive knowledge, attitudes, and behaviors include access to contraceptive information, understanding of contraceptive information, access to contraceptive services, contraceptive uptake, contraceptive continuation, and contraceptive communication or negotiation skills. A secondary aim of the review is to identify and summarize best practice recommendations for chatbot development to improve contraceptive outcomes, including the cost-effectiveness of chatbots where evidence is available. METHODS: We systematically searched peer-reviewed and gray literature (2010-2022) for papers that evaluated chatbots offering contraceptive information and services. Sources were included if they featured a chatbot and addressed an element of contraception, for example, uptake of hormonal contraceptives. Literature was assessed for methodological quality using appropriate quality assessment tools. Data were extracted from the included sources using a data extraction framework. A narrative synthesis approach was used to collate qualitative evidence as quantitative evidence was too sparse for a quantitative synthesis to be carried out. RESULTS: We identified 15 sources, including 8 original research papers and 7 gray literature papers. These sources included 16 unique chatbots. This review found the following evidence on the impact and efficacy of chatbots: a large, robust randomized controlled trial suggests that chatbots have no effect on intention to use contraception; a small, uncontrolled cohort study suggests increased uptake of contraception among adolescent girls; and a development report, using poor-quality methods, suggests no impact on improved access to services. There is also poor-quality evidence to suggest increased contraceptive knowledge from interacting with chatbot content. User engagement was mixed, with some chatbots reaching wide audiences and others reaching very small audiences. User feedback suggests that chatbots may be experienced as acceptable, convenient, anonymous, and private, but also as incompetent, inconvenient, and unsympathetic. The best practice guidance on the development of chatbots to improve contraceptive knowledge, attitudes, and behaviors is consistent with that in the literature on chatbots in other health care fields. CONCLUSIONS: We found limited and conflicting evidence on chatbots to improve contraceptive knowledge, attitudes, and behaviors. Further research that examines the impact of chatbot interventions in comparison with alternative technologies, acknowledges the varied and changing nature of chatbot interventions, and seeks to identify key features associated with improved contraceptive outcomes is needed. The limitations of this review include the limited evidence available on this topic, the lack of formal evaluation of chatbots in this field, and the lack of standardized definition of what a chatbot is.

Understanding the association between intimate partner violence and sexually transmitted infections among women in India: a propensity score matching approach.

BACKGROUND: Intimate partner violence (IPV) against women can significantly impact their overall health. While numerous studies in developing nations highlight the association between IPV and sexually transmitted infections (STIs), the evidence available within the Indian context remains limited. Therefore, this study aims to fill this knowledge gap by investigating the relationship between exposure to different forms of IPV and the occurrence of STIs, using a quasi-experimental approach. METHODS: The study used a sample of 63 851 women aged 15-49 years from the latest National Family Health Survey-5. Propensity score matching (PSM) was employed to assess the 'treatment effect' from exposure to IPV (physical, emotional or sexual) in the past 12 months on STIs. RESULTS: About 12.2% of women (95% CI: 11.7% to 12.8%) reported symptoms of STIs at the time of the survey. Approximately 31.9% (95% CI: 31.2% to 32.7%) of women reported experiencing at least one form of IPV-either physical, emotional or sexual IPV. Of all forms of IPV, physical IPV was the most prevalent, reported by 28.6%, followed by emotional IPV (13.2%) and sexual IPV (5.7%). Women who experienced any form of IPV-whether physical, sexual or emotional-reported a higher prevalence of STIs (17.8%) as compared with those who did not experience any IPV (9.5%). The findings from the PSM analysis indicated that among the three forms of IPV, the impact of sexual IPV on STIs was the most pronounced. The average treatment effect on the treated from exposure to sexual IPV on STIs was 0.15 (95% CI 0.13 to 0.17). CONCLUSION: This study provides evidence of a significant association between IPV and STIs among women in India and underscores the urgent need for intensified efforts and interventions to address both IPV and STIs, to improve the overall health and well-being of women in India.

Understanding integrated HPV testing and treatment of pre-cancerous cervical cancer in Burkina Faso, Cote d'Ivoire, Guatemala and Philippines: study protocol.

BACKGROUND: Many low- and-middle-income countries are disproportionately burdened by cervical cancer, resulting in high morbidity and mortality. HPV-DNA testing coupled with treatment with thermal ablation is a recommended screening and precancer treatment strategy, but not enough is known about how this can be effectively implemented in the context of integrated services. The (Scale Up Cervical Cancer Elimination by Secondary prevention Strategy, (SUCCESS) project is conducting a study to understand this approach, integrated into existing women's health services in Burkina Faso, Cote d'Ivoire, Guatemala, and the Philippines (2020-2024). METHODS: A hybrid effectiveness-implementation type III mixed-methods observational study design is used to assess feasibility, acceptability, and costs of integrated service delivery in 10 sites per country, selected considering urban/rural location, facility level, onsite/offsite laboratories, and health services type. In each country, a sample size of 2227 women aged 25-49 years will be enrolled with about 20% being women living with HIV. The primary outcome is proportion of HPV positive women completing precancer treatment, if eligible, within three months of screening. Data collection and analysis includes; facility and client exit surveys, key informant and client interviews, registries and project records extractions, and costing data analysis. Analysis includes descriptive statistics, context description, thematic analysis, and document analysis. Quantitative analyses will be stratified by participant's HIV status. DISCUSSION: Recruitment of study participants started in April 2022 (Burkina Faso and Côte d'Ivoire) and August 2022 (Guatemala and the Philippines). Enrolment targets for women screened, client exit, in-depth and key informant interviews conducted were reached in Burkina Faso and Cote d'Ivoire in November 2022. Guatemala and Philippines are expected to complete enrolment by June 2023. Follow-up of study Participants 12-months post-treatment is ongoing and is expected to be completed for all countries by August 2024. In LMICs, integrating cervical cancer secondary prevention services into other health services will likely require specific rather than incidental recruitment of women for screening. Reconfiguration of laboratory infrastructure and planning for sample management must be made well in advance to meet induced demand for screening. Trail Registration ClinicalTrials.Gov ID: NCT05133661 (24/11/2021).

Risk factors for neonatal mortality: an observational cohort study in Sarlahi district of rural southern Nepal.

OBJECTIVES: To assess the association between maternal characteristics, adverse birth outcomes (small-for-gestational-age (SGA) and/or preterm) and neonatal mortality in rural Nepal. DESIGN: This is a secondary observational analysis to identify risk factors for neonatal mortality, using data from a randomised trial to assess the impact of newborn massage with different oils on neonatal mortality in Sarlahi district, Nepal. SETTING: Rural Sarlahi district, Nepal. PARTICIPANTS: 40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017. MAIN OUTCOME: The outcome variable is neonatal death. Cox regression was used to estimate adjusted Hazard Ratios (aHRs) to assess the association between adverse birth outcomes and neonatal mortality. RESULTS: There were 32 004 live births and 998 neonatal deaths. SGA and/or preterm birth was strongly associated with increased neonatal mortality: SGA and preterm (aHR: 7.09, 95% CI: (4.44 to 11.31)), SGA and term/post-term (aHR: 2.12, 95% CI: (1.58 to 2.86)), appropriate-for-gestational-age/large-for-gestational-age and preterm (aHR: 3.23, 95% CI: (2.30 to 4.54)). Neonatal mortality was increased with a history of prior child deaths (aHR: 1.53, 95% CI: (1.24 to 1.87)), being a twin or triplet (aHR: 5.64, 95% CI: (4.25 to 7.48)), births at health posts/clinics or in hospital (aHR: 1.34, 95% CI: (1.13 to 1.58)) and on the way to facilities or outdoors (aHR: 2.26, 95% CI: (1.57 to 3.26)). Risk was lower with increasing maternal height from <145 cm to 145-150 cm (aHR: 0.78, 95% CI: (0.65 to 0.94)) to ≥150 cm (aHR: 0.57, 95% CI: (0.47 to 0.68)), four or more antenatal care (ANC) visits (aHR: 0.67, 95% CI: (0.53 to 0.86)) and education >5 years (aHR: 0.75, 95% CI: (0.62 to 0.92)). CONCLUSION: SGA and/or preterm birth are strongly associated with increased neonatal mortality. To reduce neonatal mortality, interventions that prevent SGA and preterm births by promoting ANC and facility delivery, and care of high-risk infants after birth should be tested. TRIAL REGISTRATION NUMBER: NCT01177111.

Chatbots to Improve Sexual and Reproductive Health: Realist Synthesis.

BACKGROUND: Digital technologies may improve sexual and reproductive health (SRH) across diverse settings. Chatbots are computer programs designed to simulate human conversation, and there is a growing interest in the potential for chatbots to provide responsive and accurate information, counseling, linkages to products and services, or a companion on an SRH journey. OBJECTIVE: This review aimed to identify assumptions about the value of chatbots for SRH and collate the evidence to support them. METHODS: We used a realist approach that starts with an initial program theory and generates causal explanations in the form of context, mechanism, and outcome configurations to test and develop that theory. We generated our program theory, drawing on the expertise of the research team, and then searched the literature to add depth and develop this theory with evidence. RESULTS: The evidence supports our program theory, which suggests that chatbots are a promising intervention for SRH information and service delivery. This is because chatbots offer anonymous and nonjudgmental interactions that encourage disclosure of personal information, provide complex information in a responsive and conversational tone that increases understanding, link to SRH conversations within web-based and offline social networks, provide immediate support or service provision 24/7 by automating some tasks, and provide the potential to develop long-term relationships with users who return over time. However, chatbots may be less valuable where people find any conversation about SRH (even with a chatbot) stigmatizing, for those who lack confidential access to digital devices, where conversations do not feel natural, and where chatbots are developed as stand-alone interventions without reference to service contexts. CONCLUSIONS: Chatbots in SRH could be developed further to automate simple tasks and support service delivery. They should prioritize achieving an authentic conversational tone, which could be developed to facilitate content sharing in social networks, should support long-term relationship building with their users, and should be integrated into wider service networks.

Cost-effectiveness of a direct to beneficiary mobile communication programme in improving reproductive and child health outcomes in India.

INTRODUCTION: Kilkari is the largest maternal messaging programme of its kind globally. Between its initiation in 2012 in Bihar and its transition to the government in 2019, Kilkari was scaled to 13 states across India and reached over 10 million new and expectant mothers and their families. This study aims to determine the cost-effectiveness of exposure to Kilkari as compared with no exposure across 13 states in India. METHODS: The study was conducted from a programme perspective using an analytic time horizon aligned with national scale-up efforts from December 2014 to April 2019. Economic costs were derived from the financial records of implementing partners. Data on incremental changes in the practice of reproductive maternal newborn and child health (RMNCH) outcomes were drawn from an individually randomised controlled trial in Madhya Pradesh and inputted into the Lives Saved Tool to yield estimates of maternal and child lives saved. One-way and probabilistic sensitivity analyses were carried out to assess uncertainty. RESULTS: Inflation adjusted programme costs were US$8.4 million for the period of December 2014-April 2019, corresponding to an average cost of US$264 298 per year of implementation in each state. An estimated 13 842 lives were saved across 13 states, 96% among children and 4% among mothers. The cost per life saved ranged by year of implementation and with the addition of new states from US$392 ($385-$393) to US$953 ($889-$1092). Key drivers included call costs and incremental changes in coverage for key RMNCH practices. CONCLUSION: Kilkari is highly cost-effective using a threshold of India's national gross domestic product of US$1998. Study findings provide important evidence on the cost-effectiveness of a national maternal messaging programme in India. TRIAL REGISTRATION: NCT03576157.

Can we design the next generation of digital health communication programs by leveraging the power of artificial intelligence to segment target audiences, bolster impact and deliver differentiated services? A machine learning analysis of survey data from rural India.

OBJECTIVES: Direct to beneficiary (D2B) mobile health communication programmes have been used to provide reproductive, maternal, neonatal and child health information to women and their families in a number of countries globally. Programmes to date have provided the same content, at the same frequency, using the same channel to large beneficiary populations. This manuscript presents a proof of concept approach that uses machine learning to segment populations of women with access to phones and their husbands into distinct clusters to support differential digital programme design and delivery. SETTING: Data used in this study were drawn from cross-sectional survey conducted in four districts of Madhya Pradesh, India. PARTICIPANTS: Study participant included pregnant women with access to a phone (n=5095) and their husbands (n=3842) RESULTS: We used an iterative process involving K-Means clustering and Lasso regression to segment couples into three distinct clusters. Cluster 1 (n=1408) tended to be poorer, less educated men and women, with low levels of digital access and skills. Cluster 2 (n=666) had a mid-level of digital access and skills among men but not women. Cluster 3 (n=1410) had high digital access and skill among men and moderate access and skills among women. Exposure to the D2B programme 'Kilkari' showed the greatest difference in Cluster 2, including an 8% difference in use of reversible modern contraceptives, 7% in child immunisation at 10 weeks, 3% in child immunisation at 9 months and 4% in the timeliness of immunisation at 10 weeks and 9 months. CONCLUSIONS: Findings suggest that segmenting populations into distinct clusters for differentiated programme design and delivery may serve to improve reach and impact. TRIAL REGISTRATION NUMBER: NCT03576157.

Acute promyelocytic leukaemia: population-based study of epidemiology and outcome with ATRA and oral-ATO from 1991 to 2021.

BACKGROUND: The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance. METHODS: Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers. RESULTS: APL occurred in 374 males and 387 females at a median age of 44 (1-97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 109/L, diagnosis during 1991-2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14-161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 109/L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010-2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens. CONCLUSIONS: There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754).

Using Location Intelligence to Evaluate the COVID-19 Vaccination Campaign in the United States: Spatiotemporal Big Data Analysis.

BACKGROUND: Highly effective COVID-19 vaccines are available and free of charge in the United States. With adequate coverage, their use may help return life back to normal and reduce COVID-19-related hospitalization and death. Many barriers to widespread inoculation have prevented herd immunity, including vaccine hesitancy, lack of vaccine knowledge, and misinformation. The Ad Council and COVID Collaborative have been conducting one of the largest nationwide targeted campaigns ("It's Up to You") to communicate vaccine information and encourage timely vaccination across the United States. More than 300 major brands, digital and print media companies, and community-based organizations support the campaigns to reach distinct audiences. OBJECTIVE: The goal of this study was to use aggregated mobility data to assess the effectiveness of the campaign on COVID-19 vaccine uptake. METHODS: Campaign exposure data were collected from the Cuebiq advertising impact measurement platform consisting of about 17 million opted-in and deidentified mobile devices across the country. A Bayesian spatiotemporal hierarchical model was developed to assess campaign effectiveness through estimating the association between county-level campaign exposure and vaccination rates reported by the Centers for Disease Control and Prevention. To minimize potential bias in exposure to the campaign, the model included several control variables (eg, age, race or ethnicity, income, and political affiliation). We also incorporated conditional autoregressive residual models to account for apparent spatiotemporal autocorrelation. RESULTS: The data set covers a panel of 3104 counties from 48 states and the District of Columbia during a period of 22 weeks (March 29 to August 29, 2021). Officially launched in February 2021, the campaign reached about 3% of the anonymous devices on the Cuebiq platform by the end of March, which was the start of the study period. That exposure rate gradually declined to slightly above 1% in August 2021, effectively ending the study period. Results from the Bayesian hierarchical model indicate a statistically significant positive association between campaign exposure and vaccine uptake at the county level. A campaign that reaches everyone would boost the vaccination rate by 2.2% (95% uncertainty interval: 2.0%-2.4%) on a weekly basis, compared to the baseline case of no campaign. CONCLUSIONS: The "It's Up to You" campaign is effective in promoting COVID-19 vaccine uptake, suggesting that a nationwide targeted mass media campaign with multisectoral collaborations could be an impactful health communication strategy to improve progress against this and future pandemics. Methodologically, the results also show that location intelligence and mobile phone-based monitoring platforms can be effective in measuring impact of large-scale digital campaigns in near real time.

Everyday capabilities were a path to resilience during COVID-19: a case study of five countries.

COVID-19 demanded urgent responses by all countries, with wide variations in the scope and sustainability of those responses. Scholarship on resilience has increasingly emphasized relational considerations such as norms and power and how they influence health systems' responses to evolving challenges. In this study, we explored what influenced countries' national pandemic responses over time considering a country's capacity to test for COVID-19. To identify countries for inclusion, we used daily reports of COVID-19 cases and testing from 184 countries between 21st January 2020 and 31st December 2020. Countries reporting test data consistently and for at least 105 days were included, yielding a sample of 52 countries. We then sampled five countries representing different geographies, income levels and governance structures (Belgium, Ethiopia, India, Israel and Peru) and conducted semi-structured key informant interviews with stakeholders working in, or deeply familiar with, national responses. Across these five countries, we found that existing health systems capacities and political leadership determined how responses unfolded, while emergency plans or pandemic preparedness documents were not fit-for-purpose. While all five countries were successful at reducing COVID-19 infections at a specific moment in the pandemic, political economy factors complicated the ability to sustain responses, with all countries experiencing larger waves of the virus in 2021 or 2022. Our findings emphasize the continued importance of foundational public health and health systems capacities, bolstered by clear leadership and multisectoral coordination functions. Even in settings with high-level political leadership and a strong multisectoral response, informants wished that they-and their country's health system-were more prepared to address the pandemic and maintain an effective response over time. Our findings challenge emergency preparedness as the dominant frame in pandemic preparedness and call for a continued emphasis on health systems strengthening to respond to future health shocks and a pandemic moving to endemic status.

Low dose paracetamol for management of patent ductus arteriosus in very preterm infants: a randomised non-inferiority trial.

OBJECTIVE: To compare the efficacy of low dose-short course intravenous paracetamol with a conventional dose regimen for early targeted closure of patent ductus arteriosus (PDA). DESIGN: Single-centre, double-blinded, active controlled, randomised non-inferiority trial. SETTING: Level III neonatal intensive care unit in Western India. PATIENTS: Preterm infants <30 weeks of gestation requiring mechanical ventilation, or continuous positive airway pressure with FiO2 ≥0.35 and diagnosed with a haemodynamically significant PDA (hsPDA) at 18-24 hours of postnatal age. INTERVENTIONS: Low dose (10 mg/kg/dose 6 hourly for 72 hours) versus conventional dose (15 mg/kg/dose 6 hourly for 120 hours) intravenous paracetamol treatment. MAIN OUTCOME MEASURES: Comparison of the rates of ductal closure at completion of sixth postnatal day, using a prespecified non-inferiority margin of 20%. RESULTS: A total of 102 infants were enrolled. The median gestational age and birth weight of the included infants were 26.4 weeks and 830 g. At completion of the sixth postnatal day, closure of PDA was achieved in 92% of infants in the low dose group as compared with 94% of those in the standard dose group (risk difference: -1.6%, 95% CI: -11.6% to 8.5%, p=0.38). The rates of rescue therapies, adverse effects and other neonatal morbidities were comparable in both groups. CONCLUSION: In very preterm infants on significant respiratory support, low dose-short course intravenous paracetamol treatment was non-inferior to a conventional dosing regime of paracetamol for closure of hsPDA in the first week of postnatal age. Larger studies with narrow margins of non-inferiority are required to confirm our findings. TRIAL REGISTRATION NUMBER: CTRI/2017/10/010012.

Factors Beyond Compensation Associated with Uptake of Voluntary Medical Male Circumcision in Zambia.

Voluntary medical male circumcision (VMMC) provides partial protection against female-to-male transmission of HIV. The Maximizing the Impact of Voluntary Medical Male Circumcision in Zambia (MAXZAM) project was a phased implementation of a demand generation strategy for VMMC through economic compensation. Previously published findings showed increased uptake of VMMC when compensation was provided. This paper is a follow-up evaluation of the MAXZAM project exploring additional factors associated with uptake of VMMC. Factors found associated include the outreach setting in which men were approached, number of information sources seen, heard, or read about VMMC, their self-reported HIV risk behaviors, their self-reported intention to go through the procedure, and their behavioral-psychographic profile. The findings highlight the importance of considering general (e.g., intensifying mass communications and targeting specific settings) and person-centered demand generation approaches (e.g., considering the client's psychographic profile and HIV risk level) to maximize effect on VMMC uptake.

Prevalence and predictors of spontaneous preterm births in Nepal: findings from a prospective, population-based pregnancy cohort in rural Nepal-a secondary data analysis.

OBJECTIVE: Preterm birth can have short-term and long-term complications for a child. Socioeconomic factors and pregnancy-related morbidities may be important to predict and prevent preterm births in low-resource settings. The objective of our study was to find prevalence and predictors of spontaneous preterm birth in rural Nepal. DESIGN: This is a secondary observational analysis of trial data (registration number NCT01177111). SETTING: Rural Sarlahi district, Nepal. PARTICIPANTS: 40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017. OUTCOME MEASURES: The outcome variable is spontaneous preterm birth. Generalized Estimating Equations Poisson regression with robust variance was fitted to present effect estimates as risk ratios. RESULT: The prevalence of spontaneous preterm birth was 14.5% (0.5% non-spontaneous). Characteristics not varying in pregnancy associated with increased risk of preterm birth were maternal age less than 18 years (adjusted risk ratio=1.13, 95% CI: 1.02 to 1.26); being Muslim (1.53, 1.16 to 2.01); first pregnancy (1.15, 1.04 to 1.28); multiple births (4.91, 4.20 to 5.75) and male child (1.10, 1.02 to 1.17). Those associated with decreased risk were maternal education >5 years (0.81, 0.73 to 0.90); maternal height ≥150 cm (0.89, 0.81 to 0.98) and being from wealthier families (0.83, 0.74 to 0.93). Pregnancy-related morbidities associated with increased risk of preterm birth were vaginal bleeding (1.53, 1.08 to 2.18); swelling (1.37, 1.17 to 1.60); high systolic blood pressure (BP) (1.47, 1.08 to 2.01) and high diastolic BP (1.41, 1.17 to 1.70) in the third trimester. Those associated with decreased risk were respiratory problem in the third trimester (0.86, 0.79 to 0.94); having poor appetite, nausea and vomiting in the second trimester (0.86, 0.80 to 0.92) and third trimester (0.86, 0.79 to 0.94); and higher weight gain from second to third trimester (0.89, 0.87 to 0.90). CONCLUSION: The prevalence of preterm birth is high in rural Nepal. Interventions that increase maternal education may play a role. Monitoring morbidities during antenatal care to intervene to reduce them through an effective health system may help reduce preterm birth.