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Abstract A fundamental goal of evaluating the performance of a clinical model is to ensure it performs well across a diverse intended patient population. A primary challenge is that the data used in model development and testing often consist of many overlapping, heterogeneous patient subgroups that may not be explicitly defined or labeled. While a model’s average performance on a dataset may be high, the model can have significantly lower performance for certain subgroups, which may be hard to detect. We describe an algorithmic framework for identifying subgroups with potential performance disparities (AFISP), which produces a set of interpretable phenotypes corresponding to subgroups for which the model’s performance may be relatively lower. This could allow model evaluators, including developers and users, to identify possible failure modes prior to wide-scale deployment. We illustrate the application of AFISP by applying it to a patient deterioration model to detect significant subgroup performance disparities, and show that AFISP is significantly more scalable than existing algorithmic approaches.

Abstract We developed and evaluated an electronic health record (EHR)-based model for suicide risk specific to an American Indian patient population. Using EHR data for all patients over 18 with a visit between 1/1/2017 and 10/2/2021, we developed a model for the risk of a suicide attempt or death in the 90 days following a visit. Features included demographics, medications, diagnoses, and scores from relevant screening tools. We compared the predictive performance of logistic regression and random forest models against existing suicide screening, which was augmented to include the history of previous attempts or ideation. During the study, 16,835 patients had 331,588 visits, with 490 attempts and 37 deaths by suicide. The logistic regression and random forest models (area under the ROC (AUROC) 0.83 [0.80–0.86]; both models) performed better than enhanced screening (AUROC 0.64 [0.61–0.67]). These results suggest that an EHR-based suicide risk model can add value to existing practices at Indian Health Service clinics.

Abstract Background The SARS-CoV-2 pandemic led to unprecedented testing demands, causing major testing delays globally. One strategy used for increasing testing capacity was pooled-testing, using a two-stage technique first introduced during WWII. However, such traditional pooled testing was used in practice only when positivity rates were below 2%. Methods Here we report the development, validation and clinical application of P-BEST - a single-stage pooled-testing strategy that was approved for clinical use in Israel. Results P-BEST is clinically validated using 3636 side-by-side tests and is able to correctly detect all positive samples and accurately estimate their Ct value. Following regulatory approval by the Israeli Ministry of Health, P-BEST was used in 2021 to clinically test 837,138 samples using 270,095 PCR tests - a 3.1fold reduction in the number of tests. This period includes the Alpha and Delta waves, when positivity rates exceeded 10%, rendering traditional pooling non-practical. We also describe a tablet-based solution that allows performing manual single-stage pooling in settings where liquid dispensing robots are not available. Conclusions Our data provides a proof-of-concept for large-scale clinical implementation of single-stage pooled-testing for continuous surveillance of multiple pathogens with reduced test costs, and as an important tool for increasing testing efficiency during pandemic outbreaks.

Background: Childhood malnutrition is a major public health concern in the tribal areas of Andhra Pradesh, India, particularly in the region of ITDA Rampachodavaram. The integration and effectiveness of digital health interventions in these underserved regions are vital for addressing this endemic issue. However, the unique challenges posed by the remote and resource- limited settings of tribal areas make the implementation of such interventions particularly complex. Moreover, the varying complexity of the digital health ecosystem in these areas adds another layer of concern to deploying digital health solutions. Objectives: 1. To explore digital health interventions related to childhood malnutrition in the Integrated Tribal Development Agency (ITDA) of Rampachodavaram. 2. To understand the dynamics of the local health system and the digital health ecosystem in the implementation of these interventions. 3. To examine the role of street-level bureaucrats in implementing digital interventions and identify the barriers and facilitators affecting this process Methodology: The research was conducted in ITDA Rampachodavaram, involving interviews with health system officials and Focus Group Discussions (FGDs) with frontline health workers. The Health System Dynamics (HSD) framework and Lipsky’s theory on street-level bureaucrats were utilized, and enriched with insights into the digital health ecosystem. Results: The study reveals significant systemic, contextual, and human factors influencing the implementation of digital health interventions. Challenges include the complex role of street-level bureaucrats and systemic barriers like inadequate training, technological limitations, and disparities in digital access and literacy. Conclusion: This study highlights the potential of digital health interventions in improving childhood malnutrition outcomes in tribal areas. It stresses the importance of adaptive, inclusive strategies and advocates for digital health equity. Empowering frontline health workers and tailoring interventions to the specific health system dynamics and digital ecosystem of tribal regions are key for effective implementation.

Objective: Cholinesterase inhibitors (CEIs) are prescribed for dementia to maintain or improve memory. Selective serotonin reuptake inhibitors (SSRIs) are also prescribed to manage psychiatric symptoms seen in dementia. What proportion of outpatients actually responds to these drugs is still unclear. Our objective was to investigate the responder rates of these medications in an outpatient setting using the electronic medical record (EMR).Methods: We used the Johns Hopkins EMR system to identify patients with dementia who were prescribed a CEI or SSRI for the first time between 2010 and 2021. Treatment effects were assessed through routinely documented clinical notes and free-text entries in which healthcare providers record clinical findings and impressions of patients. Responses were scored using a three-point Likert scale named the NOte-based evaluation method for Treatment Efficacy (NOTE) in addition to the Clinician’s Interview-Based Impression of Change Plus caregiver input (CIBIC-plus), a seven-point Likert scale used in clinical trials. To validate NOTE, the relationships between NOTE and CIBIC-plus and between NOTE and change in MMSE (Mini-Mental State Examination) before and after medication were examined. Inter-rater reliability was evaluated using Krippendorff’s alpha. The responder rates were calculated.Results: NOTE showed excellent inter-rater reliability and correlated well with CIBIC-plus and changes in MMSEs. Out of 115 CEI cases, 27.0% reported improvement and 34.8% reported stable symptoms in cognition; out of 225 SSRI cases, 69.3% reported an improvement in neuropsychiatric symptoms.Conclusion: NOTE showed high validity in measuring the pharmacotherapy effects based on unstructured clinical entries. Although our real-world observation included various types of dementia, the results were remarkably similar to what was reported in controlled clinical trials of Alzheimer’s disease and its related neuropsychiatric symptoms.

Rotavirus is a leading cause of severe diarrheal disease in infants and young children worldwide. Vaccination offers the best protection against this disease, and two rotavirus vaccines were developed in India and included in its routine immunization program. The Government of India's decision to adopt this intervention was supported by a solid base of evidence from clinical trials, as well as substantial research regarding rotavirus disease burden and the potential health and economic value of immunization. Following program implementation, multiple studies were initiated, including three evaluations of effectiveness and several investigations regarding intussusception. These additional data regarding vaccine impact, safety, and delivery from post-introduction evaluations in conditions of real-world use will further strengthen and sustain the immunization program. This manuscript evaluates the status of existing and forthcoming evidence regarding rotavirus vaccination in India through a literature review and consultation with relevant stakeholders. Studies evaluating vaccine impact, effectiveness, safety, health economics, and acceptability, as well as operational and programmatic research, were included in the review. Overall, we found that the evidence base did not contain any major gaps. Nevertheless, additional smaller-scale research studies would be valuable in providing a more complete picture of rotavirus vaccine performance and benefit. Documentation of India's experience with rotavirus vaccines may provide lessons learned for other countries in the Asia region, where rotavirus disease burden remains high, yet vaccine adoption has been slow, as well as for countries worldwide that may be considering implementation of the Indian-made rotavirus vaccines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Niranjan Bhat reports financial support was provided by Bill & Melinda Gates Foundation. Elisabeth Vodicka reports financial support was provided by Bill & Melinda Gates Foundation. Allison Clifford reports financial support was provided by Bill & Melinda Gates Foundation. Kanduri Balaji Ananth reports financial support was provided by Bill & Melinda Gates Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Worldwide, vaccine-preventable diseases have been a significant cause of mortality in the under-5 age group. To reduce the disease burden, new vaccines are being introduced in every country's immunization programmes. For this to happen, high vaccination coverage is necessary. However, rapidly identifying the areas that fail to reach the expected coverage becomes cumbersome. During recent years, lot quality assurance sampling (LQAS) has been widely used in evaluating immunization coverage across the globe. The present study aims to pilot this approach for field monitoring of a new vaccine against routine concurrent field monitoring in one of the North-Eastern states of India., Methodology: For LQAS, a community-based cross-sectional study was undertaken among 55 children aged 0-23 months in all 5 Primary health centres (lots) of Medziphema block, Dimapur, Nagaland. The total sample size for LQAS was calculated based on α = 5, β = 90 using Lemeshow and Taber-LQAS table with a target level of immunization defined as 90 % and the lower limit set to 55 %. For the concurrent field monitoring, a sample of 30 children in the same age group was selected through random sampling. Pre-designed, pre-tested questionnaire for the caregivers, scripted on a digital tool was employed with verification of immunization card and caregiver's recall. Data was analyzed using SPSS software version 25.0., Results: The study found a slight difference in the percentage of children age-appropriately vaccinated for PCV (as per the schedule) in concurrent field monitoring (93.3 %) and LQAS (90.9 %). However, no statistically significant difference was found in comparing the immunization coverage using both methodologies (p > 0.05)., Conclusion: The study findings encourage that LQAS can be considered for monitoring the immunization coverage of a newly introduced vaccine. It offers the added advantage of identifying poor/low-performing pockets that require focused attention., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objective: To assess the relative risk of mortality in infants born preterm and small for gestational age (SGA) during the first and second months of life in rural Bangladesh., Study Design: We analyzed data from a cohort of pregnant women and their babies in Sylhet, Bangladesh, assembled between 2011 and 2014. Community health workers visited enrolled babies up to 10 times from birth to age 59 days. Survival status was recorded at each visit. Gestational age was estimated from mother's reported last menstrual period. Birth weights were measured within 72 hours of delivery. SGA was defined using the INTERGROWTH-21st standard. We estimated unadjusted and adjusted hazard ratios (HRs) and corresponding 95% CIs for babies born preterm and SGA separately for the first and second month of life using bivariate and multivariable weighted Cox regression models., Results: The analysis included 17 643 singleton live birth babies. Compared with infants born at term-appropriate for gestational age, in both unadjusted and adjusted analyses, infants born preterm-SGA had the greatest risk of death in the first (HR 13.25, 95% CI 8.65-20.31; adjusted HR 12.05, 95% CI 7.82-18.57) and second month of life (HR 4.65, 95% CI 1.93-11.23; adjusted HR 4.1, 95% CI 1.66-10.15), followed by infants born preterm-appropriate for gestational age and term-SGA., Conclusions: The risk of mortality in infants born preterm and/or SGA is increased and extends through the second month of life. Appropriate interventions to prevent and manage complications caused by prematurity and SGA could improve survival during and beyond the neonatal period., Competing Interests: Declaration of Competing Interest The study was funded by the Bill & Melinda Gates Foundation (grant no. OPPGH5307). The authors do not have a commercial or other association that might pose a conflict of interest in this research., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: The Rotavirus vaccine (RVV) introduction is a landmark event in the history of Indian public health as for the first time a novel, low-cost indigenous vaccine was introduced in a short timeline between 2016 and 2019. As per WHO mandate, post-introduction evaluation (PIE) be conducted within 6 to 12 months of vaccine introduction to provide an understanding of the operational aspects of the program. For RVV PIE, an innovative approach to developing and deploying a digitized tool was employed. The present study aims to document the processes followed for digitizing the data collection and analysis tools., Methods: The development of the RVV-PIE digital tool was undertaken in two phases. In the first phase, conceptualization and iteration of the modified WHO PIE tool were undertaken. Questions were organized sequentially to ensure natural progression in responses. The finalized questionnaire was converted to a digital version and extensive dummy data was entered to improve automated qualitative data analysis. Phase 2 involved updating the draft tool and incorporating changes to provide a field-tested version for deployment., Results: The digital version of the tool was successfully developed. The GPS functionality of the tool allowed live tracking of data collection making the process more accountable. The tool was prepopulated with reference materials and data points for easy reference and retrieval by the evaluators. The digitization of the tool also allowed easy visualization of data through maps, charts, and graphs on a real-time user-friendly dashboard., Conclusions: The digitization of the PIE tool for RVV in India has been a great learning experience where the dire situation of an ongoing pandemic catapulted us towards a more efficient and comprehensive process innovation. The RVV PIE tool could serve as a customizable digital PIE tool for other health programs heralding an era of a more effective and proficient process of PIE., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Amanjot Kaur reports writing assistance was provided by Bill & Melinda Gates Foundation]., (© 2024 The Authors. Published by Elsevier Ltd.)

Epilepsy is a chronic neurological disease, characterized by spontaneous, unprovoked, recurrent seizures that may lead to long-term disability and premature death. Despite significant efforts made to improve epilepsy detection clinically and pre-clinically, the pervasive presence of noise in EEG signals continues to pose substantial challenges to their effective application. In addition, discriminant features for epilepsy detection have not been investigated yet. The objective of this study is to develop a hybrid model for epilepsy detection from noisy and fragmented EEG signals. We hypothesized that a hybrid model could surpass existing single models in epilepsy detection. Our approach involves manual noise rejection and a novel statistical channel selection technique to detect epilepsy even from noisy EEG signals. Our proposed Base-2-Meta stacking classifier achieved notable accuracy (0.98 ± 0.05), precision (0.98 ± 0.07), recall (0.98 ± 0.05), and F1 score (0.98 ± 0.04) even with noisy 5-s segmented EEG signals. Application of our approach to the specific problem like detection of epilepsy from noisy and fragmented EEG data reveals a performance that is not only superior to others, but also is translationally relevant, highlighting its potential application in a clinic setting, where EEG signals are often noisy or scanty. Our proposed metric DF-A (Discriminant feature-accuracy), for the first time, identified the most discriminant feature with models that give A accuracy or above (A = 95 used in this study). This groundbreaking approach allows for detecting discriminant features and can be used as potential electrographic biomarkers in epilepsy detection research. Moreover, our study introduces innovative insights into the understanding of these features, epilepsy detection, and cross-validation, markedly improving epilepsy detection in ways previously unavailable., (© 2024. The Author(s).)

Background: Competency-based medical education (CBME) is a method of medical training that focuses on developing learners' competencies rather than simply assessing their knowledge and skills. Attitude, ethics, and communication (AETCOM) are important components of CBME, and the use of artificial intelligence (AI) tools such as ChatGPT for CBME has not been studied. Hence, we aimed to assess the capability of ChatGPT in solving AETCOM case scenarios used for CBME in India., Materials and Methods: A total of 11 case scenarios were developed based on the AETCOM competencies. The scenarios were presented to ChatGPT, and the responses generated by ChatGPT were evaluated by three independent experts by awarding score ranging from 0 to 5. The scores were compared with a predefined score of 2.5 (50% accuracy) and 4 (80% accuracy) of a one-sample median test. Scores among the three raters were compared by the Kruskal-Wallis H test. The inter-rater reliability of the evaluations was assessed using the intraclass correlation coefficient (ICC)., Results: The mean score of solution provided by ChatGPT was 3.88 ± 0.47 (out of 5), indicating an accuracy of approximately 78%. The responses evaluated by three raters were similar (Kruskal-Wallis H P value 0.51), and the ICC value was 0.796, which indicates a relatively high level of agreement among the raters., Conclusion: ChatGPT shows moderate capability in solving AETCOM case scenarios used for CBME in India. The inter-rater reliability of the evaluations suggests that ChatGPT's responses were consistent and reliable. Further studies are needed to explore the potential of ChatGPT and other AI tools in CBME and to determine the optimal use of these tools in medical education., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Education and Health Promotion.)

Objective: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017., Design: Descriptive multi-country secondary data analysis., Setting: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America., Population: Liveborn infants from 15 population-based cohorts., Methods: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42 +0 , 39 +0 -41 +6 (reference category), 37 +0 -38 +6 , 34 +0 -36 +6 ,34 +0 -36 +6 ,32 +0 -33 +6 , 30 +0 -31 +6 , 28 +0 -29 +6 and less than 28 weeks., Main Outcome Measures: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births)., Results: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 37 0 -38 6  weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality., Conclusions: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns., (© 2024 John Wiley & Sons Ltd.)

Launched in 2016, the PMUY Programme of the Government of India aimed to provide 8 crore LPG connections to women in rural households over four years. After acquiring a new connection, some households appeared uninterested in ordering subsequent subsidized LPG refills, impacting programme's sustainability, and targeting strategy. We propose a prediction model using "Explainable Machine Learning" to anticipate the beneficiaries' refill frequency with a view to improving LPG-refills and social targeting. In this paper, we suggest an enhanced stacked SVM (ISS) model for classification, which is contrasted with state-of-art ML models: Random Forest (RF), SVM-RBF, Naive Bayes (NB), and Decision Tree (C5.0). Some of the performance matrices that are used to evaluate the models include accuracy, sensitivity, specificity, Cohen's Kappa statistics, Receiver Operating Characteristic curve (ROC), and area under the curve (AUC). The proposed approach, which was validated with 10-fold cross validation, produced the best overall accuracies for data splits of 50-50, 66-34, and 80-20. The "Explainable AI (XAI)" model has also been used to describe how models and features interact, and to discuss the importance of features and their contributions to prediction. The recommended XAI will aid in efficient "beneficiary targeting" and "policy interventions"., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Understanding the attitudes of medical students towards individuals from the lesbian, gay, bisexual, transgender, queer, questioning, intersex and asexual (LGBTQIA+) community is a prerequisite for informing competencies-based medical education (CBME) guidelines to make them LGBTQIA+ inclusive. The present study was conducted to assess the attitudes of medical undergraduate students from Indian medical colleges towards the LGBTQIA+ community., Methods: An online cross-sectional survey was conducted in medical undergraduate students across India, which measured the opinions, beliefs, and acceptance of LGBTQIA+ people using a structured questionnaire uploaded on Google Forms. After data collection, the datasheet was downloaded, cleaned, and anonymised before being imported into RStudio for analysis., Results: A total of 273 valid entries were assessed from the online survey. There was significant gender-based differences on most traditional opinions and beliefs regarding the LGBTQIA+ population (P <0.05). The female participants appeared to be more accepting of and comfortable with all denominations of LGBTQIA+. Many of the participants believed that members of the LGBTQIA+ community are more prone to sexually transmitted diseases, especially HIV/AIDS. However, a few participants also opined that the increased susceptibility to HIV/AIDS may be due to increased prevalence of intravenous drug abuse in the LGBTQIA+ community., Conclusions: There are some misconceptions about the LGBTQIA+ community among medical students. Therefore, in order to ensure LGBTQIA+ sensitive healthcare provision, there needs to be a concerted, informed effort to incorporate necessary changes in the CBME curriculum.

"Epilepsy is a chronic brain disorder that affects people of all ages. The cause of epilepsy is often unknown and its effect in different age groups is not yet investigated. The main objective of this study is to introduce a novel approach that successfully detects epilepsy even from noisy EEG signals. In addition, this study also investigates population specific epilepsy detection for providing novel insights. Correspondingly, we utilized the TUH EEG corpus database, publicly available challenging multi-channel EEG database containing detailed patient information. We applied a band-pass filter and manual noise rejection to remove noise and artifacts from EEG signals. We then utilized statistical features and correlation to select channels, and applied different transform analysis methods such as continuous wavelet transform, spectrogram, and Wigner-Ville distribution, with and without ensemble averaging, to construct an image dataset. Afterwards, we used various deep-learning models for general analysis. Our findings suggest that different models such as DenseNet201, DenseNet169, DenseNet121, VGG16, VGG19, Xception, InceptionV3, and MobileNetV2 performed better while using images generated from different approaches in general analysis. Furthermore, we split the dataset into two sections according to age for population analysis. All the models that performed well in the general analysis were used for population analysis, which provided novel insights in epilepsy detection from EEG. Our proposed framework for epilepsy detection achieved 100% accuracy, which outperforms other concurrent methods.", Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Background: Pulse oximeters are not routinely available in outpatient clinics in low- and middle-income countries. We derived clinical scores to identify hypoxemic child pneumonia., Methods: This was a retrospective pooled analysis of two outpatient datasets of 3-35 month olds with World Health Organization (WHO)-defined pneumonia in Bangladesh and Malawi. We constructed, internally validated, and compared fit & discrimination of four models predicting SpO 2  < 93% and <90%: (1) Integrated Management of Childhood Illness guidelines, (2) WHO-composite guidelines, (3) Independent variable least absolute shrinkage and selection operator (LASSO); (4) Composite variable LASSO., Results: 12,712 observations were included. The independent and composite LASSO models discriminated moderately (both C-statistic 0.77) between children with a SpO 2  < 93% and ≥94%; model predictive capacities remained moderate after adjusting for potential overfitting (C-statistic 0.74 and 0.75). The IMCI and WHO-composite models had poorer discrimination (C-statistic 0.56 and 0.68) and identified 20.6% and 56.8% of SpO 2  < 93% cases. The highest score stratum of the independent and composite LASSO models identified 46.7% and 49.0% of SpO 2  < 93% cases. Both LASSO models had similar performance for a SpO 2  < 90%., Conclusions: In the absence of pulse oximeters, both LASSO models better identified outpatient hypoxemic pneumonia cases than the WHO guidelines. Score external validation and implementation are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Schuh, Hooli, Ahmed, King, Roy, Lufesi, Islam, Mvalo, Chowdhury, Ginsburg, Colbourn, Checkley, Baqui and McCollum.)

Introduction: Leprosy also widely known by the name Hansen's disease is a chronic disease caused by Mycobacterium leprae affecting mankind with various clinico-pathological forms. It remained a major public health issue due to associated case load, morbidity and stigma attached to it. India declared elimination of leprosy in the year 2005. However, it is surprising to see that in some parts of the country, the prevalence is still significant. The objective of the study is to describe the spectrum of histopathological profile of leprosy and compare its correlation with clinical diagnosis in this post elimination era., Methods: A 24-months prospective study was conducted with clinically diagnosed leprosy cases in a tertiary care hospital in eastern India. Lesions were graded and the histopathological slides along with its bacteriological index (BI) on slit skin smears where possible was reviewed and analyzed. Agreement of histopathological finding with clinical finding was established., Results: A total of 220 cases were included in the study. On histopathology, borderline category was the most frequently reported with borderline tuberculoid the most common subtype. Most common clinical feature was hypopigmented plaque, followed by erythematous skin lesions, nodules, macules etc. Bacteriological index was studied in 192 slit skin smears. Moderate agreement between clinical and histopathological diagnosis with kappa measure of inter-rater agreement as 0.457 was noted., Conclusion: Clinico-histopathological correlation is pivotal in the accurate diagnosis of leprosy to prevent, treat, and control the resurgence of the disease in the post-elimination era., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Background: Hypoxaemic pneumonia mortality risk in low-income and middle-income countries is high in children who have been hospitalised, but unknown among outpatient children. We sought to establish the outpatient burden, mortality risk, and prognostic accuracy of death from hypoxaemia in children with suspected pneumonia in Bangladesh., Methods: We conducted a prospective community-based cohort study encompassing three upazila (subdistrict) health complex catchment areas in Sylhet, Bangladesh. Children aged 3-35 months participating in a community surveillance programme and presenting to one of three upazila health complex Integrated Management of Childhood Illness (IMCI) outpatient clinics with an acute illness and signs of difficult breathing (defined as suspected pneumonia) were enrolled in the study; because lower respiratory tract infection mortality mainly occurs in children younger than 1 year, the primary study population comprised children aged 3-11 months. Study physicians recorded WHO IMCI pneumonia guideline clinical signs and peripheral arterial oxyhaemoglobin saturations (SpO 2 ) in room air. They treated children with pneumonia with antibiotics (oral amoxicillin [40 mg/kg per dose twice per day for 5-7 days, as per local practice]), and recommended oxygen, parenteral antibiotics, and hospitalisation for those with an SpO 2 of less than 90%, WHO IMCI danger signs, or severe malnutrition. Community health workers documented the children's vital status and the date of any vital status changes during routine household surveillance (one visit to each household every 2 months). The primary outcome was death at 2 weeks after enrolment in children aged 3-11 months (primary study population) and 12-35 months (secondary study population). Primary analyses included estimating the outpatient prevalence, mortality risk, and prognostic accuracy of hypoxaemia for death in children aged 3-11 months with suspected pneumonia. Risk ratios were produced by fitting a multivariable model that regressed predefined SpO 2 ranges (<90%, 90-93%, and 94-100%) on the primary 2-week mortality outcome (binary outcome) using Poisson models with robust variance estimation. We established the prognostic accuracy of WHO IMCI guidelines for death with and without varying SpO 2 thresholds., Findings: Participants were recruited between Sept 1, 2015, to Aug 31, 2017. During the study period, a total of 7440 children aged 3-35 months with the first suspected pneumonia episode were enrolled, of whom 3848 (54·3%) with an attempted pulse oximeter measurement and 2-week outcome were included in our primary study population of children aged 3-11-months. Among children aged 3-11 months, an SpO 2 of less than 90% occurred in 102 (2·7%) of 3848 children, an SpO 2 of 90-93% occurred in 306 (8·0%) children, a failed SpO 2 measurement occurred in 67 (1·7%) children, and 24 (0·6%) children with suspected pneumonia died. Compared with an SpO 2 of 94-100% (3373 [87·7%] of 3848), the adjusted risk ratio for death was 10·3 (95% CI 3·2-32·3; p<0·001) for an SpO 2 of less than 90%, 4·3 (1·5-11·8; p=0·005) for an SpO 2 of 90-93%, and 11·4 (3·1-41·4; p<0·001) for a failed measurement. When not considering pulse oximetry, of the children who died, WHO IMCI guidelines identified only 25·0% (95% CI 9·7-46·7; six of 24 children) as eligible for referral to hospital. For identifying deaths, in children with an SpO 2 of less than 90% WHO IMCI guidelines had a 41·7% sensitivity (95% CI 22·1-63·4) and 89·7% specificity (88·7-90·7); for children with an SpO 2 of less than 90% or measurement failure the guidelines had a 54·2% sensitivity (32·8-74·4) and 88·3% specificity (87·2-89·3); and for children with an SpO 2 of less than 94% or measurement failure the guidelines had a 62·5% sensitivity (40·6-81·2) and 81·3% specificity (80·0-82·5)., Interpretation: These findings support pulse oximeter use during the outpatient care of young children with suspected pneumonia in Bangladesh as well as the re-evaluation of the WHO IMCI currently recommended threshold of an SpO 2 less than 90% for hospital referral., Funding: Fogarty International Center of the National Institutes of Health (K01TW009988), The Bill & Melinda Gates Foundation (OPP1084286 and OPP1117483), and GlaxoSmithKline (90063241)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

India had decided to roll out PCV in India in 2015, but successful implementation of any new vaccine introduction mandates an enormous effort. PCV was scaled up during the COVID-19 pandemic, which posed new, unprecedented challenges in the vaccine rollout. However, India successfully expanded PCV in the country in record time across all states and Union Territories. During the pandemic, supply-side restrictions, delayed vaccine shipments, staff shortages, and restrictions in conducting training negatively affected the roll-out of PCV across the country. However, despite the ongoing pandemic, India successfully rolled out PCV across the country in 7 months. In this review, the authors have conducted a narrative review to delineate the crucial factors that helped in the successful expansion of PCV., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

The MOF material NU-1000 was employed to host Ni tripodal complexes prepared from new organometallic precursors [HNi( κ 4 ( E , P , P , P )-E( o -C 6 H 4 CH 2 PPh 2 ) 3 ], E = Si (Ni-1), Ge (Ni-2). The new heterogeneous catalytic materials, Ni-1@NU-1000 and Ni-2@NU-1000, show the advantages of both homogeneous and heterogeneous catalysts. They catalyze the hydroboration of aldehydes and ketones more efficiently than the homogeneous Ni-1 and Ni-2, under aerobic conditions and show recyclability.

Background: Vaccines were crucial in controlling the Covid-19 pandemic. As more vaccines receive regulatory approval, stakeholders will be faced with several options and must make an appropriate choice for themselves. We proposed a multi-criteria decision analysis (MCDA) framework to guide decision-makers in comparing vaccines for the Indian context., Methods: We adhered to the ISPOR guidance for the MCDA process. Seven vaccine options were compared under ten criteria. Through three virtual workshops, we obtained opinions and weights from citizens, private-sector hospitals, and public health organisations. Available evidence was rescaled and incorporated into the performance matrix. The final score for each vaccine was calculated for the different groups. We performed different sensitivity analyses to assess the consistency of the rank list., Results: The cost, efficacy and operational score of the vaccines had the highest weights among the stakeholders. From the six scenario groups, Janssen had the highest score in four. This was driven by the advantage of having a single dose of vaccination. In the probabilistic sensitivity analysis for the overall group, Covaxin, Janssen, and Sputnik were the first three options. The participants expressed that availability, WHO approvals and safety, among others, would be crucial when considering vaccines., Conclusions: The MCDA process has not been capitalised on in healthcare decision-making in India and LMICs. Considering the available data and stakeholder preference at the time of the study, Covaxin, Janssen, and Sputnik were preferred options. The choice framework with the dynamic performance matrix is a valuable tool that could be adapted to different population groups and extended based on increasing vaccine options and emerging evidence. *ISPOR - The Professional Society for Health Economics and Outcomes Research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021., Design: Descriptive multi-country secondary data analysis., Setting: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021., Population: Liveborn infants., Methods: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study., Results: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%)., Conclusions: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs)., Design: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000., Setting: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America., Population: Live birth neonates., Methods: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies., Main Outcome Measures: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification., Results: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies., Conclusions: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: Children's early development is affected by caregiving experiences, with lifelong health and well-being implications. Governments and civil societies need population-based measures to monitor children's early development and ensure that children receive the care needed to thrive. To this end, the WHO developed the Global Scales for Early Development (GSED) to measure children's early development up to 3 years of age. The GSED includes three measures for population and programmatic level measurement: (1) short form (SF) (caregiver report), (2) long form (LF) (direct administration) and (3) psychosocial form (PF) (caregiver report). The primary aim of this protocol is to validate the GSED SF and LF. Secondary aims are to create preliminary reference scores for the GSED SF and LF, validate an adaptive testing algorithm and assess the feasibility and preliminary validity of the GSED PF., Methods and Analysis: We will conduct the validation in seven countries (Bangladesh, Brazil, Côte d'Ivoire, Pakistan, The Netherlands, People's Republic of China, United Republic of Tanzania), varying in geography, language, culture and income through a 1-year prospective design, combining cross-sectional and longitudinal methods with 1248 children per site, stratified by age and sex. The GSED generates an innovative common metric (Developmental Score: D-score) using the Rasch model and a Development for Age Z-score (DAZ). We will evaluate six psychometric properties of the GSED SF and LF: concurrent validity, predictive validity at 6 months, convergent and discriminant validity, and test-retest and inter-rater reliability. We will evaluate measurement invariance by comparing differential item functioning and differential test functioning across sites., Ethics and Dissemination: This study has received ethical approval from the WHO (protocol GSED validation 004583 20.04.2020) and approval in each site. Study results will be disseminated through webinars and publications from WHO, international organisations, academic journals and conference proceedings., Registration Details: Open Science Framework https://osf.io/ on 19 November 2021 (DOI 10.17605/OSF.IO/KX5T7; identifier: osf-registrations-kx5t7-v1)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) for children aged < 1 year in March 2015. Previous vaccine effectiveness (VE) studies for pneumonia have used invasive pneumococcal disease or chest X-rays. None have used ultrasound. We sought to determine the VE of PCV10 against sonographically-confirmed pneumonia in three subdistrict health complexes in Bangladesh., Methods: We conducted a matched case-control study between July 2015 and September 2017 in three subdistricts of Sylhet, Bangladesh. Cases were vaccine-eligible children aged 3-35 months with sonographically-confirmed pneumonia, who were matched with two types of controls by age, sex, week of diagnosis, subdistrict health complex (clinic controls) or distance from subdistrict health complex (community controls) and had an illness unlikely due to Streptococcus pneumoniae (clinic controls) or were healthy (community controls). VE was measured using multivariable conditional logistic regression., Results: We evaluated 8926 children (average age 13.3 months, 58% boys) with clinical pneumonia by ultrasound; 2470 had pneumonia with consolidations ≥ 1 cm; 1893 pneumonia cases were matched with 4238 clinic controls; and 1832 were matched with 3636 community controls. VE increased with the threshold used for consolidation size on ultrasound: the adjusted VE of ≥ 2 doses vs. non-recipients of PCV10 against pneumonia increased from 15.8% (95% CI 1.6-28.0%) for consolidations ≥ 1 cm to 29.6% (12.8-43.2%) for consolidations ≥ 1.5 cm using clinic controls and from 2.7% (- 14.2-17.2%) to 23.5% (4.4-38.8%) using community controls, respectively., Conclusions: PCV10 was effective at reducing sonographically-confirmed pneumonia in children aged 3-35 months of age when compared to unvaccinated children. VE increased with the threshold used for consolidation size on ultrasound in clinic and community controls alike. This study provides evidence that lung ultrasound is a useful alternative to chest X-ray for case-control studies evaluating the effectiveness of vaccines against pneumonia., (© 2022. The Author(s).)

Background: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh., Methods: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n = 2683) and their children (n = 2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys® test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models., Results: Overall, about one-third of women (35.8%, 95% CI = 33.7-37.9) and one-fifth of children (21.3%, 95% CI = 19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR = 1.19,95% CI = 1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR = 1.16,  95% CI = 1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR = 1.37, 95% CI = 1.10-1.71) than in children with a paternal education of ≤5 years., Conclusions: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential., Competing Interests: Disclosure of interest: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author) and declare no conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: WHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO 2 ), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO 2 threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO 2 threshold for hypoxaemia from well children in Bangladesh residing at low altitude., Methods: We prospectively enrolled well, children aged 3-35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO 2 of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO 2 distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO 2 as possible lower thresholds for hypoxaemia., Results: Our primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO 2 was 98% (IQR 96%-99%), and the 2.5th, 5th and 10th percentile SpO 2 was 91%, 92% and 94%. No child had a SpO 2 <90%. Children 3-11 months had a lower median SpO 2 (97%) than 12-23 months (98%) and 24-35 months (98%) (p=0.039). The SpO 2 distribution did not differ by sex (p=0.959)., Conclusion: A SpO 2 threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO 2 must also consider the child's clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO 2 thresholds for hypoxaemia is a key next step., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The coronavirus disease 2019 (COVID-19) pandemic is a worldwide epidemiological emergency, and the risk factors for the multiple waves with new COVID-19 strains are concerning. This study aims to identify the most significant risk factors for spreading COVID-19 to help policymakers take early measures for the next waves., Methods: We conducted the study on randomly selected 29 countries where the pandemic had a downward trend in the daily active cases curve as of June 10, 2020. We investigated the association with the standardized spreading index and demographical, environmental, socioeconomic, and government intervention. To standardize the spreading index, we accounted for the number of tests and the timeline bias. Furthermore, we performed multiple linear regression to identify the relative importance of the variables., Results: In the correlation analysis, air pollution, PM 2.5 (r = 0.37, p  = 0.0466), number of days to impose lockdown from first case (r = 0.38, p  = 0.0424) and total confirmed cases on the first lockdown (r = 0.61, p  = 0.0004) were associated with outcome measures. In the adjusted model, air pollution ( β 1  = 4.5, p  = 0.0127, |t| = 3.1) and overweight prevalence ( β 1  = 4.7, p  = 0.0187, |t| = 2.9) were the most significant exposure variable for spreading of COVID-19., Conclusion: Our findings showed that countries with larger PM 2.5 values and comparatively more overweight populations are at higher risk of spreading COVID-19. Proper preventive measures may reduce the spreading., (© 2021 The Author(s).)

Background: Bangladesh introduced the ten-valent pneumococcal conjugate vaccine (PCV10) into its national immunization program in March 2015 creating an opportunity to assess the real-world impact of PCV on invasive pneumococcal disease (IPD)., Methods: Between January 2014 and June 2018, children aged 3-35 months in three rural sub-districts of Sylhet district of Bangladesh were visited every two months to collect morbidity and care-seeking data. Children attending sub-district hospitals with pneumonia, meningitis, or sepsis were assessed for IPD after obtaining informed consent. Blood and cerebrospinal fluid were collected from enrolled children to isolate pneumococcus using culture and molecular test. Children who were age-eligible to receive the PCV and had pneumococcus isolated were enrolled as cases. Four age and sex-matched clinic and community controls were selected for each case within one to two weeks of case identification. Data on immunization status and confounders were collected. PCV coverage was estimated using vaccine coverage surveys. Case-control and incidence trend analyses were conducted to assess the impact of PCV on IPD., Results: The community cohort yielded 217,605 child years of observations and 154,773 sick child-visits to study hospitals. Pneumococcus was isolated from 44 children who were age-eligible to receive PCV; these children were enrolled as cases. The cases were matched with 166 community- and 150 clinic-controls. The matched case-control analyses using community-controls showed 83% effectiveness (95% CI: 1.57-97.1%) and clinic controls showed 90% effectiveness (95% CI: -26.0% to 99.1%) of PCV in preventing IPD. Incidence trend analysis estimated vaccine effectiveness at 80.1% (95% CI: 38.4, 93.6)., Conclusion: PCV in this pediatric population in Bangladesh was highly effective in preventing IPD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Pneumococcal conjugate vaccine (PCV) effectiveness against radiographic pneumonia in South Asia is unknown. Bangladesh introduced PCV10 in 2015 using a three dose primary series (3 + 0). We sought to measure PCV10 effectiveness for two or more vaccine doses on radiographic pneumonia among vaccine-eligible children in rural Bangladesh., Methods: We conducted a matched case-control study over two years from 2015 to 2017 using clinic and community controls in three subdistricts of Sylhet, Bangladesh. Cases were vaccine eligible 3-35 month olds at Upazila Health Complex outpatient clinics with World Health Organization-defined radiographic primary endpoint pneumonia (radiographic pneumonia). Clinic controls were matched to cases within a one week time window by age, sex, and clinic and had an illness unlikely to be Streptococcus pneumoniae; community controls were healthy and similarly matched within a one week time window by age and sex, and distance from the clinic. We estimated adjusted vaccine effectiveness (aVE) using conditional logistic regression., Results: We matched 1262 cases with 2707 clinic and 2461 community controls. Overall, aVE using clinic controls was 21.4% (95% confidence interval, -0.2%, 38.4%) for ≥2 PCV10 doses and among 3-11 month olds was 47.3% (10.5%, 69.0%) for three doses. aVE increased with higher numbers of doses in clinic control sets (p = 0.007). In contrast, aVE using community controls was 7.6% (95% confidence interval, -22.2%, 30.0%) for ≥2 doses. We found vaccine introduction in the study area faster and less variable than expected with 75% coverage on average, which reduced power. Information bias may also have affected community controls., Conclusions: Clinic control analyses show PCV10 prevented radiographic pneumonia in Bangladesh, especially among younger children receiving three doses. While both analyses were underpowered, community control enrollment - compared to clinic controls - was more difficult in a complex, pluralistic healthcare system. Future studies in comparable settings may consider alternative study designs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [EDM, SA, NHC, SJR, AMK, ADR, AAMH, FP, NS, MER, MH, HBS, AQ, NB, MS, LHM, WC, and AHB reports grants from Bill and Melinda Gates Foundation, grants from GlaxoSmithKline, during the conduct of the study.]., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Stomach cancer is a difficult-to-treat disease. Lack of detection markers and limited understanding of the disease mechanisms contribute to the aggressive nature of stomach cancer cells (SCCs). Recently, an ATPase, ATAD2 has been found to be highly expressed in stomach cancer contributing to increased malignancy. However, nothing is known about the mechanism of ATAD2 upregulation and its involvement in stomach carcinogenesis. Since hypoxic microenvironment plays a crucial role in the progression of solid tumors like stomach cancer; we have examined the regulation and function of ATAD2 expression in hypoxic SCCs. ATAD2 is induced in hypoxia-treated SCCs. Stomach adenocarcinoma and metastatic tissues with high HIF1α level also show enhanced ATAD2 expression. In the absence of hypoxia-inducible factor HIF1α, ATAD2 protein level is found to be less indicating towards a potential correlation between them. We identify the presence of HIF1α-binding site (HBS) and HIF1α ancillary site (HAS) in the ATAD2 promoter. Using both in vitro and in vivo binding studies, we confirm that HIF1α binds with the ATAD2 promoter in hypoxic condition. ATAD2 upregulation promotes proliferation and migration of SCCs exposed to hypoxia. Thus, we identify ATAD2 as a hypoxia-responsive and HIF1α-regulated gene and elucidate that upregulated expression of ATAD2 enhances tumor-promoting functions in hypoxic SCCs. Therefore, we propose ATAD2 as a promising therapeutic target for stomach cancer., Competing Interests: Declaration of competing interest The author(s) state that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Pneumonia is a leading cause of death in children of low-resource settings. Barriers to care include an early and accurate diagnosis. Lung ultrasound is a novel tool for the identification of pediatric pneumonia; however, there is currently no standardized approach to train in image acquisition and interpretation of findings in epidemiological studies. We developed a training program for physicians with limited ultrasound experience on how to use ultrasound for the diagnosis of pediatric pneumonia and how to standardize image interpretation using a panel of readers., Methods: Twenty-five physicians participating in the training program conducted lung ultrasounds in all children with suspected pneumonia, aged 3 to 35 months, presenting to three subdistrict hospitals in Sylhet, Bangladesh, between June 2015 and September 2017., Results: A total of 9051 pediatric lung ultrasound assessments were conducted through 27 months of data collection. Study physicians underwent training and all were successfully standardized, achieving 91% agreement and maintained a sensitivity and specificity of 88% and 92%, respectively, when their diagnosis was compared with experts. Overall kappa between two readers was high (0.86, 95% confidence interval [CI], 0.84-0.87), and remained high when a third expert reader was included (0.80, 95% CI, 0.79-0.81). Agreement and kappa statistics were similarly high when stratified by age, sex, presence of danger signs, or hypoxemia., Conclusions: Lung ultrasound is a novel tool for the diagnosis of pediatric pneumonia with evidence supporting its validity and feasibility of implementation. Here we introduced a training program that resulted in a high level of inter-sonographer agreement., (© 2019 The Authors. Pediatric Pulmonology published by Wiley Periodicals, Inc.)

Background: In low-income settings, community health workers (CHWs) are frequently the first point of contact for newborns. Mobile technology may aid health workers in classifying illness and providing referral and management guidance for newborn care. This study evaluates the potential for mobile health technology to improve diagnosis and case management of newborns in Bangladesh., Methods: A mobile application based on Bangladesh's Comprehensive Newborn Care Package national guidelines (mCNCP) was developed to aid CHWs in identifying and managing small and sick infants. After a 2-day training, CHWs assessed newborns at Sylhet Osmani Medical College Hospital and in the Projahnmo research site (Sylhet, Bangladesh) using either mCNCP or a comparable paper form (pCNCP), similar to standard IMCI-formatted paper forms. CHWs were randomized to conduct a block of ~ 6 newborn assessments starting with either mCNCP or pCNCP, then switched to the alternate method. Physicians using mCNCP served as gold standard assessors. CHW performance with mCNCP and pCNCP were compared using chi-squared tests of independence for equality of proportions, and logistic regressions clustered by CHW., Results: Two hundred seven total CHW assessments were completed on 101 enrolled infants. mCNCP assessments were more often fully completed and completed faster than pCNCP assessments (100% vs 23.8%, p < 0.001; 17.5 vs 23.6 min; p < 0.001). mCNCP facilitated calculations of respiratory rate, temperature, and gestational age. CHWs using mCNCP were more likely to identify small newborns (Odds Ratio (OR): 20.8, Confidence Interval (CI): (7.1, 60.8), p < 0.001), and to correctly classify 7 out of 16 newborn conditions evaluated, including severe weight loss (OR: 13.1, CI: (4.6, 37.5), p < 0.001), poor movement (OR: 6.6, CI: (2.3, 19.3), p = 0.001), hypothermia (OR: 14.9, CI: (2.7, 82.2), p = 0.002), and feeding intolerance (OR: 2.1, CI: (1.3, 3.3), p = 0.003). CHWs with mCNCP were more likely to provide counseling as needed on 4 out of 7 case management recommendations evaluated, including kangaroo mother care., Conclusions: CHWs in rural Bangladesh with limited experience using tablets successfully used a mobile application for neonatal assessment after a two-day training. mCNCP may aid frontline health workers in Bangladesh to improve completion of neonatal assessment, classification of illnesses, and adherence to neonatal management guidelines.

Background: Severe neonatal hyperbilirubinemia (>20 mg/dL) affects ∼1 million infants annually. Improved jaundice screening in low-income countries is needed to prevent bilirubin encephalopathy and mortality., Methods: The Bili-ruler is an icterometer for the assessment of neonatal jaundice that was designed by using advanced digital color processing. A total of 790 newborns were enrolled in a validation study at Brigham and Women's Hospital (Boston) and Sylhet Osmani Medical College Hospital (Sylhet, Bangladesh). Independent Bili-ruler measurements were made and compared with reference standard transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) concentrations., Results: Bili-ruler scores on the nose were correlated with TcB and TSB levels ( r = 0.76 and 0.78, respectively). The Bili-ruler distinguished different clinical thresholds of hyperbilirubinemia, defined by TcB, with high sensitivity and specificity (score ≥3.5: 90.1% [95% confidence interval (CI): 84.8%-95.4%] and 85.9% [95% CI: 83.2%-88.6%], respectively, for TcB ≥13 mg/dL). The Bili-ruler also performed reasonably well compared to TSB (score ≥3.5: sensitivity 84.5% [95% CI: 79.1%-90.3%] and specificity 83.2% [95% CI: 76.1%-90.3%] for TSB ≥11 mg/dL). Areas under the receiver operating characteristic curve for identifying TcB ≥11, ≥13, and ≥15 were 0.92, 0.93, and 0.94, respectively, and 0.90, 0.87, and 0.86 for identifying TSB ≥11, ≥13, and ≥15. Interrater reliability was high; 97% of scores by independent readers fell within 1 score of one another ( N = 88)., Conclusions: The Bili-ruler is a low-cost, noninvasive tool with high diagnostic accuracy for neonatal jaundice screening. This device may be used to improve referrals from community or peripheral health centers to higher-level facilities with capacity for bilirubin testing and/or phototherapy., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Lee and Ms Folger are currently employed by Brigham and Women’s Hospital; Little Sparrows Technologies, Inc, has been granted a sole, royalty-bearing license by Brigham and Women’s Hospital under the copyright rights to use, reproduce, and sell licensed products related to this research; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Introduction: To evaluate WHO chest radiograph interpretation processes during a pneumococcal vaccine effectiveness study of children aged 3-35 months with suspected pneumonia in Sylhet, Bangladesh., Methods: Eight physicians masked to all data were standardised to WHO methodology and interpreted chest radiographs between 2015 and 2017. Each radiograph was randomly assigned to two primary readers. If the primary readers were discordant for image interpretability or the presence or absence of primary endpoint pneumonia (PEP), then another randomly selected, masked reader adjudicated the image (arbitrator). If the arbitrator disagreed with both primary readers, or concluded no PEP, then a masked expert reader finalised the interpretation. The expert reader also conducted blinded quality control (QC) for 20% of randomly selected images. We evaluated agreement between primary readers and between the expert QC reading and the final panel interpretation using per cent agreement, unadjusted Cohen's kappa, and a prevalence and bias-adjusted kappa., Results: Among 9723 images, the panel classified 21.3% as PEP, 77.6% no PEP and 1.1% uninterpretable. Two primary readers agreed on interpretability for 98% of images (kappa, 0.25; prevalence and bias-adjusted kappa, 0.97). Among interpretable radiographs, primary readers agreed on the presence or absence of PEP in 79% of images (kappa, 0.35; adjusted kappa, 0.57). Expert QC readings agreed with final panel conclusions on the presence or absence of PEP for 92.9% of 1652 interpretable images (kappa, 0.75; adjusted kappa, 0.85)., Conclusion: Primary reader performance and QC results suggest the panel effectively applied the WHO chest radiograph criteria for pneumonia., Competing Interests: Competing interests: None declared.

The synthesis of ultrasmall supported bimetallic nanoparticles (between 1 and 3 nanometers in diameter) with well-defined stoichiometry and intimacy between constituent metals remains a substantial challenge. We synthesized 10 different supported bimetallic nanoparticles via surface inorganometallic chemistry by decomposing and reducing surface-adsorbed heterometallic double complex salts, which are readily obtained upon sequential adsorption of target cations and anions on a silica substrate. For example, adsorption of tetraamminepalladium(II) [Pd(NH 3 ) 4 2+ ] followed by adsorption of tetrachloroplatinate [PtCl 4 2- ] was used to form palladium-platinum (Pd-Pt) nanoparticles. These supported bimetallic nanoparticles show enhanced catalytic performance in acetylene selective hydrogenation, which clearly demonstrates a synergistic effect between constituent metals., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Gastric epithelial cells infected with Helicobacter pylori acquire highly invasive and metastatic characteristics. The seven in absentia homolog (Siah)2, an E3 ubiquitin ligase, is one of the major proteins that induces invasiveness of infected gastric epithelial cells. We find that p300-driven acetylation of Siah2 at lysine 139 residue stabilizes the molecule in infected cells, thereby substantially increasing its efficiency to degrade prolyl hydroxylase (PHD)3 in the gastric epithelium. This enhances the accumulation of an oncogenic transcription factor hypoxia-inducible factor 1α (Hif1α) in H. pylori-infected gastric cancer cells in normoxic condition and promotes invasiveness of infected cells. Increased acetylation of Siah2, Hif1α accumulation, and the absence of PHD3 in the infected human gastric metastatic cancer biopsy samples and in invasive murine gastric cancer tissues further confirm that the acetylated Siah2 (ac-Siah2)-Hif1α axis is crucial in promoting gastric cancer invasiveness. This study establishes the importance of a previously unrecognized function of ac-Siah2 in regulating invasiveness of H. pylori-infected gastric epithelial cells.-Kokate, S. B., Dixit, P., Das, L., Rath, S., Roy, A. D., Poirah, I., Chakraborty, D., Rout, N., Singh, S. P., Bhattacharyya, A. Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori-infected gastric epithelial cancer cells.

Helicobacter pylori is the strongest known risk-factor for gastric cancer. However, its role in gastric cancer metastasis remains unclear. Previously we have reported that H. pylori promotes gastric cancer invasiveness by stabilizing the E3 ubiquitin ligase Siah2 which is mediated by Siah2 acetylation at Lys 139 (K 139 ) residue. Here we identify that cell adhesion-related proteins testin (TES) and filamin-C (FLN-C) interact with Siah2 and get proteasomally degraded. The efficiency of TES and FLN-C degradation is significantly potentiated by K 139 -acetylated Siah2 (ac-K 139 Siah2) in infected gastric cancer cells (GCCs). ac-Siah2-mediated downregulation of TES and FLN-C disrupts filopodia structures but promotes lamellipodia formation and enhances invasiveness and migration of infected GCCs. Since H. felis-infected mice as well as human gastric cancer biopsy samples also show high level of ac-K 139 Siah2 and downregulated TES and FLN-C, we believe that acetylation of Siah2 is an important checkpoint that can be useful for therapeutic intervention., (Copyright © 2018 Elsevier Ltd. All rights reserved.)