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There is an urgent need to better understand the micronutrient demands of pregnancy due to the complex physiological adaptations during the gestational period and the importance of micronutrients in maternal-fetal health. Rigorous studies of micronutrients in pregnancy are significantly lacking due to a number of issues including the exclusion of pregnant people in research, methodological barriers to studying micronutrients, and the multidisciplinary expertise required for such studies. Stable isotopes present a unique methodological opportunity to quantify pregnancy-related changes in the absorption, distribution, metabolism, and excretion of micronutrients. We demonstrate here through a rapid review of the published literature that this approach is dramatically underutilized outside of calcium. In this perspective, we discuss the use of stable isotopes to study micronutrient physiology and our experiences in addressing the need for more studies in this area. Finally, we discuss how we might overcome major barriers to move toward a better understanding of micronutrient physiology in pregnancy.

BackgroundPaxlovid is authorized for the treatment of COVID-19 and must be used within the first 5 days of symptom onset. This limited window for initiating treatment makes rapid access critical. Federal Test-to-Treat programs provide tests, prescriptions, and medication in one visit3.ObjectiveThe objective of this study was to map the location of and identify disparities in access to Test-to-Treat programs in the United States (U.S.).MethodsWe obtained location data for public providers of Paxlovid and Test-to-Treat programs in the contiguous U.S. and examined their spatial distribution at the zip code tabulation area level. We defined zip codes as underserved if there was no Test-to-Treat program located within the zip code or within 20 miles of its boundaries.ResultsMore than 52,000,000 people—representing 16% of the continental U.S. population—do not have access to a Test-to-Treat program in their zip code or within 20 miles. The majority of zip codes representing metropolitan areas have a Test-to-Treat program within 20 miles (77%). In contrast, only 30% of small towns and 23% of rural areas have nearby access. Zip codes with a high proportion of Hispanic and Black residents were likely to have access to nearby Test-to-Treat programs (72%, 70%). In contrast, zip codes with a high proportion of Native American residents were likely to be underserved (70%). About half of high-poverty zip codes do not have access to a Test-to-Treat program within 20 miles.DiscussionDisparities in outcomes related to COVID-19 have been apparent since the beginning of the pandemic and continue to grow. While the multi-dimensional measure of social vulnerability was used to expand the federal Test-to-Treat program, some populations remain without access.

CONTEXT Early enteral feeding has been associated with adverse outcomes such as necrotizing enterocolitis in preterm and low birth weight infants. OBJECTIVES To assess effects of early enteral feeding initiation within the first days after birth compared to delayed initiation. DATA SOURCES Medline, Scopus, Web of Science, CINAHL from inception to June 30, 2021. STUDY SELECTION Randomized trials (RCTs) were included. Primary outcomes were mortality, morbidity, growth, neurodevelopment, feed intolerance, and duration of hospitalization. DATA EXTRACTION Data were extracted and pooled with random-effects models. RESULTS We included 14 randomized controlled trials with 1505 participants in our primary analysis comparing early ( CONCLUSIONS Enteral feeding within 72 hours after birth likely reduces the risk of mortality and length of hospital stay, may reduce the risk of sepsis, and may reduce weight at discharge.

BACKGROUND AND OBJECTIVES Responsive feeding may improve health outcomes in preterm and low birth weight (LBW) infants. Our objective was to assess effects of responsive compared with scheduled feeding in preterm and LBW infants. METHODS Data sources include PubMed, Scopus, Web of Science, CINAHL, LILACS, and MEDICUS. Randomized trials were screened. Primary outcomes were mortality, morbidity, growth, neurodevelopment. Secondary outcomes were feed intolerance and duration of hospitalization. Data were extracted and pooled with random-effects models. RESULTS Eleven eligible studies were identified, and data from 8 randomized control trials with 455 participants were pooled in the meta-analyses. At discharge, the mean difference in body weight between the intervention (responsive feeding) and comparison (scheduled feeding) was −2.80 g per day (95% CI −3.39 to −2.22, I2 = 0%, low certainty evidence, 4 trials, 213 participants); −0.99 g/kg per day (95% CI −2.45 to 0.46, I2 = 74%, very low certainty evidence, 5 trials, 372 participants); −22.21 g (95% CI −130.63 to 86.21, I2 = 41%, low certainty evidence, 3 trials, 183 participants). The mean difference in duration of hospitalization was −1.42 days (95% CI −5.43 to 2.59, I2 = 88%, very low certainty evidence, 5 trials, 342 participants). There were no trials assessing other growth outcomes (eg, length and head circumference) mortality, morbidity or neurodevelopment. Limitations include a high risk of bias, heterogeneity, and small sample size in included studies. CONCLUSIONS Overall, responsive feeding may decrease in-hospital weight gain. Although the evidence is very uncertain, responsive feeding may slightly decrease the duration of hospitalization. Evidence was insufficient to understand the effects of responsive compared with scheduled feeding on mortality, morbidity, linear growth, and neurodevelopmental outcomes in preterm and LBW infants.

ObjectiveTo investigate mothers’ experiences during the 2022 infant formula shortage in the United States and its perceived impacts on infants’ diet and health.MethodsMothers of infants under 8 months old were recruited from Washington D.C. using social media and neighborhood listservs and invited to participate in a virtual study meeting between June 22 and July 14, 2022. Mothers completed a brief survey with questions about their demographic characteristics, infants’ anthropometric characteristics, and infant feeding practices, and participated in an in-depth, qualitative interview about their experiences during the infant formula shortage. Survey data were analyzed using means and frequencies, as appropriate. Qualitative interviews were recorded, transcribed verbatim, coded, and thematically analyzed.ResultsThe sample (n=28) was predominantly White and highly educated. Five overarching themes were identified, including the shortage had: 1) adverse impacts on mothers’ mental and emotional health; 2) significant financial and intangible costs; and 3) led to changes in infant feeding practices; and, 4) social and family networks were helpful in navigating the shortage; and 5) mothers felt fortunate to have resources to breastfeed and/or obtain formula. Most mothers reported the shortage had not yet detrimentally impacted their infant’s health.ConclusionsEven among highly educated women with access to financial, social, structural resources, the infant formula shortage adversely impacted mothers’ mental and emotional health, and has been costly, in terms of financial and intangible costs. Findings demonstrate the urgent need to develop strategies to support mothers in feeding their infants, especially mothers who may lack the resources to locate and obtain formula.

To describe the epidemiology and referral patterns of gastroschisis patients in northern Ghana. A hospital-based retrospective review was undertaken at Tamale Teaching Hospital (TTH) Neonatal Intensive Care Unit (NICU) between 2014 and 2019. Data from gastroschisis patients were compared to patients with other surgical diagnoses. Descriptive and inferential statistics were performed with SAS. Referral flow maps were made with ArcGIS. From a total of 360 neonates admitted with surgical conditions, 12 (3%) were diagnosed with gastroschisis. Around 91% (n = 10) of gastroschisis patients were referred from other hospitals, traveling 4 h, on average. Referral patterns showed gastroschisis patients were admitted from three regions, whereas patients with other surgical diagnoses were admitted from eight regions. Only 6% (12/201) of expected gastroschisis cases were reported during the 6-year period in all regions. All gastroschisis deaths occurred within the first week of life. Improving access to surgical care and reducing neonatal mortality related to gastroschisis in northern Ghana is critical. This study provides a baseline to inform future gastroschisis interventions at TTH. Priority areas may include special management of low birth weight newborns, better referral systems, empowerment of community health workers, and increasing access to timely, affordable, and safe neonatal transport.

Critical advancement is needed in the study of human milk as a biological system that intersects and interacts with myriad internal (maternal biology) and external (diet, environment, infections) factors and its plethora of influences on the developing infant. Human-milk composition and its resulting biological function is more than the sum of its parts. Our failure to fully understand this biology in a large part contributes to why the duration of exclusive breastfeeding remains an unsettled science (if not policy). Our current understanding of human-milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation. The overly simplistic, but common, approach to analyzing single, mostly nutritive components of human milk is insufficient to understand the contribution of either individual components or the matrix within which they exist to both maternal and child health. There is a need for a shift in the conceptual approach to studying human milk to improve strategies and interventions to support better lactation, breastfeeding, and the full range of infant feeding practices, particularly for women and infants living in undernourished and infectious environments. Recent technological advances have led to a rising movement towards advancing the science of human-milk biology. Herein, we describe the rationale and critical need for unveiling the multifunctionality of the various nutritional, nonnutritional, immune, and biological signaling pathways of the components in human milk that drive system development and maturation, growth, and development in the very early postnatal period of life. We provide a vision and conceptual framework for a research strategy and agenda to change the field of human-milk biology with implications for global policy, innovation, and interventions.

Snakebite envenomings (SBEs) and other envenomings triggered by venomous animals (VAEs) represent a significant disease burden in Brazil, with 29,152 SBEs reported in 2021 alone with nearly half of those occurring in the remote Brazilian Amazon. In 2021, Brazil recorded 240,294 envenomings from snakes, scorpions, spiders, and caterpillars. Therefore, there is an unequal distribution of SBEs with high morbidity and mortality in the Brazilian Amazon. The severity of SBEs increases when patients require more than 6 h to access antivenom treatment, a common issue for the rural and indigenous populations. Understanding currently available resources and practices in Amazon remote areas of Brazil can serve to inform future interventions and guide health care policies. This study aims to develop a resource map of existing healthcare resources for the Brazilian Amazon's clinical management of VAEs with emphasis in SBEs, which will aid future strategic interventions. Data collection included a literature review, secondary data collected by government departments and organizational records, GIS mapping activities, and expert input. Our framework was guided by the three levels of healthcare service ecosystem analysis (macro, meso, and micro). Our resource map lays out a comprehensive overview of antivenom access, the distribution landscape, differences in patient transportation, and barriers to access healthcare that face populations in the Brazilian Amazon.

Congenital conditions comprise a significant portion of the global burden of surgical conditions in children. In Somaliland, over 250,000 children do not receive required surgical care annually, although the estimated costs and benefits of scale-up of children's surgical services to address this disease burden is not known.We developed a Markov model using a decision tree template to project the costs and benefits of scale-up of surgical care for children across Somaliland. We used a proxy set of congenital anomalies across Somaliland to estimate scale-up costs using three different scale-up rates. The cost-effectiveness ratio and net societal monetary benefit were estimated using these models, supported by disability weights in existing literature.Overall, we found that scale-up of surgical services at an aggressive rate (22.5%) over a 10-year time horizon is cost effective. Although the scale-up of surgical care for most conditions in the proxy set was cost effective, scale-up of hydrocephalus and spina bifida are not as cost effective as other conditions.Our analysis concludes that it is cost effective to scale-up surgical services for congenital anomalies for children in Somaliland.

BACKGROUND: Vaccines may induce non-specific effects on survival and health outcomes, in addition to protection against targeted pathogens or disease. Observational evidence suggests that infant Baccillus Calmette-Guérin (BCG) vaccination may provide non-specific survival benefits, while diphtheria-tetanus-pertussis (DTP) vaccination may increase the risk of mortality. Non-specific vaccine effects have been hypothesized to modify the effect of neonatal vitamin A supplementation (NVAS) on mortality. METHODS: 22,955 newborns in Ghana and 31,999 newborns in Tanzania were enrolled in two parallel, randomized, double-blind, placebo-controlled trials of neonatal vitamin A supplementation from 2010 to 2014 and followed until 1-year of age. Cox proportional hazard models were used to estimate associations of BCG and DTP vaccination with infant survival. RESULTS: BCG vaccination was associated with a decreased risk of infant mortality after controlling for confounders in both countries (Ghana adjusted hazard ratio (aHR): 0.51, 95% CI: 0.38-0.68; Tanzania aHR: 0.08, 95% CI: 0.07-0.10). Receiving a DTP vaccination was associated with a decreased risk of death (Ghana aHR: 0.39, 95% CI: 0.26-0.59; Tanzania aHR: 0.19, 95% CI: 0.16-0.22). There was no evidence of interaction between BCG or DTP vaccination status and infant sex or NVAS. CONCLUSION: We demonstrated that BCG and DTP vaccination were associated with decreased risk of infant mortality in Ghana and Tanzania with no evidence of interaction between DTP or BCG vaccination, NVAS, and infant sex. Our study supports global recommendations on BCG and DTP vaccination and programmatic efforts to ensure all children have access to timely vaccination. CLINICAL TRIALS REGISTRATION: Ghana (Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000582055) and Tanzania (ANZCTR: ACTRN12610000636055).

COVID-19 vaccine hesitancy among adolescents poses a challenge to the global effort to control the pandemic. This multi-country survey aimed to assess the levels and determinants of COVID-19 vaccine hesitancy among adolescents in sub-Saharan Africa between July and December 2021. The survey was conducted using computer-assisted telephone interviewing among adolescents in five sub-Saharan African countries, Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania. A rural area and an urban area were included in each country (except Ghana, which only had a rural area), with approximately 300 adolescents in each area and 2803 in total. Sociodemographic characteristics and perceptions and attitudes on COVID-19 vaccines were measured. Vaccine hesitancy was defined as definitely not getting vaccinated or being undecided on whether to get vaccinated if a COVID-19 vaccine were available. Log-binomial models were used to calculate the adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for associations between potential determinants and COVID-19 vaccine hesitancy. The percentage of COVID-19 vaccine hesitancy was 15% in rural Kersa, 24% in rural Ibadan, 31% in rural Nouna, 33% in urban Ouagadougou, 37% in urban Addis Ababa, 48% in rural Kintampo, 64% in urban Lagos, 76% in urban Dar es Salaam, and 88% in rural Dodoma. Perceived low necessity, concerns about vaccine safety, and concerns about vaccine effectiveness were the leading reasons for hesitancy. Healthcare workers, parents or family members, and schoolteachers had the greatest impacts on vaccine willingness. Perceived lack of safety (aPR: 3.61; 95% CI: 3.10, 4.22) and lack of effectiveness (aPR: 3.59; 95% CI: 3.09, 4.18) were associated with greater vaccine hesitancy. The levels of COVID-19 vaccine hesitancy among adolescents are alarmingly high across the five sub-Saharan African countries, especially in Tanzania. COVID-19 vaccination campaigns among sub-Saharan African adolescents should address their concerns and misconceptions about vaccine safety and effectiveness.

Inactivated viral vaccines have long been used in humans for diseases of global health threat (e.g., poliomyelitis and pandemic and seasonal influenza) and the technology of inactivation has more recently been used for emerging diseases such as West Nile, Chikungunya, Ross River, SARS and especially for COVID-19. The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit and risk of several vaccine platform technologies, including inactivated viral vaccines. This paper uses the BRAVATO inactivated virus vaccine template to review the features of an inactivated whole chikungunya virus (CHIKV) vaccine that has been evaluated in several preclinical studies and clinical trials. The inactivated whole CHIKV vaccine was cultured on Vero cells and inactivated by ß-propiolactone.This provides an effective, flexible system for high-yield manufacturing. The inactivated whole CHIKV vaccine has favorable thermostability profiles, compatible with vaccine supply chains. Safety data are compiled in the current inactivated whole CHIKV vaccine safety database with unblinded data from the ongoing studies: 850 participants from phase II study (parts A and B) outside of India, and 600 participants from ongoing phase II study in India, and completed phase I clinical studies for 60 subjects. Overall, the inactivated whole CHIKV vaccine has been well tolerated, with no significant safety issues identified. Evaluation of the inactivated whole CHIKV vaccine is continuing, with 1410 participants vaccinated as of 20 April 2022. Extensive evaluation of immunogenicity in humans shows strong, durable humoral immune responses.

BACKGROUND AND OBJECTIVES Cessation of exclusive breastfeeding (EBF) with early introduction of complementary food provides additional calories for catch-up growth but may also increase the risk of adverse outcomes. The objective of this study was to assess effects of exclusive breastfeeding for less than 6 months compared with 6 months in preterm and low birth weight infants. METHODS Data sources include Medline, Scopus, Web of Science, CINAHL, and Index Medicus through June 30, 2021. Study selection includes randomized trials and observational studies. Primary outcomes were mortality, morbidity, growth, and neurodevelopment. Data were extracted and pooled using random-effects models. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias of included studies. RESULTS A total of 2 studies of 307 preterm or low birth weight infants were included. None of the study results could be pooled. Both studies compared EBF for 4 months to 6 months. Growth was similar between the 4-month and 6-month EBF groups for the following outcomes: weight-for-age z-score at corrected age 12 months (mean [standard deviation], 4-month group: −1.7 [1.1], 6-month group: −1.8 [1.2], 1 study, 188 participants, low certainty evidence), absolute weight gain (gram) from 16 to 26 weeks of age (4-month group: 1004 [366], 6-month group: 1017 [350], 1 study, 119 participants, very low certainty evidence), and linear growth gain (cm) from 16 to 26 weeks of age (4-month group: 4.3 [0.9], 6-month group: 4.5 [1.2], 1 study, 119 participants, very low certainty evidence). There were no apparent differences in reported morbidity symptoms. No difference in the timing to achieve motor development milestones between the 2 groups was found (1 study; 119 participants, very low certainty evidence). A limited number of studies prevented data pooling. CONCLUSIONS The evidence is very uncertain about the effect of exclusive breastfeeding for less than 6 months for preterm and low birth weight infants. Further studies are warranted to better answer this question.

BACKGROUND AND OBJECTIVES Fast feed advancement may reduce hospital stay and infection but may increase adverse outcomes in preterm and low birth weight infants. The objective of this study was to assess effects of fast feed advancement (≥30 ml/kg per day) compared with slow feed advancement ( METHODS Data sources include Medline, Scopus, Web of Science, CINAHL, and Index Medicus through June 30, 2021. Randomized trials were selected. Primary outcomes were mortality, morbidity, growth, and neurodevelopment. Data were extracted and pooled using random-effects models. The Cochrane Risk of Bias 2 tool was used. RESULTS A total of 12 RCTs with 4291 participants were included. At discharge, there was moderate certainty evidence that fast advancement likely slightly reduces the risk of: mortality (relative risk [RR] 0.93, 95% confidence interval [95% CI] 0.73 to 1.18, I2 = 18%, 11 trials, 4132 participants); necrotizing enterocolitis (RR 0.89, 95% CI 0.68 to 1.15, I2 = 0%, 12 trials, 4291 participants); sepsis (RR 0.92, 95% CI 0.83 to 1.03, I2 = 0%, 9 trials, 3648 participants); and feed intolerance (RR 0.92, 95% CI 0.77 to 1.10, I2 = 0%, 8 trials, 1114 participants). Fast feed advancement may also reduce the risk of apnea (RR 0.72, 95% CI 0.47 to 1.12, I2 = 0%, low certainty, 2 trials, 153 participants). Fast feed advancement decreases time to regain birth weight (mean difference [MD] −3.69 days, 95% CI −4.44 to −2.95, I2 = 70%, high certainty, 6 trials, 993 participants,) and likely reduces the duration of hospitalization (MD −3.08 days, 95% CI −4.34 to −1.81, I2 = 77%, moderate certainty, 7 trials, 3864 participants). Limitations include heterogeneity between studies and small sample sizes. CONCLUSIONS Fast feed advancement reduces time to regain birth weight and likely reduces the length of hospital stay; it also likely reduces the risk of neonatal morbidity and mortality slightly. However, it may increase the risk of neurodevelopmental disability slightly. More studies are needed to understand the long-term effects of fast feed advancement.

We estimated vaccine effectiveness (VE) for prevention of influenza-associated hospitalizations among adults during the 2018–2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and testing positive for influenza were cases; patients testing negative were controls. VE was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with a mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09–associated hospitalization was 51% (95% confidence interval [CI], 25%–68%). Adjusted VE against influenza A(H3N2) virus–associated hospitalization was −2% (95% CI, −65% to 37%) and differed significantly by age, with VE of −130% (95% CI, −374% to −27%) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza A(H1N1)pdm09–associated hospitalizations, it conferred no protection against influenza A(H3N2)–associated hospitalizations. We observed negative VE for young and middle-aged adults but cannot exclude residual confounding as a potential explanation.

This resource list could serve to orient those interested in global surgery and could be supplemented with resources advocating for global surgery from clinical, population health, or policy perspectives., Key Messages The most useful resource reported was Global Surgery 2030, along with other publications, data collection tools, books and training manuals, and a documentary.This list could serve as a starting point for individuals interested in global surgery and be supplemented with resources advocating for global surgery from clinical, population health, or policy perspectives.

Nucleic acid (DNA and RNA) vaccines are among the most advanced vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. This will facilitate the assessment by key stakeholders of potential safety issues and understanding of overall benefit-risk. The structured assessment provided by the template can also help improve communication and public acceptance of licensed nucleic acid vaccines.

Background Demonstration of influenza vaccine effectiveness (VE) against hospitalized illness in addition to milder outpatient illness may strengthen vaccination messaging. Our objective was to compare patient characteristics and VE between United States (US) inpatient and outpatient VE networks. Methods We tested adults with acute respiratory illness (ARI) for influenza within 1 outpatient-based and 1 hospital-based VE network from 2015 through 2018. We compared age, sex, and high-risk conditions. The test-negative design was used to compare vaccination odds in influenza-positive cases vs influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time to testing from, season (overall VE), and underlying conditions. VE differences (ΔVE) were assessed with 95% confidence intervals (CIs) determined through bootstrapping with significance defined as excluding the null. Results The networks enrolled 14 573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median, 62 years vs 49 years) and had more high-risk conditions (median, 4 vs 1). Overall VE across seasons was 31% (95% CI, 26%–37%) among outpatients and 36% (95% CI, 27%–44%) among inpatients. Strain-specific VE (95% CI) among outpatients vs inpatients was 37% (25%–47%) vs 53% (37%–64%) against H1N1pdm09; 19% (9%–27%) vs 23% (8%–35%) against H3N2; and 46% (38%–53%) vs 46% (31%–58%) against B viruses. ΔVE was not significant for any comparison across all sites. Conclusions Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health among inpatients, influenza vaccination was effective in preventing influenza-associated hospitalizations.

Background Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged ≥65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. Results Among 1487 enrolled patients aged ≥65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV, and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] −42%, 38%) and that of HD-IIV was 32% (95% CI −3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95% CI −1%, 48%). Conclusions During 2 US influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged ≥65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

There are complex barriers that increase delays to surgical care in low- and middle-income countries, particularly among the vulnerable population of children. Understanding these barriers to surgical care can result in targeted and strategic intervention efforts to improve care for children. The three-delay model is a widely used framework in global health for evaluating barriers associated with seeking (D1), reaching (D2), and receiving health care (D3). The goal of our study is to evaluate reasons for delays in the surgical care for children in Somaliland using the three-delay framework. Data were collected in a cross-sectional study in Somaliland from 1503 children through a household survey. Among children with a surgical need, we quantified the number of children seeking, reaching, and receiving care along the surgical care continuum, according to the three-delay framework. We evaluated predictors of the three delays through a multivariate logistic regression model, including the child’s age, gender, village type, household income level, region, and household size. Of the 196 children identified with a surgical condition, 50 (27.3%) children had a delay in seeking care (D1), 28 (20.6%) children had a delay in reaching care (D2), and 84 (71.2%) children had a delay in receiving care (D3), including 10 children who also experienced D1 and D2. The main reasons cited for D1 included seeking a traditional healthcare provider, while lack of money and availability of care were main reasons cited for D2. Significant predictors for delays included household size for D1 and D3 and condition type and region for D2. Children in Somaliland experience several barriers to surgical care along the entire continuum of care, allowing for policy guidance tailored to specific local challenges and resources. Since delays in surgical care for children can substantially impact the effectiveness of surgical interventions, viewing delays in surgical care under the lens of the three-delay framework can inform strategic interventions along the pediatric surgical care continuum, thereby reducing delays and improving the quality of surgical care for children.

Significant disparities exist for timely access to cancer care for children, with the highest disparities in low- and middle-income countries (LMICs). This study aims to conduct a systematic review that identifies the factors contributing to delayed care of childhood cancers in LMICs.We will conduct a systematic review with search strings compliant with the PICO framework: (1) the Population-children (aged 0-18 years) from LMICs; (2) the Exposure-factors contributing to timely childhood cancer care; (3) the Outcome-delays in childhood cancer care.Our study is an essential step to guide strategic interventions to assess the myriad of factors that prevent children from accessing timely cancer care in LMICs. The results will be submitted for publication in a peer-reviewed journal and shared with institutions related to the field.

Background: The Masimo Total Hemoglobin SpHb® is a continuous and non-invasive handheld device to measure hemoglobin levels. Previous research has found that SpHb is able to accurately detect hemoglobin levels in adult patients with a similar degree of bias and standard deviation to point-of-care invasive method measurements. Generally, limited clinical evidence, lack of validation of Masimo at higher than and lower than hemoglobin threshold values, and scientific consensus supporting the use of Masimo for accurate hemoglobin testing for the diagnosis of anemia during pregnancy calls for further research. Methods and analysis: The proposed prospective cohort will be nested within the ongoing Pregnancy Risk and Infant Surveillance and Measurement Alliance (PRISMA) Maternal and Newborn Health (MNH) study. Three study sites (located in Zambia, Kenya, and Pakistan) will participate and collect hemoglobin data at five time points ( Conclusions: The primary aim of this study is to assess the validity of the non-invasive Masimo device compared to the gold standard method of invasive hemoglobin measurements during pregnancy and postpartum periods for the diagnosis of anemia.

IntroductionAssessing the impact of COVID-19 policy is critical for informing future policies. However, there are concerns about the overall strength of COVID-19 impact evaluation studies given the circumstances for evaluation and concerns about the publication environment. This study systematically reviewed the strength of evidence in the published COVID-19 policy impact evaluation literature.MethodsWe included studies that were primarily designed to estimate the quantitative impact of one or more implemented COVID-19 policies on direct SARS-CoV-2 and COVID-19 outcomes. After searching PubMed for peer-reviewed articles published on November 26, 2020 or earlier and screening, all studies were reviewed by three reviewers first independently and then to consensus. The review tool was based on previously developed and released review guidance for COVID-19 policy impact evaluation, assessing what impact evaluation method was used, graphical display of outcomes data, functional form for the outcomes, timing between policy and impact, concurrent changes to the outcomes, and an overall rating.ResultsAfter 102 articles were identified as potentially meeting inclusion criteria, we identified 36 published articles that evaluated the quantitative impact of COVID-19 policies on direct COVID-19 outcomes. The majority (n=23/36) of studies in our sample examined the impact of stay-at-home requirements. Nine studies were set aside because the study design was considered inappropriate for COVID-19 policy impact evaluation (n=8 pre/post; n=1 cross-section), and 27 articles were given a full consensus assessment. 20/27 met criteria for graphical display of data, 5/27 for functional form, 19/27 for timing between policy implementation and impact, and only 3/27 for concurrent changes to the outcomes. Only 1/27 studies passed all of the above checks, and 4/27 were rated as overall appropriate. Including the 9 studies set aside, reviewers found that only four of the 36 identified published and peer-reviewed health policy impact evaluation studies passed a set of key design checks for identifying the causal impact of policies on COVID-19 outcomes.DiscussionThe reviewed literature directly evaluating the impact of COVID-19 policies largely failed to meet key design criteria for inference of sufficient rigor to be actionable by policy-makers. This was largely driven by the circumstances under which policies were passed making it difficult to attribute changes in COVID-19 outcomes to particular policies. More reliable evidence review is needed to both identify and produce policy-actionable evidence, alongside the recognition that actionable evidence is often unlikely to be feasible.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

Description, Women and pregnant people are missing from high-quality research that informs nutrient reference values., Women and pregnant people have historically been underrepresented in research; this may extend to the basic research informing nutrient reference values, such as the United States’ and Canada’s Dietary Reference Intakes (DRIs). After screening the DRI reports for 23 micronutrients, we extracted metadata from 704 studies. Women were excluded in 23% of studies, and they accounted for a smaller proportion of the sample size (29%). Pregnant or lactating people were included in 17% of the studies. Studies that used rigorous design elements, such as controlled feeding and stable isotope studies, were the most likely to include men only. The majority of studies (>90%) did not report race and ethnicity. Although nutrient reference values are intended for use in the general population, we find that the basic science informing these values may not be generalizable. We call urgently upon funders and researchers to address fundamental gaps in knowledge with high-quality research.

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12–14% lower prevalence of stunting, wasting, and underweight; were 16–19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.

Background Congenital anomalies have risen to become the fifth leading cause of under-five mortality globally. The majority of deaths and disability occur in low- and middle-income countries including Ghana. This 3-year retrospective review aimed to define, for the first time, the characteristics and outcomes of neonatal surgical conditions in northern Ghana. Methods A retrospective study was conducted to include all admissions to the Tamale Teaching Hospital (TTH) neonatal intensive care unit (NICU) with surgical conditions between January 2014 and January 2017. Data were collected on demographics, diagnosis and outcomes. Descriptive analysis was performed on all data, and logistic regression was used to predict determinants of neonatal mortality. p Results Three hundred and forty-seven neonates were included. Two hundred and sixty-one (75.2%) were aged 7 days or less at presentation, with males (n = 177, 52%) slightly higher than females (n = 165, 48%). The majority were delivered by spontaneous vaginal delivery (n = 247, 88%); 191 (58%) were born in hospital. Congenital anomalies accounted for 302 (87%) of the neonatal surgical cases and 45 (96%) deaths. The most common anomalies were omphalocele (n = 48, 13.8%), imperforate anus (n = 34, 9.8%), intestinal obstruction (n = 29, 8.4%), spina bifida (n = 26, 7.5%) and hydrocephalus (n = 19, 5.5%). The overall mortality rate was 13.5%. Two-thirds of the deaths (n = 30) from congenital anomalies were conditions involving the digestive system with gastroschisis having the highest mortality of 88%. Omphalocele (n = 11, 23.4%), gastroschisis (n = 7, 14.9%) and imperforate anus (n = 6, 12.8%) contributed to the most deaths. On multivariate analysis, low birthweight was significantly associated with mortality (OR 3.59, CI 1.4–9.5, p = 0.009). Conclusion Congenital anomalies are a major global health problem associated with high neonatal mortality in Ghana. The highest burden in terms of both caseload and mortality is attributed to congenital anomalies involving the digestive system, which should be targeted to improve outcomes.

ObjectiveTo assess whether sustained, scheduled mobile health team (MHT) services increase antenatal care (ANC), postnatal care (PNC) and childhood immunisation in conflict-affected and remote regions of Afghanistan.DesignCross-sectional, population-based study from 2013 to 2017. Proportions were compared using multivariable linear regression adjusted for clustering and socio-demographic variables.Setting54 intervention and 56 control districts in eight Afghanistan provinces.Participants338 796 pregnant women and 1 693 872 children aged under 5 years.Interventions‘Intervention districts’ that received MHT services for 3 years compared with ‘control districts’ in the same province without any MHT services over the same period.Main outcome measuresDistrict-level and clinic-level ANC, PNC, childhood immunisation (pentavalent 3, measles 1), integrated management of childhood immunisation services.ResultsProportion of pregnant women receiving at least one ANC visit was higher in intervention districts (83.6%, 161 750/193 482) than control districts (61.3%, 89 077/145 314) (adjusted mean difference (AMD) 14.8%;95% CI: 1.6% to 28.0%). Proportion of children under 1 year receiving their first dose of measles vaccine was higher in intervention (73.8%, 142 738/193 412) than control districts (57.3%, 83 253/145 293) (AMD 12.8;95% CI: 2.1% to 23.5%). There was no association with PNC (AMD 2.8%;95% CI: −5.1% to 10.7%). MHTs did not increase clinic-level service provision for ANC (AMD 41.32;95% CI: -52.46 to 135.11) or any other outcomes.ConclusionsSustained, scheduled MHT services to conflict-affected and remote regions were associated with improved coverage of important maternal and child health interventions. Outreach is an essential service and not just an ‘optional extra’ for the most deprived mothers and children.

Background The Lancet Commission on Global Surgery highlighted global surgical need but offered little insight into the specific surgical challenges of children in low-resource settings. Efforts to strengthen the quality of global pediatric surgical care have resulted in a proliferation of partnerships between low-and middle-income countries (LMICs) and high-income countries (HICs). Standardized tools able to reliably measure gaps in delivery and quality of care are important aids for these partnerships. We undertook a systematic review (SR) of capacity assessment tools (CATs) focused on needs assessment in pediatric surgery. Methods A comprehensive search strategy of multiple electronic databases was conducted per PRISMA guidelines without linguistic or temporal restrictions. CATs were selected according to pre-defined inclusion criteria. Articles were assessed by two independent reviewers. Methodological quality of studies was appraised using the COSMIN checklist with 4-point scale. Results The search strategy generated 16,641 original publications, of which three CATs were deemed eligible. Eligible tools were either excessively detailed or oversimplified. None used weighted scores to identify finer granularity between institutions. No CATs comprehensively included measures of resources, outcomes, accessibility/impact and training. Discussion The results of this study identify the need for a CAT capable of objectively measuring key aspects of surgical capacity and performance in a weighted tool designed for pediatric surgical centers in LMICs. Type of Study Systematic Review. Level of Evidence II.

Objectives Suboptimal breastfeeding contributes to morbidity and mortality in children. Studies in high-income countries (HICs) show that exclusive-breastfeeding (EBF) is associated with longer breastfeeding duration. The aim of this study was to determine whether maternal reports of EBF at six months are associated with longer duration of breastfeeding during the first two years of life in a low and middle-income country (LMIC) setting, and to identify determinants of breastfeeding duration. Methods This prospective cohort includes data from an EBF promotion program in Demak District, Central Java Province, Indonesia, with a non-randomized pretest-posttest control group. Mothers and infants were followed through 26 months postnatal age. Data were analyzed using Cox proportional hazard regression with time to cessation of EBF as the outcome. Results A total of 147 families were included in the study. Longer EBF duration was not associated with prolonged duration of breastfeeding. Longer breastfeeding duration was associated with mothers who disagreed with a statement of being ashamed to breastfeed (HR 0.035, 95%CI 0.003,0.44). Risk factors for shorter breastfeeding duration included mothers’ plan to breastfeed for less than 24 months (HR 4.28 95%CI 1.91,9.60), mothers’ belief that breastfeeding less than 24 months was the norm (HR 2.98 95%CI 1.31,6.77) and exposure to EBF promotion (HR:4.09 95%CI 2.14,7.82). Conclusions In a LMIC community where long breastfeeding duration is common, EBF is not associated with breastfeeding duration. However, modifiable behavioral factors were significant predictors of breastfeeding duration. We therefore recommend that prolonged breastfeeding duration can be achieved through programs that improve breastfeeding behavior.

Background Delayed vaccination increases the time infants are at risk for acquiring vaccine-preventable diseases. Factors associated with incomplete vaccination are relatively well characterized in resource-limited settings; however, few studies have assessed immunization timeliness. Methods We conducted a prospective cohort study examining Diphtheria-Tetanus-Pertussis (DTP) vaccination timing among newborns enrolled in a Neonatal Vitamin A supplementation trial (NEOVITA) conducted in urban Dar es Salaam (n = 11,189) and rural Morogoro Region (n = 19,767), Tanzania. We used log-binomial models to assess the relationship of demographic, socioeconomic, healthcare access, and birth characteristics with late or incomplete DTP1 and DTP3 immunization. Results The proportion of infants with either delayed or incomplete vaccination was similar in Dar es Salaam (DTP1 11.5% and DTP3 16.0%) and Morogoro (DTP1 9.2% and DTP3 17.3%); however, the determinants of delayed or incomplete vaccination as well as their magnitude of association differed by setting. Both maternal and paternal education were more strongly associated with vaccination status in rural Morogoro region as compared to Dar es Salaam (p-values for heterogeneity

Consumption of diet beverages (DB) containing low-calorie sweeteners (LCS) is widespread in the United States. LCS are ingested by nursing infants upon maternal DB consumption, which may impact infants’ weight and health. This study aims to examine cross-sectional associations between infants’ LCS exposure via maternal DB intake during lactation and infants’ health outcomes. Six hundred and eighty-two mother–infant dyads at three months postpartum, from the Infant Feeding Practices Study II, 2005–2007, were included in the analysis. Maternal DB consumption during lactation was estimated using the serving size and frequency of DB consumption reported on the diet history questionnaire. Infants’ LCS exposure was estimated by multiplying maternal DB consumption and breastfeeding intensity. Infant outcomes included weight, weight-for-age and BMI-for-age z-scores, overweight, and gastrointestinal (GI) symptoms including diarrhea, reflux, and vomiting. Associations between infants’ LCS exposure and continuous and categorical outcomes were examined using linear and logistic regressions adjusting for confounders, respectively. Forty-three percent of lactating women reported DB consumption. While no significant associations were observed between infants’ LCS exposure and BMI-for-age or risk of overweight, infants’ LCS exposure was associated with a 2.78-fold increased risk of vomiting (95% confidence interval 1.05–7.34). Potential adverse effects of LCS exposure on GI symptoms require further study, and null findings on infant weight should be interpreted with caution, given the small sample size. Additional research is needed to inform recommendations for or against DB consumption during lactation.

Auro Vaccines LLC has developed a protein vaccine to prevent disease from Nipah and Hendra virus infection that employs a recombinant soluble Hendra glycoprotein (HeV-sG) adjuvanted with aluminum phosphate. This vaccine is currently under clinical evaluation in a Phase 1 study. The Benefit-Risk Assessment of VAccines by TechnolOgy Working Group (BRAVATO; ex-V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of such a vaccine platform. The structured and standardized assessment provided by the template may also helpcontribute to improved public acceptance and communication of licensed protein vaccines.

BackgroundThe global burden of disease in children is large and disproportionally affects low-income and middle-income countries (LMICs). Geospatial analysis offers powerful tools to quantify and visualise disparities in surgical care in LMICs. Our study aims to analyse the geographical distribution of paediatric surgical conditions and to evaluate the geographical access to surgical care in Somaliland.MethodsUsing the Surgeons OverSeas Assessment of Surgical Need survey and a combined survey from the WHO’s (WHO) Surgical Assessment Tool—Hospital Walkthrough and the Global Initiative for Children’s Surgery Global Assessment in Paediatric Surgery, we collected data on surgical burden and access from 1503 children and 15 hospitals across Somaliland. We used several geospatial tools, including hotspot analysis, service area analysis, Voronoi diagrams, and Inverse Distance Weighted interpolation to estimate the geographical distribution of paediatric surgical conditions and access to care across Somaliland.ResultsOur analysis suggests less than 10% of children have timely access to care across Somaliland. Patients could travel up to 12 hours by public transportation and more than 2 days by foot to reach surgical care. There are wide geographical disparities in the prevalence of paediatric surgical conditions and access to surgical care across regions. Disparities are greater among children travelling by foot and living in rural areas, where the delay to receive surgery often exceeds 3 years. Overall, Sahil and Sool were the regions that combined the highest need and the poorest surgical care coverage.ConclusionOur study demonstrated wide disparities in the distribution of surgical disease and access to surgical care for children across Somaliland. Geospatial analysis offers powerful tools to identify critical areas and strategically allocate resources and interventions to efficiently scale-up surgical care for children in Somaliland.

Expansion of access to surgical care can improve health outcomes, although the impact that scale-up of the surgical workforce will have on child mortality is poorly defined. In this study, we estimate the number of child deaths potentially avertable by increasing the surgical workforce globally to meet targets proposed by the Lancet Commission on Global Surgery. To estimate the number of deaths potentially avertable through increases in the surgical workforce, we used log-linear regression to model the association between surgeon, anesthetist and obstetrician workforce (SAO) density and surgically amenable under-5 mortality rate (U5MR), infant mortality rate (IMR), and neonatal mortality rate (NMR) for 192 countries adjusting for potential confounders of childhood mortality, including the non-surgical workforce (physicians, nurses/midwives, community health workers), gross national income per capita, poverty rate, female literacy rate, health expenditure per capita, percentage of urban population, number of surgical operations, and hospital bed density. Surgically amenable mortality was determined using mortality estimates from the UN Inter-agency Group for Child Mortality Estimation adjusted by the proportion of deaths in each country due to communicable causes unlikely to be amenable to surgical care. Estimates of mortality reduction due to upscaling surgical care to support the Lancet Commission on Global Surgery (LCoGS) minimum target of 20–40 SAO/100,000 were calculated accounting for potential increases in surgical volume associated with surgical workforce expansion. Increasing SAO workforce density was independently associated with lower surgically amenable U5MR as well as NMR (p

Background: The coronavirus disease (COVID-19) has spread worldwide with an increasing number of patients, including pregnant women and neonates. This study aims to evaluate morbidity and mortality in the COVID-19 era compared to the preceding year in the Neonatal Intensive Care Unit (NICU) at Tamale Teaching Hospital, Ghana.Methods: This is a cross-sectional study carried out on neonates admitted to NICU between March 1st to August 31st, 2019 (pre-COVID-19 era) and March 1st to August 31st, 2020 (COVID-19 era). Multivariate logistic regression was performed to identify predictors of mortality for both periods.Results: From 2,901 neonates, 1,616 (56%) were admitted before, and 1,285 (44%) were admitted during the pandemic. Admissions decreased during the COVID-19 era, reaching their lowest point between June and August 2020. Compared to the previous year, during the COVID-19 era, admissions of patients born at TTH, delivered at home, and with infections decreased from 50 to 39%, 7 to 4%, and 22 to 13%, respectively. Referred status (OR = 3.3) and vaginal delivery (OR = 1.6) were associated with an increased likelihood of mortality. For low- birth weight neonates, admissions of patients born at TTH, with vaginal and home delivery decreased from 62 to 48%, 8 to 2%, and 59 to 52%, respectively. Neonatal infections and congenital anomalies decreased from 8 to 4%, 5 to 3%, respectively. The likelihood of mortality among referred patients increased by 50%.Conclusion: We observed a marked decrease in admissions and change in the diagnosis landscape and related mortality during the pandemic. Underlying challenges, including fear, financing, and health system capacity, might intensify delays and lack of access to newborn care in northern Ghana, leading to higher rates of lifelong disabilities and mortality. Immediate damage control measures, including an improved home-based continuum of care and equipping families to participate in the newborn care with complemented m-health approaches, are needed with urgency.

Introduction: Global surgical care is increasingly recognized in the global health agenda and requires multidisciplinary engagement. Despite high interest among medical students, residents and other learners, many surgical faculty and health experts remain uniformed about global surgical care. Methods: We have operated an interdisciplinary graduate-level course in Global Surgical Care based on didactics and interactive group learning. Students completed a pre- and post-course survey regarding their learning experiences and results were analyzed using the Wilcoxon signed-rank test. Results: Fourteen students completed the pre-course survey, and 11 completed the post-course survey. Eleven students (79%) were enrolled in a Master’s degree program in global health, with eight students (57%) planning to attend medical school. The median ranking of surgery on the global health agenda was fifth at the beginning of the course and third at the conclusion (p = 0.11). Non-infectious disease priorities tended to stay the same or increase in rank from pre- to post-course. Infectious disease priorities tended to decrease in rank (HIV/AIDS, p = 0.07; malaria, p = 0.02; neglected infectious disease, p = 0.3). Students reported that their understanding of global health (p = 0.03), global surgery (p = 0.001) and challenges faced by the underserved (p = 0.03) improved during the course. When asked if surgery was an indispensable part of healthcare, before the course 64% of students strongly agreed, while after the course 91% of students strongly agreed (p = 0.3). Students reported that the interactive nature of the course strengthened their skills in collaborative problem-solving. Conclusions: We describe an interdisciplinary global surgery course that integrates didactics with team-based projects. Students appeared to learn core topics and held a different view of global surgery after the course. Similar courses in global surgery can educate clinicians and other stakeholders about strategies for building healthy surgical systems worldwide.

This reflection paper complements the WAAVP (World Association for the Advancement of Veterinary Parasitology) general anthelmintic efficacy guideline, which outlines the general principles of anthelmintic efficacy evaluation across all animal host species. It provides background to the recommendations made in the WAAVP general anthelmintic efficacy guideline, with insights into the discussions leading to specific recommendations in the general guideline or the absence thereof. Furthermore, this paper discusses recent technological advancements with potential value to the evaluation of anthelmintic efficacy that may be considered for future versions of the general or species-specific guidelines if supported by sufficient levels of evidence. Finally, it also identifies potential research questions, such as the statistical approach for comparing worm counts between groups of animals.

Background Symptoms of mild COVID‐19 illness are non‐specific and may persist for prolonged periods. Effects on quality of life of persistent poor physical or mental health associated with COVID‐19 are not well understood. Methods Adults aged ≥18 years with laboratory‐confirmed COVID‐19 and matched control patients who tested negative for SARS‐CoV‐2 infection at outpatient facilities associated with 11 medical centers in the United States were interviewed to assess symptoms, illness duration, and health‐related quality of life. Duration of symptoms, health‐related quality of life measures, and days of poor physical health by symptoms experienced during illness were compared between case patients and controls using Wilcoxon rank‐sum tests. Symptoms associated with COVID‐19 case status were evaluated by multivariable logistic regression. Results Among 320 participants included, 157 were COVID‐19 cases and 163 were SARS‐CoV‐2 negative controls. Loss of taste or smell was reported by 63% of cases and 6% of controls and was strongly associated with COVID‐19 in logistic regression models (adjusted odds ratio [aOR] = 32.4; 95% confidence interval [CI], 12.6‐83.1). COVID‐19 cases were more likely than controls to have experienced fever, body aches, weakness, or fatigue during illness, and to report ≥1 persistent symptom more than 14 days after symptom onset (50% vs 32%, P

Neonatal deaths now account for more than two-thirds of all deaths in the first year of life and for about half of all deaths in children under-five years. Sub-Saharan Africa accounts up to 41% of the total burden of neonatal deaths worldwide. Our study aims to describe causes of neonatal mortality and to evaluate predictors of timing of neonatal death at Tamale Teaching Hospital (TTH), Ghana. This retrospective study was conducted at TTH located in Northern Ghana. All neonates who died in the Neonatal Intensive Care Unit (NICU) from 2013 to 2017 were included and data was obtained from admission and discharge books and mortality records. Bivariate and multivariate logistic regression were used to assess predictors of timing of neonatal death. Out of the 8,377 neonates that were admitted at the NICU during the 5-year study period, 1,126 died, representing a mortality rate of 13.4%. Of those that died, 74.3% died within 6 days. There was an overall downward trend in neonatal mortality over the course of the 5-year study period (18.2% in 2013; 14.3% in 2017). Preterm birth complications (49.6%) and birth asphyxia (21.7%) were the top causes of mortality. Predictors of early death included being born within TTH, birth weight, and having a diagnosis of preterm birth complication or birth asphyxia. Our retrospective study found that almost 3/4 of neonatal deaths were within the first week and these deaths were more likely to be associated with preterm birth complications or birth asphyxia. Most of the deaths occurred in babies born within health facilities, presenting an opportunity to reduce our mortality by improving on quality of care provided during the perinatal period.

In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health’s COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.

Nutrient reference values are important parameters that guide nutrition and public health work globally. Micronutrient requirements during the peri-conception period are generally increased, which is essential in ensuring maternal, fetal, and neonatal health. Nevertheless, the current dietary reference intakes (DRIs) may be limited in terms of the methods used and the populations included, particularly the DRIs for pregnancy and lactation. In this proposed review, we will examine the methods (rigor of design, utilization of molecular methods, and presence of modern methods) and the population (inclusion of women, and in particular, pregnant and lactating people) in the studies used to inform the current DRIs. We will apply meta-science methods to this review, which involves formally reviewing the current evidence, and identifying opportunities to improve how we fund, perform, evaluate, and incorporate nutrition science into public health programs for better outcomes.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. The Modified Vaccinia Ankara (MVA) vector system is being explored as a platform for development of multiple vaccines. This paper reviews the molecular and biological features specifically of the MVA-BN vector system, followed by a template with details on the safety and characteristics of an MVA-BN based vaccine against Zaire ebolavirus and other filovirus strains. The MVA-BN-Filo vaccine is based on a live, highly attenuated poxviral vector incapable of replicating in human cells and encodes glycoproteins of Ebola virus Zaire, Sudan virus and Marburg virus and the nucleoprotein of the Thai Forest virus. This vaccine has been approved in the European Union in July 2020 as part of a heterologous Ebola vaccination regimen. The MVA-BN vector is attenuated following over 500 serial passages in eggs, showing restricted host tropism and incompetence to replicate in human cells. MVA has six major deletions and other mutations of genes outside these deletions, which all contribute to the replication deficiency in human and other mammalian cells. Attenuation of MVA-BN was demonstrated by safe administration in immunocompromised mice and non-human primates. In multiple clinical trials with the MVA-BN backbone, more than 7800 participants have been vaccinated, demonstrating a safety profile consistent with other licensed, modern vaccines. MVA-BN has been approved as smallpox vaccine in Europe and Canada in 2013, and as smallpox and monkeypox vaccine in the US in 2019. No signal for inflammatory cardiac disorders was identified throughout the MVA-BN development program. This is in sharp contrast to the older, replicating vaccinia smallpox vaccines, which have a known risk for myocarditis and/or pericarditis in up to 1 in 200 vaccinees. MVA-BN-Filo as part of a heterologous Ebola vaccination regimen (Ad26.ZEBOV/MVA-BN-Filo) has undergone clinical testing including Phase III in West Africa and is currently in use in large scale vaccination studies in Central African countries. This paper provides a comprehensive picture of the MVA-BN vector, which has reached regulatory approvals, both as MVA-BN backbone for smallpox/monkeypox, as well as for the MVA-BN-Filo construct as part of an Ebola vaccination regimen, and therefore aims to provide solutions to prevent disease from high-consequence human pathogens.