112 results on '"Emily R Smith"'
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2. 'It's his cheerfulness that gives me hope': A qualitative analysis of access to pediatric cancer care in Northern Tanzania.
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Madeline Metcalf, Happiness D Kajoka, Esther Majaliwa, Anna Tupetz, Catherine A Staton, João Ricardo Vissoci, Pamela Espinoza, Cesia Cotache-Condor, Henry E Rice, Blandina T Mmbaga, and Emily R Smith
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Public aspects of medicine ,RA1-1270 - Abstract
Pediatric cancer is a significant and growing burden in low- and middle-income countries. The objective of this project was to describe the factors influencing access to pediatric cancer care in Northern Tanzania using the Three Delays Model. This was a cross-sectional qualitative study conducted between June and August 2023 at Kilimanjaro Christian Medical Centre (KCMC). Using purposive sampling methods, caregivers of children obtaining pediatric cancer care at KCMC were approached for participation in in-depth interviews (IDIs) and a demographic survey. All IDIs were facilitated in Swahili by a bilingual research coordinator. Analysis utilized inductive and deductive coding approaches to identify dominant themes and sub-themes impacting access to pediatric oncology care. Data collection concluded once saturation was achieved at 13 IDIs, defined as the absence of new codes after three consecutive interviews. Participants reported significant financial barriers to accessing pediatric cancer care along the entire care continuum. In the first delay, themes included waiting for symptoms to resolve and the identification of initial symptoms. The most substantial delays occurred in delay 2, including health infrastructure at mid-level facilities, misdiagnoses, the referral system, travel, and traditional medicine. Participants did not describe delays after arrival to KCMC and rather offered perspective on their child's cancer diagnosis, their concerns while obtaining care, and their hopes for the future. Financial support provided by the Tanzanian government was the only facilitator noted by participants. We suggest targeted interventions including 1) empowerment of CHWs and local traditional healers to advocate for earlier care seeking behavior, 2) implementation of clinical structures and training at intermediary medical centers aimed at earlier referral to a treatment facility, 3) incorporation of support and education initiatives for families of children with a cancer diagnosis. Lastly, national health plans should include pediatric cancer care.
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- 2024
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3. Impact of the COVID-19 pandemic on perinatal care and outcomes: A retrospective study in a tertiary hospital in Northern Ghana.
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Alhassan Abdul-Mumin, Kingsley Appiah Bimpong, Cesia Cotache-Condor, Jonathan Oppong, Ana Maria Simono Charadan, Adam Munkaila, Joao Vitor Perez de Souza, and Emily R Smith
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Medicine ,Science - Abstract
BackgroundPerinatal mortality remains a global challenge. This challenge may be worsened by the negative effects of the COVID-19 pandemic on maternal and child health.ObjectivesExamine the impact of the COVID-19 pandemic on perinatal care and outcomes in the Tamale Teaching Hospital in northern Ghana.MethodsA hospital-based retrospective study was conducted in the Tamale Teaching Hospital. We compared antenatal care attendance, total deliveries, cesarean sections, and perinatal mortality before the COVID-19 pandemic (March 1, 2019 to February 28, 2020) and during the COVID-19 pandemic (March 1, 2020 to February 28, 2021). Interrupted time series analyses was performed to evaluate the impact of the COVID-19 pandemic on perinatal care and outcomes at TTH.ResultsA total number of 35,350 antenatal visits and 16,786 deliveries were registered at TTH from March 2019 to February 2021. Antenatal care, early neonatal death, and emergency cesarean section showed a rapid decline after the onset of the pandemic, with a progressive recovery over the following months. The total number of deliveries and fresh stillbirths showed a step change with a marked decrease during the pandemic, while the macerated stillbirths showed a pulse change, a temporary marked decrease with a quick recovery over time.ConclusionThe COVID-19 pandemic had a negative impact on perinatal care and outcomes in our facility. Pregnancy monitoring through antenatal care should be encouraged and continued even as countries tackle the pandemic.
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- 2024
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4. Understanding family-level decision-making when seeking access to acute surgical care for children: Protocol for a cross-sectional mixed methods study.
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Bria Hall, Allison Tegge, Cesia Cotache Condor, Marie Rhoads, Terri-Ann Wattsman, Angelica Witcher, Elizabeth Creamer, Anna Tupetz, Emily R Smith, Mamata Reddy Tokala, Brian Meier, and Henry E Rice
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Medicine ,Science - Abstract
BackgroundThere is limited understanding of how social determinants of health (SDOH) impact family decision-making when seeking surgical care for children. Our objectives of this study are to identify key family experiences that contribute to decision-making when accessing surgical care for children, to confirm if family experiences impact delays in care, and to describe differences in family experiences across populations (race, ethnicity, socioeconomic status, rurality).MethodsWe will use a prospective, cross-sectional, mixed methods design to examine family experiences during access to care for children with appendicitis. Participants will include 242 parents of consecutive children (0-17 years) with acute appendicitis over a 15-month period at two academic health systems in North Carolina and Virginia. We will collect demographic and clinical data. Parents will be administered the Adult Responses to Children's Symptoms survey (ARCS), the child and parental forms of the Adverse Childhood Experiences (ACE) survey, the Accountable Health Communities Health-Related Social Needs Screening Tool, and Single Item Literacy Screener. Parallel ARCS data will be collected from child participants (8-17 years). We will use nested concurrent, purposive sampling to select a subset of families for semi-structured interviews. Qualitative data will be analyzed using thematic analysis and integrated with quantitative data to identify emerging themes that inform a conceptual model of family-level decision-making during access to surgical care. Multivariate linear regression will be used to determine association between the appendicitis perforation rate and ARCS responses (primary outcome). Secondary outcomes include comparison of health literacy, ACEs, and SDOH, clinical outcomes, and family experiences across populations.DiscussionWe expect to identify key family experiences when accessing care for appendicitis which may impact outcomes and differ across populations. Increased understanding of how SDOH and family experiences influence family decision-making may inform novel strategies to mitigate surgical disparities in children.
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- 2024
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5. Towards attainment of the 2030 goal for childhood cancer survival for the World Health Organization Global Initiative for Childhood Cancer: An ecological, cross-sectional study.
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Emily R Smith, Cesia Cotache-Condor, Harold Leraas, Paul Truche, Zachary J Ward, Cristina Stefan, Lisa Force, Nickhill Bhakta, and Henry E Rice
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Public aspects of medicine ,RA1-1270 - Abstract
The World Health Organization (WHO) recently launched the Global Initiative for Childhood Cancer (GICC), with the goal of attaining at least 60% cancer survival for children worldwide by the year 2030. This study aims to describe the global patterns of childhood cancer survival in 2019 to help guide progress in attaining the GICC target goal. In this ecological, cross-sectional study, we used 5-year net childhood cancer survival (2015-2019) data from a prior micro-modeling study from 197 countries and territories. Descriptive statistics were used to analyze the patterns of overall childhood cancer survival and survival for each of the six cancer tracer diagnoses as proposed by the GICC. We used hot spot analysis to identify geographic clusters of high and low cancer survival. Most high-income countries reached at least 60% (92%, n = 59/64), net childhood cancer survival at baseline. No lower-middle-income or low-income country reached at least 60% overall cancer survival at baseline. The South-East Asia region had the highest proportion of countries that did not achieve at least 60% survival at baseline (100%, n = 10/10), followed by the African region (98%, n = 49/50). For each cancer tracer diagnosis, we found the highest number of countries that have achieved at least 60% survival was for Burkitt lymphoma (44%, n = 87/197) followed by acute lymphocytic leukemia (41%, n = 80/197).Hot spot analysis showed the highest overall survival was concentrated in North America and Europe, while the lowest survival was concentrated in Sub-Saharan Africa and South-East Asia.A majority of LMICs had not reached the WHO target goal of at least 60% survival from childhood cancer at baseline in 2019, with variable success for the six childhood cancer tracer diagnoses of the GICC. These findings provide baseline assessment of individual country performance to help achieve the GICC goal of 60% overall cancer survival globally by 2030.
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- 2024
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6. Assessment of anesthesia capacity for children in Somaliland.
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Mubarak Mohamed, Andie Grimm, Christina Williams, Cesia Cotache-Condor, Tessa L Concepcion, Shukri Dahir, Edna Adan Ismail, Henry E Rice, and Emily R Smith
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Public aspects of medicine ,RA1-1270 - Abstract
The burden of pediatric surgical conditions in Somaliland is high and the pediatric anesthesia capacity across the country remains poorly understood. The international standards developed by the World Health Organization and World Federation of Societies of Anaesthesiologists (WHO-WFSA) serve as a guideline to assess the provision of anesthetic care. This study aims to describe anesthesia capacity for children in Somaliland and assess progress towards reaching the WHO-WFSA international standards. In this cross-sectional study, anesthesia infrastructure and workforce data, as well as pediatric clinical and demographic data were collected from fifteen private, charity, and government hospitals in the six regions of Somaliland. We described anesthesia capacity in Somaliland and compared baseline data to the WHO-WFSA international standards. Overall, Somaliland did not reach most of the target goals for anesthesia capacity as defined by the WHO-WFSA. Most markers for anesthesia capacity were far behind the established targets, with deficits of 99% for anesthesiologists density, 83% for operating room density, and 83% for ventilator density. Hospitals in urban Maroodi-Jeex, and private hospitals had more supplies, infrastructure, and surgical personnel than hospitals in rural areas. There are large gaps in current anesthetic resources for children according to WHO-WFSA global standards, as well as wide disparities between regions and types of hospitals in Somaliland. Increased investment in anesthesia infrastructure and workforce is required to meet the needs of pediatric surgical patients across the country.
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- 2024
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7. Financial toxicity and acute injury in the Kilimanjaro region: An application of the Three Delays Model.
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Parker Frankiewicz, Yvonne Sawe, Francis Sakita, Blandina T Mmbaga, Catherine Staton, Anjni P Joiner, and Emily R Smith
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Medicine ,Science - Abstract
BackgroundTrauma and injury present a significant global burden-one that is exacerbated in low- and middle-income settings like Tanzania. Our study aimed to describe the landscape of acute injury care and financial toxicity in the Kilimanjaro region by leveraging the Three Delays Model.MethodsThis cross-sectional study used an ongoing injury registry and financial questionnaires collected at Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania from December 2022 until March 2023. Financial toxicity measures included catastrophic expenditure and impoverishment, in accordance with World Health Organization standards. Descriptive analysis was also performed.FindingsMost acute injury patients that presented to the KCMC Emergency Department experienced financial toxicity due to their out-of-pocket (OOP) hospital expenses (catastrophic health expenditure, CHE: 62.8%; impoverishment, IMP: 85.9%). Households within our same which experienced financial toxicity had more dependents (CHE: 18.4%; IMP: 17.9% with ≥6 dependents) and lower median monthly adult-equivalent incomes (CHE: 2.53 times smaller than non-CHE; IMP: 4.27 times smaller than non-IMP). Individuals experiencing financial toxicity also underwent more facility transfers with a higher surgical burden.InterpretationDelay 1 (decision to seek care) and Delay 2 (reaching appropriate care facility) could be significant factors for those who will experience financial toxicity. In the Tanzanian healthcare system where national health insurance is present, systematic expansions are indicated to target those who are at higher risk for financial toxicity including those who live in rural areas, experience unemployment, and have many dependents.
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- 2024
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8. Modeling the global impact of reducing out-of-pocket costs for children's surgical care.
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Emily R Smith, Pamela Espinoza, Madeline Metcalf, Osondu Ogbuoji, Cesia Cotache-Condor, Henry E Rice, and Mark G Shrime
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Public aspects of medicine ,RA1-1270 - Abstract
Over 1.7 billion children lack access to surgical care, mostly in low- and middle-income countries (LMICs), with substantial risks of catastrophic health expenditures (CHE) and impoverishment. Increasing interest in reducing out-of-pocket (OOP) expenditures as a tool to reduce the rate of poverty is growing. However, the impact of reducing OOP expenditures on CHE remains poorly understood. The purpose of this study was to estimate the global impact of reducing OOP expenditures for pediatric surgical care on the risk of CHE within and between countries. Our goal was to estimate the impact of reducing OOP expenditures for surgical care in children for 149 countries by modeling the risk of CHE under various scale-up scenarios using publicly available World Bank data. Scenarios included reducing OOP expenditures from baseline levels to paying 70%, 50%, 30%, and 10% of OOP expenditures. We also compared the impact of these reductions across income quintiles (poorest, poor, middle, rich, richest) and differences by country income level (low-income, lower-middle-income, upper-middle-income, and high-income countries).Reducing OOP expenditures benefited people from all countries and income quintiles, although the benefits were not equal. The risk of CHE due to a surgical procedure for children was highest in low-income countries. An unexpected observation was that upper-middle income countries were at higher risk for CHE than LMICs. The most vulnerable regions were Africa and Latin America. Across all countries, the poorest quintile had the greatest risk for CHE. Increasing interest in financial protection programs to reduce OOP expenditures is growing in many areas of global health. Reducing OOP expenditures benefited people from all countries and income quintiles, although the benefits were not equal across countries, wealth groups, or even by wealth groups within countries. Understanding these complexities is critical to develop appropriate policies to minimize the risks of poverty.
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- 2024
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9. Cost effectiveness and return on investment analysis for surgical care in a conflict-affected region of Sudan.
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C Phifer Nicholson, Anthony Saxton, Katherine Young, Emily R Smith, Mark G Shrime, Jon Fielder, Thomas Catena, and Henry E Rice
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Public aspects of medicine ,RA1-1270 - Abstract
The delivery of healthcare in conflict-affected regions places tremendous strains to health systems, and the economic value of surgical care in conflict settings remains poorly understood. Our aims were to evaluate the cost-effectiveness, societal economic benefits, and return on investment (ROI) for surgical care in a conflict-affected region in Sudan. We conducted a retrospective study of surgical care from January to December 2022 at the Mother of Mercy-Gidel Hospital (MMH) in the Nuba Mountains of Sudan, a semi-autonomous region characterized by chronic and cyclical conflict. We collected data on all patients undergoing surgical procedures (n = 3016), including age, condition, and procedure. We used the MMH budget and financial statements to measure direct medical and non-medical expenditures (costs) for care. We estimated the proportion of expenditures for surgical care through a survey of surgical vs non-surgical beds. The benefits of care were calculated as averted disability-adjusted life-years (DALYa) based on predicted outcomes for the most common 81% of procedures, and then extrapolated to the overall cohort. We calculated the average cost-effectiveness ratio (CER) of care. The societal economic benefits of surgical care were modeled using a human capital approach, and we performed a ROI analysis. Uncertainty was estimated using sensitivity analysis. We found that the CER for all surgical care was $72.54/DALYa. This CER is far less than the gross domestic product per capita in the comparator economy of South Sudan ($585), qualifying it as very cost-effective by World Health Organization standards. The total societal economic impact of surgical care was $9,124,686, yielding a greater than 14:1 ROI ratio. Sensitivity analysis confirmed confidence in all output models. Surgical care in this conflict-affected region of Sudan is very cost-effective, provides substantial societal economic benefits, and a high return on investment.
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- 2024
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10. Does reducing out-of-pocket costs for children’s surgical care protect families from poverty in Somaliland? A cross-sectional, national, economic evaluation modelling study
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Edna Adan Ismail, Mark G Shrime, Emily R Smith, Henry E Rice, Tessa Concepcion, Shukri Dahir, Mubarak Mohamed, Cesia Cotache-Condor, Pranav Kapoor, and Treasure Ramirez
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Medicine - Abstract
Objectives An estimated 1.7 billion children around the world do not have access to safe, affordable and timely surgical care, with the financing through out-of-pocket (OOP) expenses being one of the main barriers to care. Our study modelled the impact of reducing OOP costs related to surgical care for children in Somaliland on the risk of catastrophic expenditures and impoverishment.Design and setting This cross-sectional nationwide economic evaluation modelled several different approaches to reduction of paediatric OOP surgical costs in Somaliland.Participants and outcome measures A surgical record review of all procedures on children up to 15 years old was conducted at 15 surgically capable hospitals. We modelled two rates of OOP cost reduction (reduction of OOP proportion from 70% to 50% and from 70% to 30% reduction in OOP costs) across five wealth quintiles (poorest, poor, neutral, rich, richest) and two geographical areas (urban and rural). The outcome measures of the study are catastrophic expenditures and risk of impoverishment due to surgery. We followed the Consolidated Health Economic Evaluation Reporting Standards.Results We found that the risk of catastrophic and impoverishing expenditures related to OOP expenditures for paediatric surgery is high across Somaliland, but most notable in the rural areas and among the poorest quintiles. Reducing OOP expenses for surgical care to 30% would protect families in the richest wealth quintiles while minimally affecting the risk of catastrophic expenditure and impoverishment for those in the lowest wealth quintiles, particularly those in rural areas.Conclusion Our models suggest that the poorest communities in Somaliland lack protection against the risk of catastrophic health expenditure and impoverishment, even if OOP payments are reduced to 30% of surgical costs. A comprehensive financial protection in addition to reduction of OOP costs is required to prevent risk of impoverishment in these communities.
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- 2023
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11. Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis
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Chris Gale, Marian Knight, Kirsty Le Doare, Erica M Lokken, Laura A Magee, Peter von Dadelszen, Nathalie Broutet, Emily R Smith, Deborah Money, Stephanie Jones, Olof Stephansson, Lesley Regan, Fouzia Farooq, Christoph Lees, Julia Townson, Sami L Gottlieb, Jonas Söderling, Jorge Carrillo, Anna Thorson, Marleen Temmerman, Joyce Were, Edward Mullins, Ajay Reddy, Valerie J Flaherman, Clayton Onyango, Shabir A Madhi, Antonio Lanzone, Liona C Poon, Alice Panchaud, Musa Sekikubo, Eduard Gratacos, Renate Strehlau, Cande V. Ananth, Jorge E Tolosa, Justin S Brandt, Jennifer Hill, Erich Cosmi, Lauren Hookham, Raigam Jafet Martínez-Portilla, Francesca Crovetto, Fatima Crispi, Robert Mboizi, Jean B Nachega, Silvia Visentin, Erin Oakley, Gargi Wable Grandner, Kacey Ferguson, Yalda Afshar, Mia Ahlberg, Homa Ahmadzia, Victor Akelo, Grace Aldrovandi, Beth A Tippett Barr, Elisa Bevilacqua, Irene Fernández Buhigas, Rebecca Clifton, Jeanne Conry, Camille Delgado-López, Hema Divakar, Amanda J Driscoll, Guillaume Favre, Maria M Gil, Olivia Hernandez, Erkan Kalafat, Sammy Khagayi, Karen Kotloff, Ethan Litman, Valentina Laurita Longo, Elizabeth M McClure, Tori D Metz, Emily S Miller, Sakita Moungmaithong, Marta C Nunes, Dickens Onyango, Daniel Raiten, Gordon Rukundo, Daljit Sahota, Allie Sakowicz, Jose Sanin-Blair, Miguel Valencia-Prado, Kristina Adams Waldorf, Clare Whitehead, Murat Yassa, Jim M Tielsch, Eduard Langenegger, Nadia A. Sam-Agudu, Onesmus W. Gachuno, Denis M. Mukwege, Richard Omore, Gregory Ouma, Kephas Otieno, Zacchaeus Abaja Were, Pinar Birol İlter, Federica Meli, Giulia Bonanni, Federica Romanzi, Eleonora Torcia, Chiara di Ilio, Haylea Sweat Patrick, Vuyelwa Baba, Mary Adam, Philiswa Mlandu, and Yasmin Adam
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Introduction Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.Methods We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.Results We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection—as compared with uninfected pregnant women—were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.Conclusions This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.
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- 2023
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12. Problems with evidence assessment in COVID-19 health policy impact evaluation: a systematic review of study design and evidence strength
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Elizabeth A Stuart, Emily R Smith, Elizabeth M Stone, Eli Ben-Michael, Cathrine Axfors, Brooke Jarrett, Sarah E Wieten, Van Thu Nguyen, Beth Ann Griffin, Noah A Haber, Emma Clarke-Deelder, Avi Feller, Joshua A. Salomon, Benjamin MacCormack-Gelles, Clara Bolster-Foucault, Jamie R Daw, Laura Anne Hatfield, Carrie E Fry, Christopher B Boyer, Caroline M Joyce, Beth S Linas, Ian Schmid, Eric H Au, and Alyssa Bilinski
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Medicine - Published
- 2022
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13. Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.
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Emily R Smith, Erin Oakley, Siran He, Rebecca Zavala, Kacey Ferguson, Lior Miller, Gargi Wable Grandner, Ibukun-Oluwa Omolade Abejirinde, Yalda Afshar, Homa Ahmadzia, Grace Aldrovandi, Victor Akelo, Beth A Tippett Barr, Elisa Bevilacqua, Justin S Brandt, Natalie Broutet, Irene Fernández Buhigas, Jorge Carrillo, Rebecca Clifton, Jeanne Conry, Erich Cosmi, Camille Delgado-López, Hema Divakar, Amanda J Driscoll, Guillaume Favre, Valerie Flaherman, Christopher Gale, Maria M Gil, Christine Godwin, Sami Gottlieb, Olivia Hernandez Bellolio, Edna Kara, Sammy Khagayi, Caron Rahn Kim, Marian Knight, Karen Kotloff, Antonio Lanzone, Kirsty Le Doare, Christoph Lees, Ethan Litman, Erica M Lokken, Valentina Laurita Longo, Laura A Magee, Raigam Jafet Martinez-Portilla, Elizabeth McClure, Torri D Metz, Deborah Money, Edward Mullins, Jean B Nachega, Alice Panchaud, Rebecca Playle, Liona C Poon, Daniel Raiten, Lesley Regan, Gordon Rukundo, Jose Sanin-Blair, Marleen Temmerman, Anna Thorson, Soe Thwin, Jorge E Tolosa, Julia Townson, Miguel Valencia-Prado, Silvia Visentin, Peter von Dadelszen, Kristina Adams Waldorf, Clare Whitehead, Huixia Yang, Kristian Thorlund, and James M Tielsch
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Medicine ,Science - Abstract
We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.
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- 2022
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14. Challenges with pediatric surgical financing and universal health coverage in Guatemala: A qualitative analysis.
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Kelsey R Landrum, Bria J Hall, Emily R Smith, Walter Flores, Randall Lou-Meda, and Henry E Rice
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Public aspects of medicine ,RA1-1270 - Abstract
The financing of surgical care for children in low- and middle-income countries (LMICs) remains challenging and may restrict adherence to universal health coverage (UHC) frameworks. Our aims were to describe Guatemala's national pediatric surgical financing structure, to identify financing challenges, and to develop recommendations to improve the financing of surgical care for children. We conducted a qualitative study of the financing of surgical care for children in Guatemala's public health system with key informant interviews (n = 20) with experts in the medical, financial, and political health sectors. We used this data to generate recommendations to improve surgical care financing for children. We identified several systemic challenges to the financing of surgical care for children, including passive purchasing structures, complex political contexts, health system fragmentation, widespread use of informal fees for surgical services, and lack of earmarked funding for surgical care. Patient and provider challenges include lack of provider input in non-personnel funding decisions, and patients functioning as both financing agents and beneficiaries in the same financing stream. Key recommendations include reducing health finance system fragmentation through resource pooling, increasing earmarked funding for surgical care with quantifiable outcome measures, engagement with clinical providers in non-personnel budgetary decision-making, and use of innovative financing instruments such as resource pooling. Surgical financing for children in Guatemala requires substantial remodeling to increase access to timely, affordable, and safe surgical care and improve alignment with Guatemala's UHC scheme.
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- 2022
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15. COVID-19 vaccine hesitancy and its determinants among sub-Saharan African adolescents.
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Dongqing Wang, Angela Chukwu, Mary Mwanyika-Sando, Sulemana Watara Abubakari, Nega Assefa, Isabel Madzorera, Elena C Hemler, Abbas Ismail, Bruno Lankoande, Frank Mapendo, Ourohiré Millogo, Firehiwot Workneh, Temesgen Azemraw, Lawrence Gyabaa Febir, Christabel James, Amani Tinkasimile, Kwaku Poku Asante, Till Baernighausen, Yemane Berhane, Japhet Killewo, Ayoade M J Oduola, Ali Sie, Emily R Smith, Abdramane Bassiahi Soura, Tajudeen Raji, Said Vuai, and Wafaie W Fawzi
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Public aspects of medicine ,RA1-1270 - Abstract
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 prevalence 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 2662 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 14% in rural Kersa, 23% in rural Ibadan, 31% in rural Nouna, 32% in urban Ouagadougou, 37% in urban Addis Ababa, 48% in rural Kintampo, 65% 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: 3.52; 95% CI: 3.00, 4.13) and lack of effectiveness (aPR: 3.46; 95% CI: 2.97, 4.03) were associated with greater vaccine hesitancy. The prevalence of COVID-19 vaccine hesitancy among adolescents is 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.
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- 2022
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16. Geospatial analysis of pediatric surgical need and geographical access to care in Somaliland: a cross-sectional study
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Edna Adan Ismail, Jonathan Cook, Emily R Smith, Henry E Rice, Tessa Concepcion, Shukri Dahir, Mubarak Mohamed, Cesia F Cotache-Condor, Katelyn Moody, and John Will
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Medicine - Abstract
Background The 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.Methods Using 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.Results Our 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.Conclusion Our 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.
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- 2021
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17. Global and regional overview of the inclusion of paediatric surgery in the national health plans of 124 countries: an ecological study
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Lubna Samad, John G Meara, Emily R Smith, Henry E Rice, Emmanuel Ameh, Paul Truche, Cesia F Cotache-Condor, Kelsey Landrum, Yingling Liu, Julia Robinson, Nealey Thompson, Ryann Granzin, and Steve Bickler
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Medicine - Abstract
Objective This study evaluates the priority given to surgical care for children within national health policies, strategies and plans (NHPSPs).Participants and setting We reviewed the NHPSPs available in the WHO’s Country Planning Cycle Database. Countries with NHPSPs in languages different from English, Spanish, French or Chinese were excluded. A total of 124 countries met the inclusion criteria.Primary and secondary outcome measures We searched for child-specific and surgery-specific terms in the NHPSPs’ missions, goals and strategies using three analytic approaches: (1) count of the total number of mentions, (2) count of the number of policies with no mentions and (3) count of the number of policies with five or more mentions. Outcomes were compared across WHO regional and World Bank income-level classifications.Results We found that the most frequently mentioned terms were ‘child*’, ‘infant*’ and ‘immuniz*’. The most frequently mentioned surgery term was ‘surg*’. Overall, 45% of NHPSPs discussed surgery and 7% discussed children’s surgery. The majority (93%) of countries did not mention selected essential and cost-effective children’s procedures. When stratified by WHO region and World Bank income level, the West Pacific region led the inclusion of ‘pediatric surgery’ in national health plans, with 17% of its countries mentioning this term. Likewise, low-income countries led the inclusion of surg* and ‘pediatric surgery’, with 63% and 11% of countries mentioning these terms, respectively. In both stratifications, paediatric surgery only equated to less than 1% of the total terms.Conclusion The low prevalence of children’s surgical search terms in NHPSPs indicates that the influence of surgical care for this population remains low in the majority of countries. Increased awareness of children’s surgical needs in national health plans might constitute a critical step to scale up surgical system in these countries.
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- 2021
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18. Why you should share your data during a pandemic
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Emily R Smith and Valerie J Flaherman
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Published
- 2021
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19. Genomic epidemiology of COVID-19 in care homes in the east of England
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William L Hamilton, Gerry Tonkin-Hill, Emily R Smith, Dinesh Aggarwal, Charlotte J Houldcroft, Ben Warne, Luke W Meredith, Myra Hosmillo, Aminu S Jahun, Martin D Curran, Surendra Parmar, Laura G Caller, Sarah L Caddy, Fahad A Khokhar, Anna Yakovleva, Grant Hall, Theresa Feltwell, Malte L Pinckert, Iliana Georgana, Yasmin Chaudhry, Colin S Brown, Sonia Gonçalves, Roberto Amato, Ewan M Harrison, Nicholas M Brown, Mathew A Beale, Michael Spencer Chapman, David K Jackson, Ian Johnston, Alex Alderton, John Sillitoe, Cordelia Langford, Gordon Dougan, Sharon J Peacock, Dominic P Kwiatowski, Ian G Goodfellow, M Estee Torok, and COVID-19 Genomics Consortium UK
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COVID-19 ,SARS-CoV-2 ,genomics ,epidemiology ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns – outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.
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- 2021
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20. Timing and causes of neonatal mortality in Tamale Teaching Hospital, Ghana: A retrospective study.
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Alhassan Abdul-Mumin, Cesia Cotache-Condor, Sheila Agyeiwaa Owusu, Haruna Mahama, and Emily R Smith
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Medicine ,Science - Abstract
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.
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- 2021
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21. The psychological distress of parents is associated with reduced linear growth of children: Evidence from a nationwide population survey.
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Kun A Susiloretni, Emily R Smith, Suparmi, Marsum, Rina Agustina, and Anuraj H Shankar
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Medicine ,Science - Abstract
BackgroundStunting, an indicator of restricted linear growth, has become a primary measure of childhood undernutrition due to its persistent high prevalence globally, and importance for health and development. Although the etiology is recognized as complex, most analyses have focused on social and biomedical determinants, with limited attention on psychological factors affecting care and nurturing in the home. We assessed whether the psychological distress of parents is related to child linear growth and stunting, and documented the associated risk factors, and examined the relationship between parental distress and behavioral and other risk factors for stunting.MethodsWe used data from the Indonesia National Health Survey 2013, including 46,315 children 6-59 months of age. Multivariate linear, logistic, and multilevel multinomial logistic regression, using survey weights, were used to assess the relationship between parental distress, as assessed by the WHO Self Reporting Questionnaire (SRQ20), with height-for-age z score (HAZ), stunting, and behavioral and other risk factors for stunting.ResultsMaternal, paternal and parental distress (i.e. both maternal and paternal distress) were associated with reduced linear growth of the children by 0.086 (95% CI -0.17, -0.00), 0.11 (95% CI -0.24, -0.02) and 0.19 (95% CI -0.37, -0.00) HAZ-scores, respectively. Maternal and paternal distress increased the risk of mild stunting (HAZ ConclusionsMaternal, paternal and parental stress were associated with reduced linear growth of children. These findings highlight the complex etiology of stunting and suggest nutritional and other biomedical interventions are insufficient, and that promotion of mental and behavioral health programs for parents must be pursued as part of a comprehensive strategy to enhance child growth and development, i.e. improved caretaker capacity, integrated community development, improved parenting skills, as well as reduced gender discrimination, and domestic violence.
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- 2021
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22. Interpreting the Lancet surgical indicators in Somaliland: a cross-sectional study
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Edna Adan Ismail, Dan Poenaru, Andy J M Leather, Emily R Smith, Henry E Rice, Tessa Concepcion, Shukri Dahir, Mubarak Mohamed, and Cesia F Cotache-Condor
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Medicine - Abstract
Background The unmet burden of surgical care is high in low-income and middle-income countries. The Lancet Commission on Global Surgery (LCoGS) proposed six indicators to guide the development of national plans for improving and monitoring access to essential surgical care. This study aimed to characterise the Somaliland surgical health system according to the LCoGS indicators and provide recommendations for next-step interventions.Methods In this cross-sectional nationwide study, the WHO’s Surgical Assessment Tool–Hospital Walkthrough and geographical mapping were used for data collection at 15 surgically capable hospitals. LCoGS indicators for preparedness was defined as access to timely surgery and specialist surgical workforce density (surgeons, anaesthesiologists and obstetricians/SAO), delivery was defined as surgical volume, and impact was defined as protection against impoverishment and catastrophic expenditure. Indicators were compared with the LCoGS goals and were stratified by region.Results The healthcare system in Somaliland does not meet any of the six LCoGS targets for preparedness, delivery or impact. We estimate that only 19% of the population has timely access to essential surgery, less than the LCoGS goal of 80% coverage. The number of specialist SAO providers is 0.8 per 100 000, compared with an LCoGS goal of 20 SAO per 100 000. Surgical volume is 368 procedures per 100 000 people, while the LCoGS goal is 5000 procedures per 100 000. Protection against impoverishing expenditures was only 18% and against catastrophic expenditures 1%, both far below the LCoGS goal of 100% protection.Conclusion We found several gaps in the surgical system in Somaliland using the LCoGS indicators and target goals. These metrics provide a broad view of current status and gaps in surgical care, and can be used as benchmarks of progress towards universal health coverage for the provision of safe, affordable, and timely surgical, obstetric and anaesthesia care in Somaliland.
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- 2020
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23. Addressing inequities in the global burden of maternal undernutrition: the role of targeting
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Emily R Smith, Anita Zaidi, and Parul Christian
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Published
- 2020
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24. Towards defining the surgical workforce for children: a geospatial analysis in Brazil
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Charles Mock, Jonathan Lord, Monica Langer, Niyi Ade-Ajayi, Dan Poenaru, Harshjeet Singh Bal, Massimo Caputo, Damian Clarke, Fred Bulamba, Lubna Samad, David Cunningham, George Youngson, Michael Cooper, Tamara Fitzgerald, Henry Rice, Patrick Kamalo, Emily R Smith, Bistra Zheleva, David Drake, Emily Smith, Lars Hagander, Bassey Edem, Sridhar Gibikote, Jessica Ng, David Spiegel, Saurabh Saluja, Peter Ssenyonga, Thiago Augusto Hernandes Rocha, Joao Vissoci, Nubia Rocha, Mark Shrime, Henry E Rice, Mohamed Abdelmalak, Nurudeen Abdulraheem, Edna Adan Ismail, Eltayeb Ahmed, Sunday Ajike, Olugbemi Benedict Akintububo, Brendan Allen, Emmanuel Ameh, Shanthi Anbuselvan, Jamie Anderson, Theophilus Teddy Kojo Anyomih, Leopold Asakpa, Gudeta Assegie, Jason Axt, Ruben Ayala, Frehun Ayele, Rouma Bankole, Tahmina Banu, Tim Beacon, Stephen Bickler, Zaitun Bokhari, Hiranya Kumar Borah, Eric Borgstein, Nick Boyd, Jason Brill, Britta Budde-Schwartzman, Marilyn Butler, Bruce Bvulani, Sarah Cairo, Juan Francisco Campos Rodezno, Milind Chitnis, Maija Cheung, Bruno Cigliano, Tessa Concepcion, Scott Corlew, Sergio D’Agostino, Shukri Dahir, Bailey Deal, Miliard Derbew, Sushil Dhungel, Elizabeth Drum, Stella Eguma, Beda R. Espineda, Samuel Espinoza, Faye Evans, Jacques Fadhili Bake, Diana Farmer, Tatiana Fazecas, Mohammad Rafi Fazli, Graham Fieggen, Anthony Figaji, Jean Louis Fils, Randall Flick, Gacelle Fossi, George Galiwango, Mike Ganey, Zipporah Gathuya, Maryam Ghavami Adel, Vafa Ghorban Sabagh, Hetal Gohil, Laura Goodman, David Grabski, Sarah Greenberg, Russell Gruen, Rahimullah Hamid, Erik Hansen, William Harkness, Mauricio Herrera, Intisar Hisham, Andrew Hodges, Sarah Hodges, Ai-Xuan Holterman, Andrew Howard, Romeo Ignacio, Dawn Ireland, Enas Ismail, Rebecca Jacob, Anette Jacobsen, Deeptiman James, Ebor Jacob James, Adiyasuren Jamiyanjav, Kathy Jenkins, Guy Jensen, Maria Jimenez, Tarun John K Jacob, Walter Johnson, Anita Joselyn, Nasser Kakembo, Neema Kaseje, Bertille Ki, Phyllis Kisa, Peter Kim, Krishna Kumar, Rashmi Kumar, Charlotte Kvasnovsky, Ananda Lamahewage, Christopher Lavy, Colin Lazarus, Chelsea Lee, Basil Leodoro, Allison Linden, Katrine Lofberg, Jerome Loveland, Leecarlo Millano Lumban Gaol, Vrisha Madhuri, Pavrette Magdala, Luc Kalisya Malemo, Aeesha Malik, John Mathai, Marcia Matias, Bothwell Mbuwayesango, Merrill McHoney, Liz McLeod, Mubarak Mohamed, Ivan Molina, Ashika Morar, Zahid Mukhtar, Mulewa Mulenga, Bhargava Mullapudi, Jack Mulu, Byambajav Munkhjargal, Arlene Muzira, Mary Nabukenya, Mark Newton, Karissa Nguyen, Laurence Isaaya Ntawunga, Peter M. Nthumba, Alp Numanoglu, Benedict Nwomeh, Kristin Ojomo, Keith Oldham, Maryrose Osazuwa, Doruk Ozgediz, Emmanuel Owusu Abem, Shazia Peer, Norgrove Penny, Robin Petroze, Vithya Priya, Ekta Rai, Lola Raji, Vinitha Paul Ravindran, Desigen Reddy, Yona Ringo, Amezene Robelie, Jose Roberto Baratella, David Rothstein, Coleen Sabatini, Soumitra Saha, Lily Saldaña Gallo, John Sekabira, Bello B. Shehu, Ritesh Shrestha, Sabina Siddiqui, David Sigalet, Martin Situma, Adrienne Socci, Etienne St-Louis, Jacob Stephenson, Erin Stieber, Richard Stewart, Vinayak Shukla, Thomas Sims, Faustin Felicien Mouafo Tambo, Robert Tamburro, Mansi Tara, Ahmad Tariq, Reju Thomas, Leopold Torres Contreras, Stephen Ttendo, Benno Ure, Luca Vricella, Luis Vasquez, Vijayakumar Raju, Jorge Villacis, Gustavo Villanova, Catherine deVries, Amira Waheeb, Saber Waheeb, Albert Wandaogo, Anne Wesonga, Sigal Willner, Nyo Nyo Win, Hussein Wissanji, Paul Mwindekuma Wondoh, Garreth Wood, Benjamin Yapo, Yasmine Yousef, Denle'wende' Sylvain Zabsonre, Luis Enrique, Zea Salazar, and Adiyasuren Zevee
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Medicine - Abstract
Objectives The optimal size of the health workforce for children’s surgical care around the world remains poorly defined. The goal of this study was to characterise the surgical workforce for children across Brazil, and to identify associations between the surgical workforce and measures of childhood health.Design This study is an ecological, cross-sectional analysis using data from the Brazil public health system (Sistema Único de Saúde).Settings and participants We collected data on the surgical workforce (paediatric surgeons, general surgeons, anaesthesiologists and nursing staff), perioperative mortality rate (POMR) and under-5 mortality rate (U5MR) across Brazil for 2015.Primary and secondary outcome measures We performed descriptive analyses, and identified associations between the workforce and U5MR using geospatial analysis (Getis-Ord-Gi analysis, spatial cluster analysis and linear regression models).Findings There were 39 926 general surgeons, 856 paediatric surgeons, 13 243 anaesthesiologists and 103 793 nurses across Brazil in 2015. The U5MR ranged from 11 to 26 deaths/1000 live births and the POMR ranged from 0.11–0.17 deaths/100 000 children across the country. The surgical workforce is inequitably distributed across the country, with the wealthier South and Southeast regions having a higher workforce density as well as lower U5MR than the poorer North and Northeast regions. Using linear regression, we found an inverse relationship between the surgical workforce density and U5MR. An U5MR of 15 deaths/1000 births across Brazil is associated with a workforce level of 5 paediatric surgeons, 200 surgeons, 100 anaesthesiologists or 700 nurses/100 000 children.Conclusions We found wide disparities in the surgical workforce and childhood mortality across Brazil, with both directly related to socioeconomic status. Areas of increased surgical workforce are associated with lower U5MR. Strategic investment in the surgical workforce may be required to attain optimal health outcomes for children in Brazil, particularly in rural regions.
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- 2020
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25. The contribution of pediatric surgery to poverty trajectories in Somaliland.
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Emily R Smith, Tessa L Concepcion, Mubarak Mohamed, Shugri Dahir, Edna Adan Ismail, Henry E Rice, Anirudh Krishna, and Global Initiative for Children’s Surgery
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Medicine ,Science - Abstract
BackgroundThe provision of health care in low-income and middle-income countries (LMICs) is recognized as a significant contributor to economic growth and also impacts individual families at a microeconomic level. The primary goal of our study was to examine the relationship between surgical conditions in children and the poverty trajectories of either falling into or coming out of poverty of families across Somaliland.MethodsThis work used the Surgeons OverSeas Assessment of Surgical Need (SOSAS) tool, a validated household, cross-sectional survey designed to determine the burden of surgical conditions within a community. We collected information on household demographic characteristics, including financial information, and surgical condition history on children younger than 16 years of age. To assess poverty trajectories over time, we measured household assets using the Stages of Progress framework.ResultsWe found there were substantial fluxes in poverty across Somaliland over the study period. We confirmed our study hypothesis and found that the presence of a surgical condition in a child itself, regardless of whether surgical care was provided, either reduced the chances of moving out of poverty or increased the chances of moving towards poverty.ConclusionOur study shows that the presence of a surgical condition in a child is a strong singular predictor of poverty descent rather than upward mobility, suggesting that this stressor can limit the capacity of a family to improve its economic status. Our findings further support many existing macroeconomic and microeconomic analyses that surgical care in LMICs offers financial risk protection against impoverishment.
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- 2019
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26. Disparities in surgical care for children across Brazil: Use of geospatial analysis.
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João R N Vissoci, Cecilia T Ong, Luciano de Andrade, Thiago Augusto Hernandes Rocha, Nubia Cristina da Silva, Dan Poenaru, Emily R Smith, Henry E Rice, and Global Initiative for Children’s Surgery
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Medicine ,Science - Abstract
BackgroundHealth systems for surgical care for children in low- and middle-income countries remain poorly understood. Our goal was to characterize the delivery of surgical care for children across Brazil and to identify associations between surgical resources and childhood mortality.MethodsWe performed a cross-sectional, ecological study to analyze surgical care for children in the public health system (Sistema Único de Saúde) across Brazil from 2010 to 2015. We collected data from several national databases, and used geospatial analysis (two-step floating catchment, Getis-Ord-Gi analysis, and geographically weighted regression) to explore relationships between infrastructure, workforce, access, procedure rate, under-5 mortality rate (U5MR), and perioperative mortality rate (POMR).ResultsA total of 246,769 surgical procedures were performed in 6,007 first level/ district hospitals and 491 referral hospitals across Brazil over the study period. The surgical workforce is distributed unevenly across the country, with 0.13-0.26 pediatric surgeons per 100,000 children in the poorer North, Northeast and Midwest regions, and 0.6-0.68 pediatric surgeons per 100,000 children in the wealthier South and Southeast regions. Hospital infrastructure, procedure rate, and access to care is also unequally distributed across the country, with increased resources in the South and Southeast compared to the Northeast, North, and Midwest. The U5MR varies widely across the country, although procedure-specific POMR is consistent across regions. Increased access to care is associated with lower U5MR across Brazil, and access to surgical care differs by geographic region independent of socioeconomic status.ConclusionsThere are wide disparities in surgical care for children across Brazil, with infrastructure, manpower, and resources distributed unevenly across the country. Access to surgical care is associated with improved U5MR independent of socioeconomic status. To address these disparities, policy should direct the allocation of surgical resources commensurate with local population needs.
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- 2019
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27. Population-based rates, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa: a multi-country prospective cohort study
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Imran Ahmed, Said Mohammed Ali, Seeba Amenga-Etego, Shabina Ariff, Rajiv Bahl, Abdullah H Baqui, Nazma Begum, Nita Bhandari, Kiran Bhatia, Zulfiqar A Bhutta, Godfrey Biemba, Saikat Deb, Usha Dhingra, Brinda Dube, Arup Dutta, Karen Edmond, Fabian Esamai, Wafaie Fawzi, Amit Kumar Ghosh, Peter Gisore, Caroline Grogan, Davidson H Hamer, Julie Herlihy, Lisa Hurt, Muhammad Ilyas, Fyezah Jehan, Michel Kalonji, Jasmine Kaur, Rasheda Khanam, Betty Kirkwood, Aarti Kumar, Alok Kumar, Vishwajeet Kumar, Alexander Manu, Irene Marete, Honorati Masanja, Sarmila Mazumder, Usma Mehmood, Shambhavi Mishra, Dipak K Mitra, Erick Mlay, Sanjana Brahmawar Mohan, Mamun Ibne Moin, Karim Muhammad, Alfa Muhihi, Samuel Newton, Serge Ngaima, Andre Nguwo, Imran Nisar, Maureen O'Leary, John Otomba, Pawankumar Patil, Mohammad Abdul Quaiyum, Mohammed Hefzur Rahman, Sunil Sazawal, Katherine EA Semrau, Caitlin Shannon, Emily R Smith, Sajid Soofi, Seyi Soremekun, Venantius Sunday, Sunita Taneja, Antoinette Tshefu, Yaqub Wasan, Kojo Yeboah-Antwi, Sachiyo Yoshida, and Anita Zaidi
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Modelled mortality estimates have been useful for health programmes in low-income and middle-income countries. However, these estimates are often based on sparse and low-quality data. We aimed to generate high quality data about the burden, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa. Methods: In this prospective cohort study done in 11 community-based research sites in south Asia and sub-Saharan Africa, between July, 2012, and February, 2016, we conducted population-based surveillance of women of reproductive age (15–49 years) to identify pregnancies, which were followed up to birth and 42 days post partum. We used standard operating procedures, data collection instruments, training, and standardisation to harmonise study implementation across sites. Verbal autopsies were done for deaths of all women of reproductive age, neonatal deaths, and stillbirths. Physicians used standardised methods for cause of death assignment. Site-specific rates and proportions were pooled at the regional level using a meta-analysis approach. Findings: We identified 278 186 pregnancies and 263 563 births across the study sites, with outcomes ascertained for 269 630 (96·9%) pregnancies, including 8761 (3·2%) that ended in miscarriage or abortion. Maternal mortality ratios in sub-Saharan Africa (351 per 100 000 livebirths, 95% CI 168–732) were similar to those in south Asia (336 per 100 000 livebirths, 247–458), with far greater variability within sites in sub-Saharan Africa. Stillbirth and neonatal mortality rates were approximately two times higher in sites in south Asia than in sub-Saharan Africa (stillbirths: 35·1 per 1000 births, 95% CI 28·5–43·1 vs 17·1 per 1000 births, 12·5–25·8; neonatal mortality: 43·0 per 1000 livebirths, 39·0–47·3 vs 20·1 per 1000 livebirths, 14·6–27·6). 40–45% of pregnancy-related deaths, stillbirths, and neonatal deaths occurred during labour, delivery, and the 24 h postpartum period in both regions. Obstetric haemorrhage, non-obstetric complications, hypertensive disorders of pregnancy, and pregnancy-related infections accounted for more than three-quarters of maternal deaths and stillbirths. The most common causes of neonatal deaths were perinatal asphyxia (40%, 95% CI 39–42, in south Asia; 34%, 32–36, in sub-Saharan Africa) and severe neonatal infections (35%, 34–36, in south Asia; 37%, 34–39 in sub-Saharan Africa), followed by complications of preterm birth (19%, 18–20, in south Asia; 24%, 22–26 in sub-Saharan Africa). Interpretation: These results will contribute to improved global estimates of rates, timing, and causes of maternal and newborn deaths and stillbirths. Our findings imply that programmes in sub-Saharan Africa and south Asia need to further intensify their efforts to reduce mortality rates, which continue to be high. The focus on improving the quality of maternal intrapartum care and immediate newborn care must be further enhanced. Efforts to address perinatal asphyxia and newborn infections, as well as preterm birth, are critical to achieving survival goals in the Sustainable Development Goals era. Funding: Bill & Melinda Gates Foundation.
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- 2018
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28. Rural and urban differences in treatment status among children with surgical conditions in Uganda.
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Ashley Bearden, Anthony T Fuller, Elissa K Butler, Tu Tran, Fredrick Makumbi, Samuel Luboga, Christine Muhumuza, Vincent Ssennono, Moses Galukande, Michael Haglund, and Emily R Smith
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Medicine ,Science - Abstract
BACKGROUND:In low and middle-income countries, approximately 85% of children have a surgically treatable condition before the age of 15. Within these countries, the burden of pediatric surgical conditions falls heaviest on those in rural areas. The objective of the current study was to evaluate the relationship between rurality, surgical condition and treatment status among a cohort of Ugandan children. METHODS:We identified 2176 children from 2315 households throughout Uganda using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey. Children were randomly selected and were included in the study if they were 18 years of age or younger and had a surgical condition. Location of residence, surgical condition, and treatment status was compared among children. RESULTS:Of the 305 children identified with surgical conditions, 81.9% lived in rural areas. The most prevalent causes of surgical conditions reported among rural and urban children were masses (24.0% and 25.5%, respectively), followed by wounds due to injury (19.6% and 16.4%, respectively). Among children with untreated surgical conditions, 79.1% reside in rural areas while 20.9% reside in urban areas. Among children with untreated surgical conditions, the leading reason for not seeking surgical care among children living in both rural and urban areas was a lack of money (40.6% and 31.4%, respectively), and the leading reason for not receiving care in both rural and urban settings was a lack of money (48.0% and 42.8%, respectively). CONCLUSIONS:Our data suggest that over half of the children with a surgical condition surveyed are not receiving surgical care and a large majority of children with surgical needs were living in rural areas. Future interventions aimed at increasing surgical access in rural areas in low-income countries are needed.
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- 2018
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29. Causal language and strength of inference in academic and media articles shared in social media (CLAIMS): A systematic review.
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Noah Haber, Emily R Smith, Ellen Moscoe, Kathryn Andrews, Robin Audy, Winnie Bell, Alana T Brennan, Alexander Breskin, Jeremy C Kane, Mahesh Karra, Elizabeth S McClure, Elizabeth A Suarez, and CLAIMS research team
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Medicine ,Science - Abstract
BACKGROUND:The pathway from evidence generation to consumption contains many steps which can lead to overstatement or misinformation. The proliferation of internet-based health news may encourage selection of media and academic research articles that overstate strength of causal inference. We investigated the state of causal inference in health research as it appears at the end of the pathway, at the point of social media consumption. METHODS:We screened the NewsWhip Insights database for the most shared media articles on Facebook and Twitter reporting about peer-reviewed academic studies associating an exposure with a health outcome in 2015, extracting the 50 most-shared academic articles and media articles covering them. We designed and utilized a review tool to systematically assess and summarize studies' strength of causal inference, including generalizability, potential confounders, and methods used. These were then compared with the strength of causal language used to describe results in both academic and media articles. Two randomly assigned independent reviewers and one arbitrating reviewer from a pool of 21 reviewers assessed each article. RESULTS:We accepted the most shared 64 media articles pertaining to 50 academic articles for review, representing 68% of Facebook and 45% of Twitter shares in 2015. Thirty-four percent of academic studies and 48% of media articles used language that reviewers considered too strong for their strength of causal inference. Seventy percent of academic studies were considered low or very low strength of inference, with only 6% considered high or very high strength of causal inference. The most severe issues with academic studies' causal inference were reported to be omitted confounding variables and generalizability. Fifty-eight percent of media articles were found to have inaccurately reported the question, results, intervention, or population of the academic study. CONCLUSIONS:We find a large disparity between the strength of language as presented to the research consumer and the underlying strength of causal inference among the studies most widely shared on social media. However, because this sample was designed to be representative of the articles selected and shared on social media, it is unlikely to be representative of all academic and media work. More research is needed to determine how academic institutions, media organizations, and social network sharing patterns impact causal inference and language as received by the research consumer.
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- 2018
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30. Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries
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Emily R Smith, ScD, Anuraj H Shankar, ScD, Lee S-F Wu, MHS, Said Aboud, PhD, Seth Adu-Afarwuah, PhD, Hasmot Ali, MPH, Rina Agustina, PhD, Shams Arifeen, DrPH, Per Ashorn, PhD, Zulfiqar A Bhutta, PhD, Parul Christian, DrPH, Delanjathan Devakumar, PhD, Kathryn G Dewey, PhD, Henrik Friis, PhD, Exnevia Gomo, PhD, Piyush Gupta, MD, Pernille Kæstel, PhD, Patrick Kolsteren, PhD, Hermann Lanou, MD, Kenneth Maleta, PhD, Aissa Mamadoultaibou, MS, Gernard Msamanga, ScD, David Osrin, PhD, Lars-Åke Persson, PhD, Usha Ramakrishnan, PhD, Juan A Rivera, PhD, Arjumand Rizvi, MSC, H P S Sachdev, FRCPCH, Willy Urassa, PhD, Keith P West, Jr, DrPH, Noel Zagre, PhD, Lingxia Zeng, PhD, Zhonghai Zhu, MSc, Wafaie W Fawzi, DrPH, and Dr Christopher R Sudfeld, ScD
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Public aspects of medicine ,RA1-1270 - Abstract
Background: Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries. Methods: This two-stage meta-analysis of individual patient included data from 17 randomised controlled trials done in 14 low-income and middle-income countries, which compared multiple micronutrient supplements containing iron-folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated study-specific estimates and pooled subgroup estimates using fixed-effects models and assessed heterogeneity between subgroups with the χ2 test for heterogeneity. We did sensitivity analyses using random-effects models, stratifying by iron-folic acid dose, and exploring individual study effect. Findings: Multiple micronutrient supplements containing iron-folic acid provided significantly greater reductions in neonatal mortality for female neonates compared with male neonates than did iron-folic acid supplementation alone (RR 0·85, 95% CI 0·75–0·96 vs 1·06, 0·95–1·17; p value for interaction 0·007). Multiple micronutrient supplements resulted in greater reductions in low birthweight (RR 0·81, 95% CI 0·74–0·89; p value for interaction 0·049), small-for-gestational-age births (0·92, 0·87–0·97; p=0·03), and 6-month mortality (0·71, 0·60–0·86; p=0·04) in anaemic pregnant women (haemoglobin
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- 2017
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31. Delayed breastfeeding initiation and infant survival: A systematic review and meta-analysis.
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Emily R Smith, Lisa Hurt, Ranadip Chowdhury, Bireshwar Sinha, Wafaie Fawzi, Karen M Edmond, and Neovita Study Group
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Medicine ,Science - Abstract
To assess the existing evidence regarding breastfeeding initiation time and infant morbidity and mortality.We conducted a systematic review and meta-analysis. We searched Pubmed, Embase, Web of Science, CINAHL, Popline, LILACS, AIM, and Index Medicus to identify existing evidence. We included observational studies and randomized control trials that examined the association between breastfeeding initiation time and mortality, morbidity, or nutrition outcomes from birth through 12 months of age in a population of infants who all initiated breastfeeding. Two reviewers independently extracted data from eligible studies using a standardized form. We pooled effect estimates using fixed-effects meta-analysis.We pooled five studies, including 136,047 infants, which examined the association between very early breastfeeding initiation and neonatal mortality. Compared to infants who initiated breastfeeding ≤1 hour after birth, infants who initiated breastfeeding 2-23 hours after birth had a 33% greater risk of neonatal mortality (95% CI: 13-56%, I2 = 0%), and infants who initiated breastfeeding ≥24 hours after birth had a 2.19-fold greater risk of neonatal mortality (95% CI: 1.73-2.77, I2 = 33%). Among the subgroup of infants exclusively breastfed in the neonatal period, those who initiated breastfeeding ≥24 hours after birth had an 85% greater risk of neonatal mortality compared to infants who initiated
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- 2017
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32. Randomised controlled trial and economic analysis of an internet-based weight management programme: POWeR+ (Positive Online Weight Reduction)
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Paul Little, Beth Stuart, FD Richard Hobbs, Jo Kelly, Emily R Smith, Katherine J Bradbury, Stephanie Hughes, Peter WF Smith, Michael V Moore, Mike EJ Lean, Barrie M Margetts, Christopher D Byrne, Simon Griffin, Mina Davoudianfar, Julie Hooper, Guiqing Yao, Shihua Zhu, James Raftery, and Lucy Yardley
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obesity ,primary care ,weight loss ,internet ,Medical technology ,R855-855.5 - Abstract
Background: Behavioural counselling with intensive follow-up for obesity is effective, but in resource-constrained primary care settings briefer approaches are needed. Objectives: To estimate the clinical effectiveness and cost-effectiveness of an internet-based behavioural intervention with regular face-to-face or remote support in primary care, compared with brief advice. Design: Individually randomised three-arm parallel trial with health economic evaluation and nested qualitative interviews. Setting: Primary care general practices in the UK. Participants: Patients with a body mass index of ≥ 30 kg/m2 (or ≥ 28 kg/m2 with risk factors) identified from general practice records, recruited by postal invitation. Interventions: Positive Online Weight Reduction (POWeR+) is a 24-session, web-based weight management intervention completed over 6 months. Following online registration, the website randomly allocated participants using computer-generated random numbers to (1) the control intervention (n = 279), which had previously been demonstrated to be clinically effective (brief web-based information that minimised pressure to cut down foods, instead encouraging swaps to healthier choices and increasing fruit and vegetables, plus 6-monthly nurse weighing); (2) POWeR+F (n = 269), POWeR+ supplemented by face-to-face nurse support (up to seven contacts); or (3) POWeR+R (n = 270), POWeR+ supplemented by remote nurse support (up to five e-mails or brief telephone calls). Main outcome measures: The primary outcome was a modelled estimate of average weight reduction over 12 months, assessed blind to group where possible, using multiple imputation for missing data. The secondary outcome was the number of participants maintaining a 5% weight reduction at 12 months. Results: A total of 818 eligible individuals were randomised using computer-generated random numbers. Weight change, averaged over 12 months, was documented in 666 out of 818 participants (81%; control, n = 227; POWeR+F, n = 221; POWeR+R, n = 218). The control group maintained nearly 3 kg of weight loss per person (mean weight per person: baseline, 104.4 kg; 6 months, 101.9 kg; 12 months, 101.7 kg). Compared with the control group, the estimated additional weight reduction with POWeR+F was 1.5 kg [95% confidence interval (CI) 0.6 to 2.4 kg; p = 0.001] and with POWeR+R was 1.3 kg (95% CI 0.34 to 2.2 kg; p = 0.007). By 12 months the mean weight loss was not statistically significantly different between groups, but 20.8% of control participants, 29.2% of POWeR+F participants (risk ratio 1.56, 95% CI 0.96 to 2.51; p = 0.070) and 32.4% of POWeR+R participants (risk ratio 1.82, 95% CI 1.31 to 2.74; p = 0.004) maintained a clinically significant 5% weight reduction. The POWeR+R group had fewer individuals who reported doing another activity to help lose weight [control, 47.1% (64/136); POWeR+F, 37.2% (51/137); POWeR+R, 26.7% (40/150)]. The incremental cost to the health service per kilogram weight lost, compared with the control group, was £18 (95% CI –£129 to £195) for POWeR+F and –£25 (95% CI –£268 to £157) for POWeR+R. The probability of being cost-effective at a threshold of £100 per kilogram was 88% and 98% for POWeR+F and POWeR+R, respectively. POWeR+R was dominant compared with the control group. No harms were reported and participants using POWeR+ felt more enabled in managing their weight. The qualitative studies documented that POWeR+ was viewed positively by patients and that health-care professionals generally enjoyed supporting patients using POWeR+. Study limitations: Maintenance of weight loss after 1 year is unknown. Future work: Identifying strategies for longer-term engagement, impact in community settings and increasing physical activity. Conclusion: Clinically valuable weight loss (> 5%) is maintained in 20% of individuals using novel written materials with brief follow-up. A web-based behavioural programme and brief support results in greater mean weight loss and 10% more participants maintain valuable weight loss; it achieves greater enablement and fewer participants undertaking other weight-loss activities; and it is likely to be cost-effective. Trial registration: Current Controlled Trials ISRCTN21244703. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 4. See the NIHR Journals Library website for further project information.
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- 2017
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33. Epidemiology of pediatric surgical needs in low-income countries.
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Elissa K Butler, Tu M Tran, Neeraja Nagarajan, Joseph Canner, Anthony T Fuller, Adam Kushner, Michael M Haglund, Emily R Smith, and SOSAS 4 Country Research Group
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Medicine ,Science - Abstract
OBJECTIVE:According to recent estimates, at least 11% of the total global burden of disease is attributable to surgically-treatable diseases. In children, the burden is even more striking with up to 85% of children in low-income and middle-income countries (LMIC) having a surgically-treatable condition by age 15. Using population data from four countries, we estimated pediatric surgical needs amongst children residing in LMICs. METHODS:A cluster randomized cross-sectional countrywide household survey (Surgeons OverSeas Assessment of Surgical Need) was done in four countries (Rwanda, Sierra Leone, Nepal and Uganda) and included demographics, a verbal head to toe examination, and questions on access to care. Global estimates regarding surgical need among children were derived from combined data, accounting for country-level clustering. RESULTS:A total of 13,806 participants were surveyed and 6,361 (46.1%) were children (0-18 years of age) with median age of 8 (Interquartile range [IQR]: 4-13) years. Overall, 19% (1,181/6,361) of children had a surgical need and 62% (738/1,181) of these children had at least one unmet need. Based on these estimates, the number of children living with a surgical need in these four LMICs is estimated at 3.7 million (95% CI: 3.4, 4.0 million). The highest percentage of unmet surgical conditions included head, face, and neck conditions, followed by conditions in the extremities. Over a third of the untreated conditions were masses while the overwhelming majority of treated conditions in all countries were wounds or burns. CONCLUSION:Surgery has been elevated as an "indivisible, indispensable part of health care" in LMICs and the newly formed 2015 Sustainable Development Goals are noted as unachievable without the provision of surgical care. Given the large burden of pediatric surgical conditions in LMICs, scale-up of services for children is an essential component to improve pediatric health in LMICs.
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- 2017
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34. Economic Analysis of Children's Surgical Care in Low- and Middle-Income Countries: A Systematic Review and Analysis.
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Anthony T Saxton, Dan Poenaru, Doruk Ozgediz, Emmanuel A Ameh, Diana Farmer, Emily R Smith, and Henry E Rice
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Medicine ,Science - Abstract
Understanding the economic value of health interventions is essential for policy makers to make informed resource allocation decisions. The objective of this systematic review was to summarize available information on the economic impact of children's surgical care in low- and middle-income countries (LMICs).We searched MEDLINE (Pubmed), Embase, and Web of Science for relevant articles published between Jan. 1996 and Jan. 2015. We summarized reported cost information for individual interventions by country, including all costs, disability weights, health outcome measurements (most commonly disability-adjusted life years [DALYs] averted) and cost-effectiveness ratios (CERs). We calculated median CER as well as societal economic benefits (using a human capital approach) by procedure group across all studies. The methodological quality of each article was assessed using the Drummond checklist and the overall quality of evidence was summarized using a scale adapted from the Agency for Healthcare Research and Quality.We identified 86 articles that met inclusion criteria, spanning 36 groups of surgical interventions. The procedure group with the lowest median CER was inguinal hernia repair ($15/DALY). The procedure group with the highest median societal economic benefit was neurosurgical procedures ($58,977). We found a wide range of study quality, with only 35% of studies having a Drummond score ≥ 7.Our findings show that many areas of children's surgical care are extremely cost-effective in LMICs, provide substantial societal benefits, and are an appropriate target for enhanced investment. Several areas, including inguinal hernia repair, trichiasis surgery, cleft lip and palate repair, circumcision, congenital heart surgery and orthopedic procedures, should be considered "Essential Pediatric Surgical Procedures" as they offer considerable economic value. However, there are major gaps in existing research quality and methodology which limit our current understanding of the economic value of surgical care.
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- 2016
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35. A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Medigen COVID-19 protein vaccine
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Lila Estephan, Luke Tzu-Chi Liu, Chia En Lien, Emily R. Smith, Marc Gurwith, and Robert T. Chen
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Infectious Diseases ,General Veterinary ,General Immunology and Microbiology ,SARS-CoV-2 ,Protein ,Public Health, Environmental and Occupational Health ,Molecular Medicine ,COVID-19 ,Safety ,Vaccine ,Benefit/Risk - Abstract
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-risk assessment of several vaccine platform technologies, including protein subunit vaccines. This article uses the BRAVATO template to review the features of the MVC-COV1901 vaccine, a recombinant protein subunit vaccine based on the stabilized pre-fusion SARS-CoV-2 spike protein S-2P, adjuvanted with CpG 1018 and aluminum hydroxide, manufactured by Medigen Vaccine Biologics Corporation in Taiwan. MVC-COV1901 vaccine is indicated for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 12years of age and older. The template offers details on basic vaccine information, target pathogen and population, characteristics of antigen and adjuvant, preclinical data, human safety and efficacy data, and overall benefit-risk assessment. The clinical development program began in September 2020 and based on demonstration of favorable safety and immunogenicity profiles in 11 clinical trials in over 5,000 participants, it has been approved for emergency use based on immunobridging results for adults in Taiwan, Estwatini, Somaliland, and Paraguay. The main clinical trials include placebo-controlled phase 2 studies in healthy adults (CT-COV-21), adolescents (CT-COV-22), and elderly population (CT-COV-23) as well as 3 immunobridging phase 3 trials (CT-COV-31, CT-COV-32, and CT-COV-34) in which MVC-COV1901 was compared to AZD1222. There are also clinical trials studying MVC-COV1901 as homologous and heterologous boosters (CT-COV-24 and CT-COV-25). The totality of evidence based on ∼3 million vaccinees to date includes a mostly clean safety profile, with adverse events mostly being mild and self-limiting in both clinical development and post-marketing experience, proven immunogenic response, and real-world effectiveness data. The immunogenic profile demonstrates that MVC-COV1901 induces high levels of neutralizing and binding antibodies against SARS-CoV-2. There is a dose-dependent response and a significant correlation between binding and neutralizing antibody activity. Antigen-specific T-cell responses, particularly a Th1-biased immune response characterized by high levels of interferon gamma and IL-2 cytokines, have also been observed. Coupled with this, MVC-COV1901 has favorable thermostability and better safety profiles when compared to other authorized vaccines from different platforms, which make it potentially a good candidate for vaccine supply chains in global markets.
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- 2023
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36. Much ado about something: a response to 'COVID-19: underpowered randomised trials, or no randomised trials?'
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Emily R. Smith, Noah Haber, David Nunan, and Sarah Wieten
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Ethics ,Medicine (General) ,Opportunity cost ,Actuarial science ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Non-pharmaceutical interventions ,Psychological intervention ,Masks ,Medicine (miscellaneous) ,COVID-19 ,Context (language use) ,Statistical power ,Conjunction (grammar) ,R5-920 ,Commentary ,Medicine ,Humans ,Pharmacology (medical) ,DANMASK-19 ,Misinformation ,business ,Randomized Controlled Trials as Topic - Abstract
Non-pharmaceutical interventions (NPI) for infectious diseases such as COVID-19 are particularly challenging given the complexities of what is both practical and ethical to randomize. We are often faced with the difficult decision between having weak trials or not having a trial at all. In a recent article, Dr. Atle Fretheim argues that statistically underpowered studies are still valuable, particularly in conjunction with other similar studies in meta-analysis in the context of the DANMASK-19 trial, asking “Surely, some trial evidence must be better than no trial evidence?” However, informative trials are not always feasible, and feasible trials are not always informative. In some cases, even a well-conducted but weakly designed and/or underpowered trial such as DANMASK-19 may be uninformative or worse, both individually and in a body of literature. Meta-analysis, for example, can only resolve issues of statistical power if there is a reasonable expectation of compatible well-designed trials. Uninformative designs may also invite misinformation. Here, we make the case that—when considering informativeness, ethics, and opportunity costs in addition to statistical power—“nothing” is often the better choice.
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- 2021
37. Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period : a sequential, prospective meta-analysis
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Emily R. Smith, Erin Oakley, Gargi Wable Grandner, Gordon Rukundo, Fouzia Farooq, Kacey Ferguson, Sasha Baumann, Kristina Maria Adams Waldorf, Yalda Afshar, Mia Ahlberg, Homa Ahmadzia, Victor Akelo, Grace Aldrovandi, Elisa Bevilacqua, Nabal Bracero, Justin S. Brandt, Natalie Broutet, Jorge Carrillo, Jeanne Conry, Erich Cosmi, Fatima Crispi, Francesca Crovetto, Maria del Mar Gil, Camille Delgado-López, Hema Divakar, Amanda J. Driscoll, Guillaume Favre, Irene Fernandez Buhigas, Valerie Flaherman, Christopher Gale, Christine L. Godwin, Sami Gottlieb, Eduard Gratacós, Siran He, Olivia Hernandez, Stephanie Jones, Sheetal Joshi, Erkan Kalafat, Sammy Khagayi, Marian Knight, Karen L. Kotloff, Antonio Lanzone, Valentina Laurita Longo, Kirsty Le Doare, Christoph Lees, Ethan Litman, Erica M. Lokken, Shabir A. Madhi, Laura A. Magee, Raigam Jafet Martinez-Portilla, Torri D. Metz, Emily S. Miller, Deborah Money, Sakita Moungmaithong, Edward Mullins, Jean B. Nachega, Marta C. Nunes, Dickens Onyango, Alice Panchaud, Liona C. Poon, Daniel Raiten, Lesley Regan, Daljit Sahota, Allie Sakowicz, Jose Sanin-Blair, Olof Stephansson, Marleen Temmerman, Anna Thorson, Soe Soe Thwin, Beth A. Tippett Barr, Jorge E. Tolosa, Niyazi Tug, Miguel Valencia-Prado, Silvia Visentin, Peter von Dadelszen, Clare Whitehead, Mollie Wood, Huixia Yang, Rebecca Zavala, and James M. Tielsch
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neonatal mortality ,SARS-CoV-2 ,maternal mortality ,Medicine and Health Sciences ,Obstetrics and Gynecology ,pneumonia ,preterm birth ,COVID-2019 ,pregnancy ,small-for-gestational-age ,610 Medicine & health ,360 Social problems & social services - Abstract
Objective: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. Data sources: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. Study eligibility criteria: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. Methods: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. Results: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). Conclusion: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.
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- 2023
38. Contradictory and Missing Voices in English Education: An Invitation to English Faculty
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Emily R. Smith, Betsy A. Bowen, and Faith A. Dohm
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This article offers both a rationale and a proposal for the meaningful contribution of English faculty to the preparation of English teachers. We draw on data from teacher licensure tests and interviews with English and English Education faculty to underscore contradictions among the various voices in English education and to identify ways of bringing English faculty more meaningfully into the conversation. While analysis of our quantitative data suggests correlations between Praxis II exams and other measures of candidates' content knowledge and skills, analysis of interview transcripts and course documents reveals clear differences. We conclude with recommendations for involving English faculty in teacher preparation to balance out the contradictory and dominant voices in English education.
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- 2014
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39. Non-specific effects of BCG and DTP vaccination on infant mortality: An analysis of birth cohorts in Ghana and Tanzania
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MK Quinn, Karen M. Edmond, Wafaie W. Fawzi, Lisa Hurt, Betty R. Kirkwood, Honorati Masanja, Alfa J. Muhihi, Sam Newton, Ramadhani A Noor, Paige L. Williams, Christopher R. Sudfeld, and Emily R. Smith
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General Veterinary ,General Immunology and Microbiology ,Vaccination ,Infant, Newborn ,Public Health, Environmental and Occupational Health ,Infant ,Ghana ,Tanzania ,Sex Factors ,Infectious Diseases ,Infant Mortality ,BCG Vaccine ,Humans ,Molecular Medicine ,Birth Cohort ,Vitamin A ,Diphtheria-Tetanus-Pertussis Vaccine - Abstract
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).
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- 2022
40. Problems with evidence assessment in COVID-19 health policy impact evaluation: a systematic review of study design and evidence strength
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Alyssa Bilinski, Christopher B. Boyer, Eli Ben-Michael, Beth Ann Griffin, Carrie E. Fry, Elizabeth A. Stuart, Emma Clarke-Deelder, Noah Haber, Caroline M. Joyce, Cathrine Axfors, Elizabeth M. Stone, Sarah Wieten, Avi Feller, Benjamin MacCormack-Gelles, Brooke A. Jarrett, Ian Schmid, Beth S. Linas, Emily R. Smith, Laura A. Hatfield, Jamie R. Daw, Eric Au, Van Thu Nguyen, Clara Bolster-Foucault, and Joshua A. Salomon
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Actuarial science ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,Impact evaluation ,Health Policy ,statistics & research methods ,MEDLINE ,Inference ,COVID-19 ,Sample (statistics) ,General Medicine ,Article ,Coronavirus ,Cross-Sectional Studies ,Research Design ,Medicine ,Humans ,Set (psychology) ,Psychology ,Inclusion (education) ,Health policy - Abstract
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.
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- 2022
41. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials
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Erin Murphy, Franca Danielle, Carlos Cabello-Gutierrez, Jason A. Roberts, Juan-Manuel Anaya, Fabio Saccona, Paula A. Gaviria García, Geert Meyfroidt, Olufemi Erinoso, Joshua S. Davis, Oskar Ljungquist, Rossana Cavallo, Kathryn M Rowan, James S. Molton, Alberto Romero, Gitana Scozzari, Alexander V. Ivanov, Manaf AlQahtani, Eduardo Rego, Luis E. Argumanis, Jeffrey H. Jennings, German Jr J. Castillo, Deonne Thaddeus V. Gauiran, M. Rahman, Anne Françoise Donneau, Josephine Anne C. Lucero, Christian J. Fareli, Fresthel Monica M. Climacosa, Adrián Camacho-Ortiz, Aditya Kotecha, Nadia Birocco, Damon H. Cao, David Price, Joe Sasadeusz, Jose M. Ignacio, Antonella Cingolani, Abdulkarim Abdulrahman, Alisa Higgins, Perrine Janiaud, James Daly, Eduardo Perez-Alba, Henrik Nielsen, Cecile C. Dungog, Paul Klenerman, Fazle Rabbi Chowdhury, Diana M. Monsalve, Claudia M. Denkinger, Andreas M. Schmitt, Lyn Li Lim, Heli Harvala, Mahesh C. Patel, Alexis F. Turgeon, Akin Abayomi, Vladimir P. Baklaushev, Rachelle N. Alfonso, Fiorella Krapp, Juan E. Gallo, Januario D. Veloso, Lynn B. Bonifacio, Bryan J. McVerry, Mehdi Safdarian, Ismael F. Aomar, Yanet Ventura-Enriquez, Alric V. Mondragon, Pedrito Y. Tagayuna, Mona Landin-Olsson, Yhojan Rodríguez, Nina Khanna, André Gothot, David Grimaldi, Forhad Hossain Chowdhury, Paola M. Manzini, Farah Al-Beidh, Vivekanand Jha, Ángel Augusto Pérez-Calatayud, Inmaculada Poyato, Salvador Oyonarte, Anne Kristine H. Quero, Manuel Rojas, Carlo Francisco N. Cortez, Bernardo Camacho, Elvira Garza-González, Susan C. Morpeth, Steve Webb, Anastasia Perkina, Marissa M. Alejandria, Emma Laing, Matthew V. N. O'Sullivan, Naomi Perry, Karin Holm, Alexander Averyanov, John P. A. Ioannidis, Mutien Garigliany, Patricia J. Garcia, Ashraful Hoque, Ivy Mae S. Escasa, Jodor Lim, Paul R. Mouncey, Balasubramanian Venkatesh, Kai Zacharowski, Lise J Estcourt, Concepción López-Robles, Teresita E. Dumagay, Megan Rees, Emily R. Smith, Juan C. Díaz-Coronado, Jorge M. Llaca-Díaz, Julián Olalla, Janneke van 't Hooft, S. Rahman, Michel Moutschen, Pierre-François Laterre, Carlos A. Peña-Perez, Geneva Tatem, Mandana Pouladzadeh, Sandy C. Maganito, Lars G. Hemkens, Benjamin A. Rogers, Ryan Zarychanski, Mark Angelo C. Ang, Amy Evans, Susanna Dunachie, Tom Snelling, Claudia Galassi, Anthony C. Gordon, Ana Cardesa, Jesus A. Garcia, Colin McArthur, Akin Osibogun, Zoe McQuilten, David Moher, Juan Mauricio Pardo-Oviedo, Benoît Misset, Naomi E Hammond, Maria Clariza M. Santos, Maria Lundgren, Yeny Acosta-Ampudia, Steven Y. C. Tong, Ana M. Mata, Gorav Sharma, Sergio D’Antico, Maike Janssen, Alistair Nichol, Christian Wikén, Noah Haber, Alaa AlZamrooni, Alonso Soto, Jens Kjeldsen-Kragh, Salvador López-Cárdenas, Patricia L. Garcia, Manu Shankar-Hari, Rubén D. Manrique, Ileana Lopez-Plaza, Sally Campbell-Lee, Giovannino Ciccone, Jeser Santiago Grass Guaqueta, Miguel Marcos, Francisco M. Heralde, Richard M. Novak, Eric Hoste, Asha C. Bowen, Ignacio Marquez, Abel Costa Neto, David K. Menon, Ma Angelina L. Mirasol, Magnus Rasmussen, David Gómez-Almaguer, Erica M. Wood, Jennifer Hines, Daniel Desmecht, Olga Balionis, Thomas Benfield, Veronica Fernandez-Sanchez, Ruby Anne N King, Jesús Rodríguez-Baño, David L. Paterson, Jose M. Carnate, Carolina Ramírez-Santana, Lothar Wiese, Luciana Labanca, Cameron Green, Jose Antonio Giron-Gonzalez, Abbie Bown, Scott Berry, Agnes L.M. Evasan, Juan A. Díaz Ponce-Medrano, Manal Abduljalil, Anna Flor G. Malundo, Justin T Denholm, Amy Tang, Juan Macías, Luciana Teofili, Veerle Compernolle, Steven N. Goodman, Manuela Aguilar-Guisado, Thomas Hills, Cathrine Axfors, Tome Najdovski, Jesica A. Herrick, Bodunrin Osikomaiya, David J. Roberts, Mayur Ramesh, Francesco Giuseppe De Rosa, Francisco Javier Martínez-Marcos, Mohammed K. Ali, Gaukhar M. Yusubalieva, Carsten Müller-Tidow, Parastoo Moradi Choghakabodi, AlQahtani, Manaf [0000-0002-1523-0429], Hills, Thomas E [0000-0003-0322-5822], Hoste, Eric [0000-0001-9301-8055], Price, David J [0000-0003-0076-3123], Yusubalieva, Gaukhar M [0000-0003-3056-4889], Apollo - University of Cambridge Repository, University of Manitoba, NIHR, National Institute for Health Research, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs
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medicine.medical_specialty ,Infectious Medicine ,Convalescent plasma ,Infektionsmedicin ,Infectious and parasitic diseases ,RC109-216 ,030204 cardiovascular system & hematology ,Passive ,Placebo ,Microbiology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,1108 Medical Microbiology ,law ,Internal medicine ,Medicine and Health Sciences ,Medicine ,Humans ,030212 general & internal medicine ,COVID-19 Serotherapy ,Randomized Controlled Trials as Topic ,Science & Technology ,business.industry ,SARS-CoV-2 ,Immunization, Passive ,COVID-19 ,1103 Clinical Sciences ,Intensive care unit ,Confidence interval ,3. Good health ,TIME ,Clinical trial ,Settore MED/15 - MALATTIE DEL SANGUE ,Meta-analysis ,Clinical research ,Treatment Outcome ,Infectious Diseases ,Relative risk ,Immunization ,business ,Life Sciences & Biomedicine ,Research Article ,0605 Microbiology ,COVID-19/therapy - Abstract
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
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- 2021
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42. Determinants of delayed or incomplete diphtheria-tetanus-pertussis vaccination in parallel urban and rural birth cohorts of 30,956 infants in Tanzania
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Pranay Nadella, Emily R. Smith, Alfa Muhihi, Ramadhani A. Noor, Honorati Masanja, Wafaie W. Fawzi, and Christopher R. Sudfeld
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Child health ,Vaccination ,Urban ,Immunization ,Rural ,lcsh:RC109-216 ,Tanzania ,lcsh:Infectious and parasitic diseases - Abstract
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
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- 2019
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43. Geospatial analysis of pediatric surgical need and geographical access to care in Somaliland: a cross-sectional study
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Katelyn Moody, Shukri Dahir, Jonathan Cook, Emily R. Smith, Cesia Cotache-Condor, Tessa Concepcion, Henry E. Rice, John Will, Mubarak Mohamed, and Edna Adan Ismail
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medicine.medical_specialty ,Geospatial analysis ,Cross-sectional study ,Psychological intervention ,computer.software_genre ,Health Services Accessibility ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Child ,Poverty ,Surgeons ,Paediatric surgery ,international health services ,business.industry ,Surgical care ,General Medicine ,medicine.disease ,Hospitals ,Cross-Sectional Studies ,Hotspot (Wi-Fi) ,030220 oncology & carcinogenesis ,paediatric surgery ,Medicine ,Surgery ,epidemiology ,Medical emergency ,Rural area ,business ,computer - Abstract
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.
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- 2021
44. Development of an Interactive Global Surgery Course for Interdisciplinary Learners
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Henry E. Rice, Emily R. Smith, Alvan K Ukachukwu, John A. Gallis, Nyagetuba J. K. Muma, Grey Reavis, Tamara N. Fitzgerald, and Osondu Ogbuoji
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medicine.medical_specialty ,Students, Medical ,education ,MEDLINE ,Disease ,Infectious and parasitic diseases ,RC109-216 ,Global Health ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Multidisciplinary approach ,Group learning ,Health care ,medicine ,Global health ,Humans ,Education, Graduate ,030212 general & internal medicine ,Schools, Medical ,Original Research ,business.industry ,030503 health policy & services ,General Medicine ,medicine.disease ,Faculty ,Surgery ,Test (assessment) ,Curriculum ,Public aspects of medicine ,RA1-1270 ,0305 other medical science ,business ,Psychology - Abstract
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.
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- 2021
45. Symptoms and recovery among adult outpatients with and without COVID‐19 at 11 healthcare facilities—July 2020, United States
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Kiva A. Fisher, Samantha M. Olson, Mark W. Tenforde, Wesley H. Self, Michael Wu, Christopher J. Lindsell, Nathan I. Shapiro, D. Clark Files, Kevin W. Gibbs, Heidi L. Erickson, Matthew E. Prekker, Jay S. Steingrub, Matthew C. Exline, Daniel J. Henning, Jennifer G. Wilson, Samuel M. Brown, Ithan D. Peltan, Todd W. Rice, David N. Hager, Adit A. Ginde, H. Keipp Talbot, Jonathan D. Casey, Carlos G. Grijalva, Brendan Flannery, Manish M. Patel, Leora R. Feldstein, Kimberly W. Hart, Robert McClellan, Hsi‐nien Tan, Adrienne Baughman, Nora A. Hennesy, Brittany Grear, Kristin Mlynarczyk, Luc Marzano, Zuwena Plata, Alexis Caplan, Constance E. Ogokeh, Emily R. Smith, Sara S. Kim, Eric P. Griggs, Bridget Richards, Sonya Robinson, Kaylee Kim, Ahmed M. Kassem, Courtney N. Sciarratta, and Paula L. Marcet
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Weakness ,medicine.medical_specialty ,Epidemiology ,030312 virology ,Affect (psychology) ,Logistic regression ,SARS‐CoV‐2 ,recovery ,03 medical and health sciences ,Quality of life ,COVID‐19 ,Internal medicine ,Outpatients ,Health care ,medicine ,Humans ,symptoms duration ,0303 health sciences ,SARS-CoV-2 ,business.industry ,Public Health, Environmental and Occupational Health ,COVID-19 ,Original Articles ,convalescence ,Odds ratio ,Middle Aged ,Mental health ,Confidence interval ,Logistic Models ,Infectious Diseases ,quality of life ,Case-Control Studies ,Female ,Original Article ,Health Facilities ,medicine.symptom ,business ,anosmia - Abstract
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
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- 2021
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46. Timing and causes of neonatal mortality in Tamale Teaching Hospital, Ghana: A retrospective study
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Sheila A. Owusu, Emily R. Smith, Cesia Cotache-Condor, Alhassan Abdul-Mumin, and Haruna Mahama
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Male ,Pediatrics ,Neonatal intensive care unit ,Physiology ,Maternal Health ,Logistic regression ,Neonatal Care ,Ghana ,Geographical Locations ,Labor and Delivery ,Pregnancy ,Infant Mortality ,Medicine and Health Sciences ,Medicine ,Birth Weight ,Multidisciplinary ,Neonatal mortality ,Mortality rate ,Obstetrics and Gynecology ,Physiological Parameters ,Female ,medicine.symptom ,Research Article ,medicine.medical_specialty ,Death Rates ,Science ,Birth weight ,Preterm Birth ,Teaching hospital ,Asphyxia ,Signs and Symptoms ,Population Metrics ,Humans ,Hospitals, Teaching ,Retrospective Studies ,Population Biology ,business.industry ,Body Weight ,Infant, Newborn ,Biology and Life Sciences ,Neonates ,Infant ,Retrospective cohort study ,Health Care ,Pregnancy Complications ,People and Places ,Africa ,Birth ,Women's Health ,Clinical Medicine ,Neonatology ,business ,Developmental Biology - Abstract
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.
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- 2021
47. Young pregnant women are also at an increased risk of mortality and severe illness due to coronavirus disease 2019: analysis of the Mexican National Surveillance Program
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Emily R. Smith, Raigam Jafet Martinez-Portilla, J. Torres-Torres, Siran He, Juan Mario Solis-Paredes, Liona C. Poon, and Salvador Espino-Y-Sosa
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Adult ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,Young Adult ,Pregnancy ,Internal medicine ,Obstetrics and Gynaecology ,medicine ,Research Letter ,Humans ,Young adult ,Pregnancy Complications, Infectious ,Mexico ,business.industry ,SARS-CoV-2 ,Age Factors ,Obstetrics and Gynecology ,COVID-19 ,medicine.disease ,Increased risk ,Female ,Pregnant Women ,business ,Maternal Age - Published
- 2020
48. Protocol for meta-research on the evidence informing micronutrient dietary reference intakes for pregnant and lactating women [version 1; peer review: 2 approved]
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Siran He, Kevin C. Klatt, Ali Rahnavard, Matthew D. Barberio, Alison D. Gernand, and Emily R. Smith
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lcsh:R ,lcsh:Medicine - Abstract
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.
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- 2020
49. The Brighton Collaboration standardized template for collection of key information for risk/benefit assessment of a Modified Vaccinia Ankara (MVA) vaccine platform
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Heinz Weidenthaler, Richard C. Condit, James S. Robertson, Jean-Louis Excler, Ariane Volkmann, Emily R. Smith, Eric Evans, Robert T. Chen, Anna-Lise Williamson, Thomas Meyer, and Denny Kim
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Vaccine safety ,Modified vaccinia Ankara ,Canada ,viruses ,030231 tropical medicine ,Smallpox vaccine ,Risk/benefit assessment ,Vaccinia virus ,Review ,complex mixtures ,03 medical and health sciences ,Monkeypox ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Viral vector ,Modified Vaccinia Ankara ,medicine ,Vaccinia ,Smallpox ,media_common.cataloged_instance ,Animals ,030212 general & internal medicine ,European union ,Ebola Vaccines ,media_common ,Vaccines ,General Veterinary ,General Immunology and Microbiology ,Ebola vaccine ,business.industry ,Public Health, Environmental and Occupational Health ,medicine.disease ,Brighton Collaboration ,Virology ,Vaccination ,Europe ,Africa, Western ,Infectious Diseases ,chemistry ,Molecular Medicine ,business - Abstract
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.
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- 2020
50. Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) standardized template for collection of key information for benefit-risk assessment of live-attenuated viral vaccines
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Mike Whelan, Richard C. Condit, Robert T. Chen, Sonali Kochhar, Marc Gurwith, Bettina Klug, James S. Robertson, Jean-Louis Excler, Stephen Drew, Patricia E. Fast, David Wood, Denny Kim, Tamala Mallett Moore, Emily R. Smith, and Najwa Khuri-Bulos
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Societies, Scientific ,2019-20 coronavirus outbreak ,Benefit-risk ,Knowledge management ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,030231 tropical medicine ,Drug Evaluation, Preclinical ,Review ,Vaccines, Attenuated ,Risk Assessment ,Viral vector ,03 medical and health sciences ,0302 clinical medicine ,CEPI ,Medicine ,Humans ,030212 general & internal medicine ,Viral ,Public acceptance ,General Veterinary ,General Immunology and Microbiology ,Live ,business.industry ,Viral Vaccine ,Template ,Public Health, Environmental and Occupational Health ,COVID-19 ,Viral Vaccines ,Brighton Collaboration ,Infectious Diseases ,Attenuated ,Key (cryptography) ,Benefit risk assessment ,Molecular Medicine ,Safety ,business ,Risk assessment ,Vaccine - Abstract
Several live-attenuated viral vaccine candidates are among the COVID-19 vaccines in 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 live-attenuated viral vaccines. This will help key stakeholders assess potential safety issues and understand the benefit-risk of such vaccines. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed live-attenuated viral vaccines.
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- 2020
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