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1. P value and Bayesian analysis in randomized-controlled trials in child health research published over 10 years, 2007 to 2017: a methodological review protocol

Author

Alex Aregbesola, Allison Gates, Amanda Coyle, Shannon Sim, Ben Vandermeer, Megan Skakum, Despina Contopoulos-Ioannidis, Anna Heath, Lisa Hartling, and Terry P. Klassen

Subjects
Pvalue, Frequentist, Bayesian, Analysis, Child health, Randomized-controlled trials, Medicine
Abstract

Abstract Background There is an unresolved debate about the reliability of the interpretation of P value. Some investigators have suggested that an alternative Bayesian method is preferred in conducting health research. As randomized-controlled trials (RCTs) are important in generating research evidence, we decided to investigate the extent, if any, the inferential statistical framework in published RCTs in child health research have changed over 10 years. We aim to examine the change in P value and Bayesian analysis in RCTs in child health research papers published from 2007 to 2017. Methods We will search the Cochrane Central Register of Controlled Trials (Wiley) to identify relevant citations. We will leverage a pre-existing sample of child health RCTs published in 2007 (n=300) used in our previous study of reporting quality of pediatric RCTs. Using the same strategy and study selection methods, we will identify a comparable random sample of child health RCTs published in 2017 (n=300). Eligible studies will include RCTs in health research among individuals aged 21 years and below. One reviewer will select studies for inclusion and extract the data and another reviewer will verify these. Disagreements will be resolved by a discussion between reviewers or by involving another reviewer. We will perform a descriptive analysis of 2007 and 2017 samples and analyze the results using both the frequentist and Bayesian methods. We will present specific characteristics of the clinical trials from 2007 and 2017 in tabular and graphical forms. We will report the difference in the proportion of P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. Clustering around P values of significance, if observed, will be reported. Discussion This review will present the difference in the proportion of trials that reported on P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. The implications for future clinical research will be discussed and this research work will be published in a peer-reviewed journal. This review has the potential to help inform the need for a change in the methodological approach from the null hypothesis significance test to Bayesian methods. Systematic review registration Open Science Framework https://osf.io/aj2df

Published
2021
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2. Mother-to-child transmission of Chikungunya virus: A systematic review and meta-analysis.

Author

Despina Contopoulos-Ioannidis, Shoshana Newman-Lindsay, Camille Chow, and A Desiree LaBeaud

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BackgroundChikungunya virus (CHIKV) is an emerging arboviral infection with a global distribution and may cause fetal and neonatal infections after maternal CHIKV-infections during gestation.MethodologyWe performed a systematic review to evaluate the risk for: a) mother-to-child transmission (MTCT), b) antepartum fetal deaths (APFD), c) symptomatic neonatal disease, and d) neonatal deaths from maternal CHIKV-infections during gestation. We also recorded the neonatal clinical manifestations after such maternal infections (qualitative data synthesis). We searched PubMed (last search 3/2017) for articles, of any study design, with any of the above outcomes. We calculated the overall risk of MTCT, APFDs and risk of symptomatic neonatal disease by simple pooling. For endpoints with ≥5 events in more than one study, we also synthesized the data by random-effect-model (REM) meta-analysis.Principal findingsAmong 563 identified articles, 13 articles from 8 cohorts were included in the quantitative data synthesis and 33 articles in the qualitative data synthesis. Most cohorts reported data only on symptomatic rather than on all neonatal infections. By extrapolation also of these data, the overall pooled-MTCT-risk across cohorts was at least 15.5% (206/1331), (12.6% by REMs). The pooled APFD-risk was 1.7% (20/1203); while the risk of CHIKV-confirmed-APFDs was 0.3% (3/1203). Overall, the pooled-risk of symptomatic neonatal disease was 15.3% (203/1331), (11.9% by REMs). The pooled risk of symptomatic disease was 50.0% (23/46) among intrapartum vs 0% (0/712) among antepartum/peripartum maternal infections. Infected newborns, from maternal infections during gestation were either asymptomatic or presented within their first week of life, but not at birth, with fever, irritability, hyperalgesia, diffuse limb edema, rashes and occasionally sepsis-like illness and meningoencephalitis. The pooled-risk of neonatal death was 0.6% (5/832) among maternal infections and 2.8% (5/182) among neonatal infections; long-term neurodevelopmental delays occurred in 50% of symptomatic neonatal infections.Conclusions/significancePublished cohorts with data on the risk to the fetus and/or newborn from maternal CHIKV-infections during gestation were sparse compared to the number of recently reported CHIKV-infection outbreaks worldwide; however perinatal infections do occur, at high rates during intrapartum period, and can be related to neonatal death and long-term disabilities.

Published
2018
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4. Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.

Author

Marisa Holubar, Maria Christina Stavroulakis, Yvonne Maldonado, John P A Ioannidis, and Despina Contopoulos-Ioannidis

Subjects
Medicine, Science
Abstract

BACKGROUND:Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. METHODS:We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. RESULTS:We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target vaccination strategy depended on the inclusion of the herd protection effect. CONCLUSIONS:Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution.

Published
2017
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5. PRISMA-Children (C) and PRISMA-Protocol for Children (P-C) Extensions: a study protocol for the development of guidelines for the conduct and reporting of systematic reviews and meta-analyses of newborn and child health research

Author

Lisa Hartling, Martin Offringa, David Moher, Lisa Askie, Zulfiqar A Bhutta, Roger Soll, Mufiza Z Kapadia, and Despina Contopoulos-Ioannidis

Subjects
Medicine
Abstract

Introduction Paediatric systematic reviews differ from adult systematic reviews in several key aspects such as considerations of child tailored interventions, justifiable comparators, valid outcomes and child sensitive search strategies. Available guidelines, including PRISMA-P (2015) and PRISMA (2009), do not cover all the complexities associated with reporting systematic reviews in the paediatric population. Using a collaborative, multidisciplinary structure, we aim to develop evidence-based and consensus-based PRISMA-P-C (Protocol for Children) and PRISMA-C (Children) Extensions to guide paediatric systematic review protocol and completed review reporting.Methods and analysis This project's methodology follows published recommendations for developing reporting guidelines and involves the following six phases; (1) establishment of a steering committee representing key stakeholder groups; (2) a scoping review to identify potential Extension items; (3) three types of consensus activities including meetings of the steering committee to achieve high-level decisions on the content and methodology of the Extensions, a survey of key stakeholders to generate a list of possible items to include in the Extensions and a formal consensus meeting to select the reporting items to add to, or modify for, the Extension; (4) the preliminary checklist items generated in phase III will be evaluated against the existing evidence and reporting practices in paediatric systematic reviews; (5) extension statements and explanation and elaboration documents will provide detailed advice for each item and examples of good reporting; (6) development and implementation of effective knowledge translation of the extension checklist, and an evaluation of the Extensions by key stakeholders.Ethics and Dissemination This protocol was considered a quality improvement project by the Hospital for Sick Children's Ethics Committee and did not require ethical review. The resultant checklists, jointly developed with all relevant stakeholders, will be disseminated through peer-reviewed journals as well as national and international conference presentations. Endorsement of the checklist will be sought simultaneously in multiple journals.

Published
2016
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6. Building Programs to Eradicate Toxoplasmosis Part II: Education

Author

Mariangela Soberón Felín, Kanix Wang, Aliya Moreira, Andrew Grose, Karen Leahy, Ying Zhou, Fatima Alibana Clouser, Maryam Siddiqui, Nicole Leong, Perpetua Goodall, Morgan Michalowski, Mahmoud Ismail, Monica Christmas, Stephen Schrantz, Zuleima Caballero, Ximena Norero, Dora Estripeaut, David Ellis, Catalina Raggi, Catherine Castro, Claudia Rengifo-Herrera, Davina Moossazadeh, Margarita Ramirez, Abhinav Pandey, Kevin Ashi, Samantha Dovgin, Ashtyn Dixon, Xuan Li, Ian Begeman, Sharon Heichman, Joseph Lykins, Delba Villalobos-Cerrud, Lorena Fabrega, José Luis Sanchez Montalvo, Connie Mendivil, Mario R. Quijada, Silvia Fernández-Pirla, Valli de La Guardia, Digna Wong, Mayrene Ladrón de Guevara, Carlos Flores, Jovanna Borace, Anabel García, Natividad Caballero, Maria Theresa Moreno de Saez, Michael Politis, Stephanie Ross, Mimansa Dogra, Vishan Dhamsania, Nicholas Graves, Marci Kirchberg, Kopal Mathur, Ashley Aue, Carlos M. Restrepo, Alejandro Llanes, German Guzman, Arturo Rebellon, Kenneth Boyer, Peter Heydemann, A. Gwendolyn Noble, Charles Swisher, Peter Rabiah, Shawn Withers, Teri Hull, David Frim, David McLone, Chunlei Su, Michael Blair, Paul Latkany, Ernest Mui, Daniel Vitor Vasconcelos-Santos, Alcibiades Villareal, Ambar Perez, Carlos Andrés Naranjo Galvis, Mónica Vargas Montes, Nestor Ivan Cardona Perez, Morgan Ramirez, Cy Chittenden, Edward Wang, Laura Lorena Garcia-López, Juliana Muñoz-Ortiz, Nicolás Rivera-Valdivia, María Cristina Bohorquez-Granados, Gabriela Castaño de-la-Torre, Guillermo Padrieu, Juan David Valencia Hernandez, Daniel Celis-Giraldo, John Alejandro Acosta Dávila, Elizabeth Torres, Manuela Mejia Oquendo, José Y. Arteaga-Rivera, Dan L. Nicolae, Andrey Rzhetsky, Nancy Roizen, Eileen Stillwaggon, Larry Sawers, Francois Peyron, Martine Wallon, Emanuelle Chapey, Pauline Levigne, Carmen Charter, Migdalia De Frias, Jose Montoya, Cindy Press, Raymund Ramirez, Despina Contopoulos-Ioannidis, Yvonne Maldonado, Oliver Liesenfeld, Carlos Gomez, Kelsey Wheeler, Samantha Zehar, James McAuley, Denis Limonne, Sandrine Houze, Sylvie Abraham, Raphael Piarroux, Vera Tesic, Kathleen Beavis, Ana Abeleda, Mari Sautter, Bouchra El Mansouri, Adlaoui El Bachir, Fatima Amarir, Kamal El Bissati, Ellen Holfels, Richard Penn, William Cohen, Alejandra de-la-Torre, Gabrielle Britton, Jorge Motta, Eduardo Ortega-Barria, Isabel Luz Romero, Paul Meier, Michael Grigg, Jorge Gómez-Marín, Jagannatha Rao Kosagisharaf, Xavier Sáez Llorens, Osvaldo Reyes, and Rima McLeod

Subjects
Pediatrics, Perinatology and Child Health
Abstract

Purpose of Review Review work to create and evaluate educational materials that could serve as a primary prevention strategy to help both providers and patients in Panama, Colombia, and the USA reduce disease burden of Toxoplasma infections. Recent Findings Educational programs had not been evaluated for efficacy in Panama, USA, or Colombia. Summary Educational programs for high school students, pregnant women, medical students and professionals, scientists, and lay personnel were created. In most settings, short-term effects were evaluated. In Panama, Colombia, and USA, all materials showed short-term utility in transmitting information to learners. These educational materials can serve as a component of larger public health programs to lower disease burden from congenital toxoplasmosis. Future priorities include conducting robust longitudinal studies of whether education correlates with reduced adverse disease outcomes, modifying educational materials as new information regarding region-specific risk factors is discovered, and ensuring materials are widely accessible.

Published
2022
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7. Robustness of reported postacute health outcomes in children with SARS-CoV-2 infection : a systematic review

Author

Julian Hirt, Perrine Janiaud, Viktoria Luise Gloy, Stefan Schandelmaier, Tiago V Pereira, Despina Contopoulos-Ioannidis, Steven N Goodman, John Ioannidis, Klaus Munkholm, and Lars G Hemkens

Subjects
Pediatrics, Perinatology and Child Health
Abstract

ObjectiveTo systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children.MethodsA search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (Results21 studies including 81 896 children reported up to 97 symptoms with follow-up periods of 2.0–11.5 months. Fifteen studies had no control group. The reported proportion of children with post-COVID syndrome was between 0% and 66.5% in children with SARS-CoV-2 infection (n=16 986) and between 2.0% and 53.3% in children without SARS-CoV-2 infection (n=64 910). Only two studies made a clear causal interpretation of an association between SARS-CoV-2 infection and the main outcome of ‘post-COVID syndrome’ and provided recommendations regarding prevention measures. The robustness of all 21 studies was seriously limited due to an overall critical risk of bias.ConclusionsThe robustness of reported postacute SARS-CoV-2 infection health outcomes in children is seriously limited, at least in all the published articles we could identify. None of the studies provided evidence with reasonable certainty on whether SARS-CoV-2 infection has an impact on postacute health outcomes, let alone to what extent. Children and their families urgently need much more reliable and methodologically robust evidence to address their concerns and improve care.

Published
2023
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8. P-value and Bayesian analysis in randomized-controlled trials in child health research published in 2007 and 2017: a methodological review

Author

Alex Aregbesola, Allison Gates, Amanda Coyle, Shannon Sim, Ben Vandermeer, Megan Skakum, Despina Contopoulos-Ioannidis, Anna Heath, Lisa Hartling, and Terry P. Klassen

Abstract

Background Reliance on P-value of significance in clinical trials is a source of debate because of misconceptions and misinterpretations associated with it. Bayesian methods are suggested as an alternative approach. As randomized-controlled trials (RCTs) are essential in generating research evidence, we investigated the change in the use of P-values and Bayesian analysis and the clustering of P-values at key significance levels in child health RCTs published in 2007 and 2017. Methods We searched Cochrane Central Register of Controlled Trials to identify random samples of child health RCTs published in 2007 (n = 300) and 2017 (n = 300). Data on trial characteristics and analytic approaches were extracted. We analyzed the 600 RCTs using the frequentist and Bayesian methods. The change in the proportion of trials reporting P-values and Bayesian analyses was assessed using Pearson/Fisher Exact tests and non-informative Dirichlet priors. Results Of 600 RCTs, 535 (89%) used frequentist methods only versus 65 (11%) that included some Bayesian methods. Only 2 of the 65 trials used Bayesian inferential statistics. The use of frequentist methods decreased from (273, 91% to 262, 87%) while the inclusion of Bayesian analysis slightly increased from (27, 9% to 38, 13%) between 2007 and 2017. Although most RCTs were from Europe (172, 29%) and North America (133, 22%), the increase in proportion of trials by continent was most in Asia (mean difference (MD) = 0.14, 95% credible interval (CI) 0.08–0.20) with posterior probability (PP) of 1.00. Parallel (487, 81.2%) and cluster (58, 9.7%) RCTs were the most common RCT types but the increase in cluster RCT (0.06, 95%CI 0.02–0.11, PP = 0.99) was more than any other RCT types over 10 years. We found clustering of P-values at the significance level of 0.05 (437, 72.8%), which increased between 2007 (209, 69.7%) and 2017 (228, 76%). The smallest P-value reported in this review was 0.0001 (1, 0.2%). Conclusions The statistical framework in child health RCTs has not changed from the frequentist methods that is based on P-values with an unexplained clustering at the significance level of 0.05. Bayesian methods may increase the confidence in interpretation of results of RCTs

Published
2022
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9. Building Programs to Eradicate Toxoplasmosis Part IV: Understanding and Development of Public Health Strategies and Advances 'Take a Village'

Author

Mariangela Soberón Felín, Kanix Wang, Aliya Moreira, Andrew Grose, Karen Leahy, Ying Zhou, Fatima Alibana Clouser, Maryam Siddiqui, Nicole Leong, Perpetua Goodall, Morgan Michalowski, Mahmoud Ismail, Monica Christmas, Stephen Schrantz, Zuleima Caballero, Ximena Norero, Dora Estripeaut, David Ellis, Catalina Raggi, Catherine Castro, Davina Moossazadeh, Margarita Ramirez, Abhinav Pandey, Kevin Ashi, Samantha Dovgin, Ashtyn Dixon, Xuan Li, Ian Begeman, Sharon Heichman, Joseph Lykins, Delba Villalobos-Cerrud, Lorena Fabrega, José Luis Sanchez Montalvo, Connie Mendivil, Mario R. Quijada, Silvia Fernández-Pirla, Valli de La Guardia, Digna Wong, Mayrene Ladrón de Guevara, Carlos Flores, Jovanna Borace, Anabel García, Natividad Caballero, Claudia Rengifo-Herrera, Maria Theresa Moreno de Saez, Michael Politis, Stephanie Ross, Mimansa Dogra, Vishan Dhamsania, Nicholas Graves, Marci Kirchberg, Kopal Mathur, Ashley Aue, Carlos M. Restrepo, Alejandro Llanes, German Guzman, Arturo Rebellon, Kenneth Boyer, Peter Heydemann, A. Gwendolyn Noble, Charles Swisher, Peter Rabiah, Shawn Withers, Teri Hull, David Frim, David McLone, Chunlei Su, Michael Blair, Paul Latkany, Ernest Mui, Daniel Vitor Vasconcelos-Santos, Alcibiades Villareal, Ambar Perez, Carlos Andrés Naranjo Galvis, Mónica Vargas Montes, Nestor Ivan Cardona Perez, Morgan Ramirez, Cy Chittenden, Edward Wang, Laura Lorena Garcia-López, Guillermo Padrieu, Juliana Muñoz-Ortiz, Nicolás Rivera-Valdivia, María Cristina Bohorquez-Granados, Gabriela Castaño de-la-Torre, Juan David Valencia Hernandez, Daniel Celis-Giraldo, Juan Alejandro Acosta Dávila, Elizabeth Torres, Manuela Mejia Oquendo, José Y. Arteaga-Rivera, Dan L Nicolae, Andrey Rzhetsky, Nancy Roizen, Eileen Stillwaggon, Larry Sawers, Francois Peyron, Martine Wallon, Emanuelle Chapey, Pauline Levigne, Carmen Charter, Migdalia De Frias, Jose Montoya, Cindy Press, Raymund Ramirez, Despina Contopoulos-Ioannidis, Yvonne Maldonado, Oliver Liesenfeld, Carlos Gomez, Kelsey Wheeler, Samantha Zehar, James McAuley, Denis Limonne, Sandrine Houze, Sylvie Abraham, Raphael Piarroux, Vera Tesic, Kathleen Beavis, Ana Abeleda, Mari Sautter, Bouchra El Mansouri, Adlaoui El Bachir, Fatima Amarir, Kamal El Bissati, Ellen Holfels, Richard Penn, William Cohen, Alejandra de-la-Torre, Gabrielle Britton, Jorge Motta, Eduardo Ortega-Barria, Isabel Luz Romero, Paul Meier, Michael Grigg, Jorge Gómez-Marín, Jagannatha Rao Kosagisharaf, Xavier Sáez Llorens, Osvaldo Reyes, and Rima McLeod

Subjects
Pediatrics, Perinatology and Child Health
Abstract

Purpose of Review Review international efforts to build a global public health initiative focused on toxoplasmosis with spillover benefits to save lives, sight, cognition and motor function benefiting maternal and child health. Recent Findings Multiple countries’ efforts to eliminate toxoplasmosis demonstrate progress and context for this review and new work. Summary Problems with potential solutions proposed include accessibility of accurate, inexpensive diagnostic testing, pre-natal screening and facilitating tools, missed and delayed neonatal diagnosis, restricted access, high costs, delays in obtaining medicines emergently, delayed insurance pre-approvals and high medicare copays taking considerable physician time and effort, harmful shortcuts being taken in methods to prepare medicines in settings where access is restricted, reluctance to perform ventriculoperitoneal shunts promptly when needed without recognition of potential benefit, access to resources for care, especially for marginalized populations, and limited use of recent advances in management of neurologic and retinal disease which can lead to good outcomes.

Published
2022

10. Building Programs to Eradicate Toxoplasmosis Part I: Introduction and Overview

Author

Mariangela Soberón Felín, Kanix Wang, Aliya Moreira, Andrew Grose, Karen Leahy, Ying Zhou, Fatima Alibana Clouser, Maryam Siddiqui, Nicole Leong, Perpetua Goodall, Morgan Michalowski, Mahmoud Ismail, Monica Christmas, Stephen Schrantz, Zuleima Caballero, Ximena Norero, Dora Estripeaut, David Ellis, Catalina Raggi, Catherine Castro, Davina Moossazadeh, Margarita Ramirez, Abhinav Pandey, Kevin Ashi, Samantha Dovgin, Ashtyn Dixon, Xuan Li, Ian Begeman, Sharon Heichman, Joseph Lykins, Delba Villalobos-Cerrud, Lorena Fabrega, José Luis Sanchez Montalvo, Connie Mendivil, Mario R. Quijada, Silvia Fernández-Pirla, Valli de La Guardia, Digna Wong, Mayrene Ladrón de Guevara, Carlos Flores, Jovanna Borace, Anabel García, Natividad Caballero, Claudia Rengifo-Herrera, Maria Theresa Moreno de Saez, Michael Politis, Kristen Wroblewski, Theodore Karrison, Stephanie Ross, Mimansa Dogra, Vishan Dhamsania, Nicholas Graves, Marci Kirchberg, Kopal Mathur, Ashley Aue, Carlos M. Restrepo, Alejandro Llanes, German Guzman, Arturo Rebellon, Kenneth Boyer, Peter Heydemann, A. Gwendolyn Noble, Charles Swisher, Peter Rabiah, Shawn Withers, Teri Hull, Chunlei Su, Michael Blair, Paul Latkany, Ernest Mui, Daniel Vitor Vasconcelos-Santos, Alcibiades Villareal, Ambar Perez, Carlos Andrés Naranjo Galvis, Mónica Vargas Montes, Nestor Ivan Cardona Perez, Morgan Ramirez, Cy Chittenden, Edward Wang, Laura Lorena Garcia-López, Juliana Muñoz-Ortiz, Nicolás Rivera-Valdivia, María Cristina Bohorquez-Granados, Gabriela Castaño de-la-Torre, Guillermo Padrieu, Juan David Valencia Hernandez, Daniel Celis-Giraldo, Juan Alejandro Acosta Dávila, Elizabeth Torres, Manuela Mejia Oquendo, José Y. Arteaga-Rivera, Dan L. Nicolae, Andrey Rzhetsky, Nancy Roizen, Eileen Stillwaggon, Larry Sawers, Francois Peyron, Martine Wallon, Emanuelle Chapey, Pauline Levigne, Carmen Charter, Migdalia De Frias, Jose Montoya, Cindy Press, Raymund Ramirez, Despina Contopoulos-Ioannidis, Yvonne Maldonado, Oliver Liesenfeld, Carlos Gomez, Kelsey Wheeler, Ellen Holfels, David Frim, David McLone, Richard Penn, William Cohen, Samantha Zehar, James McAuley, Denis Limonne, Sandrine Houze, Sylvie Abraham, Raphael Piarroux, Vera Tesic, Kathleen Beavis, Ana Abeleda, Mari Sautter, Bouchra El Mansouri, Adlaoui El Bachir, Fatima Amarir, Kamal El Bissati, Alejandra de-la-Torre, Gabrielle Britton, Jorge Motta, Eduardo Ortega-Barria, Isabel Luz Romero, Paul Meier, Michael Grigg, Jorge Gómez-Marín, Jagannatha Rao Kosagisharaf, Xavier Sáez Llorens, Osvaldo Reyes, and Rima McLeod

Subjects
Pediatrics, Perinatology and Child Health
Abstract

Purpose of ReviewReview building of programs to eliminateToxoplasmainfections.Recent FindingsMorbidity and mortality from toxoplasmosis led to programs in USA, Panama, and Colombia to facilitate understanding, treatment, prevention, and regional resources, incorporating student work.SummaryStudies foundational for building recent, regional approaches/programs are reviewed. Introduction provides an overview/review of programs in Panamá, the United States, and other countries. High prevalence/risk of exposure led to laws mandating testing in gestation, reporting, and development of broad-based teaching materials aboutToxoplasma.These were tested for efficacy as learning tools for high-school students, pregnant women, medical students, physicians, scientists, public health officials and general public. Digitized, free, smart phone application effectively taught pregnant women about toxoplasmosis prevention. Perinatal infection care programs, identifying true regional risk factors, and point-of-care gestational screening facilitate prevention and care. When implemented fully across all demographics, such programs present opportunities to save lives, sight, and cognition with considerable spillover benefits for individuals and societies.

Published
2022

12. Contributors

Author

Mark J. Abzug, Elisabeth E. Adderson, Allison L. Agwu, Kevin Alby, Grace M. Aldrovandi, Upton D. Allen, Gerardo Alvarez-Hernández, Krow Ampofo, Evan J. Anderson, Margot Anderson, Stella Antonara, Monica I. Ardura, Paul M. Arguin, John C. Arnold, Naomi E. Aronson, Ann M. Arvin, Shai Ashkenazi, Edwin J. Asturias, Vahe Badalyan, Carol J. Baker, Karthik Balakrishnan, Brittany S. Barros, William J. Barson, Daniel G. Bausch, Kirsten Bechtel, Daniel K. Benjamin, David M. Berman, David A. Blanco, Karen C. Bloch, Margaret J. Blythe, Joseph A. Bocchini, Anna Bowen, William R. Bowie, Thomas G. Boyce, John S. Bradley, Michael T. Brady, Denise F. Bratcher, Paula K. Braverman, Joseph Bresee, Itzhak Brook, Kevin E. Brown, Kristina Bryant, E. Stephen Buescher, Jane L. Burns, Carrie L. Byington, Andres F. Camacho-Gonzalez, Paul Cantey, Bryan D. Carter, Mary T. Caserta, Luis A. Castagnini, Chiara Cerini, Ellen Gould Chadwick, Silvia S. Chiang, John C. Christenson, Susan E. Coffin, Melissa G. Collier, Jennifer P. Collins, Laurie S. Conklin, Beverly L. Connelly, Despina Contopoulos-Ioannidis, James H. Conway, Margaret M. Cortese, Elaine G. Cox, C. Buddy Creech, Jonathan D. Crews, Dennis J. Cunningham, Nigel Curtis, Natalie J.M. Dailey, Lara A. Danziger-Isakov, Toni Darville, Gregory A. Dasch, Irini Daskalaki, Robert S. Daum, Michael Davenport, H. Dele Davies, Fatimah S. Dawood, J. Christopher Day, Maite de la Morena, Gail J. Demmler-Harrison, Gregory P. DeMuri, Dickson D. Despommier, Karen A. Diefenbach, Kathryn M. Edwards, Morven S. Edwards, Lawrence F. Eichenfield, Dirk M. Elston, Beth Emerson, Moshe Ephros, Guliz Erdem, Marina E. Eremeeva, Jessica E. Ericson, Douglas H. Esposito, Monica M. Farley, Anat R. Feingold, Kristina N. Feja, Adam Finn, Marc Fischer, Patricia M. Flynn, LeAnne M. Fox, Michael M. Frank, Douglas R. Fredrick, Robert W. Frenck, Sheila Fallon Friedlander, Hayley A. Gans, Gregory M. Gauthier, Jeffrey S. Gerber, Francis Gigliotti, Mark A. Gilger, Carol A. Glaser, Amanda F. Goddard, Benjamin D. Gold, Jane M. Gould, Michael Green, David Greenberg, Tanya Greywal, Daniel Griffin, Patricia M. Griffin, Alexei A. Grom, Kathleen Gutierrez, Julie Gutman, Judith A. Guzman-Cottrill, Aron J. Hall, Jin-Young Han, Marvin B. Harper, Julie R. Harris, Christopher J. Harrison, David B. Haslam, Sarah J. Hawkes, J. Owen Hendley, Marion C.W. Henry, Joseph A. Hilinski, Susan L. Hills, Scott D. Holmberg, Deborah Holtzman, David K. Hong, Peter J. Hotez, Katherine K. Hsu, David A. Hunstad, Loris Y. Hwang, Mary Anne Jackson, Richard F. Jacobs, Ravi Jhaveri, Kateřina Jirků-Pomajbíková, Jeffrey L. Jones, Mahima Karki, M. Gary Karlowicz, Ben Z. Katz, Ishminder Kaur, Gilbert J. Kersh, Jay S. Keystone, Muhammad Ali Khan, David W. Kimberlin, Martin B. Kleiman, Bruce S. Klein, Karl Klontz, Barbara Knust, Andrew Y. Koh, E. Kent Korgenski, Paul Krogstad, Preeta Krishnan Kutty, Christine T. Lauren, Hillary S. Lawrence, Amy Leber, Grace M. Lee, Eugene Leibovitz, Eyal Leshem, Stéphanie Levasseur, David B. Lewis, Robyn A. Livingston, Eloisa Llata, Sarah S. Long, Ben A. Lopman, Yalda C. Lucero, Jorge Luján-Zilbermann, Katherine Luzuriaga, Noni E. MacDonald, Yvonne A. Maldonado, John Manaloor, Chitra S. Mani, Kalpana Manthiram, Gary S. Marshall, Stacey W. Martin, Almea Matanock, Catalina Matiz, Alison C. Mawle, Tony Mazzulli, Kathleen A. McGann, Kenneth McIntosh, Lucy A. McNamara, Michal Meir, Debrah Meislich, H. Cody Meissner, Elissa Meites, Asunción Mejías, Jussi Mertsola, Kevin Messacar, Mohammed Nael Mhaissen, Marian G. Michaels, Melissa B. Miller, Eric D. Mintz, John F. Modlin, Parvathi Mohan, Susan P. Montgomery, José G. Montoya, Pedro L. Moro, Anna-Barbara Moscicki, R. Lawrence Moss, Angela L. Myers, Simon Nadel, Michael N. Neely, Karen P. Neil, Joanna Nelson, Noele P. Nelson, William L. Nicholson, Victor Nizet, Amy Jo Nopper, Theresa J. Ochoa, Walter A. Orenstein, Miguel O'Ryan, Christopher D. Paddock, Harpreet Pall, Suresh Kumar Panuganti, Diane E. Pappas, Robert F. Pass, Thomas F. Patterson, Monica E. Patton, Stephen I. Pelton, Brett W. Petersen, Larry K. Pickering, Swetha Pinninti, Paul J. Planet, Andrew J. Pollard, Klara M. Posfay-Barbe, Casper S. Poulsen, Susan M. Poutanen, Ann M. Powers, Charles G. Prober, Octavio Ramilo, Shawn J. Rangel, Suchitra Rao, Sarah A. Rawstron, Jennifer S. Read, Michael D. Reed, Ryan F. Relich, Megan E. Reller, Neil Rellosa, Katherine A. Rempe, Melissa A. Reyes, Samuel E. Rice-Townsend, Frank O. Richards, José R. Romero, David A. Rosen, Christina A. Rostad, G. Ingrid J.G. Rours, Janell A. Routh, Anne H. Rowley, Lorry G. Rubin, Edward T. Ryan, Lisa Saiman, Julia S. Sammons, Laura Sass, Jason B. Sauberan, Sarah Schillie, Grant S. Schulert, Jennifer E. Schuster, Kevin L. Schwartz, Bethany K. Sederdahl, Jose A. Serpa, Kara N. Shah, Samir S. Shah, Andi L. Shane, Eugene D. Shapiro, Jana Shaw, Avinash K. Shetty, Linda M. Dairiki, George Kelly Siberry, Jane D. Siegel, Robert David Siegel, Kari A. Simonsen, Nalini Singh, Upinder Singh, P. Brian Smith, John D. Snyder, Eunkyung Song, Jennifer L. Sorrell, Emily Souder, Joseph W. St. Geme, Mary Allen Staat, J. Erin Staples, Jeffrey R. Starke, William J. Steinbach, Christen R. Stensvold, Bradley P. Stoner, Raymond A. Strikas, Jonathan B. Strober, Paul K. Sue, Deanna A. Sutton, Douglas Swanson, Jacqueline E. Tate, Marc Tebruegge, Eyasu H. Teshale, Amelia B. Thompson, George R. Thompson, Robert Thompson-Stone, Richard B. Thomson, Emily A. Thorell, Nicole H. Tobin, Philip Toltzis, James Treat, Stephanie B. Troy, Russell B. Van, Louise Elaine Vaz, Jennifer Vodzak, Ellen R. Wald, Rebecca Wallihan, Zoon Wangu, Matthew Washam, Joshua R. Watson, Rachel L. Wattier, Geoffrey A. Weinberg, A. Clinton White, Harold C. Wiesenfeld, John V. Williams, Rodney E. Willoughby, Sarah L. Wingerter, Robert R. Wittler, Karen K. Wong, Kimberly A. Workowski, Terry W. Wright, Pablo Yagupsky, Catherine Yen, Jumi Yi, Jonathan S. Yoder, Edward J. Young, Andrea L. Zaenglein, and Kanecia Zimmerman

Published
2018
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13. Contributors

Author

Elisabeth E. Adderson, Aarti Agarwal, Grace M. Aldrovandi, Upton D. Allen, Manuel R. Amieva, Krow Ampofo, Alicia D. Anderson, Margot Anderson, Paul M. Arguin, John C. Arnold, Ann M. Arvin, Shai Ashkenazi, Carol J. Baker, William J. Barson, Daniel G. Bausch, Kirsten Bechtel, Daniel K. Benjamin, Frank E. Berkowitz, Margaret J. Blythe, Joseph A. Bocchini, Michael Boeckh, Anna Bowen, William R. Bowie, Thomas G. Boyce, John S. Bradley, Michael T. Brady, Denise F. Bratcher, Paula K. Braverman, Caroline Breese Hall, Joseph S. Bresee, Itzhak Brook, Kristina Bryant, E. Stephen Buescher, Jane L. Burns, Gale R. Burstein, Carrie L. Byington, Kathy K. Byrd, Michael Cappello, Bryan D. Carter, Emily J. Cartwright, Mary T. Caserta, Chiara Cerini, Ellen Gould Chadwick, Beth Cheesebrough, P. Joan Chesney, John C. Christenson, Thomas G. Cleary, Susan E. Coffin, Laura M. Conklin, Laurie S. Conklin, Beverly L. Connelly, Despina Contopoulos-Ioannidis, James H. Conway, Margaret M. Cortese, C. Michael Cotten, Elaine Cox, Maryanne E. Crockett, James E. Crowe, Nigel Curtis, Dennis J. Cunningham, Linda Marie Dairiki Shortliffe, Toni Darville, Gregory A. Dasch, Irini Daskalaki, Robert S. Daum, Fatimah S. Dawood, Gail J. Demmler, Dickson D. Despommier, Karen A. Diefenbach, Christopher C. Dvorak, Kathryn M. Edwards, Morven S. Edwards, Lawrence F. Eichenfield, Dirk M. Elston, Janet A. Englund, Veronique Erard, Marina E. Eremeeva, Anat R. Feingold, Adam Finn, Anthony E. Fiore, Marc Fischer, Sarah J. Fitch, Patricia M. Flynn, LeAnne M. Fox, Michael M. Frank, Douglas R. Fredrick, Sheila Fallon Friedlander, Hayley A. Gans, Carla G. Garcia, Maria C. Garzon, Jeffrey S. Gerber, Michael D. Geschwind, Laura B. Gieraltowski, Francis Gigliotti, Peter H. Gilligan, Carol Glaser, Benjamin D. Gold, Brahm Goldstein, Jane M. Gould, Michael Green, David Greenberg, Patricia M. Griffin, Alexei A. Grom, Kathleen Gutierrez, Judith A. Guzman-Cottrill, Aron J. Hall, Marvin B. Harper, Christopher J. Harrison, David B. Haslam, Sarah J. Hawkes, Edward B. Hayes, Rohan Hazra, Sara Jane Heilig, J. Owen Hendley, Marion C.W. Henry, Joseph A. Hilinski, Scott D. Holmberg, Deborah Holtzman, Peter J. Hotez, Katherine K. Hsu, Dale J. Hu, Loris Y. Hwang, David Y. Hyun, Mary Anne Jackson, Richard F. Jacobs, Jeffrey L. Jones, Saleem Kamili, M. Gary Karlowicz, Ben Z. Katz, Gilbert J. Kersh, Laura M. Kester, Jay S. Keystone, David W. Kimberlin, Martin B. Kleiman, Mark W. Kline, Andrew Y. Koh, Andreas Konstantopoulos, Katalin I. Koranyi, E. Kent Korgenski, Andrew T. Kroger, Paul Krogstad, Christine T. Lauren, Hillary S. Lawrence, Eugene Leibovitz, Stéphanie Levasseur, David B. Lewis, Jay M. Lieberman, Jen-Jane Liu, Robyn A. Livingston, Eloisa Llata, Anagha R. Loharikar, Sarah S. Long, Ben A. Lopman, Bennett Lorber, Donald E. Low, Yalda C. Lucero, Jorge Luján-Zilbermann, Katherine Luzuriaga, Noni E. MacDonald, Adam MacNeil, Yvonne A. Maldonado, Chitra S. Mani, Mario J. Marcon, Gary S. Marshall, Stacey W. Martin, Catalina Matiz, Alison C. Mawle, Tony Mazzulli, George H. McCracken, Matthew B. McDonald, Robert S. McGregor, Kenneth McIntosh, Meredith McMorrow, Candice McNeil, Jennifer H. McQuiston, Debrah Meislich, H. Cody Meissner, Asunción Mejías, Manoj P. Menon, Jussi Mertsola, Marian G. Michaels, Melissa B. Miller, Eric D. Mintz, John F. Modlin, Parvathi Mohan, Susan P. Montgomery, Jose G. Montoya, Zack S. Moore, Maite de la Morena, Pedro L. Moro, Anna-Barbara Moscicki, R. Lawrence Moss, Trudy V. Murphy, Dennis L. Murray, Angela L. Myers, Simon Nadel, James P. Nataro, Michael N. Neely, William L. Nicholson, Victor Nizet, Amy Jo Nopper, Anna Norrby-Teglund, Theresa J. Ochoa, Miguel O’Ryan, Walter A. Orenstein, Christopher D. Paddock, Diane E. Pappas, Robert F. Pass, Thomas F. Patterson, Stephen I. Pelton, Larry K. Pickering, Caroline Diane Sarah Piggott, Philip A. Pizzo, Andrew J. Pollard, Klara M. Posfay-Barbe, Susan M. Poutanen, Dwight A. Powell, Alice S. Prince, Charles G. Prober, Octavio Ramilo, Shawn J. Rangel, Sarah A. Rawstron, Jennifer S. Read, Michael D. Reed, Joanna J. Regan, Megan E. Reller, Melissa A. Reyes, Peter A. Rice, Samuel E. Rice-Townsend, Frank O. Richards, Gail L. Rodgers, Pierre E. Rollin, José R. Romero, G. Ingrid J.G. Rours, Anne H. Rowley, Sharon L. Roy, Lorry G. Rubin, Guillermo M. Ruiz-Palacios, Lisa Saiman, Laura Sass, Jason B. Sauberan, Peter M. Schantz, Eileen Schneider, Gordon E. Schutze, Benjamin Schwartz, Heidi Schwarzwald, Kara N. Shah, Samir S. Shah, Andi L. Shane, Craig A. Shapiro, Eugene D. Shapiro, Umid M. Sharapov, Jana Shaw, George Kelly Siberry, Jane D. Siegel, Robert David Siegel, Nalini Singh, Upinder Singh, P. Brian Smith, John D. Snyder, David E. Soper, Mary Allen Staat, J. Erin Staples, Jeffrey R. Starke, William J. Steinbach, Ina Stephens, Joseph W. St. Geme, Bradley P. Stoner, Jonathan B. Strober, Kanta Subbarao, Deanna A. Sutton, Douglas Swanson, Leonel T. Takada, Jacqueline E. Tate, Robert V. Tauxe, Marc Tebruegge, Eyasu H. Teshale, George R. Thompson, Herbert A. Thompson, Richard B. Thomson, Emily A. Thorell, Rania A. Tohme, Robert W. Tolan, Philip Toltzis, James Treat, Stephanie B. Troy, Russell B. Van Dyke, Jorge J. Velarde, Jennifer Vodzak, Ellen R. Wald, Geoffrey A. Weinberg, A. Clinton White, Marc-Alain Widdowson, Harold C. Wiesenfeld, John V. Williams, Roxanne E. Williams, Rodney E. Willoughby, Craig M. Wilson, Sarah L. Wingerter, Jerry A. Winkelstein, Kimberly A. Workowski, Terry W. Wright, Pablo Yagupsky, Nada Yazigi, Catherine Yen, Edward J. Young, Andrea L. Zaenglein, and Theoklis E. Zaoutis

Published
2012
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14. Anticonvulsants for alcohol withdrawal

Author

Anastasia Polycarpou, Panagiotis Papanikolau, Despina Contopoulos Ioannidis, and John P. A. Ioannidis

Subjects
medicine.medical_specialty, Benzodiazepine, business.industry, medicine.drug_class, medicine.medical_treatment, Subgroup analysis, Cochrane Library, Placebo, medicine.disease, law.invention, Anticonvulsant, Randomized controlled trial, law, Relative risk, Internal medicine, Alcohol withdrawal syndrome, Medicine, business
Abstract

Background Alcohol withdrawal syndrome is a cluster of symptoms that occurs in alcohol-dependent people after cessation or reduction in alcohol use. This systematic review focuses on the evidence of anticonvulsants' use in the treatment of alcohol withdrawal symptoms. Objectives To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. Search strategy We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2004); MEDLINE (1966 to October 2004); EMBASE (1988 to October 2004) and EU-PSI PSI-Tri database with no language and publication restrictions and references of articles. Selection criteria All randomized controlled trials examining the effectiveness, safety and overall risk-benefit of an anticonvulsant in comparison with a placebo or other pharmacological treatment or another anticonvulsant were considered. Data collection and analysis The authors independently assessed trial quality extracted data. Main results Forty-eight studies, involving 3610 people were included. Despite the considerable number of randomised controlled trials, there was a variety of outcomes and of different rating scales that led to a limited quantitative synthesis of data. For the anticonvulsant versus placebo comparison, therapeutic success tended to be more common among the anticonvulsant-treated patients (relative risk (RR) 1.32; 95% confidence interval (CI) 0.92 to 1.91), and anticonvulsant tended to show a protective benefit against seizures (RR 0.57; 95% CI 0.27 to 1.19), but no effect reached formal statistical significance. For the anticonvulsant versus other drug comparison, CIWA-Ar score showed non-significant differences for the anticonvulsants compared to the other drugs at the end of treatment (weighted mean difference (WMD) -0.73; 95% CI -1.76 to 0.31). For the subgroup analysis of carbamazepine versus benzodiazepine, a statistically significant protective effect was found for the anticonvulsant (WMD -1.04; 95% CI -1.89 to -0.20), p = 0.02), but this was based on only 260 randomised participants. There was a non-significant decreased incidence of seizures (RR 0.50; 95% CI 0.18 to 1.34) favouring the patients that were treated with anticonvulsants than other drugs, and side-effects tended to be less common in the anticonvulsant-group (RR 0.56; 95% CI 0.31 to 1.02). Authors' conclusions It is not possible to draw definite conclusions about the effectiveness and safety of anticonvulsants in alcohol withdrawal, because of the heterogeneity of the trials both in interventions and the assessment of outcomes. The extremely small mortality rate in all these studies is reassuring, but data on other safety outcomes are sparse and fragmented.

Published
2005
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