Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: 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and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ).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 Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients).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 The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.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

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

New insights into Clostridium Difficile (CD) infection in Latin America : Novel description of toxigenic profiles of diarrhea-associated to CD in Bogotá, Colombia

Clostridium difficile (CD) produces antibiotic associated diarrhea and leads to a broad range of diseases. The source of CD infection (CDI) acquisition and toxigenic profile are factors determining the impact of CD. This study aimed at detecting healthcare facility onset- (HCFO) and community-onset (CO) CDI and describing their toxigenic profiles in Bogotá, Colombia. A total of 217 fecal samples from patients suffering diarrhea were simultaneously submitted to two CDI detection strategies: (i) in vitro culture using selective chromogenic medium (SCM; chromID, bioMérieux), followed verification by colony screening (VCS), and (ii) molecular detection targeting constitutive genes, using two conventional PCR tests (conv. PCR) (conv.16S y conv.gdh) and a quantitative test (qPCR.16s). The CD toxigenic profile identified by any molecular test was described using 6 tests independently for describing PaLoc and CdtLoc organization. High overall CDI frequencies were found by both SCM (52.1%) and conv. PCR (45.6% for conv.16S and 42.4% for conv.gdh), compared to reductions of up to half the frequency by VCS (27.2%) or qPCR.16S (22.6%). Infection frequencies were higher for SCM and conv.16S regarding HCFO but greater for CO concerning conv.gdh, such differences being statistically significant. Heterogeneous toxigenic profiles were found, including amplification with lok1/3 primers simultaneously with other PaLoc markers (tcdA, tcdB or tcdC). These findings correspond the first report regarding the differential detection of CDI using in vitro culture and molecular detection tests in Colombia, the circulation of CD having heterogeneous toxigenic profiles and molecular arrays which could affect the impact of CDI epidemiology. © 2018 Muñoz, Ríos-Chaparro, Herrera, Soto-De Leon, Birchenall, Pinilla, Pardo-Oviedo, Josa, Patarroyo and Ramírez

New Insights into Clostridium difficile (CD) Infection in Latin America: Novel Description of Toxigenic Profiles of Diarrhea-Associated to CD in Bogotá, Colombia

Clostridium difficile (CD) produces antibiotic associated diarrhea and leads to a broad range of diseases. The source of CD infection (CDI) acquisition and toxigenic profile are factors determining the impact of CD. This study aimed at detecting healthcare facility onset- (HCFO) and community-onset (CO) CDI and describing their toxigenic profiles in Bogotá, Colombia. A total of 217 fecal samples from patients suffering diarrhea were simultaneously submitted to two CDI detection strategies: (i) in vitro culture using selective chromogenic medium (SCM; chromID, bioMérieux), followed verification by colony screening (VCS), and (ii) molecular detection targeting constitutive genes, using two conventional PCR tests (conv.PCR) (conv.16S y conv.gdh) and a quantitative test (qPCR.16s). The CD toxigenic profile identified by any molecular test was described using 6 tests independently for describing PaLoc and CdtLoc organization. High overall CDI frequencies were found by both SCM (52.1%) and conv.PCR (45.6% for conv.16S and 42.4% for conv.gdh), compared to reductions of up to half the frequency by VCS (27.2%) or qPCR.16S (22.6%). Infection frequencies were higher for SCM and conv.16S regarding HCFO but greater for CO concerning conv.gdh, such differences being statistically significant. Heterogeneous toxigenic profiles were found, including amplification with lok1/3 primers simultaneously with other PaLoc markers (tcdA, tcdB or tcdC). These findings correspond the first report regarding the differential detection of CDI using in vitro culture and molecular detection tests in Colombia, the circulation of CD having heterogeneous toxigenic profiles and molecular arrays which could affect the impact of CDI epidemiology

Predicción espacio-temporal probabilista de la epidemia de dengue total y grave en Colombia

"Objective To establish a new predictive methodology to determine the proportion of severe dengue with respect to the annual total of dengue infections per department based on the probability theory. Materials and Methods Based on annual data on the number of infected persons by department in the period 2005-2010, the proportion of cases of severe dengue was calculated with respect to the total for each year. Probability spaces were constructed to evaluate these events in the ranges 0.5 and 0.3. Sets of ranges were determined and probability, mean square deviation and the difference between them were estimated. A prediction of the range of infected people for 2011 was made using the arithmetic average of the values of the last two years. Results The range in which the proportion of the number of people infected with severe dengue is included with respect to the total amount in each department was correctly predicted, with an effectiveness of 93.3% for the 0.5 range and 86.7% for the 0.3 range. Conclusion A mathematical spatial-temporal self-organization was found in the proportion of severe dengue with respect to the total, which allows establishing useful predictions for decision-making in public health. © 2018, Universidad Nacional de Colombia. All rights reserved.

Predicción espacio-temporal probabilista de la epidemia de dengue total y grave en Colombia

Objective To establish a new predictive methodology to determine the proportion of severe dengue with respect to the annual total of dengue infections per department based on the probability theory. Materials and Methods Based on annual data on the number of infected persons by department in the period 2005-2010, the proportion of cases of severe dengue was calculated with respect to the total for each year. Probability spaces were constructed to evaluate these events in the ranges 0.5 and 0.3. Sets of ranges were determined and probability, mean square deviation and the difference between them were estimated. A prediction of the range of infected people for 2011 was made using the arithmetic average of the values of the last two years. Results The range in which the proportion of the number of people infected with severe dengue is included with respect to the total amount in each department was correctly predicted, with an effectiveness of 93.3% for the 0.5 range and 86.7% for the 0.3 range. Conclusion A mathematical spatial-temporal self-organization was found in the proportion of severe dengue with respect to the total, which allows establishing useful predictions for decision-making in public health. © 2018, Universidad Nacional de Colombia. All rights reserved

Clinical practice guidelines for evidence-based management of sedoanalgesia in critically ill adult patients

Introducción: El óptimo manejo de la sedación, analgesia y delirium ofrece al paciente crítico comodidad y seguridad, facilita el buen desarrollo de medidas de soporte y manejo integral y disminuye complicaciones, impactando en un mejor desenlace. Objetivo: Actualizar la Guía de práctica clínica basada en la evidencia para el manejo de la sedoanalgesia en el paciente adulto críticamente enfermo publicada en Medicina Intensiva en el 2007 y dar recomendaciones para el manejo de la sedación, analgesia y delirium. Metodología: Se reunió un grupo de 21 intensivistas procedentes de 9 países de la Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva, 3 de ellos además especialistas en epidemiología clínica y metodología para elaboración de guías. Se acogió la propuesta del Grading of Recommendations Assessment, Development and Evaluation Working Group para emitir el grado de recomendación y evaluar la calidad de la evidencia. La fuerza de las recomendaciones fue calificada como 1 = fuerte, o 2 = débil, y la calidad de la evidencia como A = alta, B = moderada, o C = baja. Expertos en búsqueda de literatura apoyaron con esta estrategia de búsqueda: MEDLINE a través de PUBMED, bases de datos de la biblioteca Cochrane a través de The Cochrane Library y la base de datos Literatura Latinoamericana y del Caribe en Ciencias de la Salud. Los miembros asignados a las 11 secciones de la guía, basándose en la revisión de la literatura, presentaron las recomendaciones, sustentadas y discutidas en sesiones plenarias, aprobando aquellas que superaron el 80% del consenso. La elaboración de las guías contó con el soporte de la Asociación Colombiana de Medicina Crítica y Cuidado Intensivo. Resultados: Para la elaboración de la guía fueron finalmente seleccionadas 467 referencias, observándose un importante aumento en el número y calidad de los estudios, permitiendo realizar 64 fuertes recomendaciones con evidencia alta y moderada, contrastando con las 28 de la edición anterior. Conclusiones: Esta guía contiene recomendaciones y sugerencias basadas en la mejor evidencia para el manejo de la sedación, analgesia y delirium del paciente crítico, incluyendo un paquete de medidas (bundle). Se destacan: evaluación del dolor y la agitación/sedación mediante escalas; usar inicialmente opioides para el control de la analgesia, adicionando técnicas multimodales para disminuir consumo de opioides; promover el menor nivel de sedación necesario, evitando la sobresedación; en caso de requerir medicamentos sedantes, escoger el más apropiado, evitando el uso rutinario de benzodiazepinas; por último, identificar factores de riesgo para delirium, prevenirlo, diagnosticarlo y manejarlo, con el medicamento más conveniente, ya sea haloperidol, antipsicóticos atípicos o dexmedetomidina, evitando el uso de benzodiazepinas y disminuyendo el uso de opioides. © 2013 Elsevier España, S.L. y SEMICYUC. Todos los derechos reservadosIntroduction: Optimal management of sedation, analgesia and delirium offers comfort and security for the critical care patient, allows support measures to be applied more easily and enables an integral approach of medical care, at the same time that lowers the incidence of complications, wich translates in better patient outcomes. Objective: To update the Guía de práctica clínica basada en la evidencia para el manejo de la sedoanalgesia en el paciente adulto críticamente enfermo published in Medicina Intensiva in 2007, and give recommendations for the management of sedation, analgesia, and delirium. Methodology: A group of 21 intensivists from 9 countries of the Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva, 3 of them also specialists in clinical epidemiology and methodology, gathered for the development of guidelines. Assessment of evidence quality and recommendations were made based on the Grading of Recommendations Assessment, Development and Evaluation system. Strength of recommendations was classified as 1. =. strong, or 2. =. weak, and quality of evidence as A. =. high, B. =. moderate, or C. =. low. Two authors searched the following databases: MEDLINE through PUBMED, The Cochrane Library and Literatura Latinoamericana y del Caribe en Ciencias de la Salud and retrieved pertinent information. Members assigned to the 11 sections of the guidelines, based on the literature review, formulated the recommendations, that were discussed in plenary sessions. Only those recommendations that achieved more than 80% of consensus were approved for the final document. The Colombian Association of Critical Medicine and Intensive Care (AMCI) supported the elaboration of this guidelines. Results: Four hundred sixty-seven articles were included for review. An increase in number and quality of publications was observed. This allowed to generate 64 strong recommendations with high and moderate quality of evidence in contrast to the 28 recommendations of the previous edition. Conclusions: This Guidelines contains recommendations and suggestions based on the best evidence available for the management of sedation, analgesia and delirium of the critically ill patient, including a bundle of strategies that serves this purpose. We highlight the assessment of pain and agitation/sedation through validated scales, the use of opioids initially to apropiate analgesic control, associated with multimodal strategies in order to reduce opioide consumption; to promote the lowest level of sedation necessary avoiding over-sedation. Also, in case of the need of sedatives, choose the most appropiate for the patient needs, avoiding the use of benzodiazepines and identify risk factors for delirium, in order to prevent its occurrence, diagnose delirium and treat it with the most suitable pharmacological agent, whether it is haloperidol, atypical antipsychotics or dexmedetomidine, once again, avoiding the use of benzodiazepines and decreasing the use of opioids. © 2013 Elsevier España, S.L. y SEMICYUC

Evidence-based clinical practice guidelines for the management of sedoanalgesia and delirium in critically ill adult patients

Dada la importancia del manejo de la sedación, analgesia y delirium en las unidades de cuidados intensivos, y con el fin de actualizar las guías publicadas anteriormente, se decidió elaborar una nueva guía de práctica clínica con los soportes, manejos e intervenciones más relevantes acordes con las publicaciones recientes. Para elaborar esta guía, se reunió un grupo de 24 intensivistas procedentes de 9 países de la Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva. Se acogió la propuesta del Grading of Recommendations Assessment, Development and Evaluation Working Group para emitir el grado de recomendación y evaluar la calidad de la evidencia. Se realizó una búsqueda sistemática de la literatura utilizándose: MEDLINE, las siguientes bases de datos de la biblioteca Cochrane: Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects, National Health Service Economic Evaluation Database, y la base de datos de Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS). Finalmente, se seleccionaron 438 referencias, permitiendo realizar 47 recomendaciones fuertes con evidencia alta y moderada, 14 recomendaciones condicionales con evidencia moderada y 65 recomendaciones condicionales con evidencia baja. Se confirma la importancia del manejo inicial y multimodal del dolor, se hace énfasis en la disminución de los niveles de sedación y la utilización de sedación profunda solo en casos específicos. Aumenta la evidencia y recomendaciones para el uso de medicamentos como dexmedetomidina, remifentanil, ketamina, entre otros.Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new clinical practice guide is presented, addressing the most relevant management and intervention aspects based on the recent literature. A group of 24 intensivists from 9 countries of the Pan-American and Iberian Federation of Societies of Critical Medicine and Intensive Therapy met to develop the guidelines. Assessment of evidence quality and recommendations was made according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. A systematic search of the literature was carried out using MEDLINE, Cochrane Library databases such as the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects, the National Health Service Economic Evaluation Database and the database of Latin American and Caribbean Literature in Health Sciences (LILACS). A total of 438 references were selected. After consensus, 47 strong recommendations with high and moderate quality evidence, 14 conditional recommendations with moderate quality evidence, and 65 conditional recommendations with low quality evidence were established. Finally, the importance of initial and multimodal pain management was underscored. Emphasis was placed on decreasing sedation levels and the use of deep sedation only in specific cases. The evidence and recommendations for the use of drugs such as dexmedetomidine, remifentanil, ketamine and others were incremented. © 2019 Elsevier España, S.L.U. y SEMICYU

Additional file 2 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Additional file 2. Email invitation