Estudio comparativo de métodos de estimación en un modelo no lineal mixto

n.d.Fil: Garcia, María del Carmen - Facultad Ciencias Económicas y Estadística - Universidad Nacional de Rosario- Argentin

Effect of Colchicine vs Usual Care Alone on Intubation and 28-Day Mortality in Patients Hospitalized with COVID-19: A Randomized Clinical Trial

Importance Hospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality. Objective To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia. Design, Setting, and Participants The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription–polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021. Interventions Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine. Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first. Main Outcomes and Measures The first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days. Results A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%) in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%). Conclusions and Relevance This randomized clinical trial found that compared with usual care, colchicine did not significantly reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia.Fil: Diaz, Rafael. Estudios Clínicos Latino América; Argentina. Instituto Cardiovascular de Rosario; ArgentinaFil: Orlandini, Andrés. Estudios Clínicos Latino América; Argentina. Instituto Cardiovascular de Rosario; ArgentinaFil: Castellana, Noelia. Estudios Clínicos Latino América; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Caccavo, Alberto. Provincia de Buenos Aires. Dirección General de Cultura y Educación. Universidad Provincial del Sudoeste; ArgentinaFil: Corral, Pablo. Universidad FASTA "Santo Tomas de Aquino"; ArgentinaFil: Corral, Gonzalo. Infectología Clínica de Mayo; ArgentinaFil: Chacón, Carolina. Estudios Clínicos Latino América; Argentina. Universidad Abierta Interamericana; Argentina. Unidad Coronaria de Sanatorio Delta de Rosario; Argentina. Comite de Epidemiologia y Prevención Cardiovascular de la Federación Argentina de Cardiologia; ArgentinaFil: Lamelas, Pablo. McMaster University; Canadá. Instituto Cardiovascular de Buenos Aires; ArgentinaFil: Botto, Fernando. Instituto Cardiovascular de Buenos Aires; ArgentinaFil: Díaz, María Luz. Estudios Clínicos Latino América; Argentina. Instituto Cardiovascular de Rosario; ArgentinaFil: Domínguez, Juan Manuel. Estudios Clínicos Latino América; Argentina. Instituto Cardiovascular de Rosario; ArgentinaFil: Pascual, Andrea. Estudios Clínicos Latino América; ArgentinaFil: Rovito, Carla. Estudios Clínicos Latino América; ArgentinaFil: Galatte, Agustina. Estudios Clínicos Latino América; ArgentinaFil: Scarafia, Franco. Estudios Clínicos Latino América; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Sued, Omar. Fundación Huésped; ArgentinaFil: Gutierrez, Omar. Ministerio de Salud de Jujuy; ArgentinaFil: Jolly, Sanjit S.. McMaster University; CanadáFil: Miró, José M.. Universidad de Barcelona; EspañaFil: Eikelboom, John. McMaster University; CanadáFil: Loeb, Mark. McMaster University; CanadáFil: Maggioni, Aldo Pietro. Associazione Nazionale Medici Cardiologi Ospedalieri Research Center; ItaliaFil: Bhatt, Deepak L.. Brigham and Women’s Hospital; Estados Unidos. Harvard Medical School; Estados UnidosFil: Yusuf, Salim. McMaster University; CanadáFil: Lopez, Lorena. No especifíca;Fil: Leon de la Fuente, Ricardo Alfonso. Gobierno de la Provincia de Salta. Ministerio de Salud Pública. Hospital Papa Francisco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Forciniti, Cristian C. G.. No especifíca;Fil: Colombo, Hugo. No especifíca;Fil: Sabas, Nicolas. No especifíca;Fil: Pilón, Leonardo. No especifíca;Fil: Steren, Adriana P.. No especifíca

Safety and Effectiveness of COVID-19 Vaccines During Pregnancy: A Living Systematic Review and Meta-analysis.

BACKGROUND: Pregnant persons are susceptible to significant complications following COVID-19, even death. However, worldwide COVID-19 vaccination coverage during pregnancy remains suboptimal. OBJECTIVE: This study assessed the safety and effectiveness of COVID-19 vaccines administered to pregnant persons and shared this evidence via an interactive online website. METHODS: We followed Cochrane methods to conduct this living systematic review. We included studies assessing the effects of COVID-19 vaccines in pregnant persons. We conducted searches every other week for studies until October 2023, without restrictions on language or publication status, in ten databases, guidelines, preprint servers, and COVID-19 websites. The reference lists of eligible studies were hand searched to identify additional relevant studies. Pairs of review authors independently selected eligible studies using the web-based software COVIDENCE. Data extraction and risk of bias assessment were performed independently by pairs of authors. Disagreements were resolved by consensus. We performed random-effects meta-analyses of adjusted relative effects for relevant confounders of comparative studies and proportional meta-analyses to summarize frequencies from one-sample studies using R statistical software. We present the GRADE certainty of evidence from comparative studies. Findings are available on an interactive living systematic review webpage, including an updated evidence map and real-time meta-analyses customizable by subgroups and filters. RESULTS: We included 177 studies involving 638,791 participants from 41 countries. Among the 11 types of COVID-19 vaccines identified, the most frequently used platforms were mRNA (154 studies), viral vector (51), and inactivated virus vaccines (17). Low to very low-certainty evidence suggests that vaccination may result in minimal to no important differences compared to no vaccination in all assessed maternal and infant safety outcomes from 26 fewer to 17 more events per 1000 pregnant persons, and 13 fewer to 9 more events per 1000 neonates, respectively. We found statistically significant reductions in emergency cesarean deliveries (9%) with mRNA vaccines, and in stillbirth (75-83%) with mRNA/viral vector vaccines. Low to very low-certainty evidence suggests that vaccination during pregnancy with mRNA vaccines may reduce severe cases or hospitalizations in pregnant persons with COVID-19 (72%; 95% confidence interval [CI] 42-86), symptomatic COVID-19 (78%; 95% CI 21-94), and virologically confirmed SARS-CoV-2 infection (82%; 95% CI 39-95). Reductions were lower with other vaccine types and during Omicron variant dominance than Alpha and Delta dominance. Infants also presented with fewer severe cases or hospitalizations due to COVID-19 and laboratory-confirmed SARS-CoV-2 infection (64%; 95% CI 37-80 and 66%; 95% CI 37-81, respectively). CONCLUSIONS: We found a large body of evidence supporting the safety and effectiveness of COVID-19 vaccines during pregnancy. While the certainty of evidence is not high, it stands as the most reliable option available, given the current absence of pregnant individuals in clinical trials. Results are shared in near real time in an accessible and interactive format for scientists, decision makers, clinicians, and the general public. This living systematic review highlights the relevance of continuous vaccine safety and effectiveness monitoring, particularly in at-risk populations for COVID-19 impact such as pregnant persons, during the introduction of new vaccines. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42021281290

Criterios de información y predictivos para la selección de un modelo lineal mixto

En los estudios longitudinales las unidades experimentales se observan repetidamente en varias ocasiones. Una herramienta importante para el análisis de este tipo de datos son los modelos lineales mixtos que permiten modelar las múltiples mediciones de la variable respuesta en función de las covariables y la correlación entre las mismas. La construcción de este tipo de modelos comprende la elección de covariables, la determinación del número de efectos aleatorios y fijos, y la especificación de la estructura de correlación del error aleatorio. Para la selección del modelo “óptimo” existe una amplia gama de criterios de información y predictivos. Los valores que proporcionan los paquetes estadísticos usan para calcularlos la formulación marginal del modelo, priorizando la inferencia sobre los parámetros poblacionales. Sin embargo, algunos autores argumentan que los efectos aleatorios individuales a menudo son de interés e introducen las versiones condicionales de los mismos. El propósito de este trabajo es presentar algunos de estos criterios tanto en su versión marginal como condicional e ilustrar su uso con datos provenientes de la Encuesta Permanente de Hogares. En la aplicación se observa que el desempeño de los mismos es disímil en términos de su comportamiento de elección

Una introducción al problema de covariables que varían en el tiempo en modelos mixtos

Los estudios longitudinales están conformados por datos obtenidos midiendo repetidamente una variable respuesta a la misma unidad. En este tipo de estudios es también frecuente contar con variables explicativas que se desean incorporar al análisis. Estas covariables pueden ser fijas a lo largo de todo el período (por ejemplo el sexo biológico de una persona) o bien puedan variar a lo largo del seguimiento (por ejemplo el valor de colesterol). Los modelos lineales mixtos permiten analizar este tipo de datos, modelando, por un lado, la evolución de la respuesta promedio en función del tiempo y las covariables, mediante efectos fijos, y, por otro lado, la variación entre las respuestas repetidas dentro y entre sujetos por medio del error y los efectos aleatorios, respectivamente. Este tipo de covariables que varían en el tiempo pueden utilizarse para comparar poblaciones, para describir tendencias en el tiempo, y también para describir relaciones dinámicas con la variable respuesta. La relación entre la covariable que varía en el tiempo y la variable respuesta puede estar confundida por valores anteriores y/o posteriores de la covariable y en consecuencia esto puede conducir a inferencias engañosas sobre los pará-metros del modelo. Este estudio realiza una introducción a la problemática de incorporar cova-riables que varían con el tiempo en modelos para datos longitudinales, presentando diferentes definiciones de las mismas y enfoques metodológicosLongitudinal studies involve the collection of the same response variable repeatedly over time from the same subject/unit. In these types of studies it is also frequent to have explanatory vari-ables that could be incorporated into the analysis. These covariates can be time-independent (for example, the biological sex of a person) or they can vary throughout the follow-up (for example, the cholesterol value) and are denominated as time-varying covariates Mixed effects linear models allow analyzing this type of data, modeling separately the evolution of the average response (as a function of time and covariates through fixed effects) and the repeated response variation between and within subjects (through the error and random effects). Time-varying co-variates can be used to make comparisons across populations, to describe different time trends, and also to describe dynamic relationship with the response variable. The relationship between the time-varying covariate and the response variable may be confused by preceding and/or subsequent covariate values and therefore, misleading inferences about the model parameters can result. This study makes an introduction to the problem of time-varying covariates in longi-tudinal studies, presenting different definitions and methodological approaches.Fil:Castellana, Noelia, Facultad Ciecias Económicas y Estadística de Rosario, Universidad Nacional de Rosario, ArgentinaFil: Cometo, Esteban, Facultad Ciecias Económicas y Estadística de Rosario, Universidad Nacional de Rosario, ArgentinaFil: Rapelli, Cecilia, Facultad Ciecias Económicas y Estadística de Rosario, Universidad Nacional de Rosario, ArgentinaFil: García María del Carmen Eva, Facultad Ciecias Económicas y Estadística de Rosario, Universidad Nacional de Rosario, Argentin

Diagnósticos de influencia para los modelos lineales mixtos

En este trabajo se presentan varios enfoques para detectar unidades que tienen una magnitud distinta al resto y el efecto que producen sobre los estimadores de los parámetros del modelo. La idea general de los métodos de influencia global y local es introducir cambios en las componentes del modelo y evaluar si se producen cambios importantes en los resultados. El procedimiento comienza detectando los casos atípicos mediante la distancia de verosimilitud. Posteriormente, se descomponen los hallazgos iniciales para determinar si realmente esos casos afectan el proceso de estimación. Si esta medida general sugiere que existen unidades influyentes se tienen que determinar, a posteriori, los elementos del modelo que son influenciados. Los gráficos TRSS, que fueron propuestos recientemente, no eliminan las unidades ni alteran el modelo para identificar las unidades discordantes. El método proporciona una mayor información sobre las mediciones repetidas mediante la utilización de residuos modificados y evalúa eficazmente el efecto de unidades y observaciones discordantes en la estimación de parámetros que incluyen componentes de la variancia. Considerar unidades como influyentes no implica eliminarlas del conjunto o cambiar el modelo, pues, si los puntos afectan los efectos fijos sin ejercer demasiada influencia sobre la precisión de los parámetros de covariancia, su presencia no alterará ni las pruebas de hipótesis ni los intervalos de confianza para los parámetros de efectos fijos. Los diagnósticos de los efectos fijos utilizan una matriz de covariancias especificada para los datos, así su influencia sobre las componentes de variancia se deberían examinar primero. En la aplicación se muestra que: • Influencia global y local: los diagnósticos ayudan a detectar pacientes atípicos mediante la inspección de la distancia de verosimilitud. Sin embargo, algunas unidades que se presentaron con valores altos de la distancia de verosimilitud restringida resultan tener mayor efecto sobre los efectos fijos y otras casi sin impacto sobre los efectos fijos se muestran principalmente influyentes sobre los estimadores puntuales de covariancia. • Gráficos TRSS: detectan en general las mismas unidades que los métodos anteriores. Sin embargo, ayudan a identificar unidades con trayectorias o posiblemente con estructuras de correlación diferentes al restoMixed linear models are suitable for modeling longitudinal data. The parameter estimation of these models is performed using methods that are based on the likelihood function which are sensitive to unusual units. The influence analysis aims to detect observations/units that may produce excessive influence in the parameters estimates, in order to develop a more suitable model. The analysis is performed by introducing changes to the model components and assessing whether significant changes in the results are produced. One approach to assess the influence is the deletion case diagnosis that evaluates the effect of a unit, removing it from the dataset. This technique is considered as a global influence analysis. Another approach, the local influence, investigates the effect of introducing small perturbations in the model components on the parameter estimation. Its usage allows determining the causes for which atypical units are influential. A new diagnostic method based on studentized residual sum of squares plots allows the detection of discordant units without omitting them. In this paper, these approaches are compared considering data from a clinical trial which was designed to evaluate the cardiac safety of a new drug.Fil: Garcia, María del Carmen Facultad Ciencias Económicas y Estadística; Universidad Nacional de Rosario; Argentin

Evaluación del comportamiento de los estimadores de los parámetros de un modelo no lineal mixto. Una comparación de métodos de estimación.

n.d.Chiapella, Luciana; Facultad de Ciencias Económicas y Estadística; Universidad Nacional de Rosario; Argentina

Risk of cardiovascular events associated with positive serology for Chagas: a systematic review

BACKGROUND: Chagas disease affects mainly poor populations in Latin America. This review assesses the evidence on the independent risk of cardiovascular events associated with positive Chagas serology. METHODS: We searched for studies using the following outcomes: death, stroke, new onset heart failure, heart failure hospitalization or evidence of left ventricular dysfunction. Studies comparing patients with positive serology for Chagas with a control group with a follow-up longer than 1 year were selected. The Medline, Lilacs and Embase databases were searched on 21 January 2011 without restrictions. RESULTS: From 5236 potentially relevant studies, 25 fulfilled the inclusion criteria. Fourteen included patients with heart failure, six with severe symptoms and nine with mild symptoms or asymptomatic patients with low ejection fraction. In four studies of patients in functional class III or IV and in three studies of patients with mild symptoms, a higher risk of death was reported among those with positive serology for Chagas. Of the 11 studies of patients without symptoms or low ejection fraction, 3 showed a higher risk of mortality related to Chagas exposure. Two of these were based on the same cohort of people aged \u3e60 years. Overall, 8 out of the 14 heart failure studies and 2 out of the 11 heart damage studies adjusted for confounding factors. CONCLUSION: Positive serology for Chagas is associated with a higher risk of death for patients with heart failure. However, there is little evidence to link positive serology for Chagas with cardiovascular events in asymptomatic subjects

Prevalence, awareness, treatment and control of hypertension in rural and urban communities in Latin American countries

Objectives: The objective is to describe hypertension (HTN) prevalence, awareness, treatment and control in urban and rural communities in Latin America to inform public and policy-makers. Methods: Cross-sectional analysis from urban (n=111) and rural (n=93) communities including 33 276 participants from six Latin American countries (Argentina, Brazil, Chile, Colombia, Peru and Uruguay) were included. HTN was defined as self-reported HTN on blood pressure (BP) medication or average BP over 140/90 mmHg, awareness as self-reported HTN, and controlled as those with BP under 140/90 mmHg. Results: Mean age was 52 years, 60% were Female and 32% belonged to rural communities. HTN prevalence was 44.0%, with the lowest rates in Peru (17.7%) and the highest rates in Brazil (52.5%). 58.9% were aware of HTN diagnosis and 53.3% were receiving treatment. Prevalence of HTN were higher in urban (44.8%) than rural (42.1%) communities in all countries. Most participants who were aware of HTN were receiving medical treatment (90.5%), but only 37.6% of patients receiving medical treatment had their BP controlled (<140/<90 mmHg), with the rates being higher in urban (39.6%) than in rural (32.4%) communities. The rate of use of two or more drugs was low [36.4%, lowest in Argentina (29.6%) and highest in Brazil (44.6%)]. Statin use was low (12.3%), especially in rural areas (7.0%). Most modifiable risk factors were higher in people with HTN than people without HTN. Conclusion: HTN prevalence is high but BP control is low in Latin America, with marked differences between countries and between urban and rural settings. There is an urgent need for systematic approaches for better detection, treatment optimization and risk factor modification among those with HTN in Latin America.Fil: Lamelas, Pablo. The Population Health Research Institute; CanadáFil: Diaz, Rafael. No especifíca;Fil: Orlandini, Andres. No especifíca;Fil: Avezum, Alvaro. No especifíca;Fil: Oliveira, Gustavo. No especifíca;Fil: Mattos, Antonio. No especifíca;Fil: Lanas, Fernando. Universidad de La Frontera; ChileFil: Seron, Pamela. Universidad de La Frontera; ChileFil: Oliveros, Maria J.. Universidad de La Frontera; ChileFil: Lopez Jaramillo, Patricio. Fundación Oftalmológica de Santander; ColombiaFil: Otero, Johanna. Fundación Oftalmológica de Santander; ColombiaFil: Camacho, Paul. Fundación Oftalmológica de Santander; ColombiaFil: Miranda, Jaime. Cronicas Centro de Excelencia En Enfermedades Crónicas; PerúFil: Bernabe Ortiz, Antonio. Centro de Excelencia En Enfermedades Crónicas; PerúFil: Malaga, German. No especifíca;Fil: Irazola, Vilma. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gutierrez, Laura. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Castellana, Noelia. No especifíca;Fil: Rangarajan, Sumathy. Population Health Research Institute; CanadáFil: Yusuf, Salim. Population Health Research Institute; Canad