Leveraging vibration of effects analysis for robust discovery in observational biomedical data science.

Hypothesis generation in observational, biomedical data science often starts with computing an association or identifying the statistical relationship between a dependent and an independent variable. However, the outcome of this process depends fundamentally on modeling strategy, with differing strategies generating what can be called "vibration of effects" (VoE). VoE is defined by variation in associations that often lead to contradictory results. Here, we present a computational tool capable of modeling VoE in biomedical data by fitting millions of different models and comparing their output. We execute a VoE analysis on a series of widely reported associations (e.g., carrot intake associated with eyesight) with an extended additional focus on lifestyle exposures (e.g., physical activity) and components of the Framingham Risk Score for cardiovascular health (e.g., blood pressure). We leveraged our tool for potential confounder identification, investigating what adjusting variables are responsible for conflicting models. We propose modeling VoE as a critical step in navigating discovery in observational data, discerning robust associations, and cataloging adjusting variables that impact model output.

Mortality in patients admitted to intensive care with COVID-19: an updated systematic review and meta-analysis of observational studies.

The COVID-19 pandemic continues to cause critical illness and deaths internationally. Up to 31 May 2020, mortality in patients admitted to intensive care units (ICU) with COVID-19 was 41.6%. Since then, changes in therapeutics and management may have improved outcomes. Also, data from countries affected later in the pandemic are now available. We searched MEDLINE, Embase, PubMed and Cochrane databases up to 30 September 2020 for studies reporting ICU mortality among adult patients with COVID-19 and present an updated systematic review and meta-analysis. The primary outcome measure was death in intensive care as a proportion of completed ICU admissions, either through discharge from intensive care or death. We identified 52 observational studies including 43,128 patients, and first reports from the Middle East, South Asia and Australasia, as well as four national or regional registries. Reported mortality was lower in registries compared with other reports. In two regions, mortality differed significantly from all others, being higher in the Middle East and lower in a single registry study from Australasia. Although ICU mortality (95%CI) was lower than reported in June (35.5% (31.3-39.9%) vs. 41.6% (34.0-49.7%)), the absence of patient-level data prevents a definitive evaluation. A lack of standardisation of reporting prevents comparison of cohorts in terms of underlying risk, severity of illness or outcomes. We found that the decrease in ICU mortality from COVID-19 has reduced or plateaued since May 2020 and note the possibility of some geographical variation. More standardisation in reporting would improve the ability to compare outcomes from different reports.

Association of body mass index (BMI) with critical COVID-19 and in-hospital mortality: A dose-response meta-analysis.

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented health crisis to the entire world. As reported, the body mass index (BMI) may play an important role in COVID-19; however, this still remains unclear. The aim of this study was to explore the association between BMI and COVID-19 severity and mortality. METHODS: The Medline, PubMed, Embase and Web of science were systematically searched until August 2020. Random-effects models and dose-response meta-analysis were used to synthesize the results. Combined odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated, and the effect of covariates were analyzed using subgroup analysis and meta-regression analyses. RESULTS: A total of 16 observational studies involving 109,881 patients with COVID-19 were included in the meta-analysis. The pooled results showed that patients with a BMI ≥ 30 kg/m2 had a 2.35-fold risk (OR = 2.35, 95%CI = 1.64-3.38, P < 0.001) for critical COVID-19 and a 2.68-fold risk for COVID-19 mortality (OR = 2.68, 95%CI = 1.65-4.37, P < 0.001) compared with patients with a BMI <30 kg/m2. Subgroup analysis results showed that patients with obesity and age > 60 years was associated with a significantly increased risk of critical COVID-19 (OR = 3.11, 95%CI = 1.73-5.61, P < 0.001) and COVID-19 mortality (OR = 3.93, 95%CI = 2.18-7.09, P < 0.001). Meta-regression analysis results also showed that age had a significant influence on the association between BMI and COVID-19 mortality (Coef. = 0.036, P = 0.048). Random-effects dose-response meta-analysis showed a linear association between BMI and both critical COVID-19(Pnon-linearity = 0.242) and mortality (Pnon-linearity = 0.116). The risk of critical COVID-19 and mortality increased by 9%(OR = 1.09, 95%CI = 1.04-1.14, P < 0.001) and 6%(OR = 1.06, 95%CI = 1.02-1.10, P = 0.002) for each 1 kg/m2 increase in BMI, respectively. CONCLUSIONS: Evidence from this meta-analysis suggested that a linear dose-response association between BMI and both COVID-19 severity and mortality. Further, obesity (BMI ≥ 30 kg/m2) was associated with a significantly increased risk of critical COVID-19 and in-hospital mortality of COVID-19.

Clinical research in hospital pharmacy during the fight against COVID-19.

The health crisis resulting from the rapid spread of SARS-CoV-2 worlwide, added to the low evidence of currently used treatments has led to the development of a large number of clinical trials (CT) and observational studies. Likewise,  important measures have been adopted in healthcare and research centers  aimed at halting the pandemic as soon as possible. The objective of this study is  to gather the main aspects of the clinical research studies undertaken by the  Departments of Hospital Pharmacy (DHP) of Spain during the COVID-19 crisis. The decision of the Spanish Society of Hospital Pharmacy (SEFH) to sponsor CTs made it possible that 13% of DHP had been led at least one CT.  The Spanish Agency for Medicines and Medical Devices (AEMPS), in coordination  with Institutional Review Boards, has adopted a fast-track review procedure to  accelerate authorizations for CTs related to the treatment or prevention of  COVID-19. There have also been numerous public and private calls for financing  research projects aimed at contributing to the fight against this virus. Despite  the pandemic, actions have been taken to continue ongoing CTs and studies  while the safety and well-being of patients are guaranteed. More specifically, the AEMPS and the European Medicines Agency (EMA) have issued guidelines that  incorporate changes to CT protocols that will have to be applied until the  pandemic is over. In this health emergency, the scientific community has found  itself in a race against time to generate evidence. It is at this moment that  hospital pharmacists emerge as key players in clinical research and are  contributing to a rational, effective and safe healthcare decision-making.

La presente crisis sanitaria derivada de la rápida expansión del virus SARS-CoV- 2 a nivel mundial, así como la falta de evidencia de los tratamientos empleados  actualmente, ha provocado la aparición de un gran número de ensayos clínicos y estudios observacionales. Del mismo modo, ha ocasionado la puesta en marcha  de importantes medidas en el entorno sanitario e investigador con el fin de  conseguir detener la evolución de la pandemia lo antes posible. El objetivo del  actual trabajo es recopilar aspectos fundamentales relacionados con la  investigación clínica desarrollada por los servicios de farmacia hospitalaria  durante la crisis provocada por la COVID-19. La iniciativa de la Sociedad  Española de Farmacia Hospitalaria de actuar como promotor de ensayos clínicos  ha posibilitado que el 13% de estos servicios de farmacia hospitalaria haya  podido liderar uno. En este sentido, la Agencia Española de Medicamentos y  Productos Sanitarios, junto con los Comités de Ética de Investigación, ha  acelerado los procedimientos de autorización de nuevos ensayos clínicos  destinados a tratar o prevenir la COVID-19. Asimismo, han sido numerosas las  convocatorias públicas y privadas destinadas a la financiación de proyectos de  diversa índole con el fin de contribuir a la lucha contra este virus. A pesar de la  irrupción de la pandemia, también han surgido acciones destinadas a mantener  las actividades de los ensayos clínicos y estudios puestos previamente en  marcha, garantizando la seguridad y bienestar del paciente. Concretamente, la  Agencia Española de Medicamentos y Productos Sanitarios y la Agencia Europea  de Medicamentos han publicado guías que incluyen cambios en los protocolos de los ensayos clínicos que deben mantenerse mientras dure la pandemia. La  emergencia sanitaria actual ha obligado a la comunidad científica a la generación de evidencia a contrarreloj. Por ello, en este momento en el que se requiere del  mayor rigor posible, el farmacéutico de hospital debe alzarse como una figura  clave en la investigación en salud, contribuyendo a que las decisiones sanitarias  sean racionales, eficientes y seguras.