scholarly journals COVID-19 Associated Pulmonary Aspergillosis: Systematic Review and Patient-Level Meta-Analysis

2021 ◽  
Author(s):  
Ruwandi M. Kariyawasam ◽  
Tanis C. Dingle ◽  
Brittany E. Kula ◽  
Wendy I. Sligl ◽  
Ilan S. Schwartz
Keyword(s):  
Cohort Studies ◽  
Excess Mortality ◽  
Meta Analysis ◽  
Case Series ◽  
Rank Test ◽  
Pulmonary Aspergillosis ◽  
Exact Test ◽  
Patient Level ◽  
Level Data ◽  
Antifungal Use

Rationale Pulmonary aspergillosis may complicate COVID-19 and contribute to excess mortality in intensive care unit (ICU) patients. The incidence is unclear because of discordant definitions across studies. Objective We sought to review the incidence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA), and compare research definitions. Methods We systematically reviewed the literature for ICU cohort studies and case series including ≥3 patients with CAPA. We calculated pooled incidence. Patients with sufficient clinical details were reclassified according to 4 standardized definitions (Verweij, White, Koehler, and Bassetti). Measurements Correlations between definitions were assessed with Spearmans rank test. Associations between antifungals and outcome were assessed with Fishers Exact test. Main Results 38 studies (35 cohort studies and 3 case series) were included. Among 3,297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (pooled incidence 9.5%). 197 patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ=0.330 to 0.621, p<0.001). 38.6% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 9 days (interquartile range 5-14) in ICUs. Tracheobronchitis occured in 5.3% of patients examined with bronchoscopy. The mortality rate (50.0%) was high, irrespective of antifungal use (p=0.28); this remained true even when the analysis was restricted to patients meeting standardized definitions for CAPA. Conclusions The reported incidence of CAPA is exaggerated by use of non-standard definitions. Further research should focus on identifying patients likely to benefit from antifungals.

scholarly journals ODACH: A One-shot Distributed Algorithm for Cox model with Heterogeneous Multi-center Data

2021 ◽  
Author(s):  
Chongliang Luo ◽  
Rui Duan ◽  
Yong Chen
Keyword(s):  
Likelihood Function ◽  
Cox Model ◽  
Meta Analysis ◽  
Event Data ◽  
Time To Event ◽  
Hazard Functions ◽  
Patient Level ◽  
Time To Event Data ◽  
Level Data ◽  
Center Time

Objective: We developed and evaluated a privacy-preserving One-shot Distributed Algorithm for Cox model to analyze multi-center time-to-event data without sharing patient-level information across sites, while accounting for heterogeneity across sites by allowing site-specific baseline hazard functions and feature distributions. Materials and Methods: We constructed a surrogate likelihood function to approximate the Cox log partial likelihood function which is stratified by site, using patient-level data from a single site and aggregated information from other sites. The ODAC estimator was obtained by maximizing the surrogate likelihood function. We evaluated and compare the performance of ODACH with meta-analysis by extensive numerical studies. Results: The simulation study showed that ODACH provided estimates close to the pooled estimator, which is obtained by directly analyzing patient-level data from all sites via a stratified Cox model. The relative bias was <1% across all scenarios. As a comparison, the meta-analysis estimator, which was obtained by the inverse variance weighted average of the site-specific estimates, had substantial bias when the event rate is <5%, with the relative bias reaching 12% when the event rate is 1%. Conclusions: ODACH is a privacy-preserving and communication-efficient method for analyzing multi-center time-to-event data, which allows the baseline hazard functions as well as the distribution of covariate variables to vary across sites. It provides estimates that is close to the pooled estimator and substantially outperforms the meta-analysis estimator when the event is rare. It is thus extremely suitable for studying rare events with heterogeneous baseline hazards across sites in a distributed manner.

Abstract 17059: Re-Use of Clinical Trial Data From the NHLBI Data Repository (BioLINCC) for Patient-Level Meta-Analyses of Cardiovascular Outcomes: Challenges and Opportunities

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Helena Sviglin ◽  
Gauri Dandi ◽  
Eileen Navarro Almario ◽  
Tejas Patel ◽  
Colin O Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Cardiovascular Outcomes ◽  
Data Repository ◽  
Common Data Elements ◽  
Patient Level Data ◽  
Patient Level ◽  
Level Data ◽  
Data Elements ◽  
Meta Analyses

Introduction: An objective of the Meta-AnalyTical Interagency Group (MATIG) is to conduct patient-level meta-analyses of cardiovascular outcomes using data from publicly available repositories. We describe challenges with data re-use from a seminal trial, provide a systematic approach to identify and curate data elements for hypothesis generation, and establish stackable trials to support these analyses. Methods: We used data from the ACCORD trial to assess risk factors and their gender specific differences for the event of hospitalization or death due to heart failure (hdHF), in patients with type 2 diabetes*. We identified the data elements needed to answer the research questions, reviewed the trial protocol to verify definitions, extracted patient-level data, performed quality assessment and statistical analysis. The results showed a gender difference in the effect of intensive vs. standard glucose-lowering therapy on hdHF. To validate the findings, we sought additional trials in BioLINCC to develop a compendium for meta-analysis, and repeated these steps for each trial. Results: Challenges for reusing the ACCORD trial included access to complete patient-level data and metadata. The compendium, developed to evaluate the stackability** of data across trials, identified differences in trial designs, patient populations, study interventions, and data elements that may impact the feasibility and interpretation of meta-analysis. An example of compendium components is shown in Table 1. Conclusion: High-quality metadata facilitate re-use of trial repository data. This compendium standardizes common data elements for gender, racial and age-group specific outcome assessment in major clinical trials. It provides the framework to assess the fitness of trials for patient-level meta-analyses. Efforts are underway by MATIG to expand the compendium to include risk factors and major cardiovascular outcomes across multiple large trials for meta-analysis.

Type and intensity of FVIII exposure on inhibitor development in PUPs with haemophilia A

2015 ◽  
Vol 113 (05) ◽  
pp. 958-967 ◽  
Author(s):  
Maria Elisa Mancuso ◽  
Elena Santagostino ◽  
Gili Kenet ◽  
Mohssen Elalfy ◽  
Susanne Holzhauer ◽  
...  
Keyword(s):  
Cox Regression ◽  
Meta Analysis ◽  
Treatment Intensity ◽  
Haemophilia A ◽  
Related Factors ◽  
Inhibitor Development ◽  
Patient Level ◽  
Level Data ◽  
Statistical Approaches ◽  
The Impact

SummaryThe impact of treatment-related factors on inhibitor development in previously untreated patients (PUPs) with haemophilia A is still debated. We present the results of a collaborative, individual patient data meta-analytic project. Eligible data sources were published cohorts of PUPs for which patient-level data were available. The exposures of interest were factor (F)VIII type (recombinant [rFVIII] vs plasma-derived [pdFVIII]) and treatment intensity (≥ vs < 150 IU/kg/week) at first treatment. Family history of inhibitors, F8 mutations, age, treatment regimen (on-demand vs prophylaxis), secular trend and surgery were analysed as putative confounders using different statistical approaches (multivariable Cox regression, propensity score analyses, CART). Analyses accounted for the multi-centre origin of the data. We included 761 consecutive, unselected PUPs with moderate to severe haemophilia A from 10 centres in Egypt, Germany, Israel and Italy. A total of 27 % of patients developed inhibitors; 40 % and 22 % of patients treated with rFVIII and pdFVIII (unadjusted HR 2.2, 95 % CI 1.6–2.9), respectively; 51 % and 24 % of patients receiving high-and low-intensity treatment (unadjusted HR 2.9, 95 % CI 2.0–4.2), respectively. In adjusted analyses, only treatment intensity remained an independent predictor; the effect of FVIII type was largely due to confounding, but with a significant interaction between FVIII type and treatment intensity. This patient-level meta-analysis confirms, across different statistical approaches, that high-intensity treatment is a strong risk factor for inhibitor development. The possible role of FVIII type in subgroups is suggested by the test for interactions but could not be proven because of the limited subgroups sample sizes.

scholarly journals Forced vital capacity and cross-domain late-onset Pompe disease outcomes: an individual patient-level data meta-analysis

2019 ◽  
Vol 266 (9) ◽  
pp. 2312-2321
Author(s):  
Kenneth I. Berger ◽  
Steve Kanters ◽  
Jeroen P. Jansen ◽  
Andrew Stewart ◽  
Susan Sparks ◽  
...  
Keyword(s):  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Late Onset ◽  
Meta Analysis ◽  
Patient Level Data ◽  
Individual Patient Level ◽  
Patient Level ◽  
Cross Domain ◽  
Disease Outcomes ◽  
Level Data
Sign in / Sign up

Export Citation Format

Share Document