COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.

OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. METHODS: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization. RESULTS: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%). CONCLUSION: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.

Exploration of association rule mining for coding consistency and completeness assessment in inpatient administrative health data.

OBJECTIVE: Data quality assessment is a challenging facet for research using coded administrative health data. Current assessment approaches are time and resource intensive. We explored whether association rule mining (ARM) can be used to develop rules for assessing data quality. MATERIALS AND METHODS: We extracted 2013 and 2014 records from the hospital discharge abstract database (DAD) for patients between the ages of 55 and 65 from five acute care hospitals in Alberta, Canada. The ARM was conducted using the 2013 DAD to extract rules with support ≥0.0019 and confidence ≥0.5 using the bootstrap technique, and tested in the 2014 DAD. The rules were compared against the method of coding frequency and assessed for their ability to detect error introduced by two kinds of data manipulation: random permutation and random deletion. RESULTS: The association rules generally had clear clinical meanings. Comparing 2014 data to 2013 data (both original), there were 3 rules with a confidence difference >0.1, while coding frequency difference of codes in the right hand of rules was less than 0.004. After random permutation of 50% of codes in the 2014 data, average rule confidence dropped from 0.72 to 0.27 while coding frequency remained unchanged. Rule confidence decreased with the increase of coding deletion, as expected. Rule confidence was more sensitive to code deletion compared to coding frequency, with slope of change ranging from 1.7 to 184.9 with a median of 9.1. CONCLUSION: The ARM is a promising technique to assess data quality. It offers a systematic way to derive coding association rules hidden in data, and potentially provides a sensitive and efficient method of assessing data quality compared to standard methods.

Think global, act local: medical students contextualize global health education.

BACKGROUND: There is considerable heterogeneity in the extent to which global health education is emphasized in undergraduate medical curricula. Here, we performed an exploratory analysis to test the hypothesis that exposure to global health education may influence the attitudes of medical students toward the treatment of local vulnerable patient populations. METHODS: All pre-clerkship students at an urban Canadian university were invited to attend a voluntary global health education session on challenges in treating human immunodeficiency virus (HIV) in the developing world. Those who attended as well as those who did not completed pre- and post-session surveys measuring willingness to treat patients with HIV and related attitudes. A repeated measure analysis of variance (ANOVA) was performed to assess the effect of the intervention on attitudes toward locally affected populations. RESULTS: A total of 201 (81.4%) and 143 (58.3%) students completed the pre- and post-session surveys, respectively. Students who scored their willingness to treat patients with HIV within highest 10% of the scale on the pre-session survey were excluded from the analysis to account for a ceiling effect. On repeated measure ANOVA, willingness to treat local patients with HIV increased significantly following the session (P < 0.01). Students intending to attend the session also reported a greater propensity to treat patients with HIV than those who did not (P = 0.03). DISCUSSION: In this exploratory study, we find that following exposure to a global health lecture on the challenges of HIV in the developing world, students possessed more favorable attitudes toward the treatment of marginalized local patient populations, a finding that may be exploited in undergraduate and continuing medical education.

Serially Combining Epidemiological Designs Does Not Improve Overall Signal Detection in Vaccine Safety Surveillance.

INTRODUCTION: Vaccine safety surveillance commonly includes a serial testing approach with a sensitive method for 'signal generation' and specific method for 'signal validation.' The extent to which serial testing in real-world studies improves or hinders overall performance in terms of sensitivity and specificity remains unknown. METHODS: We assessed the overall performance of serial testing using three administrative claims and one electronic health record database. We compared type I and II errors before and after empirical calibration for historical comparator, self-controlled case series (SCCS), and the serial combination of those designs against six vaccine exposure groups with 93 negative control and 279 imputed positive control outcomes. RESULTS: The historical comparator design mostly had fewer type II errors than SCCS. SCCS had fewer type I errors than the historical comparator. Before empirical calibration, the serial combination increased specificity and decreased sensitivity. Type II errors mostly exceeded 50%. After empirical calibration, type I errors returned to nominal; sensitivity was lowest when the methods were combined. CONCLUSION: While serial combination produced fewer false-positive signals compared with the most specific method, it generated more false-negative signals compared with the most sensitive method. Using a historical comparator design followed by an SCCS analysis yielded decreased sensitivity in evaluating safety signals relative to a one-stage SCCS approach. While the current use of serial testing in vaccine surveillance may provide a practical paradigm for signal identification and triage, single epidemiological designs should be explored as valuable approaches to detecting signals.

Real-world evidence to advance knowledge in pulmonary hypertension: Status, challenges, and opportunities. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative's Real-world Evidence Working Group.

This manuscript on real-world evidence (RWE) in pulmonary hypertension (PH) incorporates the broad experience of members of the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative Real-World Evidence Working Group. We aim to strengthen the research community's understanding of RWE in PH to facilitate clinical research advances and ultimately improve patient care. Herein, we review real-world data (RWD) sources, discuss challenges and opportunities when using RWD sources to study PH populations, and identify resources needed to support the generation of meaningful RWE for the global PH community.

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

Bias, Precision and Timeliness of Historical (Background) Rate Comparison Methods for Vaccine Safety Monitoring: An Empirical Multi-Database Analysis.

Using real-world data and past vaccination data, we conducted a large-scale experiment to quantify bias, precision and timeliness of different study designs to estimate historical background (expected) compared to post-vaccination (observed) rates of safety events for several vaccines. We used negative (not causally related) and positive control outcomes. The latter were synthetically generated true safety signals with incident rate ratios ranging from 1.5 to 4. Observed vs. expected analysis using within-database historical background rates is a sensitive but unspecific method for the identification of potential vaccine safety signals. Despite good discrimination, most analyses showed a tendency to overestimate risks, with 20%-100% type 1 error, but low (0% to 20%) type 2 error in the large databases included in our study. Efforts to improve the comparability of background and post-vaccine rates, including age-sex adjustment and anchoring background rates around a visit, reduced type 1 error and improved precision but residual systematic error persisted. Additionally, empirical calibration dramatically reduced type 1 to nominal but came at the cost of increasing type 2 error.

Characteristics, outcomes, and mortality amongst 133,589 patients with prevalent autoimmune diseases diagnosed with, and 48,418 hospitalised for COVID-19: a multinational distributed network cohort analysis.

OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid COVID-19, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. DESIGN: Multinational network cohort study. SETTING: Electronic health records data from Columbia University Irving Medical Center (CUIMC) (NYC, United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment (HIRA) (South Korea). PARTICIPANTS: All patients with prevalent autoimmune diseases, diagnosed and/or hospitalised between January and June 2020 with COVID-19, and similar patients hospitalised with influenza in 2017-2018 were included. MAIN OUTCOME MEASURES: 30-day complications during hospitalisation and death. RESULTS: We studied 133,589 patients diagnosed and 48,418 hospitalised with COVID-19 with prevalent autoimmune diseases. The majority of participants were female (60.5% to 65.9%) and aged ≥50 years. The most prevalent autoimmune conditions were psoriasis (3.5 to 32.5%), rheumatoid arthritis (3.9 to 18.9%), and vasculitis (3.3 to 17.6%). Amongst hospitalised patients, Type 1 diabetes was the most common autoimmune condition (4.8% to 7.5%) in US databases, rheumatoid arthritis in HIRA (18.9%), and psoriasis in SIDIAP-H (26.4%).Compared to 70,660 hospitalised with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2% to 4.3% versus 6.3% to 24.6%). CONCLUSIONS: Patients with autoimmune diseases had high rates of respiratory complications and 30-day mortality following a hospitalization with COVID-19. Compared to influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality. Future studies should investigate predictors of poor outcomes in COVID-19 patients with autoimmune diseases. WHAT IS ALREADY KNOWN ABOUT THIS TOPIC: Patients with autoimmune conditions may be at increased risk of COVID-19 infection andcomplications.There is a paucity of evidence characterising the outcomes of hospitalised COVID-19 patients with prevalent autoimmune conditions. WHAT THIS STUDY ADDS: Most people with autoimmune diseases who required hospitalisation for COVID-19 were women, aged 50 years or older, and had substantial previous comorbidities.Patients who were hospitalised with COVID-19 and had prevalent autoimmune diseases had higher prevalence of hypertension, chronic kidney disease, heart disease, and Type 2 diabetes as compared to those with prevalent autoimmune diseases who were diagnosed with COVID-19.A variable proportion of 6% to 25% across data sources died within one month of hospitalisation with COVID-19 and prevalent autoimmune diseases.For people with autoimmune diseases, COVID-19 hospitalisation was associated with worse outcomes and 30-day mortality compared to admission with influenza in the 2017-2018 season.

Myelin water measurement in the spinal cord.

The desire to monitor the spatial-temporal characteristics of myelination in the spinal cord (SC), in the context of pathological change in demyelinating diseases or proposed neuroregenerative protocols, has led to an interest in noninvasive image-based myelin measurement methods. We present one strategy: a magnetic resonance-based measure that capitalizes on the characteristics of T(2) relaxation of water compartmentalized within tissue. In this study, 32-echo relaxation studies for measuring the myelin water fraction (MWF) were applied in healthy control SC in vivo using a sagittal inversion recovery multiecho sequence, and findings were supported with supplemental studies in bovine SC samples in vitro. Mean human MWF varied according the level of the SC examined: cervical, thoracic, and lumbar MWF was found to be 21.8 (SD=2.1)%, 24.3 (3.6)%, and 11.4 (6.4)%, respectively. Noteworthy reductions were observed in areas consistent with the expected locations of the cervical and lumbar enlargements. Average bovine MWF was 30.0 (2.7)% in white matter and 8.2 (0.4)% in gray matter. The potential applications of T(2) measurement in SC, both in characterizing disease processes like multiple sclerosis and in monitoring neuroregenerative therapies, should encourage future research in this area.

A Meta-Data Manifesto: The Need for Global Health Meta-Data.

Administrative health data recorded for individual health episodes (such as births, deaths, physician visits, and hospital stays) are being widely used to study policy-relevant scientific questions about population health, health services, and quality of care. An increasing number of international health comparisons are undertaken with these data. An essential pre-requisite to such international comparative work is a detailed characterization of existing international health data resources, so that they can be more readily used for comparisons across counties. A major challenge to such international comparative work is the variability across countries in the extent, content, and validity of existing administrative data holdings. Recognizing this, we have undertaken an international proof of concept pilot compiling detailed data about data - i.e., a "meta-data catalogue" - for existing international administrative health data holdings. We describe the methodological process for collecting these meta-data, along with some general descriptive results for selected countries included in the pilot.

Data on coding association rules from an inpatient administrative health data coded by International classification of disease - 10th revision (ICD-10) codes.

Data presented in this article relates to the research article entitled "Exploration of association rule mining for coding consistency and completeness assessment in inpatient administrative health data" (Peng et al. [1]) in preparation). We provided a set of ICD-10 coding association rules in the age group of 55 to 65. The rules were extracted from an inpatient administrative health data at five acute care hospitals in Alberta, Canada, using association rule mining. Thresholds of support and confidence for the association rules mining process were set at 0.19% and 50% respectively. The data set contains 426 rules, in which 86 rules are not nested. Data are provided in the supplementary material. The presented coding association rules provide a reference for future researches on the use of association rule mining for data quality assessment.

Learning statistical models of phenotypes using noisy labeled training data.

OBJECTIVE: Traditionally, patient groups with a phenotype are selected through rule-based definitions whose creation and validation are time-consuming. Machine learning approaches to electronic phenotyping are limited by the paucity of labeled training datasets. We demonstrate the feasibility of utilizing semi-automatically labeled training sets to create phenotype models via machine learning, using a comprehensive representation of the patient medical record. METHODS: We use a list of keywords specific to the phenotype of interest to generate noisy labeled training data. We train L1 penalized logistic regression models for a chronic and an acute disease and evaluate the performance of the models against a gold standard. RESULTS: Our models for Type 2 diabetes mellitus and myocardial infarction achieve precision and accuracy of 0.90, 0.89, and 0.86, 0.89, respectively. Local implementations of the previously validated rule-based definitions for Type 2 diabetes mellitus and myocardial infarction achieve precision and accuracy of 0.96, 0.92 and 0.84, 0.87, respectively.We have demonstrated feasibility of learning phenotype models using imperfectly labeled data for a chronic and acute phenotype. Further research in feature engineering and in specification of the keyword list can improve the performance of the models and the scalability of the approach. CONCLUSIONS: Our method provides an alternative to manual labeling for creating training sets for statistical models of phenotypes. Such an approach can accelerate research with large observational healthcare datasets and may also be used to create local phenotype models.

Using the wisdom of the crowds to find critical errors in biomedical ontologies: a study of SNOMED CT.

OBJECTIVES: The verification of biomedical ontologies is an arduous process that typically involves peer review by subject-matter experts. This work evaluated the ability of crowdsourcing methods to detect errors in SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) and to address the challenges of scalable ontology verification. METHODS: We developed a methodology to crowdsource ontology verification that uses micro-tasking combined with a Bayesian classifier. We then conducted a prospective study in which both the crowd and domain experts verified a subset of SNOMED CT comprising 200 taxonomic relationships. RESULTS: The crowd identified errors as well as any single expert at about one-quarter of the cost. The inter-rater agreement (κ) between the crowd and the experts was 0.58; the inter-rater agreement between experts themselves was 0.59, suggesting that the crowd is nearly indistinguishable from any one expert. Furthermore, the crowd identified 39 previously undiscovered, critical errors in SNOMED CT (eg, 'septic shock is a soft-tissue infection'). DISCUSSION: The results show that the crowd can indeed identify errors in SNOMED CT that experts also find, and the results suggest that our method will likely perform well on similar ontologies. The crowd may be particularly useful in situations where an expert is unavailable, budget is limited, or an ontology is too large for manual error checking. Finally, our results suggest that the online anonymous crowd could successfully complete other domain-specific tasks. CONCLUSIONS: We have demonstrated that the crowd can address the challenges of scalable ontology verification, completing not only intuitive, common-sense tasks, but also expert-level, knowledge-intensive tasks.