Validation of an internationally derived patient severity phenotype to support COVID-19 analytics from electronic health record data

Objective: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing coronavirus disease 2019 (COVID-19) with federated analyses of electronic health record (EHR) data. We sought to develop and validate a computable phenotype for COVID-19 severity. Materials and Methods: Twelve 4CE sites participated. First, we developed an EHR-based severity phenotype consisting of 6 code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of intensive care unit (ICU) admission and/or death. We also piloted an alternative machine learning approach and compared selected predictors of severity with the 4CE phenotype at 1 site. Results: The full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability-up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean area under the curve of 0.903 (95% confidence interval, 0.886-0.921), compared with an area under the curve of 0.956 (95% confidence interval, 0.952-0.959) for the machine learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared with chart review. Discussion: We developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly owing to heterogeneous pandemic conditions. Conclusions: We developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites

A knowledge-based diagnostic clinical decision support system for musculoskeletal disorders of the shoulder for use in a primary care setting

Background Twenty percent of cases seen by primary care clinicians (general practitioners; GPs) are musculoskeletal in nature, and approximately one-quarter of these are shoulder complaints. GPs are increasingly overloaded with clinical information and unfamiliarity with current research can easily lead to misdiagnosis and, in turn, to unnecessary test requests or onward specialist referrals. Well-designed diagnostic clinical decision support systems (CDSS) have been shown to facilitate clinical decision-making and reduce diagnostic errors. However, no CDSS have been developed or tested for musculoskeletal disorders.Methods We have developed a prototype knowledge-based diagnostic CDSS for musculoskeletal shoulder conditions. The CDSS uses Bayesian reasoning to diagnose six common musculoskeletal shoulder pathologies, based on current evidence and expert opinion. The CDSS was tested by comparing its diagnostic outcome against 50 case studies with known diagnosis by radiological imaging.Results The CDSS diagnostic validity and reliability was shown to be 88% with a Kappa value of 0.85 to a confidence level of 99% compared to known diagnosis by radiological imaging.Conclusions The results suggest that a Bayesian network-based CDSS is a promising instrument in the diagnosis of musculoskeletal shoulder conditions, having been shown to be valid and reliable for 50 case studies.Peer reviewe

Changes in laboratory value improvement and mortality rates over the course of the pandemic: an international retrospective cohort study of hospitalised patients infected with SARS-CoV-2

Objective To assess changes in international mortality rates and laboratory recovery rates during hospitalisation for patients hospitalised with SARS-CoV-2 between the first wave (1 March to 30 June 2020) and the second wave (1 July 2020 to 31 January 2021) of the COVID-19 pandemic. Design, setting and participants This is a retrospective cohort study of 83 178 hospitalised patients admitted between 7 days before or 14 days after PCR-confirmed SARS-CoV-2 infection within the Consortium for Clinical Characterization of COVID-19 by Electronic Health Record, an international multihealthcare system collaborative of 288 hospitals in the USA and Europe. The laboratory recovery rates and mortality rates over time were compared between the two waves of the pandemic. Primary and secondary outcome measures The primary outcome was all-cause mortality rate within 28 days after hospitalisation stratified by predicted low, medium and high mortality risk at baseline. The secondary outcome was the average rate of change in laboratory values during the first week of hospitalisation. Results Baseline Charlson Comorbidity Index and laboratory values at admission were not significantly different between the first and second waves. The improvement in laboratory values over time was faster in the second wave compared with the first. The average C reactive protein rate of change was -4.72 mg/dL vs -4.14 mg/dL per day (p=0.05). The mortality rates within each risk category significantly decreased over time, with the most substantial decrease in the high-risk group (42.3% in March-April 2020 vs 30.8% in November 2020 to January 2021, p<0.001) and a moderate decrease in the intermediate-risk group (21.5% in March-April 2020 vs 14.3% in November 2020 to January 2021, p<0.001). Conclusions Admission profiles of patients hospitalised with SARS-CoV-2 infection did not differ greatly between the first and second waves of the pandemic, but there were notable differences in laboratory improvement rates during hospitalisation. Mortality risks among patients with similar risk profiles decreased over the course of the pandemic. The improvement in laboratory values and mortality risk was consistent across multiple countries

International electronic health record-derived post-acute sequelae profiles of COVID-19 patients

The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09–1.55), heart failure (RR 1.22, 95% CI 1.10–1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07–1.31), and fatigue (RR 1.18, 95% CI 1.07–1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58–2.76), venous embolism (RR 1.34, 95% CI 1.17–1.54), atrial fibrillation (RR 1.30, 95% CI 1.13–1.50), type 2 diabetes (RR 1.26, 95% CI 1.16–1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09–1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90–3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21–2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04–1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC