Seek COVER: using a disease proxy to rapidly develop and validate a personalized risk calculator for COVID-19 outcomes in an international network.

BACKGROUND: We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated early in a pandemic. We developed COVID-19 Estimated Risk (COVER) scores that quantify a patient's risk of hospital admission with pneumonia (COVER-H), hospitalization with pneumonia requiring intensive services or death (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis using historical data from patients with influenza or flu-like symptoms and tested this in COVID-19 patients. METHODS: We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries containing data collected on or before 4/27/2020. We used a 2-step process to develop 3 scores using historical data from patients with influenza or flu-like symptoms any time prior to 2020. The first step was to create a data-driven model using LASSO regularized logistic regression, the covariates of which were used to develop aggregate covariates for the second step where the COVER scores were developed using a smaller set of features. These 3 COVER scores were then externally validated on patients with 1) influenza or flu-like symptoms and 2) confirmed or suspected COVID-19 diagnosis across 5 databases from South Korea, Spain, and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. RESULTS: Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved good performance in influenza and COVID-19 cohorts. For COVID-19 the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration varied across the validations with some of the COVID-19 validations being less well calibrated than the influenza validations. CONCLUSIONS: This research demonstrated the utility of using a proxy disease to develop a prediction model. The 3 COVER models with 9-predictors that were developed using influenza data perform well for COVID-19 patients for predicting hospitalization, intensive services, and fatality. The scores showed good discriminatory performance which transferred well to the COVID-19 population. There was some miscalibration in the COVID-19 validations, which is potentially due to the difference in symptom severity between the two diseases. A possible solution for this is to recalibrate the models in each location before use.

Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users.

OBJECTIVE: To evaluate the relative risk of cervical neoplasms among copper intrauterine device (Cu IUD) and levonorgestrel-releasing intrauterine system (LNG-IUS) users. METHODS: We performed a retrospective cohort analysis of 10,674 patients who received IUDs at Columbia University Medical Center. Our data were transformed to a common data model and are part of the Observational Health Data Sciences and Informatics network. The cohort patients and outcomes were identified by a combination of procedure codes, condition codes, and medication exposures in billing and claims data. We adjusted for confounding with propensity score stratification and propensity score 1:1 matching. RESULTS: Before propensity score adjustment, the Cu IUD cohort included 8,274 patients and the LNG-IUS cohort included 2,400 patients. The median age for both cohorts was 29 years at IUD placement. More than 95% of the LNG-IUS cohort used a device with 52 mg LNG. Before propensity score adjustment, we identified 114 cervical neoplasm outcomes. Seventy-seven (0.9%) cervical neoplasms were in the Cu IUD cohort and 37 (1.5%) were in the LNG-IUS cohort. The propensity score matching analysis identified 7,114 Cu IUD and 2,174 LNG-IUS users, with covariate balance achieved over 16,827 covariates. The diagnosis of high-grade cervical neoplasia was 0.7% in the Cu IUD cohort and 1.8% in the LNG-IUS cohort (2.4 [95% CI 1.5-4.0] cases/1,000 person-years and 5.2 [95% CI 3.7-7.1] cases/1,000 person-years, respectively). The relative risk of high-grade cervical neoplasms among Cu IUD users was 0.38 (95% CI 0.16-0.78, P<.02) compared with LNG-IUS users. By inspection, the Kaplan-Meier curves for each cohort diverged over time. CONCLUSION: Copper IUD users have a lower risk of high-grade cervical neoplasms compared with LNG-IUS users. The relative risk of cervical neoplasms of LNG-IUS users compared with the general population is unknown.

Relation of QRS shortening to cardiac output during temporary resynchronization therapy after cardiac surgery.

Cardiac resynchronization therapy (CRT) can improve cardiac function in heart failure without increasing myocardial oxygen consumption. However, CRT optimization based on hemodynamics or echocardiography is difficult. QRS duration (QRSd) is a possible alternative optimization parameter. Accordingly, we assessed QRSd optimization of CRT during cardiac surgery. We hypothesized that QRSd shortening during changes in interventricular pacing delay (VVD) would increase cardiac output (CO). Seven patients undergoing coronary artery bypass, aortic or mitral valve surgery with left ventricular (LV) ejection fraction < or =40%, and QRSd > or =100 msec were studied. CRT was implemented at epicardial pacing sites in the left and right ventricle and right atrium during VVD variation after cardiopulmonary bypass. QRSd was correlated with CO from an electromagnetic aortic flow probe. Both positive and negative correlations were observed. Correlation coefficients ranged from 0.70 to -0.74 during VVD testing. Clear minima in QRSd were observed in four patients and were within 40 msec of maximum CO in two. We conclude that QRSd is not useful for routine optimization of VVD after cardiac surgery but may be useful in selected patients. Decreasing QRSd is associated with decreasing CO in some patients, suggesting that CRT can affect determinants of QRSd and ventricular function independently.