Trends in COVID-19 patient characteristics in a large electronic health record database in the United States: A cohort study.

BACKGROUND: Electronic health record (EHR) databases provide an opportunity to facilitate characterization and trends in patients with COVID-19. METHODS: Patients with COVID-19 were identified based on an ICD-10 diagnosis code for COVID-19 (U07.1) and/or a positive SARS-CoV-2 viral lab result from January 2020 to November 2020. Patients were characterized in terms of demographics, healthcare utilization, clinical comorbidities, therapies, laboratory results, and procedures/care received, including critical care, intubation/ventilation, and occurrence of death were described, overall and by month. RESULTS: There were 393,773 patients with COVID-19 and 56,996 with a COVID-19 associated hospitalization. A greater percentage of patients hospitalized with COVID-19 relative to all COVID-19 cases were older, male, African American, and lived in the Northeast and South. The most common comorbidities before admission/infection date were hypertension (40.8%), diabetes (29.5%), and obesity (23.8%), and the most common diagnoses during hospitalization were pneumonia (59.6%), acute respiratory failure (44.8%), and dyspnea (28.0%). A total of 85.7% of patients hospitalized with COVID-19 had CRP values > 10 mg/L, 75.5% had fibrinogen values > 400 mg/dL, and 76.8% had D-dimer values > 250 ng/mL. Median values for platelets, CRP, lactate dehydrogenase, D-dimer, and fibrinogen tended to decrease from January-March to November. The use of chloroquine/hydroxychloroquine during hospitalization peaked by March (71.2%) and was used rarely by May (5.1%) and less than 1% afterwards, while the use of remdesivir had increased by May (10.0%) followed by dexamethasone by June (27.7%). All-cause mortality was 3.2% overall and 15.0% among those hospitalized; 21.0% received critical care and 16.0% received intubation/ventilation/ECMO. CONCLUSIONS: This study characterizes US patients with COVID-19 and their management during hospitalization over the first eleven months of this disease pandemic.

Identification of pregnancies and infants within a US commercial healthcare administrative claims database.

PURPOSE: Health care insurance claims databases are becoming a more common data source for studies of medication safety during pregnancy. While pregnancies have historically been identified in such databases by pregnancy outcomes, International Classification of Diseases, 10th revision Clinical Modification (ICD-10-CM) Z3A codes denoting weeks of gestation provide more granular information on pregnancies and pregnancy periods (i.e., start and end dates). The purpose of this study was to develop a process that uses Z3A codes to identify pregnancies, pregnancy periods, and links infants within a commercial health insurance claims database. METHODS: We identified pregnancies, gestation periods, pregnancy outcomes, and linked infants within the US-based Optum Research Database between 2015 and 2020 via a series of algorithms utilizing diagnosis and procedure codes on claims. The diagnosis and procedure codes included ICD-10-CM codes, Current Procedural Terminology (CPT) codes, and Healthcare Common Procedure Coding System (HCPCS) codes. RESULTS: We identified 1 030 874 pregnancies among 841 196 women of reproductive age. Of pregnancies with livebirth outcomes, 84% were successfully linked to infants. The prevalence of pregnancy outcomes (livebirth, stillbirth, ectopic, molar, and abortion) was similar to national estimates. CONCLUSIONS: This process provides an opportunity to study drug safety and care patterns during pregnancy and may be replicated in other claims databases containing ICD-10-CM, CPT, and HCPCS codes. Work is underway to validate and refine the various algorithms.

Predictors of critical care, mechanical ventilation, and mortality among hospitalized patients with COVID-19 in an electronic health record database.

BACKGROUND: There are limited data on risk factors for serious outcomes and death from COVID-19 among patients representative of the U.S. POPULATION: The objective of this study was to determine risk factors for critical care, ventilation, and death among hospitalized patients with COVID-19. METHODS: This was a cohort study using data from Optum's longitudinal COVID-19 electronic health record database derived from a network of healthcare provider organizations across the US. The study included patients with confirmed COVID-19 (presence of ICD-10-CM code U07.1 and/or positive SARS-CoV-2 test) between January 2020 and November 2020. Patient characteristics and clinical variables at start of hospitalization were evaluated for their association with subsequent serious outcomes (critical care, mechanical ventilation, and death) using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression, adjusted for demographic variables. RESULTS: Among 56,996 hospitalized COVID-19 patients (49.5% male and 72.4% ≥ 50 years), 11,967 received critical care, 9136 received mechanical ventilation, and 8526 died. The median duration of hospitalization was 6 days (IQR: 4, 11), and this was longer among patients that experienced an outcome: 11 days (IQR: 6, 19) for critical care, 15 days (IQR: 8, 24) for mechanical ventilation, and 10 days (IQR: 5, 17) for death. Dyspnea and hypoxemia were the most prevalent symptoms and both were associated with serious outcomes in adjusted models. Additionally, temperature, C-reactive protein, ferritin, lactate dehydrogenase, D-dimer, and oxygen saturation measured during hospitalization were predictors of serious outcomes as were several in-hospital diagnoses. The strongest associations were observed for acute respiratory failure (critical care: OR, 6.30; 95% CI, 5.99-6.63; ventilation: OR, 8.55; 95% CI, 8.02-9.11; death: OR, 3.36; 95% CI, 3.17-3.55) and sepsis (critical care: OR, 4.59; 95% CI, 4.39-4.81; ventilation: OR, 5.26; 95% CI, 5.00-5.53; death: OR, 4.14; 95% CI, 3.92-4.38). Treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers during hospitalization were inversely associated with death (OR, 0.57; 95% CI, 0.54-0.61). CONCLUSIONS: We identified several clinical characteristics associated with receipt of critical care, mechanical ventilation, and death among COVID-19 patients. Future studies into the mechanisms that lead to severe COVID-19 disease are warranted.

Exenatide use and incidence of pancreatic and thyroid cancer: A retrospective cohort study.

A retrospective cohort study, supplemented with a nested case-control study, was performed using two administrative databases from commercial health plans in the United States to compare the incidence of pancreatic and thyroid cancer among users of exenatide versus other antidiabetic drugs (OADs). Patients with type 2 diabetes who initiated exenatide or OADs between 1 June 2005 and 30 June 2015 were included. Pancreatic and thyroid cancers were identified using chart-validated algorithms in the cohort study. Cases in the nested case-control study were chart-confirmed pancreatic or thyroid cancers, and controls were sampled using risk-set sampling. The time-fixed analyses comparing 33 629 exenatide initiators with 49 317 propensity-score-matched OAD initiators yielded hazard ratios of 0.76 (95% confidence interval [CI] 0.47-1.21) for pancreatic cancer and 1.46 (95% CI 0.98-2.19) for thyroid cancer. Results in the time-dependent analyses by cumulative duration or dose were similar. Nested case-control analyses yielded rate ratios of 0.61 (95%CI, 0.37-1.00) for pancreatic cancer and 0.89 (95% CI, 0.64-1.24) for thyroid cancer. This observational study suggested exenatide use was not associated with an increased risk of pancreatic or thyroid cancer.

Effectiveness and Tolerability of Therapy With Once-Weekly Exenatide Versus Basal Insulin Among Injectable-Naive Patients With Type 2 Diabetes in a Real-World Setting in the United States.

A propensity-matched cohort study compared injectable-naive patients with type 2 diabetes initiating exenatide once weekly (EQW) or basal insulin (BI), from 2012 through 2015, within a U.S. electronic health record database. A1C and weight were obtained as observed or multiply imputed values at baseline and quarterly for 1 year (Q1-Q4). Hypoglycemia and gastrointestinal symptoms were identified using diagnostic codes and clinical notes. EQW (n = 2,008) and BI (n = 4,016) cohorts were comparable at baseline (mean A1C and weight: EQW, 8.3% and 107.5 kg, respectively; BI, 8.5% and 107.9 kg, respectively). A1C declined in Q2: -0.69 and -0.50 percentage points for EQW and BI, respectively, with little further change in year 1. The EQW cohort lost 0.9 kg in Q1 and 1.9 kg by the end of the year; no weight change was observed in the BI cohort. Among EQW and BI cohorts, 25.9% and 14.3% achieved both glycemic control and weight loss, respectively. In the EQW and BI cohorts, the incidence of hypoglycemia per 1,000 person-years was 52.5 and 65.7, respectively. The incidence of nausea was greater among EQW relative to BI initiators (relative rate 1.18). EQW offers an advantage compared to BI in achieving glycemic control and weight loss and a lower incidence of hypoglycemia, but is associated with greater risk of gastrointestinal symptoms.

Effectiveness and tolerability of therapy with exenatide once weekly vs basal insulin among injectable-drug-naïve elderly or renal impaired patients with type 2 diabetes in the United States.

AIM: To evaluate the effectiveness and tolerability of exenatide once weekly (EQW) compared with basal insulin (BI) among injectable-drug-naïve patients with type 2 diabetes mellitus (T2DM) who are elderly or have renal impairment (RI). MATERIALS AND METHODS: Initiators of EQW and BI with T2DM were identified for the period 2012 to 2015 within a US electronic health record database and matched by propensity score. Matched EQW and BI initiators aged ≥65 years or who had RI were compared. Data on weight, glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), blood pressure and lipids were obtained at baseline and quarterly (Q1-Q4) or semi-annually for 1 year after drug initiation. Hypoglycaemia and gastrointestinal symptoms were identified using diagnosis codes and data abstracted from clinical notes. RESULTS: Among patients aged ≥65 years, HbA1c changed by -0.50 and -0.31 percentage points from baseline to Q4 for EQW and BI initiators, respectively. Weight changed by -1.6 kg among EQW initiators compared with 0.2 kg among BI initiators. Compared with BI initiators, EQW initiators had a 1.45-fold increased risk of nausea and vomiting. Among patients with RI, HbA1c changed by -0.58 and -0.33 percentage points from baseline to Q4 for EQW and BI initiators, respectively. Weight changed by -1.9 kg for EQW initiators while BI initiators had no change in weight. EQW initiators had a 1.28-fold increased risk of constipation and diarrhoea compared with BI initiators. CONCLUSION: Regardless of age or renal function, the benefits of EQW relative to BI treatment are improved glycaemic control and increased weight loss, which should be weighed against the increased risk of gastrointestinal symptoms.

Tolerability and Effectiveness of Exenatide Once Weekly Relative to Basal Insulin Among Type 2 Diabetes Patients of Different Races in Routine Care.

INTRODUCTION: Analyses of efficacy and tolerability of pharmacologic interventions are based on clinical trials that often include predominately white populations, in part because of challenges associated with recruitment and retention of racial/ethnically diverse study populations. Using real-world electronic health record (EHR) data, we sought to evaluate the tolerability and effectiveness of exenatide once weekly (EQW), overall and relative to basal insulin (BI), according to race. METHODS: Patients with type 2 diabetes initiating EQW or BI between 2012 and 2015 were selected from the Optum EHR Research Database, a system pooling data from dozens of hospitals throughout the US. Measures of HbA1c, weight, and body mass index (BMI) were summarized at initiation and quarterly in the first year afterwards. Occurrences of gastrointestinal (GI) symptoms and hypoglycemia were identified by diagnostic codes and clinical notes, and incidence rates (IR) and relative rates (RR) were calculated. RESULTS: Overall, 4907 white patients (mean age = 57 years) and 454 African American patients (mean age = 53 years) were included. The percent change in HbA1c from initiation through 9-12 months was similar for white and African American patients [EQW-White: -6.89 (95% CI: -8.29, -5.50), EQW-African American: -5.99 (95% CI: -10.33, -1.65), BI-White: -4.68 (95% CI: -5.51, -3.86), BI-African American: -3.11 (95% CI: -5.37, -0.85)]. For EQW, percent change in weight was -1.73 (95% CI: -2.45, -1.02) for white patients and -1.11 (95% CI: -3.02, -0.81) for African American patients. No weight loss was observed among BI initiators. Relative to BI initiators, EQW initiators had lower rates of hypoglycemia [White RR: 0.82 (95% CI: 0.66, 1.01), African American RR: 0.59 (95% CI: 0.26, 1.34)]. GI symptoms were increased in white EQW initiators. CONCLUSIONS: Treatment with EQW, relative to BI, was associated with larger reductions in HbA1c and weight and reduced risk of hypoglycemia, effects that were not different for white and African American patients. FUNDING: AstraZeneca, Gothenburg, Sweden.

A cross-sectional study of the identification of prevalent asthma and chronic obstructive pulmonary disease among initiators of long-acting ß-agonists in health insurance claims data.

BACKGROUND: Claims data are potentially useful for identifying long-acting ß-agonist (LABA) use by patients with asthma, a practice that is associated with increased mortality. We evaluated the accuracy of claims data for classifying prevalent asthma and chronic obstructive pulmonary disease (COPD) among initiators of LABAs. METHODS: This study included adult LABA initiators during 2005-2008 in a US commercial health plan. Diagnosis codes from the 6 months before LABA initiation identified potential asthma or COPD and a physician adjudicated case status using abstracted medical records. We estimated the positive predictive value (PPV) and 95% confidence intervals (CI) of covariate patterns for identifying asthma and COPD. RESULTS: We sought 520 medical records at random from 225,079 LABA initiators and received 370 (71%). The PPV for at least one asthma claim was 74% (CI 63-82), and decreased as age increased. Having at least one COPD claim resulted in a PPV of 82% (CI 72-89), and of over 90% among older patients, men, and recipients of inhaled anticholinergic drugs. Only 2% (CI 0.2-7.6) of patients with a claim for COPD alone were found to have both COPD and asthma, while 9% (CI 4-16) had asthma only. Twenty-one percent (CI 14-30) of patients with claims for both diagnoses had both conditions. Among patients with no asthma or COPD claims, 62% (CI 50-72) had no confirmed diagnosis and 29% (CI 19-39) had confirmed asthma. CONCLUSIONS: Subsets of patients with asthma, COPD, and both conditions can be identified and differentiated using claims data, although categorization of the remaining patients is infeasible. Safety surveillance for off-label use of LABAs must account for this limitation.

Cardiac mortality in users of olmesartan, other angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors.

PURPOSE: Clinical trials of olmesartan for prevention of progression of renal disease in patients with diabetes showed renal protection but an unexpected imbalance in cardiac deaths. The US Food and Drug Administration requested from the manufacturer a cohort study of olmesartan, other angiotensin-receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors in a large population. METHODS: A retrospective cohort study was conducted with the cooperation of a US health insurer. Subject entry and follow-up ran from 2002 through 2009. In propensity-matched cohorts, the primary analysis considered continuous current users. Endpoints were sudden cardiac death (SCD) and all-cause mortality, identified through the US National Death Index, supplemented by insurance and hospital discharge data. Statistical estimation was based on proportional hazards analyses with 95% confidence intervals. Power calculations had shown that 25,000 olmesartan initiators would be required to detect relative risks (RRs) of SCD of twofold or greater. RESULTS: A total of 57,123 initiators of olmesartan were matched 1:2 to initiators of other ARBs and 41,801 to initiators of ACE inhibitors. Average follow-up time ranged from 8 to 9 months. Olmesartan initiators and comparators experienced similar patterns of both outcomes, with RRs ≤1.0 and upper confidence bounds ≤1.6. Among persons with prior use of hypoglycemic agents, in comparison with other ARBs, the RR of SCD for olmesartan users was 0.8, with an upper confidence bound of 2.2. CONCLUSION: The results of this well-powered study do not raise concerns for the risk of SCD or death from all causes among olmesartan users in comparison with users of other ARBs or ACE inhibitors.

Incidence of intussusception among infants in a large commercially insured population in the United States.

BACKGROUND: To estimate the incidence of intussusception among infants treated in inpatient and emergency department settings during the period preceding the US launch of second-generation rotavirus vaccines. METHODS: From a large US health insurance claims database, we sampled 100,000 infants aged 1 to 3 months at first diphtheria-tetanus-acellular pertussis vaccination between 2001 and 2005. Potential intussusception cases were identified on the basis of claims and were confirmed by medical record review. Incidence rates (IRs) and 95% confidence intervals (CIs) were estimated based on follow-up from first diphtheria-tetanus-acellular pertussis dose to up to 1 year of age, and within 21, 30, and 60 days after each dose. RESULTS: The IR of intussusception in the first year of life was 0.33/1000 person-years based on 22 confirmed cases (95% CI: 0.21-0.50/1000 person-years). The age-specific incidence peaked among infants aged 5 months (IR: 0.82/1000 person-years; 95% CI: 0.30-1.78/1000 person-years). During the 21, 30, and 60 days following any dose, the incidence per 1000 person-years was 0.27, 0.24, and 0.33, respectively. CONCLUSION: The rates described in this study can serve as a benchmark for comparison with incidences observed after the introduction of the second-generation rotavirus vaccines.

Risk of hyperkalemia in women taking ethinylestradiol/drospirenone and other oral contraceptives.

BACKGROUND: The oral contraceptive ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) contains a progestin component that possesses potassium-sparing diuretic activity similar to spironolactone. We sought to determine whether EE/DRSP use might lead to adverse effects possibly attributable to hyperkalemia. STUDY DESIGN: This was a matched cohort study in which we identified oral contraceptive (OC) initiators between July 2001 and June 2004 within a large, US health plan. We matched EE/DRSP initiators to other OC initiators in a 1:2 ratio on the basis of a prediction model (propensity score) of EE/DRSP initiation that incorporated dozens of characteristics. We identified insurance claims mentioning hyperkalemia, related clinical outcomes (electrolyte disturbances, arrhythmia, syncope, myocardial infarction) and verified the underlying condition through medical record review. RESULTS: There were 22,429 EE/DRSP initiators matched to 44,858 other OC initiators, with an average follow-up of 7.6 months. A composite clinical surrogate hyperkalemia end point occurred with equal frequency in the compared groups [118 cases in EE/DRSP and 260 in comparators; rate ratio (RR) 0.9, 95% confidence interval (CI) 0.7-1.1]. The individual hyperkalemia surrogate end points exhibited similar results. One EE/DRSP initiator and four comparators were diagnosed specifically with hyperkalemia (RR 0.5, 95% CI 0.0-4.9). The results were not different when we accounted for changes in OC use during follow-up. CONCLUSION: EE/DRSP initiators are no more likely than other OC initiators to experience hyperkalemia or related clinical outcomes which could be caused by hyperkalemia during follow-up.

Supplementary data collection with case-cohort analysis to address potential confounding in a cohort study of thromboembolism in oral contraceptive initiators matched on claims-based propensity scores.

PURPOSE: Residual confounding is a potential limitation of pharmacoepidemiologic studies, and in particular, studies based on administrative claims data that do not capture lifestyle and clinical confounders. We describe an application of the case-cohort design to assess residual confounding by thromboembolic risk factors (e.g., smoking and obesity) not captured in claims data in a claims-based cohort study of thromboembolism among matched oral contraceptive (OC) initiators. METHODS: This study was conducted using the Ingenix Research Data Mart, a database containing medical claims for approximately 12 million members of a large health plan of the United States. We randomly sampled 701 OC initiators from cohorts of ethinyl estradiol/drospirenone (n = 22,429) and other OC initiators (n = 44,858) identified in the years 2001-2004 and matched by propensity score in a claims-based cohort study. Supplementary data on risk factors not measured in the cohort study were collected from medical records for the sample. We estimated the risk ratio of thromboembolism adjusted for the supplementary variables using Cox regression modified for a case-cohort design, and compared it to the rate ratio from the cohort study. RESULTS: The risk ratio adjusted for the supplementary variables was 0.90 (95 per cent (%) confidence interval (CI): 0.49, 1.68) which was similar to the rate ratio (0.92; 95%CI: 0.50, 1.63), indicating negligible confounding by the supplementary variables in the cohort study. CONCLUSIONS: Case-cohort methods were used to assess residual confounding in a claims-based cohort study. This approach adds to a growing number of methods to evaluate residual confounding in cohort studies.

Risk of thromboembolism in women taking ethinylestradiol/drospirenone and other oral contraceptives.

OBJECTIVE: The oral contraceptive ethinylestradiol 0.03 mg/drospirenone 3 mg contains a progestin component that differs from other oral contraceptives. Case reports and prescription event monitoring suggested that ethinylestradiol/drospirenone might be associated with an elevated risk of thromboembolism. We sought to estimate the association between ethinylestradiol/drospirenone and risk of thromboembolism relative to the association among other oral contraceptives. METHODS: We identified ethinylestradiol/drospirenone initiators and a twofold larger group of other oral contraceptive initiators between June 2001 and June 2004 within a U.S. health insurer database. The comparison group was selected to have demographic and health care characteristics preceding oral contraceptive initiation that were similar to ethinylestradiol/drospirenone initiators. Thromboembolism during the follow-up of the cohorts was identified through claims for medical services, and only medical record-confirmed cases were included in analyses. The primary (as-matched) analysis used proportional hazards regression, whereas a secondary (as-treated) analysis accounted for changes in oral contraceptives during follow-up using Poisson regression. RESULTS: The 22,429 ethinylestradiol/drospirenone initiators and 44,858 other oral contraceptive initiators were followed for an average of 7.6 months, and there were 18 cases of thromboembolism in ethinylestradiol/drospirenone initiators and 39 in the comparators (rate ratio 0.9, 95% confidence interval 0.5-1.6). More than 9,000 women would need to be prescribed oral contraceptives to observe a difference of one case of thromboembolism. Results of the as-treated analysis were similar to those of the as-matched analysis. CONCLUSION: Ethinylestradiol/drospirenone initiators and initiators of other oral contraceptives are similarly likely to experience thromboembolism. LEVEL OF EVIDENCE: II.