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Introduction: During the COVID‐19 pandemic, inpatient electronic health records (EHRs) have been used to conduct public health surveillance and assess treatments and outcomes. Invasive mechanical ventilation (MV) and supplemental oxygen (O2) use are markers of severe illness in hospitalized COVID‐19 patients. In a large US system (n = 142 hospitals), we assessed documentation of MV and O2 use during COVID‐19 hospitalization in administrative data versus nursing documentation. Methods: We identified 319 553 adult hospitalizations with a COVID‐19 diagnosis, February 2020–October 2022, and extracted coded, administrative data for MV or O2. Separately, we developed classification rules for MV or O2 supplementation from semi‐structured nursing documentation. We assessed MV and O2 supplementation in administrative data versus nursing documentation and calculated ordinal endpoints of decreasing COVID‐19 disease severity. Nursing documentation was considered the gold standard in sensitivity and positive predictive value (PPV) analyses. Results: In nursing documentation, the prevalence of MV and O2 supplementation among COVID‐19 hospitalizations was 14% and 75%, respectively. The sensitivity of administrative data was 83% for MV and 41% for O2, with both PPVs above 91%. Concordance between sources was 97% for MV (κ = 0.85), and 54% for O2 (κ = 0.21). For ordinal endpoints, administrative data accurately identified intensive care and MV but underestimated hospitalizations with O2 requirements (42% vs. 18%). Conclusions: In comparison to nursing documentation, administrative data under‐ascertained O2 supplementation but accurately estimated severe endpoints such as MV. Nursing documentation improved ascertainment of O2 among COVID‐19 hospitalizations and can capture oxygen requirements in adults hospitalized with COVID‐19 or other respiratory illnesses. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE. Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09– 0.13%) in Canada to 1.01% (0.97– 1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21– 0.26%) in Canada to 0.84% (0.80– 0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06– 0.07%) in England to 1.04% (1.01– 1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24– 0.26%) in England to 1.02% (0.99– 1.04%) in the US. Conclusion: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability. Plain Language Summary: Cohort studies of patients diagnosed with COVID-19 in both the ambulatory and hospital settings have suggested that SARS-CoV-2 infection promotes hypercoagulability that could lead to arterial or venous thromboembolism. However, few studies have examined how the risk of thromboembolism with COVID-19 has evolved over time across different countries. A new collaboration was established among the regulatory authorities of Canada, Europe, and the US within the International Coalition of Medicines Regulatory Authorities to evaluate the 90-day risk of both arterial and venous thromboembolism after initial diagnosis of COVID-19 in the ambulatory or hospital setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. The study found that there was variability in the risk of both arterial and venous thromboembolism by month across the countries among patients initially diagnosed with COVID-19 in the ambulatory or hospital setting. Differences in the healthcare systems, prevalence of comorbidities in the study cohorts, and approaches to the case definitions of thromboembolism likely contributed to the variability in estimates of thromboembolism risk across the countries. [ABSTRACT FROM AUTHOR]

Purpose: Immediate‐release forms of generic mixed amphetamine salts (MAS) have been the subject of passive surveillance reports signaling lack of effectiveness. We examined switching patterns that might suggest whether long‐term users of specific MAS are more likely to switch away or switch back after use of the MAS of interest in the FDA's Sentinel Distributed Database. Methods: We required at least 60‐day continuous supply of selected MAS grouped by Abbreviated New Drug Application (ANDA) to describe patterns of switching away from and to generics approved under the ANDAs of interest among individuals ages 15–64 years with attention deficit hyperactivity disorder or narcolepsy during 2013–2019. Results: We observed the greatest number of treatment episodes for ANDA 040422 (n = 525 771), followed by ANDA 202424 (n = 181 693), ANDA 040439 (n = 62 363), ANDA 040440 (n = 21 143), and ANDA 040480 (n = 8792). Of those with switches away from their original ANDA, episodes initiated on generic products under ANDA 040422 (48.6%) and ANDA 202424 (43.0%) were most likely to switch back, while those initiated on generic product under ANDA 040480 were least likely (24.1%). Of those episodes with switches to a generic under an ANDA of interest, about one‐third (range 27.1% to 37.0%) switched back to the same product. These switches back had a median time to switch of about 30 days. Conclusions: These descriptive analyses, although subject to limitations, did not suggest increased switching away or switching back after use of the generics of interest. Continued post‐marketing surveillance is warranted. [ABSTRACT FROM AUTHOR]

Congress mandated the creation of a postmarket Active Risk Identification and Analysis (ARIA) system containing data on 100 million individuals for monitoring risks associated with drug and biologic products using data from disparate sources to complement the US Food and Drug Administration's (FDA's) existing postmarket capabilities. We report on the first 6 years of ARIA utilization in the Sentinel System (2016–2021). The FDA has used the ARIA system to evaluate 133 safety concerns; 54 of these evaluations have closed with regulatory determinations, whereas the rest remain in progress. If the ARIA system and the FDA's Adverse Event Reporting System are deemed insufficient to address a safety concern, then the FDA may issue a postmarket requirement to a product's manufacturer. One hundred ninety‐seven ARIA insufficiency determinations have been made. The most common situation for which ARIA was found to be insufficient is the evaluation of adverse pregnancy and fetal outcomes following in utero drug exposure, followed by neoplasms and death. ARIA was most likely to be sufficient for thromboembolic events, which have high positive predictive value in claims data alone and do not require supplemental clinical data. The lessons learned from this experience illustrate the continued challenges using administrative claims data, especially to define novel clinical outcomes. This analysis can help to identify where more granular clinical data are needed to fill gaps to improve the use of real‐world data for drug safety analyses and provide insights into what is needed to efficiently generate high‐quality real‐world evidence for efficacy. [ABSTRACT FROM AUTHOR]

We described care received by hospitalized children with COVID-19 or multi-system inflammatory syndrome (MIS-C) prior to the 2021 COVID-19 Omicron variant surge in the US. We identified hospitalized children <18 years of age with a COVID-19 or MIS-C diagnosis (COVID-19 not required), separately, from February 2020-September 2021 (n = 126 hospitals). We described high-risk conditions, inpatient treatments, and complications among these groups. Among 383,083 pediatric hospitalizations, 2,186 had COVID-19 and 395 had MIS-C diagnosis. Less than 1% had both COVID-19 and MIS-C diagnosis (n = 154). Over half were >6 years old (54% COVID-19, 70% MIS-C). High-risk conditions included asthma (14% COVID-19, 11% MIS-C), and obesity (9% COVID-19, 10% MIS-C). Pulmonary complications in children with COVID-19 included viral pneumonia (24%) and acute respiratory failure (11%). In reference to children with COVID-19, those with MIS-C had more hematological disorders (62% vs 34%), sepsis (16% vs 6%), pericarditis (13% vs 2%), myocarditis (8% vs 1%). Few were ventilated or died, but some required oxygen support (38% COVID-19, 45% MIS-C) or intensive care (42% COVID-19, 69% MIS-C). Treatments included: methylprednisolone (34% COVID-19, 75% MIS-C), dexamethasone (25% COVID-19, 15% MIS-C), remdesivir (13% COVID-19, 5% MIS-C). Antibiotics (50% COVID-19, 68% MIS-C) and low-molecular weight heparin (17% COVID-19, 34% MIS-C) were frequently administered. Markers of illness severity among hospitalized children with COVID-19 prior to the 2021 Omicron surge are consistent with previous studies. We report important trends on treatments in hospitalized children with COVID-19 to improve the understanding of real-world treatment patterns in this population. [ABSTRACT FROM AUTHOR]

Background To the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but are marketed as generics, as a control group to address this bias in an evaluation aiming to compare the effectiveness of generic versus brand medications. Methods and findings For commercial health insurance enrollees from the US, administrative claims data were derived from 2 databases: (1) Optum Clinformatics Data Mart (years: 2004-2013) and (2) Truven MarketScan (years: 2003-2015). For a total of 8 drug products, the following groups were compared using a cohort study design: (1) patients switching from brand-name products to AGs versus generics, and patients initiating treatment with AGs versus generics, where AG use proxied brand-name use, addressing negative perception bias, and (2) patients initiating generic versus brand-name products (bias-prone direct comparison) and patients initiating AG versus brand-name products (negative control). Using Cox proportional hazards regression after 1:1 propensity-score matching, we compared a composite cardiovascular endpoint (for amlodipine, amlodipine-benazepril, and quinapril), non-vertebral fracture (for alendronate and calcitonin), psychiatric hospitalization rate (for sertraline and escitalopram), and insulin initiation (for glipizide) between the groups. Inverse variance meta-analytic methods were used to pool adjusted hazard ratios (HRs) for each comparison between the 2 databases. Across 8 products, 2,264,774 matched pairs of patients were included in the comparisons of AGs versus generics. A majority (12 out of 16) of the clinical endpoint estimates showed similar outcomes between AGs and generics. Among the other 4 estimates that did have significantly different outcomes, 3 suggested improved outcomes with generics and 1 favored AGs (patients switching from amlodipine brand-name: HR [95% CI] 0.92 [0.88-0.97]). The comparison between generic and brand-name initiators involved 1,313,161 matched pairs, and no differences in outcomes were noted for alendronate, calcitonin, glipizide, or quinapril. We observed a lower risk of the composite cardiovascular endpoint with generics versus brand-name products for amlodipine and amlodipine-benazepril (HR [95% CI]: 0.91 [0.84-0.99] and 0.84 [0.76-0.94], respectively). For escitalopram and sertraline, we observed higher rates of psychiatric hospitalizations with generics (HR [95% CI]: 1.05 [1.01-1.10] and 1.07 [1.01-1.14], respectively). The negative control comparisons also indicated potentially higher rates of similar magnitude with AG compared to brand-name initiation for escitalopram and sertraline (HR [95% CI]: 1.06 [0.98-1.13] and 1.11 [1.05-1.18], respectively), suggesting that the differences observed between brand and generic users in these outcomes are likely explained by either residual confounding or generic perception bias. Limitations of this study include potential residual confounding due to the unavailability of certain clinical parameters in administrative claims data and the inability to evaluate surrogate outcomes, such as immediate changes in blood pressure, upon switching from brand products to generics. Conclusions In this study, we observed that use of generics was associated with comparable clinical outcomes to use of brand-name products. These results could help in promoting educational interventions aimed at increasing patient and provider confidence in the ability of generic medicines to manage chronic diseases., Author(s): Rishi J. Desai 1,*, Ameet Sarpatwari 1, Sara Dejene 1, Nazleen F. Khan 1, Joyce Lii 1, James R. Rogers 1, Sarah K. Dutcher 2, Saeid Raofi 3, Justin [...]

Key Points: Question: Is the 90-day incidence of arterial thromboembolism and venous thromboembolism higher in patients hospitalized with COVID-19 vs in patients hospitalized with influenza? Findings: In this retrospective cohort study that included 93 906 patients, hospitalization with COVID-19 before vaccine availability and during vaccine availability was significantly associated with higher 90-day risk of venous thromboembolism (adjusted hazard ratios, 1.60 and 1.89, respectively) vs hospitalization with influenza in 2018-2019, but there was no significant difference in the risk of arterial thromboembolism among those hospitalized with COVID-19 during either period (adjusted hazard ratios, 1.04 and 1.07) vs those hospitalized with influenza. Meaning: Hospitalization with COVID-19 both before and during vaccine availability was significantly associated with a higher risk of venous thromboembolism, but not arterial thromboembolism, vs hospitalization with influenza in 2018-2019. Importance: The incidence of arterial thromboembolism and venous thromboembolism in persons with COVID-19 remains unclear. Objective: To measure the 90-day risk of arterial thromboembolism and venous thromboembolism in patients hospitalized with COVID-19 before or during COVID-19 vaccine availability vs patients hospitalized with influenza. Design, Setting, and Participants: Retrospective cohort study of 41 443 patients hospitalized with COVID-19 before vaccine availability (April-November 2020), 44 194 patients hospitalized with COVID-19 during vaccine availability (December 2020-May 2021), and 8269 patients hospitalized with influenza (October 2018-April 2019) in the US Food and Drug Administration Sentinel System (data from 2 national health insurers and 4 regional integrated health systems). Exposures: COVID-19 or influenza (identified by hospital diagnosis or nucleic acid test). Main Outcomes and Measures: Hospital diagnosis of arterial thromboembolism (acute myocardial infarction or ischemic stroke) and venous thromboembolism (deep vein thrombosis or pulmonary embolism) within 90 days. Outcomes were ascertained through July 2019 for patients with influenza and through August 2021 for patients with COVID-19. Propensity scores with fine stratification were developed to account for differences between the influenza and COVID-19 cohorts. Weighted Cox regression was used to estimate the adjusted hazard ratios (HRs) for outcomes during each COVID-19 vaccine availability period vs the influenza period. Results: A total of 85 637 patients with COVID-19 (mean age, 72 [SD, 13.0] years; 50.5% were male) and 8269 with influenza (mean age, 72 [SD, 13.3] years; 45.0% were male) were included. The 90-day absolute risk of arterial thromboembolism was 14.4% (95% CI, 13.6%-15.2%) in patients with influenza vs 15.8% (95% CI, 15.5%-16.2%) in patients with COVID-19 before vaccine availability (risk difference, 1.4% [95% CI, 1.0%-2.3%]) and 16.3% (95% CI, 16.0%-16.6%) in patients with COVID-19 during vaccine availability (risk difference, 1.9% [95% CI, 1.1%-2.7%]). Compared with patients with influenza, the risk of arterial thromboembolism was not significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.04 [95% CI, 0.97-1.11]) or during vaccine availability (adjusted HR, 1.07 [95% CI, 1.00-1.14]). The 90-day absolute risk of venous thromboembolism was 5.3% (95% CI, 4.9%-5.8%) in patients with influenza vs 9.5% (95% CI, 9.2%-9.7%) in patients with COVID-19 before vaccine availability (risk difference, 4.1% [95% CI, 3.6%-4.7%]) and 10.9% (95% CI, 10.6%-11.1%) in patients with COVID-19 during vaccine availability (risk difference, 5.5% [95% CI, 5.0%-6.1%]). Compared with patients with influenza, the risk of venous thromboembolism was significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.60 [95% CI, 1.43-1.79]) and during vaccine availability (adjusted HR, 1.89 [95% CI, 1.68-2.12]). Conclusions and Relevance: Based on data from a US public health surveillance system, hospitalization with COVID-19 before and during vaccine availability, vs hospitalization with influenza in 2018-2019, was significantly associated with a higher risk of venous thromboembolism within 90 days, but there was no significant difference in the risk of arterial thromboembolism within 90 days. This cohort study uses data from the US Food and Drug Administration Sentinel System to measure the 90-day risk of arterial thromboembolism and venous thromboembolism among patients hospitalized with COVID-19 before and during COVID-19 vaccine availability vs patients hospitalized with influenza. [ABSTRACT FROM AUTHOR]

Observational studies of oseltamivir use and influenza complications could suffer from residual confounding. Using negative control risk periods and a negative control outcome, we examined confounding control in a health-insurance-claims–based study of oseltamivir and influenza complications (pneumonia, all-cause hospitalization, and dispensing of an antibiotic). Within the Food and Drug Administration's Sentinel System, we identified individuals aged ≥18 years who initiated oseltamivir use on the influenza diagnosis date versus those who did not, during 3 influenza seasons (2014–2017). We evaluated primary outcomes within the following 1–30 days (the primary risk period) and 61–90 days (the negative control period) and nonvertebral fractures (the negative control outcome) within days 1–30. We estimated propensity-score–matched risk ratios (RRs) per season. During the 2014–2015 influenza season, oseltamivir use was associated with a reduction in the risk of pneumonia (RR = 0.72, 95% confidence interval (CI): 0.70, 0.75) and all-cause hospitalization (RR = 0.54, 95% CI: 0.53, 0.55) in days 1–30. During days 61–90, estimates were near-null for pneumonia (RR = 1.04, 95% CI: 0.95, 1.15) and hospitalization (RR = 0.94, 95% CI: 0.91, 0.98) but slightly increased for antibiotic dispensing (RR = 1.14, 95% CI: 1.08, 1.21). The RR for fractures was near-null (RR = 1.09, 95% CI: 0.99, 1.20). Estimates for the 2016–2017 influenza season were comparable, while the 2015–2016 season had conflicting results. Our study suggests minimal residual confounding for specific outcomes, but results differed by season. [ABSTRACT FROM AUTHOR]

Purpose Health plan claims may provide complete longitudinal data for timely, real‐world population‐level COVID‐19 assessment. However, these data often lack laboratory results, the standard for COVID‐19 diagnosis. Methods: We assessed the validity of ICD‐10‐CM diagnosis codes for identifying patients hospitalized with COVID‐19 in U.S. claims databases, compared to linked laboratory results, among six Food and Drug Administration Sentinel System data partners (two large national insurers, four integrated delivery systems) from February 20–October 17, 2020. We identified patients hospitalized with COVID‐19 according to five ICD‐10‐CM diagnosis code‐based algorithms, which included combinations of codes U07.1, B97.29, general coronavirus codes, and diagnosis codes for severe symptoms. We calculated the positive predictive value (PPV) and sensitivity of each algorithm relative to laboratory test results. We stratified results by data source type and across three time periods: February 20–March 31 (Time A), April 1–30 (Time B), May 1–October 17 (Time C). Results: The five algorithms identified between 34 806 and 47 293 patients across the study periods; 23% with known laboratory results contributed to PPV calculations. PPVs were high and similar across algorithms. PPV of U07.1 alone was stable around 93% for integrated delivery systems, but declined over time from 93% to 70% among national insurers. Overall PPV of U07.1 across all data partners was 94.1% (95% CI, 92.3%–95.5%) in Time A and 81.2% (95% CI, 80.1%–82.2%) in Time C. Sensitivity was consistent across algorithms and over time, at 94.9% (95% CI, 94.2%–95.5%). Conclusion: Our results support the use of code U07.1 to identify hospitalized COVID‐19 patients in U.S. claims data. [ABSTRACT FROM AUTHOR]

Background: We assessed the ability to identify key data relevant to influenza and other respiratory virus surveillance in a large‐scale US‐based hospital electronic medical record (EMR) dataset using seasonal influenza as a use case. We describe characteristics and outcomes of hospitalized influenza cases across three seasons. Methods: We identified patients with an influenza diagnosis between March 2017 and March 2020 in 140 US hospitals as part of the US FDA's Sentinel System. We calculated descriptive statistics on the presence of high‐risk conditions, influenza antiviral administrations, and severity endpoints. Results: Among 5.1 million hospitalizations, we identified 29,520 hospitalizations with an influenza diagnosis; 64% were treated with an influenza antiviral within 2 days of admission, and 25% were treated >2 days after admission. Patients treated >2 days after admission had more comorbidities than patients treated within 2 days of admission. Patients never treated during hospitalization had more documentation of cardiovascular and other diseases than treated patients. We observed more severe endpoints in patients never treated (death = 3%, mechanical ventilation [MV] = 9%, intensive care unit [ICU] = 26%) or patients treated >2 days after admission (death = 2%, MV = 14%, ICU = 32%) than in patients treated earlier (treated on admission: death = 1%, MV = 5%, ICU = 23%, treated within 2 days of admission: death = 1%, MV = 7%, ICU = 27%). Conclusions: We identified important trends in influenza severity related to treatment timing in a large inpatient dataset, laying the groundwork for the use of this and other inpatient EMR data for influenza and other respiratory virus surveillance. [ABSTRACT FROM AUTHOR]

Purpose Lymphoma is a health outcome of interest for drug safety studies. Studies using administrative claims data require the accurate identification of lymphoma cases. We developed and validated an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM)‐based algorithm to identify lymphoma in healthcare claims data. Methods: We developed a three‐component algorithm to identify patients aged ≥15 years who were newly diagnosed with Hodgkin (HL) or non‐Hodgkin (NHL) lymphoma from January 2016 through July 2018 among members of four Data Partners within the FDA's Sentinel System. The algorithm identified potential cases as patients with ≥2 ICD‐10‐CM lymphoma diagnosis codes on different dates within 183 days; ≥1 procedure code for a diagnostic procedure (e.g., biopsy, flow cytometry) and ≥1 procedure code for a relevant imaging study within 90 days of the first lymphoma diagnosis code. Cases identified by the algorithm were adjudicated via chart review and a positive predictive value (PPV) was calculated. Results: We identified 8723 potential lymphoma cases via the algorithm and randomly sampled 213 for validation. We retrieved 138 charts (65%) and adjudicated 134 (63%). The overall PPV was 77% (95% confidence interval: 69%–84%). Most cases also had subtype information available, with 88% of cases identified as NHL and 11% as HL. Conclusions: Seventy‐seven percent of lymphoma cases identified by an algorithm based on ICD‐10‐CM diagnosis and procedure codes and applied to claims data were true cases. This novel algorithm represents an efficient, cost‐effective way to target an important health outcome of interest for large‐scale drug safety and public health surveillance studies. [ABSTRACT FROM AUTHOR]

Purpose To describe utilization of filgrastim and infliximab, the first two products with biosimilars approved in the United States. Methods: We identified use of filgrastim (reference, tbo‐filgrastim, and filgrastim‐sndz) and infliximab (reference, infliximab‐dyyb, and infliximab‐abda) in the Sentinel Distributed Database using Healthcare Common Procedure Coding System (HCPCS) codes and National Drug Codes (NDCs) from January 2015 to August 2018. We calculated the proportion of use by code type and assessed uptake over time. We compared baseline patient characteristics and treatment indications. Among patients with >1 exposure episode, we characterized gaps between episodes. Results: Use was identified primarily via HCPCS codes (filgrastim: 86.4%‐97.7%; infliximab: 87.8%‐100%) although some was identified via NDCs (filgrastim: 2.2%‐13.5%; infliximab: <0.1%‐6.5%). Filgrastim reference product use declined from 89.4% in January 2015 to 30.3% in June 2018, with corresponding increases in filgrastim‐sndz (0% to 49.3%) and tbo‐filgrastim (10.6% to 20.4%). Infliximab biosimilar uptake was low (9.7% in June 2018). We identified 94 846 filgrastim reference product, 27 143 tbo‐filgrastim, and 38 264 filgrastim‐sndz users. For infliximab, we identified 125 412 reference product, 1034 infliximab‐dyyb, 49 infliximab‐abda, and 4855 undetermined biosimilar users. Patients receiving filgrastim products were largely similar, but differences in age, sex, and indication were observed across infliximab product users. The median exposure episode gap ranged from 1 to 3 days for filgrastim and 48 to 50 days for infliximab. Conclusion: Use of biosimilar filgrastim has increased in the United States, but infliximab biosimilar use remains low. Data on identification of biosimilars in claims data and observed gaps between exposure episodes can be used to support drug safety studies of biosimilars. [ABSTRACT FROM AUTHOR]

The anticoagulant response to warfarin, a narrow therapeutic index drug, increases with age, which may make older patients susceptible to adverse outcomes resulting from small differences in bioavailability between generic and brand products. Using US Medicare claims linked to electronic medical records from two large hospitals in Boston, we designed a cohort study of ≥ 65‐year‐old patients. Patients were followed for a composite effectiveness outcome of ischemic stroke or venous thromboembolism, a composite safety outcome, including major hemorrhage, and a 1‐year all‐cause mortality outcome. After propensity score fine‐stratification and weighting to account for > 90 confounders, hazard ratios comparing brand vs. generic warfarin initiators (95% confidence intervals) for the effectiveness, safety, and all‐cause mortality outcomes, were 0.97 (0.65–1.46), 0.94 (0.65–1.35), and 0.84 (0.62–1.13), respectively. Results from subgroup analyses of patients with atrial fibrillation, CHADS‐VASc score ≥ 3, and HAS‐BLED score ≥ 3 were consistent with the primary analysis. [ABSTRACT FROM AUTHOR]

Objective: To estimate real-world off-label use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 1 diabetes, estimate rates of diabetic ketoacidosis (DKA), and compare them with DKA rates observed in sotagliflozin clinical trials.Research Design and Methods: We identified initiators of SGLT2 inhibitors in the Sentinel System from March 2013 to June 2018, determined the prevalence of type 1 diabetes using a narrow and a broad definition, and measured rates of DKA using administrative claims data. Standardized incidence ratios (SIRs) were calculated using age- and sex-specific follow-up time in Sentinel and age- and sex-specific DKA rates from sotagliflozin trials 309, 310, and 312.Results: Among 475,527 initiators of SGLT2 inhibitors, 0.50% and 0.92% met narrow and broad criteria for type 1 diabetes, respectively. Rates of DKA in the narrow and broad groups were 7.3/100 person-years and 4.5/100 person-years, respectively. Among patients who met narrow criteria for type 1 diabetes, rates of DKA were highest for patients aged 25-44 years, especially females aged 25-44 years (19.7/100 person-years). More DKA events were observed during off-label use of SGLT2 inhibitors in Sentinel than would be expected based on sotagliflozin clinical trials (SIR = 1.83; 95% CI 1.45-2.28).Conclusions: Real-world off-label use of SGLT2 inhibitors among patients with type 1 diabetes accounted for a small proportion of overall SGLT2 inhibitor use. However, the risk for DKA during off-label use was notable, especially among young, female patients. Although real-word rates of DKA exceeded the expectation based on clinical trials, results should be interpreted with caution due to differences in study methods, patient samples, and study drugs. [ABSTRACT FROM AUTHOR]

Methodologic research evaluating confounding due to socioeconomic status (SES) in observational studies of medications is limited. We identified 7,109 patients who initiated brand or generic atorvastatin from Medicare claims (2011–2013) linked to electronic medical records and census data. We created a propensity score (PS) containing only claims‐based covariates and augmented it with additional claims‐based proxies for SES, ZIP code, and block group level SES. Cox models with PS fine‐stratification and weighting were used to compare rates of a cardiovascular end point and emergency department visits. Adjustment with only claims‐based variables substantially improved balance on all SES variables compared with the unadjusted. Although inclusion of SES in PS models further improved balance on SES variables compared with models with claims‐based covariates only, it did not materially change point estimates for either outcome. Inclusion of claims‐based proxies may mitigate confounding by SES when aggregate‐level SES information is unavailable. [ABSTRACT FROM AUTHOR]

However, as shown in Table 1 of our article, the differences among the 2 COVID-19 cohorts and the influenza cohort were not large for the baseline variables. COVID-19 vs Influenza for Risk of Thrombotic Events in Hospitalized Patients - Reply We agree that there were differences in our study[1] in observed baseline characteristics between the cohorts of patients hospitalized with COVID-19 and influenza. [Extracted from the article]

Small changes in bioavailability of narrow therapeutic index (NTI) drugs can alter clinical outcomes, raising concern over generic NTI substitution. We surveyed pharmacists to identify their perceptions of generic NTI drugs, their frequency of performing generic NTI substitution, and predictors of this behavior. Of 710 respondents (33% response rate), 87% perceived generic NTI drugs as effective as their brand‐name versions and 94% as safe. Whereas 82% almost always performed generic NTI substitution for initial prescriptions, only 60% did for refills. Pharmacists in non‐chain settings (odds ratio (OR) = 2.37; 95% confidence interval (CI) = 1.40–4.02), in practice longer (per year OR = 1.04; 95% CI = 1.02–1.06), in states with affirmative patient consent laws (OR = 1.88; 95% CI = 1.06–3.32), and in states with NTI‐specific substitution requirements (OR = 1.95; 95% CI = 1.16–3.26) were more likely not to substitute initial prescriptions. Education of non‐chain and veteran pharmacists and elimination of affirmative patient consent and NTI‐specific substitution requirements could increase generic NTI substitution. [ABSTRACT FROM AUTHOR]

Study Objective Generic drugs contain identical active ingredients as their corresponding brand drugs and are pharmaceutically equivalent and bioequivalent, whereas authorized generic drugs (AGs) contain both identical active and inactive ingredients as their corresponding brand drugs but are marketed as generics. This study compares generic-to-brand switchback rates between generic and AGs. Design Retrospective cohort study. Data Source Claims and electronic health record data from a regional U.S. health care system. Patients The full cohort consisted of 5542 unique patients who received select branded drugs during the 6 months prior to their generic drug market availability (between 1999 and 2014) and then were switched to an AG or generic drug within 30 months of generic drug entry. For these patients, 5929 unique patient-drug combinations (867 with AGs and 5062 with generic drugs) were evaluated. Measurements and Main Results Ten drugs with AGs and generics marketed between 1999 and 2014 were evaluated. The date of the first generic prescription was considered the index date for each drug, and it marked the beginning of follow-up to evaluate the occurrence of generic-to-brand switchback patterns over the subsequent 30 months. Switchback rates were compared between patients receiving AGs versus those receiving generics using multivariable Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson Comorbidity Score, pre-index drug use characteristics, and pre-index health care utilization. Among the 5542 unique patients who switched from brand to generic or brand to AG, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for AGs compared with generics (hazard ratio [ HR] 0.86, 95% confidence interval [ CI] 0.65-1.15). The likelihood of switchback was higher for alendronate ( HR 1.64, 95% CI 1.20-2.23) and simvastatin ( HR 1.81, 95% CI 1.30-2.54) and lower for amlodipine ( HR 0.27, 95% CI 0.17-0.42) compared with the other drugs evaluated. Conclusion Overall switchback rates were similar between AG and generic drug users, indirectly supporting similar efficacy and tolerability profiles for brand and generic drugs. Reasons for differences in switchback rates among specific products need to be explored further. [ABSTRACT FROM AUTHOR]

Purpose US Food and Drug Administration approval for generic drugs relies on demonstrating pharmaceutical equivalence and bioequivalence; however, some drug products have unique attributes that necessitate product-specific approval pathways. We evaluated rates of patients' switching back to brand-name versions from generic versions of four drugs approved via such approaches. Methods We used data from Optum LifeSciences Research Database to identify patients using a brand-name version of a study drug (acarbose tablets, salmon calcitonin nasal spray, enoxaparin sodium injection, and venlafaxine extended release tablets) or a control drug. We followed patients to identify switching to generic versions and then followed those who switched to identify whether they switched back to brand-name versions. We calculated switch and switch-back rates and used Kaplan-Meier and log-rank tests to compare rates between study and control drugs. Results Our cohort included 201 959 eligible patients. Brand-to-generic switch rates ranged from 66 to 106 switches per 100 person-years for study drugs and 80 to 110 for control drugs. Rates of switch-back to brand-name versions ranged from 5 to 37 among study drugs and 3 to 53 among control drugs. Switch-back rates were higher for venlafaxine vs. sertraline ( p < 0.01) and calcitonin vs. alendronate ( p = 0.01). Switch-back rates were lower for venlafaxine vs. paroxetine ( p < 0.01) and acarbose vs. nateglinide ( p < 0.01). Rates were similar for acarbose vs. glimepiride ( p = 0.97) and for enoxaparin vs. fondiparinux ( p = 0.11). Conclusion As compared to control drugs, patients were not more likely to systematically switch back from generic to brand-name versions of the four study drugs. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To synthesize the existing literature on benefits and risks of anticoagulant use after traumatic brain injury (TBI). Design: Systematic review. A literature search was performed in MEDLINE, International Pharmaceutical Abstracts, Health Star, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) on October 11, 2012, and updated on September 2, 2013, using terms related to TBI and anticoagulants. Main Measures: Human studies evaluating the effects of post-TBI anticoagulation on venous thromboembolism, hemorrhage, mortality, or coagulation parameters with original analyses were eligible for the review. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed throughout the conduct of the review. Results: Thirty-nine eligible studies were identified from the literature, of which 23 studies with complete information on post-TBI anticoagulant use and patient outcomes were summarized in this review. Meta-analysis was unwarranted because of varying methodological design and quality of the studies. Twenty-one studies focused on the effects of pharmacological thromboprophylaxis (PTP) post-TBI on venous thromboembolism and/or progression of intracranial hemorrhage, whereas 2 randomized controlled trials analyzed coagulation parameters as the result of anticoagulation. Conclusion: Pharmacological thromboprophylaxis appears to be safe among TBI patients with stabilized hemorrhagic patterns. More evidence is needed regarding effectiveness of PTP in preventing venous thromboembolism as well as preferred agent, dose, and timing for PTP. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions (1) Assess the harmonization of structured electronic health record data (laboratory results and medications) to reference terminologies and characterize the severity of issues. (2) Identify issues of data completeness by comparing complementary data domains, stratifying by time, care setting, and provenance.Queries were distributed to 3 Data Partners (DP). Using harmonization queries, we examined the top 200 laboratory results and medications by volume, identifying outliers and computing summary statistics. The completeness queries looked at 4 conditions of interest and related clinical concepts. Counts were generated for each condition, stratified by year, encounter type, and provenance. We analyzed trends over time within and across DPs.We found that the median number of codes associated with a given laboratory/medication name (and vice versa) generally met expectations, though there were DP‐specific issues that resulted in outliers. In addition, there were drastic differences in the percentage of patients with a given concept depending on provenance.The harmonization queries surfaced several mapping errors, as well as issues with overly specific codes and records with “null” codes. The completeness queries demonstrated having access to multiple types of data provenance provides more robust results compared with any single provenance type. Harmonization errors between source data and reference terminologies may not be widespread but do exist within CDMs, affecting tens of thousands or even millions of records. Provenance information can help identify potential completeness issues with EHR data, but only if it is represented in the CDM and then populated by DPs. [ABSTRACT FROM AUTHOR]

This section presents a correction to the article "Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 1 Diabetes and Rates of Diabetic Ketoacidosis," by Christian Hampp and colleagues, published in a 2020 issue.

Abstract: The modification of protein and non-protein thiols by oxidants including hydrogen peroxide (H2O2), peroxynitrite anion (ONOO−) and hypochlorous acid (HOCl) is well documented. Using an aromatic thiol, 5-thio-2-nitrobenzoic acid, and biologically relevant oxidants, we have identified higher oxidation states of sulfur including the sulfonic acid derivative and the disulfide S-oxide, a thiosulfinate, by HPLC and mass spectrometry. The initial reaction of ONOO− with 5-thio-2-nitrobenzoic acid yielded a transient red intermediate, the sulfenate anion. The red intermediate was observed when ONOO− and H2O2 were used to oxidize 5-thio-2-nitrobenzoic acid and it persisted for several seconds at pH 7. HOCl oxidized the disulfide, 5,5′dithiobis(2-nitrobenzoic acid) to the corresponding sulfonic acid and no additional products were detected. Using this system, we can directly compare the thiol-oxidizing abilities of several oxidants. Because 5-thio-2-nitrobenzoic acid is the product of the reaction of Ellman’s reagent with protein thiols, a detailed study of its stability in biological matrices where oxidants may be generated is warranted. [Copyright &y& Elsevier]

Lasso regression is widely used for large-scale propensity score (PS) estimation in healthcare database studies. In these settings, previous work has shown that undersmoothing (overfitting) Lasso PS models can improve confounding control, but it can also cause problems of non-overlap in covariate distributions. It remains unclear how to select the degree of undersmoothing when fitting large-scale Lasso PS models to improve confounding control while avoiding issues that can result from reduced covariate overlap. Here, we used simulations to evaluate the performance of using collaborative-controlled targeted learning to data-adaptively select the degree of undersmoothing when fitting large-scale PS models within both singly and doubly robust frameworks to reduce bias in causal estimators. Simulations showed that collaborative learning can data-adaptively select the degree of undersmoothing to reduce bias in estimated treatment effects. Results further showed that when fitting undersmoothed Lasso PS-models, the use of cross-fitting was important for avoiding non-overlap in covariate distributions and reducing bias in causal estimates., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability., Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE., Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US., Conclusion: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability., Competing Interests: VLR III reports research grants to his institution from the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH); consulting fees from Entasis, Takeda, and Urovant Sciences; and participation on the FDA Drug Safety and Risk Management Advisory Committee. NMC reports research funding from FDA via a Department of Health and Human Services (HHS) contract during the conduct of the study and funding from HPHCI (a non-profit organization that conducts work for government and private organizations, including pharmaceutical companies) outside the submitted work. RAH reports grants from FDA, NIH, and Merck. AMP reports royalties from UpToDate (including for an article on anticoagulation), consulting fees via advisory board from BioMarin LLC outside the submitted work, and speaker honorarium from the American Society of Hematology. DAD reports stock options in CVS Health. JLK reports unrelated research grants to her institution from Vir Biotechnology, Pfizer, Novartis, and the Centers for Disease Control and Prevention. PRR reports unrelated research grants to his institution from Chiesi, UCB, Amgen, Johnson & Johnson, Innovative Medicines Initiative, and the European Medicines Agency. KV reports unrelated research grants to her institution from Chiesi, UCB, Amgen, Johnson & Johnson, and the European Medicines Agency. DPA reports research grants to his institution from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma as well as consulting fees from Astra Zeneca and UCB Biopharma. The authors report no other conflicts of interest in this work., (© 2024 Lo Re III et al.)

Objective: To measure the 90 day risk of arterial thromboembolism and venous thromboembolism among patients diagnosed with covid-19 in the ambulatory (ie, outpatient, emergency department, or institutional) setting during periods before and during covid-19 vaccine availability and compare results to patients with ambulatory diagnosed influenza., Design: Retrospective cohort study., Setting: Four integrated health systems and two national health insurers in the US Food and Drug Administration's Sentinel System., Participants: Patients with ambulatory diagnosed covid-19 when vaccines were unavailable in the US (period 1, 1 April-30 November 2020; n=272 065) and when vaccines were available in the US (period 2, 1 December 2020-31 May 2021; n=342 103), and patients with ambulatory diagnosed influenza (1 October 2018-30 April 2019; n=118 618)., Main Outcome Measures: Arterial thromboembolism (hospital diagnosis of acute myocardial infarction or ischemic stroke) and venous thromboembolism (hospital diagnosis of acute deep venous thrombosis or pulmonary embolism) within 90 days after ambulatory covid-19 or influenza diagnosis. We developed propensity scores to account for differences between the cohorts and used weighted Cox regression to estimate adjusted hazard ratios of outcomes with 95% confidence intervals for covid-19 during periods 1 and 2 versus influenza., Results: 90 day absolute risk of arterial thromboembolism with covid-19 was 1.01% (95% confidence interval 0.97% to 1.05%) during period 1, 1.06% (1.03% to 1.10%) during period 2, and with influenza was 0.45% (0.41% to 0.49%). The risk of arterial thromboembolism was higher for patients with covid-19 during period 1 (adjusted hazard ratio 1.53 (95% confidence interval 1.38 to 1.69)) and period 2 (1.69 (1.53 to 1.86)) than for patients with influenza. 90 day absolute risk of venous thromboembolism with covid-19 was 0.73% (0.70% to 0.77%) during period 1, 0.88% (0.84 to 0.91%) during period 2, and with influenza was 0.18% (0.16% to 0.21%). Risk of venous thromboembolism was higher with covid-19 during period 1 (adjusted hazard ratio 2.86 (2.46 to 3.32)) and period 2 (3.56 (3.08 to 4.12)) than with influenza., Conclusions: Patients diagnosed with covid-19 in the ambulatory setting had a higher 90 day risk of admission to hospital with arterial thromboembolism and venous thromboembolism both before and after covid-19 vaccine availability compared with patients with influenza., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: VLR reports research grants to his institution from the US Food and Drug Administration (FDA) during the conduct of the study and personal consulting fees from Takeda outside the submitted work. DAD reports contract research funding from FDA Sentinel Initiative via Harvard Pilgrim Health Care Institute. LBH reports contract research funding from FDA Sentinel Initiative during the conduct of the study and grants from Kaiser Permanente Garfield Memorial Fund for covid-19 related research outside the submitted work. SH reports grants from FDA, Pfizer, and Johnson & Johnson during the conduct of the study, consulting for Novo Nordisk, Arbor Pharmaceuticals, the Medullary Thyroid Cancer Consortium (Novo Nordisk, AstraZeneca, GlaxoSmithKline, and Eli Lilly), Biogen, Intercept Pharmaceuticals, Provention Bio, bluebird bio, and Amylyx Pharmaceuticals, and is a special government employee of the FDA. RAH reports grants from FDA during the conduct of the study and grants from Merck, Pfizer, and Johnson & Johnson outside of the submitted work. CNM-W works for CVS Health Clinical Trial Services LLC, an affiliate of CVS Health. She is responsible for CVS Health Clinical Trial Services activities with the FDA Sentinel Initiative, including both the Sentinel Program and BEST Program, and other Distributed Research Networks that use Sentinel infrastructure to analyze health claims data administered by Aetna, also a CVS Health affiliate. The Distributed Research Networks include Academy of Managed Care Pharmacy’s Biologics and Biosimilars Collective Intelligence Collaborative; Reagan-Udall’s Foundation IMEDS multisite research service agreements funded by Abbvie, Merck, Novartis, and Pfizer; Patient Centered Outcomes Research Institute; Research Action for Health Network; TherapeuticsMD; National Evaluation System for Health Technology Coordinating Center; and, Harvard Pilgrim Health Care Institute multisite research subcontracts funded by FDA, National Institutes of Health, Pfizer, Janssen, and GSK. To the best of her knowledge, CNM-W is not aware that any of these professional roles or activities create a conflict of interest with this project; however, she is itemizing them here for purposes of full disclosure. PAP reports contract funding support from HPHCI during the conduct of the study and outside the submitted work. AMP reports research funding to her institution from FDA during the conduct of the study and research funding from Sanofi Genzyme Research to her institution outside of the submitted work. NMC reports research funding from FDA via an HHS contract during the conduct of the study and funding from Harvard Pilgrim Health Care Institute (a non-profit organization that conducts work for government and private organizations, including pharmaceutical companies) outside of the submitted work. All other authors report no competing interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We describe the baseline characteristics and complications of individuals with influenza in the US FDA's Sentinel System by antiviral treatment timing., Design: Retrospective cohort design., Patients: Individuals aged ≥6 months with outpatient diagnoses of influenza in June 2014-July 2017, 3 influenza seasons., Methods: We identified the comorbidities, vaccination history, influenza testing, and outpatient antiviral dispensings of individuals with influenza using administrative claims data from 13 data partners including the Centers for Medicare and Medicaid Services, integrated delivery systems, and commercial health plans. We assessed complications within 30 days: hospitalization, oxygen use, mechanical ventilation, critical care, ECMO, and death., Results: There were 1,090,333 influenza diagnoses in 2014-2015; 1,005,240 in 2016-2017; and 578,548 in 2017-2018. Between 49% and 55% of patients were dispensed outpatient treatment within 5 days. In all periods >80% of treated individuals received treatment on the day of diagnosis. Those treated on days 1-5 after diagnosis had higher prevalences of diabetes, chronic obstructive pulmonary disease, asthma, and obesity compared to those treated on the day of diagnosis or not treated at all. They also had higher rates of hospitalization, oxygen use, and critical care. In 2014-2015, among those aged ≥65 years, the rates of hospitalization were 45 per 1,000 diagnoses among those treated on day 0; 74 per 1,000 among those treated on days 1-5; and 50 per 1,000 among those who were untreated., Conclusions: In a large, national analysis, approximately half of people diagnosed with influenza in the outpatient setting were treated with antiviral medications. Delays in outpatient dispensed treatment were associated with higher prevalence of comorbidities and higher rates of complication.

Objectives: To better understand patients' and pharmacists' preferences for and experiences with changes in pill appearance (size, shape, color, and markings)., Study Design: Cross-sectional., Methods: We conducted independent national surveys of patients 50 years and older taking generic drugs for depression, diabetes, epilepsy, HIV, hyperlipidemia, or hypertension and of licensed pharmacists practicing in chain, franchise, or independent pharmacies. Responses were collected between January and April 2016., Results: Of 1000 patient respondents (30% response rate), most reported experiencing changes in pill appearance (51%) and preferred to be notified about them (82%), but less than half recalled being notified (verbally: 36%; via sticker: 45%). Among patients who reported experiencing a change, 12% reported stopping their medication or using it less frequently. Of 710 pharmacist respondents (33% response rate), many reported changes in pill appearance occurring frequently in their pharmacies (47% reported that changes occurred 6 or more times per month) and more than three-fourths reported notifying patients about them often (verbally: 88%; via sticker: 77%)., Conclusions: Our findings reveal opportunities to improve patients' experiences with pill appearance changes through better notification practices and patient education.

Context: Generic drugs account for 9 out of 10 prescriptions dispensed in the United States but for a lower proportion of commonly prescribed thyroid hormone replacement therapies., Objective: Characterize temporal patterns of generic and brand-name thyroid hormone drug use, including patient and prescriber characteristics associated with brand-name use., Design and Setting: Cross-sectional longitudinal analysis of national data from a large administrative claims database from January 2007 through December 2016., Patients: Adults with insurance coverage through commercial, Medicare Advantage, and Medicare Part D health plans., Main Outcome Measures: Generic and brand-name thyroid hormone drug use., Results: From 2007 to 2016, the annual number of thyroid hormone treatment pharmacy fills increased from 8,905,836 in 2007 to 11,613,923 in 2016, 73.6% of which were for generic levothyroxine, 23.4% for brand-name levothyroxine, and the remaining for other formulations. Dispensing of generic thyroid hormone drugs increased from 59.8% in 2007 to 84.9% in 2016 and was consistently higher among Medicare Advantage and Medicare Part D when compared with the commercial beneficiary population. For all three beneficiary populations, use of brand-name products was less common among older adults and more common among women and those receiving prescriptions from endocrinologists and was more common among those of white race and with greater household income for the Medicare Advantage and commercial beneficiary populations (P < 0.001)., Conclusions: Brand-name thyroid hormone product use declined from 2007 to 2016 among three large, national insurer beneficiary populations. Although certain patient characteristics were associated with brand-name use, prescriber specialty was the strongest predictor., (Copyright © 2019 Endocrine Society.)

Objective: To synthesize the existing literature on benefits and risks of anticoagulant use after traumatic brain injury (TBI)., Design: Systematic review. A literature search was performed in MEDLINE, International Pharmaceutical Abstracts, Health Star, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) on October 11, 2012, and updated on September 2, 2013, using terms related to TBI and anticoagulants., Main Measures: Human studies evaluating the effects of post-TBI anticoagulation on venous thromboembolism, hemorrhage, mortality, or coagulation parameters with original analyses were eligible for the review. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed throughout the conduct of the review., Results: Thirty-nine eligible studies were identified from the literature, of which 23 studies with complete information on post-TBI anticoagulant use and patient outcomes were summarized in this review. Meta-analysis was unwarranted because of varying methodological design and quality of the studies. Twenty-one studies focused on the effects of pharmacological thromboprophylaxis (PTP) post-TBI on venous thromboembolism and/or progression of intracranial hemorrhage, whereas 2 randomized controlled trials analyzed coagulation parameters as the result of anticoagulation., Conclusion: Pharmacological thromboprophylaxis appears to be safe among TBI patients with stabilized hemorrhagic patterns. More evidence is needed regarding effectiveness of PTP in preventing venous thromboembolism as well as preferred agent, dose, and timing for PTP.