Summary Objective: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and potentially fatal adverse skin reactions that are most commonly triggered by certain medications. One class of medications that have been highly associated with SJS/TEN reactions are antiepileptic drugs (AEDs). We sought to quantify the risk of SJS/TEN associated with AEDs as a class, as well as individual AEDs, in the United States. Methods: An analysis was performed of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from July 2014 through December 2017. Rates of SJS/TEN were calculated for each AED compared with all other non-AEDs. Reporting odds ratios (ROR), proportional reporting ratios (PRR), and 95% confidence intervals (CI) were calculated using OpenEpi. Results: AEDs had the most reports of SJS/TEN than any other medication class with 198 reports. AEDs as a class had a ROR of 8.7 (CI 7.5–10.2) and a PRR of 8.7 (CI 7.5–10.2) compared with all other non-AEDs. The AEDs with the highest risk estimates were zonisamide (ROR: 70.2, CI 33.1–148.7; PRR: 68.7, CI 32.9–143.5), rufinamide (ROR: 60.0, CI 8.3–433.5; PRR: 58.9, CI 8.4–411.5), clorazepate (ROR: 56.0, CI 7.8–404.1; PRR: 55.1, CI 7.8–385.0), lamotrigine (ROR: 53.0, CI 43.2–64.9; PRR: 52.2, CI 42.7–63.7), phenytoin (ROR: 26.3, CI 15.5–44.7; PRR: 26.1, CI 15.4–44.2), and carbamazepine (ROR: 24.5, CI 16.0–37.5; PRR: 24.3, CI 16.0–37.1).

Word Count: 222Manuscript Word Count: 1,433 AbstractObjective: Though thrombocytopenia is a known adverse effect with linezolid, the first-in class oxazolidinone antibiotic, some have suggested a lower risk of thrombocytopenia with tedizolid, the second-in-class oxazolidinone antibiotic. We sought to evaluate adverse event reports for thrombocytopenia with tedizolid and linezolid from the Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: To assess the period since tedizolid approval, we included initial FAERS reports from ) and PRR was 11.1 (95% CI 10.38-11.87).Conclusion: We observed a significantly increased risk of thrombocytopenia of similar magnitude with both linezolid and tedizolid. Thrombocytopenia with tedizolid should be assessed with real-world comparative safety studies as more patients are treated with tedizolid.

Purpose Limited evidence is available to explain the role of four components of health-related quality of life (HRQoL) on breast and cervical cancer screening. The objective of this study was to determine the relationship between four HRQoL aspects and use of mammography and Pap test screening in US women. Methods Data were obtained from the 2012 Behavioral Risk Factor Surveillance System (BRFSS). The outcome variables were receiving mammogram <2 versus ≥2 years in women aged 50-74 years, and receiving Pap test <3 versus ≥3 years in women aged 18-64 years. Eight logistic regression models were conducted to test the role of four HRQoL aspects (general health status, physical HRQoL, mental HRQoL, and activity limitation) on the two screening variables, after adjusting for covariates. Statistical analysis accounted for the complex sampling design of the BRFSS and the a priori alpha error was set at p ≤ 0.05. Results Among respondents, approximately 74% and 78% of the women received mammography and Pap test, respectively. Three HRQoL aspects (general health status, physical HRQoL, and activity limitation) were significantly associated with mammography use (all p-values<0.05), whereas two HRQoL aspects (general health status and physical HRQoL) were significantly associated with Pap test (p-values≤0.05). All significant relationships demonstrated higher cancer screening rates among individuals with better HRQoL. Conclusions HRQoL is an important factor associated with use of mammography and Pap test. Future studies should explore the mechanisms associated with an individual's HRQoL and use HRQoL assessment as an avenue to influence adherence to use of mammography and Pap tests.

Introduction In October 2015, the Food and Drug Administration (FDA) instituted an update to the mandatory Risk Evaluation and Mitigation Strategy (REMS) program for clozapine to improve safety monitoring of hematologic events. However, the impact of the clozapine REMS program on reporting of hematologic adverse events has not been quantified. Methods We assessed adverse event reports for agranulocytosis, granulocytopenia, leukopenia, and neutropenia from the FDA Adverse Event Reporting System (FAERS) for a 1-year time period before (October 2014 to September 2015, pre-REMS) and after (October 2015 to September 2016, post-REMS) the implementation of the clozapine REMS program. The AERSMine platform was used to capture historical effect estimates (October 2004 to September 2014). Reporting odds ratios (ROR), proportional reporting ratios (PRR), and corresponding Taylor series 95% confidence intervals (CIs) were calculated for hematologic events with clozapine compared with all other medications using OpenEpi. Results Reporting rates for agranulocytosis, granulocytopenia, leukopenia, and neutropenia with clozapine all increased from the pre-REMS to post-REMS time frames, ranging from a 2-fold increase with leukopenia to a 40-fold increase with neutropenia; the composite measure of all hematologic reports had a 12-fold increase. During the post-REMS time frame, the ROR increased by 1691% (111.4, 95% CI 100.6-123.4) compared with the pre-REMS time frame (7.1, 95% CI 5.2-9.6), and the PRR increased by 1280% (83.1, 95% CI 76.8-90.0 vs 6.9, 95% CI 5.1-9.4) for the composite outcome. Discussion We observed significant increases in reports of hematologic adverse events with clozapine after the introduction of the clozapine REMS program. Future research should explore the impact of the less stringent exclusionary and discontinuation criteria on utilization (eg, expanded access) and clinical outcomes (eg, treatment effectiveness and adverse events).

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