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tudy Objective Ipilimumab, pembrolizumab, and nivolumab are checkpoint inhibitors (CPIs) that activate T-cell–mediated immune response. CPI can provide durable benefits to some cancer patients with melanoma, renal cell cancer, non–small cell lung cancer, or a growing list of other cancers. However, CPI treatment is also associated with adverse immune-mediated reactions (IMRs) that can be life-threatening. This pharmacovigilance analysis aims to characterize IMR signals in relation to CPI treatment. Design Retrospective pharmacovigilance disproportionality analysis. Data Source U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Measurements and Main Results Adverse event reports submitted to FAERS between 2011 and 2015 were analyzed. CPIs were identified by generic names, and IMRs were identified by MedDRA Preferred Terms. Empirical Bayes geometric means with corresponding 95% confidence intervals (EB05-EB95) were calculated as CPI-IMR association metrics. Signals were defined as metrics with EB05 ≥ 2.0. Overall, 1,018 IMR events were submitted for CPIs, corresponding to 76% for ipilimumab, 15% for nivolumab, and 9% for pembrolizumab. The period of data collection precluded data on the most recently approved CPI agents. IMRs consisted of 51% colitis, 16% endocrinopathies, 12% pneumonitis, 11% hepatitis, 4% infusion-related reactions, 3% nephritis, and 3% other IMRs. Colitis contributed to 63% and 41% of IMRs for ipilimumab and nivolumab, respectively. Pneumonitis and hepatitis contributed to a majority of IMRs for pembrolizumab, for which nephritis and infusion-related reactions were not reported. Signals of IMRs were detected for CPIs as a class (EB05 = 12.4) and individual agents: ipilimumab (EB05 = 13.2), nivolumab (EB05 = 15.0), and pembrolizumab (EB05 = 7.3). Colitis and pneumonitis had the strongest signals for CPIs (EB05 = 45.6 and EB05 = 17.6, respectively). Colitis was the strongest signal for ipilimumab (EB05 = 54.2), and pneumonitis was the strongest signal for nivolumab (EB05 = 48.0) and pembrolizumab (EB05 = 21.8). Conclusion Cancer immunotherapy with CPIs is associated with a multitude of IMRs, especially colitis and pneumonitis. Individual CPIs had variable IMR signals, and pharmacoepidemiologic studies are required to evaluate the identified signals.

The effect of post annealing in CdCl2 was investigated to elucidate the correlation between the evolution of the microstructure of CdTe thin films with the annealing time and the performance of CdS/CdTe thin-film solar cells made by in situ pulsed laser deposition (PLD). It has been found that the crystallinity of the annealed film is improved considerably as the CdTe polycrystalline grains evolved into grain clusters with a dendrite structure. While longer annealing time allows larger grain size, the increased film surface roughness outweighs the benefit of the improved crystallinity, resulting in increased structural disorders, such as pinholes. In fact, the concentration of the pinholes was found to increases monotonically with annealing time when it exceeds the optimal value, resulting in degradation of device performance and yield especially when pinholes appeared near the CdS/CdTe interface. This result illustrates the importance of controlling the microstructure of CdTe film and its interface with CdS to high-performance CdTe/CdS thin-film solar cells.

Study Objective Finasteride, a 5α-reductase inhibitor, is marketed in a low dose (1 mg) as a popular therapy for androgenic alopecia in young men. As case reports and small surveys have suggested a link between persistent sexual dysfunction (SD) and suicidal ideation (SI) with low-dose finasteride, the aim of this study was to detect signals of SD and SI secondary to low-dose finasteride use in young men. Design Retrospective pharmacovigilance disproportionality analysis. Data Source United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Measurements and Main Results Low-dose finasteride-related adverse event reports for men aged 18–45 years that were submitted to the FAERS between 1998 and 2013 were retrieved. Multi-item Gamma Poisson Shrinker disproportionality analysis was applied to calculate the empirical Bayes geometric mean (EBGM) and corresponding 95% confidence interval (CI) as an association metric between low-dose finasteride and the events of interest. Signals were defined as associations with thresholds of a CI lower limit of 2.0 or greater. Medical Dictionary for Regulatory Activities Preferred Terms denoting to SD and SI were identified to reflect the outcome of interest. In total, of 4910 reports, 577 persistent SD and 39 SI adverse event reports (11.8% and 7.9%, respectively) were identified for young men using low-dose finasteride; 34 (87.2%) of the 39 men with SI also experienced SD. The majority of these events were serious (e.g., contributed to the patient's death, hospitalization, or disability). Low-dose finasteride was associated with more than expected reporting of SD in young men compared with reporting of these events with all other drugs within the database (EBGM 28.0, 95% CI 26.1–30.0). Disproportional reporting in SI events was noted, although it did not reach signal threshold (EBGM 1.72; 95% CI 1.31–2.23). Among serious SD events, 43% led to disability; 28% required medical intervention, including hospitalization; and 5% were life-threatening. Six fatal SD reports were identified. Conclusion Persistent SD might be a potential risk of low-dose finasteride for androgenic alopecia therapy in young men, and this risk might contribute to SI. Our findings provide a strong hypothesis for pharmacoepidemiologic studies to further examine this association.