The effect of work shift and sleep duration on various aspects of police officers' health.

Police officers are prone to cardiovascular disease, overweight, and obesity. Because night-shift work affects sleep, a modifiable risk factor linked to chronic disease, the researchers explored the relationship among shift work, sleep, and wellness for police officers. Sleep, C-reactive protein (CRP) levels, stress, fatigue, and body mass index were used to compare officers who worked primarily day shifts to those who worked primarily evening or night shifts, and officers who slept less than 6 hours per day to those who slept at least 6 hours per day. A cross-sectional study of 85 male officers, 20 to 63 years old, was completed at three Midwestern police departments. The Pittsburgh Sleep Quality Index was used to assess sleep. A questionnaire was used to collect officer demographics and work hours. Other measurements included serum CRP, height, weight, perceived stress, and vital exhaustion. The relative risk of sleeping less than 6 hours per day for officers who primarily worked non-day shifts, compared to those who worked day shifts, was 14.27 (95% confidence interval [CI], 1.98-102.95, p < .001), and the relative risk of overall poor sleep quality for officers who slept less than 6 hours per day, compared to those who slept more hours, was 2.44 (95% CI, 1.15-5.20, p = .027). CRP was not associated with shift or sleep duration, even when adjusted for officers' ages.

HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer.

PURPOSE: Hepatobiliary adverse events (AEs) have been observed in a small proportion of patients with metastatic breast cancer (MBC) treated with lapatinib. This study sought to identify gene variants associated with lapatinib-induced ALT elevation and hepatobiliary AEs. PATIENTS AND METHODS: A two-stage pharmacogenetic investigation of ALT elevation was conducted in lapatinib-treated patients with MBC. Exploratory marker identification evaluated classical HLA alleles, candidate genes, and genome-wide screening in 37 cases with ALT greater than 3 times the upper limit of normal (ULN) and 286 controls with ALT ≤ 1× ULN, selected from 901 lapatinib-treated patients in 12 trials. Markers achieving prespecified association thresholds were progressed to an independent confirmatory data set of 24 ALT cases and 155 controls selected from a subsequent trial of 374 lapatinib-treated patients. RESULTS: Of 58 variants associated with ALT elevation in the exploratory data set, four exceeded the prespecified significance threshold in the confirmatory analysis. These variants reside in the same MHC genomic locus and include HLA-DQA1*02:01. In the confirmatory study, DQA1*02:01 allele carriage was present in 71% of ALT cases and in 21% of controls (P < .001; odds ratio, 9.0; 95% CI, 3.2 to 27.4). As a predictor of liver safety risk in ALT cases versus noncases, DQA1*02:01 had negative and positive predictive values of 0.97 (95% CI, 0.95 to 0.99) and 0.17 (95% CI 0.10 to 0.26), respectively. CONCLUSION: These results support a role for immune mechanisms in lapatinib-induced hepatotoxicity. Further work is required to determine whether testing for DQA1*02:01 allele carriage is clinically useful in managing liver safety risk during lapatinib treatment.