Gene-x-environment analysis supports protective effects of eveningness chronotype on self-reported and actigraphy-derived sleep duration among those who always work night shifts in the UK Biobank.

Previous research has linked having an eveningness chronotype with a higher tolerance for night shift work, suggesting the ability to work nights without health consequences may partially depend upon having a circadian clock optimized for these times. As chronotypes entrain over time to environmental cues, it remains unclear whether higher relative eveningness among healthy night workers reflects a moderating or mediating effect of chronotype on health. We address these concerns conducting a genome-wide association study and utilizing a polygenic score (PGS) for eveningness as a time-invariant measure of chronotype. On a sample of 53 211 workers in the UK Biobank (2006-2018), we focus on the effects of night shift work on sleep duration, a channel through which night shift work adversely affects health. We ask whether a higher predisposition toward eveningness promotes night shift work tolerance. Results indicate that regular night shift work is associated with a 13-minute (3.5%) reduction in self-reported sleep per night relative to those who never work these hours (95% confidence interval [CI] = -17:01, -8:36). We find that eveningness has a strong protective effect on night workers: a one-SD increase in the PGS is associated with a 4-minute (28%) reduction in the night shift work sleep penalty per night (CI = 0:10, 7:04). This protective effect is pronounced for those working the longest hours. Consistent patterns are observed with an actigraphy-derived measure of sleep duration. These findings indicate that solutions to health consequences of night shift work should take individual differences in chronotype into account.

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma.

BACKGOUND: Lenalidomide-based regimens are commonly used for early relapse in patients with relapsed and/or refractory multiple myeloma (RRMM) receiving at least one prior line of therapy. In the absence of head-to-head comparison, matching-adjusted indirect comparison (MAIC) was conducted to demonstrate efficacy and safety of isatuximab+carfilzomib+dexamethasone (Isa-Kd) versus daratumumab + lenalidomide + dexamethasone (Dara-Rd) in RRMM. METHODS: Patient-level data from IKEMA trial (Isa-Kd, n = 179) were matched to aggregate data from POLLUX (Dara-Rd, n = 286). Hazard ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) and overall survival (OS) were generated by weighted Cox proportional hazard models. Odds ratios (OR), 95% CI, and p-value were calculated for ≥very good partial response (≥VGPR) and treatment-emergent adverse events (TEAEs). RESULTS: After matching, no significant differences were observed between Isa-Kd and Dara-Rd in baseline characteristics except for patients with >3 prior lines (0.0% vs. 4.9%). Isa-Kd showed significantly better PFS (HR [95% CI]: 0.46 [0.24-0.86]; p = 0.0155), statistically non-significant improvement favoring Isa-Kd in OS (0.47 [0.20-1.09]; 0.0798), and ≥VGPR (OR [95% CI]: 1.53 [0.89-2.64]; p = 0.1252) than Dara-Rd. Odds of occurrence were significantly lower for some all-grade and grade 3/4 TEAEs with Isa-Kd than Dara-Rd. CONCLUSION: These results support Isa-Kd as an efficacious treatment for early relapse in non-lenalidomide refractory patients.

Cohort Trends in the Association Between Sibship Size and Educational Attainment in 26 Low-Fertility Countries.

Children with many siblings have lower average educational attainment compared with children raised in smaller families, and this disadvantage by sibship size has been observed across many countries. We still know remarkably little, however, about how sibship size disadvantage has changed within countries and how such trends vary across countries. Using comparative data from 111 surveys from 26 low-fertility countries, we find an overall trend of growing sibship size disadvantage across cohorts in the majority of countries: between the 1931-1940 birth cohort and the 1971-1980 birth cohort, 16 of 26 countries showed a statistically significant increase in sibship size disadvantage in education, while only two countries showed a significant reduction in sibship size disadvantage. The disadvantage in years of education associated with having an additional sibling increased remarkably in post-socialist (0.3) and East Asian countries (0.34) and, to a lesser extent, Western European countries (0.2). In contrast, this disadvantage showed little change in Nordic countries (0.05) and even decreased in Anglo-Saxon countries (-0.11). We discuss explanations and implications of our comparative evidence in the context of the intergenerational transmission of education.

Gender, nonstandard schedules, and partnership quality in the UK: Exploring heterogeneous effects through a quasi-experiment.

This study adopts a potential outcomes framework to explore how nonstandard schedules (i.e., employment during nights, evenings, and weekends) affect partnership quality (PQ). Competing theories of positive and negative selection are proposed based on the contention that there will be heterogeneous returns to partnerships from nonstandard schedules (in terms of penalties and benefits) that will depend on how and why partners have selected into these arrangements. Mahalanobis Distance Matching techniques are then employed to mimic blocked randomization, simulate potential outcomes and identify patterns of heterogeneous effects using a sample of 21,766 workers in co-resident partnerships included in the UK Household Longitudinal Study (2010-2017). Results indicate that after correcting for baseline selection, weekend work only negatively affects PQ for mothers, whilst nonstandard hours take their most negative effect on PQ when worked by women without children. Maternal nonstandard hour work, on the other hand, is shown to positively affect PQ. However, results suggest this positive effect may often be obscured by patterns of negative selection. That is, the mothers most commonly observed in nonstandard hours are in partnerships that stand to benefit the least. In contrast, consistent patterns of positive selection into both nonstandard days and hours are observed for men without children, demonstrating the centrality of bargaining power and household constraints for selection. Such findings highlight the need to consider complex and gendered processes of household and socioeconomic selection when studying the relationship between nonstandard schedules and outcomes relating to family cohesion.