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Dipeptidyl peptidase‐4 inhibitors (DPP‐4i) interact with sulfonylureas to increase their risk of hypoglycemia. Our population‐based study assessed whether intraclass pharmacologic heterogeneity among sulfonylureas (long‐ vs. short‐acting) and DPP‐4i (peptidomimetic vs. non‐peptidomimetic) modifies this interaction. We conducted a cohort study using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data. We assembled a cohort of patients initiating sulfonylureas (2007–2020). Using a time‐varying exposure definition, we assessed the risk of severe hypoglycemia (hospitalization with or death due to hypoglycemia) associated with (i) concomitant use of long‐acting sulfonylureas (glimepiride and glibenclamide) with DPP‐4i compared with concomitant use of short‐acting sulfonylureas (gliclazide and glipizide) with DPP‐4i; and (ii) concomitant use of sulfonylureas with peptidomimetic DPP‐4i (saxagliptin and vildagliptin) compared with concomitant use of sulfonylureas with non‐peptidomimetic DPP‐4i (sitagliptin, linagliptin, and alogliptin). Time‐dependent Cox models estimated confounder‐adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Our cohort included 196,138 sulfonylurea initiators. During a median follow‐up of 6 years, 8,576 events of severe hypoglycemia occurred. Compared with concomitant use of short‐acting sulfonylureas with DPP‐4i, concomitant use of long‐acting sulfonylureas with DPP‐4i was not associated with the risk of severe hypoglycemia (adjusted HR: 0.87, 95% CI: 0.65–1.16). Compared with concomitant use of sulfonylureas with non‐peptidomimetic DPP‐4i, concomitant use of sulfonylureas with peptidomimetic DPP‐4i was also not associated with the risk of severe hypoglycemia (HR: 0.96, 95% CI: 0.76–1.22). Intra‐class pharmacologic heterogeneity did not modify the association between concomitant use of sulfonylureas (short‐ vs. long‐acting) and DPP‐4i (peptidomimetic vs. non‐peptidomimetic) and the risk of severe hypoglycemia.

<p>  </p> <p><strong>Background:</strong> The hypoglycemic potential of beta-blockers among users of sulfonylureas, drugs that strongly increase the risk of this potentially fatal adverse effect, is not well understood. Our population-based cohort study assessed the potential association between concomitant use of sulfonylureas and beta-blockers versus use of sulfonylureas alone and the risk of severe hypoglycemia.</p> <p><strong>Methods:</strong> Using the UK's Clinical Practice Research Datalink Aurum, we included patients initiating sulfonylureas between 1998 and 2020, excluding those with beta-blocker use in the past 6 months. Time-dependent Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycemia (hospitalization with or death due to hypoglycemia; ICD-10 codes: E16.0, E16.1, E16.2) associated with current concomitant use of sulfonylureas and beta-blockers compared to current sulfonylurea use alone, adjusted for baseline confounders. We also compared current concomitant use of sulfonylureas and non-cardioselective versus cardioselective beta-blockers.</p> <p><strong>Results:</strong> Our cohort included 252,866 initiators of sulfonylureas (mean age 61.3 years, 43% female). Median follow-up was 7.9 years. The crude incidence rate of severe hypoglycemia was 7.8 per 1000/year. Concomitant use of sulfonylureas and beta-blockers was associated with an increased risk of severe hypoglycemia compared to sulfonylurea use alone (HR, 1.53; 95% CI, 1.42-1.65). There was no difference in the risk between concomitant use of sulfonylureas and non-cardioselective beta-blockers and concomitant use of sulfonylureas and cardioselective beta-blockers (HR, 0.95; 95% CI, 0.74-1.24).</p> <p><strong>Conclusion:</strong> Beta-blockers could further increase the risk of severe hypoglycemia when used concurrently with sulfonylureas. Beta-blocker cardioselectivity did not appear to play a major role in this regard. <br>  </p>

Introduction Developmental changes in adolescence make adolescents prone to experiencing negative mood and increased emotional lability. Experimental studies employing sleep restriction paradigms have shown that decreased sleep increased negative affect, but a gap exists regarding the association between sleep disorders and negative affect in adolescence. The objective of this study was to examine this association. It was hypothesized that higher levels of reported symptoms of sleep disorders would be associated with lower positive affect and higher negative affect in adolescents. Methods Participants: 101 adolescents (65 females) aged between 13 and 18 years old (M=14.69, SD=1.16). Measures: Sleep Disorders Inventory for Students was used to measure symptoms of sleep disorders and sleep patterns were measured objectively using actigraphy. Positive and Negative Affect Schedule (PANAS) was used to measure positive and negative affect. Results Correlational analyses were conducted to assess the relationship between symptoms of sleep disorders, sleep patterns, and positive and negative affect. Higher levels of reported symptoms of sleep disorders were associated with later bedtimes (r= .26, p&lt; .01), shorter sleep durations (r= -.20, p&lt; .05), increased sleep onset latency (r= .21, p&lt; .05), decreased sleep efficiency (r= -.23, p&lt; .05), and less immobile minutes (r= -.23, p&lt; .05) measured by actigraphy. Higher levels of reported symptoms of sleep disorders were associated with lower levels of positive affect (r= -.20, p&lt; .05) and higher levels of negative affect (r= .39, p&lt; .001) Conclusion Reported symptoms of sleep disorders were associated with overall poorer sleep patterns in adolescents as well as decreased positive affect and increased negative affect. Sleep specialists assisting adolescents with sleep disorders should inquire about mood regulation. Support Social Sciences and Humanities Research Council