PURPOSE: Observational studies have reported conflicting results regarding aprotinin's risk of renal dysfunction and death. A meta-analysis was conducted to summarize results and explain variation of published epidemiologic studies on risks of renal dysfunction and death associated with aprotinin.
METHODS: MEDLINE and EMBASE were systematically searched for non-experimental studies that reported risk of renal dysfunction or death with aprotinin use during cardiac surgery in adults. Random-effects meta-analyses were used to pool results across studies for each outcome. Stratified and meta-regression analyses were used to identify sources of heterogeneity.
RESULTS: Eleven relevant studies were identified and included in the analysis, including 10 that reported renal dysfunction and seven that reported death. Aprotinin was associated with renal dysfunction (risk ratio (RR), 1.42; 95%CI 1.13-1.79) and long-term mortality (hazard ratio (HR) 1.22; 95%CI 1.08-1.39). Pooled estimates were lower for short-term mortality (RR 1.16; 95%CI 0.84-1.58) and renal failure requiring dialysis (RR 1.17; 95%CI 0.99-1.38). Cardiopulmonary bypass (CPB) time, which may be on the causal pathway, was a significant source of heterogeneity, with a 29% increased risk of renal dysfunction for every 10 minute increase in CPB time (p = 0.03).
CONCLUSIONS: Despite some studies that reported no association between aprotinin and renal outcomes during cardiac surgery, the totality of epidemiologic evidence indicates an increased risk that cannot be fully explained by need for transfused red blood cells (RBCs). Epidemiologic studies also suggest an increased risk of long-term mortality associated with aprotinin as compared to various comparators used in these studies, although residual confounding cannot be ruled out.
INTRODUCTION: In 2003, more intense monitoring of patients initiating antidepressants was advised because of emerging concerns of suicidality. We sought to identify patterns of patient monitoring after antidepressant initiation in British Columbia before and after issuance of health advisories.
MATERIALS AND METHODS: We conducted a cohort study of antidepressant initiators between 1999 and 2005 using healthcare utilization data of all British Columbia residents. For the periods before (1999-2001) and after (2004-2005), health advisories concerning suicidality associated with antidepressants, we assessed monitoring intensity by calculating weekly physician and psychotherapy visit rates since antidepressant initiation. We also estimated monitoring patterns as the proportion of individuals who received weekly in-person contact during the first 4 weeks of treatment, then biweekly visits for 4 weeks, and then a visit at 12 weeks, as a proxy for intensive monitoring.
RESULTS: Patterns of monitoring intensity were similar before and after the health advisories, but the level of intensity was lower after the advisory period. Overall, monitoring intensity peaked in the 4 weeks after antidepressant initiation. Weekly numbers of visits per subject during these 4 weeks were between 0.44 and 0.49 before the advisory and from 0.39 to 0.44 after the advisory. Among all initiators stratified by year of initiation, between 21% and 25% received intensive monitoring, and this proportion generally decreased on a yearly basis.
DISCUSSION: Monitoring intensity for patients with depression initiating antidepressants decreased after the period of emergence and greater awareness of the association between antidepressants and suicidality.