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Incentives based on quality indicators such as the Surgical Care Improvement Project core measures (SCIP 1) encourage implementation of evidence-based guidelines consistently into clinical practice. Information systems with point-of-care electronic prompts (POCEPs) can facilitate adoption of processes and benchmark performance. We evaluated the effectiveness of POCEPs on rates of antibiotic administration within 60 minutes of surgical incision and effect on outcome in a prospective observational trial.SCIP 1 compliance and the corresponding outcome variable (surgical site infection [SSI]) were examined prospectively over 2 consecutive 6-month periods before (A) and after (B) POCEPs implementation at a regional health system. Secondary analysis extended the observation to two 12-month periods (A′ and B′). A 2-year (C and D) sustainability phase followed.The 19,744 procedures included 9127 and 10,617 procedures before (A) and after (B) POCEPs implementation, respectively. POCEPs increased compliance with SCIP indicators in period B by 31% (95% CI, 30.0%–32.2%) from 62% to 92% (P < 0.001) and were associated with a sustainable, contemporaneous decrease in the incidence of SSI from 1.1% to 0.7% (P = 0.003; absolute risk reduction, 0.4%; 95% CI, 0.1%–0.7%). Secondary and sustainability analysis revealed that compliance rates remained >95% with mean SSI rates lower for all periods compared with pre-POCEPs SSI rates (0.8%, 0.7%, and 0.5% vs 1.1%; P < 0.001).POCEPs increased compliance with SCIP indicators by >30% and were associated with a 0.4% absolute risk reduction in the incidence of SSI. POCEPs may be useful to modulate provider behavior and demonstrate intraoperative quality and value.