Biomarker guided antibiotic stewardship in community acquired pneumonia: A randomized controlled trial.

BACKGROUND: In community-acquired pneumonia (CAP), the role of biomarkers to shorten duration of antibiotic treatment has not been firmly established. We assessed the effectiveness of active feedback of treatment algorithms based on procalcitonin (PCT) and C-reactive protein (CRP), compared to standard care, on the duration of antibiotic treatment in patients hospitalized with community-acquired pneumonia (CAP) in non-ICU wards. METHODS AND FINDINGS: We performed a randomised, open label, parallel group, multi-centre trial in 3 Dutch teaching hospitals. Treatment was guided by a PCT algorithm, CRP algorithm or standard care. Participants were recruited by a member of the study team and randomised at day 2-3 of admission in a 1:1:1 ratio. Treatment was discontinued upon predefined thresholds of biomarkers that were assessed on admission, day 4 and days 5-7 if indicated. The primary outcome was total days on antibiotic treatment until day 30. In total 468 participants were included in this study. The median days on antibiotics (IQR) was 7 (IQR 7-10) in the control group, 4 (IQR 3-7) in the CRP group (rate ratio (RR) of 0.70, 95% CI 0.61-0.82 compared to standard care; p <0.001), and 5.5 (IQR 3-9) in the PCT group (RR of 0.78, 95% CI 0.68-0.89 compared to standard care; p <0.001). New antibiotics within the first 30 days were prescribed to 24, 23 and 35 patients in standard care, CRP and PCT groups, respectively. The hazard ratio for a new prescription in patients in the PCT group compared to standard care 1.63 (CI 0.97-2.75; p = 0.06). No difference in time to clinical stability or length of stay was found. CONCLUSIONS: A strategy of feedback of CRP-guided and PCT-guided treatment algorithms reduced the number of days on antibiotic in the first 30 days after hospital admission in non-ICU wards for CAP. The study was not powered to determine safety of shortening duration of antibiotic treatment. (NCT01964495).

Half a Century of Wilson & Jungner: Reflections on the Governance of Population Screening.

Background: In their landmark report on the "Principles and Practice of Screening for Disease" (1968), Wilson and Jungner noted that the practice of screening is just as important for securing beneficial outcomes and avoiding harms as the formulation of principles. Many jurisdictions have since established various kinds of "screening governance organizations" to provide oversight of screening practice. Yet to date there has been relatively little reflection on the nature and organization of screening governance itself, or on how different governance arrangements affect the way screening is implemented and perceived and the balance of benefits and harms it delivers. Methods: An international expert policy workshop convened by Sturdy, Miller and Hogarth. Results: While effective governance is essential to promote beneficial screening practices and avoid attendant harms, screening governance organizations face enduring challenges. These challenges are social and ethical as much as technical. Evidence-based adjudication of the benefits and harms of population screening must take account of factors that inform the production and interpretation of evidence, including the divergent professional, financial and personal commitments of stakeholders. Similarly, when planning and overseeing organized screening programs, screening governance organizations must persuade or compel multiple stakeholders to work together to a common end. Screening governance organizations in different jurisdictions vary widely in how they are constituted, how they relate to other interested organizations and actors, and what powers and authority they wield. Yet we know little about how these differences affect the way screening is implemented, and with what consequences. Conclusions: Systematic research into how screening governance is organized in different jurisdictions would facilitate policy learning to address enduring challenges. Even without such research, informal exchange and sharing of experiences between screening governance organizations can deliver invaluable insights into the social as well as the technical aspects of governance.