Estimating daily antibiotic harms: an umbrella review with individual study meta-analysis.

BACKGROUND: There is growing evidence supporting the efficacy of shorter courses of antibiotic therapy for common infections. However, the risks of prolonged antibiotic duration are underappreciated. OBJECTIVES: To estimate the incremental daily risk of antibiotic-associated harms. METHODS: We searched three major databases to retrieve systematic reviews from 2000 to 30 July 2020 in any language. ELIGIBILITY: Systematic reviews were required to evaluate shorter versus longer antibiotic therapy with fixed durations between 3 and 14 days. Randomized controlled trials included for meta-analysis were identified from the systematic reviews. PARTICIPANTS: Adult and paediatric patients from any setting. INTERVENTIONS: Primary outcomes were the proportion of patients experiencing adverse drug events, superinfections and antimicrobial resistance. RISK OF BIAS ASSESSMENT: Each randomized controlled trial was evaluated for quality by extracting the assessment reported by each systematic review. DATA SYNTHESIS: The daily odds ratio (OR) of antibiotic harm was estimated and pooled using random effects meta-analysis. RESULTS: Thirty-five systematic reviews encompassing 71 eligible randomized controlled trials were included. Studies most commonly evaluated duration of therapy for respiratory tract (n = 36, 51%) and urinary tract (n = 29, 41%) infections. Overall, 23 174 patients were evaluated for antibiotic-associated harms. Adverse events (n = 20 345), superinfections (n = 5776) and antimicrobial resistance (n = 2330) were identified in 19.9% (n = 4039), 4.8% (n = 280) and 10.6% (n = 246) of patients, respectively. Each day of antibiotic therapy was associated with 4% increased odds of experiencing an adverse event (OR 1.04, 95% CI 1.02-1.07). Daily odds of severe adverse effects also increased (OR 1.09, 95% CI 1.00-1.19). The daily incremental odds of superinfection and antimicrobial resistance were OR 0.98 (0.92-1.06) and OR 1.03 (0.98-1.07), respectively. CONCLUSION: Each additional day of antibiotic therapy is associated with measurable antibiotic harm, particularly adverse events. These data may provide additional context for clinicians when weighing benefits versus risks of prolonged antibiotic therapy.

Effect of Antibiotic-Prescribing Feedback to High-Volume Primary Care Physicians on Number of Antibiotic Prescriptions: A Randomized Clinical Trial.

Importance: Antibiotic overuse contributes to adverse drug effects, increased costs, and antimicrobial resistance. Objective: To evaluate peer-comparison audit and feedback to high-prescribing primary care physicians (PCPs) and assess the effect of targeted messaging on avoiding unnecessary antibiotic prescriptions and avoiding long-duration prescribing. Design, Setting, and Participants: In this 3-arm randomized clinical trial, administrative data collected from IQVIA's Xponent database were used to recruit the highest quartile of antibiotic-prescribing PCPs (n = 3500) in Ontario, Canada. Interventions: Physicians were randomized 3:3:1 to receive a mailed letter sent in December 2018 addressing antibiotic treatment initiation (n = 1500), a letter addressing prescribing duration (n = 1500), or no letter (control; n = 500). Outliers at the 99th percentile at baseline for each arm were excluded from analysis. Main Outcomes and Measures: The primary outcome was total number of antibiotic prescriptions over 12 months postintervention. Secondary outcomes were number of prolonged-duration prescriptions (>7 days) and antibiotic drug costs (in Canadian dollars). Robust Poisson regression controlling for baseline prescriptions was used for analysis. Results: Of the 3465 PCPs included in analysis, 2405 (69.4%) were male, and 2116 (61.1%) were 25 or more years from their medical graduation. At baseline, PCPs receiving the antibiotic initiation letter and duration letter prescribed an average of 988 and 1000 antibiotic prescriptions, respectively; at 12 months postintervention, these PCPs prescribed an average of 849 and 851 antibiotic prescriptions, respectively. For the primary outcome of total antibiotic prescriptions 12 months postintervention, there was no statistically significant difference in total antibiotic use between PCPs who received the initiation letter compared with controls (relative risk [RR], 0.96; 97.5% CI, 0.92-1.01; P = .06) and a small statistically significant difference for the duration letter compared with controls (RR, 0.95; 97.5% CI, 0.91-1.00; P = .01). For PCPs receiving the duration letter, this corresponds to an average of 42 fewer antibiotic prescriptions over 12 months. There was no statistically significant difference between the letter arms. For the initiation letter, compared with controls there was an RR of 0.98 (97.5% CI, 0.93-1.03; P = .42) and 0.97 (97.5% CI, 0.92-1.02; P = .19) for the outcomes of prolonged-duration prescriptions and antibiotic drug costs, respectively. At baseline, PCPs who received the duration letter prescribed an average of 332 prolonged-duration prescriptions with $14 470 in drug costs. There was an 8.1% relative reduction (RR, 0.92; 97.5% CI, 0.87-0.97; P < .001) in prolonged-duration prescriptions, and a 6.1% relative reduction in antibiotic drug costs (RR, 0.94; 97.5% CI, 0.89-0.99; P = .01). This corresponds to an average of 24 fewer prolonged-duration prescriptions and $771 in drug cost savings per PCP over 12 months. Conclusions and Relevance: In this randomized clinical trial, a single mailed letter to the highest-prescribing PCPs in Ontario, Canada providing peer-comparison feedback, including messaging on limiting antibiotic-prescribing durations, led to statistically significant reductions in total and prolonged-duration antibiotic prescriptions, as well as drug costs. Trial Registration: ClinicalTrials.gov Identifier: NCT03776383.

Unnecessary antibiotic prescribing in a Canadian primary care setting: a descriptive analysis using routinely collected electronic medical record data.

BACKGROUND: Unnecessary antibiotic use in the community in Canada is not well defined. Our objective was to quantify unnecessary antibiotic prescribing in a Canadian primary care setting. METHODS: We performed a descriptive analysis in Ontario from April 2011 to March 2016 using the Electronic Medical Records Primary Care database linked to other health administrative data sets at ICES. We determined antibiotic prescribing rates (per 100 patient-physician encounters) for 23 common conditions and estimated rates of unnecessary prescribing using predefined expected prescribing rates, both stratified by condition and patient age group. RESULTS: The study included 341 physicians, 204 313 patients and 499 570 encounters. The rate of unnecessary antibiotic prescribing for included conditions was 15.4% overall and was 17.6% for those less than 2 years of age, 18.6% for those aged 2-18, 14.5% for those aged 19-64 and 13.0% for those aged 65 or more. The highest unnecessary prescribing rates were observed for acute bronchitis (52.6%), acute sinusitis (48.4%) and acute otitis media (39.3%). The common cold, acute bronchitis, acute sinusitis and miscellaneous nonbacterial infections were responsible for 80% of the unnecessary antibiotic prescriptions. Of all antibiotics prescribed, 12.0% were for conditions for which they are never indicated, and 12.3% for conditions for which they are rarely indicated. In children, 25% of antibiotics were for conditions for which they are never indicated (e.g., common cold). INTERPRETATION: Antibiotics were prescribed unnecessarily for 15.4% of included encounters in a Canadian primary care setting. Almost one-quarter of antibiotics were prescribed for conditions for which they are rarely or never indicated. These findings should guide safe reductions in the use of antibiotics for the common cold, bronchitis and sinusitis.

Decision aids for people facing health treatment or screening decisions.

BACKGROUND: Decision aids are intended to help people participate in decisions that involve weighing the benefits and harms of treatment options often with scientific uncertainty. OBJECTIVES: To assess the effects of decision aids for people facing treatment or screening decisions. SEARCH METHODS: For this update, we searched from 2009 to June 2012 in MEDLINE; CENTRAL; EMBASE; PsycINFO; and grey literature. Cumulatively, we have searched each database since its start date including CINAHL (to September 2008). SELECTION CRITERIA: We included published randomized controlled trials of decision aids, which are interventions designed to support patients' decision making by making explicit the decision, providing information about treatment or screening options and their associated outcomes, compared to usual care and/or alternative interventions. We excluded studies of participants making hypothetical decisions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened citations for inclusion, extracted data, and assessed risk of bias. The primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were:A) 'choice made' attributes;B) 'decision-making process' attributes.Secondary outcomes were behavioral, health, and health-system effects. We pooled results using mean differences (MD) and relative risks (RR), applying a random-effects model. MAIN RESULTS: This update includes 33 new studies for a total of 115 studies involving 34,444 participants. For risk of bias, selective outcome reporting and blinding of participants and personnel were mostly rated as unclear due to inadequate reporting. Based on 7 items, 8 of 115 studies had high risk of bias for 1 or 2 items each.Of 115 included studies, 88 (76.5%) used at least one of the IPDAS effectiveness criteria: A) 'choice made' attributes criteria: knowledge scores (76 studies); accurate risk perceptions (25 studies); and informed value-based choice (20 studies); and B) 'decision-making process' attributes criteria: feeling informed (34 studies) and feeling clear about values (29 studies).A) Criteria involving 'choice made' attributes:Compared to usual care, decision aids increased knowledge (MD 13.34 out of 100; 95% confidence interval (CI) 11.17 to 15.51; n = 42). When more detailed decision aids were compared to simple decision aids, the relative improvement in knowledge was significant (MD 5.52 out of 100; 95% CI 3.90 to 7.15; n = 19). Exposure to a decision aid with expressed probabilities resulted in a higher proportion of people with accurate risk perceptions (RR 1.82; 95% CI 1.52 to 2.16; n = 19). Exposure to a decision aid with explicit values clarification resulted in a higher proportion of patients choosing an option congruent with their values (RR 1.51; 95% CI 1.17 to 1.96; n = 13).B) Criteria involving 'decision-making process' attributes:Decision aids compared to usual care interventions resulted in:a) lower decisional conflict related to feeling uninformed (MD -7.26 of 100; 95% CI -9.73 to -4.78; n = 22) and feeling unclear about personal values (MD -6.09; 95% CI -8.50 to -3.67; n = 18);b) reduced proportions of people who were passive in decision making (RR 0.66; 95% CI 0.53 to 0.81; n = 14); andc) reduced proportions of people who remained undecided post-intervention (RR 0.59; 95% CI 0.47 to 0.72; n = 18).Decision aids appeared to have a positive effect on patient-practitioner communication in all nine studies that measured this outcome. For satisfaction with the decision (n = 20), decision-making process (n = 17), and/or preparation for decision making (n = 3), those exposed to a decision aid were either more satisfied, or there was no difference between the decision aid versus comparison interventions. No studies evaluated decision-making process attributes for helping patients to recognize that a decision needs to be made, or understanding that values affect the choice.C) Secondary outcomes Exposure to decision aids compared to usual care reduced the number of people of choosing major elective invasive surgery in favour of more conservative options (RR 0.79; 95% CI 0.68 to 0.93; n = 15). Exposure to decision aids compared to usual care reduced the number of people choosing to have prostate-specific antigen screening (RR 0.87; 95% CI 0.77 to 0.98; n = 9). When detailed compared to simple decision aids were used, fewer people chose menopausal hormone therapy (RR 0.73; 95% CI 0.55 to 0.98; n = 3). For other decisions, the effect on choices was variable.The effect of decision aids on length of consultation varied from 8 minutes shorter to 23 minutes longer (median 2.55 minutes longer) with 2 studies indicating statistically-significantly longer, 1 study shorter, and 6 studies reporting no difference in consultation length. Groups of patients receiving decision aids do not appear to differ from comparison groups in terms of anxiety (n = 30), general health outcomes (n = 11), and condition-specific health outcomes (n = 11). The effects of decision aids on other outcomes (adherence to the decision, costs/resource use) were inconclusive. AUTHORS' CONCLUSIONS: There is high-quality evidence that decision aids compared to usual care improve people's knowledge regarding options, and reduce their decisional conflict related to feeling uninformed and unclear about their personal values. There is moderate-quality evidence that decision aids compared to usual care stimulate people to take a more active role in decision making, and improve accurate risk perceptions when probabilities are included in decision aids, compared to not being included. There is low-quality evidence that decision aids improve congruence between the chosen option and the patient's values.New for this updated review is further evidence indicating more informed, values-based choices, and improved patient-practitioner communication. There is a variable effect of decision aids on length of consultation. Consistent with findings from the previous review, decision aids have a variable effect on choices. They reduce the number of people choosing discretionary surgery and have no apparent adverse effects on health outcomes or satisfaction. The effects on adherence with the chosen option, cost-effectiveness, use with lower literacy populations, and level of detail needed in decision aids need further evaluation. Little is known about the degree of detail that decision aids need in order to have a positive effect on attributes of the choice made, or the decision-making process.