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Background: Hospital-acquired Clostridioides difficile infection (HA-CDI) rates are highly variable over time, posing problems for research assessing interventions that might improve rates. By understanding seasonality in HA-CDI rates and the impacts that other factors such as influenza admissions might have on these rates, we can account for them when establishing the relationship between interventions and infection rates. We assessed whether there were seasonal trends in HA-CDI and whether they could be accounted for by influenza rates. Methods: We assessed HA-CDI rates per 10,000 patient days, and the rate of hospitalized patients with influenza per 1,000 admissions in 4 acute-care facilities (n = 2,490 beds) in Calgary, Alberta, from January 2016 to December 2018. We used 4 statistical approaches in R (version 3.5.1 software): (1) autoregressive integrated moving average (ARIMA) to assess dependencies and trends in each of the monthly HA-CDI and influenza series; (2) cross correlation to assess dependencies between the HA-CDI and influenza series lagged over time; (3) Poisson harmonic regression models (with sine and cosine components) to assess the seasonality of the rates; and (4) Poisson regression to determine whether influenza rates accounted for seasonality in the HA-CDI rates. Results: Conventional ARIMA approaches did not detect seasonality in the HA-CDI rates, but we found strong seasonality in the influenza rates. A cross-correlation analysis revealed evidence of correlation between the series at a lag of zero (R = 0.41; 95% CI, 0.10–0.65) and provided an indication of a seasonal relationship between the series (Fig. 1). Poisson regression suggested that influenza rates predicted CDI rates (P < .01). Using harmonic regression, there was evidence of seasonality in HA-CDI rates (2 [2 df] = 6.62; P < .05) and influenza rates (2 [2 df] = 1,796.6; P < .001). In a Poisson model of HA-CDI rates with both the harmonic components and influenza admission rates, the harmonic components were no longer predictive of HA-CDI rates. Conclusions: Harmonic regression provided a sensitive means of identifying seasonality in HA-CDI rates, but the seasonality effect was accounted for by influenza admission rates. The relationship between HA-CDI and influenza rates is likely mediated by antibiotic prescriptions, which needs to be assessed. To improve precision and reduce bias, research on interventions to reduce HA-CDI rates should assess historic seasonality in HA-CDI rates and should account for influenza admissions.
Background:Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea in hospitalized patients. Probiotics have been studied as a measure to prevent CDI. Timely probiotic administration to at-risk patients receiving systemic antimicrobials presents significant challenges. We sought to determine optimal implementation methods to administer probiotics to all adult inpatients aged 55 years receiving a course of systemic antimicrobials across an entire health region. Methods: Using a randomized stepped-wedge design across 4 acute-care hospitals (n = 2,490 beds), the probiotic Bio-K+ was prescribed daily to patients receiving systemic antimicrobials and was continued for 5 days after antimicrobial discontinuation. Focus groups and interviews were conducted to identify barriers, and the implementation strategy was adapted to address the key identified barriers. The implementation strategy included clinical decision support involving a linked flag on antibiotic ordering and a 1-click order entry within the electronic medical record (EMR), provider and patient education (written/videos/in-person), and local site champions. Protocol adherence was measured by tracking the number of patients on therapeutic antimicrobials that received BioK+ based on the bedside nursing EMR medication administration records. Adherence rates were sorted by hospital and unit in 48- and 72-hour intervals with recording of percentile distribution of time (days) to receipt of the first antimicrobial. Results: In total, 340 education sessions with >1,800 key stakeholders occurred before and during implementation across the 4 involved hospitals. The overall adherence of probiotic ordering for wards with antimicrobial orders was 78% and 80% at 48 and 72 hours, respectively over 72 patient months. Individual hospital adherence rates varied between 77% and 80% at 48 hours and between 79% and 83% at 72 hours. Of 246,144 scheduled probiotic orders, 94% were administered at the bedside within a median of 0.61 days (75th percentile, 0.88), 0.47 days (75th percentile, 0.86), 0.71 days (75th percentile, 0.92) and 0.67 days (75th percentile, 0.93), respectively, at the 4 sites after receipt of first antimicrobial. The key themes from the focus groups emphasized the usefulness of the linked flag alert for probiotics on antibiotic ordering, the ease of the EMR 1-click order entry, and the importance of the education sessions. Conclusions: Electronic clinical decision support, education, and local champion support achieved a high implementation rate consistent across all sites. Use of a 1-click order entry in the EMR was considered a key component of the success of the implementation and should be considered for any implementation strategy for a stewardship initiative. Achieving high prescribing adherence allows more precision in evaluating the effectiveness of the probiotic strategy.
Funding: Partnerships for Research and Innovation in the Health System, Alberta Innovates/Health Solutions Funding: Award