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Acute kidney injury is common among hospitalized individuals, particularly those exposed to certain medications, and is associated with substantial morbidity and mortality. In a pragmatic, open-label, National Institutes of Health-funded, parallel group randomized controlled trial (clinicaltrials.gov NCT02771977), we investigate whether an automated clinical decision support system affects discontinuation rates of potentially nephrotoxic medications and improves outcomes in patients with AKI. Participants included 5060 hospitalized adults with AKI and an active order for any of three classes of medications of interest: non-steroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system inhibitors, or proton pump inhibitors. Within 24 hours of randomization, a medication of interest was discontinued in 61.1% of the alert group versus 55.9% of the usual care group (relative risk 1.08, 1.04 – 1.14, p = 0.0003). The primary outcome – a composite of progression of acute kidney injury, dialysis, or death within 14 days - occurred in 585 (23.1%) of individuals in the alert group and 639 (25.3%) of patients in the usual care group (RR 0.92, 0.83 – 1.01, p = 0.09). Trial Registration Clinicaltrials.gov NCT02771977. In a multicenter randomized trial, researchers found that electronic alerts increased the rate of discontinuation of potential nephrotoxins. This did not translate into improved clinical outcomes, except among those exposed to proton-pump inhibitors.

IntroductionAlthough studies have examined the utility of clinical decision support tools in improving acute kidney injury (AKI) outcomes, no study has evaluated the effect of real-time, personalised AKI recommendations. This study aims to assess the impact of individualised AKI-specific recommendations delivered by trained clinicians and pharmacists immediately after AKI detection in hospitalised patients.Methods and analysisKAT-AKI is a multicentre randomised investigator-blinded trial being conducted across eight hospitals at two major US hospital systems planning to enrol 4000 patients over 3 years (between 1 November 2021 and 1 November 2024). A real-time electronic AKI alert system informs a dedicated team composed of a physician and pharmacist who independently review the chart in real time, screen for eligibility and provide combined recommendations across the following domains: diagnostics, volume, potassium, acid–base and medications. Recommendations are delivered to the primary team in the alert arm or logged for future analysis in the usual care arm. The planned primary outcome is a composite of AKI progression, dialysis and mortality within 14 days from randomisation. A key secondary outcome is the percentage of recommendations implemented by the primary team within 24 hours from randomisation. The study has enrolled 500 individuals over 8.5 months. Two-thirds were on a medical floor at the time of the alert and 17.8% were in an intensive care unit. Virtually all participants were recommended for at least one diagnostic intervention. More than half (51.6%) had recommendations to discontinue or dose-adjust a medication. The median time from AKI alert to randomisation was 28 (IQR 15.8–51.5) min.Ethics and disseminationThe study was approved by the ethics committee of each study site (Yale University and Johns Hopkins institutional review board (IRB) and a central IRB (BRANY, Biomedical Research Alliance of New York). We are committed to open dissemination of the data through clinicaltrials.gov and sharing of data on an open repository as well as publication in a peer-reviewed journal on completion.Trial registration numberNCT04040296.

•Elevated risk of febrile seizures after PCV13 vaccine but not after influenza vaccine.•Risk of febrile seizures after PCV13 low compared to overall risk in this population.•No clear evidence for elevated risk after concomitant vaccination. Evidence on the risk of febrile seizures after inactivated influenza vaccine (IIV) and 13-valent pneumococcal conjugate vaccine (PCV13) is mixed. In the FDA-sponsored Sentinel Initiative, we examined risk of febrile seizures after IIV and PCV13 in children 6–23 months of age during the 2013–14 and 2014–15 influenza seasons. Using claims data and a self-controlled risk interval design, we compared the febrile seizure rate in a risk interval (0–1 days) versus control interval (14–20 days). In exploratory analyses, we assessed whether the effect of IIV was modified by concomitant PCV13 administration. Adjusted for age, calendar time and concomitant administration of the other vaccine, the incidence rate ratio (IRR) for risk of febrile seizures following IIV was 1.12 (95% CI 0.80, 1.56) and following PCV13 was 1.80 (95% CI 1.29, 2.52). The attributable risk for febrile seizures following PCV13 ranged from 0.33 to 5.16 per 100,000 doses by week of age. The age and calendar-time adjusted IRR comparing exposed to unexposed time was numerically larger for concomitant IIV and PCV13 (IRR 2.80, 95% CI 1.63, 4.83), as compared to PCV13 without concomitant IIV (IRR 1.54, 95% CI 1.04, 2.28), and the IRR for IIV without concomitant PCV13 suggested no independent effects of IIV (IRR 0.94, 95% CI 0.63, 1.42). Taken together, this suggests a possible interaction between IIV and PCV13, though our study was not sufficiently powered to provide a precise estimate of the interaction. We found an elevated risk of febrile seizures after PCV13 vaccine but not after IIV. The risk of febrile seizures after PCV13 is low compared to the overall risk in this population of children, and the risk should be interpreted in the context of the importance of preventing pneumococcal infections.

Abstract Background Evidence on the risk of febrile seizures (FS) after vaccination with inactivated influenza vaccine (IIV) and 13-valent pneumococcal conjugate vaccine (PCV13) is mixed. Among children 6–23 months, we examined the risk of FS following IIV and PCV13 during the 2013–14 and 2014–15 influenza seasons, for which vaccine virus strains were the same. Methods We used claims data from 4 large national insurers in the FDA-sponsored Sentinel Initiative, which was developed to monitor the safety of FDA-regulated medical products. With a self-controlled risk interval design, the risk of FS in 0–1 days following IIV and following PCV13 was compared with a comparison interval (14–20 days), adjusting for confounding by age, calendar time, and concomitant vaccination with the other vaccine. In exploratory analyses, we assessed whether the effect of IIV is modified by concomitant administration of PCV13. Results During the study period, 355,486 children received IIV and 581,868 received PCV13. We observed an incidence rate ratio (IRR) of 1.12 (95% CI 0.80, 1.56) for the risk of FS following IIV after adjustment for age, calendar time and concomitant PCV13. PCV13 was associated with an increased risk of FS (IRR adjusted for age, calendar time and concomitant IIV, 1.80, 95% CI 1.29, 2.52). The attributable risk for PCV13 ranged from 0.33 to 5.16 per 100,000 doses. The age and calendar-time adjusted IRR comparing exposed time to unexposed time was greater for concomitant IIV and PCV13 (IRR 2.80, 95% CI 1.63, 4.83), as compared with that for PCV13 without concomitant IIV (IRR 1.54, 95% CI 1.04, 2.28). However, the formal test assessing for interaction between IIV and PCV13 was not statistically significant. Conclusion We found an elevated risk of FS after PCV13 vaccine but not after IIV, when adjusting for concomitant administration of the other vaccine. We found some evidence to suggest that concomitant administration of IIV with PCV13 might interact to increase the risk beyond the independent effects of PCV13, but the study was not powered to assess this interaction. The risk of seizures associated with PCV13 is low compared with a child’s lifetime risk of FS. Findings should be interpreted in the context of the importance of preventing influenza and pneumococcal infections in young children. Disclosures L. Li, sanofi pasteur: The author is currently employed by Sanofi Genzyme, which shares the same parent company as sanofi pasteur, the manufacturer of the Flu vaccine. However, the work was done while this author was still employed by Harvard Pilgrim Health Care Institute., No financial benefit received