Evaluation of the effectiveness of an automated sepsis predictive tool on patient outcomes.

PURPOSE: To evaluate the effectiveness of a multidisciplinary, hospital-wide program as part of an electronic sepsis alert tool. MATERIALS AND METHODS: We used data from 15 hospitals about adult patients with severe sepsis or septic shock. Nine intervention hospitals implemented an Epic sepsis prediction tool, education, and standardized order sets (six control hospitals did not). A difference-in-difference approach evaluated their effectiveness: 1) pre-implementation period (January 1, 2016-November 15, 2018) and 2) implementation period (November 16, 2018-June 30, 2019). RESULTS: Outcomes included mortality, receipt of the SEP-1 bundle of care, broad spectrum antibiotic use, ICU stay, and length of stay of 6926 patients. The difference of 6.7 percentage points between the intervention and control groups in SEP-1 bundle completion was not statistically significant (p = 0.105). The increase over time for antibiotic administration ≤1 h of time zero was not larger for hospitals in the intervention group (11.7%) compared to the control-group (7.6%, p = 0.084). Differences among hospitals in both groups were not statistically different for mortality (p = 0.174), ICU stays (p = 0.174), and length of stay (p = 0.652) from pre- to implementation period. CONCLUSIONS: The intervention to facilitate timely sepsis care did not improve patient outcomes among those with severe sepsis or septic shock.

Kidney Recovery and Death in Critically Ill Patients With COVID-19-Associated Acute Kidney Injury Treated With Dialysis: The STOP-COVID Cohort Study.

RATIONALE & OBJECTIVE: Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with coronavirus disease 2019 (COVID-19). We examined the clinical factors that determine kidney recovery in this population. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 4,221 adults not receiving KRT who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the "ICU cohort"). Among these, 876 developed AKI-KRT after admission to the ICU (the "AKI-KRT subcohort"). EXPOSURE: The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of KRT initiation. OUTCOME: The outcome for the ICU cohort was estimated glomerular filtration rate (eGFR) at hospital discharge. A 3-level outcome (death, kidney nonrecovery, and kidney recovery at discharge) was analyzed for the AKI-KRT subcohort. ANALYTICAL APPROACH: The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. RESULTS: Among a total of 4,221 patients in the ICU cohort, 2,361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower baseline eGFR, with ORs of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for baseline eGFR 31-60, 16-30, ≤15 mL/min/1.73 m2, respectively, compared with eGFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (ORs of 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and <50 mL/d of urine, respectively, compared to ≥500 mL/d of urine). LIMITATIONS: Later recovery events may not have been captured due to lack of postdischarge follow-up. CONCLUSIONS: Lower baseline eGFR and reduced urine output at the time of KRT initiation are each strongly and independently associated with kidney nonrecovery among critically ill patients with COVID-19.

SCN2A-Developmental and Epileptic Encephalopathies: Challenges to trial-readiness for non-seizure outcomes.

OBJECTIVE: SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both. We sought to characterize the level and pattern of development in children with SCN2A variants, and to address the sensitivity of the Vineland Adaptive Behavior Scales (VABS) in measuring changes over time in children with SCN2A-DEEs. METHODS: Clinical histories for participants with pathogenic SCN2A variants in the Simons SearchLight project were analyzed for descriptive purposes. VABS scores obtained at study entry and yearly thereafter were analyzed for floor and ceiling effects, change with age, and association with epilepsy through use of regression and longitudinal regression methods. RESULTS: Sixty-four participants (50 with epilepsy, 30 [47%] female, median age 49 months, interquartile range [IQR] 28 to 101) were included. Histories of birth complications (N = 34, 54%), neonatal neurological signs (N = 45, 74%), and other neurological symptoms (N = 31, 48%) were common and similar in epilepsy and nonepilepsy subgroups. Mean standardized VABS scores (Composite 53.5; Motor, 55.8, Communication, 54.1, Socialization, 59.4, and Daily living skills, 55.1) reflected performance ~3 standard deviations below the normative test average. In longitudinal regression analyses, standardized scores decreased between 1.3 and 2.8 points per year, suggesting regression of abilities. Raw score analyses, however, revealed several subdomains with substantial floor effects (eg, community use); other raw scores increased with increasing age. Participants with epilepsy scored 0.6 to 1 SD lower than those without epilepsy (all P's < .05). SIGNIFICANCE: The VABS, as standardly administered, has shortcomings for addressing growth or regression in individuals with SCN2A-DEEs. Some subdomain raw scores reflected substantial floor effects. Raw scores increased so slowly over time that standardized scores declined. Alternative measures sensitive to incremental meaningful change are required if outcomes such as adaptive behavior are to be primary outcomes in short-term clinical trials.