Update to the Neonatal Early-Onset Sepsis Calculator Utilizing a Contemporary Cohort.

BACKGROUND AND OBJECTIVES: The Kaiser Permanente Neonatal Early-Onset Sepsis (EOS) Calculator has been an effective tool for risk stratification to safely reduce newborn antibiotic exposure. The calculator was derived from data on infants born between 1993 and 2007. Since that time, US obstetric practice has adopted universal antepartum screening for group B Streptococcus and intrapartum antibiotic prophylaxis guidance has changed. Our objective was to update the EOS calculator using a contemporary birth cohort and determine the effect of these changes on EOS case ascertainment and antibiotic recommendations. METHODS: The study included infants born at ≥35 weeks' gestation at 14 hospitals between January 2010 and December 2020 (n = 412 595 infants, EOS cases = 113). Model coefficients were re-estimated and the point estimates of the likelihood ratios for clinical status used to calculate the posterior probability of EOS. We compared the number of EOS cases correctly identified by each model (sensitivity) and the proportion of infants for whom empirical antibiotics are recommended. RESULTS: The original model had a sensitivity of 0.76 (95% confidence interval 0.63-0.85), while the updated model had a sensitivity of 0.80 (95% confidence interval 0.68-0.89), P = .15. The recommended empirical antibiotic use was 3.5% with the original model and 3.7% with the updated model, P < .0001. For each additional case identified by the updated model, an additional 158 infants would be treated with antibiotics. CONCLUSIONS: Both the original and updated EOS calculators are effective tools for quantifying EOS risk among infants born at ≥35 weeks' gestation.

Default Palliative Care Consultation for Seriously Ill Hospitalized Patients: A Pragmatic Cluster Randomized Trial.

Importance: Increasing inpatient palliative care delivery is prioritized, but large-scale, experimental evidence of its effectiveness is lacking. Objective: To determine whether ordering palliative care consultation by default for seriously ill hospitalized patients without requiring greater palliative care staffing increased consultations and improved outcomes. Design, Setting, and Participants: A pragmatic, stepped-wedge, cluster randomized trial was conducted among patients 65 years or older with advanced chronic obstructive pulmonary disease, dementia, or kidney failure admitted from March 21, 2016, through November 14, 2018, to 11 US hospitals. Outcome data collection ended on January 31, 2019. Intervention: Ordering palliative care consultation by default for eligible patients, while allowing clinicians to opt-out, was compared with usual care, in which clinicians could choose to order palliative care. Main Outcomes and Measures: The primary outcome was hospital length of stay, with deaths coded as the longest length of stay, and secondary end points included palliative care consult rate, discharge to hospice, do-not-resuscitate orders, and in-hospital mortality. Results: Of 34 239 patients enrolled, 24 065 had lengths of stay of at least 72 hours and were included in the primary analytic sample (10 313 in the default order group and 13 752 in the usual care group; 13 338 [55.4%] women; mean age, 77.9 years). A higher percentage of patients in the default order group received palliative care consultation than in the standard care group (43.9% vs 16.6%; adjusted odds ratio [aOR], 5.17 [95% CI, 4.59-5.81]) and received consultation earlier (mean [SD] of 3.4 [2.6] days after admission vs 4.6 [4.8] days; P < .001). Length of stay did not differ between the default order and usual care groups (percent difference in median length of stay, -0.53% [95% CI, -3.51% to 2.53%]). Patients in the default order group had higher rates of do-not-resuscitate orders at discharge (aOR, 1.40 [95% CI, 1.21-1.63]) and discharge to hospice (aOR, 1.30 [95% CI, 1.07-1.57]) than the usual care group, and similar in-hospital mortality (4.7% vs 4.2%; aOR, 0.86 [95% CI, 0.68-1.08]). Conclusions and Relevance: Default palliative care consult orders did not reduce length of stay for older, hospitalized patients with advanced chronic illnesses, but did improve the rate and timing of consultation and some end-of-life care processes. Trial Registration: ClinicalTrials.gov Identifier: NCT02505035.

Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study.

OBJECTIVES: In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients' referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Adult members before COVID-19 vaccine availability (1 February 2020-31 January 2021) with positive SARS-CoV-2 tests. INTERVENTION: Virtual programme to track and treat patients with 'CHCT programme'. OUTCOMES: The outcomes were (1) COVID-19-related emergency department visit, (2) COVID-19-related hospitalisation and (3) inpatient mortality or 30-day hospice referral. MEASURES: We estimated the average effect comparing patients who were and were not treated by CHCT. We estimated propensity scores using an ensemble super learner (random forest, XGBoost, generalised additive model and multivariate adaptive regression splines) and augmented inverse probability weighting. RESULTS: There were 98 585 patients with COVID-19. The majority were followed by CHCT (n=80 067, 81.2%). Patients followed by CHCT were older (mean age 43.9 vs 41.6 years, p<0.001) and more comorbid with COmorbidity Point Score, V.2, score ≥65 (1.7% vs 1.1%, p<0.001). Unadjusted analyses showed more COVID-19-related emergency department visits (9.5% vs 8.5%, p<0.001) and hospitalisations (3.9% vs 3.2%, p<0.001) in patients followed by CHCT but lower inpatient death or 30-day hospice referral (0.3% vs 0.5%, p<0.001). After weighting, there were higher rates of COVID-19-related emergency department visits (estimated intervention effect -0.8%, 95% CI -1.4% to -0.3%) and hospitalisation (-0.5%, 95% CI -0.9% to -0.1%) but lower inpatient mortality or 30-day hospice referral (-0.5%, 95% CI -0.7% to -0.3%) in patients followed by CHCT. CONCLUSIONS: Despite CHCT following older patients with higher comorbidity burden, there appeared to be a protective effect. Patients followed by CHCT were more likely to present to acute care and less likely to die inpatient.

The intensity of anticoagulant dosing in hospitalized patients with COVID-19: An observational, comparative effectiveness study.

BACKGROUND: The question of anticoagulant dosing in hospitalized patients with coronavirus disease-2019 (COVID-19) is unresolved, with randomized trials showing mixed results and heterogeneity of treatment effects for in-hospital death. OBJECTIVE: To examine the association between the intensity of anticoagulation and clinical outcomes in hospitalized patients with COVID-19. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of patients with COVID-19 and respiratory impairment who were hospitalized between 3/1/2020-12/31/2020 in two Kaiser Permanente regions. EXPOSURE AND MAIN OUTCOME: We fit propensity score models using categorical regression to estimate the probability of receiving standard prophylactic, intermediate, or full-dose anticoagulation beginning on the day of admission or on the day of first respiratory deterioration. Exposure was defined by the highest dose on the day of admission or within 24 hours after deterioration. The primary outcome was in-hospital death. RESULTS: We included 17,130 patients in the day of admission analysis and 4,924 patients who experienced respiratory deterioration. There were no differences in propensity score-adjusted odds of in-hospital death for patients who received either intermediate (odds ratio [OR]: 1.00, 95% confidence intervals [CI] 0.89-1.12) or full anticoagulation (OR: 1.00, 95% CI: 0.85-1.17) compared with standard prophylaxis beginning on the day of admission. Similarly, there were no differences in in-hospital death for either intermediate (OR: 1.22, 95% CI: 0.82-1.82) or full anticoagulation (OR: 1.50, 95% CI: 0.90-2.51) compared with standard prophylaxis on the day of deterioration. CONCLUSION: Results of this real-world, comparative effectiveness study showed no differences in in-hospital death among newly admitted or deteriorating patients with COVID-19 who received intermediate-dose or full anticoagulation compared with standard prophylaxis.

Among-Hospital Variation in Intensive Care Unit Admission Practices and Associated Outcomes for Patients with Acute Respiratory Failure.

Rationale: We have previously shown that hospital strain is associated with intensive care unit (ICU) admission and that ICU admission, compared with ward admission, may benefit certain patients with acute respiratory failure (ARF). Objectives: To understand how strain-process-outcomes relationships in patients with ARF may vary among hospitals and what hospital practice differences may account for such variation. Methods: We examined high-acuity patients with ARF who did not require mechanical ventilation or vasopressors in the emergency department (ED) and were admitted to 27 U.S. hospitals from 2013 to 2018. Stratifying by hospital, we compared hospital strain-ICU admission relationships and hospital length of stay (LOS) and mortality among patients initially admitted to the ICU versus the ward using hospital strain as a previously validated instrumental variable. We also surveyed hospital practices and, in exploratory analyses, evaluated their associations with the above processes and outcomes. Results: There was significant among-hospital variation in ICU admission rates, in hospital strain-ICU admission relationships, and in the association of ICU admission with hospital LOS and hospital mortality. Overall, ED patients with ARF (n = 45,339) experienced a 0.82-day shorter median hospital LOS if admitted initially to the ICU compared with the ward, but among the 27 hospitals (n = 224-3,324), this effect varied from 5.85 days shorter (95% confidence interval [CI], -8.84 to -2.86; P < 0.001) to 4.38 days longer (95% CI, 1.86-6.90; P = 0.001). Corresponding ranges for in-hospital mortality with ICU compared with ward admission revealed odds ratios from 0.08 (95% CI, 0.01-0.56; P < 0.007) to 8.89 (95% CI, 1.60-79.85; P = 0.016) among patients with ARF (pooled odds ratio, 0.75). In exploratory analyses, only a small number of measured hospital practices-the presence of a sepsis ED disposition guideline and maximum ED patient capacity-were potentially associated with hospital strain-ICU admission relationships. Conclusions: Hospitals vary considerably in ICU admission rates, the sensitivity of those rates to hospital capacity strain, and the benefits of ICU admission for patients with ARF not requiring life support therapies in the ED. Future work is needed to more fully identify hospital-level factors contributing to these relationships.

Risk of severe COVID-19 infection among adults with prior exposure to children.

Susceptibility and severity of COVID-19 infection vary widely. Prior exposure to endemic coronaviruses, common in young children, may protect against SARS-CoV-2. We evaluated risk of severe COVID-19 among adults with and without exposure to young children in a large, integrated healthcare system. Adults with children 0-5 years were matched 1:1 to adults with children 6-11 years, 12-18 years, and those without children based upon a COVID-19 propensity score and risk factors for severe COVID-19. COVID-19 infections, hospitalizations, and need for intensive care unit (ICU) were assessed in 3,126,427 adults, of whom 24% (N = 743,814) had children 18 years or younger, and 8.8% (N = 274,316) had a youngest child 0-5 years. After 1:1 matching, propensity for COVID-19 infection and risk factors for severe COVID-19 were well balanced between groups. Rates of COVID-19 infection were slightly higher for adults with exposure to older children (incident risk ratio, 1.09, 95% confidence interval, [1.05-1.12] and IRR 1.09 [1.05-1.13] for adults with children 6-11 and 12-18, respectively), compared to those with children 0-5 years, although no difference in rates of COVID-19 illness requiring hospitalization or ICU admission was observed. However, adults without exposure to children had lower rates of COVID-19 infection (IRR 0.85, [0.83-0.87]) but significantly higher rates of COVID-19 hospitalization (IRR 1.49, [1.29-1.73]) and hospitalization requiring ICU admission (IRR 1.76, [1.19-2.58]) compared to those with children aged 0-5. In a large, real-world population, exposure to young children was associated with less severe COVID-19 illness. Endemic coronavirus cross-immunity may play a role in protection against severe COVID-19.

Adults hospitalized with breakthrough COVID-19 have lower mortality than matched unvaccinated adults.

BACKGROUND: Coronavirus disease 2019 (COVID-19) breakthrough infections are common. OBJECTIVE: Evaluate in-hospital mortality of patients with COVID-19 by vaccination status using retrospective cohort study. METHODS: We generated propensity scores for receipt of full vaccination in adults requiring supplemental oxygen hospitalized at Kaiser Permanente Northern California (1 April 2021 to 30 November 2021) with positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction tests. Optimal matching of fully vaccinated/unvaccinated patients was performed comparing in-hospital mortality. RESULTS: Of 7305 patients, 1463 (20.0%) were full, 138 (1.9%) were partial, and 5704 (78.1%) were unvaccinated. Fully vaccinated were older than partial or unvaccinated (71.0, 63.0, and 54.0 years, respectively, p < 0.001) with more comorbidities (Comorbidity Point Scores 33.0, 22.0, and 10.0, p < 0.001) and immunosuppressant (11.5%, 8.7%, and 3.0%, p < 0.001) or chemotherapy exposure (2.8%, 0.7%, and 0.4%, p < 0.001). Fewer fully vaccinated patients died compared to matched unvaccinated (9.0% vs. 16.3%, p < 0.0001). CONCLUSION: Fully vaccinated patients are less likely to die compared to matched unvaccinated patients.

Prospective evaluation of social risks, physical function, and cognitive function in prediction of non-elective rehospitalization and post-discharge mortality.

BACKGROUND: Increasing evidence suggests that social factors and problems with physical and cognitive function may contribute to patients' rehospitalization risk. Understanding a patient's readmission risk may help healthcare providers develop tailored treatment and post-discharge care plans to reduce readmission and mortality. This study aimed to evaluate whether including patient-reported data on social factors; cognitive status; and physical function improves on a predictive model based on electronic health record (EHR) data alone. METHODS: We conducted a prospective study of 1,547 hospitalized adult patients in 3 Kaiser Permanente Northern California hospitals. The main outcomes were non-elective rehospitalization or death within 30 days post-discharge. Exposures included patient-reported social factors and cognitive and physical function (obtained in a pre-discharge interview) and EHR-derived data for comorbidity burden, acute physiology, care directives, prior utilization, and hospital length of stay. We performed bivariate comparisons using Chi-square, t-tests, and Wilcoxon rank-sum tests and assessed correlations between continuous variables using Spearman's rho statistic. For all models, the results reported were obtained after fivefold cross validation. RESULTS: The 1,547 adult patients interviewed were younger (age, p = 0.03) and sicker (COPS2, p < 0.0001) than the rest of the hospitalized population. Of the 6 patient-reported social factors measured, 3 (not living with a spouse/partner, transportation difficulties, health or disability-related limitations in daily activities) were significantly associated (p < 0.05) with the main outcomes, while 3 (living situation concerns, problems with food availability, financial problems) were not. Patient-reported cognitive (p = 0.027) and physical function (p = 0.01) were significantly lower in patients with the main outcomes. None of the patient-reported variables, singly or in combination, improved predictive performance of a model that included acute physiology and longitudinal comorbidity burden (area under the receiver operator characteristic curve was 0.716 for both the EHR model and maximal performance of a random forest model including all predictors). CONCLUSIONS: In this insured population, incorporating patient-reported social factors and measures of cognitive and physical function did not improve performance of an EHR-based model predicting 30-day non-elective rehospitalization or mortality. While incorporating patient-reported social and functional status data did not improve ability to predict these outcomes, such data may still be important for improving patient outcomes.

Developing a shared sepsis data infrastructure: a systematic review and concept map to FHIR.

The development of a shared data infrastructure across health systems could improve research, clinical care, and health policy across a spectrum of diseases, including sepsis. Awareness of the potential value of such infrastructure has been heightened by COVID-19, as the lack of a real-time, interoperable data network impaired disease identification, mitigation, and eradication. The Sepsis on FHIR collaboration establishes a dynamic, federated, and interoperable system of sepsis data from 55 hospitals using 2 distinct inpatient electronic health record systems. Here we report on phase 1, a systematic review to identify clinical variables required to define sepsis and its subtypes to produce a concept mapping of elements onto Fast Healthcare Interoperability Resources (FHIR). Relevant papers described consensus sepsis definitions, provided criteria for sepsis, severe sepsis, septic shock, or detailed sepsis subtypes. Studies not written in English, published prior to 1970, or "grey" literature were prospectively excluded. We analyzed 55 manuscripts yielding 151 unique clinical variables. We then mapped variables to their corresponding US Core FHIR resources and specific code values. This work establishes the framework to develop a flexible infrastructure for sharing sepsis data, highlighting how FHIR could enable the extension of this approach to other important conditions relevant to public health.

Exploratory analysis of novel electronic health record variables for quantification of healthcare delivery strain, prediction of mortality, and prediction of imminent discharge.

OBJECTIVE: To explore the relationship between novel, time-varying predictors for healthcare delivery strain (eg, counts of patient orders per hour) and imminent discharge and in-hospital mortality. MATERIALS AND METHODS: We conducted a retrospective cohort study using data from adults hospitalized at 21 Kaiser Permanente Northern California hospitals between November 1, 2015 and October 31, 2020 and the nurses caring for them. Patient data extracted included demographics, diagnoses, severity measures, occupancy metrics, and process of care metrics (eg, counts of intravenous drip orders per hour). We linked these data to individual registered nurse records and created multiple dynamic, time-varying predictors (eg, mean acute severity of illness for all patients cared for by a nurse during a given hour). All analyses were stratified by patients' initial hospital unit (ward, stepdown unit, or intensive care unit). We used discrete-time hazard regression to assess the association between each novel time-varying predictor and the outcomes of discharge and mortality, separately. RESULTS: Our dataset consisted of 84 162 161 hourly records from 954 477 hospitalizations. Many novel time-varying predictors had strong associations with the 2 study outcomes. However, most of the predictors did not merely track patients' severity of illness; instead, many of them only had weak correlations with severity, often with complex relationships over time. DISCUSSION: Increasing availability of process of care data from automated electronic health records will permit better quantification of healthcare delivery strain. This could result in enhanced prediction of adverse outcomes and service delays. CONCLUSION: New conceptual models will be needed to use these new data elements.