Adaptation of the Risk Analysis Index for Frailty Assessment Using Diagnostic Codes.

Importance: Frailty is associated with adverse outcomes after even minor physiologic stressors. The validated Risk Analysis Index (RAI) quantifies frailty; however, existing methods limit application to in-person interview (clinical RAI) and quality improvement datasets (administrative RAI). Objective: To expand the utility of the RAI utility to available International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) administrative data, using the National Inpatient Sample (NIS). Design, Setting, and Participants: RAI parameters were systematically adapted to ICD-10-CM codes (RAI-ICD) and were derived (NIS 2019) and validated (NIS 2020). The primary analysis included survey-weighed discharge data among adults undergoing major surgical procedures. Additional external validation occurred by including all operative and nonoperative hospitalizations in the NIS (2020) and in a multihospital health care system (UPMC, 2021-2022). Data analysis was conducted from January to May 2023. Exposures: RAI parameters and in-hospital mortality. Main Outcomes and Measures: The association of RAI parameters with in-hospital mortality was calculated and weighted using logistic regression, generating an integerized RAI-ICD score. After initial validation, thresholds defining categories of frailty were selected by a full complement of test statistics. Rates of elective admission, length of stay, hospital charges, and in-hospital mortality were compared across frailty categories. C statistics estimated model discrimination. Results: RAI-ICD parameters were weighted in the 9 548 206 patients who were hospitalized (mean [SE] age, 55.4 (0.1) years; 3 742 330 male [weighted percentage, 39.2%] and 5 804 431 female [weighted percentage, 60.8%]), modeling in-hospital mortality (2.1%; 95% CI, 2.1%-2.2%) with excellent derivation discrimination (C statistic, 0.810; 95% CI, 0.808-0.813). The 11 RAI-ICD parameters were adapted to 323 ICD-10-CM codes. The operative validation population of 8 113 950 patients (mean [SE] age, 54.4 (0.1) years; 3 148 273 male [weighted percentage, 38.8%] and 4 965 737 female [weighted percentage, 61.2%]; in-hospital mortality, 2.5% [95% CI, 2.4%-2.5%]) mirrored the derivation population. In validation, the weighted and integerized RAI-ICD yielded good to excellent discrimination in the NIS operative sample (C statistic, 0.784; 95% CI, 0.782-0.786), NIS operative and nonoperative sample (C statistic, 0.778; 95% CI, 0.777-0.779), and the UPMC operative and nonoperative sample (C statistic, 0.860; 95% CI, 0.857-0.862). Thresholds defining robust (RAI-ICD <27), normal (RAI-ICD, 27-35), frail (RAI-ICD, 36-45), and very frail (RAI-ICD >45) strata of frailty maximized precision (F1 = 0.33) and sensitivity and specificity (Matthews correlation coefficient = 0.26). Adverse outcomes increased with increasing frailty. Conclusion and Relevance: In this cohort study of hospitalized adults, the RAI-ICD was rigorously adapted, derived, and validated. These findings suggest that the RAI-ICD can extend the quantification of frailty to inpatient adult ICD-10-CM-coded patient care datasets.

Association Between Medicare's Sepsis Reporting Policy (SEP-1) and the Documentation of a Sepsis Diagnosis in the Clinical Record.

STUDY DESIGN: Interrupted time series analysis of a retrospective, electronic health record cohort. OBJECTIVE: To determine the association between the implementation of Medicare's sepsis reporting measure (SEP-1) and sepsis diagnosis rates as assessed in clinical documentation. BACKGROUND: The role of health policy in the effort to improve sepsis diagnosis remains unclear. PATIENTS AND METHODS: Adult patients hospitalized with suspected infection and organ dysfunction within 6 hours of presentation to the emergency department, admitted to one of 11 hospitals in a multi-hospital health system from January 2013 to December 2017. Clinician-diagnosed sepsis, as reflected by the inclusion of the terms "sepsis" or "septic" in the text of clinical notes in the first two calendar days following presentation. RESULTS: Among 44,074 adult patients with sepsis admitted to 11 hospitals over 5 years, the proportion with sepsis documentation was 32.2% just before the implementation of SEP-1 in the third quarter of 2015 and increased to 37.3% by the fourth quarter of 2017. Of the 9 post-SEP-1 quarters, 8 had odds ratios for a sepsis diagnosis >1 (overall range: 0.98-1.26; P value for a joint test of statistical significance = 0.005). The effects were clinically modest, with a maximum effect of an absolute increase of 4.2% (95% CI: 0.9-7.8) at the end of the study period. The effect was greater in patients who did not require vasopressors compared with patients who required vasopressors ( P value for test of interaction = 0.02). CONCLUSIONS: SEP-1 implementation was associated with modest increases in sepsis diagnosis rates, primarily among patients who did not require vasoactive medications.

Feasibility of Embedding a Scalable, Virtually Enabled Biorepository in the Electronic Health Record for Precision Medicine.

Importance: A cornerstone of precision medicine is the identification and use of biomarkers that help subtype patients for targeted treatment. Such an approach requires the development and subsequent interrogation of large-scale biobanks linked to well-annotated clinical data. Traditional means of creating these data-linked biobanks are costly and lengthy, especially in acute conditions that require time-sensitive clinical data and biospecimens. Objectives: To develop a virtually enabled biorepository and electronic health record (EHR)-embedded, scalable cohort for precision medicine (VESPRE) and compare the feasibility, enrollment, and costs of VESPRE with those of a traditional study design in acute care. Design, Setting, and Participants: In a prospective cohort study, the EHR-embedded screening alert was generated for 3428 patients, and 2199 patients (64%) were eligible and screened. Of these, 1027 patients (30%) were enrolled. VESPRE was developed for regulatory compliance, feasibility, internal validity, and cost in a prospective cohort of 1027 patients (aged ≥18 years) with sepsis-3 within 6 hours of presentation to the emergency department. The VESPRE infrastructure included (1) automated EHR screening, (2) remnant blood collection for creation of a virtually enabled biorepository, and (3) automated clinical data abstraction. The study was conducted at an academic institution in southwestern Pennsylvania from October 17, 2017, to June 6, 2019. Main Outcomes and Measures: Regulatory compliance, enrollment, internal validity of automated screening, biorepository acquisition, and costs. Results: Of the 1027 patients enrolled in the study, 549 were included in the proof-of-concept analysis (305 [56%] men); median (SD) age was 59 (17) years. VESPRE collected 12 963 remnant blood and urine samples and demonstrated adequate feasibility for clinical, biomarker, and microbiome analyses. Over the 20-month test, the total cost beyond the existing operations infrastructure was $39 417.50 ($14 880.00 project management, $22 717.50 laboratory supplies/staff, and $1820.00 data management)-approximately $39 per enrolled patient vs $239 per patient for a traditional cohort study. Conclusions and Relevance: Results of this study suggest that, in a large US health system that collects data using a common EHR platform and centralized laboratory system, VESPRE, a large-scale, inexpensive EHR-embedded infrastructure for precision medicine can be used. Tested in the sepsis setting, VESPRE appeared to capture a high proportion of eligible patients at low incremental cost.

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.

BACKGROUND: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. METHODS: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. FINDINGS: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. INTERPRETATION: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. FUNDING: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

Sepsis Surveillance Using Adult Sepsis Events Simplified eSOFA Criteria Versus Sepsis-3 Sequential Organ Failure Assessment Criteria.

OBJECTIVES: Sepsis-3 defines organ dysfunction as an increase in the Sequential Organ Failure Assessment score by greater than or equal to 2 points. However, some Sequential Organ Failure Assessment score components are not routinely recorded in all hospitals' electronic health record systems, limiting its utility for wide-scale sepsis surveillance. The Centers for Disease Control and Prevention recently released the Adult Sepsis Event surveillance definition that includes simplified organ dysfunction criteria optimized for electronic health records (eSOFA). We compared eSOFA versus Sequential Organ Failure Assessment with regard to sepsis prevalence, overlap, and outcomes. DESIGN: Retrospective cohort study. SETTING: One hundred eleven U.S. hospitals in the Cerner HealthFacts dataset. PATIENTS: Adults hospitalized in 2013-2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified clinical indicators of presumed infection (blood cultures and antibiotics) concurrent with either: 1) an increase in Sequential Organ Failure Assessment score by 2 or more points (Sepsis-3) or 2) 1 or more eSOFA criteria: vasopressor initiation, mechanical ventilation initiation, lactate greater than or equal to 2.0 mmol/L, doubling in creatinine, doubling in bilirubin to greater than or equal to 2.0 mg/dL, or greater than or equal to 50% decrease in platelet count to less than 100 cells/µL (Centers for Disease Control and Prevention Adult Sepsis Event). We compared area under the receiver operating characteristic curves for discriminating in-hospital mortality, adjusting for baseline characteristics. Of 942,360 patients in the cohort, 57,242 (6.1%) had sepsis by Sequential Organ Failure Assessment versus 41,618 (4.4%) by eSOFA. Agreement between sepsis by Sequential Organ Failure Assessment and eSOFA was good (Cronbach's alpha 0.81). Baseline characteristics and infectious diagnoses were similar, but mortality was higher with eSOFA (17.1%) versus Sequential Organ Failure Assessment (14.4%; p < 0.001) as was discrimination for mortality (area under the receiver operating characteristic curve, 0.774 vs 0.759; p < 0.001). Comparisons were consistent across subgroups of age, infectious diagnoses, and comorbidities. CONCLUSIONS: The Adult Sepsis Event's eSOFA organ dysfunction criteria identify a smaller, more severely ill sepsis cohort compared with the Sequential Organ Failure Assessment score, but with good overlap and similar clinical characteristics. Adult Sepsis Events may facilitate wide-scale automated sepsis surveillance that tracks closely with the more complex Sepsis-3 criteria.

The global burden of sepsis: barriers and potential solutions.

Sepsis is a major contributor to the global burden of disease. The majority of sepsis cases and deaths are estimated to occur in low and middle-income countries. Barriers to reducing the global burden of sepsis include difficulty quantifying attributable morbidity and mortality, low awareness, poverty and health inequity, and under-resourced and low-resilience public health and acute health care delivery systems. Important differences in the populations at risk, infecting pathogens, and clinical capacity to manage sepsis in high and low-resource settings necessitate context-specific approaches to this significant problem. We review these challenges and propose strategies to overcome them. These strategies include strengthening health systems, accurately identifying and quantifying sepsis cases, conducting inclusive research, establishing data-driven and context-specific management guidelines, promoting creative clinical interventions, and advocacy.

Mortality Changes Associated with Mandated Public Reporting for Sepsis. The Results of the New York State Initiative.

RATIONALE: In 2013, the New York State Department of Health (NYSDOH) began a mandatory state-wide initiative to improve early recognition and treatment of severe sepsis and septic shock. OBJECTIVES: This study examines protocol initiation, 3-hour and 6-hour sepsis bundle completion, and risk-adjusted hospital mortality among adult patients with severe sepsis and septic shock. METHODS: Cohort analysis included all patients from all 185 hospitals in New York State reported to the NYSDOH from April 1, 2014, to June 30, 2016. A total of 113,380 cases were submitted to NYSDOH, of which 91,357 hospitalizations from 183 hospitals met study inclusion criteria. NYSDOH required all hospitals to submit and follow evidence-informed protocols (including elements of 3-h and 6-h sepsis bundles: lactate measurement, early blood cultures and antibiotic administration, fluids, and vasopressors) for early identification and treatment of severe sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: Compliance with elements of the sepsis bundles and risk-adjusted mortality were studied. Of 91,357 patients, 74,293 (81.3%) had the sepsis protocol initiated. Among these individuals, 3-hour bundle compliance increased from 53.4% to 64.7% during the study period (P < 0.001), whereas among those eligible for the 6-hour bundle (n = 35,307) compliance increased from 23.9% to 30.8% (P < 0.001). Risk-adjusted mortality decreased from 28.8% to 24.4% (P < 0.001) in patients among whom a sepsis protocol was initiated. Greater hospital compliance with 3-hour and 6-hour bundles was associated with shorter length of stay and lower risk and reliability-adjusted mortality. CONCLUSIONS: New York's statewide initiative increased compliance with sepsis-performance measures. Risk-adjusted sepsis mortality decreased during the initiative and was associated with increased hospital-level compliance.

Evaluation of Repeated Quick Sepsis-Related Organ Failure Assessment Measurements Among Patients With Suspected Infection.

OBJECTIVES: Among patients with suspected infection, a single measurement of the quick Sepsis-related Organ Failure Assessment has good predictive validity for sepsis, yet the increase in validity from repeated measurements is unknown. We sought to determine the incremental predictive validity for sepsis of repeated quick Sepsis-related Organ Failure Assessment measurements over 48 hours compared with the initial measurement. DESIGN: Retrospective cohort study. SETTING: Twelve hospitals in southwestern Pennsylvania in 2012. PATIENTS: All adult medical and surgical encounters in the emergency department, hospital ward, postanesthesia care unit, and ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1.3 million adult encounters, we identified those with a first episode of suspected infection. Using the maximum quick Sepsis-related Organ Failure Assessment score in each 6-hour epoch from onset of suspected infection until 48 hours later, we characterized repeated quick Sepsis-related Organ Failure Assessment with: 1) summary measures (e.g., mean over 48 hr), 2) crude trajectory groups, and 3) group-based trajectory modeling. We measured the predictive validity of repeated quick Sepsis-related Organ Failure Assessment using incremental changes in the area under the receiver operating characteristic curve for in-hospital mortality beyond that of baseline risk (age, sex, race/ethnicity, and comorbidity). Of 37,591 encounters with suspected infection, 1,769 (4.7%) died before discharge. Both the mean quick Sepsis-related Organ Failure Assessment at 48 hours (area under the receiver operating characteristic, 0.86 [95% CI, 0.85-0.86]) and crude trajectory groups (area under the receiver operating characteristic, 0.83 [95% CI, 0.83-0.83]) improved predictive validity compared with initial quick Sepsis-related Organ Failure Assessment (area under the receiver operating characteristic, 0.79 [95% CI, 0.78-0.80]) (p < 0.001 for both). Group-based trajectory modeling found five trajectories (quick Sepsis-related Organ Failure Assessment always low, increasing, decreasing, moderate, and always high) with greater predictive validity than the initial measurement (area under the receiver operating characteristic, 0.85 [95% CI, 0.84-0.85]; p < 0.001). CONCLUSIONS: Repeated measurements of quick Sepsis-related Organ Failure Assessment improve predictive validity for sepsis using in-hospital mortality compared with a single measurement of quick Sepsis-related Organ Failure Assessment at the time a clinician suspects infection.

Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) Score With Excess Hospital Mortality in Adults With Suspected Infection in Low- and Middle-Income Countries.

Importance: The quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score has not been well-evaluated in low- and middle-income countries (LMICs). Objective: To assess the association of qSOFA with excess hospital death among patients with suspected infection in LMICs and to compare qSOFA with the systemic inflammatory response syndrome (SIRS) criteria. Design, Settings, and Participants: Retrospective secondary analysis of 8 cohort studies and 1 randomized clinical trial from 2003 to 2017. This study included 6569 hospitalized adults with suspected infection in emergency departments, inpatient wards, and intensive care units of 17 hospitals in 10 LMICs across sub-Saharan Africa, Asia, and the Americas. Exposures: Low (0), moderate (1), or high (≥2) qSOFA score (range, 0 [best] to 3 [worst]) or SIRS criteria (range, 0 [best] to 4 [worst]) within 24 hours of presentation to study hospital. Main Outcomes and Measures: Predictive validity (measured as incremental hospital mortality beyond that predicted by baseline risk factors, as a marker of sepsis or analogous severe infectious course) of the qSOFA score (primary) and SIRS criteria (secondary). Results: The cohorts were diverse in enrollment criteria, demographics (median ages, 29-54 years; males range, 36%-76%), HIV prevalence (range, 2%-43%), cause of infection, and hospital mortality (range, 1%-39%). Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. Compared with a low or moderate score, a high qSOFA score was associated with increased risk of death overall (19% vs 6%; difference, 13% [95% CI, 11%-14%]; odds ratio, 3.6 [95% CI, 3.0-4.2]) and across cohorts (P < .05 for 8 of 9 cohorts). Compared with a low qSOFA score, a moderate qSOFA score was also associated with increased risk of death overall (8% vs 3%; difference, 5% [95% CI, 4%-6%]; odds ratio, 2.8 [95% CI, 2.0-3.9]), but not in every cohort (P < .05 in 2 of 7 cohorts). High, vs low or moderate, SIRS criteria were associated with a smaller increase in risk of death overall (13% vs 8%; difference, 5% [95% CI, 3%-6%]; odds ratio, 1.7 [95% CI, 1.4-2.0]) and across cohorts (P < .05 for 4 of 9 cohorts). qSOFA discrimination (area under the receiver operating characteristic curve [AUROC], 0.70 [95% CI, 0.68-0.72]) was superior to that of both the baseline model (AUROC, 0.56 [95% CI, 0.53-0.58; P < .001) and SIRS (AUROC, 0.59 [95% CI, 0.57-0.62]; P < .001). Conclusions and Relevance: When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.

Children with Chronic Disease Bear the Highest Burden of Pediatric Sepsis.

OBJECTIVE: To describe the contemporary epidemiology of pediatric sepsis in children with chronic disease, and the contribution of chronic diseases to mortality. We examined the incidence and hospital mortality of pediatric sepsis in a nationally representative sample and described the contribution of chronic diseases to hospital mortality. STUDY DESIGN: We analyzed the 2013 Nationwide Readmissions Database using a retrospective cohort design. We included non-neonatal patients <19 years of age hospitalized with sepsis. We examined patient characteristics, the distribution of chronic disease, and the estimated national incidence, and described hospital mortality. We used mixed effects logistic regression to explore the association between chronic diseases and hospital mortality. RESULTS: A total of 16 387 admissions, representing 14 243 unique patients, were for sepsis. The national incidence was 0.72 cases per 1000 per year (54 060 cases annually). Most (68.6%) had a chronic disease. The in-hospital mortality was 3.7% overall-0.7% for previously healthy patients and 5.1% for patients with chronic disease. In multivariable analysis, oncologic, hematologic, metabolic, neurologic, cardiac and renal disease, and solid organ transplantation were associated with increased in-hospital mortality. CONCLUSIONS: More than 2 of 3 children admitted with sepsis have ≥1 chronic disease and these patients have a higher in-hospital mortality than previously healthy patients. The burden of sepsis in hospitalized children is greatest in pediatric patients with chronic disease.

Reporting of Sepsis Cases for Performance Measurement Versus for Reimbursement in New York State.

OBJECTIVES: Under "Rory's Regulations," New York State Article 28 acute care hospitals were mandated to implement sepsis protocols and report patient-level data. This study sought to determine how well cases reported under state mandate align with discharge records in a statewide administrative database. DESIGN: Observational cohort study. SETTING: First 27 months of mandated sepsis reporting (April 1, 2014, to June 30, 2016). PATIENTS: Hospitalizations with sepsis at New York State Article 28 acute care hospitals. INTERVENTION: Sepsis regulations with mandated reporting. MEASUREMENTS AND MAIN RESULTS: We compared cases reported to the New York State Department of Health Sepsis Clinical Database with discharge records in the Statewide Planning and Research Cooperative System database. We classified discharges as 1) "coded sepsis discharges"-a diagnosis code for severe sepsis or septic shock and 2) "possible sepsis discharges," using Dombrovskiy and Angus criteria. Of 111,816 sepsis cases reported to the New York State Department of Health Sepsis Clinical Database, 105,722 (94.5%) were matched to discharge records in Statewide Planning and Research Cooperative System. The percentage of coded sepsis discharges reported increased from 67.5% in the first quarter to 81.3% in the final quarter of the study period (mean, 77.7%). Accounting for unmatched cases, as many as 82.7% of coded sepsis discharges were potentially reported, whereas at least 17.3% were unreported. Compared with unreported discharges, reported discharges had higher rates of acute organ dysfunction (e.g., cardiovascular dysfunction 63.0% vs 51.8%; p < 0.001) and higher in-hospital mortality (30.2% vs 26.1%; p < 0.001). Hospital characteristics (e.g., number of beds, teaching status, volume of sepsis cases) were similar between hospitals with a higher versus lower percent of discharges reported, p values greater than 0.05 for all. Hospitals' percent of discharges reported was not correlated with risk-adjusted mortality of their submitted cases (Pearson correlation coefficient 0.11; p = 0.17). CONCLUSIONS: Approximately four of five discharges with a diagnosis code of severe sepsis or septic shock in the Statewide Planning and Research Cooperative System data were reported in the New York State Department of Health Sepsis Clinical Database. Incomplete reporting appears to be driven more by underrecognition than attempts to game the system, with minimal bias to risk-adjusted hospital performance measurement.

Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014.

Importance: Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective: To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population: Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures: Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures: Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results: A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, -2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (-3.3%/y [95% CI, -5.6% to -1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (-1.3%/y [95% CI, -3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (-7.0%/y [95% CI, -8.8% to -5.2%], P < .001), as did death or discharge to hospice (-4.5%/y [95% CI, -6.1% to -2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23). Conclusions and Relevance: In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.

Effects of Physician-targeted Pay for Performance on Use of Spontaneous Breathing Trials in Mechanically Ventilated Patients.

RATIONALE: Pay for performance is an increasingly common quality improvement strategy despite the absence of robust supporting evidence. OBJECTIVES: To determine the impact of a financial incentive program rewarding physicians for the completion of daily spontaneous breathing trials (SBTs) in three academic hospitals. METHODS: We compared data from mechanically ventilated patients from 6 months before to 2 years after introduction of a financial incentive program that provided annual payments to critical care physicians contingent on unit-level SBT completion rates. We used Poisson regression to compare the frequency of days on which SBTs were completed among eligible patients and days on which patients were excluded from SBT eligibility among all mechanically ventilated patients. We used multivariate regression to compare risk-adjusted duration of mechanical ventilation and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: The cohort included 7,291 mechanically ventilated patients with 75,621 ventilator days. Baseline daily SBT rates were 96.8% (hospital A), 16.4% (hospital B), and 74.7% (hospital C). In hospital A, with the best baseline performance, there was no change in SBT rates, exclusion rates, or duration of mechanical ventilation across time periods. In hospitals B and C, with lower SBT completion rates at baseline, there was an increase in daily SBT completion rates and a concomitant increase in exclusions from eligibility. Duration of mechanical ventilation decreased in hospital C but not in hospital B. Mortality was unchanged for all hospitals. CONCLUSIONS: In hospitals with low baseline SBT completion, physician-targeted financial incentives were associated with increased SBT rates driven in part by increased exclusion rates, without consistent improvements in outcome.

Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

IMPORTANCE: The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE: To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION: Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706,399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES: Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0-3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES: For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS: In the primary cohort, 148,907 encounters had suspected infection (n = 74,453 derivation; n = 74,454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62-0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64-0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73-0.76; P < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73-0.76; P < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78-0.80; P < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75-0.77; P < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome. CONCLUSIONS AND RELEVANCE: Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis.

Effect of public reporting on intensive care unit discharge destination and outcomes.

RATIONALE: Public reporting of hospital performance is designed to improve healthcare outcomes by promoting quality improvement and informing consumer choice, but these programs may carry unintended consequences. OBJECTIVE: To determine whether publicly reporting in-hospital mortality rates for intensive care unit (ICU) patients influenced discharge patterns or mortality. METHODS: We performed a retrospective cohort study taking advantage of a natural experiment in which California, but not other states, publicly reported hospital-specific severity-adjusted ICU mortality rates between 2007 and 2012. We used multivariable logistic regression adjusted for patient, hospital, and regional characteristics to compare mortality rates and discharge patterns between California and states without public reporting for Medicare fee-for-service ICU admissions from 2005 through 2009 using a difference-in-differences approach. MEASUREMENTS AND MAIN RESULTS: We assessed discharge patterns using post-acute care use and acute care hospital transfer rates and mortality using in-hospital and 30-day mortality rates. The study cohort included 936,063 patients admitted to 646 hospitals. Compared with control subjects, admission to a California ICU after the introduction of public reporting was associated with a reduced odds of post-acute care use in post-reform year 2 (ratio of odds ratios [ORs], 0.94; 95% confidence interval [CI], 0.91-0.96) and increased odds of transfer to another acute care hospital in both post-reform years (year 1: ratio of ORs, 1.08; 95% CI, 1.01-1.16; year 2: ratio of ORs, 1.43; 95% CI, 1.33-1.53). There were no significant differences in in-hospital or 30-day mortality. CONCLUSIONS: Public reporting of ICU in-hospital mortality rates was associated with changes in discharge patterns but no change in risk-adjusted mortality.

Critical care bed growth in the United States. A comparison of regional and national trends.

RATIONALE: Although the number of intensive care unit (ICU) beds in the United States is increasing, it is unknown whether this trend is consistent across all regions. OBJECTIVES: We sought to better characterize regional variation in ICU bed changes over time and identify regional characteristics associated with these changes. METHODS: We used data from the Centers for Medicare and Medicaid Services and the U.S. Census to summarize the numbers of hospitals, hospital beds, ICU beds, and ICU occupancy at the level of Dartmouth Atlas hospital referral region from 2000 to 2009. We categorized regions into quartiles of bed change over the study interval and examined the relationship between change categories, regional characteristics, and population characteristics over time. MEASUREMENTS AND MAIN RESULTS: From 2000 to 2009 the national number of ICU beds increased 15%, from 67,579 to 77,809, mirroring population. However, there was substantial regional variation in absolute changes (median, +16 ICU beds; interquartile range, -3 to +51) and population-adjusted changes (median, +0.9 ICU beds per 100,000; interquartile range, -3.8 to +5.9), with 25.0% of regions accounting for 74.8% of overall growth. At baseline, regions with increasing numbers of ICU beds had larger populations, lower ICU beds per 100,000 capita, higher average ICU occupancy, and greater market competition as measured by the Herfindahl-Hirschman Index (P < 0.001 for all comparisons). CONCLUSIONS: National trends in ICU bed growth are not uniformly reflected at the regional level, with most growth occurring in a small number of highly populated regions.

Hospital-level variation in ICU admission and critical care procedures for patients hospitalized for pulmonary embolism.

BACKGROUND: Variation in the use of ICUs for low-risk conditions contributes to health system inefficiency. We sought to examine the relationship between ICU use for patients with pulmonary embolism (PE) and cost, mortality, readmission, and procedure use. METHODS: We performed a retrospective cohort study including 61,249 adults with PE discharged from 263 hospitals in three states between 2007 and 2010. We generated hospital-specific ICU admission rate quartiles and used a series of multilevel models to evaluate relationships between admission rates and risk-adjusted in-hospital mortality, readmission, and costs and between ICU admission rates and several critical care procedures. RESULTS: Hospital quartiles varied in unadjusted ICU admission rates for PE (range, ≤ 15% to > 31%). Among all patients, there was a small trend toward increased use of arterial catheterization (0.6%-1.1%, P < .01) in hospital quartiles with higher levels of ICU admission. However, use of invasive mechanical ventilation (14.4%-7.9%, P < .01), noninvasive ventilation (6.6%-3.0%, P < .01), central venous catheterization (14.6%-11.3%, P < .02), and thrombolytics (11.0%-4.7%, P < .01) in patients in the ICU declined across hospital quartiles. There was no relationship between ICU admission rate and risk-adjusted hospital mortality, costs, or readmission. CONCLUSIONS: Hospitals vary widely in ICU admission rates for acute PE without a detectable impact on mortality, cost, or readmission. Patients admitted to ICUs in higher-using hospitals received many critical care procedures less often, suggesting that these patients may have had weaker indications for ICU admission. Hospitals with greater ICU admission may be appropriate targets for improving efficiency in ICU admissions.

Geographic access to high capability severe acute respiratory failure centers in the United States.

OBJECTIVE: Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States. DESIGN: Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008-2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims. SETTING: Nonfederal acute care hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air. CONCLUSIONS: Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate referral center access in the case of disasters and pandemics will depend highly on local and regional care coordination across political boundaries.

Severe sepsis in pre-hospital emergency care: analysis of incidence, care, and outcome.

RATIONALE: Severe sepsis is common and highly morbid, yet the epidemiology of severe sepsis at the frontier of the health care system-pre-hospital emergency care-is unknown. OBJECTIVES: We examined the epidemiology of pre-hospital severe sepsis among emergency medical services (EMS) encounters, relative to acute myocardial infarction and stroke. METHODS: Retrospective study using a community-based cohort of all nonarrest, nontrauma King County EMS encounters from 2000 to 2009 who were transported to a hospital. MEASUREMENTS AND MAIN RESULTS: Overall incidence rate of hospitalization with severe sepsis among EMS encounters, as well as pre-hospital characteristics, admission diagnosis, and outcomes. Among 407,176 EMS encounters, we identified 13,249 hospitalizations for severe sepsis, of whom 2,596 died in the hospital (19.6%). The crude incidence rate of severe sepsis was 3.3 per 100 EMS encounters, greater than for acute myocardial infarction or stroke (2.3 per 100 and 2.2 per 100 EMS encounters, respectively). More than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport, and 80% of cases were diagnosed on admission. Pre-hospital care intervals, on average, exceeded 45 minutes for those hospitalized with severe sepsis. One-half or fewer of patients with severe sepsis were transported by paramedics (n = 7,114; 54%) or received pre-hospital intravenous access (n = 4,842; 37%). CONCLUSIONS: EMS personnel care for a substantial and increasing number of patients with severe sepsis, and spend considerable time on scene and during transport. Given the emphasis on rapid diagnosis and intervention for sepsis, the pre-hospital interval may represent an important opportunity for recognition and care of sepsis.

Defining and measuring successful emergency care networks: a research agenda.

The demands on emergency services have grown relentlessly, and the Institute of Medicine (IOM) has asserted the need for "regionalized, coordinated, and accountable emergency care systems throughout the country." There are large gaps in the evidence base needed to fix the problem of how emergency care is organized and delivered, and science is urgently needed to define and measure success in the emerging network of emergency care. In 2010, Academic Emergency Medicine convened a consensus conference entitled "Beyond Regionalization: Integrated Networks of Emergency Care." This article is a product of the conference breakout session on "Defining and Measuring Successful Networks"; it explores the concept of integrated emergency care delivery and prioritizes a research agenda for how to best define and measure successful networks of emergency care. The authors discuss five key areas: 1) the fundamental metrics that are needed to measure networks across time-sensitive and non-time-sensitive conditions; 2) how networks can be scalable and nimble and can be creative in terms of best practices; 3) the potential unintended consequences of networks of emergency care; 4) the development of large-scale, yet feasible, network data systems; and 5) the linkage of data systems across the disease course. These knowledge gaps must be filled to improve the quality and efficiency of emergency care and to fulfill the IOM's vision of regionalized, coordinated, and accountable emergency care systems.