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1.  Hospital-Level Variation in the Use of Intensive Care 
Health Services Research  2012;47(5):2060-2080.
Objective
To determine the extent to which hospitals vary in the use of intensive care, and the proportion of variation attributable to differences in hospital practice that is independent of known patient and hospital factors.
Data Source
Hospital discharge data in the State Inpatient Database for Maryland and Washington States in 2006.
Study Design
Cross-sectional analysis of 90 short-term, acute care hospitals with critical care capabilities.
Data Collection/Methods
We quantified the proportion of variation in intensive care use attributable to hospitals using intraclass correlation coefficients derived from mixed-effects logistic regression models after successive adjustment for known patient and hospital factors.
Principal Findings
The proportion of hospitalized patients admitted to an intensive care unit (ICU) across hospitals ranged from 3 to 55 percent (median 12 percent; IQR: 9, 17 percent). After adjustment for patient factors, 19.7 percent (95 percent CI: 15.1, 24.4) of total variation in ICU use across hospitals was attributable to hospitals. When observed hospital characteristics were added, the proportion of total variation in intensive care use attributable to unmeasured hospital factors decreased by 26–14.6 percent (95 percent CI: 11, 18.3 percent).
Conclusions
Wide variability exists in the use of intensive care across hospitals, not attributable to known patient or hospital factors, and may be a target to improve efficiency and quality of critical care.
doi:10.1111/j.1475-6773.2012.01402.x
PMCID: PMC3513618  PMID: 22985033
Intensive care; critical illness; variation; hospitals
2.  Trends in Mortality and Early Central Line Placement in Septic Shock: True, True, and Related? 
Critical care medicine  2013;41(6):1577-1578.
doi:10.1097/CCM.0b013e318283cc36
PMCID: PMC4040497  PMID: 23685581
intensive care; outcomes research; health services; statistical data analysis; claims analysis; ICD codes
3.  Advancing Clinical Practice and Policy through Guidelines. The Role of the American Thoracic Society 
In the face of an overwhelmingly large and growing medical literature, providers often turn to clinical practice guidelines to inform the decisions they make with patients. By systematically appraising the evidence and providing transparent recommendations for practice, guidelines have the potential to improve both bedside decision-making and health policy. This potential has not been fully realized because most guidelines lack transparency, are tainted by conflicts of interest, or fail to employ rigorous methods to appraise the evidence. To address the shortcomings of past guidelines, the Institute of Medicine (IOM) published recommendations for trustworthy guidelines, effectively setting the “gold standard” for what constitutes a high-quality guideline. Along with many other groups that develop guidelines, the American Thoracic Society (ATS) is rapidly evolving processes for development and implementation to meet many of the IOM standards. This Pulmonary Perspective describes the rapidly changing landscape of clinical practice guidelines, the role of the ATS in this landscape, and the activities the ATS is engaged in to ensure that the guidelines it produces are of the highest quality with the broadest impact.
doi:10.1164/rccm.201301-0009PP
PMCID: PMC3707361  PMID: 23392437
clinical practice variation; standards of care; evidence-based medicine; professional organizations; pay for performance
4.  Making ICU prognostication patient centered: is there a role for dynamic information? 
Critical care medicine  2013;41(4):1136-1138.
doi:10.1097/CCM.0b013e31827c03eb
PMCID: PMC3677817  PMID: 23528758
prognosis; critical care; statistical models; severity of illness index; long-term survivors
5.  Using existing data to address important clinical questions in critical care 
Critical care medicine  2013;41(3):886-896.
Objective
With important technological advances in healthcare delivery and the internet, clinicians and scientists now have access to overwhelming number of available databases capturing patients with critical illness. Yet investigators seeking to answer important clinical or research questions with existing data have few resources that adequately describe the available sources and the strengths and limitations of each. This article reviews an approach to selecting a database to address health services and outcomes research questions in critical care, examines several databases that are commonly used for this purpose, and briefly describes some strengths and limitations of each.
Data Sources
Narrative review of the medical literature.
Summary
The available databases that collect information on critically ill patients are numerous and vary in the types of questions they can optimally answer. Selection of a data source must not only consider accessibility, but also the quality of the data contained within the database, and the extent to which it captures the necessary variables for the research question. Questions seeking causal associations (e.g. effect of treatment on mortality) usually either require secondary data that contain detailed information about demographics, laboratories, and physiology to best address non-random selection or sophisticated study design. Purely descriptive questions (e.g. incidence of respiratory failure) can often be addressed using secondary data with less detail such as administrative claims. Though each database has its own inherent limitations, all secondary analyses will be subject to the same challenges of appropriate study design and good observational research.
Conclusion
The literature demonstrates that secondary analyses can have significant impact on critical care practice. While selection of the optimal database for a particular question is a necessary part of high-quality analyses, it is not sufficient to guarantee an unbiased study. Thoughtful and well-constructed study design and analysis approaches remain equally important pillars of robust science. Only through responsible use of existing data will investigators ensure that their study has the greatest impact on critical care practice and outcomes.
doi:10.1097/CCM.0b013e31827bfc3c
PMCID: PMC3684417  PMID: 23328262
Epidemiology; intensive care; outcomes research; health services; health policy; statistical data analysis; factual databases; medical records systems
6.  Race and timeliness of transfer for revascularization in patients with acute myocardial infarction 
Medical care  2011;49(7):662-667.
Objectives
Patients with acute myocardial infarction (AMI) who are admitted to hospitals without coronary revascularization are frequently transferred to hospitals with this capability. We sought to determine if the timeliness of hospital transfer and quality of destination hospitals differed between black and white patients.
Methods
We evaluated all white and black Medicare beneficiaries admitted with AMI at non-revascularization hospitals in 2006 who were transferred to a revascularization hospital. We compared hospital length of stay prior to transfer and the transfer destination's 30-day risk-standardized mortality rate (RSMR) for AMI between black and white patients. We used hierarchical regression to adjust for patient characteristics and examine within- and across-hospital effects of race on 30-day mortality and length of stay prior to transfer.
Results
A total of 25,947 (42%) white and 2,345 (37%) black patients with AMI were transferred from 857 urban and 774 rural non-revascularization hospitals to 928 revascularization hospitals. Median (IQR) length of stay prior to transfer was 1 day (1-3) for white patients and 2 days (1-4) for black patients (p<0.001). In adjusted models, black patients tended to be transferred more slowly than white patients, a finding due to both across-hospital and within-hospital effects. For example, within an given urban hospital black patients were transferred an additional 0.24 days (95% CI 0.03-0.44) later than white patients. Additionally, the lengths of stay prior to transfer for all patients at urban hospitals increased by 0.37 days (95% CI 0.28-0.47) for every 20% increase in the proportion of AMI patients who were black. These results were attenuated in rural hospitals. The RSMR of the revascularization hospital to which patients were ultimately sent did not differ between black and white patients
Conclusions
Black patients are transferred more slowly to revascularization hospitals after AMI than white patients, resulting from both less timely transfers within hospitals as well as admission to hospitals with greater delays in transfer; however, 30-day mortality of the revascularization hospital to which both groups were sent to appeared similar. Race-based delays in transfer may contribute to known racial disparities in outcomes of AMI.
doi:10.1097/MLR.0b013e31821d98b2
PMCID: PMC3905793  PMID: 21677592
Healthcare Disparities; Patient Transfer; Critical Care; Cardiovascular Diseases; Quality Indicators
7.  A Simple Clinical Predictive Index for Objective Estimates of Mortality in Acute Lung Injury 
Critical care medicine  2009;37(6):1913-1920.
Objective
We sought to develop a simple point score that would accurately capture the risk of hospital death for patients with acute lung injury (ALI).
Design
This is a secondary analysis of data from two randomized trials. Baseline clinical variables collected within 24 hours of enrollment were modeled as predictors of hospital mortality using logistic regression and bootstrap resampling to arrive at a parsimonious model. We constructed a point score based on regression coefficients.
Setting
Medical centers participating in the Acute Respiratory Distress Syndrome Clinical Trials network (ARDSnet).
Patients
Model development: 414 patients with non-traumatic ALI participating in the low tidal volume arm of the ARDSnet ARMA study. Model validation: 459 patients participating in the ARDSnet ALVEOLI study.
Interventions
None
Measurements and Main Results
Variables comprising the prognostic model were: hematocrit <26% (1 point), bilirubin ≥ 2 mg/dl (1 point), fluid balance greater than 2.5 liters positive (1 point), and age (1 point for age 40–64, 2 points for age ≥ 65 years). Predicted mortality (95% confidence interval) for 0, 1, 2, 3, and 4+ point totals was 8% (5–14%), 17% (12–23%), 31% (26–37%), 51% (43–58%), and 70% (58–80%), respectively. There was excellent agreement between predicted and observed mortality in the validation cohort. Observed mortality for 0, 1, 2, 3, and 4+ point totals in the validation cohort was 12%, 16%, 28%, 47%, and 67%, respectively. Compared to the APACHE III score, areas under the receiver operating characteristic curve for the point score were greater in the development cohort (0.72 vs. 0.67, p=0.09) and lower in the validation cohort (0.68 vs. 0.75, p=0.03).
Conclusions
Mortality in ALI patients can be predicted using an index of four readily-available clinical variables with good calibration. This index may help inform prognostic discussions, but validation in non-clinical trial populations is necessary before widespread use.
doi:10.1097/CCM.0b013e3181a009b4
PMCID: PMC2731230  PMID: 19384214
Acute respiratory distress syndrome; acute lung injury; Respiratory Distress Syndrome; Adult; Human ARDS; Statistical Model; logistic models; mortality determinants; Mortality; In-Hospital; Acute Physiology and Chronic Health Evaluation; APACHE III; Bayesian Prediction; Prognosis
8.  Age-, sex-, and race-based differences among patients enrolled versus not enrolled in acute lung injury clinical trials 
Critical care medicine  2010;38(6):1450-1457.
Objective
Little is known about the participation of racial/ethnic minorities, women, and the elderly into critical care clinical trials. We sought to characterize the representation of racial and ethnic minorities, women and older patients in clinical trials of patients with acute lung injury (ALI) and to determine the reasons for non-enrollment.
Design, Setting, an Patients
We performed a cross-sectional analysis of pooled screening logs from 44 academic hospitals participating in three multi-center, randomized, controlled trials conducted by the Acute Respiratory Distress Syndrome Network (ARDSnet) from 1996 to 2005.
Intervention
None
Measurements and Main Results
We calculated odds ratios (OR) of enrollment for age, sex, racial groups, and the OR for the presence of each exclusion criterion by age, sex, and race adjusted for demographics, ALI risk factor, study, and study center. 10.4% of 17,459 screened patients with ALI were enrolled. The median (range) enrollment by center was 15% (2–88%). Older patients of both sexes were less likely to be enrolled, but older women were more likely to be enrolled than older men. The adjusted OR (95% confidence interval [CI]) for enrollment among men ≥75 years of age was 0.59 (0.45–0.77) and for women ≥75 years of age was 0.45 (0.32–0.62), compared to men <35 years of age. There were no differences in the likelihood of enrollment among all racial/ethnic groups. Older patients and men were less likely to be enrolled because of medical comorbidity. Among all patients who were not enrolled, black patients and their families refused participation more often than white patients.
Conclusions
Older patients are less likely to be enrolled in ALI clinical trials. There is no evidence that women or racial/ethnic minorities are underrepresented in ALI clinical trials.
doi:10.1097/CCM.0b013e3181de451b
PMCID: PMC3799957  PMID: 20386308
Critical Illness; Ethics, Research; Healthcare Disparities; Research Methodology; Aged
9.  The Effect of Pre-PPACA Medicaid Eligibility Expansion in New York State on Access to Specialty Surgical Care 
Medical care  2014;52(9):790-795.
Background
Critics argue that expanding health insurance coverage through Medicaid may not result in improved access to care. The ACA provides reimbursement incentives aimed at improving access to primary care services for new Medicaid beneficiaries; however, there are no such incentives for specialty services. Using the natural experiment of Medicaid expansion in New York State in October 2001, we examined whether Medicaid expansion increased access to common musculoskeletal procedures for Medicaid beneficiaries.
Methods
From the State Inpatient Database for NY State, we identified 19–64 year old patients who received; lower extremity large joint replacement, spine procedures and upper/lower extremity fracture/dislocation repair from January 1998–December 2006. We used interrupted time series analysis to evaluate the association between Medicaid expansion and trends in the relative and absolute number of Medicaid beneficiaries who received these musculoskeletal procedures.
Results
Prior to Medicaid expansion, we observed a slight but steady temporal decline in the proportion of musculoskeletal surgical patients who were Medicaid beneficiaries. Following expansion this trend reversed and by 5 years after Medicaid expansion, the proportion of musculoskeletal surgical patients who were Medicaid beneficiaries was 4.7 percentage points (95% CI 3.9, 5.5) higher than expected based on the pre-expansion time trend.
Conclusions
Medicaid expansion in NY State significantly improved access to common musculoskeletal procedures, for Medicaid beneficiaries.
doi:10.1097/MLR.0000000000000175
PMCID: PMC4262819  PMID: 24984209
access; Medicaid; specialist; specialty; surgical
10.  Influenza Pneumonia Surveillance among Hospitalized Adults May Underestimate the Burden of Severe Influenza Disease 
PLoS ONE  2014;9(11):e113903.
Background
Studies seeking to estimate the burden of influenza among hospitalized adults often use case definitions that require presence of pneumonia. The goal of this study was to assess the extent to which restricting influenza testing to adults hospitalized with pneumonia could underestimate the total burden of hospitalized influenza disease.
Methods
We conducted a modelling study using the complete State Inpatient Databases from Arizona, California, and Washington and regional influenza surveillance data acquired from CDC from January 2003 through March 2009. The exposures of interest were positive laboratory tests for influenza A (H1N1), influenza A (H3N2), and influenza B from two contiguous US Federal Regions encompassing the study area. We identified the two outcomes of interest by ICD-9-CM code: respiratory and circulatory hospitalizations, as well as critical illness hospitalizations (acute respiratory failure, severe sepsis, and in-hospital death). We linked the hospitalization datasets with the virus surveillance datasets by geographic region and month of hospitalization. We used negative binomial regression models to estimate the number of influenza-associated events for the outcomes of interest. We sub-categorized these events to include all outcomes with or without pneumonia diagnosis codes.
Results
We estimated that there were 80,834 (95% CI 29,214–174,033) influenza-associated respiratory and circulatory hospitalizations and 26,760 (95% CI 14,541–47,464) influenza-associated critical illness hospitalizations. When a pneumonia diagnosis was excluded, the estimated number of influenza-associated respiratory and circulatory hospitalizations was 24,816 (95% CI 6,342–92,624). The estimated number of influenza-associated critical illness hospitalizations was 8,213 (95% CI 3,764–20,799). Around 30% of both influenza-associated respiratory and circulatory hospitalizations, as well as influenza-associated critical illness hospitalizations did not have pneumonia diagnosis codes.
Conclusions
Surveillance studies which only consider hospitalizations that include a diagnosis of pneumonia may underestimate the total burden of influenza hospitalizations.
doi:10.1371/journal.pone.0113903
PMCID: PMC4244176  PMID: 25423025
11.  Intensive Care Unit Outcomes Among Patients With Lung Cancer in the Surveillance, Epidemiology, and End Results–Medicare Registry 
Journal of Clinical Oncology  2012;30(14):1686-1691.
Purpose
Lung cancer is the leading cause of cancer-related mortality. Intensive care unit (ICU) use among patients with cancer is increasing, but data regarding ICU outcomes for patients with lung cancer are limited.
Patients and Methods
We used the Surveillance, Epidemiology, and End Results (SEER) –Medicare registry (1992 to 2007) to conduct a retrospective cohort study of patients with lung cancer who were admitted to an ICU for reasons other than surgical resection of their tumor. We used logistic and Cox regression to evaluate associations of patient characteristics and hospital mortality and 6-month mortality, respectively. We calculated adjusted associations for mechanical ventilation receipt with hospital and 6-month mortality.
Results
Of the 49,373 patients with lung cancer admitted to an ICU for reasons other than surgical resection, 76% of patients survived the hospitalization, and 35% of patients were alive 6 months after discharge. Receipt of mechanical ventilation was associated with increased hospital mortality (adjusted odds ratio, 6.95; 95% CI, 6.89 to 7.01; P < .001), and only 15% of these patients were alive 6 months after discharge. Of all ICU patients with lung cancer, the percentage of patients who survived 6 months from discharge was 36% for patients diagnosed in 1992 and 32% for patients diagnosed in 2005, whereas it was 16% and 11% for patients who received mechanical ventilation, respectively.
Conclusion
Most patients with lung cancer enrolled in Medicare who are admitted to an ICU die within 6 months of admission. To improve patient-centered care, these results should guide shared decision making between patients with lung cancer and their clinicians before an ICU admission.
doi:10.1200/JCO.2011.40.0846
PMCID: PMC3383114  PMID: 22473159
12.  Trends in the incidence of noncardiogenic acute respiratory failure: the role of race 
Critical Care Medicine  2012;40(5):1532-1538.
Objective
We sought to examine trends in the race-specific incidence of acute respiratory failure in the United States.
Design
Retrospective cohort study.
Setting
We used the National Hospital Discharge Survey (NHDS) database (1992-2007), an annual survey of approximately 500 hospitals weighted to provide national hospitalization estimates.
Patients
All incident cases of noncardiogenic acute respiratory failure hospitalized in the United States.
Interventions
None
Measurements and Main Results
We identified noncardiogenic acute respiratory failure by the presence of ICD–9 codes for respiratory failure or pulmonary edema (518.4, 518.5, 518.81, 518.82) and mechanical ventilation (96.7x), excluding congestive heart failure. Incidence rates were calculated using yearly census estimates standardized to the age and sex distribution of the 2000 census population. Annual cases of noncardiogenic acute respiratory failure increased from 86,755 in 1992 to 323,474 in 2007. Noncardiogenic acute respiratory failure among black Americans increased from 56.4 (95% CI 39.7 – 73.1) to 143.8 (95% CI 123.8 – 163.8) cases per 100,000 in 1992 and 2007, respectively. Among white Americans, the incidence of noncardiogenic acute respiratory failure increased from 31.2 (95% CI 26.2-36.5) to 94.0 (95% CI 86.7 – 101.2) cases per 100,000 in 1992 and 2007, respectively. The average annual incidence of noncardiogenic acute respiratory failure over the entire study period was 95.1 (95% CI 93.9 – 96.4) cases per 100,000 for black Americans compared to 66.5 (95% CI 65.8 – 67.2) cases per 100,000 for white Americans (rate ratio = 1.43, 95% CI 1.42-1.44). Overall in–hospital mortality was greater for other-race Americans, but only among patients with ≥ 2 organ failures (57% [95% CI 56-59%] for other-race, 51% [95% CI, 50-52%] for white, 50% [95% CI, 49-51%] for black).
Conclusions
The incidence of noncardiogenic acute respiratory failure in the United States increased between 1992 and 2007. Black and other-race Americans are at greater risk of developing noncardiogenic acute respiratory failure compared to white Americans.
doi:10.1097/CCM.0b013e31824518f2
PMCID: PMC3329645  PMID: 22511134
Respiratory failure; health status disparities; epidemiology; National Hospital Discharge Survey; international classification of diseases; acute lung injury
13.  Intravenous access during pre-hospital emergency care of non-injured patients: a population-based outcome study 
Annals of Emergency Medicine  2011;59(4):296-303.
Study objective
Advanced, pre-hospital procedures such as intravenous access are commonly performed by emergency medical services (EMS) personnel, yet little evidence supports their use among non-injured patients. We evaluated the association between pre-hospital, intravenous access and mortality among non-injured, non-arrest patients.
Methods
We analyzed a population-based cohort of adult (aged ≥18 years) non-injured, non-arrest patients transported by four advanced life support agencies to one of 16 hospitals from January 1, 2002 until December 31, 2006. We linked eligible EMS records to hospital administrative data, and used multivariable logistic regression to determine the risk-adjusted association between pre-hospital, intravenous access and hospital mortality. We also tested whether this association differed by patient acuity using a previously published, out-of-hospital triage score.
Results
Among 56,332 eligible patients, one half (N=28,978, 50%) received pre-hospital intravenous access from EMS personnel. Overall hospital mortality in patients who did and did not receive intravenous access was 3%. However, in multivariable analyses, the placement of pre-hospital, intravenous access was associated with an overall reduction in odds of hospital mortality (OR=0.68, 95%CI: 0.56, 0.81). The beneficial association of intravenous access appeared to depend on patient acuity (p=0.13 for interaction). For example, the OR of mortality associated with intravenous access was 1.38 (95%CI: 0.28, 7.0) among those with lowest acuity (score = 0). In contrast, the OR of mortality associated with intravenous access was 0.38 (95%CI: 0.17, 0.9) among patients with highest acuity (score ≥ 6).
Conclusions
In this population-based cohort, pre-hospital, intravenous access was associated with a reduction in hospital mortality among non-injured, non-arrest patients with the highest acuity.
doi:10.1016/j.annemergmed.2011.07.021
PMCID: PMC3227749  PMID: 21872970
14.  Improving risk classification of critical illness with biomarkers: a simulation study 
Journal of critical care  2013;28(5):541-548.
Purpose
Optimal triage of patients at risk of critical illness requires accurate risk prediction, yet little data exists on the performance criteria required of a potential biomarker to be clinically useful.
Materials and Methods
We studied an adult cohort of non-arrest, non-trauma emergency medical services encounters transported to a hospital from 2002–2006. We simulated hypothetical biomarkers increasingly associated with critical illness during hospitalization, and determined the biomarker strength and sample size necessary to improve risk classification beyond a best clinical model.
Results
Of 57,647 encounters, 3,121 (5.4%) were hospitalized with critical illness and 54,526 (94.6%) without critical illness. The addition of a moderate strength biomarker (odds ratio=3.0 for critical illness) to a clinical model improved discrimination (c-statistic 0.85 vs. 0.8, p<0.01), reclassification (net reclassification improvement=0.15, 95%CI: 0.13,0.18), and increased the proportion of cases in the highest risk categoryby+8.6% (95%CI: 7.5,10.8%). Introducing correlation between the biomarker and physiological variables in the clinical risk score did not modify the results. Statistically significant changes in net reclassification required a sample size of at least 1000 subjects.
Conclusions
Clinical models for triage of critical illness could be significantly improved by incorporating biomarkers, yet, substantial sample sizes and biomarker strength may be required.
doi:10.1016/j.jcrc.2012.12.001
PMCID: PMC3707977  PMID: 23566734
Biomarker; simulation; sample size; reclassification
15.  Prehospital intravenous access and fluid resuscitation in severe sepsis: an observational cohort study 
Critical Care  2014;18(5):533.
Introduction
Prompt treatment of severe sepsis in the Emergency Department reduces deaths, but the role of prehospital fluid resuscitation is unknown. We sought to determine the risk-adjusted association between prehospital fluid administration and hospital mortality among emergency medical services (EMS) patients admitted with severe sepsis.
Methods
We performed a prospective, observational study of patients hospitalized with severe sepsis on admission among 45,394 adult EMS encounters taken to 15 hospitals from 11/2009 to 12/2010 by a two-tier EMS system in King County, Washington. The region mandated recording of prehospital intravenous catheter and fluid administration in prehospital records, along with detailed demographic, incident, physiologic, and hospital adjustment variables. We determined the effect of prehospital intravenous catheter or fluid versus no catheter or fluid on all-cause mortality using multivariable logistic regression.
Results
Of all encounters, 1,350 met criteria for severe sepsis on admission, of whom 205 (15%) died by hospital discharge, 312 (23%) received prehospital intravenous fluid, 90 (7%) received a prehospital catheter alone and 948 (70%) did not receive catheter or fluid. EMS administered a median prehospital fluid volume of 500 mL (interquartile range (IQR): 200, 1000 mL). In adjusted models, the administration of any prehospital fluid was associated with reduced hospital mortality (Odds ratio =0.46; 95% Confidence interval: 0.23, 0.88; P =0.02) compared to no prehospital fluid. The odds of hospital mortality were also lower among severe sepsis patients treated with prehospital intravenous catheter alone (Odds ratio =0.3; 95% Confidence interval: 0.17 to 0.57; P <0.01).
Conclusions
In a population-based study, the administration of prehospital fluid and placement of intravenous access were associated with decreased odds of hospital mortality compared with no prehospital catheter or fluid.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0533-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s13054-014-0533-x
PMCID: PMC4212132  PMID: 25260233
16.  Out-of-Hospital Fluid in Severe Sepsis: Effect on Early Resuscitation in the Emergency Department 
Background
Early identification and treatment of patients with severe sepsis improves outcome, yet the role of out-of-hospital intravenous (IV) fluid is unknown.
Objective
To determine if the delivery of out-of-hospital fluid in patients with severe sepsis is associated with reduced time to achievement of goal-oriented resuscitation in the emergency department (ED).
Methods
We performed a secondary data analysis of a retrospective cohort study in a metropolitan, tertiary care, university-based medical center supported by a two-tiered system of out-of-hospital emergency medical services (EMS) providers. We studied the association between delivery of out-of-hospital fluid by advanced life support (ALS) providers and the achievement of resuscitation endpoints (central venous pressure [CVP] ≥8 mmHg, mean arterial pressure [MAP] ≥65 mmHg, and central venous oxygen saturation [ScvO2] ≥70%) within six hours after triage during early goal-directed therapy (EGDT) in the ED.
Results
Twenty five (48%) of 52 patients transported by ALS with severe sepsis received out-of-hospital fluid. Data for age, gender, source of sepsis, and presence of comorbidities were similar between patients who did and did not receive out-of-hospital fluid. Patients receiving out-of-hospital fluid had lower out-of-hospital mean (± standard deviation) systolic blood pressure (95 ± 40 mmHg vs. 117 ± 29 mmHg; p = 0.03) and higher median (interquartile range) Sequential Organ Failure Assessment (SOFA) scores in the ED (7 [5–8] vs. 4 [4–6]; p = 0.01) than patients not receiving out-of-hospital fluid. Despite greater severity of illness, patients receiving out-of-hospital fluid approached but did not attain a statistically significant increase in the likelihood of achieving MAP ≥65 mmHg within six hours after ED triage (70% vs. 44%, p = 0.09). On average, patients receiving out-of-hospital fluid received twice the fluid volume within one hour after ED triage (1.1 L [1.0–2.0 L] vs. 0.6 L [0.3–1.0 L]; p 0.01). No difference in achievement of goal CVP (72% vs. 60%; p = 0.6) or goal ScvO2 (54% vs. 36%; p = 0.25) was observed between groups.
Conclusions
Less than half of patients with severe sepsis transported by ALS received out-of-hospital fluid. Patients receiving out-of-hospital IV access and fluids approached but did not attain a statistically significant increase in the likelihood of achieving goal MAP during EGDT. These preliminary findings require additional investigation to evaluate the optimal role of out-of-hospital resuscitation in treating patients with severe sepsis.
doi:10.3109/10903120903524997
PMCID: PMC4053434  PMID: 20199228
sepsis; resuscitation; fluids; intravenous fluids; prehospital
17.  Prediction of Critical Illness During Out-of-Hospital Emergency Care 
Context
Early identification of nontrauma patients in need of critical care services in the emergency setting may improve triage decisions and facilitate regionalization of critical care.
Objectives
To determine the out-of-hospital clinical predictors of critical illness and to characterize the performance of a simple score for out-of-hospital prediction of development of critical illness during hospitalization.
Design and Setting
Population-based cohort study of an emergency medical services (EMS) system in greater King County, Washington (excluding metropolitan Seattle), that transports to 16 receiving facilities.
Patients
Nontrauma, non–cardiac arrest adult patients transported to a hospital by King County EMS from 2002 through 2006. Eligible records with complete data (N=144 913) were linked to hospital discharge data and randomly split into development (n=87 266 [60%]) and validation (n=57 647 [40%]) cohorts.
Main Outcome Measure
Development of critical illness, defined as severe sepsis, delivery of mechanical ventilation, or death during hospitalization.
Results
Critical illness occurred during hospitalization in 5% of the development (n=4835) and validation (n=3121) cohorts. Multivariable predictors of critical illness included older age, lower systolic blood pressure, abnormal respiratory rate, lower Glasgow Coma Scale score, lower pulse oximetry, and nursing home residence during out-of-hospital care (P<.01 for all). When applying a summary critical illness prediction score to the validation cohort (range, 0-8), the area under the receiver operating characteristic curve was 0.77 (95% confidence interval [CI], 0.76-0.78), with satisfactory calibration slope (1.0). Using a score threshold of 4 or higher, sensitivity was 0.22 (95% CI, 0.20-0.23), specificity was 0.98 (95% CI, 0.98-0.98), positive likelihood ratio was 9.8 (95% CI, 8.9-10.6), and negative likelihood ratio was 0.80 (95% CI, 0.79-0.82). A threshold of 1 or greater for critical illness improved sensitivity (0.98; 95% CI, 0.97-0.98) but reduced specificity (0.17; 95% CI, 0.17-0.17).
Conclusions
In a population-based cohort, the score on a prediction rule using out-of-hospital factors was significantly associated with the development of critical illness during hospitalization. This score requires external validation in an independent population.
doi:10.1001/jama.2010.1140
PMCID: PMC3949007  PMID: 20716737
18.  Hospital level variation in the use of intensive care 
Health services research  2012;47(5):2060-2080.
Objective
To determine the extent to which hospitals vary in the use of intensive care, and the proportion of variation attributable to differences in hospital practice that is independent of known patient and hospital factors.
Data source
Hospital discharge data in the State Inpatient Database for Maryland and Washington states in 2006.
Study design
Cross sectional analysis of 90 short-term acute, care hospitals with critical care capabilities.
Data collection/methods
We quantified the proportion of variation in intensive care use attributable to hospitals using intraclass correlation coefficients derived from mixed effects logistic regression models after successive adjustment for known patient and hospital factors.
Principal findings
The proportion of hospitalized patients admitted to an ICU across hospitals ranged from 3% to 55% (median 12%; IQR:9, 17%). After adjustment for patient factors, 19.7% (95%CI: 15.1, 24.4) of total variation in ICU use across hospitals was attributable to hospitals. When observed hospital characteristics were added, the proportion of total variation in intensive care use attributable to unmeasured hospital factors decreased by 26% to 14.6% (95% CI:11, 18.3%).
Conclusions
Wide variability exists in the use of intensive care across hospitals, not attributable to known patient or hospital factors, and may be a target to improve efficiency and quality of critical care.
doi:10.1111/j.1475-6773.2012.01402.x
PMCID: PMC3513618  PMID: 22985033
intensive care; critical illness; variation; hospitals
19.  Acute Respiratory Distress Syndrome after Trauma: Development and Validation of a Predictive Model 
Critical Care Medicine  2012;40(8):2295-2303.
Objective
To determine early clinical predictors of Acute Respiratory Distress Syndrome (ARDS) after major traumatic injury and characterize the performance of this ARDS prediction model, and two previously published ARDS prediction models, in an independent cohort of severely injured patients.
Design
Prospective cohort study
Setting
University-affiliated level I trauma center in Seattle, WA, and nine hospitals participating in the Inflammation and Host Response to Injury Consortium.
Patients
Model derivation utilized data from 224 patients participating in a randomized controlled trial. All models were validated in an independent cohort of 1,762 trauma patients.
Measurements and Main Results
Variables strongly associated with ARDS in bivariate analysis (p<0.01) were entered into a multiple logistic regression equation to generate an ARDS predictive model. We evaluated the performance of all models using the area under the receiver operator characteristic (ROC) curve. ARDS occurred in 79 subjects (35%) belonging to the development cohort and in 423 subjects (24%) from the validation cohort. Multivariable predictors of ARDS after trauma included subject age, Acute Physiology and Chronic Health Evaluation (APACHE) II Score, injury severity score, and the presence of blunt traumatic injury, pulmonary contusion, massive transfusion, and flail chest injury (area under the ROC curve 0.79 [95% C.I. 0.73, 0.85]). Validation of the prediction model resulted in an area under the ROC curve of 0.71 (95% C.I. 0.68, 0.74). Our model's performance in the validation cohort was superior to that of two other published ARDS prediction models (0.65 [95% C.I. 0.63, 0.68] and 0.66 [95% C.I. 0.64, 0.69], p<0.01 for all comparisons).
Conclusions
Using routinely available clinical data, our prediction model identifies patients at high risk for ARDS early after severe traumatic injury. This predictive model could facilitate enrollment of subjects into future clinical trials designed to prevent this serious complication.
doi:10.1097/CCM.0b013e3182544f6a
PMCID: PMC3400931  PMID: 22809905
Respiratory Distress Syndrome, Acute; Wounds and Injuries; Multiple Trauma, Receiver Operating Characteristic
20.  The Population Burden of Long-Term Survivorship after Severe Sepsis Among Older Americans 
Background
Severe sepsis is associated with persistent high-levels of morbidity among older survivors. But the impact of severe sepsis on population health—particularly population levels of disability—is unknown.
Objectives
Ascertain the absolute number of patients surviving at least 3 years after severe sepsis in Medicare, and estimate their burden of cognitive dysfunction and disability.
Design
Retrospective cohort analysis of Medicare data.
Setting
All short-stay inpatient hospitals in the United States, 1996–2008.
Participants
Patients aged 65 and older.
Measurements
Severe sepsis was detected using a standard administrative definition. Case-fatality, prevalence and incidence rates were calculated.
Results
There were 637,867 Medicare patients alive at the end of 2008 who survived severe sepsis 3 or more years earlier. An estimated 476,862 (95% CI: 455,026, 498,698) had functional disability, with 106,311 (95% CI: 79,692, 133,930) survivors having moderate-to-severe cognitive impairment. The annual number of new 3-year survivors following severe sepsis rose 119% during 1998–2008. The increase in survivorship resulted from more new diagnoses of severe sepsis rather than a change in case fatality rates; severe sepsis rates rose from 13.0 per 1,000 Medicare beneficiary-years to 25.8 (p<0.001), whereas 3-year case fatality rates changed much less, from 73.5%to 71.3% (p<0.001) for the same cohort. Increasing rates of organ dysfunction among hospitalized patients drove the increase in severe sepsis incidence, with an additional small contribution from population aging.
Conclusions
Sepsis survivorship, which carries with it substantial long-term morbidity, is a common and rapidly growing public health problem for older Americans. There has been little change in long-term case fatality, despite changes in practice. Clinicians should anticipate more frequent sequelae of severe sepsis in their patient populations.
doi:10.1111/j.1532-5415.2012.03989.x
PMCID: PMC3374893  PMID: 22642542
Medicare; severe sepsis; disability; population health
21.  Duration of resuscitation efforts and subsequent survival after in-hospital cardiac arrest 
Lancet  2012;380(9852):1473-1481.
Background
During in-hospital cardiac arrests, it is uncertain how long resuscitation should continue prior to termination of efforts. We hypothesized that the duration of resuscitation varies across hospitals, and that patients at hospitals with longer attempts have higher survival rates.
Methods
Between 2000 and 2008, we identified 64,339 patients with cardiac arrests at 435 hospitals within a large national registry. For each hospital, we calculated the median duration of resuscitation before termination of efforts among its non-survivors as a measure of the hospital’s overall tendency for longer attempts. We then determined the association between a hospital’s tendency for longer attempts and risk-adjusted survival using multilevel regression models.
Findings
The overall proportion of patients achieving immediate survival with return of spontaneous circulation (ROSC) was 48·5% while 15·4% survived to discharge. For patients achieving ROSC, the median resuscitation time was 12 minutes (IQR: 6–21) while it was 20 minutes (IQR: 14–30) for those not achieving ROSC (i.e., non-survivors). Compared with patients at hospitals with the shortest attempts (median duration, 16 minutes), patients at hospitals with the longest attempts (median duration, 25 minutes) had a higher likelihood of ROSC (adjusted risk-ratio 1·12, [95% CI: 1·06–1·18]; p <0·001) and survival to discharge (adjusted risk-ratio 1·12, [95% CI: 1·02–1·23]; p=0·021). These findings were more prominent in cardiac arrests due to asystole and pulseless electrical activity (p for interaction<0.01 for both ROSC and survival to discharge).
Interpretation
The duration of resuscitation attempts varies across hospitals. Patients at hospitals with longer attempts have a higher likelihood of ROSC and survival to discharge, particularly when the arrest is due to asystole and pulseless electrical activity.
Funding
The American Heart Association, the Robert Wood Johnson Foundation Clinical Scholars Program, the National Institutes of Health.
doi:10.1016/S0140-6736(12)60862-9
PMCID: PMC3535188  PMID: 22958912
22.  Variation in use of intensive care for adults with diabetic ketoacidosis* 
Critical care medicine  2012;40(7):2009-2015.
Objective
Intensive care unit (ICU) beds are limited, yet few guidelines exist for triage of patients to the ICU, especially patients at low-risk for mortality. The frequency with which low-risk patients are admitted to ICUs in different hospitals is unknown. Our objective was to assess variation in use of intensive care for patients with diabetic ketoacidosis (DKA), a common condition with a low-risk of mortality.
Design
Observational study using the New York State Inpatient Database (2005-2007).
Setting
159 New York State acute care hospitals.
Patients
15,994 adult (≥18) hospital admissions with a primary diagnosis of DKA (ICD-9-CM 250.1x).
Interventions
None.
Measurements and Main Results
We calculated reliability- and risk-adjusted ICU utilization, hospital length of stay (LOS), and mortality. We identified hospital-level factors associated with increased likelihood of ICU admission after controlling for patient characteristics using multilevel mixed-effects logistic regression analyses; we assessed the amount of residual variation in ICU utilization using the intra-class correlation coefficient. Use of intensive care for DKA patients varied widely across hospitals (adjusted range: 2.1% to 87.7%), but was not associated with hospital LOS or mortality. After multilevel adjustment, hospitals with a high volume of DKA admissions admitted DKA patients to the ICU less often (OR 0.40, p=0.002, highest quintile compared to lowest) whereas hospitals with higher rates of ICU utilization for all non-DKA inpatients admitted DKA patients to the ICU more frequently (OR 1.31, p=0.001, for each additional ten percent increase). In the multi-level model, more than half (58%) of the variation in ICU admission practice attributable to hospitals remained unexplained.
Conclusions
We observed variation across hospitals in use of intensive care for DKA patients that was not associated with differences in hospital LOS or mortality. Institutional practice patterns appear to impact admission decisions and represent a potential target for reduction of resource utilization in higher use institutions.
doi:10.1097/CCM.0b013e31824e9eae
PMCID: PMC3561634  PMID: 22564962
Diabetic Ketoacidosis; Delivery of Health Care; Physician’s Practice Patterns
23.  The Effect of Insurance Status on Mortality and Procedural Use in Critically Ill Patients 
Rationale: Lack of health insurance may be an independent risk factor for mortality and differential treatment in critical illness.
Objectives: To determine whether uninsured critically ill patients had differences in 30-day mortality and critical care service use compared with those with private insurance and to determine if outcome variability could be attributed to patient-level or hospital-level effects.
Methods: Retrospective cohort study using Pennsylvania hospital discharge data with detailed clinical risk adjustment, from fiscal years 2005 and 2006, consisting of 167 general acute care hospitals, with 138,720 critically ill adult patients 64 years of age or younger.
Measurements and Main Results: Measurements were 30-day mortality and receipt of five critical care procedures. Uninsured patients had an absolute 30-day mortality of 5.7%, compared with 4.6% for those with private insurance and 6.4% for those with Medicaid. Increased 30-day mortality among uninsured patients persisted after adjustment for patient characteristics (odds ratio [OR], 1.25 for uninsured vs. insured; 95% confidence interval [CI], 1.04–1.50) and hospital-level effects (OR, 1.26; 95% CI, 1.05–1.51). Compared with insured patients, uninsured patients had decreased risk-adjusted odds of receiving a central venous catheter (OR, 0.84; 95% CI, 0.72–0.97), acute hemodialysis (OR, 0.59; 95% CI, 0.39–0.91), and tracheostomy (OR, 0.43; 95% CI, 0.29–0.64).
Conclusions: Lack of health insurance is associated with increased 30-day mortality and decreased use of common procedures for the critically ill in Pennsylvania. Differences were not attributable to hospital-level effects, suggesting that the uninsured have a higher mortality and receive fewer procedures when compared with privately insured patients treated at the same hospitals.
doi:10.1164/rccm.201101-0089OC
PMCID: PMC3208649  PMID: 21700910
insurance; intensive care unit; critical care; mortality
24.  Out-of-hospital characteristics and care of patients with severe sepsis: a cohort study 
Journal of critical care  2010;25(4):553-562.
Purpose
Early recognition and treatment in severe sepsis improves outcomes. Yet, out-of-hospital patient characteristics and emergency medical services (EMS) care in severe sepsis is understudied. Our goal was to describe out-of-hospital characteristics and EMS care in patients with severe sepsis, and evaluate associations between out-of-hospital characteristics and severity of organ dysfunction in the emergency department (ED).
Materials & Methods
We performed a secondary data analysis of existing data from patients with severe sepsis transported by EMS to an academic medical center. We constructed multivariable linear regression models to determine if out-of-hospital factors are associated with serum lactate and SOFA in the ED.
Results
Two hundred sixteen patients with severe sepsis arrived by EMS. Median serum lactate in the ED was 3.0 mmol/L (IQR:2.0-5.0) and median SOFA score was 4 (IQR:2-6). Sixty-three percent (135) of patients were transported by advanced life support providers and 30% (62) received IV fluid. Lower out-of-hospital Glasgow coma scale (GCS) was independently associated with elevated serum lactate (p<0.01). Out-of-hospital hypotension, greater respiratory rate, and lower GCS were associated with greater SOFA (p<0.01).
Conclusions
Out-of-hospital fluid resuscitation occurred in less than one-third of patients with severe sepsis, and routinely measured out-of-hospital variables were associated with greater serum lactate and SOFA in the ED.
doi:10.1016/j.jcrc.2010.02.010
PMCID: PMC2904432  PMID: 20381301
emergency medical services; hypotension; out-of-hospital; sepsis; lactic acid; multiple organ failure
25.  Red blood cell transfusion and outcomes in patients with acute lung injury, sepsis and shock 
Critical Care  2011;15(5):R221.
Introduction
In this study, we sought to determine the association between red blood cell (RBC) transfusion and outcomes in patients with acute lung injury (ALI), sepsis and shock.
Methods
We performed a secondary analysis of new-onset ALI patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial (2000 to 2005) who had a documented ALI risk factor of sepsis or pneumonia and met shock criteria (mean arterial pressure (MAP) < 60 mmHg or vasopressor use) within 24 hours of randomization. Using multivariable logistic regression, we examined the association between RBC transfusion and 28-day mortality after adjustment for age, sex, race, randomization arm and Acute Physiology and Chronic Health Evaluation III score. Secondary end points included 90-day mortality and ventilator-free days (VFDs). Finally, we examined these end points among the subset of subjects meeting prespecified transfusion criteria defined by five simultaneous indicators: hemoglobin < 10.2 g/dL, central or mixed venous oxygen saturation < 70%, central venous pressure ≥ 8 mmHg, MAP ≥ 65 mmHg, and vasopressor use.
Results
We identified 285 subjects with ALI, sepsis, shock and transfusion data. Of these, 85 also met the above prespecified transfusion criteria. Fifty-three (19%) of the two hundred eighty-five subjects with shock and twenty (24%) of the subset meeting the transfusion criteria received RBC transfusion within twenty-four hours of randomization. We found no independent association between RBC transfusion and 28-day mortality (odds ratio = 1.49, 95% CI (95% confidence interval) = 0.77 to 2.90; P = 0.23) or VFDs (mean difference = -0.35, 95% CI = -4.03 to 3.32; P = 0.85). Likewise, 90-day mortality and VFDs did not differ by transfusion status. Among the subset of patients meeting the transfusion criteria, we found no independent association between transfusion and mortality or VFDs.
Conclusions
In patients with new-onset ALI, sepsis and shock, we found no independent association between RBC transfusion and mortality or VFDs. The physiological criteria did not identify patients more likely to be transfused or to benefit from transfusion.
doi:10.1186/cc10458
PMCID: PMC3334766  PMID: 21936902
erythrocyte transfusion; respiratory distress syndrome; adult therapy; sepsis therapy; treatment outcome; intensive care unit; respiration; artificial

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