We study the performance and behavior of Value at Risk (VaR) measures used by a number of large banks during and before the financial crisis. Alternative benchmark VaR measures, including GARCH-based measures, are also estimated directly from the banks' trading revenues and help to explain the bank VaR performance results. While highly conservative in the pre-crisis period, bank VaR exceedances were excessive and clustered in the crisis period. All benchmark VaRs were more accurate in the pre-crisis period with GARCH VaR measures the most accurate in the crisis period having lower exceedance rates with no exceedance clustering. Variance decompositions indicate a limited ability of the banks' VaR methodologies to adjust to the crisis-period market conditions. Despite their weaker performance, the bank VaRs exhibited greater predictive power for a measure of realized PnL volatility than benchmark VaR measures. Benchmark Expected Shortfall measures are also considered.

Department of Quality and Patient Safety, OhioHealth Riverside Methodist Hospital, Columbus, OH * See also p. 729 and 738. Dr. O’Brien served as a board member for the Sepsis Alliance (Chair of the Board of Directors) and Global Sepsis Alliance (Executive Board); consulted for OrthoClinical Diagnostics (served on advisory board for OrthoClinical Diagnostics; travel and lodging provided; honorarium donated to Sepsis Alliance); lectured for Medical Simulation Corporation (MSC) (honorarium was donated directly to Sepsis Alliance), General Electric (GE) (gave three talks on sepsis at GE’s booth at National Teaching Institute for American Association of Critical-Care Nurses in Denver, CO; travel and lodging provided; honorarium donated to Sepsis Alliance), and MSC (gave talk sponsored by Medical Simulation Corporation; honorarium donated to Sepsis Alliance); and disclosed other support from Wolters-Kluwer (participated in video about sepsis sponsored by Wolters-Kluwer; travel and lodging provided; honorarium donated to Sepsis Alliance) and Edwards LifeSciences (visited with member of Congress regarding General Accounting Office report on sepsis; collaborated with Edwards LifeSciences on planning visits).

Üblicherweise wird starkes Übergewicht mit eher negativen gesundheitlichen Ereignissen verbunden, wie dem Auftreten von Herz-Kreislauf-Erkrankungen, Diabetes mellitus und manchen Krebsarten. Das sog. Adipositas-Paradoxon beschreibt dagegen, dass bei einigen Krankheiten übergewichtige Patienten – also Personen mit bereits bestehender Erkrankung – höhere Überlebensraten aufweisen als normalgewichtige. Für Patienten mit Sepsis hat das jetzt eine US-amerikanische Gruppe untersucht.

OBJECTIVES:Although critical care physicians view obesity as an independent poor prognostic marker, growing evidence suggests that obesity is, instead, associated with improved mortality following ICU admission. However, this prior empirical work may be biased by preferential admission of obese patients to ICUs, and little is known about other patient-centered outcomes following critical illness. We sought to determine whether 1-year mortality, healthcare utilization, and functional outcomes following a severe sepsis hospitalization differ by body mass index.DESIGN:Observational cohort study.SETTING:U.S. hospitals.PATIENTS:We analyzed 1,404 severe sepsis hospitalizations (1999-2005) among Medicare beneficiaries enrolled in the nationally representative Health and Retirement Study, of which 597 (42.5%) were normal weight, 473 (33.7%) were overweight, and 334 (23.8%) were obese or severely obese, as assessed at their survey prior to acute illness. Underweight patients were excluded a priori.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Using Medicare claims, we identified severe sepsis hospitalizations and measured inpatient healthcare facility use and calculated total and itemized Medicare spending in the year following hospital discharge. Using the National Death Index, we determined mortality. We ascertained pre- and postmorbid functional status from survey data. Patients with greater body mass indexes experienced lower 1-year mortality compared with nonobese patients, and there was a dose-response relationship such that obese (odds ratio = 0.59; 95% CI, 0.39-0.88) and severely obese patients (odds ratio = 0.46; 95% CI, 0.26-0.80) had the lowest mortality. Total days in a healthcare facility and Medicare expenditures were greater for obese patients (p < 0.01 for both comparisons), but average daily utilization (p = 0.44) and Medicare spending were similar (p = 0.65) among normal, overweight, and obese survivors. Total function limitations following severe sepsis did not differ by body mass index category (p = 0.64).CONCLUSIONS:Obesity is associated with improved mortality among severe sepsis patients. Due to longer survival, obese sepsis survivors use more healthcare and result in higher Medicare spending in the year following hospitalization. Median daily healthcare utilization was similar across body mass index categories.

Objective Although there is a growing recognition of the importance of active communication behaviours from the incoming clinician receiving a patient handover, there are currently no agreed-upon measures to objectively describe those behaviours. This study sought to identify differences in incoming clinician communication behaviours across levels of clinical training for physicians and nurses. Methods Handover observations were conducted during shift changes for attending physicians, resident physicians, registered nurses and nurse practitioners in three medical intensive care units from July 2011 to August 2012. Measures were the number of interjections from the incoming clinician and the communication mode of those interjections. Each collaborative cross-check, a specific type of interactive question, was subsequently classified by level of assertiveness. Results 133 patient handovers were analysed. Statistical differences were found in both measures. Higher levels of training were associated with fewer interjections, and a higher proportion of interactive questioning to detect erroneous assessments and actions by the incoming provider. All groups were observed to use the least assertive level of a collaborative cross-check, which contributed to misunderstandings. Nurses used less assertive collaborative cross-checks than physicians. Conclusions Differences across clinician type and levels of clinical training were found in both measures during patient handovers. The findings suggest that training could enable physicians and nurses to learn communication competencies during patient handovers which were used more frequently by more experienced practitioners, including interjecting less frequently and using interactive questioning strategies to clarify understanding, and assertively question the appropriateness of diagnoses, treatment plans and prognoses. Accompanying cultural change initiatives might be required to routinely employ these strategies in the clinical setting, particularly for nursing personnel.

ABSTRACT In an era of escalating resistance and a lack of new antimicrobial discovery, stewardship programs must utilize knowledge of pharmacodynamics to achieve maximal exposure in the treatment of Pseudomonas aeruginosa infections. We evaluated the clinical and economic outcomes associated with extended-infusion cefepime in the treatment of P. aeruginosa infections. This single-center study compared inpatients who received cefepime for bacteremia and/or pneumonia admitted from 1 January 2008 through 30 June 2010 (a 30-min infusion of 2 g every 8 h) to those admitted from 1 July 2010 through 31 May 2011 (a 4-h infusion of 2 g every 8 h). The overall mortality was significantly lower in the group that received extended-infusion treatment (20% versus 3%; P = 0.03). The mean length of stay was 3.5 days less for patients who received extended infusion ( P = 0.36), and for patients admitted to the intensive care unit the mean length of stay was significantly less in the extended-infusion group (18.5 days versus 8 days; P = 0.04). Hospital costs were $23,183 less per patient, favoring the extended-infusion treatment group ( P = 0.13). We conclude that extended-infusion treatment with cefepime provides increased clinical and economic benefits in the treatment of invasive P. aeruginosa infections.

As health care expenditures increase, payers, including the Centers for Medicare and Medicaid Services, are moving away from reimbursement based on types and volume of services to an emphasis on quality of provided care, an approach called value-based purchasing (VBP). Because it is tied to reimbursement, VBP creates economic motivation to measure and improve care. VBP is proceeding without high-level evidence supporting its effectiveness in improving health care quality. Rising health care costs, however, make VBP an attractive approach for curtailing costs and emphasizing improved quality, and VBP is likely to become a more prevalent mechanism of reimbursement for providers and facilities.

OBJECTIVES:Lung-protective ventilation with lower tidal volume and lower plateau pressure improves mortality in patients with acute lung injury and acute respiratory distress syndrome. We sought to determine the incidence of elevated plateau pressure in acute lung injury /acute respiratory distress syndrome patients receiving lower tidal volume ventilation and to determine the factors that predict elevated plateau pressure in these patients.PATIENTS:We used data from 1398 participants in Acute Respiratory Distress Syndrome Network trials, who received lower tidal volume ventilation (≤ 6.5mL/kg predicted body weight).DESIGN:We considered patients with a plateau pressure greater than 30cm H2O and/or a tidal volume less than 5.5mL/kg predicted body weight on study day 1 to have "elevated plateau pressure." We used logistic regression to identify baseline clinical variables associated with elevated plateau pressure and to develop a model to predict elevated plateau pressure using a subset of 1,188 patients. We validated the model in the 210 patients not used for model development.SETTING:Medical centers participating in Acute Respiratory Distress Syndrome Network clinical trials.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Of the 1,398 patients in our study, 288 (20.6%) had elevated plateau pressure on day 1. Severity of illness indices and demographic factors (younger age, greater body mass index, and non-white race) were independently associated with elevated plateau pressure. The multivariable logistic regression model for predicting elevated plateau pressure had an area under the receiving operator characteristic curve of 0.71 for both the developmental and the validation subsets.CONCLUSIONS:acute lung injury patients receiving lower tidal volume ventilation often have a plateau pressure that exceeds Acute Respiratory Distress Syndrome Network goals. Race, body mass index, and severity of lung injury are each independently associated with elevated plateau pressure. Selecting a smaller initial tidal volume for non-white patients and patients with higher severity of illness may decrease the incidence of elevated plateau pressure. Prospective studies are needed to evaluate this approach.

INTRODUCTION:Metformin has anti-inflammatory and anti-thrombotic effects that may improve the outcome of critical illness, but clinical data are limited. We examined the impact of preadmission metformin use on mortality among intensive care unit (ICU) patients with type 2 diabetes.METHODS:We conducted this population-based cohort study among all persons admitted to the 17 ICUs in Northern Denmark (population approximately 1.8 million). We focused on all patients with type 2 diabetes who were admitted to the ICUs between January 2005 and December 2011. Through individual-level linkage of population-based medical databases, type 2 diabetes was identified using a previously validated algorithm including hospital diagnoses, filled prescriptions for anti-diabetic drugs, and elevated HbA1c levels. Metformin use was identified by filled prescriptions within 90 days before admission. Covariates included surgery, preadmission morbidity, diabetes duration, and concurrent drug use. We computed 30-day mortality and hazard ratios (HRs) of death using Cox regression adjusted for covariates, both overall and after propensity score matching.RESULTS:We included 7,404 adult type 2 diabetes patients, representing 14.0% of 52,964 adult patients admitted to the ICUs. Among type 2 diabetes patients, 1,073 (14.5%) filled a prescription for metformin as monotherapy within 90 days before admission and 1,335 (18.0%) received metformin in combination with other anti-diabetic drugs. Thirty-day mortality was 17.6% among metformin monotherapy users, 17.9% among metformin combination therapy users, and 25.0% among metformin non-users. The adjusted HRs were 0.80 (95% confidence interval (CI): 0.69, 0.94) for metformin monotherapy users and 0.83 (95% CI: 0.71, 0.95) for metformin combination therapy users, compared to non-users. Propensity-score-matched analyses yielded the same results. The association was evident across most subgroups of medical and surgical ICU patients, but most pronounced in elderly patients and in patients with well-controlled diabetes. Former metformin use was not associated with decreased mortality.CONCLUSIONS:Preadmission metformin use was associated with reduced 30-day mortality among medical and surgical intensive care patients with type 2 diabetes.

Performance measures (PMs) are specified metrics by which a health-care provider's care can be compared with national benchmarks. The use of PMs is a key component of efforts to improve the quality and value of health care. The National Quality Forum (NQF) is the federally recognized endorser of PMs. From 2006 to 2009, the Quality Improvement Committee (QIC) of the American College of Chest Physicians engaged in the review of proposed PMs as a member of the NQF. This article provides a review of the QIC's experience with PMs and NQF membership and the lessons learned, an overview of the enhancements made to the NQF endorsement process in 2010 and 2011, and a discussion of the next steps that would further strengthen the measure development and endorsement processes and increase the likelihood of measurement leading to better patient outcomes.

Background Data on the prognostic impact of diabetes and diabetic complications in intensive care unit (ICU) patients are limited and inconsistent. We, therefore, examined mortality in ICU patients with type 2 diabetes with and without pre-existing heart and kidney diseases compared with nondiabetic patients. Design We conducted this population-based cohort study in Northern Denmark during 20052011. We included all ICU patients aged 40years or older from the 17 ICUs in the area and identified type 2 diabetes by either a filled prescription for an antidiabetic drug, a previous diagnosis of diabetes, or an elevated glycosylated haemoglobin level. Diabetic patients were disaggregated according to pre-existing diagnoses of heart disease (myocardial infarction or heart failure) and kidney disease. We estimated 1-year mortality by the KaplanMeier method and hazard ratios of death (HRs) during follow-up using Cox regression, controlling for confounding factors and stratified by relevant subgroups. Results Among 45018 ICU patients, 7219 (16 center dot 0%) had type 2 diabetes. Overall, 1-year mortality was 36 center dot 0% in ICU patients with type 2 diabetes, rising to 54 center dot 6% in patients with pre-existing heart and kidney diseases, compared with 29 center dot 1% in nondiabetic patients. Comparing diabetic with nondiabetic patients, the adjusted 0- to 30-day HR was 1 center dot 20 (95% confidence interval (CI): 1 center dot 131 center dot 26) and 1 center dot 19 (95% CI: 1 center dot 101 center dot 28) during the 31- to 365-day follow-up period. Pre-existing kidney disease further increased the impact of diabetes, while heart disease alone had no such effect. Conclusions ICU patients with type 2 diabetes had higher 1-year mortality compared with nondiabetic ICU patients, particularly those with pre-existing kidney disease.

Objective: To determine the association between excess weight and processes of care and outcomes for critically ill adults. Design: Prospective cohort study. Setting: Three medical intensive care units at two hospitals. Patients: Five hundred eighty mechanically ventilated adult patients admitted between February 1, 2006 and January 31, 2008. Interventions: None. Measurements and Main Results: After adjusting weight based on the recorded fluid balance before enrollment, 21.9% of subjects were categorized into different body mass index categories than without this adjustment. We used a competing risk analysis with events of interest considered death during hospitalization and successful liberation from mechanical ventilation. We found no statistically significant difference between body mass index categories (<25 kg/m2 vs. 25 to <30 kg/m2 vs. ≥30 kg/m2) in the competing risks analyses when the results were unadjusted or adjusted for severity of illness and comorbidities. When the analyses were adjusted for the use of continuous infusions of opioids and/or sedatives and ventilator parameters (tidal volume per ideal body weight, positive end-expiratory pressure, and airway pressure), subjects with an overweight fluid-balance–adjusted body mass index had significantly lower hazard ratios for dying while hospitalized (adjusted hazard ratio 0.68 [95% confidence interval 0.47–0.99], p = .044), and those with an obese fluid-adjusted body mass index had significantly higher hazard ratios for successful extubation (adjusted hazard ratio 1.53 [95% confidence interval 1.14–2.06], p = .005). An analysis of longer-term mortality found lower adjusted hazard ratios for subjects with overweight (adjusted hazard ratio 0.74 [95% confidence interval 0.56–0.96]) and obese (adjusted hazard ratio 0.74 [95% confidence interval 0.59–0.94]) fluid-balance–adjusted body mass indices. Conclusions: Processes of provided care may affect the observed association between excess weight and outcomes for critically ill adults and should be considered when making inferences about observed results. It is unknown if disparities in processes of care are due to clinically justified reasons for variation, bias against heavier patients, or other reasons.

Performance measures (PMs) are specified metrics by which a health-care provider's care can be compared with national benchmarks. The use of PMs is a key component of efforts to improve the quality and value of health care. The National Quality Forum (NQF) is the federally recognized endorser of PMs. From 2006 to 2009, the Quality Improvement Committee (QIC) of the American College of Chest Physicians engaged in the review of proposed PMs as a member of the NQF. This article provides a review of the QIC's experience with PMs and NQF membership and the lessons learned, an overview of the enhancements made to the NQF endorsement process in 2010 and 2011, and a discussion of the next steps that would further strengthen the measure development and endorsement processes and increase the likelihood of measurement leading to better patient outcomes.

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Center for Critical Care, The Ohio State University Medical Center, Columbus, OH (O'Brien) The Ohio State University Medical Center, Department of Internal Medicine, Columbus, OH (Prescott) Dr. O'Brien received funding from the National Heart, Lung and Blood Institute and the National Institutes of Health Clinical Research Loan Repayment Program; he received industrial grant support from Zemplar, ARDS Network, Ely Lilly, Aerogen, and Pneuma Pharmaceuticals. He consulted for Ely Lilly, Keimar Inc, and was a consultant to the Medical Simulation Corporation and is on the board of directors for the Sepsis Alliance. Dr. Prescott has not disclosed any potential conflicts of interest.

RATIONALE Little is known about the consequences of intensivists’ work schedules, or intensivist continuity of care. OBJECTIVES To assess the impact of weekend respite for intensivists, with consequent reduction in continuity of care, on them and their patients. METHODS In five medical intensive care units (ICUs) in four academic hospitals we performed a prospective, cluster-randomized, alternating trial of two intensivist staffing schedules. Daily coverage by a single intensivist in half-month rotations (continuous schedule) was compared with weekday coverage by a single intensivist, with weekend cross-coverage by colleagues (interrupted schedule). We studied consecutive patients admitted to study units, and the intensivists working in four of the participating units. MEASUREMENTS AND MAIN RESULTS The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates. The primary intensivist outcome was physician burnout. Analysis was by multivariable regression. A total of 45 intensivists and 1,900 patients participated in the study. Continuity of care differed between schedules (patients with multiple intensivists = 28% under continuous schedule vs. 62% under interrupted scheduling; P < 0.0001). LOS and mortality were nonsignificantly higher under continuous scheduling (ΔICU LOS 0.36 d, P = 0.20; Δhospital LOS 0.34 d, P = 0.71; ICU mortality, odds ratio = 1.43, P = 0.12; hospital mortality, odds ratio = 1.17,P = 0.41). Intensivists experienced significantly higher burnout, work–home life imbalance, and job distress working under the continuous schedule. CONCLUSIONS Work schedules where intensivists received weekend breaks were better for the physicians and, despite lower continuity of intensivist care, did not worsen outcomes for medical ICU patients.

Alongside the growing epidemic of obesity, there is a proliferation of observational studies examining excess body weight as a potential risk factor for poor outcomes from various procedures and diseases, including critical illness.1,2 Some studies bolster the evidence that increasing weight is associated with excess mortality and morbidity.3–5 However, in this issue of Anesthesia & Analgesia, Nafiu et al. suggest a lack of deleterious effects of obesity on short-term outcomes among elderly patients (>65 years) undergoing vascular surgery,6 consistent with some other studies of obesity and acute illness.7–10 These investigators examined the association between preoperative body mass index (BMI) and immediate postoperative morbidity and mortality using the National Surgical Quality Improvement Program database. After risk adjustment, the odds ratio for postoperative (up to 30 days) mortality was highest among underweight patients and lowest among overweight patients or those with class I obesity (BMI 30 to 34.9 kg/m2). Even severe obesity (BMI ≥ 40 kg/m2) did not appreciably increase the risk of mortality. Underweight patients also had greater morbidity and longer length of stay after surgery. These results provide little support for the idea that excess weight increases the risk of surgical complications in elderly patients undergoing vascular procedures. However, because the majority of these procedures were not emergent (<15%), surgeons had some discretion in selecting patients for surgery. Hence, perhaps the lack of association between excess weight and patient outcomes is due to appropriate patient selection with exclusion of the higher BMI patients who may have been higher risk. If this were true, one might expect that such selection would result in similar risk-adjusted mortality between the normal and increased BMI patients. However, this was not the case. Instead, patients with overweight and obese BMIs appeared to have some degree of protection from negative outcomes. We speculate that this finding may arise, at least in part, because of discrimination against heavier patients. While direct evidence of such discrimination is lacking from the current study, there is circumstantial evidence that supports our speculation. Bias against obese individuals by medical professionals is well documented11–13 and may include disparities in care provided, including among ambulatory14,15 and critically ill patients.16 In the current study, obese patients were younger, more functionally independent, more commonly nonsmokers, and less likely to have disseminated cancer, recent weight loss, or a do-not-resuscitate order than did patients with normal BMIs. Some of these differences may be due to the interaction between vascular disease and excess weight (e.g., obese patients manifest symptoms of vascular disease at a younger age); however, it is also possible that heavier patients must be “healthier” than patients with normal BMIs for surgeons to consider them of equal risk and recommend and perform surgery. A prior study suggested that physicians attributed an increased risk of mortality to obesity in cases of septic shock, independent of APACHE II score or number of organ failures.17 This potential bias in selection for surgery could be explored by determining whether BMI is an independent predictor of referral for, and receipt of, a vascular surgical procedure. Thus, this study prompts us to ask whether surgeons are less likely to perform vascular surgical procedures (particularly nonemergent surgery) if a patient is obese. This study also raises questions about potential differences in medical care provided, in both the pre- and perioperative periods. Considering that obesity is associated with greater health care resource utilization,18 it would be interesting to explore whether more intense medical management prior to surgery (e.g., blood pressure control, diabetes management) reduced obese patients' operative risk. Similarly, the presence of comorbidities prior to surgery may have led to greater attention to their management in the perioperative period. Future research should consider such questions. The study's findings regarding underweight patients also deserve comment. Considering the higher rate of preoperative functional dependence (32.7% vs. 19.9% among normal BMI patients) and admission from a location other than home (12.9% vs. 8.7%, respectively), one could infer that this underweight group is not healthy and thin, but is underweight because of underlying disease, including frailty19 in these older patients. In addition to higher mortality, these underweight patients suffered higher rates of postoperative complications, including cardiac arrest, delayed weaning from mechanical ventilation, pneumonia, and reintubation. Their average hospital length of stay was almost 50% longer than for those with normal BMIs. Potentially confounding some of these associations was a higher rate of emergency surgery in underweight patients. Further investigation directed at underweight patients would be helpful to further explore these noteworthy findings. In particular, the effectiveness of preoperative efforts to mitigate complications via improving nutritional status and normalizing a patient's BMI before elective surgery is worthy of further study. In most cases, vascular surgery procedures have a more profound effect on patients' morbidity than mortality. Even among this relatively high-risk group of elderly patients, operative mortality was <5%. As a result, patient-centered outcomes, such as quality of life and functional status, should be incorporated into decision-making regarding surgical intervention. Some patients may prefer accepting a small, but increased, risk of immediate postoperative mortality for a possible substantial improvement in longer-term functional status. For example, those who were functionally dependent preoperatively had almost 4 times the odds of death within 30 days. In isolation, this suggests that the operative risk among these patients might out-weigh the benefit. However, a patient might be willing to accept this risk if there is the potential for greater return to functional independence after the surgery. Future studies should consider patients' perspectives regarding balancing mortality and morbidity. Integral to informing this balance is a need for research that longitudinally evaluates long-term patient-centered outcomes after surgery. For example, although excess weight was not associated with increased complications in the immediate postoperative period, longer-term follow-up might identify complications occurring after hospital discharge, which would be important information for patients and surgeons. The current study is a welcome addition to the literature examining BMI and patient outcomes. Although BMI is a readily available and apparent clinical variable, its true utility is realized when it is readily modifiable. Modification could include efforts to change a patient's BMI (e.g., through weight loss or weight gain) or to provide therapies aimed at mitigating increased risks associated with body weight. Although many questions remain, it is clear that excess weight should not be considered a risk factor for poor short-term outcomes among elderly vascular surgery patients, but further exploration of the worse outcomes experienced by underweight patients is clearly warranted.

Introduction: Socio-demographic and clinical factors associated with increased sepsis risk, including older age, non-white race and specific co-morbidities, are more common among patients with Medicare or Medicaid or no health insurance. We hypothesized that patients with Medicare and/or Medicaid or without health insurance have a higher risk of sepsis-associated hospitalization or sepsis-associated death than those with private health insurance.Methods: We performed a retrospective cohort study of records from the 2003 Nationwide Inpatient Sample. We stratified the study cohort by Medicare age-qualification (18 to 64 and 65+ years old). We examined the association between insurance category and sepsis diagnosis and death among admissions involving sepsis. We used validated diagnostic codes to determine the presence of sepsis, co-morbidities and organ dysfunction and to provide risk-adjustment.Results: Among patients 18 to 64 years old, those with Medicaid (adjusted odds ratio (AOR) 1.50), Medicare (AOR 1.96), Medicaid + Medicare (AOR 2.22) and the uninsured (AOR 1.18) had significantly higher risk-adjusted odds of a sepsis-associated admission than those with private insurance (all P < 0.0001). Those with Medicaid (AOR 1.17, P < 0.001) and those without insurance (AOR 1.45, P < 0.001) also had significantly higher adjusted odds of sepsis-associated hospital mortality than those with private insurance. Among those 65+ years old, those with Medicaid (AOR 1.43), Medicare alone (AOR 1.13) or Medicaid + Medicare (AOR 1.62) had significantly higher risk-adjusted odds of sepsis-associated admission than those with private insurance and Medicare (all P < 0.0001). Among sepsis patients 65+, uninsured patients had significantly higher risk-adjusted odds (AOR 1.45, P = 0.0048) and those with Medicare alone had significantly lower risk-adjusted odds (AOR 0.92, P = 0.0072) of hospital mortality than those with private insurance and Medicare. Lack of health insurance remained associated with sepsis-associated mortality after stratification of hospitals into quartiles based on rates of sepsis-associated admissions or mortality in both age strata.Conclusions: Risks of sepsis-associated hospitalization and sepsis-associated death vary by insurance. These increased risks were not fully explained by the available socio-demographic factors, co-morbidities or hospital rates of sepsis-related admissions or deaths.

INTRODUCTION:Mortality is the most widely accepted outcome measure in randomized controlled trials of therapies for critically ill adults, but most of these trials fail to show a statistically significant mortality benefit. The reasons for this are unknown.METHODS:We searched five high impact journals (Annals of Internal Medicine, British Medical Journal, JAMA, The Lancet, New England Journal of Medicine) for randomized controlled trials comparing mortality of therapies for critically ill adults over a ten year period. We abstracted data on the statistical design and results of these trials to compare the predicted delta (delta; the effect size of the therapy compared to control expressed as an absolute mortality reduction) to the observed delta to determine if there is a systematic overestimation of predicted delta that might explain the high prevalence of negative results in these trials.RESULTS:We found 38 trials meeting our inclusion criteria. Only 5/38 (13.2%) of the trials provided justification for the predicted delta. The mean predicted delta among the 38 trials was 10.1% and the mean observed delta was 1.4% (P < 0.0001), resulting in a delta-gap of 8.7%. In only 2/38 (5.3%) of the trials did the observed delta exceed the predicted delta and only 7/38 (18.4%) of the trials demonstrated statistically significant results in the hypothesized direction; these trials had smaller delta-gaps than the remainder of the trials (delta-gap 0.9% versus 10.5%; P < 0.0001). For trials showing non-significant trends toward benefit greater than 3%, large increases in sample size (380% - 1100%) would be required if repeat trials use the observed delta from the index trial as the predicted delta for a follow-up study.CONCLUSIONS:Investigators of therapies for critical illness systematically overestimate treatment effect size (delta) during the design of randomized controlled trials. This bias, which we refer to as "delta inflation", is a potential reason that these trials have a high rate of negative results."Absence of evidence is not evidence of absence."