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RATIONALE: Variation in practice and outcomes, not explained by patient or illness characteristics, is common in health care, including in intensive care units (ICUs). OBJECTIVE: To quantify within-ICU, between-physician variation in resource use in a single medical ICU. METHODS: This was a prospective, noninterventional study in a medical ICU where nine intensivists provide care in 14-d rotations. Consecutive sample consisted of 1,184 initial patient admissions whose care was provided by a single intensivist. Multivariate models were constructed for average daily discretionary costs, ICU length of stay, and hospital mortality, adjusting for patient and illness characteristics, and workload. MEASUREMENTS AND MAIN RESULTS: The identity of the intensivist was a significant predictor for average daily discretionary costs (p < 0.0001), but not ICU length of stay (p = 0.33) or hospital mortality (p = 0.83). The intensivists had more influence on costs than all other variables except the severity and type of acute illness. Average daily discretionary costs varied by 43% across the different intensivists, equating to a mean difference of $1,003 per admission between the highest and lowest terciles of intensivists. CONCLUSIONS: There are large differences among intensivists in the amount of resources they use to manage critically ill patients. Higher resource use was not associated with lower length of stay or mortality. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care.Design: Prospective cohort study.Setting: Five US teaching hospitals between 1989 and 1994.Subjects: A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories.Main Outcome Measures: Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results.Results: By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49 300 ($17 000, $30 500, $56 600) with RHC and $35 700 ($11 300, $20 600, $39 200) without RHC. Mean length of stay in the ICU was 14.8 (5, 9, 17) days with RHC and 13.0 (4, 7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful.Conclusion: In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study. [ABSTRACT FROM AUTHOR]

Indications for right heart catheterization are changing. But is the procedure still being used inappropriately? Find out when the benefits of use outweigh the risks, when they don't, and when it's simply not clear. [ABSTRACT FROM AUTHOR]

Background: Patient age may influence decisions to withhold life-sustaining treatments, independent of patients' preferences for or ability to benefit from such treatments. Controversy exists about the appropriateness of using age as a criterion for making treatment decisions.Objective: To determine the effect of age on decisions to withhold life-sustaining therapies.Design: Prospective cohort study.Setting: Five medical centers participating in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT).Patients: 9105 hospitalized adults who had one of nine illnesses associated with an average 6-month mortality rate of 50%.Measurements: Outcomes were the presence and timing of decisions to withhold ventilator support, surgery, and dialysis. Adjustment was made for sociodemographic characteristics, prognoses, baseline function, patients' preferences for life-extending care, and physicians' understanding of patients' preferences for life-extending care.Results: The median patient age was 63 years; 44% of patients were women, and 53% survived to 180 days. In adjusted analyses, older age was associated with higher rates of withholding each of the three life-sustaining treatments studied. For ventilator support, the rate of decisions to withhold therapy increased 15% with each decade of age (hazard ratio, 1.15 [95% CI, 1.12 to 1.19]); for surgery, the increase per decade was 19% (hazard ratio, 1.19 [CI, 1.12 to 1.27]); and for dialysis, the increase per decade was 12% (hazard ratio, 1.12 [CI, 1.06 to 1.19]). Physicians underestimated older patients' preferences for life-extending care; adjustment for this underestimation resulted in an attenuation of the association between age and decisions to withhold treatments.Conclusion: Even after adjustment for differences in patients' prognoses and preferences, older age was associated with higher rates of decisions to withhold ventilator support, surgery, and dialysis. [ABSTRACT FROM AUTHOR]

Background: Renal failure requiring dialysis in the setting of hospitalization for serious illness is a poor prognostic sign, and dialysis and aggressive care are sometimes withheld.Objective: To evaluate the clinical outcomes and cost-effectiveness of initiating dialysis and continuing aggressive care for seriously ill hospitalized patients.Design: Prospective cohort study and cost-effectiveness analysis.Setting: Five geographically diverse teaching hospitals.Patients: 490 patients (median age, 61 years; 58% women) enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) in whom dialysis was initiated.Measurements: Survival, functional status, quality of life, and health care costs. Life expectancy was estimated by extrapolating survival data (up to 4.4 years of follow-up) using a declining exponential function. Utilities (quality-of-life weights) were estimated by using time-tradeoff questions. Costs were based on data from SUPPORT and published Medicare data.Results: Median duration of survival was 32 days, and only 27% of patients were alive after 5 months. Survivors reported a median of one dependency in activities of daily living, and 62% rated their quality of life as "good" or better. Overall, the estimated cost per quality-adjusted life-year saved by initiating dialysis and continuing aggressive care rather than withholding dialysis and allowing death to occur was $128,200. For the 103 patients in the worst prognostic category, the estimated cost per quality-adjusted life-year was $274,100; for the 94 patients in the best prognostic category, the cost per quality-adjusted life-year was $61,900.Conclusions: For the few patients who survived, clinical outcomes were fairly good. With the exception of patients with the best prognoses, however, the cost-effectiveness of initiating dialysis and continuing aggressive care far exceeded $50,000 per quality-adjusted life-year, a commonly cited threshold for cost-effective care. [ABSTRACT FROM AUTHOR]

Background: Physicians are frequently unaware of patient preferences for end-of-life care. Identifying and exploring barriers to patient-physician communication about end-of-life issues may help guide physicians and their patients toward more effective discussions.Objective: To examine correlates and associated outcomes of patient communication and patient preferences for communication with physicians about cardiopulmonary resuscitation and prolonged mechanical ventilation.Design: Prospective cohort study.Setting: Five tertiary care hospitals.Patients: 1832 (85%) of 2162 eligible patients completed interviews.Measurements: Surveys of patient characteristics and preferences for end-of-life care; perceptions of prognosis, decision making, and quality of life; and patient preferences for communication with physicians about end-of-life decisions.Results: Fewer than one fourth (23%) of seriously ill patients had discussed preferences for cardiopulmonary resuscitation with their physicians. Of patients who had not discussed their preferences for resuscitation, 58% were not interested in doing so. Of patients who had not discussed and did not want to discuss their preferences, 25% did not want resuscitation. In multivariable analyses, patient factors independently associated with not wanting to discuss preferences for cardiopulmonary resuscitation included being of an ethnicity other than black (adjusted odds ratio [OR], 1.48 [95% CI, 1.10 to 1.99), not having an advance directive (OR, 1.35 [CI, 1.04 to 1.76]), estimating an excellent prognosis (OR, 1.72 [CI, 1.32 to 2.59]), reporting fair to excellent quality of life (OR, 1.36 [CI, 1.05 to 1.76]), and not desiring active involvement in medical decisions (OR, 1.33 [CI, 1.07 to 1.65]). Factors independently associated with wanting to discuss preferences for resuscitation but not doing so included being black (OR, 1.53 [CI, 1.11 to 2.11]) and being younger (OR, 1.14 per 10-year interval younger [CI, 1.04 to 1.25]).Conclusions: Among seriously ill hospitalized adults, communication about preferences for cardiopulmonary resuscitation is uncommon. A majority of patients who have not discussed preferences for end-of-life care do not want to do so. For patients who do not want to discuss their preferences, as well as patients with an unmet need for such discussions, failure to discuss preferences for cardiopulmonary resuscitation and mechanical ventilation may result in unwanted interventions. [ABSTRACT FROM AUTHOR]

Background: Alleviating the problems faced by dying persons and their families has drawn substantial public attention, but little is known about the experience of dying.Objective: To characterize the experience of dying from the perspective of surrogate decision makers, usually close family members (89%).Design: Prospective cohort study.Setting: Five teaching hospitals.Patients: Persons who had one of nine serious medical conditions or were 80 years of age or older who died and for whom a surrogate decision maker completed an interview about the death.Measurements: Medical records were reviewed and surrogate decision makers were interviewed.Results: 4124 of 9105 seriously ill patients died (46%); 408 of 1176 elderly patients died (35%). The patients' family members were interviewed after 3357 persons (73%) had died. Of 1541 patients who survived the enrollment hospitalization, 46% died during a later hospitalization. In the last 3 days of life, 55% of patients were conscious. Among these patients, pain, dyspnea, and fatigue were prevalent. Four in 10 patients had severe pain most of the time. Severe fatigue affected almost 8 in 10 patients. More than 1 in 4 patients had moderate dysphoria. Sixty-three percent of patients had difficulty tolerating physical or emotional symptoms. Overall, 11% of patients had a final resuscitation attempt. A ventilator was used in one fourth of patients, and a feeding tube was used in four tenths of patients. Most patients (59%) were reported to prefer a treatment plan that focused on comfort, but care was reported to be contrary to the preferred approach in 10% of cases.Conclusions: Most elderly and seriously ill patients died in acute care hospitals. Pain and other symptoms were commonplace and troubling to patients. Family members believed that patients preferred comfort, but life-sustaining treatments were often used. These findings indicate important opportunities to improve the care of dying patients. [ABSTRACT FROM AUTHOR]

Background: Medical treatment decisions should be based on the preferences of informed patients or their proxies and on the expected outcomes of treatment. Because seriously ill patients are at risk for cardiac arrest, examination of do-not-resuscitate (DNR) practices affecting them provides useful insights into the associations between various factors and medical decision making.Objective: To examine the association between patients' preferences for resuscitation (along with other patient and physician characteristics) and the frequency and timing of DNR orders.Design: Prospective cohort study.Setting: 5 teaching hospitals.Patients: 6802 seriously ill hospitalized patients enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT) between 1989 and 1994.Measurements: Patients and their surrogates were interviewed about patients' cardiopulmonary resuscitation preferences, medical records were reviewed to determine disease severity, and a multivariable regression model was constructed to predict the time to the first DNR order.Results: The patients' preference for cardiopulmonary resuscitation was the most important predictor of the timing of DNR orders, but only 52% of patients who preferred not to be resuscitated actually had DNR orders written. The probability of surviving for 2 months was the next most important predictor of the timing of DNR orders. Although DNR orders were not linearly related to the probability of surviving for 2 months, they were written earlier and more frequently for patients with a 50% or lower probability of surviving for 2 months. Orders were written more quickly for patients older than 75 years of age, regardless of prognosis. After adjustment for these and other influential patient characteristics, the use and timing of DNR orders varied significantly among physician specialties and among hospitals.Conclusions: Patients' preferences and short-term prognoses are associated with the timing of DNR orders. However, the substantial variation seen among hospital sites and among physician specialties suggests that there is room for improvement. In this study, DNR orders were written earlier for patients older than 75 years of age, regardless of prognosis. This finding suggests that physicians may be using age in a way that is inconsistent with the reported association between age and survival. The process for making decisions about DNR orders needs to be improved if such orders are to routinely and accurately reflect patients' preferences and probable outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Serious illness often causes economic hardship for patients' families. However, it is not known whether this hardship is associated with a preference for the goal of care to focus on maximizing comfort instead of maximizing life expectancy or whether economic hardship might give rise to disagreement between patients and surrogates over the goal of care. METHODS: We performed a cross-sectional study of 3158 seriously ill patients (median age, 63 years; 44% women) at 5 tertiary medical centers with 1 of 9 diagnoses associated with a high risk of mortality. Two months after their index hospitalization, patients and surrogates were surveyed about patients' preferences for the primary goal of care: either care focused on extending life or care focused on maximizing comfort. Patients and surrogates were also surveyed about the financial impact of the illness on the patient's family. RESULTS: A report of economic hardship on the family as a result of the illness was associated with a preference for comfort care over life-extending care (odds ratio, 1.26; 95% confidence interval, 1.07-1.48) in an age-stratified bivariate analysis. Similarly, in a multivariable analysis controlling for patient demographics, illness severity, functional dependency, depression, anxiety, and pain, economic hardship on the family remained associated with a preference for comfort care over life-extending care (odds ratio, 1.31; 95% confidence interval, 1.10-1.57). Economic hardship on the family did not affect either the frequency or direction of patient-surrogate disagreements about the goal of care. CONCLUSIONS: In patients with serious illness, economic hardship on the family is associated with preferences for comfort care over life-extending care. However, economic hardship on the family does not appear to be a factor in patient-surrogate disagreements about the goal of care. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a simple prognostic scoring system to identify patients in nontraumatic coma at high risk for poor outcomes using data available early in the hospital course.Design: Prospective cohort study.Setting: Five geographically diverse academic medical centers.Patients: A total of 596 patients in nontraumatic coma enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), including 247 in the model derivation set and 349 in the model validation set.Main Outcome Measures: Death and severe disability by 2 months.Main Results: For the 596 patients studied (median age, 67 years; 52% female), the primary cause of coma was cardiac arrest in 31% and cerebral infarction or intracerebral hemorrhage in 36%. At 2 months 69% had died, 20% had survived with known severe disability, 8% were known to have survived without severe disability, and 3% survived with unknown functional status. Five clinical variables available on day 3 after enrollment were associated independently with 2-month mortality: abnormal brain stem response (adjusted odds ratio [OR] = 3.2; 95% confidence interval [CI], 1.3 to 8.1), absent verbal response (OR = 4.6; 95% CI, 1.8 to 11.7), absent withdrawal response to pain (OR = 4.3; 95% CI, 1.7 to 10.8), creatinine level greater than or equal to 132.6 mumol/L (1.5 mg/dL) (OR = 4.5; 95% CI, 1.8 to 11.0), and age of 70 years or older (OR = 5.1; 95% CI, 2.2 to 12.2). Mortality at 2 months for patients with four or five of these risk factors was 97% (58/60; 95% CI, 88% to 100%) in the validation set. Brain stem and motor responses best predicted death or severe disability by 2 months. For patients with either an abnormal brain stem response or absent motor response to pain, the rate of death or severe disability at 2 months was 96% (185/193; 95% CI, 92% to 98%) in the validation set.Conclusions: Five readily available clinical variables identify a large subgroup of patients in nontraumatic coma at high risk for poor outcomes. This risk stratification approach offers physicians, patients, and patients' families information that may prove useful in patient care decisions and resource allocation. [ABSTRACT FROM AUTHOR]

Objective: To examine the impact of illness on the families of seriously ill adults and to determine the correlates of adverse economic impact.Design: Data were collected during the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT), a prospective cohort study of outcomes, preferences, and decision making in seriously ill hospitalized adults and their families.Setting: Five tertiary care hospitals in the United States.Participants: The 2661 seriously ill patients in nine diagnostic categories who survived their index hospitalization and were discharged home were eligible for this analysis. Surrogate and/or patient interviews about the impact of illness on the family were obtained for 2129 (80%) of these patients (mean age, 62 years; 43% women; 6-month survival, 75%).Outcome Measures: Surrogates and patients were surveyed to determine the frequency of adverse caregiving and economic burdens. Multivariable analyses were performed to determine correlates of loss of family savings.Results: One third (34%) of patients required considerable caregiving assistance from a family member. In 20% of cases, a family member had to quit work or make another major life change to provide care for the patient. Loss of most or all of the family savings was reported by 31% of families, whereas 29% reported loss of the major source of income. Patient factors independently associated with loss of the family's savings on multivariable analysis included poor functional status (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.10 to 1.78 for patients needing assistance with three or more activities of daily living), lower family income (OR, 1.74; 95% CI, 1.37 to 2.21 for those with annual incomes below $25,000), and young age (OR, 2.85; 95% CI, 2.13 to 3.82 for those younger than 45 years compared with those 65 years or older).Conclusions: Many families of seriously ill patients experience severe caregiving and financial burdens. Families of younger, poorer, and more functionally dependent patients are most likely to report loss of most or all of the family's savings. [ABSTRACT FROM AUTHOR]

Background: Although nearly 1 million older adults are admitted for emergency general surgery conditions yearly, the extent to which baseline health influences the development and treatment of emergency general surgery conditions is unknown. We evaluated baseline health and older patients with and without emergency general surgery conditions., Methods: We used the prospectively collected Medicare Current Beneficiary Survey with Medicare claims and 2 validated health frameworks: (1) Deficit Accumulation Frailty Score and (2) Complex Multimorbidity. Self-reported health and function items were used to derive pre-emergency general surgery conditions Deficit Accumulation Frailty Score and Complex Multimorbidity scores. Deficit Accumulation Frailty Score ranges from 0 (no frailty deficits) to 100 (all possible deficits present). Complex Multimorbidity is a 3-point categorical rank based on the presence of chronic conditions, functional limitations, and geriatric syndromes. Specific survey factors were also examined to determine association with development of emergency general surgery conditions or use of operative management., Results: Of 54,417 individuals, 1,960 had emergency general surgery conditions (median age 79 [interquartile range 73-84]). Patients with emergency general surgery conditions had significantly higher Deficit Accumulation Frailty Score (19 [interquartile range 11-31] vs 14 [8-24]) and were more likely to be in the most severe Complex Multimorbidity category (38% vs 29%). Emergency general surgery conditions patients had higher proportions of nearly every health category, with the most striking differences in functional limitations. Patients who were treated nonoperatively had the poorest overall baseline health., Conclusion: Patients who developed emergency general surgery conditions had more severe health burden than patients who did not, particularly in functional status. Clinicians must better understand the interaction between baseline health vulnerability and emergency surgical disease to improve prognostication and ensure alignment of patient goals and treatment strategies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The State of Ohio in the United States has the legislation for two different protocols of do-not-resuscitate orders. The objective of this study was to examine the clinical/demographic factors and outcomes associated with the two different do-not-resuscitate orders., Design: Data were concurrently and retrospectively collected from August 2002 to December 2005. The clinical/demographic factors of do-not-resuscitate patients were compared with those of non-do-not-resuscitate patients, and the clinical/demographic factors of do-not-resuscitate comfort care-arrest patients were compared with those of do-not-resuscitate comfort care patients., Setting: An ICU in a university-affiliated hospital located at Northeast Ohio in the United States., Patients: A sample of 2,440 patients was collected: 389 patients were do-not-resuscitate; and 2,051 patients were non-do-not-resuscitate. Among the 389 do-not-resuscitate patients, 194 were do-not-resuscitate comfort care-arrest patients and 91 were do-not-resuscitate comfort care patients., Interventions: None., Measurements and Main Results: The factors associated with do-not-resuscitate were older age, race and ethnicity with white race, more severe clinical illness at admission to the ICU, and longer stay before admission to the ICU. Comparing do-not-resuscitate comfort care-arrest patients with do-not-resuscitate comfort care patients, those with more severe clinical illness, longer ICU stay before making a do-not-resuscitate decision, and being cared for by only one intensivist during ICU stay were significantly associated with do-not-resuscitate comfort care decisions. For 149 do-not-resuscitate patients who eventually survived to hospital discharge and 86 do-not-resuscitate patients who eventually did not, only eight (5.4%) and 23 (26.7%) had the order written within 48 hours before the end of ICU stay, respectively., Conclusions: Our study showed that some clinical/demographic factors predicted do-not-resuscitate comfort care orders. This study also suggested that Ohio's Do-Not-Resuscitate Law, clearly indicating two different protocols of do-not-resuscitate orders, facilitated early do-not-resuscitate decision.

Background: Little other than subjective judgment is available to help clinicians determine when a patient should be transferred out of the intensive care unit., Objective: To assess whether remaining in the intensive care unit longer than judged to be medically necessary is associated with increased 30-day mortality., Methods: This prospective, observational cohort study was performed in a 13-bed, closed-model, adult medical intensive care unit of a county-owned, university-affiliated hospital that often has difficulty transferring patients to general care areas because of a lack of available beds. Analysis included all 2401 survivors of intensive care from the study period. Delay in discharge from the intensive care unit was defined as time elapsed between the request for transfer and the actual transfer. Logistic regression was used to assess the association of discharge delay with 30-day mortality, adjusting for demographics, comorbid conditions, type and severity of acute illness, care limitations in the unit, and other potential confounding variables. Nonlinear relationships with continuous variables were modeled with restricted cubic splines., Results: Overall, 30-day mortality was 10.1%. Mean discharge delay was 9.6 (SD, 11.7) hours; 9.9% had a discharge delay exceeding 24 hours. The relationship of 30-day mortality to discharge delay was statistically significant and U-shaped, with the nadir at 20 hours., Conclusions: These data indicate an optimal time window for patients to leave the intensive care unit, with increased mortality not only if they leave earlier but also if they leave later than this optimal timing.

Background: The pulmonary artery catheter (PAC) remains widely used in acute lung injury (ALI) despite known complications and little evidence of improved short-term mortality. Concurrent with NHLBI ARDS Clinical Trials Network Fluid and Catheters Treatment Trial (FACTT), we conducted a prospectively-defined comparison of healthcare costs and long-term outcomes for care with a PAC vs. central venous catheter (CVC). We explored if use of the PAC in ALI is justified by a beneficial cost-effectiveness profile., Methods: We obtained detailed bills for the initial hospitalization. We interviewed survivors using the Health Utilities Index Mark 2 questionnaire at 2, 6, 9 and 12 m to determine quality of life (QOL) and post-discharge resource use. Outcomes beyond 12 m were estimated from federal databases. Incremental costs and outcomes were generated using MonteCarlo simulation., Results: Of 1001 subjects enrolled in FACTT, 774 (86%) were eligible for long-term follow-up and 655 (85%) consented. Hospital costs were similar for the PAC and CVC groups ($96.8k vs. $89.2k, p = 0.38). Post-discharge to 12 m costs were higher for PAC subjects ($61.1k vs. 45.4k, p = 0.03). One-year mortality and QOL among survivors were similar in PAC and CVC groups (mortality: 35.6% vs. 31.9%, p = 0.33; QOL [scale: 0-1]: 0.61 vs. 0.66, p = 0.49). MonteCarlo simulation showed PAC use had a 75.2% probability of being more expensive and less effective (mean cost increase of $14.4k and mean loss of 0.3 quality-adjusted life years (QALYs)) and a 94.2% probability of being higher than the $100k/QALY willingness-to-pay threshold., Conclusion: PAC use increased costs with no patient benefit and thus appears unjustified for routine use in ALI., Trial Registration: www.clinicaltrials.gov NCT00234767.

Objective: Treatment and prevention of hyperglycemia has been advocated for subjects with sepsis. Glucose variability, rather than the glucose level, has also been shown to be an important factor associated with in-hospital mortality, in general, critically ill patients. Our objective was to determine the association between glucose variability and hospital mortality in septic patients and the expression of glucose variability that best reflects this risk., Design: Retrospective, single-center cohort study., Setting: Academic, tertiary care hospital., Patients: Adult subjects hospitalized for >1 day, with a diagnosis of sepsis were included., Interventions: None., Measurements: Glucose variability was calculated for all subjects as the average and standard deviation of glucose, the mean amplitude of glycemic excursions, and the glycemic lability index. Hospital mortality was the primary outcome variable. Logistic regression was used to determine the odds of hospital death in relation to measures of glucose variability after adjustment for important covariates., Main Results: Of the methods used to measure glucose variability, the glycemic lability index had the best discrimination for mortality (area under the curve = 0.67, p < 0.001). After adjustment for confounders, including the number of organ failures and the occurrence of hypoglycemia, there was a significant interaction between glycemic lability index and average glucose level, and the odds of hospital mortality. Higher glycemic lability index was not independently associated with mortality among subjects with average glucose levels above the median for the cohort. However, subjects with increased glycemic lability index, but lower average glucose values had almost five-fold increased odds of hospital mortality (odds ratio = 4.73, 95% confidence interval = 2.6-8.7) compared with those with lower glycemic lability index., Conclusions: Glucose variability is independently associated with hospital mortality in septic patients. Strategies to reduce glucose variability should be studied to determine whether they improve the outcomes of septic patients.

Rationale: ICU-acquired paresis (ICUAP) is common in survivors of critical illness. There is significant associated morbidity, including prolonged time on the ventilator and longer hospital stay. However, it is unclear whether ICUAP is independently associated with mortality, as sicker patients are more prone and existing studies have not adjusted for this., Objectives: To test the hypothesis that ICUAP is independently associated with increased mortality. Secondarily, to determine if handgrip dynamometry is a concise measure of global strength and is independently associated with mortality., Methods: A prospective multicenter cohort study was conducted in intensive care units (ICU) of five academic medical centers. Adults requiring at least 5 days of mechanical ventilation without evidence of preexisting neuromuscular disease were followed until awakening and were then examined for strength., Measurements and Main Results: We measured global strength and handgrip dynamometry. The primary outcome was in-hospital mortality and secondary outcomes were hospital and ICU-free days, ICU readmission, and recurrent respiratory failure. Subjects with ICUAP (average MRC score of < 4) had longer hospital stays and required mechanical ventilation longer. Handgrip strength was lower in subjects with ICUAP and had good test performance for diagnosing ICUAP. After adjustment for severity of illness, ICUAP was independently associated with hospital mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 2.4-25.3; P = 0.001). Separately, handgrip strength was independently associated with hospital mortality (OR, 4.5; 95% CI, 1.5-13.6; P = 0.007)., Conclusions: ICUAP is independently associated with increased hospital mortality. Handgrip strength is also independently associated with poor hospital outcome and may serve as a simple test to identify ICUAP. Clinical trial registered with www.clinicaltrials.gov (NCT00106665).

Background: The effect on long-term mortality of decisions made to withhold life-supporting therapies (LST) for critically ill patients is unclear. We hypothesized that mortality 60 days after ICU admission is not influenced by a decision to withhold use of LST in the context of otherwise providing all indicated care., Methods: We studied 2,211 consecutive, initial admissions to the adult, medical ICU of a university-affiliated teaching hospital. To achieve balanced groups for comparing outcomes, we created a multivariable regression model for the probability (propensity score [PS]) of having an order initiated in the ICU to withhold LST. Each of the 201 patients with such an order was matched to the patient without such an order having the closest PS; mortality rates were compared between the matched pairs. Cox survival analysis was performed to extend the main analysis., Results: The matched pairs were well balanced with respect to all of the potentially confounding variables. Sixty days after ICU admission, 50.5% of patients who had an order initiated in the ICU to withhold life support had died, compared to 25.8% of those lacking such orders (risk ratio, 2.0; 95% confidence interval, 1.5 to 2.6). Survival analysis indicated that the difference in mortality between the two groups continued to increase for approximately 1 year., Conclusion: Contrary to our hypothesis, decisions made in the ICU to withhold LST were associated with increased mortality rate to at least 60 days after ICU admission.

Objective: Hospital mortality outcomes for acute myocardial infarction (AMI) patients are a focus of quality improvement programs conducted by government agencies. AMI mortality risk-adjustment models using administrative data typically adjust for baseline differences in mortality risk with a limited set of common and definite comorbidities. In this study, we present an AMI mortality risk-adjustment model that adjusts for comorbid disease and for AMI severity using information from secondary diagnoses reported as present at admission for California hospital patients., Study Design and Setting: AMI patients were selected from California hospital administrative data for 1996 through 1999 according to criteria used by the California Hospital Outcomes Project Report on Heart Attack Outcomes, a state-mandated public report that compares hospital mortality outcomes. We compared results for the new model to two mortality risk-adjustment models used to assess hospital AMI mortality outcomes by the state of California, and to two other models used in prior research., Results: The model using present-at-admission diagnoses obtained substantially better discrimination between predicted survival and inpatient death than the other models we considered., Conclusion: AMI mortality risk-adjustment methods can be meaningfully improved using present-at-admission diagnoses to identify comorbid disease and conditions related closely to AMI.

Background & Aims: Patients with steroid-refractory ulcerative colitis face a difficult treatment decision between colectomy and therapy with infliximab or cyclosporine. The aim of this study was to understand how individual patient preferences for the various treatment outcomes influence the optimal treatment decision for a given patient., Methods: A Markov model was used to simulate treatment with total colectomy with an ileo pouch-anal anastomosis (TC/IPAA), cyclosporine (CSA), infliximab (INFLX), and infliximab followed by cyclosporine for treatment failures (INFLX-->CSA). Utility weights for treatment outcomes were elicited from 48 patients using both time trade-off and visual rating scale methods. Preference sets were applied to the model to identify the therapy that maximized quality-adjusted life years (QALYs) for each patient. Sensitivity analyses were performed to assess model robustness., Results: Optimal treatment was highly variable among patients (INFLX-->CSA = 42%, 20/48; TC/IPAA = 37%, 18/48; CSA = 21%, 10/48; INFLX = 0%, 0/48). However, when average preference weights from our sample were applied to the model, medical treatments were superior to TC (CSA = .26 QALYs gained vs TC/IPAA; INFLX-->CSA = .25 QALYs gained vs TC/IPAA)., Conclusions: Patient preferences have a clear impact on the optimal treatment for steroid-refractory ulcerative colitis. Although averaged preferences support the use of medical interventions, a third of individual patients may benefit most from proceeding directly to colectomy. Failure to fully assess individual preferences may result in suboptimal treatment for these patients.

Background: Optimal fluid management in patients with acute lung injury is unknown. Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion., Methods: In a randomized study, we compared a conservative and a liberal strategy of fluid management using explicit protocols applied for seven days in 1000 patients with acute lung injury. The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days and measures of lung physiology., Results: The rate of death at 60 days was 25.5 percent in the conservative-strategy group and 28.4 percent in the liberal-strategy group (P=0.30; 95 percent confidence interval for the difference, -2.6 to 8.4 percent). The mean (+/-SE) cumulative fluid balance during the first seven days was -136+/-491 ml in the conservative-strategy group and 6992+/-502 ml in the liberal-strategy group (P<0.001). As compared with the liberal strategy, the conservative strategy improved the oxygenation index ([mean airway pressure x the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen]x100) and the lung injury score and increased the number of ventilator-free days (14.6+/-0.5 vs. 12.1+/-0.5, P<0.001) and days not spent in the intensive care unit (13.4+/-0.4 vs. 11.2+/-0.4, P<0.001) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days (10 percent vs. 14 percent, P=0.06)., Conclusions: Although there was no significant difference in the primary outcome of 60-day mortality, the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures. These results support the use of a conservative strategy of fluid management in patients with acute lung injury. (ClinicalTrials.gov number, NCT00281268 [ClinicalTrials.gov].)., (Copyright 2006 Massachusetts Medical Society.)

Background: The balance between the benefits and the risks of pulmonary-artery catheters (PACs) has not been established., Methods: We evaluated the relationship of benefits and risks of PACs in 1000 patients with established acute lung injury in a randomized trial comparing hemodynamic management guided by a PAC with hemodynamic management guided by a central venous catheter (CVC) using an explicit management protocol. Mortality during the first 60 days before discharge home was the primary outcome., Results: The groups had similar baseline characteristics. The rates of death during the first 60 days before discharge home were similar in the PAC and CVC groups (27.4 percent and 26.3 percent, respectively; P=0.69; absolute difference, 1.1 percent; 95 percent confidence interval, -4.4 to 6.6 percent), as were the mean (+/-SE) numbers of both ventilator-free days (13.2+/-0.5 and 13.5+/-0.5; P=0.58) and days not spent in the intensive care unit (12.0+/-0.4 and 12.5+/-0.5; P=0.40) to day 28. PAC-guided therapy did not improve these measures for patients in shock at the time of enrollment. There were no significant differences between groups in lung or kidney function, rates of hypotension, ventilator settings, or use of dialysis or vasopressors. Approximately 90 percent of protocol instructions were followed in both groups, with a 1 percent rate of crossover from CVC- to PAC-guided therapy. Fluid balance was similar in the two groups, as was the proportion of instructions given for fluid and diuretics. Dobutamine use was uncommon. The PAC group had approximately twice as many catheter-related complications (predominantly arrhythmias)., Conclusions: PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy. These results, when considered with those of previous studies, suggest that the PAC should not be routinely used for the management of acute lung injury. (ClinicalTrials.gov number, NCT00281268.)., (Copyright 2006 Massachusetts Medical Society.)

Background: Mortality risk adjustment is a key component of studies that examine the statistical relationship between hospital lung cancer operation volume and in-hospital mortality. Previous studies of this relationship have used different methods of adjusting for factors that influence mortality risk, but none have adjusted for differences in comorbid disease using only diagnoses identified as present-at-admission., Methods: This study uses adjustments for conditions identified as present-at-admission to examine the statistical relationship between the volume of lung cancer operations and mortality among 14,456 California hospital patients, and compares these results to other methods of risk adjustment similar to those used in previous studies., Results: Mortality risk adjustment using present-at-admission diagnoses yielded better discrimination and explained more of the variability in observed deaths. Large increases in hospital procedure volume were associated with much smaller decreases in mortality risk than those estimated using comparable risk-adjustment models., Conclusions: Present-at-admission diagnoses can be used to improve mortality risk adjustment and may allow a more accurate assessment of the relationship between procedure volume and mortality risk.

Study Objective: To use an existing database from a large cohort study with follow-up as long as 5.5 years to assess the extended prognosis of patients who survived their hospitalizations for severe acute respiratory failure (ARF)., Design, Setting, and Patients: Secondary analysis of an inception cohort of 1,722 patients with ARF requiring mechanical ventilation from five major medical centers who were entered into the prospective Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment. The 1,075 patients (62.4%) who survived hospitalization had systematic follow-up of vital status for a median time of 662 days (interquartile range, 327 to 1,049 days; range, 2 to 2,014 days). Interviews performed a median of 5 months after hospital discharge assessed functional capacity and quality of life (QOL). The main outcome measure was survival after hospital discharge. Secondary measures were functional status and QOL. Cox proportional hazard regression identified factors influencing posthospital survival., Results: The median survival time after hospital discharge for ARF was > 5.3 years. The posthospital survival time was shorter for those with older age, male gender, several preexisting comorbid conditions, worse prehospital functional status, greater acute physiologic derangement, and a do-not-resuscitate order while in the hospital, and for those discharged to a location other than home. Five months after hospital discharge, 48% of survivors needed help with at least one activity of daily living, and 27% rated their QOL as poor or fair. However, most of these impairments were present before respiratory failure occurred., Conclusions: Extended survival is common among patients with ARF who require mechanical ventilation and who survive hospitalization. Among these patients, only a small fraction of the impairment in activity and QOL can be considered to be a sequela of the respiratory failure or its therapy. These findings are relevant to the care decisions for such critically ill patients.

Background: Racial and ethnic disparities in mortality have been demonstrated in several diseases. African Americans are hospitalized at a significantly higher rate than whites for aspiration pneumonia; however, no studies have investigated racial and ethnic disparities in mortality in this population., Objective: To assess the independent effect of race and ethnicity on in-hospital mortality among aspiration pneumonia discharges while comprehensively controlling for comorbid diseases, and to assess whether the prevalence and effects of comorbid illness differed across racial and ethnic categories., Design, Setting, and Participants: Retrospective cohort study of 41,581 patients admitted to California hospitals for aspiration pneumonia from 1996 through 1998, using principal and secondary diagnoses present on admission., Measurement: The primary outcome measure was in-hospital mortality., Results: The adjusted odds of in-hospital death for African-American compared with white discharges [odds ratio (OR)=1.01; 95% confidence interval (CI), 0.91-1.11] was not significantly different. The odds of death for Asian compared with white discharges was significantly lower (OR=0.83; 95% CI, 0.75-0.91). Hispanics had a significantly lower odds of death (OR=0.90; 95% CI, 0.82-0.988) compared to non-Hispanics. Comorbid diseases were more prevalent among African Americans and Asians than whites, and among Hispanics compared to non-Hispanics. Differences in effects of comorbid disease on mortality risk by race and ethnicity were not statistically significant., Conclusion: Asians have a lower risk of death, and the risk of death for African Americans is not significantly different from whites in this analysis of aspiration pneumonia discharges. Hispanics have a lower risk of death than non-Hispanics. While there are differences in prevalence of comorbid disease by racial and ethnic category, the effects of comorbid disease on mortality risk do not differ meaningfully by race or ethnicity.

Purpose: Multiple factors have affected the decline in autopsy rates. Our goal was to determine the relation of physicians' recommendations regarding autopsy, as well as patient and surrogate decision-maker characteristics, to autopsy performance., Methods: We assessed measures related to autopsy performance using data from two teaching institutions in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments. We included patients who had died within 6 months of their index hospitalization and for whom information was available on autopsy performance, physicians' response to questions about autopsy, and interviews with surrogate decision makers about autopsy performance. We assessed the association between autopsy performance and the strength of a physician's recommendation for autopsy, adjusting for patient, surrogate, and physician characteristics., Results: Of the 680 patients who died, 59% (n = 402) met our inclusion criteria. Based on physician and surrogate responses, the expected autopsy rate was 42% while the actual autopsy rate was 23%. The autopsy rate was higher when the physician's recommendation for autopsy was strong or very strong at the time of death compared with when autopsy was not recommended strongly or not at all (P <0.001). The strength of the physician's postmortem recommendation was independently associated with autopsy performance after adjusting for patient, surrogate, and physician characteristics (P <0.001)., Conclusion: Autopsies are less likely to be performed when not recommended strongly or not at all. Training physicians (or others) how to recommend autopsies may increase autopsy rates.

In patients with diaphragm paralysis, ventilation to the basal lung zones is reduced, whereas in patients with paralysis of the rib cage muscles, ventilation to the upper lung zones in reduced. Inspiration produced by either rib cage muscle or diaphragm contraction alone, therefore, may result in mismatching of ventilation and perfusion and in gas-exchange impairment. To test this hypothesis, we assessed gas exchange in 11 anesthetized dogs during ventilation produced by either diaphragm or intercostal muscle contraction alone. Diaphragm activation was achieved by phrenic nerve stimulation. Intercostal muscle activation was accomplished by electrical stimulation by using electrodes positioned epidurally at the T(2) spinal cord level. Stimulation parameters were adjusted to provide a constant tidal volume and inspiratory flow rate. During diaphragm (D) and intercostal muscle breathing (IC), mean arterial Po(2) was 97.1 +/- 2.1 and 88.1 +/- 2.7 Torr, respectively (P < 0.01). Arterial Pco(2) was lower during D than during IC (32.6 +/- 1.4 and 36.6 +/- 1.8 Torr, respectively; P < 0.05). During IC, oxygen consumption was also higher than that during D (0.13 +/- 0.01 and 0.09 +/- 0.01 l/min, respectively; P < 0.05). The alveolar-arterial oxygen difference was 11.3 +/- 1.9 and 7.7 +/- 1.0 Torr (P < 0.01) during IC and D, respectively. These results indicate that diaphragm breathing is significantly more efficient than intercostal muscle breathing. However, despite marked differences in the pattern of inspiratory muscle contraction, the distribution of ventilation remains well matched to pulmonary perfusion resulting in preservation of normal gas exchange.

Objective: To use diagnoses reported as present at admission in California hospital discharge abstract data to identify categories of comorbid disease and conditions related to aspiration pneumonia and to assess their association with hospital mortality., Study Design and Setting: The study population included all persons hospitalized in California from 1996 through 1999, with a principal diagnosis of aspiration pneumonia. Present at admission diagnoses representing comorbid diseases were separated from conditions closely related to aspiration pneumonia by a physician panel through a computer supported Delphi process. Multivariable logistic regression was used to assess the probability of hospital death after adjusting for these patient characteristics. The statistical performance of this method was compared to the performance of two independent methods for measuring comorbid disease. The practical significance of differences in statistical performance was assessed by comparing the estimated effects of age, race, and ethnicity after adjustments using each method., Results: Mortality risk adjustment using present at admission diagnoses resulted in substantially better statistical performance and in different measurements of the adjusted effects of age, race, and ethnicity., Conclusion: Reporting present at admission diagnoses in hospital discharge data yields meaningful improvements in hospital mortality risk adjustment.

Background and Purpose: The ischemic stroke population is heterogeneous. Even in balanced randomized trials, patient heterogeneity biases estimates of the treatment effect toward no effect when dichotomous end points are used. Risk adjustment statistically addresses some of the heterogeneity and can reduce bias in the treatment effect estimate. The purpose of this study was to estimate the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) tPA data set with and without adjustment for baseline differences., Methods: Using a prespecified predictive model, we calculated unadjusted and risk-adjusted odds ratios (ORs) for favorable outcome for the Barthel Index, National Institutes of Health Stroke Scale, and Glasgow Outcome Scale for the patients in the NINDS tPA stroke trial. To assess the importance of the difference, a new sample size was calculated through the use of the risk-adjusted analysis., Results: We analyzed 615 subjects. The ORs for the Barthel Index were 1.76 (unadjusted) and 2.04 (adjusted). The National Institutes of Health Stroke Scale and Glasgow Outcome Scale analyses also demonstrated increased ORs after adjustment. The estimated sample size required for the adjusted comparison was 13% smaller than the unadjusted sample., Conclusions: Risk adjustment in this data set suggests that the true treatment effect was larger than estimated by the unadjusted analysis. Stroke clinical trials should include prospective risk adjustment methodologies.

Background: Six multivariable models predicting 3-month outcome of acute ischemic stroke have been developed and internally validated previously. The purpose of this study was to externally validate the previous models in an independent data set., Summary of Report: We predicted outcomes for 299 patients with ischemic stroke who received placebo in the National Institute of Neurological Disorders and Stroke rt-PA trial. The model equations used 6 acute clinical variables and head CT infarct volume at 1 week as independent variables and 3-month National Institutes of Health Stroke Scale, Barthel Index, and Glasgow Outcome Scale as dependent variables. Previously developed model equations were used to forecast excellent and devastating outcome for subjects in the placebo tissue plasminogen activator data set. Area under the receiver operator characteristic curve was used to measure discrimination, and calibration charts were used to measure calibration. The validation data set patients were more severely ill (National Institutes of Health Stroke Scale and infarct volume) than the model development subjects. Area under the receiver operator characteristic curves demonstrated remarkably little degradation in the validation data set and ranged from 0.75 to 0.89. Calibration curves showed fair to good calibration., Conclusions: Our models have demonstrated excellent discrimination and acceptable calibration in an external data set. Development and validation of improved models using variables that are all available acutely are necessary.

Objective: To estimate the cost effectiveness of aggressive care for patients with nontraumatic coma., Design: Cost-effectiveness analysis., Setting: Five academic medical centers., Patients: Patients with nontraumatic coma enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). Patients with reversible metabolic causes of coma such as diabetic ketoacidosis or uremia were excluded., Measurements: We calculated the incremental cost effectiveness of continuing aggressive care vs. withholding cardiopulmonary resuscitation and ventilatory support after day 3 of coma. We estimated life expectancy based on up to 4.6 yrs of follow-up. Utilities (quality-of-life weights) were estimated using time-tradeoff questions. Costs were based on hospital fiscal data and Medicare data. Separate analyses were conducted for two prognostic groups based on five risk factors assessed on day 3 of coma: age > or = 70 yrs, abnormal brainstem response, absent verbal response, absent withdrawal to pain, and serum creatinine > or = 132.6 micromol/L (1.5 mg/dL)., Results: For the 596 patients studied, the median (25th, 75th percentile) age was 67 yrs (range, 55-77), and 52% were female. By 2 months after enrollment, 69% had died, 19% were severely disabled, 7% had survived without severe disability, and 4% had survived with unknown functional status. The incremental cost effectiveness of the more aggressive care strategy was $140,000 (1998 dollars) per quality-adjusted life year (QALY) for high-risk patients (3-5 risk factors, 93% 2-month mortality) and $87,000/QALY for low-risk patients (0-2 risk factors, 49% mortality). In sensitivity analyses, the incremental cost per QALY did not fall below $50,000/QALY, even with wide variation in our baseline estimates., Conclusions: Continuing aggressive care after day 3 of nontraumatic coma is associated with a high cost per QALY gained, especially for patients at high risk for poor outcomes. Earlier decisions to withhold life-sustaining treatments for patients with very poor prognoses may yield considerable cost savings.

Objective: The purpose of this study was to determine the accuracy of outpatient endometrial biopsy and saline sonohysterography for the evaluation of abnormal uterine bleeding., Study Design: Eligible participants included women aged 25 to 69 years who complained of persistent uterine bleeding, despite medical treatment. One hundred forty-four patients consented and were followed up prospectively: 1 patient did not successfully complete a saline sonohysterography because of discomfort, 143 patients underwent an endometrial biopsy and saline sonohysterography as outpatients, 113 patients underwent a definitive surgical intervention (hysteroscopy/dilatation and curettage or hysterectomy), 20 patients did not complete a gold standard measure, and 10 patients were lost to follow-up., Results: The combination of endometrial biopsy and saline sonohysterography for the 113 patients who completed the study had a sensitivity and specificity for the detection of abnormal pathologic features of 97.0% (95% CI, 88.6-99.5) and 70.2% (95% CI, 55.0-82.2) and a positive and negative predictive value of 82.1% (95% CI, 71.4-89.5) and 94.3% (95% CI, 79.6-99.0) compared with hysteroscopy/curettage or hysterectomy., Conclusion: The high sensitivity and high negative predictive value of saline sonohysterography combined with endometrial biopsy make this technique useful for the evaluation of abnormal uterine bleeding. It may allow some patients to avoid more invasive operative procedures; however, it is important to recognize the limitations in the predictive value of this diagnostic modality.

Purpose: To determine the accuracy of admission committee members' predictions regarding which applicants are likely to become generalists, and to determine which applicant characteristics are used and should be used in making these predictions., Method: Thirteen characteristics of each applicant who entered medical school in 1990-1993 and graduated in 1994-1997 were obtained from their applications. Committee members reviewed these characteristics and assigned a probability of each applicant's choosing a generalist career. Just before their graduation, the students were surveyed to ascertain their career plans. The relationships between the characteristics and career predictions were analyzed using regression models. A secondary analysis examined the relationship between the students' stated career preferences at matriculation and career plans at graduation., Results: The accuracy of the committee members' predictions was low. Predictions of generalist careers were significantly related to seven applicant characteristics: rural legal residence, gender (women), lower science grades, lower MCAT science scores, lower levels of parents' education, no reported research activity, and higher levels of community service. In contrast, the students' actual generalist career plans at graduation were significantly related only to gender (women) and higher levels of community service. In the secondary analysis, applicants' stated career preferences at matriculation were the strongest predictor of their having generalist career plans at graduation., Conclusions: Admission committee members often made inaccurate predictions about applicants' career plans. This may be because they based their judgments on applicants' characteristics that were not significantly related to the students' career plans at graduation.

Background: As the incidence of diabetic nephropathy increases, especially in minority populations, more simultaneous pancreas-kidney (SPK) transplants are being performed both in the United States and worldwide. The role of matching on SPK outcomes and organ allocation remains controversial. The purpose of this analysis was to determine the influence of HLA matching using currently employed criteria on 5-year SPK graft survival., Methods: We performed an analysis of all 3,316 SPK transplants performed in the United States reported to the United Network for Organ Sharing (UNOS) between December 31, 1988 and December 31, 1994. Kaplan-Meier unadjusted 1- and 5-year graft survival with log rank comparisons and Cox multivariable regression models that adjusted for 12 confounding variables were used to analyze the influence of HLA matching on outcomes., Results: Despite low-grade HLA or DR matching or high levels of common reactive groups (CREG) mismatching, 1- and 5-year allograft survival rates were 90% and 78% for kidney, and 85% and 75% for pancreas transplantation., Conclusions: SPK transplantation is associated with excellent outcomes independent of the level of HLA matching. These data support the hypothesis that SPK transplants need not be allocated based on matching criteria, thus minimizing organ ischemia time and promoting a more racially equitable allocation for SPKs in the US today.

Background & Aims: The cost-utility of infliximab is unknown. The aim of this study was to determine the incremental cost-utility (CU(inc)) of medical therapy for Crohn's disease (CD) perianal fistula., Methods: A Markov model was used to simulate a 1-year treatment period with the following: 6-mercaptopurine and metronidazole [6MP/met] (comparator), 3 infliximab infusions + 6MP/met as second-line therapy (intervention I), infliximab with episodic reinfusion (intervention II), and 6MP/met + infliximab as second-line therapy (intervention III). Utilities were elicited from patients with CD and healthy individuals by standard gamble, and costs were obtained from hospital billing data. Uncertainty was assessed by sensitivity analysis., Results: All strategies had similar effectiveness. Interventions I, II, and III were slightly more effective, but also more costly than 6MP/met (Intervention I: CU(inc) = $355,450/quality-adjusted life-years [QALY]; Intervention II: CU(inc) = $360,900/QALY; Intervention III: CU(inc) = $377,000/QALY). If the cost of infliximab were reduced to $304 per infusion, the CU(inc) for intervention II would be $54,050/QALY., Conclusions: Based on available data, all strategies had similar effectiveness in our model, but infliximab was much more expensive than 6MP/met. The incremental benefit of infliximab for treating CD perianal fistulae over a 1-year period may not justify the higher cost. Prospective studies directly comparing 6MP/met and infliximab are warranted.