Nucleated red blood cells, critical illness survivors and postdischarge outcomes: a cohort study.

BACKGROUND: Little is known about risk factors associated with out-of-hospital outcomes in survivors of critical illness. We hypothesized that the presence of nucleated red blood cells in patients who survived critical care would be associated with adverse outcomes following hospital discharge. METHODS: We performed a two-center observational cohort study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. All data were obtained from the Research Patient Data Registry at Partners HealthCare. We studied 2878 patients, age ≥ 18 years, who received critical care between 2011 and 2015 and survived hospitalization. The exposure of interest was nucleated red blood cells occurring from 2 days prior to 7 days after critical care initiation. The primary outcome was mortality in the 90 days following hospital discharge. Secondary outcome was unplanned 30-day hospital readmission. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both nucleated red blood cells and outcome. Adjustment included age, race (white versus nonwhite), gender, Deyo-Charlson Index, patient type (medical versus surgical), sepsis and acute organ failure. RESULTS: In patients who received critical care and survived hospitalization, the absolute risk of 90-day postdischarge mortality was 5.9%, 11.7%, 15.8% and 21.9% in patients with 0/µl, 1-100/µl, 101-200/µl and more than 200/µl nucleated red blood cells respectively. Nucleated red blood cells were a robust predictor of postdischarge mortality and remained so following multivariable adjustment. The fully adjusted odds of 90-day postdischarge mortality in patients with 1-100/µl, 101-200/µl and more than 200/µl nucleated red blood cells were 1.77 (95% CI, 1.23-2.54), 2.51 (95% CI, 1.36-4.62) and 3.72 (95% CI, 2.16-6.39) respectively, relative to patients without nucleated red blood cells. Further, the presence of nucleated red blood cells is a significant predictor of the odds of unplanned 30-day hospital readmission. CONCLUSION: In critically ill patients who survive hospitalization, the presence of nucleated red blood cells is a robust predictor of postdischarge mortality and unplanned hospital readmission.

Long term mortality in critically ill burn survivors.

INTRODUCTION: Little is known about long term survival risk factors in critically ill burn patients who survive hospitalization. We hypothesized that patients with major burns who survive hospitalization would have favorable long term outcomes. METHODS: We performed a two center observational cohort study in 365 critically ill adult burn patients who survived to hospital discharge. The exposure of interest was major burn defined a priori as >20% total body surface area burned [TBSA]. The modified Baux score was determined by age + %TBSA+ 17(inhalational injury). The primary outcome was all-cause 5year mortality based on the US Social Security Administration Death Master File. Adjusted associations were estimated through fitting of multivariable logistic regression models. Our final model included adjustment for inhalational injury, presence of 3rd degree burn, gender and the acute organ failure score, a validated ICU risk-prediction score derived from age, ethnicity, surgery vs. medical patient type, comorbidity, sepsis and acute organ failure covariates. Time-to-event analysis was performed using Cox proportional hazard regression. RESULTS: Of the cohort patients studied, 76% were male, 29% were non white, 14% were over 65, 32% had TBSA >20%, and 45% had inhalational injury. The mean age was 45, 92% had 2nd degree burns, 60% had 3rd degree burns, 21% received vasopressors, and 26% had sepsis. The mean TBSA was 20.1%. The mean modified Baux score was 72.8. Post hospital discharge 5year mortality rate was 9.0%. The 30day hospital readmission rate was 4%. Patients with major burns were significantly younger (41 vs. 47 years) had a significantly higher modified Baux score (89 vs. 62), and had significantly higher comorbidity, acute organ failure, inhalational injury and sepsis (all P<0.05). There were no differences in gender and the acute organ failure score between major and non-major burns. In the multivariable logistic regression model, major burn was associated with a 3 fold decreased odds of 5year post-discharge mortality compared to patients with TBSA<20% [OR=0.29 (95%CI 0.11-0.78; P=0.014)]. The adjusted model showed good discrimination [AUC 0.81 (95%CI 0.74-0.89)] and calibration (Hosmer-Lemeshow χ2 P=0.67). Cox proportional hazard multivariable regression modeling, adjusting for inhalational injury, presence of 3rd degree burn, gender and the acute organ failure score, showed that major burn was predictive of lower mortality following hospital admission [HR=0.34 (95% CI 0.15-0.76; P=0.009)]. The modified Baux score was not predictive for mortality following hospital discharge [OR 5year post-discharge mortality=1.00 (95%CI 0.99-1.02; P=0.74); HR for post-discharge mortality=1.00 (95% CI 0.99-1.02; P=0.55)]. CONCLUSIONS: Critically ill patients with major burns who survive to hospital discharge have decreased 5year mortality compared to those with less severe burns. ICU Burn unit patients who survive to hospital discharge are younger with less comorbidities. The observed relationship is likely due to the relatively higher physiological reserve present in those who survive a Burn ICU course which may provide for a survival advantage during recovery after major burn.

Hypernatremia at Hospital Discharge and Out of Hospital Mortality Following Primary Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: In patients with intracerebral hemorrhage (ICH), it is not clear if hypernatremia is merely a marker of disease severity or if elevated sodium levels are harmful. We hypothesized that hypernatremia at hospital discharge in primary ICH patients would be associated with increased mortality following discharge. METHODS: We performed a two-center observational study of critically ill ICH patients in Boston. We studied 5100 patients, age ≥18 years, who were diagnosed with ICH (ICD-9 code 431), received medical or surgical critical care between 1997 and 2011 and survived hospitalization. The exposure of interest was serum sodium within 24 h of hospital discharge, categorized as Na ≤ 145 mmol/L and Na > 145 mmol/L. The primary outcome was 30-day post-discharge mortality. Odds ratios were estimated by logistic regression models adjusted for age, race, gender, Deyo-Charlson Index, patient type (medical versus surgical) and sepsis. RESULTS: In ICH patients who received critical care and survived hospitalization, the serum sodium at discharge was a predictor of post-discharge mortality. Patients with a discharge Na > 145 mmol/L have an OR for mortality in the 30 days following hospital discharge of 1.82 (95 %CI 1.38-2.38; P < 0.001) and an adjusted OR of 1.87 (95 %CI 1.40-2.48; P < 0.001) both relative to patients with a discharge Na ≤ 145 mmol/L. The adjusted model showed good discrimination AUC 0.77 (95 %CI 0.74-0.79) and calibration (Hosmer-Lemeshow χ (2) P = 0.68). CONCLUSIONS: In critically ill ICH patients who survive hospitalization, hypernatremia at the time of discharge is a robust predictor of post-discharge mortality.

Association of Model for End-Stage Liver Disease Score and Mortality in Trauma Patients With Chronic Liver Disease.

IMPORTANCE: The Model for End-Stage Liver Disease (MELD) score is predictive of trauma outcomes. OBJECTIVE: To determine whether a decrease in MELD score is associated with improved mortality in critically ill trauma patients. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective registry study of critically ill trauma patients 18 years or older with chronic liver disease treated between August 3, 1998, and January 5, 2012, at 2 level I trauma centers in Boston, Massachusetts. The consecutive sample included 525 patients (male, 373 [71.0%]; white, 399 [76.0%]; mean [SD] age, 55.0 [12.4] years). EXPOSURES: Change in MELD score from intensive care unit (ICU) admission to 48 to 72 hours later. MAIN OUTCOMES AND MEASURES: Thirty-day all-cause mortality. RESULTS: The mean (SD) MELD score at ICU admission was 19.3 (9.7). The 30-day mortality was 21.9%. The odds of 30-day mortality with a change in MELD score of less than -2, -2 to -1, +1 to +4, and greater than +4 were 0.23 (95% CI, 0.10-0.51), 0.30 (95% CI, 0.10-0.85), 0.57 (95% CI, 0.27-1.20), and 1.31 (95% CI, 0.58-2.96), respectively, relative to a change in MELD score of 0 and adjusted for age, sex, race, Charlson/Deyo Index, sepsis, number of acute organ failures, International Classification of Diseases, Ninth Revision-based injury severity score, and ICU admission MELD score. CONCLUSIONS AND RELEVANCE: A decrease in MELD score within 72 hours of ICU admission is associated with improved mortality.

Acute Kidney Injury After Craniotomy Is Associated With Increased Mortality: A Cohort Study.

BACKGROUND: Acute kidney injury (AKI) is a serious postoperative complication. OBJECTIVE: To determine whether AKI in patients after craniotomy is associated with heightened 30-day mortality. METHODS: We performed a 2-center, retrospective cohort study of 1656 craniotomy patients who received critical care between 1998 and 2011. The exposure of interest was AKI defined as meeting RIFLE (Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease) class risk, injury, and failure criteria, and the primary outcome was 30-day mortality. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both AKI and mortality. Additionally, mortality in craniotomy patients with AKI was analyzed with a risk-adjusted Cox proportional hazards regression model and propensity score matching as a sensitivity analysis. RESULTS: The incidences of RIFLE class risk, injury, and failure were 5.7%, 2.9%, and 1.3%, respectively. The odds of 30-day mortality in patients with RIFLE class risk, injury, or failure fully adjusted were 2.79 (95% confidence interval [CI], 1.76-4.42), 7.65 (95% CI, 4.16-14.07), and 14.41 (95% CI, 5.51-37.64), respectively. Patients with AKI experienced a significantly higher risk of death during follow-up; hazard ratio, 1.82 (95% CI, 1.34-2.46), 3.37 (95% CI, 2.36-4.81), and 5.06 (95% CI, 2.99-8.58), respectively, fully adjusted. In a cohort of propensity score-matched patients, RIFLE class remained a significant predictor of 30-day mortality. CONCLUSION: Craniotomy patients who suffer postoperative AKI are among a high-risk group for mortality. The severity of AKI after craniotomy is predictive of 30-day mortality. ABBREVIATIONS: AKI, acute kidney injuryAPACHE II, Acute Physiology and Chronic Health Evaluation IICI, confidence intervalCPT, Current Procedural TerminologyICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical ModificationRIFLE, risk, injury, failure, loss of kidney function, and end-stage kidney diseaseRPDR, Research Patient Data Registry.

Increases in pre-hospitalization serum 25(OH)D concentrations are associated with improved 30-day mortality after hospital admission: A cohort study.

CONTEXT: Pre-hospital vitamin D status may be a modifiable risk factor for all-cause mortality among hospitalized patients. OBJECTIVE: To examine the association between increases in serum 25-hydroxyvitamin D [25(OH)D] levels during the year before hospitalization and risk of 30-day all-cause mortality after hospital admission. DESIGN: Retrospective cohort study. SETTING: Two Boston teaching hospitals. PATIENTS OR OTHER PARTICIPANTS: We studied 4344 adults hospitalized between 1993 and 2011 who had serum 25(OH)D concentrations measured at least twice within 7-365 days before the index hospitalization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The exposure of interest was change in pre-hospital serum 25(OH)D concentrations. The main outcome was 30-day all-cause mortality. We used mixed-effects logistic regression to describe how 30-day mortality differed with changes in pre-hospital 25(OH)D concentrations. Additionally, the odds of 30-day mortality in patients with pre-hospital 25(OH)D increases of ≥10 ng/mL was compared to that of patients with increases of <10 ng/mL. RESULTS: In a mixed-effect logistic regression model adjusted for age, gender, race, type (medical/surgical), Deyo-Charlson Index, creatinine and hematocrit, 30-day all-cause mortality rate was 8% (95%CI: 1-15) lower for each 10 ng/mL increase in pre-hospital 25(OH)D (P = 0.025) compared with the 30-day all-cause mortality rate in the entire cohort. In an adjusted logistic regression model, absolute changes of ≥10 ng/mL in patients with initial 25(OH)D concentrations < 20 ng/mL (n = 1944) decreased the odds of 30-day all-cause mortality by 48% (adjusted OR 0.52; 95%CI 0.30-0.93; P = 0.026) compared to patients with changes of <10 ng/mL. CONCLUSIONS: In patients with initial 25(OH)D < 20 ng/mL, subsequent improvements in vitamin D status before hospitalization are associated with decreased odds of 30-day all-cause mortality after hospital admission. A causal relation may not be inferred from this observational study.

Association between blood alcohol concentration and mortality in critical illness.

OBJECTIVE: In animal models of renal, intestinal, liver, cardiac, and cerebral ischemia, alcohol exposure is shown to reduce ischemia-reperfusion injury. Inpatient mortality of trauma patients is shown to be decreased in a dose-dependent fashion relative to blood alcohol concentration (BAC) at hospital admission. In this study, we examined the association between BAC at hospital admission and risk of 30-day mortality in critically ill patients. DESIGN: We performed a 2-center observational study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. SETTING: Medical and surgical intensive care units in 2 teaching hospitals in Boston, Massachusetts. PATIENTS: We studied 11850 patients, 18 years or older, who received critical care between 1997 and 2007. The exposure of interest was the BAC determined in the first 24 hours of hospital admission and categorized a priori as BAC less than 10 mg/dL (below level of detection), 10 to 80 mg/dL, 80 to 160 mg/dL, and greater than 160 mg/dL. The primary outcome was all-cause mortality in the 30 days after critical care initiation. Secondary outcomes included 90- and 365-day mortality after critical care initiation. Mortality was determined using the US Social Security Administration Death Master File, and 365-day follow-up was present in all cohort patients. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both BAC and mortality. Adjustment included age, sex, race (white or nonwhite), type (surgical vs medical), Deyo-Charlson index, sepsis, acute organ failure, trauma, and chronic liver disease. RESULTS: Thirty-day mortality of the cohort was 13.7%. Compared to patients with BAC levels less than 10 mg/dL, patients with levels greater than or equal to 10 mg/dL had lower odds of 30-day mortality; for BAC levels 10 to 79.9 mg/dL, the OR was 0.53 (95% confidence interval [CI], 0.40-0.70); for BAC levels 80 to 159.9 mg/dL, it was 0.36 (95% CI, 0.26-0.49); and for BAC levels greater than or equal to 160 mg/dL, it was 0.35 (95% CI, 0.27-0.44). After multivariable adjustment, the OR of 30-day mortality was 0.97 (0.72-1.31), 0.79 (0.57-1.10), and 0.69 (0.54-0.90), respectively. When the cohort was analyzed with sepsis as the outcome of interest, the multivariable adjusted odds of sepsis in patients with BAC 80 to 160 mg/dL or greater than 160 mg/dL were 0.72 (0.50-1.04) or 0.68 (0.51-0.90), respectively, compared to those with BAC less than 10 mg/dL. In a subset of patients with blood cultures drawn (n=4065), the multivariable adjusted odds of bloodstream infection in patients with BAC 80 to 160 mg/dL or greater than 160 mg/dL were 0.53 (0.27-1.01) or 0.49 (0.29-0.83), respectively, compared to those with BAC less than 10 mg/dL. CONCLUSIONS: Analysis of 11850 adult patients showed that having a detectable BAC at hospitalization was associated with significantly decreased odds of 30-day mortality after critical care. Furthermore, BAC greater than 160 mg/dL is associated with significantly decreased odds of developing sepsis and bloodstream infection.

Association between prehospital vitamin D status and incident acute respiratory failure in critically ill patients: a retrospective cohort study.

OBJECTIVE: We hypothesise that low 25-hydroxyvitamin D (25(OH)D) levels before hospitalisation are associated with increased risk of acute respiratory failure. DESIGN: Retrospective cohort study. SETTING: Medical and Surgical Intensive care units of two Boston teaching hospitals. PATIENTS: 1985 critically ill adults admitted between 1998 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was prehospital serum 25(OH)D categorised as ≤10 ng/mL, 11-19.9 ng/mL, 20-29.9 ng/mL and ≥30 ng/mL. The primary outcome was acute respiratory failure excluding congestive heart failure determined by International Classification of Diseases Ninth Edition (ICD-9) coding and validated against the Berlin Definition of acute respiratory sistress syndrome. Association between 25(OH)D and acute respiratory failure was assessed using logistic regression, while adjusting for age, race, sex, Deyo-Charlson Index and patient type (medical vs surgical). In the cohort, the mean age was 63 years, 45% were male and 80% were white; 25(OH)D was ≤10 ng/mL in 8% of patients, 11-19.9 ng/mL in 24%, 20-29.9 ng/mL in 24% and ≥30 ng/mL in 44% of patients. Eighteen per cent (n=351) were diagnosed with acute respiratory failure. Compared to patients with 25(OH)D ≥30 ng/mL, patients with lower 25(OH)D levels had significantly higher adjusted odds of acute respiratory failure (≤10 ng/mL, OR=1.84 (95% CI 1.22 to 2.77); 11-19.9 ng/mL, OR=1.60 (95% CI 1.19 to 2.15); 20-29.9 ng/mL, OR=1.37 (95% CI 1.01 to 1.86)). CONCLUSIONS: Prehospital 25(OH)D was associated with the risk of acute respiratory failure in our critically ill patient cohort.

Association between pre-hospital vitamin D status and hospital-acquired new-onset delirium.

The goal of the present study was to determine whether pre-hospital 25-hydroxyvitamin D (25(OH)D) levels are associated with the risk of hospital-acquired new-onset delirium (HANOD). We performed a retrospective cohort study of 4508 adult inpatients at two teaching hospitals in Boston from 1993 to 2006. All patients had 25(OH)D levels measured before hospital admission. The main outcome measure was HANOD, defined as the onset of delirium during an acute care hospitalisation. Patients with a history of delirium or dementia, or those with a diagnosis of delirium or dementia upon acute care hospitalisation were excluded from the analysis. To test the association of pre-hospital 25(OH)D levels with HANOD, we constructed a multivariable logistic regression model to adjust for clinically relevant covariates. Among our patient cohort, the mean 25(OH)D level was 22 (sd 13) ng/ml and approximately 4% of patients met the criteria for HANOD. Following adjustment for age, sex, race (non-white v. white), patient type (medical v. surgical) and Deyo-Charlson Index, patients with 25(OH)D levels < 10, 10-19·9 and 20-29·9 ng/ml had higher odds of HANOD than patients with 25(OH)D levels ≥ 30 ng/ml: OR 2·15 (95% CI 1·32, 3·50), OR 1·54 (95% CI 0·98, 2·43) and OR 1·23 (95% CI, 0·76, 1·99), respectively. These data support the rationale for randomised, controlled trials to test the role of vitamin D supplementation in the prevention of HANOD.

Derivation and validation of the acute organ failure score to predict outcome in critically ill patients: a cohort study.

OBJECTIVES: Prediction models for ICU mortality rely heavily on physiologic variables that may not be available in large retrospective studies. An alternative approach when physiologic variables are absent stratifies mortality risk by acute organ failure classification. DESIGN: Retrospective cohort study. SETTING: Two large teaching hospitals in Boston, MA. SUBJECTS: Ninety-two thousand eight hundred eighty-six patients aged 18 years old or older admitted between November 3, 1997, and February 25, 2011, who received critical care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The derivation cohort consisted of 35,566 patients from Brigham and Women's Hospital, and the validation cohort comprised 57,320 patients from Massachusetts General Hospital. Acute organ failure was determined for each patient based on International Classification of Diseases, 9th Revision, Clinical Modification code combinations. The main outcome measure was 30-day mortality. A clinical prediction model was created based on a logistic regression model describing the risk of 30-day mortality as a function of age, medical versus surgical patient type, Deyo-Charlson index, sepsis, and type acute organ failure (respiratory, renal, hepatic, hematologic, metabolic, and neurologic) after ICU admission. We computed goodness-of fit statistics and c-statistics as measures of model calibration and 30-day mortality discrimination, respectively. Thirty-day mortality occurred in 5,228 of 35,566 patients (14.7%) assigned to the derivation cohort. The clinical prediction model was predictive for 30-day mortality. The c-statistic for the clinical prediction model was 0.7447 (95% CI, 0.74-0.75) in the derivation cohort and 0.7356 (95% CI, 0.73-0.74) in the validation cohort. For both the derivation and validation cohorts, the Hosmer-Lemeshow chi-square p values indicated good model fit. In a smaller cohort of 444 patients with Acute Physiologic and Chronic Health Evaluation II scores determined, differences in model discrimination of 30-day mortality between the clinical prediction model and Acute Physiologic and Chronic Health Evaluation II were not significant (chi-square=0.76; p=0.38). CONCLUSIONS: An acute organ failure-based clinical prediction model shows good calibration and discrimination for 30-day mortality in the critically ill. The clinical prediction model compares favorably to Acute Physiologic and Chronic Health Evaluation II score in the prediction of 30-day mortality in the critically ill. This score may be useful for severity of illness risk adjustment in observational studies where physiologic data are unavailable.

The association of acute kidney injury in the critically ill and postdischarge outcomes: a cohort study*.

OBJECTIVE: Hospital readmissions contribute significantly to the cost of inpatient care and are targeted as a marker for quality of care. Little is known about risk factors associated with hospital readmission in survivors of critical illness. We hypothesized that acute kidney injury in patients who survived critical care would be associated with increased risk of 30-day postdischarge hospital readmission, postdischarge mortality, and progression to end-stage renal disease. DESIGN: Two center observational cohort study. SETTING: Medical and surgical ICUs at the Brigham and Women's Hospital and the Massachusetts General Hospital in Boston, Massachusetts. PATIENTS: We studied 62,096 patients, 18 years old and older, who received critical care between 1997 and 2012 and survived hospitalization. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: : All data was obtained from the Research Patient Data Registry at Partners HealthCare. The exposure of interest was acute kidney injury defined as meeting Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease Risk, Injury or Failure criteria occurring 3 days prior to 7 days after critical care initiation. The primary outcome was hospital readmission in the 30 days following hospital discharge. The secondary outcome was mortality in the 30 days following hospital discharge. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both acute kidney injury and readmission status. Adjustment included age, race (white vs nonwhite), gender, Deyo-Charlson Index, patient type (medical vs surgical) and sepsis. Additionally, long-term progression to End Stage Renal Disease in patients with acute kidney injury was analyzed with a risk-adjusted Cox proportional hazards regression model. The absolute risk of 30-day readmission was 12.3%, 19.0%, 21.2%, and 21.1% in patients with No Acute Kidney Injury, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Injury, and Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Failure, respectively. In patients who received critical care and survived hospitalization, acute kidney injury was a robust predictor of hospital readmission and post-discharge mortality and remained so following multivariable adjustment. The odds of 30-day post-discharge hospital readmission in patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, or Failure fully adjusted were 1.44 (95% CI, 1.25-1.66), 1.98 (95% CI, 1.66-2.36), and 1.55 (95% CI, 1.26-1.91) respectively, relative to patients without acute kidney injury. Further, the odds of 30-day post-discharge mortality in patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, or Failure fully adjusted per our primary analysis were 1.39 (95% CI, 1.28-1.51), 1.46 (95% CI, 1.30-1.64), and 1.42 (95% CI, 1.26-1.61) respectively, relative to patients without acute kidney injury. The addition of the propensity score to the multivariable model did not change the point estimates significantly. Finally, taking into account age, gender, race, Deyo-Charlson Index, and patient type, we observed a relationship between acute kidney injury and development of end-stage renal disease. Patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, Failure experienced a significantly higher risk of end-stage renal disease during follow-up than patients without acute kidney injury (hazard ratio, 2.03; 95% CI, 1.56-2.65; hazard ratio, 3.99; 95% CI, 3.04-5.23; hazard ratio, 10.40; 95% CI, 8.54-12.69, respectively). CONCLUSIONS: Patients who suffer acute kidney injury are among a high-risk group of ICU survivors for adverse outcomes. In patients treated with critical care who survive hospitalization, acute kidney injury is a robust predictor of subsequent unplanned hospital readmission. In critical illness survivors, acute kidney injury is also associated with the odds of 30-day postdischarge mortality and the risk of subsequent end-stage renal disease.

Association between prehospital vitamin D status and hospital-acquired Clostridium difficile infections.

OBJECTIVE: To investigate whether preadmission 25-hydroxyvitamin D (25(OH)D) levels are associated with the risk of hospital-acquired Clostridium difficile infection (HACDI). MATERIALS AND METHODS: Our retrospective cohort study focused on 568 adult patients from 2 Boston teaching hospitals between August 1993 and November 2006. All patients had 25(OH)D levels measured before hospitalization and were at risk for HACDI (defined as the presence of C difficile toxin A or B in stool samples obtained >48 hours after hospitalization). We performed multivariable regression analyses to test the association of prehospital 25(OH)D levels with HACDI while adjusting for clinically relevant covariates. RESULTS: In these 568 patients, mean (SD) 25(OH)D level was 19 (12) ng/mL, and 11% of patients met criteria for incident HACDI. Following adjustment for age, sex, race (nonwhite vs white), patient type (medical vs surgical), and Deyo-Charlson index, patients with 25(OH)D levels <10 ng/mL had higher odds of HACDI (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.01-8.34) compared with patients with 25(OH)D levels ≥30 ng/mL. When patients with HACDI were analyzed relative to a larger patient cohort without HACDI (n = 5047), those with 25(OH)D levels <10 ng/mL (OR, 4.96; 95% CI, 1.84-13.38) and 10-19.9 ng/mL (OR, 3.36; 95% CI, 1.28-8.85) had higher adjusted odds of HACDI compared with patients with 25(OH)D levels ≥30 ng/mL. CONCLUSIONS: In our cohort of adult patients, vitamin D status before hospital admission was inversely associated with the risk of developing HACDI. These data support the need for randomized, controlled trials to test the role of vitamin D supplementation to prevent HACDI.

Evidence for a U-shaped relationship between prehospital vitamin D status and mortality: a cohort study.

OBJECTIVE: The objective of the study was to examine the association between prehospital serum 25-hydroxyvitamin D [25(OH)D]and the risk of mortality after hospital admission. DESIGN: We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011. SETTING: The study was conducted at two Boston teaching hospitals. PATIENTS: A total of 24,094 adult inpatients participated in the study. INTERVENTION: There was no intervention. MEASUREMENTS: All patients had serum 25(OH)D measured before hospitalization. The exposure of interest was 25(OH)D categorized as less than 10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 30-49.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and 70 ng/mL or greater. The main outcome measure was 90-day mortality. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression with inclusion of potential confounders. RESULTS: After adjustment for age, gender, race (white vs nonwhite), patient type (surgical vs medical), season of 25(OH)D draw, and the Deyo-Charlson index, patients with 25(OH)D levels less than 30 ng/mL or 60 ng/mL or greater had higher odds of 90-day mortality compared with patients with levels of 30-49.9 ng/mL [adjusted OR (95% confidence interval) for 25(OH)D <10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and ≥70 ng/mL was 2.01 (1.68-2.40), 1.89 (1.64-2.18), 1.34 (1.16-1.56), 0.94 (0.69-1.26), 1.52 (1.03-2.25), and 1.69 (1.09-2.61), respectively, compared with patients with 25(OH)D levels 30-49.9 ng/mL]. LIMITATIONS: A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study. CONCLUSIONS: Analysis of 24 094 adult patients showed that 25(OH)D levels less than 20 ng/mL and 60 ng/mL or greater before hospitalization were associated with an increased odds of 90-day mortality. Although previous reports have suggested an association between low vitamin D status and mortality, these data raise the issue of potential harm from high serum 25(OH)D levels, provide a rationale for an upper limit to supplementation, and emphasize the need for caution in the use of extremely high doses of vitamin D among patients.

The association of red cell distribution width at hospital discharge and out-of-hospital mortality following critical illness*.

OBJECTIVES: Red cell distribution width is associated with mortality and bloodstream infection risk in the critically ill. In hospitalized patients with critical illness, it is not known if red cell distribution width can predict subsequent risk of all-cause mortality following hospital discharge. We hypothesized that an increase in red cell distribution width at hospital discharge in patients who survived to discharge following critical care would be associated with increased postdischarge mortality. DESIGN: Two-center observational cohort study SETTING: : All medical and surgical ICUs at the Brigham and Women's Hospital and Massachusetts General Hospital. PATIENTS: We studied 43,212 patients, who were 18 years old or older and received critical care between 1997 and 2007 and survived hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was red cell distribution width within 24 hours of hospital discharge and categorized a priori in quintiles as less than or equal to 13.3%, 13.3-14.0%, 14.0-14.7%, 14.7-15.8%, and more than 15.8%. The primary outcome was all-cause mortality in the 30 days following hospital discharge. Secondary outcomes included 90-day and 365-day mortality following hospital discharge. Mortality was determined using the U.S. Social Security Administration Death Master File, and 365-day follow-up was present in all cohort patients. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both red cell distribution width and mortality. Adjustment included age, race, gender, Deyo-Charlson Index, patient type (medical vs surgical), sepsis, and number of organs with acute failure. In patients who received critical care and survived hospitalization, the discharge red cell distribution width was a robust predictor of all-cause mortality and remained so following multivariable adjustment. Patients with a discharge red cell distribution width of 14.0-14.7%, 14.7-15.8%, and more than 15.8% have an odds ratio for mortality in the 30 days following hospital discharge of 2.86 (95% CI, 2.25-3.62), 4.57 (95% CI, 3.66-5.72), and 8.80 (95% CI, 7.15-10.83), respectively, all relative to patients with a discharge red cell distribution width less than or equal to 13.3%. Following multivariable adjustment, patients with a discharge red cell distribution width of 14.0-14.7%, 14.7-15.8%, and more than 15.8% have an odds ratio for mortality in the 30 days following hospital discharge of 1.63 (95% CI, 1.27-2.07), 2.36 (95% CI, 1.87-2.97), and 4.18 (95% CI, 3.36-5.20), respectively, all relative to patients with a discharge red cell distribution width less than or equal to 13.3%. Similar significant robust associations post multivariable adjustments are seen with death by days 90 and 365 postdischarge. Estimating the receiver-operating characteristic area under the curve shows that discharge red cell distribution width has moderate discriminative power for mortality 30 days following hospital discharge (area under the curve = 0.70; SE 0.006; 95% CI, 0.69-0.71; p < 0.0001). CONCLUSION: In patients treated with critical care who survive hospitalization, an elevated red cell distribution width at the time of discharge is a robust predictor of subsequent all-cause patient mortality. Increased discharge red cell distribution width likely reflects the presence of proinflammatory state, oxidative stress, arterial underfilling, or a combination, thereof which may explain the observed impact on patient survival following discharge. Elevated red cell distribution width at hospital discharge may identify ICU survivors who are at risk for adverse outcomes following hospital discharge.

Diabetes mellitus and community-acquired bloodstream infections in the critically ill.

INTRODUCTION: Community-acquired bloodstream infections have not been studied related to diabetes mellitus in the critically ill. HYPOTHESIS: We hypothesized that the diagnosis of diabetes mellitus and poor chronic glycemic control would increase the risk of community-acquired bloodstream infections (CA-BSIs) in the critically ill. METHODS: We performed an observational cohort study between 1998 and 2007 in 2 teaching hospitals in Boston, Massachusetts. We studied 2551 patients 18 years or older, who received critical care within 48 hours of admission and had blood cultures obtained within 48 hours of admission. The exposure of interest was diabetes mellitus defined by International Classification of Diseases, Ninth Revision, Clinical Modification, code 250.xx in outpatient or inpatient records. The primary end point was CA-BSI (<48 hours of hospital admission). Patients with a single coagulase-negative Staphylococcus positive blood culture were not considered to have bloodstream infection. Associations between diabetes groups and bloodstream infection were estimated by bivariable and multivariable logistic regression models. Subanalyses included evaluation of the association between hemoglobin A1c (HbA1c) and bloodstream infection, diabetes and risk of sepsis, and the proportion of the association between diabetes and CA-BSI that was mediated by acute glycemic control. RESULTS: Diabetes is a predictor of CA-BSI. After adjustment for age, sex, race, patient type (medical vs surgical), and acute organ failure, the risk of bloodstream infection was significantly higher in patients with diabetes (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.10-1.82; P = .006) relative to patients without diabetes. The adjusted risk of bloodstream infection was increased in patients with HbA1c of 6.5% or higher (OR, 1.31; 95% CI, 1.04-1.65; P = .02) relative to patients with HbA1c less than 6.5%. Furthermore, the adjusted risk of sepsis was significantly higher in patients with diabetes (OR, 1.26; 95% CI, 1.04-1.54; P = .02) relative to patients without diabetes. Maximum glucose did not significantly mediate the relationship between diabetes mellitus diagnosis and CA-BSI. CONCLUSIONS: A diagnosis of diabetes mellitus and HbA1c of 6.5% or higher is associated with the risk of CA-BSI in the critically ill.

Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill.

OBJECTIVE: We hypothesized that deficiency in 25-hydroxyvitamin D prior to hospital admission would be associated with sepsis in the critically ill. DESIGN: Two-center observational study of patients treated in medical and surgical ICUs. SETTING: Two hundred nine medical and surgical intensive care beds in two teaching hospitals in Boston, MA. PATIENTS: Three thousand three hundred eighty-six patients, 18 years old or older, in whom 25-hydroxyvitamin D was measured prior to hospitalization between 1998 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: : Preadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (≤ 15 ng/mL), insufficiency (15-30 ng/mL), and sufficiency (≥ 30 ng/mL). The primary outcome was sepsis as defined by International Classification of Diseases, 9th Edition, Clinical Modification and validated by the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine, American College of Chest Physicians, American Thoracic Society, and Surgical Infection Society international sepsis definitions conference guidelines. Logistic regression examined the presence of sepsis 3 days prior to critical care initiation to 7 days after critical care initiation. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for the risk of sepsis. In the full cohort, 25-hydroxyvitamin D deficiency is a significant predictor for the risk of International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Deyo-Charlson index (adjusted odds ratio, 1.51 [95% CI, 1.17-1.94]; p = 0.001) relative to patients with 25-hydroxyvitamin D sufficiency. In a subset of cohort patients enriched for those with International Classification of Diseases, 9th Edition, Clinical Modification-diagnosed sepsis (n = 444), preadmission 25-hydroxyvitamin D deficiency is a significant predictor for the risk of conference guideline-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Acute Physiology and Chronic Health Evaluation II (adjusted odds ratio, 2.05 [95% CI, 1.19-3.52]; p = 0.009) relative to patients with 25-hydroxyvitamin D sufficiency. Furthermore, in cohort patients with International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis (n = 568), the multivariable adjusted risk of 90-day mortality was 1.6-fold higher in those with preadmission 25-hydroxyvitamin D values in the insufficient and deficient range, compared with those with preadmission vitamin D sufficiency (adjusted odds ratio, 1.63 [95% CI, 1.11-2.39]; p = 0.01). CONCLUSION: 25-hydroxyvitamin D deficiency prior to hospital admission is a significant predictor of sepsis in the critically ill. Additionally, patients with sepsis who are not vitamin D sufficient have an increased risk of mortality following critical care initiation.

Outcome of recommendations for radiographic follow-up of pneumonia on outpatient chest radiography.

OBJECTIVE: Follow-up chest radiographs are frequently recommended by radiologists to document the clearing of radiographically suspected pneumonia. However, the clinical utility of follow-up radiography is not well understood. The purpose of this study was to examine the incidence of important pulmonary pathology revealed during follow-up imaging of suspected pneumonia on outpatient chest radiography. MATERIALS AND METHODS: Reports of 29,138 outpatient chest radiography examinations performed at an academic medical center in 2008 were searched to identify cases in which the radiologist recommended follow-up chest radiography for presumed community-acquired pneumonia (n = 618). Descriptions of index radiographic abnormalities were recorded. Reports of follow-up imaging (radiography and CT) performed during the period from January 2008 to January 2010 were reviewed to assess the outcome of the index abnormality. Clinical history, demographics, microbiology, and pathology reports were reviewed and recorded. RESULTS: Compliance with follow-up imaging recommendations was 76.7%. In nine of 618 cases (1.5%), a newly diagnosed malignancy corresponded to the abnormality on chest radiography initially suspected to be pneumonia. In 23 of 618 cases (3.7%), an alternative nonmalignant disease corresponded with the abnormality on chest radiography initially suspected to be pneumonia. Therefore, in 32 of 618 patients (5.2%), significant new pulmonary diagnoses were established during follow-up imaging of suspected pneumonia. CONCLUSION: Follow-up imaging of radiographically suspected pneumonia leads to a small number of new diagnoses of malignancy and important nonmalignant diseases, which may alter patient management.

The association between primary language spoken and all-cause mortality in critically ill patients.

PURPOSE: The study objective was to investigate the association between primary language spoken and all-cause mortality in critically ill patients. MATERIALS AND METHODS: We performed a cohort study on 48 581 patients 18 years or older who received critical care between 1997 and 2007 in 2 Boston hospitals. The exposure of interest was primary language spoken determined by the patient or family members who interacted with administrative staff during hospital registration. The primary outcome was 30-day mortality. Associations between language and mortality were estimated by bivariable and multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both language and mortality. Adjustment included age, race, sex, Deyo-Charlson index, patient type (medical vs surgical), sepsis, creatinine, hematocrit, white blood count, and number of organs with acute failure. RESULTS: Validation showed that primary language spoken was highly accurate for a statement in the medical record noting the language spoken that matched the assigned language. Patients whose primary language spoken was not English had improved outcomes (odds ratio 30-day mortality, 0.69 [95% confidence interval, 0.60-0.81; P < .001), relative to patients with English as the primary language spoken, fully adjusted. Similar significant associations are seen with death by days 90 and 365 as well as in-hospital mortality. The improved survival in patients with a non-English primary language spoken is not confounded by indicators of severity of disease and is independent of the specific language spoken and neighborhood poverty rate, a proxy for socioeconomic status. There are significant limitations inherent to large database studies that we have acknowledged and addressed with controlling for measured confounding and evaluation of effect modification. CONCLUSIONS: In a regional cohort, not speaking English as a primary language is associated with improved outcomes after critical care. Our observations may have clinical relevance and illustrate the intersection of several factors in critical illness outcome including severity of illness, comorbidity, and social and economic factors.

Association between prehospital vitamin D status and hospital-acquired bloodstream infections.

BACKGROUND: Alterations in immune function can predispose patients to nosocomial infections. Few studies have explored potentially modifiable host factors that may improve immune function and decrease risk of hospital-acquired bloodstream infection (HABSI). Vitamin D is a key regulator of innate and adaptive immune systems that may influence host susceptibility to infections. OBJECTIVE: We investigated the association between prehospital serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of HABSI. DESIGN: We performed a retrospective cohort study of 2135 adult patients from 2 Boston teaching hospitals. All patients had 25(OH)D concentrations measured before hospitalization between 1993 and 2010. The main outcome measure was HABSI, which was defined as positive blood cultures from samples drawn 48 h after hospital admission. Coagulase-negative Staphylococcus isolates were not considered to be bloodstream infections. Associations between 25(OH)D groups and HABSI were estimated by using bivariable and multivariable logistic regression models. Adjusted ORs were estimated with the inclusion of covariate terms thought to plausibly interact with both 25(OH)D concentration and HABSI. RESULTS: Compared with patients with 25(OH)D concentrations ≥30 ng/mL, patients with concentrations <30 ng/mL had higher odds of HABSI. For 25(OH)D concentrations <10 ng/mL, the OR was 2.33 (95% CI: 1.45, 3.74); for 25(OH)D concentrations from 10 to 19.9 ng/mL, the OR was 1.60 (95% CI: 1.04, 2.46); and for 25(OH)D concentrations from 20 to 29.9 ng/mL, the OR was 1.13 (95% CI: 0.69, 1.84). After adjustment for age, sex, race (nonwhite compared with white), patient type (medical compared with surgical), and Deyo-Charlson index, the ORs of HABSI were 1.95 (95% CI: 1.22, 3.12), 1.36 (95% CI: 0.89, 2.07), and 0.98 (95% CI: 0.60, 1.62), respectively. CONCLUSIONS: The analysis of 2135 adult patients showed that 25(OH)D concentrations <10 ng/mL before hospitalization were associated with significantly increased odds of developing HABSI. These data support the initiation of randomized trials to test the role of vitamin D supplementation in HABSI prevention.