Search tips
Search criteria

Results 1-25 (44)

Clipboard (0)

Select a Filter Below

Year of Publication
1.  Alcohol Screening Scores and 90 Day Outcomes in Patients with Acute Lung Injury 
Critical care medicine  2013;41(6):1518-1525.
The effects of excess alcohol consumption (alcohol misuse) on outcomes in patients with acute lung injury (ALI) have been inconsistent, and there are no studies examining this association in the era of low tidal volume ventilation and a fluid conservative strategy. We sought to determine whether validated scores on the Alcohol Use Disorders Identification Test (AUDIT) that correspond to past year abstinence (zone 1), low-risk drinking (zone 2), mild to moderate alcohol misuse (zone 3), and severe alcohol misuse (zone 4) are associated with poor outcomes in patients with ALI.
Secondary analysis.
The Acute Respiratory Distress Syndrome (ARDS) network, a consortium of 12 university centers (44 hospitals) dedicated to the conduct of multi-center clinical trials in patients with acute lung injury.
Patients meeting consensus criteria for ALI enrolled in one of three recent ARDS network clinical trials.
Measurements and Main Results
Of 1,133 patients enrolled in one of three ARDS network studies, 1,037 patients had an AUDIT score available for analysis. Alcohol misuse was common with 70 (7%) of patients having AUDIT scores in zone 3 and 129 (12%) patients in zone 4. There was a u-shaped association between validated AUDIT zones and death or persistent hospitalization at 90 days (34% in zone 1, 26% in zone 2, 27% in zone 3, 36% in zone 4; p < 0.05 for comparison of zone 1 to zone 2 and zone 4 to zone 2). In a multiple logistic regression model, there was a significantly higher odds of death or persistent hospitalization in patients in AUDIT zone 4 when compared to those in zone 2 (adjusted OR 1.70; 95% CI 1.00, 2.87; p = 0.048).
Severe, but not mild to moderate alcohol misuse is independently associated with an increased risk of death or persistent hospitalization at 90 days in ALI patients.
PMCID: PMC4048714  PMID: 23538449
alcohol use disorders identification test; acute lung injury; alcohol use disorder; alcohol misuse; unhealthy alcohol use
2.  The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance 
The European respiratory journal  2013;43(1):276-285.
Acute respiratory distress syndrome (ARDS) continues to be a major healthcare problem, affecting >190 000 people in the USA annually, with a mortality of 27–45%, depending on the severity of the illness and comorbidities. Despite advances in clinical care, particularly lung protective strategies of mechanical ventilation, most survivors experience impaired health-related quality of life for years after the acute illness. While most patients survive the acute illness, a subset of ARDS survivors develops a fibroproliferative response characterised by fibroblast accumulation and deposition of collagen and other extracellular matrix components in the lung.
Historically, the development of severe fibroproliferative lung disease has been associated with a poor prognosis with high mortality and/or prolonged ventilator dependence. More recent studies also support a relationship between the magnitude of the fibroproliferative response and long-term health-related quality of life. The factors that determine which patients develop fibroproliferative ARDS and the cellular mechanisms responsible for this pathological response are not well understood.
This article reviews our current understanding of the contribution of pulmonary dysfunction to mortality and to quality of life in survivors of ARDS, the mechanisms driving pathological fibroproliferation and potential therapeutic approaches to prevent or attenuate fibroproliferative lung disease.
PMCID: PMC4015132  PMID: 23520315
3.  The role of infection and comorbidity: Factors that influence disparities in sepsis 
Critical care medicine  2006;34(10):2576-2582.
Large healthcare disparities exist in the incidence of sepsis based on both race and gender. We sought to determine factors that may influence the occurrence of these healthcare disparities, with respect to the source of infection, causal organisms, and chronic comorbid medical conditions.
Historical cohort study.
U.S. acute care hospitals from 1979 to 2003.
Hospitalized patients with a diagnosis of sepsis were identified from the National Hospital Discharge Survey per codes of the International Statistical Classification of Diseases, Ninth Revision (ICD-9CM). Chronic comorbid medical conditions and the source and type of infection were characterized by corresponding ICD-9CM diagnoses.
Measurements and Main Results
Sepsis incidence rates are mean cases per 100,000 after age adjustment to the 2000 U.S. Census. Males and nonwhite races were confirmed at increased risk for sepsis. Both proportional source distribution and incidence rates favored respiratory sources of sepsis in males (36% vs. 29%, p < .01) and genitourinary sources in females (35% vs. 27%, p < .01). Incidence rates for all common sources of sepsis were greater in nonwhite races, but proportional source distribution was approximately equal. After stratification by the source of infection, males (proportionate ratio 1.16, 95% confidence interval 1.04–1.29) and black persons (proportionate ratio 1.25, 95% confidence interval 1.18–1.32) remained more likely to have Gram-positive infections. Chronic comorbid conditions that alter immune function (chronic renal failure, diabetes mellitus, HIV, alcohol abuse) were more common in nonwhite sepsis patients, and cumulative comorbidities were associated with greater acute organ dysfunction. Compared with white sepsis patients, non-white sepsis patients had longer hospital length of stay (2.0 days, 95% confidence interval 1.9–2.1) and were less likely to be discharged to another medical facility (30% whites, 25% blacks, 18% other races). Case-fatality rates were not significantly different across racial and gender groups.
Healthcare disparities exist in the incidence of sepsis within all major sources of infection, and males and blacks have greater frequency of Gram-positive infections independent of the infection source. The differential distribution of specific chronic comorbid medical conditions may contribute to these disparities. Large cohort and administrative studies are required to confirm discrete root causes of sepsis disparities.
PMCID: PMC3926300  PMID: 16915108
sepsis; healthcare disparities; comorbidities; infection
4.  Chest Computed Tomography Features are Associated with Poorer Quality of Life in Acute Lung Injury Survivors 
Critical care medicine  2013;41(2):445-456.
Despite decreasing mortality rates in acute lung injury (ALI), studies of long term physical function in ALI survivors have consistently reported poorer quality of life persisting years into recovery for reasons that are not completely understood. We sought to determine if pulmonary dysfunction is independently associated with functional impairment among ALI survivors, and to determine if high resolution computed tomography could be used to predict its development.
Secondary analysis of data from a randomized controlled trial in ALI.
Intensive care units at three academic medical centers.
Patients diagnosed with ALI who had high resolution computed tomography scans performed at 14 and/or 180 days after diagnosis.
Measurements and main results
An objective radiologic scoring system was used to quantify patterns present on chest high resolution computed tomography obtained at 14 and 180 days in patients with ALI. These scores were correlated in univariable and multivariable analyses with pulmonary function testing and quality of life survey data obtained at 180 days. Eighty-nine patients had evaluable data at day 14, and 47 at 180 days. At 180 days, increased radiologic scores for reticulation were associated with a decreased total lung capacity, forced vital capacity, and diffusing capacity for carbon monoxide (p values all <0.002). Decrements in quality of life attributable to pulmonary dysfunction were most strongly associated with higher radiologic scores. Additionally, radiologic scores at 14 days independently predicted poorer quality of life at 180 days, accounting for age, severity of illness, pneumonia as the ALI risk factor, and length of time on mechanical ventilation.
Among survivors of ALI, increasing chest high resolution computed tomography involvement correlated with restrictive physiology and poorer health related quality of life, implicating pulmonary dysfunction as a potential contributor to activity limitation in these patients.
PMCID: PMC3671861  PMID: 23263616
reticulation; biomarker; restriction; fibroproliferation; radiologic; pulmonary function
5.  Remote Source Document Verification in Two National Clinical Trials Networks: A Pilot Study 
PLoS ONE  2013;8(12):e81890.
Barriers to executing large-scale randomized controlled trials include costs, complexity, and regulatory requirements. We hypothesized that source document verification (SDV) via remote electronic monitoring is feasible.
Five hospitals from two NIH sponsored networks provided remote electronic access to study monitors. We evaluated pre-visit remote SDV compared to traditional on-site SDV using a randomized convenience sample of all study subjects due for a monitoring visit. The number of data values verified and the time to perform remote and on-site SDV was collected.
Thirty-two study subjects were randomized to either remote SDV (N=16) or traditional on-site SDV (N=16). Technical capabilities, remote access policies and regulatory requirements varied widely across sites. In the adult network, only 14 of 2965 data values (0.47%) could not be located remotely. In the traditional on-site SDV arm, 3 of 2608 data values (0.12%) required coordinator help. In the pediatric network, all 198 data values in the remote SDV arm and all 183 data values in the on-site SDV arm were located. Although not statistically significant there was a consistent trend for more time consumed per data value (minutes +/- SD): Adult 0.50 +/- 0.17 min vs. 0.39 +/- 0.10 min (two-tailed t-test p=0.11); Pediatric 0.99 +/- 1.07 min vs. 0.56 +/- 0.61 min (p=0.37) and time per case report form: Adult: 4.60 +/- 1.42 min vs. 3.60 +/- 0.96 min (p=0.10); Pediatric: 11.64 +/- 7.54 min vs. 6.07 +/- 3.18 min (p=0.10) using remote SDV.
Because each site had different policies, requirements, and technologies, a common approach to assimilating monitors into the access management system could not be implemented. Despite substantial technology differences, more than 99% of data values were successfully monitored remotely. This pilot study demonstrates the feasibility of remote monitoring and the need to develop consistent access policies for remote study monitoring.
PMCID: PMC3857788  PMID: 24349149
6.  Diagnosis and treatment of post-extubation dysphagia: Results from a National Survey 
Journal of critical care  2012;27(6):578-586.
This study sought to determine the utilization of speech-language pathologist (SLPs) for the diagnosis and treatment of post-extubation dysphagia in survivors of mechanical ventilation.
We designed, validated, and mailed a survey to 1,966 inpatient SLPs who routinely evaluate patients for post-extubation dysphagia.
The majority of SLP diagnostic evaluations (60%; 95% CI = 59–62%) were performed using clinical techniques with uncertain accuracy. Instrumental diagnostic tests (such as fluoroscopy and endoscopy) are more likely to be available at university than community hospitals. After adjusting for hospital size and academic affiliation, instrumental test use varied significantly by geographical region. Treatments for post-extubation dysphagia usually involved dietary adjustment (76%; 95% CI = 73–79%) and postural changes/compensatory maneuvers (86%; 95% CI = 84–88%), rather than on interventions aimed to improve swallowing function (24%; 95% CI = 21–27%).
SLPs frequently evaluate acute respiratory failure survivors. However, diagnostic evaluations rely mainly upon bedside techniques with uncertain accuracy. The use of instrumental tests varies by geographic location and university affiliation. Current diagnostic practices and feeding decisions for critically ill patients should be viewed with caution until further studies determine the accuracy of bedside detection methods.
PMCID: PMC3518658  PMID: 23084136
Mechanical Ventilation; Intratracheal Intubation; Respiratory Aspiration; Dysphagia; Swallowing Disorders
7.  Simple Frailty Score Predicts Post-Operative Complications Across Surgical Specialties 
American journal of surgery  2013;206(4):544-550.
Our purpose was to determine the relationship between pre-operative frailty and the occurrence of postoperative complications following colorectal and cardiac operations.
Study Design
Patients ≥65 years undergoing elective colorectal or cardiac surgery were enrolled. Seven baseline frailty traits were measured pre-operatively: Katz Score ≤5, Timed Up-and-Go ≥15 seconds, Charlson Index ≥3, anemia<35%, Mini-Cog score ≤3, albumin<3.4gm/dL and ≥1 fall within six-months. Patients were categorized by the number of positive traits: non-frail: 0–1 trait, pre-frail: 2–3 traits and frail: ≥4 traits.
201 subjects (age 74±6 years) were studied. Preoperative frailty was associated with increased postoperative complications following colorectal (non-frail 21%, pre-frail 40% and frail 58%; p=0.016) and cardiac operations (non-frail 17%, pre-frail 28% and frail 56%; p<0.001). This finding in both groups was independent of advancing age. Frail individuals in both groups had longer hospital stays and higher 30-day readmission rates. Receiver operating characteristic curves examining frailty’s ability to forecast complications were: colorectal (0.702; p=0.004) and cardiac (0.711; p<0.001).
A simple pre-operative frailty score defines older adults at higher risk for postoperative complications across surgical specialties.
PMCID: PMC3788864  PMID: 23880071
8.  Slower Walking Speed Forecasts Increased Postoperative Morbidity and One-Year Mortality Across Surgical Specialties 
Annals of surgery  2013;258(4):582-590.
The purpose of this study was to determine the relationship between the timed up-and-go test and postoperative morbidity and one-year mortality, and to compare the timed up-and-go to the standard-of-care surgical risk calculators for prediction of postoperative complications.
In this prospective cohort study, patients 65 years and older undergoing elective colorectal and cardiac operations with a minimum of one-year follow-up were included. The timed up-and-go test was performed preoperatively. This timed test starts with the subject standing from a chair, walking ten feet, returning to the chair, and ends after the subject sits. Timed up-and-go results were grouped: Fast≤10 sec, Intermediate=11-14 sec, Slow≥15 sec. Receiver operating characteristic curves were used to compare the three timed-up-and-go groups to current standard-of-care surgical risk calculators at forecasting postoperative complications.
This study included 272 subjects (mean age of 74±6 years). Slower timed up-and-go was associated with an increased postoperative complications following colorectal (fast-13%, intermediate-29% and slow-77%;p<0.001) and cardiac (fast-11%, intermediate-26% and slow-52%;p<0.001) operations. Slower timed up-and-go was associated with increased one-year mortality following both colorectal (fast-3%, intermediate-10% and slow-31%;p=0.006) and cardiac (fast-2%, intermediate-3% and slow-12%;p=0.039) operations. Receiver operating characteristic area under curve of the timed up-and-go and the risk calculators for the colorectal group was 0.775 (95% CI:0.670,0.880) and 0.554 (95% CI:0.499,0.609), and for the cardiac group was 0.684 (95% CI:0.603,0.766) and 0.552 (95% CI:0.477,0.626).
Slower timed up-and-go forecasted increased postoperative complications and one-year mortality across surgical specialties. Regardless of operation performed, the timed up-and-go compared favorably to the more complex risk calculators at forecasting postoperative complications.
PMCID: PMC3771691  PMID: 23979272
9.  Surrogate and Patient Discrepancy Regarding Consent for Critical Care Research 
Critical care medicine  2012;40(9):2590-2594.
Critically ill patients frequently display impaired decision making capacity due to their underlying illness and the use of sedating medications. Health care providers often rely on surrogates to make decisions for medical care and participation in clinical research. However, the accuracy of surrogate decisions for a variety of critical care research studies is poorly understood.
Cross-sectional observational study
Academic medical center
Medical ICU patients and their designated surrogates
Patients were asked if they would consent to participate in hypothetical research studies of increasing complexity, and surrogates independently indicated whether they would consent to enroll the patient in the same scenarios.
Overall, 69 MICU patients were enrolled into the study. The majority of surrogates were either the spouse (58%) or parent (22%) of the patient. The percentage of patients that would agree to participate in a research study and the percentage of surrogates that would agree to have the patient enrolled into a research study both declined as the risk of the study increased (P < 0.001 for both analyses). In addition, the overall discrepancy, the false negative rates, and the false positive rates between patient and surrogates were greater as the risk of the study increased (P <0.001, P < 0.001, and P = 0.049 respectively). Kappa values for all seven scenarios demonstrated less than moderate agreement (range 0.03–0.41).
There are significant discrepancies in the willingness to participate in various types of clinical research proposals between critically ill patients and their surrogate decision makers. The results of this study raise concerns about the use of surrogate consent for inclusion of critically ill patients into research protocols.
PMCID: PMC3674768  PMID: 22732283
critical care; informed consent; surrogate; medical ethics; research design
10.  Symptoms of Post-traumatic Stress Disorder Among Pediatric Acute Care Nurses 
Journal of Pediatric Nursing  2011;27(4):357-365.
PMCID: PMC3381608  PMID: 22703683
11.  Transfusion-related acute lung injury in ICU patients admitted with gastrointestinal bleeding 
Intensive care medicine  2010;36(10):1710-1717.
Transfusion of blood components is common in patients admitted to the intensive care unit (ICU) for gastrointestinal (GI) bleeding, yet the incidence and risk factors for development of transfusion-related acute lung injury (TRALI) in these patients are unknown.
Patients admitted to a medical ICU for GI bleeding (n = 225) were analyzed for patient-and transfusion-specific risk factors for development of TRALI.
In transfused patients (n = 150), the incidence of TRALI was 15% [95% confidence interval (CI), 10–21%] and accounted for 76% (22/29) of all acute lung injury (ALI) cases. Transfused patients with end-stage liver disease (ESLD) (n = 72) developed TRALI more frequently than those without ESLD (29% versus 1%, p < 0.01). Fresh frozen plasma (FFP) was temporally associated with TRALI in 86% of cases. Transfusion-specific risk factors for development of TRALI included number of transfused units of FFP and nonleukoreduced red blood cells. Patient-specific risk factors included Model for End-Stage Liver Disease (MELD) score, admission serum albumin level, and presence of ALI risk factors.
TRALI is common in critically ill ESLD patients with gastrointestinal bleeding. Nonleukoreduced red blood cells and FFP are significant transfusion-specific risk factors and their use should be re-evaluated in bleeding patients with ESLD.
PMCID: PMC3727900  PMID: 20658125
Transfusion-related acute lung injury; Transfusion complications; Acute respiratory distress syndrome; Variceal bleeding; Chronic liver disease; Plasma transfusion
12.  Preoperative Cognitive Dysfunction Is Related to Adverse Postoperative Outcomes in the Elderly 
Pre-operative risk stratification is commonly performed by assessing end organ function (such as cardiac and pulmonary) to define post-operative risk. Little is known about impaired pre-operative cognition and outcomes. The purpose of this study was to evaluate the impact of baseline impaired cognition on post-operative outcomes in geriatric surgery patients.
Study Design
Prospectively, subjects 65 years and older undergoing a planned elective operation requiring post-operative ICU admission were recruited. Pre-operative baseline cognition was assessed using the validated Mini-Cog test. Impaired cognition was defined as a Mini-Cog score of ≤3. Delirium was assessed using the Confusion Assessment Method-ICU by a trained research team. Adverse outcomes were defined using the Veterans Affairs Surgical Quality Improvement Program definitions.
186 subjects were included with an average age of 73±6 years. Eighty-two subjects (44%) had baseline impaired cognition. The impaired cognition group had the unadjusted outcomes: increased incidence of ≥1 post-operative complication (41% versus 24%; p=.011), higher incidence of delirium (78% versus 37%; p<.001), longer hospital stays (15±14 versus 9±9 days; p=.008), higher rate of discharge institutionalization (42% versus 18%; p=.001) and higher six-month mortality (13% versus 5%; p=.040). Adjusting for potential confounders determined by univariate analysis, logistic regression found impaired cognition was still associated to the occurrence of one or more post-operative complications (odds ratio 2.401; 95% confidence interval 1.185, 4.865; p=0.015). Kaplan-Meier survival analysis revealed higher mortality in the impaired cognition group (Log-Rank p =.008).
Baseline cognitive impairment in older adults undergoing major elective operations is related to adverse post-operative outcomes including increased complications, length of stay and long-term mortality. Improved understanding of baseline cognition and surgical outcomes may aid surgical decision-making in older adults.
PMCID: PMC3383613  PMID: 22626912
13.  Growth differentiation factor-15 and prognosis in acute respiratory distress syndrome: a retrospective cohort study 
Critical Care  2013;17(3):R92.
We sought to determine whether higher levels of the novel biomarker growth differentiation factor-15 (GDF-15) are associated with poor outcomes and the presence of pulmonary vascular dysfunction (PVD) in patients with acute respiratory distress syndrome (ARDS).
We conducted a retrospective cohort study in patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment (FACT) Trial. Patients enrolled in the FACT Trial who received a pulmonary artery catheter (PAC), had plasma available from the same study day and sufficient hemodynamic data to determine the presence of PVD were included. Logistic regression was used to determine the association between GDF-15 level and 60-day mortality.
Of the 513 patients enrolled in the FACT Trial assigned to receive a PAC, 400 were included in this analysis. Mortality at 60 days was significantly higher in patients whose GDF-15 levels were in the third (28%) or fourth (49%) quartile when compared to patients with GDF-15 levels in the first quartile (12%) (P <0.001). Adjusting for severity of illness measured by APACHE III score, the odds of death for patients with GDF-15 levels in the fourth quartile when compared to the first quartile was 4.26 (95% CI 2.18, 10.92, P <0.001). When added to APACHE III alone for prediction of 60-day mortality, GDF-15 levels increased the area under the receiver operating characteristic curve from 0.72 to 0.77. At an optimal cutoff of 8,103 pg/mL, the sensitivity and specificity of GDF-15 for predicting 60-day mortality were 62% (95% CI 53%, 71%) and 76% (95% CI 71%, 81%), respectively. Levels of GDF-15 were not useful in identifying the presence of PVD, as defined by hemodynamic measurements obtained by a PAC.
In patients with ARDS, higher levels of GDF-15 are significantly associated with poor outcome but not PVD.
PMCID: PMC3706804  PMID: 23706007
Acute respiratory distress syndrome; pulmonary vascular dysfunction; risk prediction; growth differentiation factor-15
14.  Severity of Acute Illness is Associated with Baseline Readiness to Change in Medical Intensive Care Unit Patients with Unhealthy Alcohol Use 
Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one-third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use.
Materials and Methods
We performed a cross-sectional observational study of current regular drinkers in three medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patient’s acute illness was assessed by calculating the Acute Physiology and Chronic Healthy Evaluation II score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires.
Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHEII score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale) (p< 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term).
Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy alcohol use as potential effect modifiers.
PMCID: PMC3251713  PMID: 21950704
15.  The presence of resilience is associated with a healthier psychological profile in ICU nurses: Results of a national survey 
ICU nurses are repeatedly exposed to work related stresses resulting in the development of psychological disorders including posttraumatic stress disorder and burnout syndrome. Resilience is a learnable multidimensional characteristic enabling one to thrive in the face of adversity. In a national survey, we sought to determine whether resilience was associated with healthier psychological profiles in intensive care unit nurses.
Surveys were mailed to 3500 randomly selected ICU nurses across the United States and included: demographic questions, the Posttraumatic Diagnostic Scale, Hospital Anxiety and Depression Scale, Maslach Burnout Inventory and the Connor-Davidson Resilience Scale.
Measurements and Main Results
Overall, 1239 of the mailed surveys were returned for a response rate of 35%, and complete data was available on a total of 744 nurses. Twenty-two percent of the intensive care unit nurses were categorized as being highly resilient. The presence of high resilience in these nurses was significantly associated with a lower prevalence of posttraumatic stress disorder, symptoms of anxiety or depression, and burnout syndrome (<0.001 for all comparisons). In independent multivariable analyses adjusting for five potential confounding variables, the presence of resilience was independently associated with a lower prevalence of posttraumatic stress disorder (p < 0.001), and a lower prevalence of burnout syndrome (p < 0.001).
The presence of psychological resilience was independently associated with a lower prevalence of posttraumatic stress disorder and burnout syndrome in intensive care unit nurses. Future research is needed to better understand coping mechanisms employed by highly resilient nurses and how they maintain a healthier psychological profile.
PMCID: PMC3276701  PMID: 21974793
Resilience; posttraumatic stress disorder; burnout syndrome; ICU nurses
17.  A randomized trial of recombinant human GM-CSF for patients with acute lung injury* 
Critical care medicine  2012;40(1):90-97.
Despite recent advances in critical care and ventilator management, acute lung injury (ALI) and the Acute Respiratory Distress Syndrome (ARDS) continue to cause significant morbidity and mortality. Granulocyte-macrophage colony stimulating factor (GM-CSF) may be beneficial for patients with ARDS.
To determine whether intravenous infusion of GM-CSF would improve clinical outcomes for patients with ALI/ARDS.
A randomized, double-blind, placebo-controlled clinical trial of human recombinant GM-CSF vs. placebo. The primary outcome was days alive and breathing without mechanical ventilatory support within the first 28 days after randomization. Secondary outcomes included mortality and organ failure free days.
Medical and Surgical Intensive Care Units at three academic medical centers.
One hundred-thirty individuals with ALI of at least three days duration were enrolled, out of a planned cohort of 200 subjects.
Patients were randomized to receive human recombinant GM-CSF (64 subjects, 250 μg/M2) or placebo (66 subjects) by intravenous infusion daily for 14 days. Patients received mechanical ventilation using a lung protective protocol.
Measurements and Main Results
There was no difference in ventilator-free days between groups (10.7 ± 10.3 days placebo vs. 10.8 ± 10.5 days GM-CSF, p=0.82). Differences in 28-day mortality (23% in placebo vs. 17% in patients receiving GM-CSF (p=0.31)) and organ failure free days (12.8 ± 11.3 days placebo vs. 15.7 ± 11.9 days GM-CSF, p=0.16) were not statistically significant. There were similar numbers of serious adverse events in each group.
In a randomized phase II trial, GM-CSF treatment did not increase the number of ventilator free days in patients with ALI/ARDS. A larger trial would be required to determine whether treatment with GM-CSF might alter important clinical outcomes such as mortality or multiorgan failure. ( number, NCT00201409 [])
PMCID: PMC3242850  PMID: 21926600
Acute Respiratory Distress Syndrome; growth factors; sepsis; innate immunity
18.  Frailty Predicts Increased Hospital and Six-Month Healthcare Cost Following Colorectal Surgery in Older Adults 
American Journal of Surgery  2011;202(5):511-514.
The purpose of this study was to determine the relationship of frailty and six-month post-operative costs.
Subjects ≥65 years undergoing elective colorectal operations were enrolled in a prospective observational study. Frailty was assessed by a validated measure of function, cognition, nutrition, co-morbidity burden and geriatric syndromes. Frailty was quantified by summing the number of positive characteristics in each subject.
Sixty subjects (mean age 75±8 years) were studied. Inpatient mortality was 2% (n=1). Overall, 40% (n=24) of subjects were considered non-frail, 22% (n=13) were pre-frail and 38% (n=22) were frail. With advancing frailty, hospital cost increased (p<.001) and cost from discharge to six-months increased (p<.001). Higher degrees of frailty were related to increased rates of discharge institutionalization (p<.001) and thirty-day readmission (p=.044).
A simple, brief pre-operative frailty assessment accurately forecasts increased surgical hospital costs and post-discharge to six-month healthcare costs following colorectal operations in older adults.
PMCID: PMC3346286  PMID: 21890098
Geriatric; Surgery; Financial; Frailty; Healthcare resources
19.  Comparative Effectiveness Research in Lung Diseases and Sleep Disorders 
The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed.
PMCID: PMC3265273  PMID: 21965016
randomized controlled trials; observational studies; implementation; study designs; methodology
20.  Physical Therapy Management and Patient Outcomes following ICU-Acquired Weakness: A Case Series 
Background and Purpose
Individuals with critical illness experience dysfunction of many body systems including the neuromuscular system. Neuromuscular impairments result in a syndrome referred to as ICU-acquired weakness which may lead to difficulty with activities and participation. The purposes of this case series were to 1) describe safety and feasibility of physical intervention in individuals with ICU acquired weakness mechanically ventilated for at least 7 days; and 2) characterize physical therapist management and patient outcomes.
Case Description
Nineteen patients with ICU-acquired weakness who required mechanical ventilation for at least 7 days were enrolled over a 1-year period.
Physical therapy (PT) was provided 5 day/wk for 30 minutes per session.
Outcome measures included manual muscle tests and item scores from the Functional Independence Measure (FIM). Participants completed 170 PT sessions. Only 20 sessions (12%) were stopped before 30 minutes. Seventeen participants survived to discharge; no PT-related adverse events occurred. At discharge, participants who went home showed a trend toward greater independence and strength compared to those who were discharged to another level of care. Median total hospital days was 28 for those discharged to home and 22 for those discharged to other level of care.
This case series demonstrates safety and feasibility of PT intervention for patients with ICU-acquired weakness requiring mechanical ventilation for at least 7 days. The examination and intervention procedures are described and could be implemented with other similar individuals in the hospital setting. Future studies should investigate frequency and duration of physical intervention, both during hospitalization and post discharge.
PMCID: PMC3178045  PMID: 21934375
ICU-Acquired weakness; Physical Therapy
21.  Differential effect of plasma and red blood cell transfusion on acute lung injury and infection risk following liver transplantation 
Liver Transplantation  2011;17(2):149-158.
Patients with chronic liver disease are at an increased risk of developing transfusion-associated acute lung injury (TRALI) from plasma containing blood products. Similarly, red blood cell transfusions have been associated with post-operative and nosocomial infections in surgical and critical care populations. Patients undergoing liver transplantation receive a large amount of cellular and plasma containing blood products, but it is presently unclear which blood components are associated with these post-operative complications.
A retrospective cohort study of 525 consecutive liver transplant patients revealed a peri-operative TRALI incidence of 1.3% (7/525), 95%CI [0.6%–2.7%], associated with an increased hospital mortality (28.6% (2/7) vs. 2.9% (15/518), p=0.02) and intensive care unit (ICU) length of stay (2 days, [1–11] vs. 0 days [0–2], 0.03). Only high plasma containing blood products (plasma and platelets) were associated with the development of TRALI. A total of 14.3% (74/525) of patients developed a post-operative infection which was also associated with an increased in-hospital mortality (10.8% (8/74) vs. 2.0% (9/451), p < 0.01) and prolonged length of stay. Multivariate logistic regression identified the number of red blood cell units transfused (adj OR 1.08 95%CI [1.02–1.14], p<0.01), the presence of peri-operative renal dysfunction and re-operation to be significantly associated with post-operative infection.
Patients undergoing liver transplantation are at high risk of developing post-operative complications from blood transfusion. Plasma containing blood products were associated with the development of TRALI while red blood cells were associated with the development of post-operative infection in a dose dependent manner.
PMCID: PMC3399914  PMID: 21280188
transfusion-related acute lung injury; nosocomial infection; Pulmonary Edema; Blood Component Transfusion; Liver Cirrhosis
22.  Accumulated Frailty Characteristics Predict Postoperative Discharge Institutionalization in the Geriatric Patient 
Frailty is a state of increased vulnerability to health-related stressors and can be measured by summing the number of frailty characteristics present in an individual. Discharge institutionalization (rather than discharge to home) represents disease burden and functional dependence following hospitalization. Our aim was to determine the relationship between frailty and need for post-operative discharge institutionalization.
Study Design
Subjects ≥65 years undergoing major elective operations requiring post-operative ICU admission were enrolled. Discharge institutionalization was defined as need for institutionalized care at hospital discharge. Fourteen pre-operative frailty characteristics were measured in six domains: co-morbidity burden, function, nutrition, cognition geriatric syndromes and extrinsic frailty.
223 subjects (mean age 73±6 years) were studied. Discharge institutionalization occurred in 30% (66). Frailty characteristics related to need for post-operative discharge institutionalization included: older age, Charlson ≥3, Hematocrit <35%, any functional dependence, Up-and-Go ≥15 seconds, albumin <3.4 mg/dL, Mini-Cog ≤3, and having fallen within six-months (p<.0001 for all comparisons). Multivariate logistic regression retained prolonged timed up-and-go (p<.0001) and any functional dependence (p<.0001) as the variables most closely related to need for discharge institutionalization. An increased number of frailty characteristics present in any one subject resulted in increased rate of discharge institutionalization.
Nearly one in three geriatric patients required discharge to an institutional care facility following major surgery. The frailty characteristics of prolonged up-and-go and any functional dependence were most closely related to the need for discharge institutionalization. Accumulation of a higher number of frailty characteristics in any one geriatric patient increased their risk of discharge institutionalization.
PMCID: PMC3132184  PMID: 21435921
24.  Secondary Prevention in the Intensive Care Unit: Does ICU Admission Represent a “Teachable Moment?” 
Critical care medicine  2011;39(6):1500-1506.
Cigarette smoking and unhealthy alcohol use are common causes of preventable morbidity and mortality that frequently result in admission to an intensive care unit. Understanding how to identify and intervene in these conditions is important because critical illness may provide a “teachable moment.” Furthermore, the Joint Commission recently proposed screening and receipt of an intervention for tobacco use and unhealthy alcohol use as candidate performance measures for all hospitalized patients. Understanding the efficacy of these interventions may help drive evidence-based institution of programs, if deemed appropriate.
Data Sources
A summary of the published medical literature on interventions for unhealthy alcohol use and smoking obtained through a PubMed search.
Interventions focusing on behavioral counseling for cigarette smoking in hospitalized patients have been extensively studied. Several studies include or focus on critically ill patients. The evidence demonstrates that behavioral counseling leads to increased rates of smoking cessation but the effect depends on the intensity of the intervention. The identification of unhealthy alcohol use can lead to brief interventions. These interventions are particularly effective in trauma patients with unhealthy alcohol use. However, the current literature would not support routine delivery of brief interventions for unhealthy alcohol use in the medical ICU population.
ICU admission represents a “teachable moment” for smokers and some patients with unhealthy alcohol use. Future studies should assess the efficacy of brief interventions for unhealthy alcohol use in medical ICU patients. In addition, identification of the timing and optimal individual to conduct the intervention will be necessary.
PMCID: PMC3180919  PMID: 21494113
To define the pre-operative risk factors, outcomes and adverse events related to the motor subtypes of post-operative delirium.
Prospective cohort study.
Referral medical center.
Subjects 50 years and older with planned post-operative intensive care unit admission following an elective operation were recruited.
Main Outcome Measures
Pre-operatively, a standardized frailty assessment was performed. Post-operatively, delirium and its motor subtypes were measured using the validated tools of the Confusion Assessment Method-ICU and the Richmond Agitation Sedation Scale. Statistical analysis included univariate (t test and chi-square) and ANOVA with post-hoc analysis.
Delirium occurred in 43% (74/172); including the motor subtypes of hypoactive 68% (50/74), mixed 31% (23/74) and hyperactive 1% (1/74). Subjects with hypoactive delirium were found to be older (71±9 vs. 65±9 years; p=0.002) and more anemic (36±8% vs. 41±6%, *p=0.002). Subjects with hypoactive delirium were found to have higher six-month mortality (32% (16/50) vs. 9% (2/23); p=0.041). Delirium related adverse events occurred in 24% (18/74) of delirious subjects; pulled lines/tubes occurred more frequently in the mixed group (p=0.006) and decubitus ulcers were more common in the hypoactive group (p=0.002).
Delirium motor subtypes alert the clinician to differing prognosis and adverse event profiles in the post-operative geriatric patient. Hypoactive delirium is the most common motor subtype and is associated with worse prognosis (one in three six-month mortality). Delirium motor subtypes are related to differing adverse event profiles; this knowledge can modify the management of the delirious elderly patient.
PMCID: PMC3346288  PMID: 21422360

Results 1-25 (44)