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1.  Depressive Symptoms and Impaired Physical Function after Acute Lung Injury 
Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear.
Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions.
Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment.
Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms.
Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes.
doi:10.1164/rccm.201103-0503OC
PMCID: PMC3297105  PMID: 22161158
depression; recovery of function; critical illness; critical care; acute lung injury
2.  Does ICU Severity of Illness Influence Recall of Baseline Physical Function? 
Journal of critical care  2011;26(6):634.e1-634.e7.
Purpose
To evaluate if severity of illness in the intensive care unit influences patients' retrospective recall of their baseline physical function from prior to hospital admission.
Materials and Methods
A prospective cohort study of 193 acute lung injury (ALI) survivors who, prior to hospital discharge, retrospectively reported their pre-hospitalization physical function using the SF-36 quality of life survey.
Results
Four measures were used to evaluate ICU severity of illness: (1) Acute Physiology and Chronic Health Evaluation II Acute Physiologic Score at ICU admission, (2) Lung Injury Score at ALI diagnosis, (3) Sequential Organ Failure Assessment (SOFA) score at study enrollment, and (4) maximum daily SOFA score during the entire ICU stay. In multivariable linear regression analysis, no measure of severity of illness was associated with prehospitalization Physical Function. Education level significantly modified the relationship between ICU severity of illness and baseline Physical Function with lower educational attainment having a stronger association with baseline physical function.
Conclusion
ICU severity of illness was not associated with patients' retrospectively recalled baseline physical function. Patients with a lower level of education maybe more influenced by ICU severity of illness, but the magnitude of this effect may not be clinically meaningful.
doi:10.1016/j.jcrc.2011.05.009
PMCID: PMC3191318  PMID: 21737233
Critical care; Quality of life; Respiratory distress syndrome, adult; Health status; Mental recall; Bias, epidemiologic
3.  Repeated Attempts using Different Strategies are Important for Timely Contact with Study Participants 
Journal of clinical epidemiology  2010;64(10):1144-1151.
Objective
To study the effect of different mail- and phone-based strategies, along with patient- and research-related factors, on the time to contact with research participants.
Study Design and Setting
A prospective evaluation of a 12-week standardized protocol (embedded with two randomized trials of mail- and phone-based strategies) for contacting existing research participants for recruitment into a related study.
Result
Of 146 participants, 87 were eligible for contact via the standardized protocol and 63 (72%) of these were successfully contacted within 12 weeks after multiple mail- and phone-based efforts. Using Cox proportional hazards regression analysis, the different mail and phone strategies showed no significant difference in the time to contact with participants. Of 34 patient- and research-related factors evaluated, only 2 were independently associated with time to contact among all 146 participants: (1) participants having their last visit conducted outside of the research clinic due to patient illness/condition had a longer time to contact; and (2) those with a self-reported chronic fatigue history had a shorter time to contact.
Conclusion
Few patient characteristics and research-related factors accurately predict time to contact. Repeated attempts using different strategies are important to successful and timely contact with study participants.
doi:10.1016/j.jclinepi.2010.08.007
PMCID: PMC3116960  PMID: 21109398
patient selection; risk factors; cohort studies; patient participation; respiratory distress syndrome, adult
4.  The functional comorbidity index had high inter-rater reliability in patients with acute lung injury 
BMC Anesthesiology  2012;12:21.
Background
The Functional Comorbidity Index (FCI) was recently developed to predict physical function in acute lung injury patients using comorbidity data. Our objectives were to determine: (1) the inter-rater reliability of the FCI collected using in-patient discharge summaries (primary objective); and (2) the accuracy and predictive validity of the FCI collected using hospital discharge summaries and admission records versus complete chart review (secondary objectives).
Methods
For reliability, we evaluated the FCI’s intraclass correlation coefficient (ICC) among trained research staff performing data collection for 421 acute lung injury patients enrolled in a prospective cohort study. For validity and accuracy, we compared the detection of FCI comorbidities across three types of inpatient medical records, and the association of the respective FCI scores obtained with patients’ SF-36 physical function subscale (PFS) scores at 1-year follow-up.
Results
Inter-rater reliability was near-perfect (ICC 0.91; 95% CI 0.89-0.94). Hospital admission records and discharge summaries (vs. complete chart review) significantly underestimated the total FCI score. However, using multivariable linear regression, FCI scores collected using each of the three types of inpatient medical records had similar associations with PFS, suggesting similar predictive value.
Conclusions
Data collection using in-patient discharge summaries represents a reliable and valid method for collecting FCI comorbidity information.
doi:10.1186/1471-2253-12-21
PMCID: PMC3517372  PMID: 22974239
Comorbidity; Intensive care unit; Reproducibility of results; Respiratory distress syndrome, Adult
5.  Short-Term Mortality Prediction for Acute Lung Injury Patients: External Validation of the ARDSNet Prediction Model 
Objective
An independent cohort of acute lung injury (ALI) patients was used to evaluate the external validity of a simple prediction model for short-term mortality previously developed using data from ARDS Network (ARDSNet) trials.
Design, Setting, and Patients
Data for external validation were obtained from a prospective cohort study of ALI patients from 13 ICUs at four teaching hospitals in Baltimore, Maryland.
Measurements and Main Results
Of the 508 non-trauma, ALI patients eligible for this analysis, 234 (46%) died in-hospital. Discrimination of the ARDSNet prediction model for inhospital mortality, evaluated by the area under the receiver operator characteristics curves (AUC), was 0.67 for our external validation dataset versus 0.70 and 0.68 using APACHE II and the ARDSNet validation dataset, respectively. In evaluating calibration of the model, predicted versus observed in-hospital mortality for the external validation dataset was similar for both low risk (ARDSNet model score = 0) and high risk (score = 3 or 4+) patient strata. However, for intermediate risk (score = 1 or 2) patients, observed in-hospital mortality was substantially higher than predicted mortality (25.3% vs. 16.5% and 40.6% vs. 31.0% for score = 1 and 2, respectively). Sensitivity analyses limiting our external validation data set to only those patients meeting the ARDSNet trial eligibility criteria and to those who received mechanical ventilation in compliance with the ARDSNet ventilation protocol, did not substantially change the model’s discrimination or improve its calibration.
Conclusions
Evaluation of the ARDSNet prediction model using an external ALI cohort demonstrated similar discrimination of the model as was observed with the ARDSNet validation dataset. However, there were substantial differences in observed versus predicted mortality among intermediate risk ALI patients. The ARDSNet model provided reasonable, but imprecise, estimates of predicted mortality when applied to our external validation cohort of ALI patients.
doi:10.1097/CCM.0b013e31820ead31
PMCID: PMC3129473  PMID: 21336135
respiratory distress syndrome; adult; statistical model; mortality determinants; prognosis; health status indicators; intensive care units
6.  Estimating the Causal Effect of Low Tidal Volume Ventilation on Survival in Patients with Acute Lung Injury† 
Summary
Acute lung injury (ALI) is a condition characterized by acute onset of severe hypoxemia and bilateral pulmonary infiltrates. ALI patients typically require mechanical ventilation in an intensive care unit. Low tidal volume ventilation (LTVV), a time-varying dynamic treatment regime, has been recommended as an effective ventilation strategy. This recommendation was based on the results of the ARMA study, a randomized clinical trial designed to compare low vs. high tidal volume strategies (The Acute Respiratory Distress Syndrome Network, 2000) . After publication of the trial, some critics focused on the high non-adherence rates in the LTVV arm suggesting that non-adherence occurred because treating physicians felt that deviating from the prescribed regime would improve patient outcomes. In this paper, we seek to address this controversy by estimating the survival distribution in the counterfactual setting where all patients assigned to LTVV followed the regime. Inference is based on a fully Bayesian implementation of Robins’ (1986) G-computation formula. In addition to re-analyzing data from the ARMA trial, we also apply our methodology to data from a subsequent trial (ALVEOLI), which implemented the LTVV regime in both of its study arms and also suffered from non-adherence.
doi:10.1111/j.1467-9876.2010.00757.x
PMCID: PMC3197806  PMID: 22025809
Bayesian inference; Causal inference; Dynamic treatment regime; G-computation formula
7.  Early mobilisation of intensive care unit patient: the challenges of morbid obesity and multiorgan failure 
BMJ Case Reports  2010;2010:bcr09.2009.2257.
A 44-year-old morbidly obese (body mass index 69 kg/m2) woman presented to our medical intensive care unit (ICU) with septic shock and multiorgan failure requiring mechanical ventilation, a vasopressor infusion, and haemodialysis. Before this admission, the patient reported being able to ambulate approximately 3 m with a walker. Intensive physical therapy was started on ICU day 2, and the patient was successfully mobilised throughout her ICU stay despite the extreme challenges posed by her morbid obesity and critical illness. After only a 9 day stay, the patient was discharged directly home from the medical ICU, walking a total distance of 37 m in a single physical therapy session.
doi:10.1136/bcr.09.2009.2257
PMCID: PMC3027523  PMID: 22461852
8.  Sleep Deprivation in Critical Illness: Its Role in Physical and Psychological Recovery 
Critically ill patients frequently experience poor sleep, characterized by frequent disruptions, loss of circadian rhythms, and a paucity of time spent in restorative sleep stages. Factors that are associated with sleep disruption in the intensive care unit (ICU) include patient-ventilator dysynchrony, medications, patient care interactions, and environmental noise and light. As the field of critical care increasingly focuses on patients' physical and psychological outcomes following critical illness, understanding the potential contribution of ICU-related sleep disruption on patient recovery is an important area of investigation. This review article summarizes the literature regarding sleep architecture and measurement in the critically ill, causes of ICU sleep fragmentation, and potential implications of ICU-related sleep disruption on patients' recovery from critical illness. With this background information, strategies to optimize sleep in the ICU are also discussed.
doi:10.1177/0885066610394322
PMCID: PMC3299928  PMID: 21220271
sleep; sleep deprivation; intensive care unit; mental health; outcomes
9.  Inter-rater reliability of manual muscle strength testing in ICU survivors and simulated patients 
Intensive care medicine  2010;36(6):1038-1043.
Objective
The goal of the paper is to determine inter-rater reliability of trained examiners performing standardized strength assessments using manual muscle testing (MMT).
Design, subjects, and setting
The authors report on 19 trainees undergoing quality assurance within a multi-site prospective cohort study.
Intervention
Inter-rater reliability for specially trained evaluators (“trainees”) and a reference rater, performing MMT using both simulated and actual patients recovering from critical illness was evaluated.
Measurements and results
Across 26 muscle groups tested by 19 trainee-reference rater pairs, the median (interquartile range) percent agreement and intraclass correlation coefficient (ICC; 95% CI) were: 96% (91, 98%) and 0.98 (0.95, 1.00), respectively. Across all 19 pairs, the ICC (95% CI) for the overall composite MMT score was 0.99 (0.98–1.00). When limited to actual patients, the ICC was 1.00 (95% CI 0.99–1.00). The agreement (kappa; 95% CI) in detecting clinically significant weakness was 0.88 (0.44–1.00).
Conclusions
MMT has excellent inter-rater reliability in trained examiners and is a reliable method of comprehensively assessing muscle strength.
doi:10.1007/s00134-010-1796-6
PMCID: PMC2891143  PMID: 20213068
Diagnostic techniques and procedures; Epidemiologic research design; Muscle strength; Muscle weakness; Physical examination; Reproducibility of results
10.  Beyond Mortality 
Mortality in National Heart, Lung and Blood Institute–sponsored clinical trials of treatments for acute lung injury (ALI) has decreased dramatically during the past two decades. As a consequence, design of such trials based on a mortality outcome requires ever-increasing numbers of patients. Recognizing that advances in clinical trial design might be applicable to these trials and might allow trials with fewer patients, the National Heart, Lung and Blood Institute convened a workshop of extramural experts from several disciplines. The workshop assessed the current state of clinical research addressing ALI, identified research needs, and recommended: (1) continued performance of trials evaluating treatments of patients with ALI; (2) development of strategies to perform ALI prevention trials; (3) observational studies of patients without ALI undergoing prolonged mechanical ventilation; and (4) development of a standardized format for reporting methods, endpoints, and results of ALI trials.
doi:10.1164/rccm.201001-0024WS
PMCID: PMC2874454  PMID: 20224063
clinical trials; acute respiratory distress syndrome; pulmonary diseases; edema; inflammation
11.  Impact of a statewide intensive care unit quality improvement initiative on hospital mortality and length of stay: retrospective comparative analysis 
Objective To evaluate whether implementation of the Michigan Keystone ICU project, a comprehensive statewide quality improvement initiative focused on reduction of infections, was associated with reductions in hospital mortality and length of stay for adults aged 65 or more admitted to intensive care units.
Design Retrospective comparative study, using data from Medicare claims.
Setting Michigan and Midwest region, United States.
Population The study period (October 2001 to December 2006) spanned two years before the project was initiated to 22 months after its implementation. The study sample included hospital admissions for patients treated in 95 study hospitals in Michigan (238 937 total admissions) compared with 364 hospitals in the surrounding Midwest region (1 091 547 total admissions).
Main outcome measures Hospital mortality and length of hospital stay.
Results The overall trajectory of mortality outcomes differed significantly between the two groups upon implementation of the project (Wald test χ2=8.73, P=0.033). Reductions in mortality were significantly greater for the study group than for the comparison group 1-12 months (odds ratio 0.83, 95% confidence interval 0.79 to 0.87 v 0.88, 0.85 to 0.90, P=0.041) and 13-22 months (0.76, 0.72 to 0.81 v 0.84, 0.81 to 0.86, P=0.007) after implementation of the project. The overall trajectory of length of stay did not differ significantly between the groups upon implementation of the project (Wald test χ2=2.05, P=0.560). Group differences in adjusted length of stay compared with baseline did not reach significance during implementation of the project (−0.45 days, 95% confidence interval −0.62 to −0.28 v −0.35, −0.52 to −0.19) or during post-implementation months 1-12 (−0.59, −0.80 to −0.37 v −0.42, −0.59 to −0.25) and 13-22 (−0.67, −0.91 to −0.43 v −0.54, −0.72 to −0.37).
Conclusions Implementation of the Keystone ICU project was associated with a significant decrease in hospital mortality in Michigan compared with the surrounding area. The project was not, however, sufficiently powered to show a significant difference in length of stay.
doi:10.1136/bmj.d219
PMCID: PMC3031651  PMID: 21282262
12.  A knowledge translation collaborative to improve the use of therapeutic hypothermia in post-cardiac arrest patients: protocol for a stepped wedge randomized trial 
Background
Advances in resuscitation science have dramatically improved survival rates following cardiac arrest. However, about 60% of adults that regain spontaneous circulation die before leaving the hospital. Recently it has been shown that inducing hypothermia in cardiac arrest survivors immediately following their arrival in hospital can dramatically improve both overall survival and neurological outcomes. Despite the strong evidence for its efficacy and the apparent simplicity of this intervention, recent surveys show that therapeutic hypothermia is delivered inconsistently, incompletely, and often with delay.
Methods and design
This study will evaluate a multi-faceted knowledge translation strategy designed to increase the utilization rate of induced hypothermia in survivors of cardiac arrest across a network of 37 hospitals in Southwestern Ontario, Canada. The study is designed as a stepped wedge randomized trial lasting two years. Individual hospitals will be randomly assigned to four different wedges that will receive the active knowledge translation strategy according to a sequential rollout over a number of time periods. By the end of the study, all hospitals will have received the intervention. The primary aim is to measure the effectiveness of a multifaceted knowledge translation plan involving education, reminders, and audit-feedback for improving the use of induced hypothermia in survivors of cardiac arrest presenting to the emergency department. The primary outcome is the proportion of eligible OHCA patients that are cooled to a body temperature of 32 to 34°C within six hours of arrival in the hospital. Secondary outcomes will include process of care measures and clinical outcomes.
Discussion
Inducing hypothermia in cardiac arrest survivors immediately following their arrival to hospital has been shown to dramatically improve both overall survival and neurological outcomes. However, this lifesaving treatment is frequently not applied in practice. If this trial is positive, our results will have broad implications by showing that a knowledge translation strategy shared across a collaborative network of hospitals can increase the number of patients that receive this lifesaving intervention in a timely manner.
Trial Registration
ClinicalTrials.gov Trial Identifier: NCT00683683
doi:10.1186/1748-5908-6-4
PMCID: PMC3031244  PMID: 21235799
13.  Deciding who to admit to a critical care unit 
BMJ : British Medical Journal  2007;335(7630):1103-1104.
Scarce resources may cause doctors to be pessimistic about prognosis and refuse critical care admissions
doi:10.1136/bmj.39378.654329.80
PMCID: PMC2099542  PMID: 17975253
14.  Are Intensive Care Factors Associated with Depressive Symptoms Six Months after Acute Lung Injury? 
Critical care medicine  2009;37(5):1702-1707.
Objective
To evaluate intensive care-related factors as predictors of depressive symptoms 6 months after acute lung injury (ALI)
Design
Prospective cohort study
Setting
Thirteen intensive care units (ICUs) in 4 hospitals in Baltimore, MD
Patients
Consecutive ALI survivors (n = 160; 71% from medical ICUs) screened for depressive symptoms at six months post-ALI
Interventions
None
Measurements and Main Results
We prospectively measured 12 features of critical illness and ICU care and used multivariable regression to evaluate associations with depressive symptoms as measured by the Hospital Anxiety and Depression (HAD) depression score. The prevalence of a positive screening for depression (score ≥8) at 6 months post-ALI was 26%. Depressive symptoms were significantly associated with surgical (versus medical or trauma) ICU admission (relative risk [RR] 2.2, 95% confidence interval [CI] 1.1 – 4.2), maximum daily Sequential Organ Failure Assessment score of >10 (RR 2.1, 95% CI 1.1 – 3.5), and mean daily ICU benzodiazepine dose of ≥75mg of midazolam-equivalent (RR 2.1, 95% CI 1.1 – 3.5).
Conclusions
Depressive symptoms at 6 months post-ALI are common and potentially associated with ICU-related factors. Mechanisms by which critical illness and intensive care management associate with depressive symptoms merit further investigation.
doi:10.1097/CCM.0b013e31819fea55
PMCID: PMC2769249  PMID: 19357507
depression; intensive care units; respiratory distress syndrome; adult; critical care; outcome assessment (health care)
15.  Pulmonary vs Nonpulmonary Sepsis and Mortality in Acute Lung Injury 
Chest  2008;134(3):534-538.
Background
Acute lung injury (ALI) is a frequent complication of sepsis. It is unclear if a pulmonary vs nonpulmonary source of sepsis affects mortality in patients with sepsis-induced ALI.
Methods
Two hundred eighty-eight consecutive patients with sepsis-induced ALI from 14 ICUs at four hospitals in Baltimore,MDwere prospectively classified as having a pulmonary vs nonpulmonary source of sepsis. Multiple logistic regression was conducted to evaluate the independent association of a pulmonary vs nonpulmonary source of sepsis with inpatient mortality.
Results
In an unadjusted analysis, in-hospital mortality was lower for pulmonary vs nonpulmonary source of sepsis (42% vs 66%, p < 0.0001). Patients with pulmonary sepsis had lower acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, shorter ICU stays prior to the development of ALI, and higher lung injury scores. In the adjusted analysis, several factors were predictive of mortality: age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 to 1.06), Charlson comorbidity index (OR, 1.15; 95% CI, 1.02 to 1.30), ICU length of stay prior to ALI diagnosis (OR, 1.19; 95% CI, 1.01 to 1.39), APACHE II score (OR, 1.07; 95% CI, 1.03 to 1.12), lung injury score (OR, 1.64; 95% CI, 1.11 to 2.43), SOFA score (OR, 1.15; 95% CI, 1.06 to 1.26), and cumulative fluid balance in the first 7 days after ALI diagnosis (OR, 1.06; 95% CI, 1.03 to 1.10). A pulmonary vs nonpulmonary source of sepsis was not independently associated with mortality (OR, 0.72; 95% CI, 0.38 to 1.35).
Conclusions
Although lower mortality was observed for ALI patients with a pulmonary vs nonpulmonary source of sepsis, this finding is likely due to a lower severity of illness in those with pulmonary sepsis. Pulmonary vs nonpulmonary source of sepsis was not independently predictive of mortality for patients with ALI.
doi:10.1378/chest.08-0309
PMCID: PMC2849158  PMID: 18641112
ARDS; critical illness; mortality; sepsis
16.  Improving data quality control in quality improvement projects 
Background
The results of many quality improvement (QI) projects are gaining wide-spread attention. Policy-makers, hospital leaders and clinicians make important decisions based on the assumption that QI project results are accurate. However, compared with clinical research, QI projects are typically conducted with substantially fewer resources, potentially impacting data quality. Our objective was to provide a primer on basic data quality control methods appropriate for QI efforts.
Methods
Data quality control methods should be applied throughout all phases of a QI project. In the design phase, project aims should guide data collection decisions, emphasizing quality (rather than quantity) of data and considering resource limitations. In the data collection phase, standardized data collection forms, comprehensive staff training and a well-designed database can help maximize the quality of the data. Clearly defined data elements, quality assurance reviews of both collection and entry and system-based controls reduce the likelihood of error. In the data management phase, missing data should be quickly identified and corrected with system-based controls to minimize the missing data. Finally, in the data analysis phase, appropriate statistical methods and sensitivity analysis aid in managing and understanding the effects of missing data and outliers, in addressing potential confounders and in conveying the precision of results.
Conclusion
Data quality control is essential to ensure the integrity of results from QI projects. Feasible methods are available and important to help ensure that stakeholder's decisions are based on accurate data.
doi:10.1093/intqhc/mzp005
PMCID: PMC2734082  PMID: 19218334
data quality; research design; data reporting; quality controls
17.  Sustaining reductions in catheter related bloodstream infections in Michigan intensive care units: observational study 
Objectives To evaluate the extent to which intensive care units participating in the initial Keystone ICU project sustained reductions in rates of catheter related bloodstream infections.
Design Collaborative cohort study to implement and evaluate interventions to improve patients’ safety.
Setting Intensive care units predominantly in Michigan, USA.
Intervention Conceptual model aimed at improving clinicians’ use of five evidence based recommendations to reduce rates of catheter related bloodstream infections rates, with measurement and feedback of infection rates. During the sustainability period, intensive care unit teams were instructed to integrate this intervention into staff orientation, collect monthly data from hospital infection control staff, and report infection rates to appropriate stakeholders.
Main outcome measures Quarterly rate of catheter related bloodstream infections per 1000 catheter days during the sustainability period (19-36 months after implementation of the intervention).
Results Ninety (87%) of the original 103 intensive care units participated, reporting 1532 intensive care unit months of data and 300 310 catheter days during the sustainability period. The mean and median rates of catheter related bloodstream infection decreased from 7.7 and 2.7 (interquartile range 0.6-4.8) at baseline to 1.3 and 0 (0-2.4) at 16-18 months and to 1.1 and 0 (0.0-1.2) at 34-36 months post-implementation. Multilevel regression analysis showed that incidence rate ratios decreased from 0.68 (95% confidence interval 0.53 to 0.88) at 0-3 months to 0.38 (0.26 to 0.56) at 16-18 months and 0.34 (0.24-0.48) at 34-36 months post-implementation. During the sustainability period, the mean bloodstream infection rate did not significantly change from the initial 18 month post-implementation period (−1%, 95% confidence interval −9% to 7%).
Conclusions The reduced rates of catheter related bloodstream infection achieved in the initial 18 month post-implementation period were sustained for an additional 18 months as participating intensive care units integrated the intervention into practice. Broad use of this intervention with achievement of similar results could substantially reduce the morbidity and costs associated with catheter related bloodstream infections.
doi:10.1136/bmj.c309
PMCID: PMC2816728  PMID: 20133365
18.  ICU staffing and patient outcomes: more work remains 
Critical Care  2009;13(1):101.
Many studies have demonstrated that closed intensive care units (ICUs), staffed by trained intensivists, are associated with improved patient outcomes. However, the mechanisms by which ICU organizational factors, such as physician staffing, influence patient outcomes are unclear. One potential mechanism is the increased utilization of evidence-based practices in closed ICUs. Cooke and colleagues investigated this hypothesis in a cohort of 759 acute lung injury patients in 23 ICUs in King County, Washington, USA. Although closed ICUs were independently associated with a modestly lower mean tidal volume, this finding did not explain the mortality benefit associated with a closed ICU model in this patient cohort. Future studies should evaluate other potential mechanisms by which closed ICUs improve patient outcomes. An improved understanding of these mechanisms may yield new targets for improving the quality of medical care for all ICU patients.
doi:10.1186/cc7113
PMCID: PMC2688090  PMID: 19183427
19.  Intensive Care Unit Hypoglycemia Predicts Depression during Early Recovery from Acute Lung Injury 
Critical care medicine  2008;36(10):2726-2733.
Objective
To evaluate the association between intensive care unit (ICU) blood glucose levels and depression following acute lung injury (ALI)
Design
Prospective cohort study
Setting
Twelve ICUs in 4 hospitals in Baltimore, MD
Patients
Consecutive ALI survivors (n = 104) monitored during 1,717 ICU patient-days and screened for depression at three months after ALI
Interventions
None
Measurements and Main Results
The prevalence of a positive screening test for depression (Hospital Anxiety and Depression [HAD] depression sub-scale score ≥8) at follow-up was 28%. After adjustment for confounders, patients with a mean daily minimum ICU glucose <100 mg/dL had significant increases in mean depression score [2.1 points, 95% confidence interval (CI) 0.6 – 3.7] and in the likelihood of a positive depression screening test [relative risk (RR) 2.6, 95% CI 1.2 – 4.2]. Patients with documented hypoglycemia <60 mg/dL during their ICU stay also had greater symptoms of depression (2.0 points, 95% CI 0.5 – 3.5; RR 3.6, 95% CI 1.8 – 5.1). Other factors independently associated with a positive depression screening test included body mass index >40 kg/m2 (RR 3.3, 95% CI 1.2 – 4.2), baseline depression/anxiety (RR 3.9, 95% CI 1.5 – 6.5), and mean daily ICU benzodiazepine dose >100mg of midazolam-equivalent (RR 2.4, 95% CI 1.1 – 3.8).
Conclusions
Hypoglycemia in the ICU is associated with an increased risk of positive screening for depression during early recovery from ALI. Baseline depressive symptoms, morbid obesity, and ICU benzodiazepine dose were also associated with post-ALI depressive symptoms. These findings warrant increased glucose monitoring for ICU patients at risk for hypoglycemia and further research on how patient and ICU management factors may contribute to post-ICU depression.
doi:10.1097/CCM.0b013e31818781f5
PMCID: PMC2605796  PMID: 18766087
hypoglycemia; depression; intensive care units; respiratory distress syndrome; adult; critical care; blood glucose
20.  Mortality in sepsis versus non-sepsis induced acute lung injury 
Critical Care  2009;13(5):R150.
Introduction
Sepsis-induced acute lung injury (ALI) has been reported to have a higher case fatality rate than other causes of ALI. However, differences in the severity of illness in septic vs. non-septic ALI patients might explain this finding.
Methods
520 patients enrolled in the Improving Care of ALI Patients Study (ICAP) were prospectively characterized as having sepsis or non sepsis-induced ALI. Biologically plausible risk factors for in-hospital death were considered in multiple logistic regression models to evaluate the independent association of sepsis vs. non-sepsis ALI risk factors with mortality.
Results
Patients with sepsis-induced ALI had greater illness severity and organ dysfunction (APACHE II and SOFA scores) at ALI diagnosis and higher crude in-hospital mortality rates compared with non-sepsis ALI patients. Patients with sepsis-induced ALI received similar tidal volumes, but higher levels of positive end expiratory pressure, and had a more positive net fluid balance in the first week after ALI diagnosis. In multivariable analysis, the following variables (odds ratio, 95% confidence interval) were significantly associated with hospital mortality: age (1.04, 1.02 to 1.05), admission to a medical intensive care unit (ICU) (2.76, 1.42 to 5.36), ICU length of stay prior to ALI diagnosis (1.15, 1.03 to 1.29), APACHE II (1.05, 1.02 to 1.08), SOFA at ALI diagnosis (1.17, 1.09 to 1.25), Lung Injury Score (2.33, 1.74 to 3.12) and net fluid balance in liters in the first week after ALI diagnosis (1.06, 1.03 to 1.09). Sepsis did not have a significant, independent association with mortality (1.02, 0.59 to 1.76).
Conclusions
Greater severity of illness contributes to the higher case fatality rate observed in sepsis-induced ALI. Sepsis was not independently associated with mortality in our study.
doi:10.1186/cc8048
PMCID: PMC2784371  PMID: 19758459
21.  Posttraumatic Stress Disorder in General Intensive Care Unit Survivors: A Systematic Review 
General hospital psychiatry  2008;30(5):421-434.
Objective
Our objective was to summarize and critically review data on the prevalence of posttraumatic stress disorder (PTSD) in general intensive care unit (ICU) survivors, risk factors for post-ICU PTSD, and the impact of post-ICU PTSD on health-related quality of life (HRQOL).
Methods
We conducted a systematic literature review using Medline, EMBASE, Cochrane Library, CINAHL, PsycINFO, and a hand-search of thirteen journals.
Results
Fifteen studies were eligible. The median point prevalence of questionnaire-ascertained “clinically significant” PTSD symptoms was 22% (n = 1,104), and the median point prevalence of clinician-diagnosed PTSD was 19% (n = 93). Consistent predictors of post-ICU PTSD included prior psychopathology, greater ICU benzodiazepine administration, and post-ICU memories of in-ICU frightening and/or psychotic experiences. Female sex and younger age were less consistent predictors, and severity of critical illness was consistently not a predictor. Post-ICU PTSD was associated with substantially lower HRQOL.
Conclusions
The prevalence of PTSD in ICU survivors is high and negatively impacts survivors’ HRQOL. Future studies should comprehensively address how patient-specific factors (e.g., pre-ICU psychopathology), ICU management factors (e.g., administration of sedatives), and ICU clinical factors (e.g., in-ICU delirium) relate to one another and to post-ICU PTSD. Clinicians caring for the growing population of ICU survivors should be aware of PTSD risk factors and monitor patients’ needs for early intervention.
doi:10.1016/j.genhosppsych.2008.05.006
PMCID: PMC2572638  PMID: 18774425
stress disorder; posttraumatic; critical care; intensive care unit; risk factors; outcome assessment (health care)
22.  Red Blood Cell Transfusion Practices in Acute Lung Injury: What do patient factors contribute? 
Critical care medicine  2009;37(6):1935-1940.
Objective
To describe red blood cell (RBC) transfusion practices and evaluate the association between patient-related factors and pre-transfusion hemoglobin concentration in acute lung injury (ALI).
Design
Secondary analysis of prospectively collected data
Setting
9 intensive care units (ICUs) in 3 teaching hospitals in Baltimore, MD
Patients
249 consecutive, mechanically ventilated ALI patients
Interventions
None
Measurements and Main Results
Simple and multiple linear regression analyses were used to evaluate the association between the nadir hemoglobin concentration on the day of initial RBC transfusion and 20 patient-level demographic, clinical and ICU treatment factors as well as ICU type. Of 249 ALI patients, 47% received a RBC transfusion in the ICU without evidence of active hemorrhage or acute cardiac ischemia. The mean (standard deviation [SD]) nadir hemoglobin on the day of first transfusion was 7.7 (1.1) g/dL with 67%, 36%, 15%, and 5% of patients transfused at >7, >8, >9, and >10g/dL, respectively. Transfused patients received a mean (SD) of 5 (6) RBC units from ALI diagnosis to ICU discharge. Pre-hospital use of iron or erythropoietin and platelet transfusion in the ICU were independently associated with lower pre-transfusion hemoglobin concentrations. No patient factors were associated with higher hemoglobin concentrations. Admission to a surgical (vs. medical) ICU was associated with a 0.6 g/dL (95% CI: 0.1, 1.1 g/dL) higher pre-transfusion hemoglobin.
Conclusions
ALI patients commonly receive RBC transfusions in the ICU. The pre-transfusion hemoglobin observed in our study was lower than earlier studies, but a restrictive strategy was not universally adopted. Patient factors do not explain the gap between clinical trial evidence and routine transfusion practices. Future studies should further explore ICU- and physician-related factors as a source of variability in transfusion practice.
doi:10.1097/CCM.0b013e3181a0022d
PMCID: PMC2729062  PMID: 19384204
blood transfusion; erythrocyte indices; respiratory distress syndrome; adult; intensive care units; outcome and process assessment (health care)
23.  Bench-to-bedside review: Mobilizing patients in the intensive care unit – from pathophysiology to clinical trials 
Critical Care  2009;13(4):216.
As the mortality from critical illness has improved in recent years, there has been increasing focus on patient outcomes after hospital discharge. Neuromuscular weakness acquired in the intensive care unit (ICU) is common, persistent, and often severe. Immobility due to prolonged bed rest in the ICU may play an important role in the development of ICU-acquired weakness. Studies in other patient populations have demonstrated that moderate exercise is beneficial in altering the inflammatory milieu associated with immobility, and in improving muscle strength and physical function. Recent studies have demonstrated that early mobility in the ICU is safe and feasible, with a potential reduction in short-term physical impairment. However, early mobility requires a significant change in ICU practice, with reductions in heavy sedation and bed rest. Further research is required to determine whether early mobility in the ICU can improve patients' short-term and long-term outcomes.
doi:10.1186/cc7885
PMCID: PMC2750129  PMID: 19664166
24.  Creating High Reliability in Health Care Organizations 
Health Services Research  2006;41(4 Pt 2):1599-1617.
Objective
The objective of this paper was to present a comprehensive approach to help health care organizations reliably deliver effective interventions.
Context
Reliability in healthcare translates into using valid rate-based measures. Yet high reliability organizations have proven that the context in which care is delivered, called organizational culture, also has important influences on patient safety.
Model for Improvement
Our model to improve reliability, which also includes interventions to improve culture, focuses on valid rate-based measures. This model includes (1) identifying evidence-based interventions that improve the outcome, (2) selecting interventions with the most impact on outcomes and converting to behaviors, (3) developing measures to evaluate reliability, (4) measuring baseline performance, and (5) ensuring patients receive the evidence-based interventions. The comprehensive unit-based safety program (CUSP) is used to improve culture and guide organizations in learning from mistakes that are important, but cannot be measured as rates.
Conclusions
We present how this model was used in over 100 intensive care units in Michigan to improve culture and eliminate catheter-related blood stream infections—both were accomplished. Our model differs from existing models in that it incorporates efforts to improve a vital component for system redesign—culture, it targets 3 important groups—senior leaders, team leaders, and front line staff, and facilitates change management—engage, educate, execute, and evaluate for planned interventions.
doi:10.1111/j.1475-6773.2006.00567.x
PMCID: PMC1955341  PMID: 16898981
Patient safety; quality; reliability; culture
25.  Systematic review identifies number of strategies important for retaining study participants 
Journal of clinical epidemiology  2007;60(8):757-765.
Objective
Loss to follow-up threatens internal and external validity yet little research has examined ways to limit participant attrition. We conducted a systematic review of studies with a primary focus on strategies to retain participants in health care research.
Study Design
We completed searches of PubMed, CINAHL, CENTRAL, Cochrane Methodology Register, and EMBASE (August 2005). We also examined reference lists of eligible articles and relevant reviews. A data-driven thematic analysis of the retention strategies identified common themes.
Results
We retrieved 3,068 citations, 21 studies were eligible for inclusion. We abstracted 368 strategies and from these identified 12 themes. The studies reported a median of 17 strategies across a median of six themes. The most commonly reported strategies were systematic methods of participant contact and scheduling. Studies with retention rates lower than the mean rate (86%) reported fewer strategies. There was no difference in the number of themes used.
Conclusion
Available evidence suggests that investigators should consider using a number of retention strategies across several themes to maximize the retention of participants. Further research, including explicit evaluation of the effectiveness of different strategies, is needed.
doi:10.1016/j.jclinepi.2006.11.023
PMCID: PMC1997303  PMID: 17606170
patient participation; patient dropouts; in-person follow-up; follow-up studies; cohort studies; systematic review

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