Anemia in Critically Ill Patients With Acute Respiratory Distress Syndrome and Posthospitalization Physical Outcomes.

OBJECTIVE: Anemia is common during critical illness and often persists after hospital discharge; however, its potential association with physical outcomes after critical illness is unclear. Our objective was to assess the associations between hemoglobin at intensive care unit (ICU) and hospital discharge with physical status at 3-month follow-up in acute respiratory distress syndrome (ARDS) survivors. METHODS: This is a secondary analysis of a multisite prospective cohort study of 195 mechanically ventilated ARDS survivors from 13 ICUs at 4 teaching hospitals in Baltimore, Maryland. Multivariable regression was utilized to assess the relationships between ICU and hospital discharge hemoglobin concentrations with measures of physical status at 3 months, including muscle strength (Medical Research Council sumscore), exercise capacity (6-minute walk distance [6MWD]), and self-reported physical functioning (36-Item Short-Form Health Survey [SF-36v2] Physical Function score and Activities of Daily Living [ADL] dependencies). RESULTS: Median (interquartile range) hemoglobin concentrations at ICU and hospital discharge were 9.5 (8.5-10.7) and 10.0 (9.0-11.2) g/dL, respectively. In multivariable regression analyses, higher ICU discharge hemoglobin concentrations (per 1 g/dL) were associated with greater 3-month 6MWD mean percent of predicted (3.7% [95% confidence interval 0.8%-6.5%]; P = .01) and fewer ADL dependencies (-0.2 [-0.4 to -0.1]; P = .02), but not with percentage of maximal muscle strength (0.7% [-0.9 to 2.3]; P = .37) or SF-36v2 normalized Physical Function scores (0.8 [-0.3 to 1.9]; P = .15). The associations of physical outcomes and hospital discharge hemoglobin concentrations were qualitatively similar, but none were statistically significant. CONCLUSIONS: In ARDS survivors, higher hemoglobin concentrations at ICU discharge, but not hospital discharge, were significantly associated with improved exercise capacity and fewer ADL dependencies. Future studies are warranted to further assess these relationships.

Laryngeal Injury and Upper Airway Symptoms After Endotracheal Intubation During Surgery: A Systematic Review and Meta-analysis.

Laryngeal injury from intubation can substantially impact airway, voice, and swallowing, thus necessitating multidisciplinary interventions. The goals of this systematic review were (1) to review the types of laryngeal injuries and their patient-reported symptoms and clinical signs resulting from endotracheal intubation in patients intubated for surgeries and (2) to better understand the overall the frequency at which these injuries occur. We conducted a search of 4 online bibliographic databases (ie, PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature [CINAHL], and The Cochrane Library) and ProQuest and Open Access Thesis Dissertations (OPTD) from database inception to September 2019 without restrictions for language. Studies that completed postextubation laryngeal examinations with visualization in adult patients who were endotracheally intubated for surgeries were included. We excluded (1) retrospective studies, (2) case studies, (3) preexisting laryngeal injury/disease, (4) patients with histories of or surgical interventions that risk injury to the recurrent laryngeal nerve, (5) conference abstracts, and (6) patient populations with nonfocal, neurological impairments that may impact voice and swallowing function, thus making it difficult to identify isolated postextubation laryngeal injury. Independent, double-data extraction, and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Collaboration's criteria. Twenty-one articles (1 cross-sectional, 3 cohort, 5 case series, 12 randomized controlled trials) representing 21 surgical studies containing 6140 patients met eligibility criteria. The mean patient age across studies reporting age was 49 (95% confidence interval [CI], 45-53) years with a mean intubation duration of 132 (95% CI, 106-159) minutes. Studies reported no injuries in 80% (95% CI, 69-88) of patients. All 21 studies presented on type of injury. Edema was the most frequently reported mild injury, with a prevalence of 9%-84%. Vocal fold hematomas were the most frequently reported moderate injury, with a prevalence of 4% (95% CI, 2-10). Severe injuries that include subluxation of the arytenoids and vocal fold paralysis are rare (<1%) outcomes. The most prevalent patient complaints postextubation were dysphagia (43%), pain (38%), coughing (32%), a sore throat (27%), and hoarseness (27%). Overall, laryngeal injury from short-duration surgical intubation is common and is most often mild. No uniform guidelines for laryngeal assessment postextubation from surgery are available and hoarseness is neither a good indicator of laryngeal injury or dysphagia. Protocolized screening for dysphonia and dysphagia postextubation may lead to improved identification of injury and, therefore, improved patient outcomes and reduced health care utilization.

Real-Time Intracellular Temperature Imaging Using Lanthanide-Bearing Polymeric Micelles.

Measurement of thermogenesis in individual cells is a remarkable challenge due to the complexity of the biochemical environment (such as pH and ionic strength) and to the rapid and yet not well-understood heat transfer mechanisms throughout the cell. Here, we present a unique system for intracellular temperature mapping in a fluorescence microscope (uncertainty of 0.2 K) using rationally designed luminescent Ln3+-bearing polymeric micellar probes (Ln = Sm, Eu) incubated in breast cancer MDA-MB468 cells. Two-dimensional (2D) thermal images recorded increasing the temperature of the cells culture medium between 296 and 304 K shows inhomogeneous intracellular temperature progressions up to ∼20 degrees and subcellular gradients of ∼5 degrees between the nucleolus and the rest of the cell, illustrating the thermogenic activity of the different organelles and highlighting the potential of this tool to study intracellular processes.

Return to work and lost earnings after acute respiratory distress syndrome: a 5-year prospective, longitudinal study of long-term survivors.

BACKGROUND: Delayed return to work is common after acute respiratory distress syndrome (ARDS), but has undergone little detailed evaluation. We examined factors associated with the timing of return to work after ARDS, along with lost earnings and shifts in healthcare coverage. METHODS: Five-year, multisite prospective, longitudinal cohort study of 138 2-year ARDS survivors hospitalised between 2004 and 2007. Employment and healthcare coverage were collected via structured interview. Predictors of time to return to work were evaluated using Fine and Grey regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data. RESULTS: Sixty-seven (49%) of the 138 2-year survivors were employed prior to ARDS. Among 64 5-year survivors, 20 (31%) never returned to work across 5-year follow-up. Predictors of delayed return to work (HR (95% CI)) included baseline Charlson Comorbidity Index (0.77 (0.59 to 0.99) per point; p=0.04), mechanical ventilation duration (0.67 (0.55 to 0.82) per day up to 5 days; p<0.001) and discharge to a healthcare facility (0.49 (0.26 to 0.93); p=0.03). Forty-nine of 64 (77%) 5-year survivors incurred lost earnings, with average (SD) losses ranging from US$38 354 (21,533) to US$43 510 (25,753) per person per year. Jobless, non-retired survivors experienced a 33% decrease in private health insurance and concomitant 37% rise in government-funded coverage. CONCLUSIONS: Across 5-year follow-up, nearly one-third of previously employed ARDS survivors never returned to work. Delayed return to work was associated with patient-related and intensive care unit/hospital-related factors, substantial lost earnings and a marked rise in government-funded healthcare coverage. These important consequences emphasise the need to design and evaluate vocation-based interventions to assist ARDS survivors return to work.

Evaluation of a Measurement System to Assess ICU Team Performance.

OBJECTIVE: Measuring teamwork is essential in critical care, but limited observational measurement systems exist for this environment. The objective of this study was to evaluate the reliability and validity of a behavioral marker system for measuring teamwork in ICUs. DESIGN: Instances of teamwork were observed by two raters for three tasks: multidisciplinary rounds, nurse-to-nurse handoffs, and retrospective videos of medical students and instructors performing simulated codes. Intraclass correlation coefficients were calculated to assess interrater reliability. Generalizability theory was applied to estimate systematic sources of variance for the three observed team tasks that were associated with instances of teamwork, rater effects, competency effects, and task effects. SETTING: A 15-bed surgical ICU at a large academic hospital. SUBJECTS: One hundred thirty-eight instances of teamwork were observed. Specifically, we observed 88 multidisciplinary rounds, 25 nurse-to-nurse handoffs, and 25 simulated code exercises. INTERVENTIONS: No intervention was conducted for this study. MEASUREMENTS AND MAIN RESULTS: Rater reliability for each overall task ranged from good to excellent correlation (intraclass correlation coefficient, 0.64-0.81), although there were seven cases where reliability was fair and one case where it was poor for specific competencies. Findings from generalizability studies provided evidence that the marker system dependably distinguished among teamwork competencies, providing evidence of construct validity. CONCLUSIONS: Teamwork in critical care is complex, thereby complicating the judgment of behaviors. The marker system exhibited great potential for differentiating competencies, but findings also revealed that more context specific guidance may be needed to improve rater reliability.

Factors associated with missed assessments in a 2-year longitudinal study of acute respiratory distress syndrome survivors.

BACKGROUND: To evaluate participant-related variables associated with missing assessment(s) at follow-up visits during a longitudinal research study. METHODS: This is a prospective, longitudinal, multi-site study of 196 acute respiratory distress syndrome (ARDS) survivors. More than 30 relevant sociodemographic, physical status, and mental health variables (representing participant characteristics prior to ARDS, at hospital discharge, and at the immediately preceding follow-up visit) were evaluated for association with missed assessments at 3, 6, 12, and 24-month follow-up visits (89-95% retention rates), using binomial logistic regression. RESULTS: Most participants were male (56%), white (58%), and ≤ high school education (64%). Sociodemographic characteristics were not associated with missed assessments at the initial 3-month visit or subsequent visits. The number of dependencies in Activities of Daily Living (ADLs) at hospital discharge was associated with higher odds of missed assessments at the initial visit (OR: 1.26, 95% CI: 1.12, 1.43). At subsequent 6-, 12-, and 24 months visits, post-hospital discharge physical and psychological status were not associated with subsequent missed assessments. Instead, the following were associated with lower odds of missed assessments: indicators of poorer health prior to hospital admission (inability to walk 5 min (OR: 0.46; 0.23, 0.91), unemployment due to health (OR: 0.47; 0.23, 0.96), and alcohol abuse (OR: 0.53; 0.28, 0.97)) and having the preceding visit at the research clinic rather than at home/facility, or by phone/mail (OR: 0.54; 0.31, 0.96). Inversely, variables associated with higher odds of missed assessments at subsequent visits include: functional dependency prior to hospital admission (i.e. dependency with > = 2 Instrumental Activities of Daily Living (IADLs) (OR: 1.96; 1.08, 3.52), and missing assessments at preceding visit (OR: 2.26; 1.35, 3.79). CONCLUSIONS: During the recovery process after hospital discharge, dependencies in physical functioning (e.g. ADLs, IADLs) prior to hospitalization and at hospital discharge were associated with higher odds of missed assessments. Conversely, other indicators of poorer health at baseline were associated with lower odds of missed assessments after the initial post-discharge visit. To reduce missing assessments, longitudinal clinical research studies may benefit from focusing additional resources on participants with dependencies in physical functioning prior to hospitalization and at hospital discharge.

Are physical measures related to patient-centred outcomes in ARDS survivors?

OBJECTIVE: To inform selection of physical measures for studies of acute respiratory distress syndrome (ARDS) survivors within 12 months of ARDS. METHODS: Secondary analysis of data from 6-month survivors participating in a US multicentre prospective study (ARDSNet Long-Term Outcome Study, N=134) or a multisite prospective study in Baltimore, Maryland, USA (Improving Care of Acute Lung Injury Patients, N=99). Physical measures, assessed at 6-month follow-up, were categorised according to the WHO's International Classification of Disability and Health: body functions and structures, activity and participation. Patient-centred outcomes were evaluated at 6 and 12 months: survival, hospitalisation, alive at home status and health-related quality of life. Pearson correlation, linear and logistic regression models were used to quantify associations of physical measures with patient-centred outcomes. MAIN RESULTS: No 6-month body functions and structures measure demonstrated consistent association with 6-month or 12-month outcomes in multivariable regression. The 6 min walk test, an activity measure, was associated with 6-month Short-Form 36 (SF-36) physical component scores (PCS, ß range: 0.99 to 1.52, p<0.05). Participation measures (Functional Performance Inventory, FPI; Instrumental Activities of Daily Living, IADLs) were associated with SF-36 PCS (ß range: FPI, 1.51-1.52; IADL, -1.88 to -1.32; all p<0.05) and Euro-QOL-5D utility score (ß range: FPI, 2.00-3.67; IADL, -2.89 to -2.50; all p<0.01) at 6 and 12 months. CONCLUSIONS: Participation measures better reflect patient's quality of life than measures of body functions and structures within 12 months of ARDS among 6-month survivors, and are recommended for inclusion as a core measure in future studies.

Muscle Weakness and 5-Year Survival in Acute Respiratory Distress Syndrome Survivors.

OBJECTIVES: To longitudinally evaluate the association of post-ICU muscle weakness and associated trajectories of weakness over time with 5-year survival. DESIGN: Longitudinal prospective cohort study over 5 years of follow-up. SETTING: Thirteen ICUs in four hospitals in Baltimore, MD. PATIENTS: One hundred fifty-six acute respiratory distress syndrome survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Strength was evaluated with standardized manual muscle testing using the Medical Research Council sum score (range, 0-60; higher is better), with post-ICU weakness defined as sum score less than 48. Muscle strength was assessed at hospital discharge and at 3, 6, 12, 24, 36, and 48 months after acute respiratory distress syndrome. At discharge, 38% of patients had muscle weakness. Every one point increase in sum score at discharge was associated with improved survival (hazard ratio [95% CI], 0.96 [0.94-0.98]), with similar findings longitudinally (0.95 [0.93-0.98]). Having weakness at discharge was associated with worse 5-year survival (1.75 [1.01-3.03]), but the association was attenuated (1.54 [0.82-2.89]) when evaluated longitudinally over follow-up. Persisting and resolving trajectories of muscle weakness, occurring in 50% of patients during follow-up, were associated with worse survival (3.01 [1.12-8.04]; and 3.14 [1.40-7.03], respectively) compared to a trajectory of maintaining no muscle weakness. CONCLUSIONS: At hospital discharge, greater than one third of acute respiratory distress syndrome survivors had muscle weakness. Greater strength at discharge and throughout follow-up was associated with improved 5-year survival. In patients with post-ICU weakness, both persisting and resolving trajectories were commonly experienced and associated with worse survival during follow-up.

Healthcare Resource Use and Costs in Long-Term Survivors of Acute Respiratory Distress Syndrome: A 5-Year Longitudinal Cohort Study.

OBJECTIVE: To evaluate the time-varying relationship of annual physical, psychiatric, and quality of life status with subsequent inpatient healthcare resource use and estimated costs. DESIGN: Five-year longitudinal cohort study. SETTING: Thirteen ICUs at four teaching hospitals. PATIENTS: One hundred thirty-eight patients surviving greater than or equal to 2 years after acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postdischarge inpatient resource use data (e.g., hospitalizations, skilled nursing, and rehabilitation facility stays) were collected via a retrospective structured interview at 2 years, with prospective collection every 4 months thereafter, until 5 years postacute respiratory distress syndrome. Adjusted odds ratios for hospitalization and relative medians for estimated episode of care costs were calculated using marginal longitudinal two-part regression. The median (interquartile range) number of inpatient admission hospitalizations was 4 (2-8), with 114 patients (83%) reporting greater than or equal to one hospital readmission. The median (interquartile range) estimated total inpatient postdischarge costs over 5 years were $58,500 ($19,700-157,800; 90th percentile, $328,083). Better annual physical and quality of life status, but not psychiatric status, were associated with fewer subsequent hospitalizations and lower follow-up costs. For example, greater grip strength (per 6 kg) had an odds ratio (95% CI) of 0.85 (0.73-1.00) for inpatient admission, with 23% lower relative median costs, 0.77 (0.69-0.87). CONCLUSIONS: In a multisite cohort of long-term acute respiratory distress syndrome survivors, better annual physical and quality of life status, but not psychiatric status, were associated with fewer hospitalizations and lower healthcare costs.

One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome: prospective follow-up of SAILS randomised trial.

BACKGROUND: Prior randomised trials have evaluated statins in patients with sepsis and acute respiratory distress syndrome (ARDS), but there has been no comprehensive evaluation of long-term effects, despite potential neuromuscular and mental health adverse effects of these drugs. AIM: To evaluate the effect of rosuvastatin versus placebo on survival, physical function and performance, and mental health outcomes in patients with sepsis-associated ARDS. METHODS: Prospective follow-up evaluation of the ARDS Clinical Trials Network Statins for Acutely Injured Lungs from Sepsis trial of rosuvastatin versus placebo in 568 mechanically ventilated patients with sepsis-associated ARDS, with blinded 6-month outcome assessment performed in the 272 eligible survivors for age-adjusted and sex-adjusted 36-Item Short Form Health Survey (SF-36) physical function and mental health domains, and in 84 eligible survivors for the 6 min walk test, along with secondary outcomes evaluations of survival, and additional patient-reported and performance-based measures at 6-month and 12-month follow-up. RESULTS: Over 1-year follow-up, there was no significant difference in cumulative survival in the rosuvastatin versus placebo groups (58% vs 61%; p=0.377), with survivors demonstrating substantial impairments in physical function and mental health. Rosuvastatin versus placebo had no effect (mean treatment effect (95% CI)) on SF-36 physical function (0 (-7 to 8), p=0.939) or mental health (-6 (-12 to 1) p=0.085) domains, 6 min walk distance (per cent predicted: 2 (-9 to 14), p=0.679) or the vast majority of secondary outcomes. CONCLUSIONS: Over 1-year follow-up, patients with sepsis-associated ARDS had high cumulative mortality, with survivors commonly experiencing impairments in physical functioning and performance, and mental health. Randomisation to rosuvastatin had no effect on these outcomes. TRIAL REGISTRATION NUMBER: NCT00979121 and NCT00719446.

Evaluating Physical Outcomes in Acute Respiratory Distress Syndrome Survivors: Validity, Responsiveness, and Minimal Important Difference of 4-Meter Gait Speed Test.

OBJECTIVE: To examine the reliability, validity, responsiveness, and minimal important difference of the 4-m gait speed test in acute respiratory distress syndrome survivors. DESIGN: Secondary analyses of data from two longitudinal follow-up studies of acute respiratory distress syndrome survivors. Test-retest and inter-rater reliability, construct validity (convergent, discriminant, and known group), predictive validity, and responsiveness were examined. The minimal important difference was estimated using anchor- and distribution-based approaches. SETTING: A national multicenter prospective study (ARDSNet Long-Term Outcome Study) and a multisite prospective study in Baltimore, MD (Improving Care of Acute Lung Injury Patients). PATIENTS: Acute respiratory distress syndrome survivors with 4-m gait speed assessment up to 60 months after acute respiratory distress syndrome (ARDSNet Long-Term Outcome Study, n = 184; Improving Care of Acute Lung Injury Patients, n = 122). INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Four-meter gait speed was assessed at 6- and 12-month follow-up (ARDSNet Long-Term Outcome Study) and 36-, 48-, and 60-month follow-up (Improving Care of Acute Lung Injury Patients). Excellent test-retest (intraclass correlation, 0.89-0.99 across studies and follow-up) and inter-rater (intraclass correlation, 0.97) reliability were found. Convergent validity was supported by moderate-to-strong correlations (69% of 32 > 0.40) with other physical function measures. Discriminant validity was supported by weak correlations (86% of 28 < 0.30) with mental health measures. Survivors with impaired versus nonimpaired measures of muscle strength and pulmonary function had significantly slower 4-m gait speed (all but one p < 0.05). Furthermore, 4-m gait speed significantly predicted future hospitalization and health-related quality of life. Gait speed changes were consistent with reported changes in function, supporting responsiveness. The estimated 4-m gait speed minimal important difference was 0.03-0.06 m/s. CONCLUSIONS: The 4-m gait speed is a reliable, valid, and responsive measure of physical function in acute respiratory distress syndrome survivors. The estimated minimal important difference will facilitate sample size calculations for clinical studies evaluating the 4-m gait speed test in acute respiratory distress syndrome survivors.

Timing of low tidal volume ventilation and intensive care unit mortality in acute respiratory distress syndrome. A prospective cohort study.

RATIONALE: Reducing tidal volume decreases mortality in acute respiratory distress syndrome (ARDS). However, the effect of the timing of low tidal volume ventilation is not well understood. OBJECTIVES: To evaluate the association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time. METHODS: Multivariable, time-varying Cox regression analysis of a multisite, prospective study of 482 patients with ARDS with 11,558 twice-daily tidal volume assessments (evaluated in milliliter per kilogram of predicted body weight [PBW]) and daily assessment of other mortality predictors. MEASUREMENTS AND MAIN RESULTS: An increase of 1 ml/kg PBW in initial tidal volume was associated with a 23% increase in ICU mortality risk (adjusted hazard ratio, 1.23; 95% confidence interval [CI], 1.06-1.44; P = 0.008). Moreover, a 1 ml/kg PBW increase in subsequent tidal volumes compared with the initial tidal volume was associated with a 15% increase in mortality risk (adjusted hazard ratio, 1.15; 95% CI, 1.02-1.29; P = 0.019). Compared with a prototypical patient receiving 8 days with a tidal volume of 6 ml/kg PBW, the absolute increase in ICU mortality (95% CI) of receiving 10 and 8 ml/kg PBW, respectively, across all 8 days was 7.2% (3.0-13.0%) and 2.7% (1.2-4.6%). In scenarios with variation in tidal volume over the 8-day period, mortality was higher when a larger volume was used earlier. CONCLUSIONS: Higher tidal volumes shortly after ARDS onset were associated with a greater risk of ICU mortality compared with subsequent tidal volumes. Timely recognition of ARDS and adherence to low tidal volume ventilation is important for reducing mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00300248).

Cooccurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study.

OBJECTIVE: To evaluate the cooccurrence, and predictors of remission, of general anxiety, depression, and posttraumatic stress disorder symptoms during 2-year follow-up in survivors of acute lung injury treated in an ICU. DESIGN: Prospective cohort study, with follow-up at 3, 6, 12, and 24 months post-acute lung injury. SETTING: Thirteen medical and surgical ICUs in four hospitals. PATIENTS: Survivors among 520 patients with acute lung injury. MEASUREMENTS AND MAIN RESULTS: The outcomes of interest were measured using the Hospital Anxiety and Depression Scale anxiety and depression subscales (scores ≥ 8 indicating substantial symptoms) and the Impact of Event Scale-Revised (scores ≥ 1.6 indicating substantial posttraumatic stress disorder symptoms). Of the 520 enrolled patients, 274 died before 3-month follow-up; 186 of 196 consenting survivors (95%) completed at least one Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised assessment during 2-year follow-up, and most completed multiple assessments. Across follow-up time points, the prevalence of suprathreshold general anxiety, depression, and posttraumatic stress disorder symptoms ranged from 38% to 44%, 26% to 33%, and 22% to 24%, respectively; more than half of the patients had suprathreshold symptoms in at least one domain during 2-year follow-up. The majority of survivors (59%) with any suprathreshold symptoms were above threshold for two or more types of symptoms (i.e., general anxiety, depression, and/or posttraumatic stress disorder). In fact, the most common pattern involved simultaneous general anxiety, depression, and posttraumatic stress disorder symptoms. Most patients with general anxiety, depression, or posttraumatic stress disorder symptoms during 2-year follow-up had suprathreshold symptoms at 24-month (last) follow-up. Higher Short-Form-36 physical functioning domain scores at the prior visit were associated with a greater likelihood of remission from general anxiety and posttraumatic stress disorder symptoms during follow-up. CONCLUSIONS: The majority of acute lung injury survivors had clinically significant general anxiety, depression, or posttraumatic stress disorder symptoms, and these symptoms tended to co-occur across domains. Better physical functioning during recovery predicted subsequent remission of general anxiety and posttraumatic stress disorder symptoms.

Cognitive screening among acute respiratory failure survivors: a cross-sectional evaluation of the Mini-Mental State Examination.

INTRODUCTION: The Mini-Mental State Examination (MMSE) is a common cognitive screening test, but its utility in identifying impairments in survivors of acute respiratory failure is unclear. The purpose of this study was to evaluate MMSE performance versus a concurrently administered detailed neuropsychological test battery in survivors of acute respiratory failure. METHODS: This cross-sectional analysis used data from the ARDSNet Long Term Outcomes Study (ALTOS) and Awakening and Breathing Controlled Trial (ABC). Participants were 242 survivors of acute respiratory failure. The MMSE and detailed neuropsychological tests were administered at 6 and 12 months post-hospital discharge for the ALTOS study, and at hospital discharge, 3 and 12 months for the ABC study. Overall cognitive impairment identified by the MMSE (score <24) was compared to impairments identified by the neuropsychological tests. We also matched orientation, registration, attention, memory and language domains on the MMSE to the corresponding neuropsychological test. Pairwise correlations, sensitivity, specificity, positive and negative predictive values, and agreement were assessed. RESULTS: Agreement between MMSE and neuropsychological tests for overall cognitive impairment was fair (42 to 80%). Specificity was excellent (≥93%), but sensitivity was poor (19 to 37%). Correlations between MMSE domains and corresponding neuropsychological tests were weak to moderate (6 months: r = 0.11 to 0.28; 12 months: r = 0.09 to 0.34). The highest correlation between the MMSE and neuropsychological domains was for attention at 6 months (r = 0.28) and language at 12 months (r = 0.34). CONCLUSIONS: In acute respiratory failure survivors, the MMSE has poor sensitivity in detecting cognitive impairment compared with concurrently administered detailed neuropsychological tests. MMSE results in this population should be interpreted with caution.

Risk factors for physical impairment after acute lung injury in a national, multicenter study.

RATIONALE: Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size. OBJECTIVES: To evaluate risk factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization. METHODS: A prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form [SF]-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness-related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status. MEASUREMENTS AND MAIN RESULTS: At 6 and 12 months, respectively, mean (± SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (± 8%) and 93% (± 9%), 6-minute-walk distance (as percent-predicted) was 64% (± 22%) and 67% (± 26%), and SF-36 Physical Function score (as percent-predicted) was 61% (± 36%) and 67% (± 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes. CONCLUSIONS: Patients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors' physical outcomes.

Thermodynamic glass transition in a spin glass without time-reversal symmetry.

Spin glasses are a longstanding model for the sluggish dynamics that appear at the glass transition. However, spin glasses differ from structural glasses in a crucial feature: they enjoy a time reversal symmetry. This symmetry can be broken by applying an external magnetic field, but embarrassingly little is known about the critical behavior of a spin glass in a field. In this context, the space dimension is crucial. Simulations are easier to interpret in a large number of dimensions, but one must work below the upper critical dimension (i.e., in d < 6) in order for results to have relevance for experiments. Here we show conclusive evidence for the presence of a phase transition in a four-dimensional spin glass in a field. Two ingredients were crucial for this achievement: massive numerical simulations were carried out on the Janus special-purpose computer, and a new and powerful finite-size scaling method.

Corticosteroids and transition to delirium in patients with acute lung injury.

OBJECTIVE: Delirium is common in mechanically ventilated patients in the ICU and associated with short- and long-term morbidity and mortality. The use of systemic corticosteroids is also common in the ICU. Outside the ICU setting, corticosteroids are a recognized risk factor for delirium, but their relationship with delirium in critically ill patients has not been fully evaluated. We hypothesized that systemic corticosteroid administration would be associated with a transition to delirium in mechanically ventilated patients with acute lung injury. DESIGN: Prospective cohort study. SETTING: Thirteen ICUs in four hospitals in Baltimore, MD. PATIENTS: Five hundred twenty mechanically ventilated adult patients with acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Delirium evaluation was performed by trained research staff using the validated Confusion Assessment Method for the ICU screening tool. A total of 330 of the 520 patients (64%) had at least two consecutive ICU days of observation in which delirium was assessable (e.g., patient was noncomatose), with a total of 2,286 days of observation and a median (interquartile range) of 15 (9, 28) observation days per patient. These 330 patients had 99 transitions into delirium from a prior nondelirious, noncomatose state. The probability of transitioning into delirium on any given day was 14%. Using multivariable Markov models with robust variance estimates, the following factors (adjusted odds ratio; 95% CI) were independently associated with transition to delirium: older age (compared to < 40 years old, 40-60 yr [1.81; 1.26-2.62], and ≥ 60 yr [2.52; 1.65-3.87]) and administration of any systemic corticosteroid in the prior 24 hours (1.52; 1.05-2.21). CONCLUSIONS: After adjusting for other risk factors, systemic corticosteroid administration is significantly associated with transitioning to delirium from a nondelirious state. The risk of delirium should be considered when deciding about the use of systemic corticosteroids in critically ill patients with acute lung injury.

Timing of limitations in life support in acute lung injury patients: a multisite study*.

OBJECTIVE: Substantial variability exists in the timing of limitations in life support for critically ill patients. Our objective was to investigate how the timing of limitations in life support varies with changes in organ failure status and time since acute lung injury onset. DESIGN, SETTING, AND PATIENTS: This evaluation was performed as part of a prospective cohort study evaluating 490 consecutive acute lung injury patients recruited from 11 ICUs at three teaching hospitals in Baltimore, MD. INTERVENTIONS: None. MEASUREMENTS: The primary exposure was proportion of days without improvement in Sequential Organ Failure Assessment score, evaluated as a daily time-varying exposure. The outcome of interest was a documented limitation in life support defined as any of the following: 1) no cardiopulmonary resuscitation, 2) do not reintubate, 3) no vasopressors, 4) no hemodialysis, 5) do not escalate care, or 6) other limitations (e.g., "comfort care only"). MAIN RESULTS: For medical ICU patients without improvement in daily Sequential Organ Failure Assessment score, the rate of limitation in life support tripled in the first 3 days after acute lung injury onset, increased again after day 5, and peaked at day 19. Compared with medical ICU patients, surgical ICU patients had a rate of limitations that was significantly lower during the first 5 days after acute lung injury onset. In all patients, more days without improvement in Sequential Organ Failure Assessment scores was associated with limitations in life support, independent of the absolute magnitude of the Sequential Organ Failure Assessment score. CONCLUSIONS: Persistent organ failure is associated with an increase in the rate of limitations in life support independent of the absolute magnitude of Sequential Organ Failure Assessment score, and this association strengthens during the first weeks of treatment. During the first 5 days after acute lung injury onset, limitations were significantly more common in medical ICUs than surgical ICUs.

Physical complications in acute lung injury survivors: a two-year longitudinal prospective study.

OBJECTIVE: Survivors of severe critical illness frequently develop substantial and persistent physical complications, including muscle weakness, impaired physical function, and decreased health-related quality of life. Our objective was to determine the longitudinal epidemiology of muscle weakness, physical function, and health-related quality of life and their associations with critical illness and ICU exposures. DESIGN: A multisite prospective study with longitudinal follow-up at 3, 6, 12, and 24 months after acute lung injury. SETTING: Thirteen ICUs from four academic teaching hospitals. PATIENTS: Two hundred twenty-two survivors of acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At each time point, patients underwent standardized clinical evaluations of extremity, hand grip, and respiratory muscle strength; anthropometrics (height, weight, mid-arm circumference, and triceps skin fold thickness); 6-minute walk distance, and the Medical Outcomes Short-Form 36 health-related quality of life survey. During their hospitalization, survivors also had detailed daily evaluation of critical illness and related treatment variables. Over one third of survivors had objective evidence of muscle weakness at hospital discharge, with most improving within 12 months. This weakness was associated with substantial impairments in physical function and health-related quality of life that persisted at 24 months. The duration of bed rest during critical illness was consistently associated with weakness throughout 24-month follow-up. The cumulative dose of systematic corticosteroids and use of neuromuscular blockers in the ICU were not associated with weakness. CONCLUSIONS: Muscle weakness is common after acute lung injury, usually recovering within 12 months. This weakness is associated with substantial impairments in physical function and health-related quality of life that continue beyond 24 months. These results provide valuable prognostic information regarding physical recovery after acute lung injury. Evidence-based methods to reduce the duration of bed rest during critical illness may be important for improving these long-term impairments.

Age and decisions to limit life support for patients with acute lung injury: a prospective cohort study.

INTRODUCTION: The proportion of elderly Americans admitted to the intensive care unit (ICU) in the last month of life is rising. Hence, challenging decisions regarding the appropriate use of life support are increasingly common. The objective of this study was to estimate the association between patient age and the rate of new limitations in the use of life support, independent of daily organ dysfunction status, following acute lung injury (ALI) onset. METHODS: This was a prospective cohort study of 490 consecutive patients without any limitations in life support at the onset of ALI. Patients were recruited from 11 ICUs at three teaching hospitals in Baltimore, Maryland, USA, and monitored for the incidence of six pre-defined limitations in life support, with adjustment for baseline comorbidity and functional status, duration of hospitalization before ALI onset, ICU severity of illness, and daily ICU organ dysfunction score. RESULTS: The median patient age was 52 (range: 18 to 96), with 192 (39%) having a new limitation in life support in the ICU. Of patients with a new limitation, 113 (59%) had life support withdrawn and died, 53 (28%) died without resuscitation, and 26 (14%) survived to ICU discharge. Each ten-year increase in patient age was independently associated with a 24% increase in the rate of limitations in life support (Relative Hazard 1.24; 95% CI 1.11 to 1.40) after adjusting for daily ICU organ dysfunction score and all other covariates. CONCLUSIONS: Older critically ill patients are more likely to have new limitations in life support independent of their baseline status, ICU-related severity of illness, and daily organ dysfunction status. Future studies are required to determine whether this association is a result of differences in patient preferences by age, or differences in the treatment options discussed with the families of older versus younger patients.