Understanding Patients' Perceived Health After Critical Illness: Analysis of Two Prospective, Longitudinal Studies of ARDS Survivors.

BACKGROUND: Perceived health is one of the strongest determinants of subjective well-being, but it has received little attention among survivors of ARDS. RESEARCH QUESTION: How well do self-reported measures of physical, emotional, and social functioning predict perceived overall health (measured using the EQ-5D visual analog scale [EQ-5D-VAS]) among adult survivors of ARDS? Are demographic features, comorbidity, or severity of illness correlated with perceived health after controlling for self-reported functioning? STUDY DESIGN AND METHODS: We analyzed the ARDSNet Long Term Outcomes Study (ALTOS) and Improving Care of Acute Lung Injury Patients (ICAP) Study, two longitudinal cohorts with a total of 823 survivors from 44 US hospitals, which prospectively assessed survivors at 6 and 12 months after ARDS. Perceived health, evaluated using the EQ-5D-VAS, was predicted using ridge regression and self-reported measures of physical, emotional, and social functioning. The difference between observed and predicted perceived health was termed perspective deviation (PD). Correlations between PD and demographics, comorbidities, and severity of illness were explored. RESULTS: The correlation between observed and predicted EQ-5D-VAS scores ranged from 0.68 to 0.73 across the two cohorts and time points. PD ranged from -80 to +34 and was more than the minimum clinically important difference for 52% to 55% of survivors. Neither demographic features, comorbidity, nor severity of illness were correlated strongly with PD, with |r| < 0.25 for all continuous variables in both cohorts and time points. The correlation between PD at 6- and 12-month assessments was weak (ALTOS: r = 0.22, P < .001; ICAP: r = 0.20, P = .02). INTERPRETATION: About half of survivors of ARDS showed clinically important differences in actual perceived health vs predicted perceived health based on self-reported measures of functioning. Survivors of ARDS demographic features, comorbidities, and severity of illness were correlated only weakly with perceived health after controlling for measures of perceived functioning, highlighting the challenge of predicting how individual patients will respond psychologically to new impairments after critical illness.

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.

Factors Associated With Home Visits in a 5-Year Study of Acute Respiratory Distress Syndrome Survivors.

BACKGROUND: Participant retention is vital for longitudinal studies. Home visits may increase retention, but little is known about the subset of patients they benefit. OBJECTIVE: To evaluate patient-related variables associated with home visits. METHODS: In a 5-year, longitudinal, multisite, prospective study of 195 survivors of acute respiratory distress syndrome, in-person assessments were conducted at a research clinic. Home visits were offered to participants who could not attend the clinic. Associations between having a home visit, prior follow-up visit status, and baseline and in-hospital patient variables were evaluated with multivariable, random-intercept logistic regression models. The association between home visits and patients' posthospital clinical status was evaluated with a subsequent regression model adjusted for these variables. RESULTS: Participants had a median age of 49 years and were 56% male and 58% White. The following had independent associations with home visits (adjusted odds ratio [95% CI]): age (per year: 1.03 [1.00-1.05]) and immediately preceding visit incomplete (2.46 [1.44-4.19]) or at home (8.24 [4.57-14.86]). After adjustment for prior-visit status and baseline and hospitalization variables, these posthospital patient outcome variables were associated with a subsequent home visit: instrumental activities of daily living (≥ 2 vs < 2 dependencies: 2.32 [1.29-4.17]), EQ-5D utility score (per 0.1-point decrease: 1.15 [1.02-1.30]), and 6-minute walk test (per 10-percentage-point decrease in percent-predicted distance: 1.50 [1.26-1.79]). CONCLUSIONS: Home visits were important for retaining older and more physically impaired study participants, helping reduce selection bias caused by excluding them.

Acute Respiratory Failure Survivors' Physical, Cognitive, and Mental Health Outcomes: Quantitative Measures versus Semistructured Interviews.

Rationale: Increasingly, patients are surviving acute respiratory failure (ARF), prompting the need to better understand standardized outcome measures commonly used during ARF follow-up studies. Objectives: Investigate standardized outcome measures (patient-reported physical and mental health measures, and cognitive testing) compared with findings from semistructured, qualitative interviews. Methods: As part of two ARF multicenter follow-up studies, standardized outcome measures were obtained, followed by qualitative evaluation via an in-depth, semistructured interview conducted and coded by two independent researchers. Qualitative interviews revealed the following post-ARF survivorship themes: physical impairment; anxiety, depression, and post-traumatic stress disorder symptoms; and cognitive impairment. Scores from standardized measures related to these themes were compared for ARF survivors reporting versus not reporting these themes in their qualitative interviews. Results: Of 59 invited ARF survivors, 48 (81%) completed both standardized outcome measures and qualitative interviews. Participants' median (interquartile range) age was 53 (43-64) years; 54% were female, and 88% were living independently before hospitalization. The two independent reviewers classifying the presence or absence of themes from the qualitative interviews had excellent agreement (κ = 0.80). There were significantly worse scores on standardized outcome measures for survivors reporting (vs. not reporting) physical and mental health impairments in their qualitative interviews. However, standardized cognitive test scores did not differ between patients reporting versus not reporting cognitive impairments in their qualitative interviews. Conclusions: These findings support the use of recommended, commonly used standardized outcome measures for physical and mental health impairments in ARF survivorship research. However, caution is needed in interpreting self-reported cognitive function compared with standardized cognitive testing.

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.

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.

Feasibility of a Nurse-Managed Pain, Agitation, and Delirium Protocol in the Surgical Intensive Care Unit.

BACKGROUND: Society of Critical Care Medicine guidelines recommend the use of pain, agitation, and delirium protocols in the intensive care unit. The feasibility of nurse management of such protocols in the surgical intensive care unit has not been well assessed. OBJECTIVES: To evaluate the percentage of adherent medication interventions for patients assessed by using a pain, sedation, and delirium protocol. METHODS: Data on all adult patients admitted to a surgical intensive care unit from January 2013 through September 2013 who were assessed at least once by using a pain, sedation, and delirium protocol were retrospectively reviewed. Protocol adherence was evaluated for interventions implemented after a nursing assessment. Patients were further divided into 2 groups on the basis of adherence, and achievement of pain and sedation goals was evaluated between groups. RESULTS: Data on 41 patients were included. Of the 603 pain assessments, 422 (70.0%) led to an intervention adherent to the protocol. Of the 249 sedation assessments, 192 (77.1%) led to an adherent intervention. Among patients with 75% or greater adherent pain interventions, all interventions met pain goals with significantly less fentanyl than that used in interventions that did not meet goals. Despite 75% or greater adherence with interventions for sedation assessments, only 8.7% of the interventions met sedation goals. CONCLUSIONS: A nurse-managed pain, agitation, and delirium protocol can be feasibly implemented in a surgical intensive care unit.

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.

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.

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.

Recovery from Dysphagia Symptoms after Oral Endotracheal Intubation in Acute Respiratory Distress Syndrome Survivors. A 5-Year Longitudinal Study.

RATIONALE: Nearly 60% of patients who are intubated in intensive care units (ICUs) experience dysphagia after extubation, and approximately 50% of them aspirate. Little is known about dysphagia recovery time after patients are discharged from the hospital. OBJECTIVES: To determine factors associated with recovery from dysphagia symptoms after hospital discharge for acute respiratory distress syndrome (ARDS) survivors who received oral intubation with mechanical ventilation. METHODS: This is a prospective, 5-year longitudinal cohort study involving 13 ICUs at four teaching hospitals in Baltimore, Maryland. The Sydney Swallowing Questionnaire (SSQ), a 17-item visual analog scale (range, 0-1,700), was used to quantify patient-perceived dysphagia symptoms at hospital discharge, and at 3, 6, 12, 24, 36, 48, and 60 months after ARDS. An SSQ score greater than or equal to 200 was used to indicate clinically important dysphagia symptoms at the time of hospital discharge. Recovery was defined as an SSQ score less than 200, with a decrease from hospital discharge greater than or equal to 119, the reliable change index for SSQ score. Fine and Gray proportional subdistribution hazards regression analysis was used to evaluate patient and ICU variables associated with time to recovery accounting for the competing risk of death. MEASUREMENTS AND MAIN RESULTS: Thirty-seven (32%) of 115 patients had an SSQ score greater than or equal to 200 at hospital discharge; 3 died before recovery. All 34 remaining survivors recovered from dysphagia symptoms by 5-year follow-up, 7 (23%) after 6 months. ICU length of stay was independently associated with time to recovery, with a hazard ratio (95% confidence interval) of 0.96 (0.93-1.00) per day. CONCLUSIONS: One-third of orally intubated ARDS survivors have dysphagia symptoms that persist beyond hospital discharge. Patients with a longer ICU length of stay have slower recovery from dysphagia symptoms and should be carefully considered for swallowing assessment to help prevent complications related to dysphagia.

A systematic review finds limited data on measurement properties of instruments measuring outcomes in adult intensive care unit survivors.

BACKGROUND AND OBJECTIVE: There is a growing number of studies evaluating the physical, cognitive, mental health, and health-related quality of life (HRQOL) outcomes of adults surviving critical illness. However, there is little consensus on the most appropriate instruments to measure these outcomes. To inform the development of such consensus, we conducted a systematic review of the performance characteristics of instruments measuring physical, cognitive, mental health, and HRQOL outcomes in adult intensive care unit (ICU) survivors. METHODS: We searched PubMed, Embase, PsycInfo, Cumulative Index of Nursing and Allied Health Literature, and The Cochrane Library in March 2015. We also conducted manual searches of reference lists of eligible studies and relevant review articles. Two people independently selected studies, completed data abstraction, and assessed the quality of eligible studies using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) initiative checklist. RESULTS: We identified 20 studies which explicitly evaluated measurement properties for 21 different instruments assessing outcomes in ICU survivors. Eleven of the instruments assessed quality of life, with few instruments assessing other domains. Of the nine measurement properties evaluated on the COSMIN checklist, six were assessed in <10% of the evaluations. Overall quality of eligible studies was generally poor to fair based on the COSMIN checklist. CONCLUSIONS: Although an increasing number of studies measure physical, cognitive, mental health, and HRQOL outcomes in adult ICU survivors, data on the measurement properties of such instruments are sparse and generally of poor to fair quality. Empirical analyses evaluating the performance of instruments in adult ICU survivors are needed to advance research in this field.

Physical declines occurring after hospital discharge in ARDS survivors: a 5-year longitudinal study.

PURPOSE: Survivors of acute respiratory distress syndrome (ARDS) are at high risk for new or ongoing physical declines after hospital discharge. The objective of our study was to evaluate the epidemiology of physical declines over 5-year follow-up and identify patients at risk for decline. METHODS: This multi-site prospective cohort study evaluated ARDS survivors who completed a physical status assessment at 3 or 6 months post-discharge. Three measures were evaluated: muscle strength (Medical Resource Council sumscore); exercise capacity [6-min walk test (6MWT)]; physical functioning [36-Item Short Form Health Survey (SF-36 survey)]. Patients were defined as "declined" if a comparison of their current and prior score showed a decrease that was greater than the Reliable Change Index-or if the patient died. Risk factors [pre-ARDS baseline status, intensive care unit (ICU) illness severity, and other intensive care variables] were evaluated using longitudinal, generalized linear regression models for each measure. RESULTS: During the follow-up of 193 ARDS survivors (55 % male; median age 49 years), 166 (86 %) experienced decline in ≥1 physical measure (including death) and 133 (69 %) experienced a physical decline (excluding death). For all measures, age was a significant risk factor [odds ratios (OR) 1.34-1.69 per decade; p < 0.001]. Pre-ARDS comorbidity (Charlson Index) was independently associated with declines in strength and exercise capacity (OR 1.10 and 1.18, respectively; p < 0.02), and organ failure [maximum daily Sequential Organ Failure Assessment (SOFA) score in ICU] was associated with declines in strength (OR 1.06 per 1 point of SOFA score; p = 0.02). CONCLUSIONS: Over the follow-up period, the majority of ARDS survivors experienced a physical decline, with older age and pre-ICU comorbidity being important risk factors for this decline.

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.

Rosuvastatin versus placebo for delirium in intensive care and subsequent cognitive impairment in patients with sepsis-associated acute respiratory distress syndrome: an ancillary study to a randomised controlled trial.

BACKGROUND: Delirium is common in mechanically ventilated patients and is associated with cognitive impairment lasting at least 1 year after hospital discharge. Preclinical and observational studies suggest that the use of statins might reduce delirium in intensive care. We assessed whether the pleiotropic effects of statins can reduce delirium in intensive care and decrease subsequent cognitive impairment in a randomised controlled trial. METHODS: We did this ancillary study within the SAILS trial, a randomised controlled trial assessing mortality and ventilator-free days for rosuvastatin versus placebo for patients with sepsis-associated acute respiratory distress syndrome. This study was done at 35 hospitals in the USA. Patients were randomly assigned in permuted blocks of eight and stratified by hospital to receive either rosuvastatin (40 mg loading dose and then 20 mg daily until the earliest of 3 days after discharge from intensive care, study day 28, or death) or placebo. Patients and investigators were masked to treatment assignment. Delirium was assessed with the validated Confusion Assessment Method for intensive care. Cognitive function was assessed with tests for executive function, language, verbal reasoning and concept formation, and working, immediate, and delayed memory. We defined cognitive impairment as having one of these domains at least two SDs below population norms or at least two domains at least 1·5 SDs below norms. The primary endpoint was daily delirium status in intensive care up to 28 days in the intention-to-treat population and secondary endpoints were cognitive function at 6 months and 12 months. This trial is registered with ClinicalTrials.gov (NCT00979121 and NCT00719446). FINDINGS: 272 patients were assessed for delirium daily in intensive care. The mean proportion of days with delirium was 34% (SD 30%) in the rosuvastatin group versus 31% (29%) in the placebo group; hazard ratio 1·14, 95% CI 0·92-1·41, p=0·22. At 6 months, 19 (36%) of 53 patients in the rosuvastatin group versus 29 (38%) of 77 in the placebo group had cognitive impairment, with no significant difference between groups (treatment effect 0·93, 95% CI 0·39-2·22; p=0·87). At 12 months, 20 (30%) of 67 patients versus 23 (28%) of 81 patients had cognitive impairment, with no significant difference between groups (treatment effect 1·1, 95% CI 0·5-2·6; p=0·82). INTERPRETATION: Most patients had delirium, with around a third of survivors having cognitive impairment over 1 year of follow-up. Despite encouraging preclinical and observational studies, this trial shows no benefit of rosuvastatin in reducing delirium in intensive care or cognitive impairment during 12 months of follow-up although the study was not powered for superiority. Thus, there is continued need to evaluate interventions aimed at attenuating intensive care and post-intensive-care cognitive impairments commonly observed in this population. FUNDING: National Heart, Lung and Blood Institute; Johns Hopkins Institute for Clinical and Translational Research; the SAILS trial was also supported by AstraZeneca.

Updated systematic review identifies substantial number of retention strategies: using more strategies retains more study participants.

BACKGROUND AND OBJECTIVE: The retention of participants in studies is important for the validity of research. We updated our prior systematic review (2005) to assess retention strategies for in-person follow-up in health care studies. METHODS: We searched PubMed, Cumulative Index of Nursing and Allied Health Literature, Cochrane Controlled Trials Register, Cochrane Methodology Register, and Embase (August 2013) for English-language reports of studies that described retention strategies for in-person follow-up in health care studies. We abstracted each retention strategy, and two authors independently classified each retention strategy with one of the themes developed in our prior review. RESULTS: We identified 88 studies (67 newly identified studies), six of which were designed to compare retention strategies, whereas the remainder described retention strategies and retention rates. There were 985 strategies abstracted from the descriptive studies (617 from new studies), with a median (interquartile range) number of strategies per study of 10 (7 to 17) and a median (interquartile range) number of themes per study of 6 (4 to 7). Financial incentives were used in 47 (57%) of the descriptive studies. We classified 28% of the strategies under the theme of "contact and scheduling methods," with 83% of the identified studies using at least one strategy within this theme. The number of strategies used was positively correlated with retention rate (P = 0.027), but the number of themes was not associated with retention rate (P = 0.469). CONCLUSION: The number of studies describing retention strategies has substantially increased since our prior review. However, the lack of comparative studies and the heterogeneity in the types of strategies, participant population and study designs, prohibits synthesis to determine the types of cohort retention strategies that were most effective. However, using a larger number of retention strategies, across five or six different themes, appears to retain more study participants.

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.

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).