Association Between Tracheostomy and Functional, Neuropsychological, and Healthcare Utilization Outcomes in the RECOVER Cohort.

Tracheostomy is commonly performed in critically ill patients requiring prolonged mechanical ventilation (MV). We evaluated the outcomes of tracheostomy in patients who received greater than or equal to 1 week MV and were followed for 1 year. DESIGN: In this secondary analysis of a prospective observational study, we compared outcomes in tracheostomy versus nontracheostomy patients. Outcomes post ICU included Functional Independence Measure (FIM) subscales, 6-Minute Walk Test (6MWT), Short Form 36 (SF36), Medical Research Council (MRC) Scale, pulmonary function tests (PFTs), Impact of Event Scale (IES), Beck Depression Inventory-II (BDI-II), and vital status and disposition. SETTING: Nine University affiliated ICUs in Canada. PATIENTS: Medical/surgical patients requiring MV for 7 or more days who were enrolled in the Towards RECOVER Study. MEASUREMENTS AND MAIN RESULTS: Of 398 ICU survivors, 193 (48.5%) received tracheostomy, on median ICU day 14 (interquartile range [IQR], 8-0 d). Patients with tracheostomy were older, had similar severity of illness, had longer MV duration and ICU and hospital stays, and had higher risk of ICU readmission (odds ratio [OR], 1.9; 95% CI, 1.0-3.2) and hospital mortality (OR, 2.6; 95% CI, 1.1-6.1), but not 1-year mortality (hazard ratio, 1.41; 95% CI, 0.88-1.2). Over 1 year, tracheostomy patients had lower FIM-Total (7.7 points; 95% CI, 2.2-13.2); SF36, IES, and BDI-II were similar. From 3 months, tracheostomy patients had 12% lower 6MWT (p = 0.0008) and lower MRC score (3.4 points; p = 0.006). Most PFTs were 5-8% lower in the tracheostomy group. Tracheostomy patients had similar specialist visits (rate ratio, 0.63; 95% CI, 0.28-2.4) and hospital readmissions (OR, 0.82; 95% CI, 0.54-1.3) but were less likely to be at home at hospital discharge and 1 year. CONCLUSIONS: Patients who received tracheostomy had more ICU and hospital care and higher hospital mortality compared with patients who did not receive a tracheostomy. In 1 year follow-up, tracheostomy patients required a higher daily burden of care, expressed by FIM.

Monitoring and auditing protocol adherence, data integrity and ethical conduct of a randomized clinical trial: A case study.

PURPOSE: To categorize, quantify and interpret findings documented in feedback letters of monitoring or auditing visits for an investigator-initiated, peer-review funded multicenter randomized trial testing probiotics for critically ill patients. MATERIALS & METHODS: In 37 Canadian centers, monitoring and auditing visits were performed by 3 trained individuals; findings were reported in feedback letters. At trial termination, we performed duplicate content analysis on letters, categorizing observations first into unique findings, followed by 10 pre-determined trial quality management domains. We further classified each observation into a) missing operational records, b) errors in process, and potential threats to c) data integrity, d) patient privacy or e) safety. RESULTS: Across 37 monitoring or auditing visits, 75 unique findings were categorized into 10 domains. Most frequently, observations were in domains of training documentation (180/566 [32%]) and the informed consent process (133/566 [23%]). Most observations were missing operational records (438/566 [77%]) rather than errors in process (128/566 [23%]). Of 75 findings, 13 (62/566 observations [11%]) posed a potential threat to data integrity, 1 (1/566 observation [0.18%]) to patient privacy, and 9 (49/566 observations [8.7%]) to patient safety. CONCLUSIONS: Monitoring and auditing findings predominantly concerned missing documentation with minimal threats to data integrity, patient privacy or safety. TRIAL REGISTRATION: PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial): NCT02462590.

Determinants of Depressive Symptoms at 1 Year Following ICU Discharge in Survivors of ≥ 7 Days of Mechanical Ventilation: Results From the RECOVER Program, a Secondary Analysis of a Prospective Multicenter Cohort Study.

BACKGROUND: Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver factors associated with the development of these symptoms. METHODS: This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II [BDI-II]), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay [LOS]), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months. RESULTS: BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale [P = .28] and Center for Epidemiologic Studies Depression Scale [P = .74]). CONCLUSIONS: Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders.

One-Year Outcomes in Caregivers of Critically Ill Patients.

BACKGROUND: Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU). METHODS: We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge. RESULTS: The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time. CONCLUSIONS: In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).

The RECOVER Program: Disability Risk Groups and 1-Year Outcome after 7 or More Days of Mechanical Ventilation.

RATIONALE: Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design. OBJECTIVES: To stratify patients for post-ICU disability and recovery to 1 year after critical illness. METHODS: We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling. MEASUREMENTS AND MAIN RESULTS: The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk for post ICU disability, ICU and post-ICU healthcare use, and disposition. Patients less than 42 years with ICU length of stay less than 2 weeks had the best function and fewest deaths at 1 year compared with patients greater than 66 years with ICU length of stay greater than 2 weeks who sustained the worst disability and 40% 1-year mortality. Depressive symptoms (17%) and post-traumatic stress disorder (18%) persisted at 1 year. CONCLUSIONS: ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay. These groups determine 1-year recovery and healthcare use and are independent of admitting diagnosis and illness severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00896220).

A National Survey of Critical Care Physicians' Knowledge, Attitudes, and Perceptions of Antimicrobial Stewardship Programs.

OBJECTIVE: Antimicrobial stewardship is a process designed to optimize antimicrobial therapy by ensuring patients get the right antimicrobials at the right dose and at the right time. Antimicrobial stewardship programs (ASPs) are increasingly being implemented in health care institutions, are required by some accreditation bodies, and have the potential for maximum impact in intensive care units (ICUs). We administered a survey to critical care physicians across Canada to better understand their knowledge, attitudes, and perceptions on the utility of ASPs in improving patient care. DESIGN, SETTING, AND PATIENTS: We distributed a Web-based survey to physicians who attend in Canadian ICUs. Respondents were identified through the membership lists of multiple critical care organizations. Content validity, utility, clarity, and test-retest reliability were evaluated prior to distribution. Survey items assessed ASP knowledge, attitudes, and experiences. Attitudes toward ASPs were assessed on a 5-point Likert-type scale. MEASUREMENTS AND MAIN RESULTS: The survey was completed by 185 physicians, with a response rate of 29% (n = 185/634) for all physicians contacted. A majority (74%) of respondents reported that there was at least 1 component of an ASP at their institution. Most (86%) respondents agreed or strongly agreed that the patients in their ICU benefit from an ASP, with 81% reporting the ASP increases their knowledge of appropriate antimicrobial use in the ICU setting. Only 11% of respondents reported they felt that time spent interacting with the ASP team was an inefficient use of their time, and only 7% expressed concern that the ASP negatively affected their autonomy. CONCLUSION: Based on our survey results, Canadian intensivists are supportive of antimicrobial stewardship in ICUs and feel that ASPs provide a valuable service to both patients and clinicians.

Characteristics and Outcomes of Eligible Nonenrolled Patients in a Mechanical Ventilation Trial of Acute Respiratory Distress Syndrome.

RATIONALE: Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion. OBJECTIVES: To describe characteristics and outcomes of eligible nonenrolled (ENE) patients in a multicenter trial of mechanical ventilation strategies. METHODS: Within the OSCILLATE trial of high-frequency oscillation (HFO) versus conventional ventilation (CV) in adults with adult respiratory distress syndrome, and with approval from research ethics boards, we collected a minimal dataset on patients who satisfied eligibility criteria but were not enrolled. We categorized ENE patients as ENE-HFO and ENE-CV based on receipt of HFO at any time. We used multivariable logistic regression to assess the association between ENE status and mortality. MEASUREMENTS AND MAIN RESULTS: A total of 548 patients were randomized, and 546 were ENE. The most common reasons for ENE were no consent (42%), physician refusal (24%), missed randomization window (15%), and current HFO use (14%). Compared with randomized patients in respective arms of the trial, ENE-HFO patients were younger and had worse lung injury, whereas ENE-CV patients had lower illness severity. ENE status was independently associated with mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84; P = 0.02), with no significant interaction with ventilation treatment group. CONCLUSIONS: Nonenrollment was common, with approximately one ENE patient for every randomized patient. Our study suggests that enrollment in trials of mechanical ventilation may be associated with improved outcomes compared with standard care and highlights the need for prospective tracking and transparent reporting of ENE patients as part of trial management.

Coenrollment in a randomized trial of high-frequency oscillation: prevalence, patterns, predictors, and outcomes*.

OBJECTIVE: Enrollment of individual patients into more than one study has been poorly evaluated. The objective of this study was to describe the characteristics of patients, researchers and centers involved in coenrollment, studies precluding coenrollment, and the prevalence, patterns, predictors, and outcomes of coenrollment in a randomized clinical trial. DESIGN, SETTING, METHODS: We conducted an observational study nested within the OSCILLation for Acute Respiratory Distress Syndrome Treated Early Trial, which compared high-frequency oscillatory ventilation to conventional ventilation. We collected patient, center, and study data on coenrollment in randomized patients. Multilevel regression examined factors independently associated with coenrollment, considering clustering within centers. We examined the effect of coenrollment on safety and the trial outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 127 of 548 randomized patients (23.2%) were coenrolled in 25 unique studies. Coenrollment was reported in 17 of 39 centers (43.6%). Patients were most commonly coenrolled in one additional randomized clinical trial (76; 59.8%). Coenrollment was less likely in older patients (odds ratio, 0.87; 95% CI, 0.76-0.997), and in ICUs with greater than 26 beds (odds ratio, 0.56; 95% CI, 0.34-0.94), and more likely by investigators with more than 11 years of experience (odds ratio, 1.73; 95% CI, 1.06-2.82), by research coordinators with more than 8 years of experience (odds ratio, 1.87; 95% CI, 1.11-3.18) and in Canada (odds ratio, 4.66; 95% CI, 1.43-15.15). Serious adverse events were similar between coenrolled high-frequency oscillatory ventilation and control patients. Coenrollment did not modify the treatment effect of high-frequency oscillatory ventilation on hospital mortality. CONCLUSIONS: Coenrollment occurred in 23% of patients, commonly in younger patients, in smaller centers with more research infrastructure, and in Canada. Coenrollment did not influence patient safety or trial results.

Changing support needs of survivors of complex critical illness and their family caregivers across the care continuum: a qualitative pilot study of Towards RECOVER.

INTRODUCTION: Survivors of complex critical illness and their family caregivers require support during their recovery, rehabilitation, and return to community living; however, the nature of these supports and how they may change over time remain unclear. Using the Timing It Right framework as a conceptual guide, this qualitative pilot study explored survivors' and caregivers' needs during the episode of critical illness through their return to independent living. METHODS: Five survivors and seven family caregivers were recruited and consented from the main Towards RECOVER pilot study, designed to characterize the long term outcomes of survivors of the ICU who have been mechanically ventilated for more than one week. Using the Timing It Right framework, we prospectively conducted qualitative interviews to explore participants' experiences and needs for information, emotional support, and training at 3, 6, 12, and 24 months after intensive care unit (ICU) discharge. We completed 26 interviews, which were audio recorded, professionally transcribed, checked for accuracy, and analyzed using framework methodology. RESULTS: In this small pilot sample, caregiver and patient perspectives were related and, therefore, are presented together. We identified 1 overriding theme: survivors do not experience continuity of medical care during recovery after critical illness. Three subthemes highlighted the following: (1) informational needs change across the care continuum, (2) fear and worry exist when families do not know what to expect, and (3) survivors transition from dependence to independence. CONCLUSIONS: Interventions designed to improve family outcomes after critical illness should address both survivors' and caregivers' support needs as they change across the illness and recovery trajectory. Providing early intervention and support and clarifying expectations for transitions in care and recovery may decrease fears of the unknown for both caregivers and survivors. Ongoing family-centered follow-up programs may also help survivors regain independence and help caregivers manage their perceived responsibility for the patients' health. Using these insights for intervention development could ultimately improve long-term outcomes for both survivors and caregivers.

Enhancing the informed consent process for critical care research: strategies from a thromboprophylaxis trial.

BACKGROUND: Critically ill patients lack capacity for decisions about research participation. Consent to enrol these patients in studies is typically obtained from substitute decision-makers. OBJECTIVE: To present strategies that may optimise the process of obtaining informed consent from substitute decision-makers for participation of critically ill patients in trials. We use examples from a randomised trial of heparin thromboprophylaxis in the intensive care unit (PROTECT, clinicaltrials.gov NCT00182143). METHODS: 3764 patients were randomised, with an informed consent rate of 82%; 90% of consents were obtained from substitute decision-makers. North American PROTECT research coordinators attended three meetings to discuss enrolment: (1) Trial start-up (January 2006); (2) Near trial closure (January 2010); and (3) Post-publication (April 2011). Data were derived from slide presentations, field notes from break-out groups and plenary discussions, then analysed inductively. RESULTS: We derived three phases for the informed consent process: (1) Preparation for the Consent Encounter; (2) The Consent Encounter; and (3) Follow-up to the Consent Encounter. Specific strategies emerged for each phase: Phase 1 (four strategies); Phase 2 (six strategies); and Phase 3 (three strategies). CONCLUSION: We identified 13 strategies that may improve the process of obtaining informed consent from substitute decision-makers and be generalisable to other settings and studies.

Co-enrollment of critically ill patients into multiple studies: patterns, predictors and consequences.

INTRODUCTION: Research on co-enrollment practices and their impact are limited in the ICU setting. The objectives of this study were: 1) to describe patterns and predictors of co-enrollment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of co-enrollment on clinical and trial outcomes. METHODS: In an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the co-enrollment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among co-enrolled and non-co-enrolled patients. RESULTS: Among 3,746 patients enrolled in PROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial), 713 (19.0%) were co-enrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study and 9.4% in both). Six factors independently associated with co-enrollment (all P < 0.001) were illness severity (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.19 to 1.53 for each 10-point Acute Physiology and Chronic Health Evaluation (APACHE) II score increase), substitute decision-makers providing consent, rather than patients (OR 3.31, 2.03 to 5.41), experience of persons inviting consent (OR 2.67, 1.74 to 4.11 for persons with > 10 years' experience compared to persons with none), center size (all ORs > 10 for ICUs with > 15 beds), affiliation with trials groups (OR 5.59, 3.49 to 8.95), and main trial rather than pilot phase (all ORs > 8 for recruitment year beyond the pilot). Co-enrollment did not influence clinical or trial outcomes or risk of adverse events. CONCLUSIONS: Co-enrollment was strongly associated with features of the patients, research personnel, setting and study. Co-enrollment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis and further research are needed on the complex topic of co-enrollment during critical illness.

High-frequency oscillation in early acute respiratory distress syndrome.

BACKGROUND: Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes. METHODS: In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause. RESULTS: On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01). CONCLUSIONS: In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254, and ClinicalTrials.gov numbers, NCT00474656 and NCT01506401.).

Rates and determinants of informed consent: a case study of an international thromboprophylaxis trial.

BACKGROUND: Successful completion of randomized trials depends upon efficiently and ethically screening patients and obtaining informed consent. Awareness of modifiable barriers to obtaining consent may inform ongoing and future trials. OBJECTIVE: The objective of this study is to describe and examine determinants of consent rates in an international heparin thromboprophylaxis trial (Prophylaxis for ThromboEmbolism in Critical Care Trial, clinicaltrials.gov NCT00182143). DESIGN: Throughout the 4-year trial, research personnel approached eligible critically ill patients or their substitute decision makers for informed consent. Whether consent was obtained or declined was documented daily. SETTING: The trial was conducted in 67 centers in 6 countries. MEASUREMENTS AND MAIN RESULTS: A total of 3764 patients were randomized. The overall consent rate was 82.2% (range, 50%-100%) across participating centers. Consent was obtained from substitute decision makers and patients in 90.1% and 9.9% of cases, respectively. Five factors were independently associated with consent rates. Research coordinators with more experience achieved higher consent rates (odds ratio [OR], 3.43; 95% confidence interval, 2.42-4.86; P < .001 for those with >10 years of experience). Consent rates were higher in smaller intensive care units with less than 15 beds compared with intensive care units with 15 to 20 beds, 21 to 25 beds, and greater than 25 beds (all ORs, <0.5; P < .001) and were higher in centers with more than 1 full-time research staff (OR, 1.95; 95% confidence interval, 1.28-2.99; P < .001). Consent rates were lower in centers affiliated with the Canadian Critical Care Trials Group or the Australian and New Zealand Intensive Care Society Clinical Trials Group compared with other centers (OR, 0.57; 95% confidence interval, 0.42-0.77; P < .001). Finally, consent rates were highest during the pilot trial, lowest during the initiation of the full trial, and increased over years of recruitment (P < .001). CONCLUSIONS: Characteristics of study centers, research infrastructure, and experience were important factors associated with successfully procuring informed consent to participate in this thromboprophylaxis trial.

Radiologic outcomes at 5 years after severe ARDS.

OBJECTIVE: Few studies have systematically evaluated high-resolution CT (HRCT) imaging of the thorax 5 years after severe ARDS to determine the association between radiologic fi ndings and functional disability. The primary aim of this study was to determine chest radiologic abnormalities at 5 years in survivors of severe ARDS from the University of Toronto ARDS cohort. The secondary aim was to determine the relationship between the observed radiologic abnormalities on HRCT scan and pulmonary symptoms, pulmonary function test abnormalities, and healthrelated quality of life at 5-year follow-up. METHODS: HRCT scans were obtained in 24 of 64 eligible patients. Three anatomically comparable levels were selected for scoring, and each level was divided into four quadrants. The extent and distribution of individual CT image patterns (ground glass opacifi cation, intense parenchymal opacifi cation, reticular pattern, and decreased attenuation) were also reported. RESULTS: Eighteen patients (75%) had abnormal fi ndings on HRCT imaging. These findings were minor and in the nondependent lung zones. No correlation was found between radiologic findings and patient symptoms, pulmonary function tests, 6-min walk distances, or heath-related quality of life measures. CONCLUSIONS: Exercise and functional limitations experienced by survivors of severe ARDS are unlikely to be related to structural lung disease and may be more consistent with extrapulmonary muscle weakness.

Research ethics board approval for an international thromboprophylaxis trial.

BACKGROUND: Research ethics board (REB) review of scientific protocols is essential, ensuring participants' dignity, safety, and rights. The objectives of this study were to examine the time from submission to approval, to analyze predictors of approval time, and to describe the scope of conditions from REBs evaluating an international thromboprophylaxis trial. METHODS: We generated survey items through literature review and investigators' discussions, creating 4 domains: respondent and institutional demographics, the REB application process, and alternate consent models. We conducted a document analysis that involved duplicate assessment of themes from REB critique of the protocol and informed consent forms (ICF). RESULTS: Approval was granted from 65 REB institutions, requiring 58 unique applications. We analyzed 44 (75.9%) of 58 documents and surveys. Survey respondents completing the applications had 8 (5-12) years of experience; 77% completed 4 or more REB applications in previous 5 years. Critical care personnel were represented on 54% of REBs. The time to approval was a median (interquartile range) of 75 (42, 150) days, taking longer for sites with national research consortium membership (89.1 vs 31.0 days, P = .03). Document analysis of the application process and ICF yielded 5 themes: methodology, data management, consent procedures, cataloguing, and miscellaneous. Protocol-specific themes focused on trial implementation, external critiques, and budget. The only theme specific to the ICF was risks and benefits. The most frequent comments on the protocol and ICF were about methodology and miscellaneous issues; ICF comments also addressed study risks and benefits. CONCLUSIONS: More studies on methods to enhance efficiency and consistency of the REB approval processes for clinical trials are needed while still maintaining high ethical standards.

Self-reported depressive symptoms and memory complaints in survivors five years after ARDS.

BACKGROUND: Survivors of ARDS report depressive symptoms and memory complaints, the prevalence of which after 5 years is unknown. METHODS: We administered instruments assessing symptoms of depression (Beck Depression Inventory II [BDI-II]) and memory complaints (Memory Assessment Clinics Self-Rating Scale [MAC-S]) to 64 survivors of ARDS from four university-affiliated ICUs 5 years after ICU discharge. We compared BDI-II scores to quality of life (Medical Outcomes Study 36-Item Short Form [SF-36]) mental health domains (role emotional, mental health, mental component summary), compared BDI-II and MAC-S scores to earlier scores (median, 22 months postdischarge), and examined return to work. RESULTS: Forty-three (67.2%), 46 (71.9%), and 38 (59.4%) patients fully completed the BDI-II, MAC-S ability subscale, and MAC-S frequency of occurrence subscale, respectively. Responders were young (median, 48 years; first-third quartile [Q1-Q3], 39-61 years) with high illness severity. The median BDI-II score was 10 (Q1-Q3, 3-18); eight of 43 (18.6%) had moderate to severe depressive symptoms compared with 14 of 43 (32.6%) earlier (P = .15, n = 38 with paired data). Median MAC-S ability and MAC-S frequency scores were 81 (Q1-Q3, 57-92) and 91.5 (Q1-Q3, 76-105), respectively, similar to earlier scores (P = .67 and P = .64, respectively); 0% to 4.3% scored > 2 SDs below population norms. Higher BDI-II score was predicted by higher earlier BDI-II score, slower recovery of organ function, and longer duration of mechanical ventilation and ICU stay. Higher MAC-S score was predicted by higher earlier MAC-S score. SF-36 mental health domain scores were very stable (P = .57-.83). BDI-II and SF-36 mental health domains were negatively correlated (Spearman coefficient, -0.50 to -0.82). Most patients returned to work regardless of depressive symptoms (minimal to mild, 31 of 35 [88.6%]; moderate to severe, five of eight [62.5%]; P = .12). CONCLUSIONS: Compared with ∼ 2 years postdischarge from the ICU, depressive symptoms and memory complaints were similar at 5 years. Mental health domains of the SF-36 may not be sensitive to small changes in mood symptoms.

Functional disability 5 years after acute respiratory distress syndrome.

BACKGROUND: There have been few detailed, in-person interviews and examinations to obtain follow-up data on 5-year outcomes among survivors of the acute respiratory distress syndrome (ARDS). METHODS: We evaluated 109 survivors of ARDS at 3, 6, and 12 months and at 2, 3, 4, and 5 years after discharge from the intensive care unit. At each visit, patients were interviewed and examined; underwent pulmonary-function tests, the 6-minute walk test, resting and exercise oximetry, chest imaging, and a quality-of-life evaluation; and reported their use of health care services. RESULTS: At 5 years, the median 6-minute walk distance was 436 m (76% of predicted distance) and the Physical Component Score on the Medical Outcomes Study 36-Item Short-Form Health Survey was 41 (mean norm score matched for age and sex, 50). With respect to this score, younger patients had a greater rate of recovery than older patients, but neither group returned to normal predicted levels of physical function at 5 years. Pulmonary function was normal to near-normal. A constellation of other physical and psychological problems developed or persisted in patients and family caregivers for up to 5 years. Patients with more coexisting illnesses incurred greater 5-year costs. CONCLUSIONS: Exercise limitation, physical and psychological sequelae, decreased physical quality of life, and increased costs and use of health care services are important legacies of severe lung injury.

Education and support needs during recovery in acute respiratory distress syndrome survivors.

INTRODUCTION: There is a limited understanding of the long-term needs of survivors of the acute respiratory distress syndrome (ARDS) as they recover from their episode of critical illness. The Timing it Right (TIR) framework, which emphasizes ARDS survivors' journey from the ICU through to community re-integration, may provide a valuable construct to explore the support needs of ARDS survivors during their recovery. METHODS: Twenty-five ARDS survivors participated in qualitative interviews examining their needs for educational, emotional and tangible support for each phase of the TIR framework. Transcripts were analyzed using framework methodology. RESULTS: ARDS survivors' support needs varied across the illness trajectory. During the ICU stay, survivors were generally too ill to require information. The transfer to the general ward was characterized by anxiety surrounding decreased surveillance and concern for future health and treatment. Information needs focused on the events surrounding the acute illness, while physical and emotional needs revolved around physical therapy and psychological support for depression and anxiety. As patients were preparing for hospital discharge, they expressed a desire for specific information about the recovery and rehabilitation process following an episode of ARDS (e.g., outpatient physiotherapy, long-term sequela of the illness). Once in the community, survivors wanted guidance on home care, secondary prevention, and ARDS support groups. CONCLUSIONS: Our findings support the need for future educational and support interventions to meet the changing needs of ARDS survivors during their recovery.

Self-reported symptoms of depression and memory dysfunction in survivors of ARDS.

BACKGROUND: Survivors of ARDS have well documented physical limitations, but psychological effects are less clear. We determined the prevalence of self-reported depression and memory dysfunction in ARDS survivors. METHODS: Six to 48 (median 22) months after ICU discharge, we administered instruments assessing depression symptoms (Beck Depression Inventory-II [BDI-II]) and memory dysfunction (Memory Assessment Clinics Self-Rating Scale [MAC-S]) to 82 ARDS patients who were enrolled in a prospective cohort study in four university-affiliated ICUs. RESULTS: Sixty-one (74%), 64 (78%), and 61 (74%) patients fully completed the BDI-II, MAC-S (Ability subscale), and MAC-S (Frequency of Occurrence subscale) instruments. Responders (similar to nonresponders) were young (median 42 years, interquartile range [IQR] 35 to 56), with high admission illness severity and organ dysfunction. The median BDI-II score was 12 (IQR 5 to 25). Twenty-five (41%) patients reported moderate-severe depression symptoms and were less likely to return to work than those with minimal-mild symptoms (8/25 [32%] vs 25/36 [69%]; p = 0.005). Median MAC-S (Ability) and MAC-S (Frequency of Occurrence) scores were 76 (IQR 61 to 93) and 91 (IQR 77 to 102), respectively; 8%, 16%, and 20% scored > 2, > 1.5, and > 1 SD(s), respectively, below age-adjusted population norms for each subscale. BDI-II and MAC-S scores were negatively correlated (Spearman coefficient -0.58 and -0.50 for Ability and Frequency of Occurrence subscales, respectively; p < 0.0001). Univariable analyses showed no demographic or illness-severity predictors of BDI-II (including the Cognitive subscale) or MAC-S (both subscales); results were similar when restricted to patients whose primary language was English. CONCLUSIONS: ARDS survivors report a high prevalence of depression symptoms and a lower prevalence of memory dysfunction 6 to 48 months after ICU discharge. Depression symptoms may hinder the return to work, or patients may report these symptoms because of inability to re-enter the workforce.

Chronic sleep disorders in survivors of the acute respiratory distress syndrome.

PURPOSE: Sleep disruption is well recognized in the Intensive Care Unit. Poor sleep quality likely continues following discharge from hospital in several patients and becomes a chronic disorder in some. The aim of this study was to describe the etiology of chronic sleep complaints in survivors of ARDS. METHODS: Seven ARDS survivors with no previous sleep complaints who reported difficulty sleeping 6 months or more following discharge from hospital were evaluated. Sleep quality was assessed subjectively with a sleep history and the Insomnia Severity Index and objectively with polysomnography. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. RESULTS: A chronic sleep disorder was identified in each patient who reported difficulty sleeping. The primary sleep disorder was chronic conditioned insomnia (5 patients), parasomnia (1 patient) and obstructive sleep apnea (1 patient). In addition, 4 patients had periodic leg movements, which was of uncertain clinical significance. CONCLUSION: Chronic sleep disorders, which originate during the acute illness, are present in some ARDS survivors several months after discharge from hospital. If unrecognized, lack of treatment may contribute to impaired quality of life and incomplete rehabilitation from their critical illness.