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.).

ISSLS PRIZE IN BIOENGINEERING SCIENCE 2019: biomechanical changes in dynamic sagittal balance and lower limb compensatory strategies following realignment surgery in adult spinal deformity patients.

STUDY DESIGN: A longitudinal cohort study. OBJECTIVE: To define a set of objective biomechanical metrics that are representative of adult spinal deformity (ASD) post-surgical outcomes and that may forecast post-surgical mechanical complications. Current outcomes for ASD surgical planning and post-surgical assessment are limited to static radiographic alignment and patient-reported questionnaires. Little is known about the compensatory biomechanical strategies for stabilizing sagittal balance during functional movements in ASD patients. METHODS: We collected in-clinic motion data from 15 ASD patients and 10 controls during an unassisted sit-to-stand (STS) functional maneuver. Joint motions were measured using noninvasive 3D depth mapping sensor technology. Mathematical methods were used to attain high-fidelity joint-position tracking for biomechanical modeling. This approach provided reliable measurements for biomechanical behaviors at the spine, hip, and knee. These included peak sagittal vertical axis (SVA) over the course of the STS, as well as forces and muscular moments at various joints. We compared changes in dynamic sagittal balance (DSB) metrics between pre- and post-surgery and then separately compared pre- and post-surgical data to controls. RESULTS: Standard radiographic and patient-reported outcomes significantly improved following realignment surgery. From the DSB biomechanical metrics, peak SVA and biomechanical loads and muscular forces on the lower lumbar spine significantly reduced following surgery (- 19 to - 30%, all p < 0.05). In addition, as SVA improved, hip moments decreased (- 28 to - 65%, all p < 0.05) and knee moments increased (+ 7 to + 28%, p < 0.05), indicating changes in lower limb compensatory strategies. After surgery, DSB data approached values from the controls, with some post-surgical metrics becoming statistically equivalent to controls. CONCLUSIONS: Longitudinal changes in DSB following successful multi-level spinal realignment indicate reduced forces on the lower lumbar spine along with altered lower limb dynamics matching that of controls. Inadequate improvement in DSB may indicate increased risk of post-surgical mechanical failure. These slides can be retrieved under Electronic Supplementary Material.

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).

Association of Days Alive and at Home at Day 90 After Intensive Care Unit Admission With Long-term Survival and Functional Status Among Mechanically Ventilated Patients.

Importance: Many conventional end points in randomized clinical trials of interventions for critically ill patients do not account for patient-centered concerns such as time at home, physical function, and quality of life after critical illness. Objective: To establish whether days alive and at home at day 90 (DAAH90) is associated with long-term survival and functional outcomes in mechanically ventilated patients. Design, Setting, and Participants: The RECOVER prospective cohort study was conducted from February 2007 to March 2014, using data from 10 intensive care units (ICUs) in Canada. Patients were included in the baseline cohort if they were aged 16 years or older and underwent invasive mechanical ventilation for 7 or more days. The follow-up cohort analyzed here comprised RECOVER patients who were alive and had functional outcomes ascertained at 3, 6, and 12 months. Secondary data analysis occurred from July 2021 to August 2022. Exposures: Composite of survival and days alive and at home at day 90 after ICU admission (DAAH90). Main Outcomes and Measures: Functional outcomes at 3, 6, and 12 months were evaluated with the Functional Independence Measure (FIM), the 6-Minute Walk Test (6MWT), the Medical Research Council (MRC) Scale for Muscle Strength, and the 36-Item Short Form Health Survey physical component summary (SF-36 PCS). Mortality was evaluated at 1 year from ICU admission. Ordinal logistic regression was used to describe the association between DAAH90 tertiles and outcomes. Cox proportional hazards regression models were used to examine the independent association of DAAH90 tertiles with mortality. Results: The baseline cohort comprised 463 patients. Their median age was 58 years (IQR, 47-68 years), and 278 patients (60.0%) were men. In these patients, Charlson Comorbidity Index score, Acute Physiology and Chronic Health Evaluation II score, ICU intervention (eg, kidney replacement therapy or tracheostomy), and ICU length of stay were independently associated with lower DAAH90. The follow-up cohort comprised 292 patients. Their median age was 57 years (IQR, 46-65 years), and 169 patients (57.9%) were men. Among patients who survived to day 90, lower DAAH90 was associated with higher mortality at 1 year after ICU admission (tertile 1 vs tertile 3: adjusted hazard ratio [HR], 0.18 [95% CI, 0.07-0.43]; P < .001). At 3 months of follow-up, lower DAAH90 was independently associated with lower median scores on the FIM (tertile 1 vs tertile 3, 76 [IQR, 46.2-101] vs 121 [IQR, 112-124.2]; P = .04), 6MWT (tertile 1 vs tertile 3, 98 [IQR, 0-239] vs 402 [IQR, 300-494]; P < .001), MRC (tertile 1 vs tertile 3, 48 [IQR, 32-54] vs 58 [IQR, 51-60]; P < .001), and SF-36 PCS (tertile 1 vs tertile 3, 30 [IQR, 22-38] vs 37 [IQR, 31-47]; P = .001) measures. Among patients who survived to 12 months, being in tertile 3 vs tertile 1 for DAAH90 was associated with higher FIM score at 12 months (estimate, 22.4 [95% CI, 14.8-30.0]; P < .001), but this association was not present for ventilator-free days (estimate, 6.0 [95% CI, -2.2 to 14.1]; P = .15) or ICU-free days (estimate, 5.9 [95% CI, -2.1 to 13.8]; P = .15) at day 28. Conclusions and Relevance: In this study, lower DAAH90 was associated with greater long-term mortality risk and worse functional outcomes among patients who survived to day 90. These findings suggest that the DAAH90 end point reflects long-term functional status better than standard clinical end points in ICU studies and may serve as a patient-centered end point in future clinical trials.

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.

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.

Redundant role of tissue-selective TAF(II)105 in B lymphocytes.

Regulated gene expression is a complex process achieved through the function of multiple protein factors acting in concert at a given promoter. The transcription factor TFIID is a central component of the machinery regulating mRNA synthesis by RNA polymerase II. This large multiprotein complex is composed of the TATA box binding protein (TBP) and several TBP-associated factors (TAF(II)s). The recent discovery of multiple TBP-related factors and tissue-specific TAF(II)s suggests the existence of specialized TFIID complexes that likely play a critical role in regulating transcription in a gene- and tissue-specific manner. The tissue-selective factor TAF(II)105 was originally identified as a component of TFIID derived from a human B-cell line. In this report we demonstrate the specific induction of TAF(II)105 in cultured B cells in response to bacterial lipopolysaccharide (LPS). To examine the in vivo role of TAF(II)105, we have generated TAF(II)105-null mice by homologous recombination. Here we show that B-lymphocyte development is largely unaffected by the absence of TAF(II)105. TAF(II)105-null B cells can proliferate in response to LPS, produce relatively normal levels of resting antibodies, and can mount an immune response by producing antigen-specific antibodies in response to immunization. Taken together, we conclude that the function of TAF(II)105 in B cells is likely redundant with the function of other TAF(II)105-related cellular proteins.

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.

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.