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Rationale: Family caregivers of patients with acute cardiorespiratory failure are at high risk for distress, which is typically defined as the presence of psychological symptoms such as anxiety, depression, or posttraumatic stress. Interventions to reduce caregiver distress and increase wellness have been largely ineffective to date. An incomplete understanding of caregiver wellness and distress may hinder efforts at developing effective support interventions. Objectives: To allow family caregivers to define their experiences of wellness and distress 6 months after patient intensive care unit (ICU) admission and to identify moderators that influence wellness and distress. Methods: Primary family caregivers of adult patients admitted to the medical ICU with acute cardiorespiratory failure were invited to participate in a semistructured interview 6 months after ICU admission as part of a larger prospective cohort study. Interview guides were used to assess caregiver perceptions of their own well-being, record caregiver descriptions of their experiences of family caregiving, and identify key stress events and moderators that influenced well-being during and after the ICU admission. This study was guided by the Chronic Traumatic Stress Framework conceptual model, and data were analyzed using the five-step framework approach. Results: Among 21 interviewees, the mean age was 58 years, 67% were female, and 76% were White. Nearly half of patients (47%) had died before the caregiver interview. At the time of the interview, 9 caregivers endorsed an overall sense of distress, 10 endorsed a sense of wellness, and 2 endorsed a mix of both. Caregivers defined their experiences of wellness and distress as multidimensional and composed of four main elements: 1 ) positive versus negative physical and psychological outcomes, 2 ) high versus low capacity for self-care, 3 ) thriving versus struggling in the caregiving role, and 4 ) a sense of normalcy versus ongoing life disruption. Postdischarge support from family, friends, and the community at large played a key role in moderating caregiver outcomes. Conclusions: Caregiver wellness and distress are multidimensional and extend beyond the absence or presence of psychological outcomes. Future intervention research should incorporate novel outcome measures that include elements of self-efficacy, preparedness, and adaptation and optimize postdischarge support for family caregivers.

Importance: Overall, 1 in 3 family caregivers of patients who require intensive care unit (ICU) admission will experience significant posttraumatic stress symptoms (PTSSs), but little is known about how PTSSs evolve over time. Measuring PTSS trajectories could facilitate the development of targeted interventions to improve mental health outcomes for family caregivers of critically ill patients., Objective: To measure 6-month PTSS trajectories among caregivers of patients with acute cardiorespiratory failure., Design, Setting, and Participants: This prospective cohort study was conducted in the medical ICU of a large academic medical center among adult patients requiring (1) vasopressors for shock, (2) high-flow nasal cannula, (3) noninvasive positive pressure ventilation, or (4) invasive mechanical ventilation. Each patient was enrolled along with their primary caregiver, ie, the unpaid individual who provided the most physical, emotional, or financial support prior to ICU admission., Main Outcomes and Measures: Family caregiver PTSSs were assessed using the Impact of Events Scale-Revised within 48 hours of ICU admission, following ICU discharge, and 3 and 6 months after enrollment. Latent class growth analysis was used to measure PTSS trajectories. Preselected patient and caregiver characteristics measured at ICU admission were analyzed for association with trajectory membership. Six-month patient and caregiver outcomes were analyzed by caregiver trajectory., Results: Overall, 95 family caregivers were enrolled and provided baseline data; mean (SD) age was 54.2 (13.6) years, 72 (76%) were women, 22 (23%) were Black individuals, and 70 (74%) were White individuals. Three trajectories were identified: persistently low (51 caregivers [54%]), resolving (29 [31%]), and chronic (15 [16%]). Low caregiver resilience, prior caregiver trauma, high patient severity of illness, and good patient premorbid functional status were associated with the chronic trajectory. Caregivers with the chronic PTSS trajectory had worse 6-month health-related quality of life (mean [SD] total 36-item Short Form Survey score, persistently low trajectory: 104.7 [11.3]; resolving trajectory: 101.7 [10.4]; chronic trajectory: 84.0 [14.4]; P < .001) and reduced effectiveness at work (mean [SD] perceived effectiveness at work score, persistently low trajectory: 86.0 [24.2]; resolving trajectory: 59.1 [32.7]; chronic trajectory: 72.3 [18.4]; P = .009)., Conclusions and Relevance: In this study, 3 distinct PTSS trajectories among ICU family caregivers were observed, with 16% of caregivers experiencing chronic PTSSs over the subsequent 6 months. Family caregivers with persistent PTSS had lower resilience, prior trauma, higher patient severity of illness, and higher baseline patient functional status compared with family caregivers with persistently low PTSS, with adverse effects on quality of life and work. Identifying these caregivers is an essential first step to develop interventions tailored to those with the greatest need for support.

Context: Outcomes after cardiopulmonary resuscitation (CPR) remain poor. We have spent 10 years investigating an "informed assent" (IA) approach to discussing CPR with chronically ill patients/families. IA is a discussion framework whereby patients extremely unlikely to benefit from CPR are informed that unless they disagree, CPR will not be performed because it will not help achieve their goals, thus removing the burden of decision-making from the patient/family, while they retain an opportunity to disagree., Objectives: Determine the acceptability and efficacy of IA discussions about CPR with older chronically ill patients/families., Methods: This multi-site research occurred in three stages. Stage I determined acceptability of the intervention through focus groups of patients with advanced COPD or malignancy, family members, and physicians. Stage II was an ambulatory pilot randomized controlled trial (RCT) of the IA discussion. Stage III is an ongoing phase 2 RCT of IA versus attention control in in patients with advanced chronic illness., Results: Our qualitative work found the IA approach was acceptable to most patients, families, and physicians. The pilot RCT demonstrated feasibility and showed an increase in participants in the intervention group changing from "full code" to "do not resuscitate" within two weeks after the intervention. However, Stages I and II found that IA is best suited to inpatients. Our phase 2 RCT in older hospitalized seriously ill patients is ongoing; results are pending., Conclusions: IA is a feasible and reasonable approach to CPR discussions in selected patient populations., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Severe Acute Brain Injury (SABI) is neurologically devastating, and surrogates for these patients may struggle with particularly complex decisions due to substantial prognostic uncertainty., Objectives: To compare anxiety and depression symptoms over time between SABI surrogates and non-SABI surrogates for patients requiring prolonged mechanical ventilation (PMV)., Methods: We conducted a secondary analysis of the data from a multicenter randomized trial of a decision aid intervention for surrogates of adults experiencing PMV. Eligible patients were enrolled from medical, surgical, trauma, cardiac, and neurologic intensive care units (ICUs). ICU admitting diagnoses were used to identify patients experiencing SABI. We compared anxiety and depression symptoms as measured by the Hospital Anxiety and Depression Scale score 6 months after trial enrollment between surrogates of patients with SABI and surrogates of patients experiencing PMV for other reasons., Results: Our analysis included 206 patients, 60 (29%) with SABI and 146 (71%) without SABI, and their primary surrogate decision makers. After adjusting for potential confounders including surrogate demographics, surrogate financial distress, patient severity of illness baseline GCS, and patient health status at 6 months, we found that surrogates of patients experiencing SABI had higher symptoms of anxiety and depression than surrogates of non-SABI patients (adjusted mean difference 3.6, 95% CI 1.2-6.0)., Conclusion: Surrogates of PMV patients with SABI experience persistently elevated anxiety and depression symptoms over 6 months compared to surrogates of PMV patients without SABI. Further work is needed to understand contributors to prolonged distress in this higher risk population., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Symptoms of posttraumatic stress disorder (PTSD) are common among surrogate decision makers of patients with chronic critical illness (CCI). PTSD symptoms can be categorized into clusters including intrusion, avoidance, and hyperarousal, each of which has been associated with distinct outcomes and treatment responses. Our objective was to determine which symptom cluster was predominant among surrogates of patients with CCI., Design: Secondary analysis of data from a clinical trial of a communication intervention., Setting: The original trial was conducted in medical intensive care units at three tertiary-care centers and one community hospital., Patients: Patients with CCI (≥7 d of mechanical ventilation and not expected to die or to be weaned from the ventilator in the subsequent 72 hr) and their surrogates., Interventions: None., Measurements and Main Results: Surrogate PTSD symptoms were measured 90 days after onset of patient CCI using the Impact of Events Scale-Revised (IES-R). The IES-R includes a total score (range, 0-88, higher scores indicate severe symptoms) as well as three subscales that assess intrusion, avoidance, and hyperarousal (range of intrusion and avoidance scores 0-32 and range of hyperarousal score 0-24). Intrusion symptoms were most severe (mean score, 10.3; 95% CI, 9.3-11.2), followed by avoidance (mean score, 8.0; 95% CI, 7.2-8.8). Hyperarousal symptoms were lowest (mean score, 5.1; 95% CI, 4.5-5.7). In a multivariable linear regression model, we found that surrogates of patients who died had higher odds of intrusion (β, 5.52; p < 0.0001) and avoidance (β, 3.29; p = 0.001) symptoms than surrogates of patients who lived, even after adjusting for baseline symptoms of anxiety and depression. Patient death was not associated with hyperarousal symptoms., Conclusions: Intrusive thoughts are the most severe PTSD symptom in surrogates of patients experiencing CCI, with intensified symptoms among surrogates of patients who died. These results have the potential to inform tailored treatment strategies to reduce PTSD symptoms in this population., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: To obtain information on how family visitor restriction during the COVID-19 pandemic has impacted the workplace experience of physicians and nurses in the medical intensive care unit, and to assess differences by profession., Materials and Methods: We developed a survey containing closed- and open-ended questions, applying both quantitative and qualitative analyses to our results., Results: Of the 74 respondents, 29 (38%) were nurses and 45 (62%) were physicians. Nurses reported positive changes to daily workflow and the ability to provide medical care, while physicians reported negative changes in these areas. Both groups reported decreased comprehension and increased distress among families, and decreased ability to provide end-of-life care. For the qualitative analysis, eight themes were identified: the patient's room as space, creation of a new space through virtual communication, time, increased complexity of care, challenges around the use of technology, adjustments to team roles and responsibilities, desire for families to return, and internal tension., Conclusion: Intensive care physicians and nurses reported both positive and negative effects of family visitor restriction during the COVID-19 pandemic, with significant differences based on profession. Both groups expressed concern for an overall negative impact of visitor restriction on healthcare workers, patients, and their families., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Rationale: Surrogate decision-makers of patients with chronic critical illness (CCI) are at high risk for symptoms of post-traumatic stress disorder (PTSD). Whether patient health status after hospital discharge is a risk factor for surrogate PTSD symptoms is not known. Objectives: To determine the association between patient health status 90 days after the onset of CCI and surrogate symptoms of PTSD. Methods: We performed a secondary analysis of the data from a multicenter randomized trial of a communication intervention for adult patients with CCI and their surrogate decision-makers. Results: Surrogate PTSD symptoms were measured at 90 days using the Impact of Events Scale-Revised. For patients who were alive at 90 days, location was used as a marker of health status and included the following categories: 1 ) home (relatively good health and low acuity), 2 ) acute rehabilitation (moderate care needs and impairments, generally expected to improve), 3 ) skilled nursing facility (moderate care needs and impairments, generally not expected to improve significantly or quickly), 4 ) long-term acute care facility (persistently high acute care needs and functional impairment), and 5 ) readmission to an acute care hospital (suggesting the highest acuity of illness and care needs of the cohort). Patients who died before 90 days were categorized as deceased. In the analyses, 365 surrogates and 256 patients were included. Among patients, 49% were female, and the mean age was 59 years. Among surrogates, 71% were female, and the mean age was 51 years. A directed acyclic graph was constructed to identify covariates to be included in the model. Compared with symptoms seen among surrogates of patients living at home, heightened PTSD symptoms were seen among surrogates of patients who were readmitted to an acute care hospital (β coefficient, 15.9; 95% confidence interval [CI], 4.5 to 27.3) or had died (β coefficient, 14.8; 95% CI, 8.8 to 20.9) at 90 days. Conclusions: Surrogates of patients with CCI who have died or have been readmitted to an acute care hospital at 90 days experience increased PTSD symptoms as compared with surrogates of patients who are living at home. These patients and surrogates represent a readily identifiable group who may benefit from enhanced emotional support.

To use latent class growth analysis to identify posttraumatic stress disorder symptom trajectories in ICU family caregivers., Design: Prospective cohort study., Setting: The medical ICU at a tertiary-care center in the United States., Participants: Adult patients experiencing acute cardiorespiratory failure (defined as requiring at least one of the following: 1) vasopressors, 2) noninvasive positive pressure ventilation, 3) high-flow nasal cannula, or 4) mechanical ventilation) were enrolled in a pair with their primary family caregivers., Measurements and Main Results: Participants were enrolled within the first 48 hours of ICU admission. Family caregiver posttraumatic stress disorder symptoms were measured using the Impact of Events Scale-Revised at four time points: at enrollment, shortly after ICU discharge, and at 3 and 6 months after ICU discharge. The data were examined using latent class growth analysis to identify posttraumatic stress disorder symptom trajectories. Two distinct symptom trajectories were identified: a persistently high trajectory, characterized by high posttraumatic stress disorder symptoms at initial assessment, which remained elevated over time, and a persistently low trajectory, characterized by low posttraumatic stress disorder symptoms at initial assessment, which remained low over time. Approximately two-thirds of caregivers belonged to the persistently high trajectory, and one-third of caregivers belonged to the persistently low trajectory., Conclusions: Using latent class growth analysis to measure 6-month ICU family caregiver posttraumatic stress disorder symptom trajectories, we identified two distinct trajectories (persistently low and persistently high). A larger cohort study is warranted to further delineate posttraumatic stress disorder trajectories in this population, with the ultimate goal of targeting high-risk caregivers for interventions to reduce psychologic distress and improve long-term caregiver outcomes., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Rationale: Inhaled treprostinil may improve oxygenation and have additional antiinflammatory effects in early acute hypoxemic respiratory failure, potentially preventing or reducing the severity of acute respiratory distress syndrome (ARDS). Objectives: To determine whether administration of inhaled treprostinil to patients at risk for ARDS is feasible, safe, and efficacious. Methods: We performed a double-blind, placebo-controlled, single-center randomized pilot trial at a quaternary care academic medical center. Patients with acute hypoxemia due to pneumonia or signs of low-pressure pulmonary edema with a unilateral or bilateral infiltrate on chest imaging and a 4 L/min supplemental oxygen requirement not requiring positive pressure ventilation were evaluated. Randomized patients received study drug or placebo (2:1 ratio). Treatment was initiated at 6 breaths every 4 hours and titrated up to 12 breaths. Subjects were maintained on treatment for 7 days and then tapered off over a period of 4 days. Study drug was stopped if positive pressure ventilation was required (invasive or noninvasive). Results: Fourteen patients were enrolled over a period of 31 months. Baseline characteristics were not significantly different between treatment groups with respect to age, sex, race, Acute Physiologic Assessment and Chronic Health Evaluation score, lung injury prediction score, or baseline mean oxygen saturation as measured by pulse oximetry (Sp O 2 ):fraction of inspired oxygen (Fi O 2 ) ratio. Trends in daily baseline and 30-minute postdose Sp O 2 :Fi O 2 ratio for all treatment points were not significantly different between placebo and treprostinil. Four patients required positive pressure ventilation in the treprostinil group versus one in the placebo group. Conclusions: Inhaled treprostinil administration is feasible in patients at risk for ARDS but was not associated with improvement in the Sp O 2 :Fi O 2 ratio relative to placebo. Drug-associated adverse events were not severe nor unexpected based on the known adverse effect profile of inhaled treprostinil. The clinical benefit of this intervention is unclear at this time in the absence of larger studies.Clinical trial registered with Clinicaltrials.gov (NCT02370095).

Purpose: Intermediate care units (IMCUs) represent an alternative care setting with nurse staffing levels between those of the general ward and the intensive care unit (ICU). Despite rising prevalence, little is known about IMCU practices across US hospitals. The purpose of this study is to characterize utilization patterns and assess for variation., Materials and Methods: A 14-item survey was distributed to a random nationwide sample of pulmonary and critical care physicians between January and April 2017., Results: A total of 51 physicians from 24 different states completed the survey. Each response represented a unique institution, the majority of which were public (59%), academic (73%), and contained at least 1 IMCU (65%). Of the IMCUs surveyed, 58% operated as 1 mixed unit that admitted medical, cardiac, and surgical patients as opposed to having separate subspecialty units. Ninety-one percent of units admitted step-down patients from the ICU, but 39% of units accepted a mix of step-up patients, step-down patients, postoperative patients, and patients from the emergency department. Intensivists managed care in 21% of units whereas 36% had no intensivist involvement., Conclusion: Organization practices vary considerably between IMCUs across institutions. The impact of different organization practices on patient outcomes should be assessed.

Purpose: To identify specific components of ICU clinician supportive care and communication that are associated with increased post-traumatic stress disorder (PTSD) symptoms for surrogate decision makers of patients with chronic critical illness (CCI)., Methods: We conducted a secondary analysis of data from a randomized controlled trial of palliative care-led meetings to provide information and support for CCI surrogates. The primary outcome for this secondary analysis was PTSD symptoms at 90 days, measured by the Impact of Event Scale-Revised (IES-R). Caregiver perceptions of clinician support and communication were assessed using a version of the After-Death Bereaved Family Member Interview (ADBFMI) instrument modified for use in non-bereaved in addition to bereaved caregivers. The association between ADBFMI items and IES-R score was analyzed using multiple linear regression., Results: Ninety-day follow up was complete for 306 surrogates corresponding to 224 patients. Seventy-one percent of surrogates were female, and the mean age was 51 years. Of the domains, negative perception of the patient's physical comfort and emotional support was associated with the greatest increase in surrogate PTSD symptoms (beta coefficient 1.74, 95% CI 0.82-2.65). The three specific preselected items associated with increased surrogate PTSD symptoms were surrogate perception that clinicians did not listen to concerns (beta coefficient 10.7, 95% CI 3.6-17.9), failure of the physician to explain how the patient's pain would be treated (beta coefficient 12.1, 95% CI 4.9-19.3), and lack of sufficient religious contact (beta coefficient 11.7, 95% CI 2-21.3)., Conclusion: Modifiable deficits in ICU clinician support and communication were associated with increased PTSD symptoms among CCI surrogates.

Rationale: Chronically critically ill patients are often dependent on family members for surrogate decision-making, and these surrogates are at high risk for emotional distress. We hypothesized that patient- and surrogate-specific risk factors for surrogate post-traumatic stress disorder (PTSD) symptoms can be identified early in the course of chronic critical illness., Objectives: To identify risk factors for PTSD symptoms in surrogate decision-makers of chronically critically ill patients., Methods: We performed a secondary analysis of the database from a multicenter randomized trial of a communication intervention for chronic critical illness patients and surrogates. Variables preselected for plausible mechanism for increasing PTSD symptoms and identifiable by Day 10 of mechanical ventilation were included in the analysis for association with surrogate PTSD symptoms at 90 days, as measured by the Impact of Events Score-Revised (IES-R). Patient factors included demographics, insurance status, baseline functional status, chronic comorbidities, illness severity, and presence of advance directive. Surrogate variables included demographics, education level and employment, religion, relationship to patient, and Hospital Anxiety and Depression Scale score measured at enrollment. Multivariable linear regression models were then constructed for 26 potential risk factors, including biologically or mechanistically plausible confounders for each, with IES-R score as the outcome. All models were adjusted for multiple respondents, using a mixed model, considering the patients as a random factor., Results: Our analysis included 306 surrogates for 224 patients. A total of 49% of patients were female, and mean age was 59 years (95% confidence interval [CI], 56.4-60.7). A total of 71% of surrogates were female, and mean age was 51 years (95% CI, 49.3-52.4). After examining each potential risk factor in a separate multivariable model, only Day-10 surrogate Hospital Anxiety and Depression Scale score (β coefficient = 1.02; 95% CI, 0.73-1.30) and patient unresponsiveness (β coefficient = 8.39; 95% CI, 0.83-15.95) were associated with higher IES-R scores., Conclusions: Among surrogate decision-makers for chronically critically ill patients, high anxiety and depression scores and patient unresponsiveness on or near Day 10 of mechanical ventilation are risk factors for PTSD symptoms at 90 days.

Background: Previous research investigating the impact of delayed intensive care unit (ICU) transfer on outcomes has utilized subjective criteria for defining critical illness., Objective: To investigate the impact of delayed ICU transfer using the electronic Cardiac Arrest Risk Triage (eCART) score, a previously published early warning score, as an objective marker of critical illness., Design: Observational cohort study., Setting: Medical-surgical wards at 5 hospitals between November 2008 and January 2013., Patients: Ward patients., Intervention: None., Measurements: eCART scores were calculated for all patients. The threshold with a specificity of 95% for ICU transfer (eCART ≥ 60) denoted critical illness. A logistic regression model adjusting for age, sex, and surgical status was used to calculate the association between time to ICU transfer from first critical eCART value and in-hospital mortality., Results: A total of 3789 patients met the critical eCART threshold before ICU transfer, and the median time to ICU transfer was 5.4 hours. Delayed transfer (>6 hours) occurred in 46% of patients (n = 1734) and was associated with increased mortality compared to patients transferred early (33.2% vs 24.5%, P < 0.001). Each 1-hour increase in delay was associated with an adjusted 3% increase in odds of mortality (P < 0.001). In patients who survived to discharge, delayed transfer was associated with longer hospital length of stay (median 13 vs 11 days, P < 0.001)., Conclusions: Delayed ICU transfer is associated with increased hospital length of stay and mortality. Use of an evidence-based early warning score, such as eCART, could lead to timely ICU transfer and reduced preventable death. Journal of Hospital Medicine 2016;11:757-762. © 2016 Society of Hospital Medicine., Competing Interests: and Source of Funding: This research was funded in part by an institutional Clinical and Translational Science Award grant (UL1 RR024999; PI: Dr. Julian Solway). Dr. Churpek is supported by a career development award from the National Heart, Lung, and Blood Institute (K08 HL121080). Drs. Churpek and Edelson have a patent pending (ARCD. P0535US.P2) for risk stratification algorithms for hospitalized patients. In addition, Dr. Edelson has received research support from Philips Healthcare (Andover, MA), research support from the American Heart Association (Dallas, TX) and Laerdal Medical (Stavanger, Norway). She has ownership interest in Quant HC (Chicago, IL), which is developing products for risk stratification of hospitalized patients., (© 2016 Society of Hospital Medicine.)

Disruption of gap junctional intercellular communication (GJIC) is associated with tumor progression during multistage carcinogenesis. A coordinated interaction of epithelial tumor cells with the stromal environment via growth factors is a prerequisite for tumor invasion. Here, the involvement of growth factors in downregulation of homologous GJIC of dermal fibroblasts, used as model for stromal cells, was examined. Tumor cell derived transforming growth factor-beta1 (TGF-beta1), having oncogenic activities at late stages of carcinogenesis, was identified as being responsible for downregulation of GJIC via an increase in the level of reactive oxygen species in stromal fibroblasts. Lowering the level of reactive oxygen species by antioxidants, such as the cell-permeable N-acetyl-L-cysteine, prevented TGF-beta1-mediated downregulation of intercellular communication between confluent fibroblasts.