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Can Coping-Skills Training Help Patients Who Have Received Intensive Hospital Care to Cope with Depression and Anxiety?
Christopher E. Cox, MD, MPH1,2, Catherine L. Hough, MD, MSci3, Shannon S. Carson, MD4, Douglas B. White, MD, MAS5, Jeremy M. Kahn, MD, MSci5, Maren K. Olsen, PhD6,7, Derek M. Jones, MDiv1,2, Tamara
J. Somers, PhD8, Sarah A. Kelleher, PhD8, Laura S. Porter, PhD8
1Department of Medicine, Division of Pulmonary & Critical Care Medicine, Duke University, Durham, North Carolina; [email protected], [email protected] 2Program to Support People and Enhance Recovery, Duke University, Durham, North Carolina 3Department of Medicine, Division of Pulmonary & Critical Care Medicine, University of Washington, Seattle, Washington; [email protected] 4Department of Medicine, Division of Pulmonary & Critical Care Medicine, University of North Carolina, Chapel Hill, North Carolina; [email protected] 5Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; [email protected], [email protected] 6Department of Biostatistics, Duke University, Durham, North Carolina; [email protected] 7Center for Health Services Research in Primary Care, Durham VA Medical Center, Durham, North Carolina 8Department of Psychiatry and Behavioral Science, Duke University, Durham, North Carolina; [email protected], [email protected], [email protected]
Original Project Title: Improving Psychological Distress Among Critical Illness Survivors and Their Informal Caregivers PCORI Project ID: 195 ClinicalTrials.gov ID NCT01983254 HSRProj: 20142219
To cite this document, please use: Cox C, Hough C, Carson Set al. 2018. Can Coping-Skills Training Help Patients Who Have Received Intensive Hospital Care to Cope with Depression and Anxiety? Washington, DC: Patient-Centered Outcomes Research Institute (PCORI). https://doi.org/10.25302/9.2018.CER.195
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Study design and concept: CEC, LSP, CLH, SSC, JMK, DBW, MKO Writing and review: CEC, MKO, DMJ, JMK, LSP, CLH, SSC, DBW, TJS, SAK Analyses: MKO, CEC, DMJ Obtaining data: DMJ, CEC, CLH, SSC, DBW, TJS, SAK Acquisition of funding: CEC Final approval: CEC, MKO, DMJ, LSP, CLH, SSC, DBW, JMK, TJS, SAK Accountable for all aspects of work: CEC
Corresponding author:
Christopher Cox Duke University Medical Center / Division of Pulmonary & Critical Care Medicine Box 102043 / Durham, NC 27710 [email protected] / Telephone: (919) 681-7232 / Fax: (919) 681-8359
Grant support: This research was made possible by contract number 195 from the Patient-Centered
Outcomes Research Institute (PCORI). The content is solely the responsibility of the authors and does
not necessarily represent the official views of PCORI. Dr. Olsen was also supported by the Center of
Innovation for Health Services Research in Primary Care (CIN 13-410) at the Durham VA Medical Center.
Key words: critical illness, psychological distress, depression, patient reported outcomes, patient-
centeredness
Short title: Coping skills training for ICU survivors
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Table of Contents
ABSTRACT ............................................................................................................................. 4
KEY POINTS ........................................................................................................................... 6
INTRODUCTION ..................................................................................................................... 7
METHODS ............................................................................................................................. 7
Setting, governance, and oversight ........................................................................................................................... 7
Enrollment ................................................................................................................................................................. 8
Coping skills training (CST) intervention .................................................................................................................... 9
Education program comparator ................................................................................................................................ 9
Data collection .......................................................................................................................................................... 9
Outcome measures ................................................................................................................................................. 10
Statistical analysis ................................................................................................................................................... 10
RESULTS .............................................................................................................................. 12
DISCUSSION ........................................................................................................................ 26
CONCLUSIONS ..................................................................................................................... 28
REFERENCES ........................................................................................................................ 29
APPENDIX............................................................................................................................ 33
ACKNOWLEDGMENTS .......................................................................................................... 80
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Abstract
Importance: Many survivors of critical illness and their family members experience significant
psychological distress after hospital discharge.
Objective: To determine if assigning participants to a postdischarge coping skills training (CST) program
reduces patient and family psychological distress compared with assigning participants to an educational
program.
Design: A multicenter randomized clinical trial conducted between December 2013 and February 2016.
Setting: Five academic and community hospitals.
Participants: Adult patients (≥ 18 years) who received mechanical ventilation > 48 hours were
randomized individually after discharge; 1 family member per patient was also offered a chance to
participate. Ten patient and family member stakeholders participated as advisors in the planning and
conduct of this study.
Interventions: Participants assigned to CST were offered 6 30-minute weekly telephone calls with a
psychologist. CST was designed to teach coping strategies for managing distress related to critical illness.
CST participants also received access to a complementary study website. An education program
comparator included 2 telephone calls to review printed and web-based information about critical
illness.
Main outcomes and measures: The primary outcome was the Hospital Anxiety and Depression Scale
(HADS) summary score assessed among patients 3 months postrandomization. Secondary outcomes
included HADS depression and anxiety subscale scores and posttraumatic stress disorder symptoms
measured using the Impact of Events Scale-Revised scale assessed at 3 and 6 months.
Results: Among 175 patients randomized to CST (n = 86) or education (n = 89), 131 (75%) completed the
6-month follow-up. Of the patients, 44 (25%) did not complete the study, generally because of death or
medical illness. At 3 months, there were no significant differences between the CST and education
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groups in HADS summary score improvement (difference 1.3 [95% CI: –0.9, 3.4], p = 0.24). Secondary
outcomes for patients and family members were similar by treatment group at 3 and 6 months. A priori
exploratory secondary analyses revealed that among patients with high baseline distress (HADS
summary score > 14), those randomized to CST had improved HADS summary scores (difference –4.6,
[95% CI: –8.6, –0.6], p = 0.02) compared with education participants at 6 months.
Limitations: Nearly 40% more participants than planned to offset higher-than-expected attrition
observed after consent but before randomization. Additionally, the generalizability of our results may be
limited because the cohort was drawn largely from academic institutions.
Conclusions and relevance: Among critical illness survivors, CST did not reduce symptoms of
psychological distress compared with an education program. However, among patients with high
baseline distress, CST may have improved symptoms of distress at 6 months. Future efforts to reduce
psychological distress among critical illness survivors will require greater patient engagement and should
specifically target high-risk populations.
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Key points
Question: Does a postdischarge coping skills training (CST) intervention delivered by telephone and
online reduce symptoms of depression, anxiety, and posttraumatic stress disorder compared with a
similarly delivered critical illness education program?
Findings: In this randomized clinical trial that included 175 patients and 86 family members, CST did not
reduce psychological distress compared with education overall. Exploratory analyses suggest that
symptoms of psychological distress may have been reduced among patients with high levels of baseline
distress in the CST group, but not the education group.
Meaning: CST did not reduce symptoms of psychological distress among a general population of
intensive care unit survivors. The CST intervention requires further study among patients with high
baseline distress and should include features that enhance participant engagement to aid in adherence.
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Introduction
Acute respiratory failure requiring mechanical ventilation in an intensive care unit (ICU) affects more
than a million persons in the United States alone each year.1 In addition to the physical and cognitive
disability associated with critical illness that has been the focus of much research,2,3 ICU survivors and
their family members suffer from symptoms of depression, anxiety, and posttraumatic stress disorder
(PTSD) that may persist for more than 1 year at 10-fold higher rates than in the general population.4-10
However, few effective postdischarge interventions address ICU survivors’ psychological distress. More
broadly, patients commonly experience barriers accessing traditional postdischarge psychological
interventions because of acquired disability, distance from specialized centers, and financial distress.11,12
Coping is an active response for managing the demands of stressful events such as the experience of
critical illness.13,14 While the use of adaptive coping skills (e.g., relaxation, positive reframing, problem
solving) is associated with increased self-efficacy and decreased psychological distress, ICU patients and
their family members report infrequent use of such strategies.15,16 Coping skills training (CST)
interventions based on cognitive-behavioral principles have been effective in helping patients with
cancer and other medical conditions manage a variety of symptoms and types of psychological
distress.17,18 To address ICU survivors’ distress as well as the inherent difficulty of accessing personalized
care during critical illness recovery, we developed a telephone-based CST program. In a pilot evaluation,
ICU patients and their family members acquired adaptive coping skills and experienced improvement in
symptoms of psychological distress.19
To further evaluate the effects of the CST intervention augmented with web content, we conducted a
multicenter randomized trial testing the hypothesis that a postdischarge CST program compared with a
standardized education program would result in fewer symptoms of depression, anxiety, and PTSD.
Methods
Setting, governance, and oversight
The institutional review boards of the participating sites (Duke, University of Washington, University of
North Carolina at Chapel Hill, University of Pittsburgh) approved the study protocol (Online Appendix). A
10-member panel of layperson research stakeholders from diverse backgrounds participated through
the entirety of the project to ensure a patient-centered approach was applied to the conception of the
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key research question, the development of the protocol, the general approach to inclusion and
exclusions, and the choice of outcomes (eMethods, pp. 2-3). An independent data safety monitoring
board approved the protocol and reviewed performance, data quality, and safety at 6-month intervals.
Enrollment
We attempted to enroll patient–informal caregiver dyads for participation in this trial. Between
December 2013 and April 2015, clinical research coordinators identified all patients meeting inclusion
criteria through daily electronic health record–based screening of consecutive medical and surgical ICU
patients. The coordinator obtained permission from the ICU attending physician to approach the patient
and/or his or her legal representative for written informed consent at the time of transfer from the ICU
to the ward.
Patient inclusion criteria were age ≥ 18, receipt of mechanical ventilation for > 48 consecutive hours,
and successful extubation before hospital discharge. For each patient, the unit of subsequent
randomization, we attempted to enroll for intervention participation 1 family member aged ≥ 18 years
who expected to provide significant postdischarge assistance.20 Patients without an available family
member were still eligible. Patient exclusions included preexisting or current cognitive impairment
(defined by chart review for evidence of dementia or 3 or more errors on a brief 6-item in-person
cognitive screen), treatment for severe mental illness during the 6 months preceding admission,
residence at a location other than home immediately before admission, poor English fluency, ICU
attending expectation of survival < 3 months, inability to complete study procedures as determined by
study staff, and failure to return home within 3 months after discharge. Exclusions for family members
included history of cognitive impairment and poor English fluency determined by need for a translator
to participate in medical decision making.
Randomization to coping skills training (CST) or education program groups was performed by the
electronic data system after completion of the first postdischarge interview, which was completed
within 2 weeks of patient arrival home from either the hospital or a postacute care facility. A password-
protected computerized system allocated patients at a 1:1 treatment group ratio with blocks of 4,
stratifying by 3 factors to ensure balance: severity of baseline patient psychological distress (Hospital
Anxiety and Depression Scale [HADS] summary score [≤ 14 versus > 14]), days of mechanical ventilation
(≤ 7 versus > 7), and study site. Printed material was mailed to each participant that included
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instructions for accessing a password-protected, treatment group–specific website hosting videos and
other content. The interventions (described in detail on eMethods pp. 4-6) began 1 week after
randomization.
Coping skills training (CST) intervention
One of 2 clinical psychologists (TJS, SAK) was randomly assigned to each patient. The CST intervention
was delivered in 6 weekly telephone sessions, each lasting about 30 minutes, that addressed (1)
relaxation exercises, (2) progressive muscle relaxation, (3) pleasant activities and the activity–-rest cycle,
(4) communication, (5) cognitive restructuring and pleasant imagery, and (6) review and planning for
sustainability.19 Psychologists taught each skill by providing a description and rationale for its use,
leading participants through practice with feedback in the context of any self-reported ongoing
stressors, helping participants plan how to apply the skill in real life, and highlighting relevant web-based
content. In addition to the patient participants learning the skills themselves, family members were
encouraged to coach the patients in applying the skills and using the web content on a day-to-day basis.
Education program comparator
As a comparator and control condition, we designed an education program to address poor
comprehension of critical illness, a common finding that is associated with distress and that has been
responsive to past interventions.21 This program consisted of 6 informational videos with accompanying
web-based content. Study staff with content expertise in critical illness conducted 2 30-minute calls with
participants during the 6-week intervention period to review materials and answer related questions.
Data collection
Trained coordinators blinded to treatment group collected clinical data. Participants completed study
surveys by telephone with treatment group–blinded Duke coordinators or by a password-protected
electronic patient-reported outcomes system at 3 time periods: within 2 weeks after arrival home from
either the hospital or a postacute care facility (preintervention), 3 months postrandomization
(immediate postintervention), and 6 months postrandomization.22 Interviews were delayed for at least 4
weeks for family members of patients known to have died during follow-up. Study staff used scheduled
phone calls, postcards, letters, and emails to prompt completion of intervention sessions and surveys.
Participants were compensated $10 for each of 3 interviews completed. Follow-up was completed in
February 2016.
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Outcome measures
The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS) summary score
assessed at 3 months after randomization.23 HADS summary scores can range from 0 (best) to 42
(worst). The minimal clinically important difference in HADS score is 1.5 to 2 units.24,25
Secondary outcomes included the 7-item HADS anxiety and depression subscale scores, which can range
from 0 to 21. A HADS subscale score > 7 represents significant distress. Other secondary outcomes
included the Impact of Events Scale-Revised (IES-R) PTSD symptom score, a 22-item scale with scores
ranging from 0 (best) to 88 (worst)26; quality of life as measured with the EuroQOL-5 visual analog scale
(range 0 [worst] to 100 [best])27; global mental and physical health status assessed with the PROMIS
Global Short Form (range of each 4 [worst] to 20 [best])28; adaptive coping behaviors (active coping, use
of emotional support, positive reframing, planning, and acceptance) measured by the Brief COPE (range
10 [worst] to 40 [best])29; and self-efficacy using a 4-item scale adapted from Lorig and colleagues (item
range 1 [worst] to 10 [best]).30 At each scheduled survey, participants could report up to 3 stressors in
their own words, rating each stressor’s severity on a scale of 0 (not at all severe) to 10 (extremely
severe), as well as record the number of weeks spent at home (i.e., not hospitalized) throughout follow-
up, an outcome suggested by the stakeholder group.
Statistical analysis
Based on previous studies,19,31 190 (95 in each treatment group) patients were needed to detect a HADS
summary score difference of 4 units at 3 months post-randomization with 90% power and a type I error
rate of 5%, assuming a baseline standard deviation of 8.7, a correlation between baseline and 3 months
of 0.4, and a 3-month dropout rate of 10%.32
We conducted the primary analysis of the HADS summary score and the secondary survey outcomes
using a linear mixed-effects model with an unstructured covariance (using PROC MIXED in SAS
[computer program]. Version 9.4. Cary, NC). Model parameters included a common intercept (which
constrains the baseline means to be equal), stratification variables (baseline HADS summary score
stratum [centered], duration of mechanical ventilation stratum [centered], and site [centered]),
indicator variables for months 3 and 6, and a CST indicator interacted with months 3 and 6. We used
contrast statements to estimate the difference between the groups from baseline to each of the follow-
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ups. We tested the primary hypothesis by examining the 3-month estimated group difference in mean
HADS summary score improvement, 95% CI, and P value.
We originally chose the stratification variables of baseline HADS summary score (≤ 14 or > 14) and
ventilator days (≤ 7 or > 7) because of their suspected association with the outcome variables.
Therefore, we also examined the intervention group effect on primary and secondary outcomes within
each of these strata using a general linear model with unstructured covariance. Model parameters
included separate intercepts for the low and high levels of each strata; indicator variables for months 3
and 6; indicators for the CST intervention interacted with months 3 and 6; indicators of the strata
interacted with months 3 and 6; and the 3-way interaction of the strata indicator variable, CST
intervention, and months 3 and 6.
We used all available data, including data from patients who were lost to follow-up or died during the
study, in all analyses. We conducted primary and secondary survey outcome analyses with full likelihood
methods, which are valid under a missing data framework in which the missing values may depend on
intervention group, site, initial HADS summary score stratum, duration of ventilation stratum, and any
observed outcome values.33,34 We also conducted a sensitivity analysis in which additional predictors of
missing values were explored and included in a multiple imputation procedure.35 We examined all
baseline patient demographic and clinical characteristics presented in Tables 1 and 2 for potential
inclusion in the imputation model. We examined these variables descriptively and via chi-square and t
tests by dropout yes/no and intervention complier yes/no. We included in the imputation model
variables with p < 0.20, which included randomization group, site, marital status, medical ICU,
education, discharged home, caregiver enrolled, length of ICU stay, HADS summary, length of
mechanical ventilation, and financial distress. Additionally, we included all baseline variables for all
outcomes in the imputation model.
We generated 10 multiple imputations for the missing 3- and 6-month outcomes via the MCMC option
in PROC MI. We assessed model convergence via EM iterations to convergence as well as ACF and time
series plots of the mean week 56 weight. We drew imputations every 100 iterations. We analyzed the 10
imputed data sets with a general linear model including a common intercept, stratification variables
(baseline HADS summary score stratum [centered], duration of mechanical ventilation stratum
[centered], and site [centered]), indicator variables for months 3 and 6, and indicators for the CST
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intervention interacted with each of the follow-up time point indicator variables. We combined the 10
sets of model estimates and standard errors using PROC MIANALZE.
Estimated mean differences, 95% confidence intervals, and P values are reported for all comparisons,
with p < 0.05 considered statistically significant. We identified primary and secondary outcomes a priori,
and we made no adjustments for multiple comparisons. We used SAS version 9.4 for analyses. Further
details, including the statistical code, are provided in the eMethods (pp. 7-14).
Results
Of 411 potentially eligible patients, 277 proved informed consent, and 175 were randomized to CST (n =
86) or education (n = 89) (Figure 1). Of these, 86 (49%) had an eligible family member who was enrolled.
Treatment groups appeared balanced in baseline characteristics (Table 1, eTable 1). Patients on average
were middle-aged and severely ill, with an expected hospital mortality of about 50% based on the mean
Acute Physiologic Assessment and Chronic Health Evaluation (APACHE II) score. Family members were
primarily spouses/partners (n = 41, 48%) or parents (n = 12, 14%). Approximately a third of patients had
been treated for a psychiatric condition in the 3 months preceding admission.
Patients experienced relatively long hospitalizations (mean ~25 days) (eTable 2). Of the patients, 52
(30%) were discharged to a postacute care facility before eventually returning home. Readmission
occurred among 43 (25%) of patients during follow-up.
A total of 54 (63%) patients in the CST group and 58 (65%) in the education group were adherent to
intervention procedures, defined as completion of 1 or more calls (CST group) or self-reported viewing
of intervention material (education group) (Figure 2 . Missed CST sessions were mostly related to
medical illness (n = 24, 42%), loss to contact (n = 9, 16%), or death (n = 5, 9%).Only 5 (6%) CST patients
who were physically and cognitively able completed no sessions.
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Figure 1: Flow of patients and family members.
CST = coping skills training; EP = education program. *Some participants met more than 1 exclusion criterion.
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Table 1: Baseline characteristics of patients and their family members
Characteristic
Patients Family Members
Coping Skills
Training
(n = 86)
Education
Program
(n = 89)
Coping Skills
Training
(n = 39)
Education
Program
(n = 47)
Age, mean (SD), years 49.7 (13.8) 53.7 (13.5) 50.0 (14.9) 52.9 (15.2)
Female gender, no. (%) 38 (44) 37 (42) 33 (85) 36 (77)
Race, no. (%)
White 60 (70) 64 (72) 35 (90) 38 (81)
Black 21 (24) 17 (19) 4 (10) 8 (17)
American Indian/Alaskan Native 0 2 (2) 0 1 (2)
Asian 2 (2) 0 0 0
Native Hawaiian or other Pacific Islander 1 (1) 0 0 0
Multiple races 1 (1) 5 (6) 0 0
Don’t know or don’t wish to answer 1 (1) 1 (1) 0 0
Hispanic ethnicity, no. (%) 0 2 (2) 0 1 (2)
Marital status, no. (%)
Married or live with partner 44 (51) 45 (51) 30 (77) 32 (68)
Divorced or separated 20 (24) 22 (25) 2 (5) 3 (6)
Single 18 (21) 19 (21) 7 (18) 11 (23)
Widowed 4 (5) 3 (3) 0 1 (2)
Highest level of education, no. (%)
High school graduate or less 37 (43) 36 (40) 16 (41) 18 (38)
Trade, technical, or vocational school; some college 23 (27) 25 (28) 9 (23) 10 (21)
College degree or higher 26 (30) 28 (32) 13 (33) 19 (40)
Missing 0 0 1 (3) 0
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Employment status prior to hospitalization, no. (%)
Working full time 29 (34) 29 (33) 17 (44) 14 (30)
Working part time 6 (7) 6 (7) 5 (13) 5 (11)
Unemployed, looking for work 3 (3) 7 (8) 3 (8) 4 (9)
Homemaker full time 2 (2) 2 (2) 5 (13) 4 (9)
Student 2 (2) 1 (1) 1 (3) 1 (2)
Retired 12 (14) 17 (19) 5 (13) 16 (34)
Disabled 32 (37) 27 (30) 3 (8) 3 (6)
Caring for young children at home, no. (%) 61 (71) 69 (78) 27 (69) 35 (74)
Living with patient before admission, no. (%) - - 26 (67) 29 (62)
Relationship to patient, no. (%)
Spouse or partner - - 17 (44) 24 (51)
Parent - - 7 (18) 5 (11)
Brother or sister - - 4 (10) 3 (6)
Child - - 3 (8) 3 (6)
Other family - - 0 3 (6)
Friend - - 2 (5) 1 (2)
Missing - - 6 (15) 8 (17)
Insurance status, no. (%)
Commercial 39 (45) 38 (43) - -
Medicare 25 (29) 30 (34) - -
Medicaid 16 (19) 12 (13) - -
None 4 (5) 7 (8) - -
Other 2 (2) 2 (2) - -
Financial distress at randomization, no. (%)
Short on money and need more to pay bills 17 (20) 18 (20) 8 (21) 8 (17)
Barely have enough to pay bills and for basic needs 19 (22) 10 (11) 10 (26) 6 (13)
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Have enough money for just a few extra things 34 (40) 34 (38) 12 (31) 16 (34)
Completely comfortable 16 (19) 27 (30) 8 (21) 17 (36)
Religion or faith, no. (%)
Christian 69 (80) 65 (73) 28 (72) 32 (68)
None 10 (12) 11 (12) 6 (15) 9 (19)
Hindu, Buddhist, Taoism, or other Eastern Asian 1 (1) 0 0 1 (2)
Jewish 0 1 (1) 0 0
Other 6 (7) 12 (13) 5 (13) 5 (11)
Treated for psychiatric condition in the 3 months before
admission, no. (%)a
Depression 27 (31) 20 (22) 9 (23) 5 (11)
Anxiety 24 (28) 17 (19) 12 (31) 9 (19)
Posttraumatic stress disorder 4 (5) 6 (7) 2 (5) 2 (4)
Other psychological condition 1 (1) 0 0 0
Alcohol abuse in the month before hospitalization, no. (%) 18 (21) 14 (16) - -
Drug abuse in the month before hospitalization, no. (%) 8 (9) 5 (6) - -
Health literacy,b mean (SD) 7.4 (3.3) 6.9 (3.4) 5.0 (2.2) 4.9 (2.0)
Chronic medical comorbidities, b mean (SD) 3.6 (2.8) 3.8 (2.8) - -
Site, no. (%)
1 33 (38) 35 (39) 10 (26) 18 (38)
2 19 (22) 17 (19) 14 (36) 12 (26)
3 18 (21) 19 (21) 10 (26) 12 (26)
4 16 (19) 18 (20) 5 (13) 5 (11)
Treating ICU at time of eligibility, no. (%)
Medicine 43 (50) 41 (46) - -
General surgery 14 (16) 20 (22) - -
Cardiology 12 (14) 9 (10) - -
17
Trauma 11 (13) 14 (16) - -
Neurology and neurosurgery 6 (6) 5 (5) - -
APACHE II score on day of enrollment,b mean (SD) 26.3 (7.7) 25.4 (8.7) - -
a Participants could report multiple conditions.
b Citations in eMethods page 10.
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Figure 2: Patient adherence with group-based treatment programs.
This figure displays adherence status as well as reasons for nonadherence by treatment group as well as reasons for missed sessions (*) for the coping skills training (CST) group. Each circle represents 1 patient. The number of sessions completed by each patient is indicted on the horizontal axis. CST adherence is defined as completing at least 1 session. CST patients completed 228 sessions. Only 5 (6%) CST patients who were physically and cognitively able completed no sessions. Education program (EP) group adherence is based on self-report that they viewed the online modules (“Viewed”) or not (“Didn’t view”). Of able patients, 112 (93%) were adherent. Also see eFigures 1, 2, and 3.
Post-randomization interviews were completed by 136 (81%) and 131 (80%) of patients alive at 3 and 6
months, respectively. Similarly, 69 (80%) and 66 (77%) interviews were completed by family members at
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3 and 6 months, respectively. The reasons for patient dropout at 6 months included loss to contact (n =
18, 10%), serious illness (n = 14, 8%), and death (n = 12, 7%) (eFigures 2, 3).
Results of the primary analysis revealed no significant difference in mean HADS summary score between
the CST and education patient groups at either 3 months (16.6 and 15.3; between-group difference in
change 1.3 [95% CI, –0.9, 3.4], p = 0.24) or 6 months (15.6 and 15.9; between-group difference in change
–0.3 [95% CI, –2.7, 2.0], p = 0.78; see Table 2; eTable 3 demonstrates similar results from the multiple
imputation analysis). Similarly, no significant between-group differences were present in HADS anxiety
and depression subscales. IES-R scores were similar for CST patients and education patients at 3 months
(31.0 versus 27.9; between-group difference in change 3.1 [95% CI, –1.9, 8.1], p = 0.22) and 6 months
(29.4 versus 25.8; between-group difference in change 3.6 [95% CI, –2.7, 10.0], p = 0.26). Additionally,
there were no statistically significant differences in physical or mental health status, quality of life, self-
efficacy, and coping (Table 2) or days at home during follow-up (eTable 4). We observed no significant
between-group differences among family members for primary and secondary outcomes at 3 and 6
months (eTable 5). Patients’ self-reported stressors persisted largely unchanged throughout follow-up in
severity and type, with physical disability and financial distress mentioned frequently (eTable 6, eFigure
4).
There were significant group-based differences in outcomes by the prespecified stratification variables
in exploratory analyses. Among patients with high distress at baseline (HADS summary score > 14; n =
60, 34%), CST recipients experienced significant improvement in 6-month, though not 3-month,
outcomes including HADS summary scores (15.5 versus 20.2, between-group difference –4.6 [95% CI –
8.6, –0.6], p = 0.02), HADS depression scores (6.6 versus 9.6, between-group difference –3.0 [95% CI: –
5.4, –0.7], p = 0.01), global mental health (12.0 versus 9.7, between-group difference 2.3 [95% CI: 0.05,
4.1], p=0.01), and quality of life (59.5 versus 48.3, between-group difference 11.2 [95% CI 0.02, 22.4], p =
0.0496; Table 3). Proposed mechanistic metrics were improved as well, including self-efficacy (5.9 versus
4.5; between-group difference 1.4 [95% CI: 0.2, 2.5], p = 0.02).
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Table 2: Model estimated primary and secondary outcomes, patients with baseline HADS > 14 (n = 60).a
Baseline 3 Months Postrandomization 6 Months Postrandomization
Estimate (SE)
EP Estimate
(SE)
CST
Estimate
(SE)
Mean Difference
in Change From
Baseline Between
Groups (95% CI) p
EP
Estimate
(SE)
CST
Estimate
(SE)
Mean Difference
in Change From
Baseline Between
Groups (95% CI)
p
Primary Outcome
HADS summaryb 16.0 (0.6) 15.3 (0.9) 16.6 (0.9) 1.3 (–0.9, 3.4) 0.24 15.9 (1.0) 15.6 (1.0) –0.3 (–2.7, 2.0) 0.78
HADS anxietyb 8.3 (0.4) 8.3 (0.6) 8.6 (0.6) 0.3 (–1.0, 1.6) 0.65 8.5 (0.6) 8.3 (0.6) –0.2 (–1.6, 1.2) 0.78
HADS depressionb 7.6 (0.4) 6.7 (0.5) 7.6 (0.5) 0.9 (–0.4, 2.1) 0.16 7.2 (0.6) 7.0 (0.6) –0.2 (–1.6, 1.2) 0.76
Secondary Outcomes
IES-Rb 31.6 (2.1) 27.9 (2.6) 31.0 (2.6) 3.1 (–1.9, 8.1) 0.22 25.8 (2.9) 29.4 (2.9) 3.6 (–2.7,10.0) 0.26
Global physical healthc 10.9 (0.3) 11.9 (0.4) 11.6 (0.4) –0.3(–1.3, 0.6) 0.53 11.5 (0.4) 12.0 (0.4) 0.4 (–0.5, 1.4) 0.36
Global mental healthc 12.2 (0.4) 12.1 (0.5) 11.4 (0.5) –0.7 (–1.8, 0.3) 0.16 11.8 (0.5) 11.9 (0.5) 0.08 (–0.9, 1.1) 0.88
EQ-5D quality of lifec 63.7 (2.7) 65.3 (3.3) 62.3 (3.3) –3.0 (–9.6, 3.6) 0.37 60.7 (3.1) 61.0 (3.2) 0.3 (–5.9, 6.6) 0.92
Brief COPEc 32.4 (0.8) 31.1 (1.0) 30.3 (1.0) –0.8 (–3.0, 1.4) 0.49 30.0 (1.1) 29.6 (1.1) –0.4 (–2.9, 2.1) 0.75
Self-efficacyc 5.8 (0.3) 5.4 (0.3) 5.8 (0.3) 0.3 (–0.3, 1.0) 0.31 5.8 (0.3) 6.2 (0.3) 0.4 (–0.2, 1.0) 0.23
a General linear models were used to compare mean differences in outcomes between the coping skills training (CST) and education program
(EP) groups. HADS = Hospital Anxiety and Depression Scale; EQ-5D = EuroQOL-5 visual analog scale
21
b Negative values in mean score difference for these outcomes indicate more improved scores for the CST group. For example, at 6 months
postrandomization, the estimated mean total HADS score was 15.6 in the CST group compared with 15.9 in the EP group. The differential change
from baseline was –0.3 (95% CI: –2.7, 2.0) (i.e., 0.3 points of improvement) more in the CST group than the EP group, but this difference was not
statistically significant (p = 0.78). c Positive values in mean score difference for these outcomes indicate more improved scores for the CST group. For example, at 6 months
postrandomization, the estimated mean global physical health score was 12.0 in the CST group compared with 11.5 in the EP group. The
differential change from baseline was 0.4 (95% CI: –0.5, 1.4) (i.e., 0.4 points of improvement) more in the CST group than the EP group, but this
difference was not statistically significant (p = 0.36).
22
Table 3: Model estimated primary and secondary outcomes, patients ventilated > 7 days (n = 47).a
a General linear models were used to compare mean differences in outcomes between CST and EP groups.
b Negative values in mean score difference for these outcomes indicate more improved scores for the CST group. For example, at 6 months
postrandomization, the estimated mean total HADS score was 15.6 in the CST group compared with 15.9 in the EP group. The differential change
from baseline was –0.3 (95% CI: –2.7, 2.0) (i.e., 0.3 points of improvement) more in the CST group than the EP group, but this difference was not
statistically significant (p = 0.78).
Baseline 3 Months Postrandomization 6 Months Postrandomization
Estimate (SE)
CST Estimate
(SE)
EP
Estimate
(SE)
Mean Difference
in Change From
Baseline Between
Groups (95% CI) p
CST
Estimate
(SE)
EP
Estimate
(SE)
Mean Difference
in Change From
Baseline Between
Groups (95% CI)
p
Primary Outcome
HADS summaryb 16.0 (0.6) 16.6 (0.9) 15.3 (0.9) 1.3 (–0.9, 3.4) 0.24 15.6 (1.0) 15.9 (1.0) –0.3 (–2.7, 2.0) 0.78
HADS anxietyb 8.3 (0.4) 8.6 (0.6) 8.3 (0.6) 0.3 (–1.0, 1.6) 0.65 8.3 (0.6) 8.5 (0.6) –0.2 (–1.6, 1.2) 0.78
HADS depressionb 7.6 (0.4) 7.6 (0.5) 6.7 (0.5) 0.9 (–0.4, 2.1) 0.16 7.0 (0.6) 7.2 (0.6) –0.2 (–1.6, 1.2) 0.76
Secondary Outcomes
IES-Rb 31.6 (2.1) 31.0 (2.6) 27.9 (2.6) 3.1 (–1.9, 8.1) 0.22 29.4 (2.9) 25.8 (2.9) 3.6 (–2.7,10.0) 0.26
Global physical healthc 10.9 (0.3) 11.6 (0.4) 11.9 (0.4) –0.3(–1.3, 0.6) 0.53 12.0 (0.4) 11.5 (0.4) 0.4 (–0.5, 1.4) 0.36
Global mental healthc 12.2 (0.4) 11.4 (0.5) 12.1 (0.5) –0.7 (–1.8, 0.3) 0.16 11.9 (0.5) 11.8 (0.5) 0.08 (–0.9, 1.1) 0.88
EQ-5D quality of lifec 63.7 (2.7) 62.3 (3.3) 65.3 (3.3) –3.0 (–9.6, 3.6) 0.37 61.0 (3.2) 60.7 (3.1) 0.3 (–5.9, 6.6) 0.92
Brief COPEc 32.4 (0.8) 30.3 (1.0) 31.1 (1.0) –0.8 (–3.0, 1.4) 0.49 29.6 (1.1) 30.0 (1.1) –0.4 (–2.9, 2.1) 0.75
Self-efficacyc 5.8 (0.3) 5.8 (0.3) 5.4 (0.3) 0.3 (–0.3, 1.0) 0.31 6.2 (0.3) 5.8 (0.3) 0.4 (–0.2, 1.0) 0.23
23
c Positive values in mean score difference for these outcomes indicate more improved scores for the CST group. For example, at 6 months postrandomization, the estimated mean global physical health score was 12.0 in the CST group compared with 11.5 in the EP group. The differential change from baseline was 0.4 (95% CI: –0.5, 1.4) (i.e., 0.4 points of improvement) more in the CST group than the EP group, but this difference was not statistically significant (p = 0.36).
24
Table 4: Outcomes analyzed by days of mechanical ventilation stratification variable: ventilation > 7 days.
Baseline 3 Months Postrandomization 6 Months Postrandomization
Estimate
(SE)
CST
Estimate
(SE)
EP
Estimate
(SE)
Mean Difference
in Change From
Baseline Between
Groups (95% CI) p
CST
Estimate
(SE)
EP
Estimate
(SE)
Mean Difference
in Change From
Baseline Between
Groups (95% CI)
p
Primary Outcome
HADS totala 10.33 (1.17) 12.53
(1.53)
8.47
(1.70)
4.07
(0.05, 8.08)
0.047 10.82
(1.71)
8.93 (1.83) 1.89
(–2.61, 6.40)
0.41
HADS anxietya 5.78
(0.70)
5.83
(0.90)
4.54
(1.00)
1.29
(–1.11, 3.69)
0.29 5.56
(1.01)
4.95 (1.09) 0.61
(–2.07, 3.28)
0.66
HADS depressiona 4.56
(0.63)
6.60
(0.87)
3.96
(0.98)
2.64
(0.21, 5.08)
0.03 5.13
(0.97)
3.97 (1.04) 1.16
(–1.51, 3.84)
0.39
Secondary Outcomes
IES-Ra 21.60 (2.96) 24.87
(3.77)
21.35
(4.20)
3.52
(–6.36, 13.41)
0.48 25.80
(4.71)
21.52
(5.04)
4.28
(–8.59, 17.14)
0.51
Global physical healthb 12.29 (0.43) 12.22
(0.70)
13.13
(0.78)
–0.91
(–2.86, 1.03)
0.36 12.96
(0.71)
12.57
(0.76)
0.39
(–1.53, 2.31)
0.69
Global mental healthb 14.09 (0.54) 12.33
(0.76)
14.50
(0.84)
–2.18
(–4.21, –0.15)
0.04 13.29
(0.78)
14.29
(0.83)
–1.00
(–3.05, 1.06)
0.34
EQ-5D quality of lifeb 73.04 (3.72) 62.07
(4.64)
77.89
(5.13)
–15.82
(–28.53, –3.11)
0.02 70.64
(5.20)
68.24
(5.24)
2.40
(–10.89, 15.69)
0.72
25
A total of 47 (27%) patients received ventilation > 7 days. General linear models were used to compare mean differences in outcomes between CST and EP groups, with an intervention group effect by days of ventilation stratification variable (0 = ≤ 7 and 1 = > 7). Data are displayed as mean (standard error) and mean difference (95% confidence interval). a For these outcomes, negative values in mean score difference indicate more improved scores for the CST group. b For these outcomes, positive values in mean score difference indicate more improved scores for the CST group.
Brief COPEb 32.73 (0.98) 32.73
(0.98)
30.01
(1.72)
1.27
(–3.22, 5.76)
0.58 29.90
(1.79)
28.46
(1.96)
1.44
(–3.66, 6.54)
0.58
Self-efficacyb 6.73
(0.35)
6.36
(0.51)
6.72
(0.56)
–0.36
(–1.73, 1.02)
0.61 6.78
(0.50)
7.14 (0.53) –0.36
(–1.71, 0.99)
0.60
26
In contrast, among those with > 7 days of ventilation (n = 47, 27%), education program patients had
improvements at 3 months in mean HADS summary score (12.5 versus 8.5, between-group difference
4.0 [95% CI: 0.05, 8.1] p = 0.047), HADS depression score (6.6 versus 4.0, between-group difference 2.6
[95% CI: 0.2, 5.1], p = 0.03), global mental health (12.3 versus 14.5, between-group difference –2.2 [95%
CI –4.2, –0.2], p = 0.04), and quality of life (62.1 versus 77.9, between-group difference –15.8 [95% CI: –
28.5, –3.1], p = 0.02; Table 4). However, these differences were not sustained at 6 months.
Discussion
In a large multicenter clinical trial of ICU survivors and their family members, we found that a telephone-
and web-based coping skills training (CST) program initiated after discharge did not reduce symptoms of
depression, anxiety, and PTSD at 3 or 6 months among either patients or family members compared
with an education program control. A priori exploratory subgroup analyses, however, revealed that
among patients with high levels of baseline distress, CST reduced symptoms of psychological distress
and improved quality of life at 6 months compared with the education control at a magnitude of clinical
importance.
There are a number of potential explanations for lack of an overall effect among a general population of
ICU survivors. First, the intervention’s impact was likely attenuated by the decision to include a broadly
representative sample of patients without consideration of their degree of functional debilitation or
distress at the time of randomization in order to increase the generalizability of the results. For example,
patients were allowed up to 3 months to return home after hospital discharge to allow participation by
those discharged to postacute care facilities, a subgroup known to have high levels of distress.36
However, these patients were more likely to drop out of the study due to unresolved illness. Also,
similar to recent approaches among ICU survivor–targeted interventions,37 we opted not to exclude
patients with low baseline distress because we hypothesized that the intervention might prevent an
increase in distress over time as the stresses of chronic critical illness and caregiving burden
accumulated.38 Yet participants’ baseline distress on average was less than observed in a previous
pilot,19 thus limiting the intervention’s potential for effect. Second, patients’ illnesses were severe,
persistent, and disruptive throughout follow-up, leading to a lower-than-planned intervention dose
despite 6620 contact attempts (mean 27.6 [SD 12.1] per participant) by study staff (eTable 9).
27
Other interventions for ICU survivors’ distress have been evaluated in both inpatient (e.g., ICU diaries,39
in-ICU psychologist intervention40) and outpatient (e.g., self-help rehabilitation manuals,41 ICU survivor
clinics,42 case management programs37) settings, though these have demonstrated little effect on
depression and anxiety symptoms.43,44 But despite CST’s similar lack of a primary effect, this study
provides valuable insights that can improve future efforts to alleviate psychological distress among
those who experience a serious illness or who may be unable to access traditional face-to-face therapy.
Our findings suggest that future approaches to addressing distress among ICU survivors should possibly
focus on improving the identification of ICU survivors with high levels of distress. However, illness
severity and delirium limit the accuracy of in-hospital distress screening among patients, while family
members’ distress is not clearly associated with patient demographics or clinical characteristics.38 In
addition to developing prediction models for functional and psychological phenotyping,45 screening for
distress soon after discharge using web- or SMS text-based surveys may better capture patients with
high levels of distress.16,22
Novel strategies are also required to increase participant retention, a chronic and complex problem
encountered in all long-term follow-up studies involving critically ill patients. As expected, nearly two-
thirds of missed intervention sessions were among those whose illness persisted or worsened.
Surprisingly, however, adherence was lower among participants with shorter durations of life support,
perhaps because they recovered sufficiently to resume bandwidth-limiting duties at work and home
(eTable 10). Past work has shown that acute critical illness may make a greater global impact in
comparison with that related to a worsening of a chronic condition.46 While addressing all of these
factors will be challenging, improving intervention usability could significantly increase retention
through better engagement with patients during the dynamic processes of recovery and social
reintegration.47
Study limitations are notable. We needed to enroll nearly 40% more participants than planned to offset
higher-than-expected attrition observed after consent but before randomization. While the effect on
the observed results is unknown, our ability to characterize those who dropped out will inform future
efforts to conduct more efficient ICU-based trials. Because the cohort was drawn largely from academic
institutions, our results may not reflect the experience of those treated in other settings. However, the
cohort was geographically diverse and the investigators included a group of patient and family member
28
research stakeholders to ensure a patient- and family-centered perspective.20 Last, recent research has
highlighted novel adaptive coping styles in the context of ICU survivorship that, while not included in our
intervention, could better personalize future iterations.16,48
Conclusions
Among a general population of ICU survivors and their family members, a telephone- and web-based
coping skills training program did not reduce symptoms of depression, anxiety, and PTSD compared with
an education program. However, exploratory analyses suggest that among patients with high baseline
levels of distress, CST might have reduced symptoms of psychological distress in comparison with
control at 6 months. Future efforts to reduce psychological distress in this population will require
greater patient engagement and likely target patients with elevated levels of baseline distress.
29
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APPENDIX
34
eSupplement: Effects of a telephone- and web-based coping skills training program for survivors of critical illness and their family members: a randomized clinical trial Contents A. eMethods 1. Layperson stakeholder plan and process 2. Detailed explanation of interventions 3. Inclusion and exclusion criteria and approach (expanded) 4. Other variables of interest collected with citations 5. Statistical analysis (expanded) *6. Timeline of responses to address dropout during the conduct of the study *7. Amendments to the study B. eResults Tables eTable 1: Additional baseline characteristics of patients and family members eTable 2: Clinical characteristics and outcomes of patients eTable 3: Model estimated outcomes, patients (multiple imputation) eTable 4: Weeks not at home analysis eTable 5: Model estimated outcomes, family members eTable 6: Self-rated stressors, patients eTable 7: Outcomes by HADS >14 stratification variable, patients eTable 8: Outcomes by ventilator days >7 stratification variable, patients eTable 9: Study staff contact attempts eTable 10: Factors associated with adherence and dropout *eTable 11: Client Satisfaction Questionnaire scores, patients *eTable 12: Outcomes by HADS >14, patients (multiple imputation) *eTable 13: Outcomes by HADS ≤14, patients *eTable 14: Outcomes by HADS ≤14, patients (multiple imputation) *eTable 15: Outcomes by ventilator days >7, patients (multiple imputation) *eTable 16: Outcomes by ventilator days ≤7, patients *eTable 17: Outcomes by ventilator days ≤7, patients (multiple imputation) Figures eFigure 1: Timeline of study events for patients eFigure 2: Study completion status by group, patients eFigure 3: Study completion status by group, family members eFigure 4: Self-reported stressors and change over time among patients eFigure 5: Outcomes by ventilator days stratification variable, patients C. eReferences for Supplement
35
*not referenced in manuscript A. eMethods 1. Layperson stakeholder plan and process Overview of stakeholder engagement plan (from PFA 195 grant application, 2012): Our patient and stakeholder engagement plan is framed by the PCORI Methodology Group Report. It focused on the interaction between the investigators and a group of patient/family stakeholders. Although patients and families at other sites will also be closely involved, this more intensive interaction in North Carolina will allow frequent face to face meetings at low expense and allow direct interaction with community-based resources. This “core group” will then interact more broadly with patients and families at other sites, as well as national patient and research groups. Identification of Key Stakeholders (from PFA 195 grant application, 2012): We identified a diverse group of stakeholders including patients, family members, patient support and advocacy groups, research groups, and professional societies. Our stakeholder selection process was approved by Duke’s Institutional Review Board (Protocol #00037478). We reviewed relevant case histories from our past research studies, evaluated community resources, and performed internet searchers for national foundations. The process of engagement was transparent and no conflicts of interest were identified. Our 10 patient and family stakeholders are diverse in gender, age (range 30 to 80), ethnicity (African-American and Caucasian), socioeconomic status, urban vs rural, time since critical illness (range 1-5 years), occupation (active working and retired), and general experience with critical illness (relatively full recovery vs significant residual disability): • Patient 1 and Family member 1: Patient 1 is a middle-aged survivor of the acute respiratory distress syndrome and Family member 1 is her partner and informal caregiver (also a nurse and health systems IT expert). They live in rural North Carolina. Patient 1, a laboratory technician at a local hospital, has had repeated episodes of acute respiratory failure and feels that she has not yet recovered completely. She is now supported by disability payments. They mention that better strategies for family support are needed after ICU discharge. • Patient 2 and Family member 2: Patient 2 is a young survivor of the acute respiratory distress syndrome. Family member 2 is his mother, a retired nurse, who was Patient 1’s informal caregiver for over 2 years. Together, they live in a socioeconomically depressed urban area in North Carolina. They are interested in helping people to get emotional and informational support after discharge from the hospital. They describe the experience of critical illness as life changing. • Patient 3 and Family member 3: Dyad 3 is an elderly couple who live in rural North Carolina. Patient 3 experienced prolonged mechanical ventilation after a traumatic accident and Family member 3 was his caregiver. They think that people have such different needs after critical illness that a single intervention is unlikely to be applicable to all. They believe that flexible, supportive programs are best. • Patient 4 and Family member 4: Patient 4 is a survivor of acute respiratory failure who was managed in a community hospital for nearly a month and underwent tracheotomy, leading to voice problems. Her husband works part time now in rural North Carolina. Family member 4 identifies as a highly stressed caregiver who says that better support systems are needed for families after discharge. Both stress that they think it is a good idea to improve the post-discharge experience and help those with communication difficulties. • Patient 5 and Family member 5: Patient 5 is a survivor of acute respiratory failure secondary to trauma. His wife, Family member 5, works full time. Patient 5 noted that there are few support systems for patients and families after discharge, and wants to help establish such a structure.
Partners’ involvement in developing the study design (from PFA 195 grant application, 2012): Stakeholders, particularly patients and their family members, were involved in this project in various ways from
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the ground up starting in research initiated by our group in 2008 (indirect involvement) until the current trial (an active stakeholder group).1 A multi-step process, beginning with open-ended questioning of “what is important to your quality of life,” led to the development of study interventions, study design, and outcomes measures proposed during interactions that began during the planning stages for the grant application. More recently, our group of stakeholders involved in the current proposal have contributed to intervention editing, study design recrafting, addition of new study outcomes (e.g., “days at home during follow up”), and in drafting both a governance plan and a dissemination plan. This interaction occurred primarily by teleconference and email, though some face to face meeting was performed as well. Brief summary of actual patient and family research stakeholder involvement in study. The involvement of the patient and family stakeholders described in Section 1 above began before the research grant application was submitted. In a series of meetings (by telephone due to the great distance that separated stakeholders), stakeholders generally agreed that some help was needed for ICU survivors and their families to improve quality of life. A number of frameworks were discussed that included emotional, physical, and caregiver supports. After a great deal of discussion over numerous calls, it was decided that we focus on alleviating distress. Yet stakeholders also felt strongly that a usual care control was unacceptable to them. This led to the development of a critical illness education program as a comparator, with the justification that while this was perhaps not currently standard of care it should be given how simple it would be to distribute. Outcomes were discussed and debated, as well. Depression, anxiety, PTSD, and quality of life were unanimously approved. Some felt that it would be important to include measures of how much time a person spent at home, as opposed to in the hospital, after they started the study. After funding, investigators and stakeholders met more frequently to discuss design issues. Importantly, study inclusion and exclusion criteria. We could find no strong evidence to support a very narrow approach, i.e., enforcing extremely strict inclusion criteria or specific baseline levels of distress. Instead, stakeholders felt strongly that a broad, inclusive approach was ‘most fair.’ Investigators debated inclusions and exclusions at great length and eventually agreed on a broad inclusion strategy given how little is known about predicting trajectories of either psychological of physical symptoms among ICU survivors and their family members. Through the study, the Duke-based study team met in person with the stakeholders at dinner 2-3 times per year. Email messages were commonly used and telephone conferences were held throughout each study year as well. At each meeting, we reviewed experiences to date, discussed progress, and planned out next steps including dissemination of data. Stakeholders reviewed de-identified interval reports free of group-based distinctions that were sent to DSMB members and the Duke IRB. Significant portions of time were also spent brainstorming about other ways to assist ICU survivors. While this overview is brief, we must emphasize that the input and assistance of the patient and family stakeholders was substantial and important to the conduct of the CSTEP trial.
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2. Detailed explanation of interventions Coping skills training (CST) program Patient-caregiver dyads will receive a total of 6 weekly, 30-minute telephone sessions conducted by an experienced psychologist. Although our past work used more frequent but shorter telephone calls, participants reported that fewer calls were preferred, even if they were longer. In response, reduced the number of sessions needed to cover key material by grouping related topics and also enhanced CST’s adaptability to individual stressors of current importance (Figure). The total CST dose we will deliver is similar and should be adequate to demonstrate clinically meaningful reductions in psychosocial distress based on our past studies and pilot research.2,3 The overall CST goals are to teach subjects (1) a variety of coping strategies for managing the emotional distress and multisystemic problems related to critical illness and (2) how to apply and maintain coping skills long-term. The intervention’s format and content are modeled after effective CST interventions our group has performed 4-7 and informed both by ICU outcomes studies and our recent pilot work.1,8-11
The outline of the specific coping skills taught is shown in Table. In the initial session, participants will be provided with a rationale in which coping skills are described as a way to manage current identified problems as well as minimize the effects of other problems experienced during recovery. A key exercise will be participants’ identification of major perceived stresses as a context for real life coping skills application. Depending on needs and concerns voiced by participants, the interventionist will direct future sessions toward timely topics. One session will introduce relaxation training as a way to cope with problems that arise when trying to be active, using a three-step behavioral rehearsal procedure. During another session, participants will be encouraged to increase activity through use of activity-rest cycling and pleasant activity scheduling.12 In activity-rest cycling, patients identify activities that they have trouble tolerating and learn to break them up into periods of moderate activity and rest. Pleasant imagery aids in managing emotional distress related to symptoms such as weakness.13 In another, subjects will learn communication skills as an aid to developing effective coping skills. An additional session introduces cognitive restructuring exercises to demonstrate the relation between thoughts, feelings, and behavior. The interventionist will help participants identify instances in which their interpretations of an event might be restructured in a more adaptive manner using calming self-statements. Another session introduces problem-solving guidelines, an intervention that has demonstrated efficacy in a variety of contexts.2 In the last session, we will focus on a review of learned coping skills, discuss progress in utilizing the coping skills, address challenges in applying the coping skills, and develop a plan for maintenance of gains. Potential problems in coping efforts will identified and plans to deal with them developed. It should be emphasized that the above plan is a blueprint for therapy, the course of which can be adapted to address moments of crisis or particular problem areas experienced by participants. Study handouts and brief videos of interventionist-led sessions and will be posted on a password-protected website. If a dyad member dropped out, the other member was allowed to continue the intervention.
Topics for coping skills training sessions
1. Relaxation training & behavioral rehearsal
4. Communication exercise and mini-practice
2. Progressive muscle relaxation
5. Cognitive restructuring and pleasant imagery
3. Pleasant activities and activity-rest cycle
6. Maintenance planning
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Education program Educational programs are perceived as logical and credible by patients, have demonstrated value in reducing distress in other studies, and were requested specifically by our stakeholders as a needed intervention.14,15 The primary goal of this intervention is to provide educational information about the nature and treatment of critical illness. The topics are based on informational needs reported by patients and families who have experienced critical illness (Table).1,16 Its presentation and discussion format is similar to our group’s past multi-session protocols.6,17,18 Participant dyads will receive 2 phone calls from Duke CRC 2 with an identical duration (~30 minutes) to the CST intervention. Subjects will be sent a printed manual post-discharge with handouts summarizing the content of each session. Brief videos of interventionist-led sessions and study handouts will be posted on a password-protected website for participants. If a dyad member dropped out, the other member was allowed to continue the intervention. Study website and resources for each treatment group. The study website, CSTEPstudy.org, was built for three purposes: • to describe the study for potential participants • to provide resources (text, video, audio) for participants' use from each treatment group, and • to provide transparency to the general public with information about this study that was funded by a
government-associated entity Each treatment group had a tab reserved for their use (i.e., 'Green Group' and 'Orange Group'). Group members could access only their group's materials using a unique password that was provided to them after randomization. CST group participants' resources included a series of 6 videos (~10-15 min in length each) produced by study staff that largely mirrored the general planned content for the 6 telephone sessions shown in the Table on Page 4 above. Handouts in PDF format were available for download that served to augment each session. Links to contact the study team were also present. EP group participants' resources included a series of 6 videos (~10-15 minutes in length each) produced by study staff that described topics shown in the Table above. Handouts in PDF format were available for download that served to augment each session. Links to contact the study team were also present. Screenshots from the website are shown on the next page.
Topics for Education Program 1. Acute respiratory failure:
causes, diagnosis 4. Exercise & critical illness
2. Hospital & post- discharge ICU treatments
5. Post-discharge support resources
3. Neuromuscular weakness 6. Informational resources
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Screenshots from study website for both treatment groups' content:
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3. Inclusions and exclusions (taken from study electronic manual of operations) Patient inclusion criteria were age ≥18, mechanical ventilation for more than 48 consecutive hours, and currently extubated. Patients could still be included if they lacked an informal caregiver, their informal caregiver declined to participate, or if their caregiver became ineligible after consent but before randomization. We attempted to enroll one family member for each patient defined as the person aged ≥18 years most likely to provide the most post-discharge care. Caregivers were allowed to participate in all study procedures if the patient withdrew from the study after randomization for any reason. Patient exclusions included pre-existing or current cognitive impairment, residence at a location other than home immediately before hospital admission, need for translator because of poor English fluency, expected survival <3 months, discharged to hospice (outpatient or inpatient), treatment for severe mental illness within 6 months preceding hospital admission, or unable to complete study procedures as determined by study staff. Post-consent, pre-randomization ineligibility criteria for patients included becoming too ill to participate, development of significant cognitive disability, suicidality, failure to return home within 3 months after hospital discharge, or death. Exclusions for caregivers included a history of significant cognitive impairment or English fluency poor enough to require a medical translator. Inclusion assessment for patients 1. Mechanical ventilation1 for >48 consecutive hours and currently extubated □ yes □ no 2. Age ≥18 years □ yes □ no If the answer for any criterion is NO, STOP - the patient (and informal caregiver) should NOT be included. If ALL answers are YES, the patient can be included in the study 1 Mechanical Ventilation = Currently receiving invasive mechanical ventilation, via orotracheal or nasotracheal tube or via tracheotomy. Pre-consent ineligibility (i.e., exclusion) criteria for patients Step 1 Pre-existing, significant cognitive impairment1 □ yes □ no Residing in a location other than home before admission □ yes □ no Need for a translator because of poor English fluency □ yes □ no Expected survival <3 months per attending physician □ yes □ no Discharged to hospice (outpatient or inpatient) □ yes □ no Not liberated from mechanical ventilation at the time of discharge2 □ yes □ no Patient lacks decisional capacity3 □ yes □ no Patient suddenly died □ yes □ no Treatment for severe mental illness within the past 6 months (e.g., depression with psychosis, suicidality, or schizophrenia as per medical record) □ yes □ no Unable to complete study procedures as determined by study staff (e.g., multiple planned surgeries, active polysubstance abuse) □ yes □ no If answer is YES for any criterion, STOP - the patient AND caregiver are ineligible. If ALL answers are NO, the patient is potentially eligible. Proceed to Step 2.
1Advanced dementia or other significant neurological impairment that affects ability to do activities of daily living.
2 Liberated from ventilator = breathing without mechanical ventilation (either invasive or non-invasive, [ i.e. CPAP or BiPAP]) for 4 consecutive days (whether or not subsequently reintubated during the hospitalization) or at the time of hospital discharge. Non-invasive ventilation for sleep disordered breathing (i.e., sleep apnea) does not count in this calculation. A patient who is liberated from the
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ventilator could be receiving oxygen supplementation via nasal cannula or mask and/or could still have tracheotomy tube in place. The date of ventilator liberation is the date that began the 4-day period. 3Clinical capacity to participate in effective decision making. Study and/or clinical staff are confident that the patient has clinical capacity to provide consent or participate in clinical decision making. That is, in the judgment of the examiner, the patient—after reading the IRB approved patient consent document (or having it read to them):
-Can understand the terms of participation in the study • the purpose of the study • what will be required of study participants • the potential risks, benefits and alternatives of study participation • pros & cons of study involvement
-Can communicate a choice in his/her own words (or write on a communication board)
Step 2 The following cognitive screen only has to be completed if all other criteria in Step 1 above are marked “no.” Script: “Now I would like to ask you some questions to have you use your memory. I’m going to name three objects. Please wait until I say all three words, and then I’d like you to repeat them to me. Okay? [PAUSE] Please repeat these words for me: Apple, Table, Penny.” Can you repeat those words now? CORRECT INCORRECT A. Apple…………………………………………………………………. 1 0 B. Table………………………………………………………………….. 1 0 C. Penny…………………………………………………………………. 1 0 D. What year is this?................................................. 1 0 E. What month is this?............................................. 1 0 F. What is the day of the week?............................... 1 0 What were the three words I asked you to remember?
CORRECT INCORRECT G. Apple………………………………………………………………….. 1 0 H. Table………………………………………………………………….. 1 0 I. Penny…………………………………………………………………. 1 0 Current significant cognitive impairment, an exclusion criterion, is defined as 3 errors on 6-Item cognitive screen—see below) incorrect responses. Cognitive impairment? □ yes □ no If cognitive impairment is present, STOP - the patient AND caregiver are ineligible. If cognitive impairment is not present, the patient is eligible. Proceed to discuss study and obtain written informed consent. Inclusion criteria, family members 1. Person expected to provide the majority of post-discharge help to patient □ yes □ no 2. Age ≥18 years □ yes □ no If the answer for any criterion is NO, the caregiver should be marked as “Not Included”. However, the patient can still be enrolled.
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Pre-Consent Ineligibility (i.e. Exclusion) Criteria for family members Need for a translator because of poor English fluency □ yes □ no History of significant cognitive impairment1 □ yes □ no 1Advanced dementia or other significant neurological impairment that affects ability to do activities of daily living. If answer for any criterion is YES, the caregiver is ineligible but the patient may still be enrolled. Post-consent (and pre-randomization) ineligibility (i.e., exclusion) criteria Patients Patient became too ill to participate □ yes □ no Patient developed significant cognitive impairment1 □ yes □ no Patient died □ yes □ no Patient has not arrived home within 3 months after hospital discharge □ yes □ no Patient exhibits suicidality □ yes □ no
1 Cognitive impairment that affects ability to do activities of daily living.
If answer is YES for any criterion, STOP - the patient AND caregiver are ineligible Caregiver Caregiver no longer available □ yes □ no Caregiver exhibits suicidality □ yes □ no If answer is YES for any caregiver criterion, the caregiver is ineligible but the patient may still be enrolled. A new caregiver may be added before randomization.
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4. Other variables of interest collected during study In addition to the outcomes described in the main manuscript, we also collected information on potential covariates including: A. Sociodemographic measures • B. Clinical characteristics including: • - critical illness severity (APACHE II score)19 • - presence of ICU delirium (Confusion Assessment Method-Intensive Care Unit [CAM-ICU] as documented in the
electronic health record as ‘positive’ during the index ICU stay)20 • - health literacy (Peterson’s 3-item scale)21 • - quality of ICU communication (Engelberg's and Curtis' Quality of Communication scale summary item)22 • - cognitive function (Modified Telephone Interview for Cognitive Status [TICS-m])23 • - caregiver burden (Caregiver Reaction Assessment scale item ‘my daily activities are centered around care for my
loved one’)24 • - hope (NIH / NeuroQOL Positive Affect and Well-Being Item Bank v1, item 12) • - optimism (Life Optimism Test item ‘overall I expect more good things to happen to me than bad things’)25 • - social support (NIH PROMIS FSE item se31059x2) • - chronic medical comorbidities (Charlson Index)26 • - previous and current psychological therapies •
• C. Satisfaction with intervention. • The Client Satisfaction Scale (8-item version; score range 0 [worst] to 32 [best]) was administered. Additionally, open
ended questions were asked at the conclusion of the final study interview to obtain feedback about the interventions.27
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5. Statistical analysis, expanded Methods and SAS Code In the following code for the primary and secondary outcome models, the analysis dataset – outstack – is stacked and sorted, in ascending order by patient (variable name=personID) and time point (variable name=interview), such that there is one record per patient per time point. In the model, INT2 and INT3 are indicator variables for the 3 and 6 month interviews, respectively; CST is the indicator variable for the CST group; “HADS_strata_center” and “vent_strata_center” are baseline HADS strata (≤14, >14) and number of ventilator days strata (< ≤7 days, >7 days) indicators centered such that the intercept represents the overall mean in the sample; and, finally, “e1, e2, and e3” represent the effect coding for the 4 study sites (Duke Medical Center and Duke Regional Hospital included as a single site). SAS Code for the following outcomes (presented in Table 3): HADS summary score, HADS depression subscale score, HADS anxiety subscale score, IES-R, Global physical health, Global mental health, EQ-5D quality of life visual analog scale, self-efficacy, and Brief COPE. proc mixed data = outstack; class PERSONID INTERVIEW collsiteID ; model &outcome = INT2 INT3 CST*INT2 CST*INT3 e1 e2 e3 hads_strata_center vent_strata_center /ddfm=kr solution residual cl; repeated INTERVIEW/subject = PERSONID type = un rcorr; ods select SolutionF estimates; estimate 'Common Intercept' intercept 1 /cl; estimate 'Education at 3MO' intercept 1 INT2 1 /cl; estimate 'Education at 6MO' intercept 1 INT3 1 /cl; estimate 'CST at 3MO' intercept 1 INT2 1 CS*INT2 1 /cl; estimate 'CST at 6MO' intercept 1 INT3 1 CS*INT3 1 0/cl; run; SAS Code for the following outcomes (presented in Figure 3, eFigure 5, and eTables 6, 7, 11, 12, 13, 14, 15, 16): HADS summary score, HADS depression subscale score, HADS anxiety subscale score, IES-R, Global physical health, Global mental health, EQ-5D quality of life visual analog scale, self-efficacy, and Brief COPE.
proc mixed data = outstack; class PERSONID INTERVIEW ; model &outcome = INT2 INT3 CS*INT2 CS*INT3 hads_strata hads_strata*INT2 hads_strata*INT3 hads_strata*CS*INT2 hads_strata*CS*INT3 /ddfm=kr solution cl; repeated INTERVIEW/subject = PERSONID type = un rcorr; estimate 'Education Intercept:low HADS' intercept 1 hads_strata 0 /cl;
estimate 'Education at 3MO:low HADS' intercept 1 hads_strata 0 INT2 1 hads_strata*INT2 0; estimate 'Education at 6MO:low HADS' intercept 1 hads_strata 0 INT3 1 hads_strata*INT3 0;
estimate 'CS Intercept:low HADS' intercept 1 hads_strata 0; estimate 'CS at 3MO:low HADS' intercept 1 hads_strata 0 INT2 1 hads_strata*INT2 0 CS*INT2 1 hads_strata*CS*INT2 0; estimate 'CS at 6MO:low HADS' intercept 1 hads_strata 0 INT3 1 hads_strata*INT3 0 CS*INT3 1 hads_strata*CS*INT3 0;
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estimate 'CS vs ED at 3MO:low HADS' CS*INT2 1 hads_strata*CS*INT2 0; estimate 'CS vs ED at 6MO:low HADS' CS*INT3 1 hads_strata*CS*INT3 0; estimate 'Education Intercept:high HADS' intercept 1 hads_strata 1 ; estimate 'Education at 3MO:high HADS' intercept 1 hads_strata 1 INT2 1 hads_strata*INT2 1; estimate 'Education at 6MO:high HADS' intercept 1 hads_strata 1 INT3 1 hads_strata*INT3 1 ; estimate 'CS Intercept:high HADS' intercept 1 hads_strata 1; estimate 'CS at 3MO:high HADS' intercept 1 hads_strata 1 INT2 1 hads_strata*INT2 1 CS*INT2 1 hads_strata*CS*INT2 1; estimate 'CS at 6MO:high HADS' intercept 1 hads_strata 1 INT3 1 hads_strata*INT3 1 CS*INT3 1 hads_strata*CS*INT3 1; estimate 'CS vs ED at 3MO:high HADS' CS*INT2 1 hads_strata*CS*INT2 1; estimate 'CS vs ED at 6MO:high HADS' CS*INT3 1 hads_strata*CS*INT3 1;
Multiple Imputation Sensitivity Analysis Methods All baseline patient demographic and clinical characteristics presented in Tables 1 and 2 were examined for potential inclusion into the imputation model. These variables were examined descriptively and via chi-square and t-tests by dropout yes/no and intervention complier yes/no. Variables with p <0.20 were included in the imputation model, and these included: randomization group, site, marital status, medical ICU, education, discharged home, caregiver enrolled, length of ICU stay, HADS summary, length of mechanical ventilation, and financial distress. Additionally, all baseline variables for all outcomes were included in the imputation model. Ten multiple imputations for the missing 3 and 6 month outcomes were generated via the MCMC option in PROC MI. Model convergence was assessed via EM iterations to convergence as well as ACF and time series plots of the mean week 56 weight. Imputations were drawn every 100 iterations. The ten imputed datasets were analyzed with a general linear model including a common intercept, stratification variables (baseline HADS summary score stratum [centered], duration of mechanical ventilation stratum [centered], and site [centered]), indicator variables for months 3 and 6, and indicators for the CST intervention interacted with each of the follow-up time point indicator variables. The ten sets of model estimates and standard errors were combined using PROC MIANALZE. Multiple imputation results are shown in eTables 2, 11, 13, and 16. In the following code for the imputation model, the dataset – outdata – has only one record per patient; the outcomes measured at multiple time points are separate variables and are included via macro variables in the imputation model for each outcome. For example, HADS_total_int1 is the HADS summary at baseline, and in the imputation model for the HADS summary, & var2 and & var3 represent the HADS summary at 3 month and 6 month interviews, respectively.
Code proc mi data=misspatt out=outdata nimpute=10 seed=&seed; mcmc chain=single initial=EM niter=100; var groupID collsiteID married icutype_med edu_3level discharge_home careyes icustay_total ventdays_total paybills IES_total_int1 globalMH_total_int1 globalPH_total_int1 qol_int1 HADS_total_int1 cope_total_int1 selfeff_total_int1
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&var2 &var3 ; run; *round outcome variables to minimum and maximum of scales; data &outdata2; set &outdata1; if &var2 < &min then &var2= &min; else if &var2 > &max then &var2= &max; if &var3 < &min then &var3= &min; else if &var3 > &max then &var3=&max; run; *stack data to 3 time points – baseline, 3 month, and 6 months; data mi_int1; set &outdata2; keep _imputation_ personID groupID EDUC CS e1 e2 e3 hads_strata vent_strata hads_strata_center vent_strata_center unc collsiteID &var1 interview int2 int3 &y ; &y=&var1; interview=1; int2=0; int3=0; unc=0; if collsiteID=4 then unc=1; run; data mi_int2; set &outdata2; keep _imputation_ personID groupID EDUC CS e1 e2 e3 hads_strata vent_strata hads_strata_center vent_strata_center unc collsiteID &var2 interview int2 int3 &y ; &y=&var2; interview=2; int2=1; int3=0; unc=0; if collsiteID=4 then unc=1; run; data mi_int3; set &outdata2; keep _imputation_ personID groupID EDUC CS e1 e2 e3 hads_strata vent_strata hads_strata_center vent_strata_center unc collsiteID &var3 interview int2 int3 &y; &y=&var3; interview=3; int2=0; int3=1; unc=0; if collsiteID=4 then unc=1; run; data midata_stack; set mi_int1 mi_int2 mi_int3; run;
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proc sort data=midata_stack; by _imputation_ PERSONID interview; run; *analysis model of stacked, imputed dataset (results of this model presented in eTable2) ; proc mixed data = midata_stack; class PERSONID INTERVIEW ; model &y = INT2 INT3 CS*INT2 CS*INT3 e1 e2 e3 hads_strata_center vent_strata_center /ddfm=kr solution covb; repeated INTERVIEW/subject = PERSONID type = un rcorr; by _imputation_; estimate 'commonint' intercept 1; estimate 'ed 3MO' intercept 1 int2 1; estimate 'ed 6MO' intercept 1 int3 1; estimate 'cst 3MO' intercept 1 int2 1 cs*int2 1; estimate 'cst 6MO' intercept 1 int3 1 cs*int3 1; ods output SolutionF=mixparms_eff covB=mixcovb_eff estimates=estimates_eff; run; *extract model estimates and combine across imputations; ods trace on; ods output ParameterEstimates=MIEst_eff; proc mianalyze parms(classvar=full)=mixparms_eff; modeleffects Intercept INT2 INT3 CS*INT2 CS*INT3 e1 e2 e3 hads_strata_center vent_strata_center; run; 6. Approach to address dropout during study We encountered dropout that exceeded expectations during the course of the study that at the time were not clearly understood as due to illness or other factors. We assumed that modifiable factors existed, and focused our attention on a series of adaptations designed to improve retention and intervention adherence as
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documented below. CG=caregiver; CRC=clinical research coordinator; ePRO=electronic patient reported outcomes; VOIP=voice over internet provider.
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7. Study amendments and protocol modifications There were 28 amendments made to the study between February 7, 2013 and May 23, 2016, after the protocol’s initial approval by the Duke Coordinating Center Institutional Review Board. There were 2 protocol amendments made during the conduct of the study: • On October 10, 2013, the duration of ventilation inclusion criterion was decreased from 96 to 48
hours after discussion among study investigators and research stakeholders. This amendment was approved by all site IRBs before participant enrollment began.
• On February 21, 2014, the automated Distress Management Protocol was discontinued. This automated protocol allowed the electronic data system to notify investigators in real time if any participant’s HADS or IES-R scores exceeded pre-specified cutoff values signifying psychological distress that may be severe and require a psychological professional’s attention. The reason for discontinuation was that the protocol had only been used three times, and participants seemed surprised by the check-in calls from the PI to ensure they did not need a referral to a mental health professional.
The remaining 26 amendments were not directly relevant to the study protocol: • N=15: Study personnel changes and updates • N=4: Uploads of annual IRB approval letters from sites • N=4: Related to updated study materials (e.g., videos, websites, postcard templates). • N=3: Related to the conduct of two exploratory sub-studies that followed the completion of primary
study enrollment.
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B. eResults eTable 1: Additional baseline characteristics of patients and their family members
Characteristic
Patients Family members Coping skills
training n=86
Education program
n=89
Coping skills training
n=39
Education program
n=47 ICU admission source, no. (%)
Emergency room 30 (35) 35 (39) - -
Transfer from another hospital 29 (34) 30 (34) - -
Hospital ward 15 (17) 14 (16) - -
Post-operative 12 (14) 10 (11) - -
Health literacy,* mean (SD) 7.4 (3.3) 6.9 (3.4) 5.0 (2.2) 4.9 (2.0)
Perceived social support,* no. (%), always/usually 68 (80) 69 (78) 29 (64) 37 (78)
Optimism,* no. (%), agree/strongly agree 74 (86) 78 (88) 36 (92) 35 (74)
Hope,* no. (%), always/usually 58 (68) 60 (67) 24 (61) 34 (72)
Brief COPE total score,* mean (SD) 31.4 (7.5) 33.3 (5.2) 32.1 (5.8) 32.1 (6.8)
Active coping subscale score, mean (SD) 6.0 (1.8) 6.5 (1.6) 6.4 (1.7) 6.3 (1.7)
Emotional support subscale score, mean (SD) 6.6 (1.8) 6.9 (1.8) 5.8 (2.3) 6.5 (1.8)
Positive reframing subscale score, mean (SD) 6.1 (2.0) 6.4 (1.6) 6.2 (1.7) 6.4 (1.7)
Planning subscale score, mean (SD) 6.0 (2.1) 6.3 (1.7) 6.4 (1.7) 6.0 (1.9)
Acceptance subscale score, mean (SD) 6.9 (1.7) 7.1 (1.2) 7.3 (1.2) 7.0 (1.6)
* Questionnaires and citations on eMethods page 10 above.
51
eTable 2: Clinical characteristics and outcomes of patients
Characteristic
Coping skills training
n=86
Education program
n=89 Hospital length of stay, mean (SD) 24.5 (14.7) 24.6 (20.1)
Intensive care unit length of stay, mean (SD) 10.2 (6.6) 10.5 (9.4)
Mechanical ventilator days, mean (SD) 6.6 (4.2) 6.2 (4.2)
Notable events during hospitalization, no. (%)
Major surgery 36 (42) 41 (46)
Acute myocardial infarction 6 (7) 1 (1)
Cardiac arrest 4 (5) 5 (6)
Hospital discharge disposition, no. (%)
Home, independent 35 (41) 40 (45)
Home with home health care services 25 (29) 23 (26)
Inpatient rehabilitation facility 12 (14) 15 (17)
Skilled nursing facility 12 (14) 6 (7)
Long term acute care hospital 0 4 (4)
Transfer to other acute care hospital 1 (1) 0
Other 1 (1) 1 (1)
Hospital readmission during follow up, no. (%)
Patients with 1 readmission 18 (26) 12 (16)
Patients with >1 readmission 6 (7) 7 (9)
Missing 17 (20) 14 (16)
Disposition at 6-month follow up, no. (%)
Alive, home 62 (72) 68 (76)
Alive, facility 0 1 (1)
Dead 6 (7) 6 (7)
Unknown 18 (21) 14 (16)
Became too ill to continue 9 (10) 5 (6)
Lost to contact 9 (10) 9 (10)
52
eTable 3: Model estimated outcomes (multiple imputation), patients a
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate (SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p Primary outcome HADS summary b 16.1 (0.6) 15.2 (0.9) 16.6 (0.9) 1.4 (-0.6,3.5) 0.16 15.6 (1.0) 15.4 (1.0) -0.2 (-2.3,2.0) 0.89 HADS anxiety b 8.2 (0.4) 8.0 (0.6) 8.6 (0.6) 0.6 (-0.7,1.8) 0.37 8.2 (0.6) 8.3 (0.7) 0.1 (-1.4,1.5) 0.93 HADS depression b 7.7 (0.4) 7.0 (0.6) 7.7 (0.5) 0.7 (-0.5,1.9) 0.26 7.4 (0.6) 7.0 (0.6) -0.4 (-1.7,0.9) 0.56 Secondary outcomes IES-R b 31.9 (2.1) 27.9 (2.5) 31.0 (2.6) 3.1 (-1.8,8.0) 0.21 26.7 (2.8) 30.2 (2.8) 3.5 (-2.9,9.9) 0.28 Global physical health c 10.9 (0.3) 11.9 (0.5) 11.5 (0.4) -0.4(-1.4,0.5) 0.37 11.4 (0.4) 11.8 (0.4) 0.4 (-0.5,1.4) 0.40 Global mental health c 12.1 (0.4) 12.0 (0.5) 11.5 (0.5) -0.5 (-1.5,0.5) 0.32 11.7 (0.5) 12.0 (0.5) 0.3 (-0.7,1.3) 0.57 EQ-5D quality of life c 64.0 (2.7) 65.7 (3.5) 62.8 (3.2) -2.9 (-8.9,3.1) 0.35 60.7 (3.2) 60.8 (3.1) 0.1 (-5.9,6.0) 0.99 Self-efficacy c 5.7 (0.2) 5.2 (0.3) 5.5 (0.3) 0.3 (-0.3, 0.9) 0.31 5.6 (0.3) 6.0 (0.3) 0.4 (-0.2, 1.0) 0.21 Brief COPE c 32.4 (0.8) 30.8 (1.0) 30.0 (1.0) -0.8 (-2.9,1.4) 0.48 29.9 (1.1) 29.6 (1.1) -0.3 (-2.6, 2.1) 0.83
a Missing outcome variables were multiply imputed (total of ten imputations). General linear models were used to compare mean differences in outcomes between CST (coping skills training) and education program (EP) groups; model estimates and standard errors combined across the ten imputations. b For these outcomes, negative values in mean score difference indicate more improved scores for the CST group. For example, at 6-months post-randomization, the estimated mean total HADS score was 15.4 in the CST group as compared to 15.6 in the EP group. The differential change from baseline was -0.2 (95% CI: -2.3, 2.0) (i.e., 0.2 points of improvement) in the CST group compared to the EP group, but this difference was not statistically significant (p=0.89). c For these outcomes, positive values in mean score difference indicate more improved scores for the CST group. For example, at 6-months post-randomization, the estimated mean global physical health score was 11.8 in the CST group as compared to 11.4 in the EP group. The
53
differential change from baseline was 0.4 (95% CI: -0.5, 1.4) (i.e., 0.4 points of improvement) in the CST group compared to EP group, but this difference was not statistically significant (p=0.40).
54
eTable 4: Weeks not at home analyses At the 3- and 6-month follow up interviews patients were asked to identify weeks not at home since the previous interview. Responses across interviews were combined to represent the entire 24-week follow up. This analysis included 144 of the 175 randomized patients because patients with only baseline data were excluded (n=14 in EP group and n=17 in CST group). For patients who completed only the 3-month follow up, the minimum possible value is 0 weeks not at home and the maximum possible value is 12 weeks not at home; whereas, for patients who completed the 6-month follow up, the maximum possible value is 24 weeks not at home. Lower mean values indicate a positive result of more time at home. Four different regression modeling options were explored for this outcome variable: standard negative binomial, zero-inflated negative binomial, marginalized zero-inflated negative binomial, and two-part negative binomial (also known as a hurdle regression model). All models included the main effect of group, the baseline HADS summary score stratum [centered], and duration of mechanical ventilation stratum [centered]. The two-part negative binomial model had the best fit (i.e., lowest AIC value). This model divides the outcome into two parts (0 vs > 0) and (> 0) = and fits a mixture model with a logistic for the first part and a truncated negative binomial for the second part, where the negative binomial part includes an offset term for the number of weeks followed (12 or 24). Results EP patients (n=75) had a mean of 1.6 (SD=3.5; median 0) weeks not at home, and CST patients (n=69) had a mean of 1.3 (SD=3.0; median 0) weeks not at home. However, 27% (n=20) of EP patients had at least one week not at home, and 38% (n=26) of CST patients had at least one week not at home. Among the n=20 EP patients with at least one week not at home, the mean number of weeks not at home was 6 (SD=4.5; median 5), and among the n=26 CST patients with at least one week not at home, the mean number of weeks not at home was 3.6 (SD=4.0; median=1.5). See Figure below for distribution of outcomes.
Negative binomial model part 1: Patients in the Coping Skills arm are more likely to have > 0 weeks not at home, but this difference is not statistically significant (OR=1.74; p=0.13).
Effect Estimate Standard
Error 95% Confidence Limits p
Lower Upper
Intercept -1.16 0.40 -1.94 -0.38 0.004
CST 0.56 0.37 -0.16 1.27 0.13
hads_strata_center 0.31 0.39 -0.45 1.1 0.42
vent_strata_center -0.4785 0.4429 -1.3466 0.3895 0.28
55
Negative binomial model part 2: Among those with at least one week not at home, patients randomized to CST had an estimated mean number of weeks not at home that was 0.26 (exp(-1.33)) times lower than patients randomized to EP (p=0.07).
Parameter Estimates for Truncated Negative Binomial Model
Effect Estimate Standard Error
z Value Pr > |z| 95% Confidence Limits
Lower Upper
Intercept -2.3 1.60 -1.43 0.15 -5.41 0.85
CST -1.33 0.72 -1.84 0.07 -2.74 0.09
hads_strata_center -1.41 0.73 -1.92 0.05 -2.84 0.03
vent_strata_center 0.54 0.70 0.77 0.44 -0.82 1.90
Scale Parameter 8.16 16.12
56
eTable 5: Model estimated primary and secondary outcomes, family members. General linear models were used to compare mean differences in family member outcomes between CST and EP groups. a For these outcomes, negative values in mean score difference indicate more improved scores for the CST group. For example, at 3-months post-randomization, the estimated mean total IES score was 26.5 in the CST group as compared to 27.1 in the EP group. The differential change from baseline was -0.5 (95% CI: -8.0, 7.0) (i.e., 0.5 points of improvement) more in the CST group than the EP group, but this difference was not statistically significant (p=0.89). b For these outcomes, positive values in mean score difference indicate more improved scores for the CST group. For example, at 3-months post-randomization, the estimated mean self-efficacy score was 7.7 in the CST group as compared to 7.4 in the EP group. The differential change from baseline was 0.3 (95% CI: -0.5, 1.0) (i.e., 0.3 points of improvement) more in the CST group than the EP group, but this difference was not statistically significant (p=0.48).
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p Primary outcome HADS summary a 12.9 (1.0) 10.8 (1.1) 12.2 (1.1) 1.4 (-0.9,3.7) 0.23 11.0 (1.0) 12.1 (1.1) 1.1 (-0.9,3.20 0.27 HADS anxiety a 7.7 (0.6) 6.4 (0.6) 7.2 (0.7) 0.8 (-0.6,2.2) 0.27 6.1 (0.6) 6.9 (0.6) 0.8 (-0.6,2.2) 0.26 HADS depression a 5.2 (0.5) 4.4 (0.6) 5.1 (0.6) 0.7 (-0.7,2.1) 0.31 4.9 (0.6) 5.3 (0.6) 0.5 (-1.0,1.9) 0.52 Secondary outcomes IES-R a 28.6 (2.2) 27.1 (3.1) 26.5 (3.3) -0.5 (-8.0,7.0) 0.89 19.8 (3.1) 23.7 (3.3) 3.8 (-4.4,12.0) 0.36 Global physical health b 14.8 (0.3) 14.6 (0.4) 14.5 (0.4) -0.1 (-1.0,0.8) 0.79 14.7 (0.4) 14.5 (0.4) -0.2 (-1.0,0.7) 0.71 Global mental health b 13.7 (0.4) 13.8 (0.5) 13.8 (0.6) -0.03 (-1.2,1.1) 0.96 13.9 (0.5) 13.3 (0.5) -0.7 (-1.8,0.4) 0.20 Brief COPE b 32.8 (0.8) 28.8 (1.2) 29.9 (1.3) 1.1 (-2.0,4.2) 0.47 28.5 (1.3) 27.5 (1.5) -1.0 (-4.8,2.8) 0.61 Self-efficacy b 7.1 (0.3) 7.4 (0.3) 7.7 (0.3) 0.3 (-0.5,1.0) 0.48 7.3 (0.4) 7.0 (0.4) -0.3 (-1.2,0.6) 0.47
57
eTable 6: Self-rated stressors. We allowed self-report of stressors from participants at each interview. These data were derived from a single prompt question included in each of three interviews: What is the most stressful thing in your life right now? Below, the primary stressors in patients’ own words is demonstrated as rated on a scale of 0 (no distress) to 100 (extreme distress). Primary stressors reported at each interview are analyzed below.
Timing CST, n=86
EP, n=89 Missing,* n p
Interview 1, mean (SD) 64.9 (30.1) 63.6 (27.9) 16 0.51
Interview 2, mean (SD) 60.1 (28.1) 62.2 (26.1) 65 0.59
Interview 3, mean (SD) 62.2 (29.4) 54.5 (27.3) 66 0.58
*Includes number who responded with 'none.'
58
eTable 7: Outcomes analyzed by baseline HADS summary score stratification variable: HADS >14. General linear models were used to compare mean differences in outcomes between CST and EP groups. A total of 60 (34%) patients had elevated distress at baseline (i.e., HADS summary score >14). Intervention group effect by HADS summary score stratification variable (0= ≤14 and 1= >14). Data are displayed as mean (standard error) and mean difference (95% confidence interval). a Negative values in mean score difference indicate more improved scores for the CST group. b Positive values in mean score difference indicate more improved scores for the CST group. P<0.05 are in bold. Also see Figure 3 in manuscript and eTable 12.
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p
Primary outcome
HADS total a 21.70 (0.58)
18.08 (1.33)
18.10 (1.33)
0.02 (-3.71, 3.75)
0.99 20.17 (1.45)
15.54 (1.49)
-4.63 (-8.61, -0.64)
0.02
HADS anxiety a 11.22 (0.41)
9.68 (0.80)
9.25 (0.86)
-0.43 (-2.67, 1.81)
0.70 10.58 (0.88)
8.78 (0.91) -1.80 (-4.21, 0.61)
0.14
HADS depression a 10.48 (0.39)
8.39 (0.78)
8.59 (0.85)
-0.20 (-2.05, 2.44)
0.86 9.64 (0.83)
6.60 (0.85) -3.03 (-5.36, -0.71)
0.01
Secondary outcomes
IES-R a 39.77 (2.27)
33.56 (3.35)
36.05 (3.63)
2.50 (-6.60, 11.60)
0.54 32.91 (4.19)
32.91 (4.26)
0 (-11.49, 11.49)
1.00
Global physical health b 10.1 (0.3)
10.6 (0.6)
10.9 (0.7)
0.3 (-1.5, 2.0)
0.78 10.0 (0.6)
11.4 (0.6)
1.3 (-0.3, 3.0)
0.11
Global mental health b 10.33 (0.39)
10.61 (0.69)
11.05 (0.73)
0.45 (-1.45, 2.34)
0.64 9.72 (0.67)
11.98 (0.68)
2.26 (0.47, 4.06)
0.01
EQ-5D quality of life b 56.33 (2.98)
62.93 (4.46)
60.28 (4.80)
-2.65 (-15.04, 9.74)
0.67 48.31 (4.19)
59.51 (4.30)
11.20 (0.02, 22.37)
0.0496
Brief COPE b 32.42 (0.86)
28.51 (1.44)
30.63 (1.54)
2.12 (-1.97, 6.21)
0.31 29.94 (1.67)
30.96 (1.69)
1.02 (-3.56, 5.60)
0.66
59
eTable 8: Outcomes analyzed by days of mechanical ventilation stratification variable: ventilation >7 days. General linear models were used to compare mean differences in outcomes between CST and EP groups. A total of 47 (27%) patients received ventilation >7 days. Intervention group effect by days of ventilation stratification variable (0= ≤7 and 1= >7). Data are displayed as mean (standard error) and mean difference (95% confidence interval). a For these outcomes, negative values in mean score difference indicate more improved scores for the CST group. b For these outcomes, positive values in mean score difference indicate more improved scores for the CST group. P<0.05 are in bold. Also see eFigure 5.
Self-efficacy b 5.36 (0.28)
4.36 (0.43)
5.08 (0.42)
0.72 (-0.48, 1.91)
0.24 4.49 (0.41)
5.85 (0.42) 1.35 (0.23, 2.47)
0.02
60
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p Primary outcome
HADS total a 10.33 (1.17) 8.47 (1.70)
12.53 (1.53)
4.07 (0.05, 8.08)
0.047 8.93 (1.83)
10.82 (1.71)
1.89 (-2.61, 6.40)
0.41
HADS anxiety a 5.78 (0.70)
4.54 (1.00)
5.83 (0.90)
1.29 (-1.11, 3.69)
0.29 4.95 (1.09)
5.56 (1.01)
0.61 (-2.07, 3.28)
0.66
HADS depression a 4.56 (0.63)
3.96 (0.98)
6.60 (0.87)
2.64 (0.21, 5.08)
0.03 3.97 (1.04)
5.13 (0.97) 1.16 (-1.51, 3.84)
0.39
Secondary outcomes
IES-R a 21.60 (2.96) 21.35 (4.20)
24.87 (3.77)
3.52 (-6.36, 13.41)
0.48 21.52 (5.04)
25.80 (4.71)
4.28 (-8.59, 17.14)
0.51
Global physical healthb 12.29 (0.43) 13.13 (0.78)
12.22 (0.70)
-0.91 (-2.86, 1.03)
0.36 12.57 (0.76)
12.96 (0.71)
0.39 (-1.53, 2.31)
0.69
Global mental health b 14.09 (0.54) 14.50 (0.84)
12.33 (0.76)
-2.18 (-4.21, -0.15)
0.04 14.29 (0.83)
13.29 (0.78)
-1.00 (-3.05, 1.06)
0.34
EQ-5D quality of life b 73.04 (3.72) 77.89 (5.13)
62.07 (4.64)
-15.82 (-28.53, -3.11)
0.02 68.24 (5.24)
70.64 (5.20)
2.40 (-10.89, 15.69)
0.72
Brief COPE b 32.73 (0.98) 30.01 (1.72)
32.73 (0.98)
1.27 (-3.22, 5.76)
0.58 28.46 (1.96)
29.90 (1.79)
1.44 (-3.66, 6.54)
0.58
Self-efficacy b 6.73 (0.35)
6.72 (0.56)
6.36 (0.51)
-0.36 (-1.73, 1.02)
0.61 7.14 (0.53)
6.78 (0.50) -0.36 (-1.71, 0.99)
0.60
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eTable 9: Communication contact frequency and methods. This table quantifies the types of participant contact attempts to either complete sessions or study interviews.
Group status Patients, n Total
contacts, n Mean (SD), per patient
Range (min-max)
Both groups overall 175 6,620 27.6 (12.1) 8-66 Phone 5,222 16.1 (9.2) 2-45
Email 994 5.8 (4.3) 1-21 Mail 404 2.3 (1.3) 1-7
Education 89 2,008 22.6 (10.1) 8-52
Coping Skills 86 2,818 32.8 (11.9) 13-66
No sessions completed 31 1,140 36.8 (12.1) 13-62
1 to 5 sessions completed 24 835 34.8 (12.0) 19-66
All 6 sessions completed 31 843 27.2 (9.8) 14-59
62
eTable 10: Factors associated with adherence and dropout across both treatment groups (p <0.20). Of 175 patients randomized, 63 patients were non-adherent with their treatment program and 44 dropped out by the time of the 6-month follow up interview. Variables examined using chi-square tests included: age, pre-admission Charlson comorbidity score, APACHE II score, length of hospital stay, length of ICU stay, ventilator days, baseline HADS summary score, baseline IES-R score, intervention group, gender, family member enrolled, study site, discharged disposition, employment status, type of stressor identified at baseline, financial distress at baseline, education status, marital status, treated for psychological distress before admission (i.e., anxiety, depression, or PTSD), race, treatment ICU, and insurance type. See also Figure 2 and eFigures 2 and 3.
Characteristic Adherence status Dropout status
Adherent (n=112)
Non-adherent (n=63) p
Retained (n=131) Dropped out (n=44) p
Ventilator days, mean (95% CI) 7.0 (6.1, 7.8) 5.4 (4.6, 6.3) 0.02 - - >0.20
Financial distress, no. (%) 0.03 >0.20 Short on money and need more to pay bills 17 (49%) 18 (51%) - - Barely have enough to pay bills 16 (55%) 13 (45%) - - Have enough for just a few extra things 45 (66%) 23 (34%) - - Completely comfortable 34 (79%) 9 (21%) - - Education status, no. (%) 0.04 0.16 ≤High school graduate 39 (53%) 34 (47%) 50 (68%) 23 (32%) Trade school or some college 33 (69%) 15 (31%) 36 (75%) 12 (25%) College or more 40 (74%) 14 (26%) 45 (83%) 9 (16%) Marital status, no. (%) 0.11 0.11 Single 50 (58%) 36 (42%) 69 (80%) 17 (20%) Married 62 (70%) 27 (30%) 62 (70%) 27 (30%)
ICU length of stay, mean (95% CI) 11.0 (9.4, 12.6) 9.3 (7.4, 11.1) 0.18 - - >0.20
HADS summary score, baseline, mean (95% CI) - - >0.20 11.8 (10.5, 13.1) 15.2 (12.7, 17.7) 0.01
Family member enrolled, no. (%) >0.20 0.03
63
No - - 61 (68%) 29 (32%) Yes - - 70 (82%) 15 (18%) Discharge disposition, no. (%) >0.20 0.05 Home - - 87 (71%) 36 (29%) Facility - - 44 (85%) 8 (15%) Site, no. (%) >0.20 0.08 2 - - 21 (58%) 15 (42%) 3 - - 26 (76%) 8 (24%) 4 - - 29 (78%) 8 (22%) 1 - - 55 (81%) 13 (19%) ICU type, no. (%) >0.20 0.10 Medical - - 77 (71%) 32 (29%) Surgical - - 54 (82%) 12 (18%)
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eTable 11: Client satisfaction questionnaire (CSQ-8). The CSQ-8 was used to assess participants' satisfaction with the treatment programs at the final (6-month) interview. Scores are not clinically significantly different by treatment group. These scores represent 'good' to 'very good' satisfaction ratings, as the CSQ-8 is scored from 0 (worst) to 32 (best).
Group Patients, n Missing, n Mean SD
Education 89 29 26.2 4.1
Coping Skills 86 33 27.0 4.1
No sessions completed 31 15 26.3 3.9
1 to 5 sessions completed 24 12 24.8 5.5
All 6 sessions completed 31 6 28.6 2.8
65
eTable 12: Outcomes analyzed by baseline HADS summary score stratification variable: HADS >14. Missing outcome variables were multiply imputed (total of ten imputations). General linear models were used to compare mean differences in outcomes between CST and EP groups; model estimates and standard errors combined across the ten imputations. A total of 60 (34%) patients had elevated baseline distress (i.e., HADS summary score >14). Intervention group effect by HADS summary score stratification variable (0= ≤14 and 1= >14). Data are displayed as mean (standard error) and mean difference (95% confidence interval). a Negative values in mean score difference indicate more improved scores for the CST group. b Positive values in mean score difference indicate more improved scores for the CST group. P<0.05 are shown in bold. See also eTable 7.
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p
Primary outcome
HADS total a 21.70 (0.58)
17.85 (1.33)
18.64 (1.47)
0.78 (-2.74, 4.31)
0.66 19.15 (1.63)
16.26 (1.45)
-2.89 (-6.81, 1.03)
0.15
HADS anxiety a 11.22 (0.41)
9.19 (0.76)
9.71 (0.95)
0.52 (-1.71, 2.75)
0.65 9.84 (0.82)
9.24 (0.99) -0.59 (-2.95, 1.77)
0.62
HADS depression a 10.48 (0.39)
8.58 (0.78)
8.58 (0.80)
-0.001 (-1.96, 1.96)
0.99 9.63 (0.92)
6.91 (0.88) -2.73 (-5.22, -0.24)
0.03
Secondary outcomes
IES-R a 39.77 (2.27)
32.82 (3.30)
35.59 (3.63)
2.77 (-6.23, 11.77)
0.54 33.27 (3.75)
33.67 (3.86)
0.40 (-9.71, 10.50)
0.94
Global physical health b 10.1 0.34)
10.89 (0.74)
10.77 (0.64)
-0.12 (-1.94, 1.70)
0.90 10.12 (0.60)
11.20 (0.59)
1.08 (-0.53, 2.68)
0.19
Global mental health b 10.33 (0.39)
10.44 (0.64)
11.04 (0.63)
0.60 (-1.10, 2.30)
0.49 9.93 (0.73)
11.76 (0.65)
1.83 (0.04, 3.63)
0.045
EQ-5D quality of life b 56.33 (2.98)
62.71 (4.72)
60.13 (3.98)
-2.58 (-13.42, 8.25)
0.64 50.20 (4.62)
57.88 (3.97)
7.68 (-3.70, 19.06)
0.18
Brief COPE b 32.42 (0.86)
28.24 (1.40)
30.07 (1.54)
1.83 (-2.13, 5.79)
0.36 29.47 (1.64)
30.52 (1.50)
1.05 (-2.83, 4.94)
0.59
66
eTable 13: Outcomes analyzed by baseline HADS summary score stratification variable: HADS ≤14. General linear models were used to compare mean differences in outcomes between CST and EP groups. A total of 115 (66%) patients had low baseline distress (i.e., HADS summary score ≤14). Intervention group effect by HADS summary score stratification variable (0= ≤14 and 1= >14). a Negative values in mean score difference indicate more improved scores for the CST group. b Positive values in mean score difference indicate more improved scores for the CST group. Data are displayed as mean (standard error) and mean difference (95% confidence interval). See also eTable 14.
Self-efficacy b 5.36 (0.28)
4.26 (0.43)
4.86 (0.42)
0.59 (-0.48, 1.66)
0.28 4.45 (0.43)
5.64 (0.37) 1.19 (0.16, 2.22)
0.02
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate (SE)
CST estimate (SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate (SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p
Primary outcome
HADS total a 7.95 (0.42) 8.62 (0.89)
10.27 (0.91)
1.65 (-0.76, 4.05)
0.18 8.53 (0.95)
10.07 (1.00)
1.54 (-1.08, 4.17)
0.25
HADS anxiety a 3.94 (0.30) 4.74 (0.54)
5.27 (0.55)
0.53 (-0.92, 1.97)
0.48 4.59 (0.58)
5.07 (0.61)
0.48 (-1.11, 206)
0.56
HADS depression a 4.01 (0.28) 3.81 (0.52)
4.89 (0.53)
1.08 (-0.37, 2.53)
0.14 3.86 (0.54)
4.93 (0.58)
1.06 (-0.47, 2.60)
0.17
Secondary outcomes
IES-R a 19.53 (1.64)
17.05 (2.27)
20.14 (2.31)
3.09 (-2.78, 8.95)
0.30 14.41 (2.72)
19.55 (2.90)
5.15 (-2.46, 12.75)
0.18
Global physical health b 12.63 (0.24)
13.76 (0.42)
12.63 (0.24)
-0.53 (-1.67, 0.61)
0.36 13.53 (0.40)
13.58 (0.42)
0.05 (-1.06, 1.15)
0.93
Global mental health b 14.80 (0.28)
14.63 (0.46)
13.43 (0.47)
-1.20 (-2.07, 0.29)
0.14 14.59 (0.44)
13.70 (0.46)
-0.89 (-2.07, 0.29)
0.14
EQ-5D quality of life b 76.71 (2.15)
76.17 (2.91)
73.13 (2.97)
-3.04 (-10.80, 4.71)
0.44 75.61 (2.75)
71.11 (2.96)
-4.50 (-11.94, 2.95)
0.23
Brief COPE b 32.24 (0.62)
32.13 (0.95)
30.02 (0.97)
-2.11 (-4.74, 0.52)
0.11 29.98 (1.07)
28.84 (1.13)
-1.14 (-4.11, 1.83)
0.45
67
eTable 14: Outcomes analyzed by baseline HADS summary score stratification variable: HADS ≤14. Missing outcome variables were multiply imputed (total of ten imputations). General linear models were used to compare mean differences in outcomes between CST and EP groups; model estimates and standard errors combined across the ten imputations. 115 (66%) patients had low baseline distress (i.e., HADS summary score ≤14). Intervention group effect by HADS summary score stratification variable (0= ≤14 and 1= >14). a Negative values indicate improved scores for the CST group. b Positive values indicate improved scores for the CST group. Data are displayed as mean (standard error) and mean difference (95% CI). See also eTable 13.
Self-efficacy b 7.23 (0.20) 7.20 (0.28)
7.23 (0.20)
0.16 (-0.60, 0.92)
0.68 7.62 (0.27)
7.58 (0.28)
-0.04 (-0.78, 0.69)
0.91
68
eTable 15: Outcomes analyzed by days of mechanical ventilation stratification variable: ventilation >7 days. Missing outcome variables were multiply imputed (total of ten imputations). General linear models were used to compare mean differences in outcomes between CST and EP groups; model estimates and standard errors are combined across the ten imputations. 47 (27%) patients received ventilation >7 days. Intervention group effect by days of ventilation stratification variable (0= ≤7 and 1= >7). a Negative values in mean score difference indicate improved scores for the CST group. b Positive values in mean score difference indicate improved scores for the CST group. Data are displayed as mean (standard error) and mean difference (95% CI). P<0.05 in bold. See eTable 8.
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p
Primary outcome
HADS total a 7.95 (0.42)
8.66 (0.86)
10.38 (0.90)
1.72 (-0.59, 4.02)
0.14 8.60 (0.93)
9.80 (0.95) 1.20 (-1.26, 3.66)
0.34
HADS anxiety a 3.94 (0.30)
4.69 (0.53)
5.27 (0.52)
0.57 (-0.82, 1.97)
0.42 4.62 (0.60)
5.00 (0.64) 0.38 (-1.32, 2.09)
0.66
HADS depression a 4.01 (0.28)
4.01 (0.53)
5.00 (0.52)
0.98 (-0.41, 2.38)
0.17 4.13 (0.56)
4.91 (0.59) 0.78 (-0.75, 2.31)
0.31
Secondary outcomes
IES-R a 19.53 (1.64)
17.16 (2.23)
20.40 (2.27)
3.24 (-2.21, 8.69)
0.24 15.03 (2.76)
20.10 (2.79)
5.07 (-2.77,12.90)
0.20
Global physical health b 12.63 (0.24)
13.84 (0.42)
13.24 (0.45)
-0.60 (-1.71, 0.51)
0.29 13.41 (0.41)
13.47 (0.46)
0.06 (-1.08, 1.20)
0.92
Global mental health b 14.80 (0.28)
14.52 (0.43)
13.46 (0.47)
-1.06 (-2.21, 0.10)
0.07 14.41 (0.44)
13.92 (0.47)
-0.49 (-1.70, 0.71)
0.42
EQ-5D quality of life b 76.71 (2.15)
75.84 (2.89)
72.98 (3.06)
-2.87 (-10.13, 4.40)
0.44 74.89 (2.69)
71.02 (2.97)
-3.87 (-11.15, 3.42)
0.30
Brief COPE b 32.21 (0.62)
32.05 (0.93)
29.85 (0.92)
-2.21 (-4.69, 0.28)
0.08 29.97 (1.06)
28.99 (1.19)
-0.98 (-3.89, 1.93)
0.51
Self-efficacy b 7.23 (0.20)
7.01 (0.28)
7.19 (0.29)
0.17 (-0.55, 0.89)
0.64 7.49 (0.26)
7.48 (0.30) -0.01 (-0.75, 0.73)
0.98
69
eTable 16: Outcomes analyzed by days of mechanical ventilation stratification variable: ventilation ≤7 days. General linear models were used to compare mean differences in outcomes between CST and EP groups. A total of 128 (73%) patients received ventilation ≤7 days. Intervention group effect by days of ventilation stratification variable (0= ≤7 and 1= >7). For these outcomes, negative values in mean score difference indicate more improved scores for the CST group. b For these outcomes, positive values in mean score difference indicate more improved scores for the CST group. Data are displayed as mean (standard error) and mean difference (95% confidence interval). See also eTable 17.
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p
Primary outcome
HADS total a 10.34 (1.14)
9.14 (1.54)
13.0 (1.50)
3.85 (0.11, 7.60)
0.04 9.71 (1.61)
11.23 (1.61)
1.52 (-2.44, 5.48)
0.45
HADS anxiety a 5.77 (0.69)
4.91 (0.93)
6.01 (0.89)
1.10 (-1.08, 3.28)
.32 5.34 (1.00)
5.58 (1.00)
0.24 (-2.16, 2.64)
0.84
HADS depression a 4.57 (0.62)
4.37 (0.97)
6.88 (0.87)
2.51 (0.25, 4.78)
0.03 4.76 (1.11)
5.49 (0.93) 0.73 (-2.02, 3.47)
0.60
Secondary outcomes
IES-R a 21.92 (2.90)
20.96 (3.89)
25.75 (3.62)
4.78 (-4.26, 13.82)
0.30 20.78 (4.85)
25.97 (4.56)
5.19 (-7.29, 17.67)
0.41
Global physical health b 12.23 (0.42)
13.39 (0.80)
12.13 (0.73)
-1.26 (-3.28, 0.77)
0.22 12.57 (0.77)
12.69 (0.74)
0.12 (-2.05, 2.29) 0.91
Global mental health b 14.04 (0.53)
14.03 (0.75)
12.26 (0.75)
-1.77 (-3.61, 0.06)
0.06 13.99 (0.77)
13.35 (0.76)
-0.64 (-2.67, 1.38)
0.53
EQ-5D quality of life b 73.38 (3.63)
76.96 (5.41)
63.82 (4.72)
-13.14 (-25.62, -0.65)
0.04 69.94 (4.81)
68.79 (5.04)
-1.15 (-14.03, 11.73)
0.86
Brief COPE b 32.71 (0.96)
30.41 (1.55)
31.04 (1.54)
0.63 (-3.52, 4.77)
0.77 28.93 (1.85)
30.15 (1.69)
1.22 -3.66, 6.10)
0.62
Self-efficacy b 6.69 (0.34) 6.55 (0.48)
6.20 (0.48)
-0.35 (-1.55, 0.86)
0.57 7.04 (0.46)
6.72 (0.49) -0.32 (-1.52, 0.87)
0.59
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p
Primary outcome
HADS total a 13.47 (0.69)
12.86 (0.91)
13.05 (0.98)
0.19 (-2.15, 2.53)
0.87 13.42 (0.98)
12.42 (1.06)
-1.00 (-3.58, 1.58)
0.44
HADS anxiety a 6.66 (0.41)
6.95 (0.53)
6.96 (0.58)
0.01 (-1.38, 1.41)
0.99 7.06 (0.58)
6.66 (0.63) -0.40 (-1.93, 1.13)
0.61
HADS depression a 6.81 (0.37)
5.82 (0.52)
5.96 (0.57)
0.14 (-1.28, 1.56)
0.85 6.27 (0.55)
5.68 (0.60) -0.59 (-2.12, 0.94)
0.44
Secondary outcomes
IES-R a 28.15 (1.74)
23.08 (2.24)
25.61 (2.43)
2.52 (-3.24, 8.29)
0.39 20.17 (2.68)
23.47 (2.91)
3.29 (-4.06, 10.64)
0.38
Global physical health b 11.58 (0.25)
12.61 (0.42)
12.61 (0.45)
-0.01 (-1.15, 1.13)
0.99 12.33 (0.40)
12.83 (0.44)
0.49 (-0.61, 1.59)
0.38
Global mental health b 12.98 (0.32)
12.94 (0.45)
12.72 (0.49)
-0.22 (-1.40, 0.97)
0.72 12.63 (0.45)
12.99 (0.48)
0.36 (-0.82, 1.54)
0.55
EQ-5D quality of life b 68.58 (2.19)
69.81 (2.77)
71.89 (3.00)
2.08 (-5.41, 9.57)
0.58 66.10 (2.84)
65.78 (3.06)
-0.31 (-7.76, 7.13)
0.93
Brief COPE b 32.16 (0.58)
31.29 (0.91)
29.77 (0.99)
-1.52 (-4.12, 1.09)
0.25 30.32 (1.02)
29.36 (1.11)
-0.96 (-3.85, 1.92)
0.51
Self-efficacy b 6.54 (0.21)
6.17 (0.30)
6.74 (0.32)
0.57 (-0.22, 1.36)
0.16 6.50 (0.28)
7.11 (0.30) 0.61 (-0.16, 1.38)
0.12
70
eTable 17: Primary and secondary outcomes analyzed by days of mechanical ventilation stratification variable: ventilation ≤7 days. Missing outcome variables were multiply imputed (total of ten imputations). General linear models were used to compare mean differences in outcomes between CST and EP groups; model estimates and standard errors combined across the ten imputations. A total of 128 (73%) patients received ventilation ≤7 days. Intervention group effect by days of ventilation stratification variable (0= ≤7 and 1= >7). a Negative values in mean score difference indicate more improved scores for the CST group. b Positive values in mean score difference indicate more improved scores for the CST group. Data are displayed as mean (standard error) and mean difference (95% confidence interval). See also eTable 16.
Baseline 3 months post-randomization 6 months post-randomization
Estimate (SE)
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI) p
EP estimate
(SE)
CST estimate
(SE)
Mean difference in change from
baseline between groups (95% CI)
p
Primary outcome
HADS total a 13.5 (0.7)
12.8 (0.9)
13.3 (1.0)
0.5 (-1.7,2.7)
0.66 13.1 (1.1)
12.3 (1.0)
-0.8 (-3.3,1.6)
0.51
HADS anxiety a 6.8 (0.4)
6.7 (0.6)
7.1 (0.6)
0.4 (-1.0,1.8)
0.60 6.8 (0.6)
6.8 (0.7)
0.0 (-1.6,1.6)
0.99
HADS depression a 6.8 (0.4)
6.0 (0.5)
6.0 (0.5)
-0.1 (-1.4,1.2)
0.91 6.5 (0.6)
5.6 (0.6)
-0.9 (-2.4,0.7)
0.29
Secondary outcomes
IES-R a 28.1 (1.8)
23.1 (2.2)
25.5 (2.6)
2.4 (-3.4,8.3)
0.41 21.4 (2.6)
24.3 (2.9)
2.8 (-4.4,10.1)
0.44
Global physical healthb 11.6 (0.3)
12.6 (0.5)
12.5 (0.4)
-0.1 (-1.2,1.0)
0.81 12.2 (0.4)
12.7 (0.4)
0.5 (-0.6,1.6)
0.36
Global mental health b 13.0 (0.3)
12.8 (0.4)
12.8 (0.5)
-0.02 (-1.2,1.2)
0.97 12.5 (0.5)
13.1 (0.5)
0.6 (-0.5,1.8)
0.28
EQ-5D quality of life b 68.4 (2.2)
69.3 (3.2)
70.5 (2.7)
1.1 (-6.5,8.7)
0.77 65.1 (2.9)
65.6 (3.0)
0.5 (-6.1,7.3)
0.88
Brief COPE b 32.1 (0.6)
30.8 (0.9)
29.5 (1.0)
-1.3 (-4.0,1.3)
0.32 30.1 (1.0)
29.3 (1.1)
-0.8 (-3.4,1.8)
0.54
71
Self-efficacy b 6.6 (0.2)
5.9 (0.3)
6.5 (0.3)
0.6 (-0.2,1.3)
0.15 6.2 (0.3)
6.9 (0.3)
0.7 (-0.1,1.5)
0.10
72
eFigure 1: Timeline for clinical milestones and completion of study procedures for patients by treatment group.
73
eFigure 2: Study completion status by study milestone for patients by group. Height of bars is proportional to patient number. Reasons for dropout are shown at each study milestone.
74
eFigure 3: Study completion status by study milestone for family members by treatment group. Height of bars is proportional to number of family members. Reasons for dropout are shown at each study milestone.
75
eFigure 4: Self-reported stressors and change over time among 175 patients. The width of each box is proportional to the number of patients responding with a self-reported primary stressor that could be categorized in one of the 6 stressor domains shown below (number also shown in each box). Domains were derived from separate qualitative analyses from 1,464 separate instances of stressors across all 3 interviews (patients 928 stressors, family members 536 stressors). Lines represent transitions from one time point’s stressor to the time of the subsequent study interview. The width of each line is proportional to the number of patients whose responses matched the trajectory. Lack of response (explained primarily by death and persistent illness) increases over time, predominantly among patients who initially reported health concerns. See also eTable 6.
76
eFigure 5: Outcomes
by mechanical ventilation stratification variable for patients. Model estimated means and standard deviations are shown for each outcome at 3 and 6 months by ventilator days (≤7 [left side] vs. >7 [right side]) for both treatment groups. Coping skills training values are shown as red lines while education program values are shown as blue. Horizontal axis values are in months; the vertical axis represents outcome value magnitude. All p>0.05 by treatment group at 3 and 6 months using general linear models unless otherwise indicated. For example, while estimated mean
77
HADS summary scores for education program patients ventilated for 7 or more days were lower compared to coping skills training patients at 3 months (p=0.04), this difference was not sustained at 6 months. Also see eTable 8.
78
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Acknowledgments
Thanks to the patients and family members who participated, the patient and family research
stakeholders (Emily Bass, Ron Bass, Lisa Boyd, Lynelle Fox, Joyce Odom (deceased), Darius
Odom, Frieda Waisner, Harold Waisner, Rhonda Zack, and Mark Zack), the clinical research
coordinator team (Khalida Arif, Summer Choudhury, Colin Johnston, Joyce Lanier, Mary Key,
Melissa McCullough, Stella Ogake, Megan Potter, Wen Regan, Anne-Marie Shields, Anna Ungar,
and Brenda Walton), the Data Coordinating Center team at the University of North Carolina-
Chapel Hill (Roger Akers, Brian Cass, Mattias Jonsson, and Maria Tobin), the Data Safety
Monitoring Board (Todd Rice, Tim Ahles, and Vernon Chinchilli), Verena Knowles, and Francis J.
Keefe.
Copyright© 2018. Duke University. All Rights Reserved.
Disclaimer:
The [views, statements, opinions] presented in this report are solely the responsibility of the author(s) and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute® (PCORI®), its Board of Governors or Methodology Committee.
Acknowledgement:
Research reported in this report was [partially] funded through a Patient-Centered Outcomes Research Institute® (PCORI®) Award (# 195) Further information available at: https://www.pcori.org/research-results/2012/can-coping-skills-training-help-patients-who-have-received-intensive-hospital
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