Multisite Randomized Clinical Trial Research Articles

Role of relative-reinforcement value of alcohol-free activities during recovery from alcohol use disorder in an adult clinical sample.

Behavioral economic theory has been extensively applied to understand alcohol use disorder (AUD). Applications of behavioral economic theory conceptualize AUD as a pattern of harmful alcohol use over extended periods of time in which choices between drinking or engaging in alcohol-free activities favor drinking. Recovery, in contrast, entails a sustained shift toward a pattern of selecting rewarding alcohol-free activities. The present study examined whether alcohol-free activity engagement and the relative-reinforcement value (RRV) of engaging in those activities predicted AUD treatment outcomes via secondary analysis of data from Project MATCH, a multisite randomized clinical trial examining behavioral treatments for AUD (N = 1,279, 75.8% male, 81.0% non-Hispanic White, 9.5% Black, 7.7% Hispanic/Latino, 1.5% American Indian/Alaska Native, < 1% Asian American, and other race/ethnicity). Regression analyses indicated that every additional alcohol-free activity reported at 6 months posttreatment was associated with 7% fewer drinking days, 5% fewer heavy drinking days, and approximately one less drink per drinking day, as well as with significant improvements in depression, purpose in life, and psychosocial functioning at 12 months following treatment. Consistent with behavioral economic theory, higher RRV of alcohol-free activities also predicted significant reductions in drinking and improvements in functioning, and these associations were stronger compared to results for alcohol-free activity frequency only. The findings highlight the importance of understanding environmental contexts conducive to recovery and support the value of increasing alcohol-free activity engagement and the RRV of engaging in such activities to facilitate reductions in drinking and improved functioning among individuals with AUD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Protocol for a randomized clinical trial to confirm the effectiveness of online guided self-help family-based treatment for adolescent anorexia nervosa

BackgroundThe leading evidence-based treatment for anorexia nervosa (AN) in adolescents is Family-based Treatment (FBT). However, due to the intensive training requirements and lack of practitioners, it is often difficult for families to access FBT. Thus, innovations that improve access to care are needed. A pilot randomized study of a guided self-help version of Family-based Treatment (GSH-FBT) that utilized approximately 1/4 the amount of therapist time compared to FBT found that the approach was acceptable and appeared to achieve similar outcomes. The study protocol detailed in this manuscript compares the efficiency (clinician time) of GSH-FBT to Family-based Treatment via Videoconferencing (FBT-V) in a fully powered study in achieving clinical outcomes through a multi-site randomized clinical trial across the US and Ontario, Canada. MethodsThis study will randomize the families of adolescents ages 12–18 (n = 200) who meet DSM-5 criteria for AN to receive either GSH-FBT or FBT-V. Participants will be randomized to 15 sixty-minute sessions of FBT-V or to 10 twenty-minute sessions of online GSH-FBT. Major assessments will be conducted by a masked assessor at baseline, within treatment, at the end of treatment (EOT), and 6 and 12 months after the end of treatment (EOT). The primary outcomes of this study are changes to body weight and eating disorder cognitions relative to clinician time used (relative efficiency of treatment modality). ConclusionsThe findings of this study may help increase access to care by providing a time efficient, affordable, more scalable intervention for adolescent AN compared to standard FBT.

The role of emotion dysregulation and interpersonal dysfunction in nonsuicidal self-injury during dialectical behavior therapy for borderline personality disorder

Dialectical Behaviour Therapy (DBT) is an evidence-based treatment for borderline personality disorder (BPD), with findings demonstrating improvements in various BPD features and related behaviours, such as nonsuicidal self-injury (NSSI). Theory and research suggest that reductions in emotion dysregulation and interpersonal dysfunction could account for at least some of the reduction in NSSI observed during the course of DBT. The current research investigated: 1) the trajectory of changes in emotion dysregulation, interpersonal dysfunction, and NSSI over the course of DBT, and 2) whether changes in emotion dysregulation mediate the relationship between changes in interpersonal dysfunction and changes in NSSI over treatment. One hundred and twenty individuals with BPD enrolled in a multi-site randomized-clinical trial were assessed at five timepoints over 12 months of standard DBT. Results indicated that interpersonal dysfunction and NSSI decreased over the course of DBT. Emotion dysregulation decreased in a quadratic manner such that most of the gains in emotion dysregulation occurred in earlier phases of DBT. Although changes in interpersonal dysfunction predicted changes in emotion dysregulation, changes in emotion dysregulation did not mediate the relationship between changes in interpersonal dysfunction and changes in NSSI.

Multi-site randomized trial of a collaborative palliative and oncology care model for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) receiving non-intensive therapy.

LBA6508 Background: Patients with AML and high-risk MDS receiving non-intensive chemotherapy have substantial quality of life (QOL) impairments and often do not engage in timely discussions with their clinicians about their end-of-life (EOL) care preferences. Yet interventions to optimize EOL care delivery and QOL for this population are lacking. Methods: We conducted a multi-site randomized clinical trial of a collaborative palliative and oncology care model compared to usual care in 115 adult patients with AML and high-risk MDS receiving non-intensive therapy at two tertiary care academic hospitals. Patients with a new diagnosis or relapse/ refractory disease were eligible to participate within 30 days of initiating therapy. Patients assigned to the intervention met with a palliative care clinician monthly in the outpatient setting and a minimum of twice weekly during every hospital admission. Patients assigned to usual care were seen by palliative care only upon request. We used Natural Language Processing methods to interrogate the Electronic Health Record (EHR) with a validated algorithm to collect documented EOL care preferences. The primary outcome was to compare time from documentation of EOL care preferences to death between the study arms. Secondary outcomes obtained from the EHR include rates of documentation of EOL care preferences, hospitalization, and hospice utilization at the EOL. Patient-reported secondary outcomes include discussions with clinicians about EOL care preferences, QOL (Functional Assessment of Cancer Therapy – Leukemia), and psychological distress (Hospital Anxiety and Depression Scale) at 3 months after enrollment. Results: We enrolled 51.8% (115/222) of eligible patients. The rate of documented EOL care discussions in the EHR was higher among intervention patients vs. usual care (96.5% vs. 68.4%, P&lt;0.001). Overall, 61.7% (71/115) of patients died, and those receiving the intervention had a longer time from documentation of EOL care preferences to death (41 days vs. 1.5 days, P&lt;0.001). Intervention patients were more likely to report discussing their EOL care preferences with their clinicians (56.9% vs. 14.0%, P&lt;0.001), and less likely to be hospitalized in the last 30 days of life (70.6% vs. 91.9%, P=0.031). There was no difference in hospice utilization at the EOL. At 3 months, patients assigned to the intervention reported better QOL (138.6 vs. 125.5, P=0.010), but no difference in depression or anxiety symptoms compared to those assigned to usual care. Conclusions: Palliative care significantly improved rates of discussion and documentation of EOL care preferences, reduced hospitalization at the EOL, and improved QOL in patients with AML and high-risk MDS. Clinical trial information: NCT03310918 .

Problems most concerning to parents of children with ADHD and emotional dysregulation in a randomized controlled trial of multinutrients: MADDY secondary analysis.

With dual focus on structured, objective quantification of parent observations of child's behavior and identifying behaviors most amenable to change, this report examines Parent Target Problems (PTP) as a secondary outcome in a randomized clinical trial (RCT) of children with attention-deficit/ hyperactivity disorder (ADHD) in which one primary outcome, Clinical Global Impression-Improvement, showed a significant advantage of multinutrients over placebo and the other, Likert-type parent ratings, showed significant improvement in both groups, without significant difference between them. In a multisite 8-week RCT of broad-spectrum micronutrients ("multinutrients"), parents of children ages 6-12 (N = 126, 73% male, 88% white) with ADHD and emotional dysregulation nominated their child's most concerning problem(s) at baseline and quantified them by frequency, duration, impairment, and consequences. At subsequent visits, parents re-quantified the problem(s). Blinded child psychiatrists independently reviewed the PTPs and rated change at two timepoints compared to baseline. PTPs were grouped into 9 categories. Mean ratings were compared between active and placebo groups and explored by category. By week 8, a significant separation favored multinutrients: 38% of the multinutrient group were "definitely improved" or better, compared to 25% of the placebo group, and ratings of "no change" or "worse" occurred in 35% with placebo versus 23% with multinutrients (p = 0.04). Inattention (72.2%) and emotional dysregulation (69.1%) were the most frequently reported PTP categories. Inattention and internalizing symptoms improved more with multinutrients than placebo (p = 0.01, d = 0.55; p = 0.03, d = 0.80, respectively). The multinutrient advantage was not significant for 7 other symptoms, including hyperactivity/impulsivity, aggression, autistic symptoms, or emotional dysregulation/irritable oppositionality. This secondary analysis found that the multinutrients, compared to placebo, were associated with improvements in parental concerns overall, and in two domains specifically: inattention and internalizing symptoms (anxiety/depression), but not in seven domains: hyperactivity/impulsivity, aggression, autistic symptoms or physiological symptoms, peer relationships or emotional dysregulation/irritable oppositionality.

Using virtual multiteam systems to conduct a multisite randomized clinical trial in the part C early intervention system: Benefits, challenges, and lessons learned

Background/AimsCOVID-19 necessitated a shift to virtual data collection for many research projects, providing the opportunity for novel approaches to carrying out multi-site clinical trials. Virtual multiteam systems (VMTS) are a type of team structure in which multiple geographically dispersed teams collaborate using technology-mediated communication. The article presents a case study of our use of VMTS, in response to COVID-19, to carry out a multisite randomized hybrid effectiveness-implementation trial of a caregiver-implemented intervention. MethodsWe describe how we modified our team structure from predominantly site-specific, co-located teams to predominantly cross-site, virtual teams. We then present examples of how we have conducted the two primary data collection activities virtually. To demonstrate the feasibility of this approach, we present participant demographic information, the percent of cross-site data collection activities, and fidelity data. ResultsIn the first 20 months of data collection, we have enrolled 108 EI providers and 132 families, with 17% and 9% attrition respectively. The family sample is highly diverse in terms of race/ethnicity, parent education, and household income. The majority of provider training activities and roughly 50% of family assessment activities have been conducted cross-site. Fidelity is high, with no differences across site. ConclusionsOur data illustrate the feasibility of using virtual teams, training, and assessment in a multisite clinical trial in the Part C system. We discuss the strengths and challenges of this approach, as well as lessons learned to facilitate the planning of future multisite randomized clinical trials which may benefit from this approach. Clinical TrialsNCT05114538

Apical Suspension Repair for Vaginal Vault Prolapse

The optimal surgical repair of vaginal vault prolapse after hysterectomy remains undetermined. To compare the efficacy and safety of 3 surgical approaches for vaginal vault prolapse after hysterectomy. This was a multisite, 3-arm, superiority and noninferiority randomized clinical trial. Outcomes were assessed biannually up to 60 months, until the last participant reached 36 months of follow-up. Settings included 9 clinical sites in the US National Institute of Child Health and Human Development (NICHD) Pelvic Floor Disorders Network. Between February 2016 and April 2019, women with symptomatic vaginal vault prolapse after hysterectomy who desired surgical correction were randomized. Data were analyzed from November 2022 to January 2023. Mesh-augmented (either abdominally [sacrocolpopexy] or through a vaginal incision [transvaginal mesh]) vs transvaginal native tissue repair. The primary outcome was time until composite treatment failure (including retreatment for prolapse, prolapse beyond the hymen, or prolapse symptoms) evaluated with survival models. Secondary outcomes included patient-reported symptom-specific results, objective measures, and adverse events. Of 376 randomized participants (mean [SD] age, 66.1 [8.7] years), 360 (96%) had surgery, and 296 (82%) completed follow-up. Adjusted 36-month failure incidence was 28% (95% CI, 20%-37%) for sacrocolpopexy, 29% (95% CI, 21%-38%) for transvaginal mesh, and 43% (95% CI, 35%-53%) for native tissue repair. Sacrocolpopexy was found to be superior to native tissue repair (adjusted hazard ratio [aHR], 0.57; 99% CI, 0.33-0.98; P = .01). Transvaginal mesh was not statistically superior to native tissue after adjustment for multiple comparisons (aHR, 0.60; 99% CI, 0.34-1.03; P = .02) but was noninferior to sacrocolpopexy (aHR, 1.05; 97% CI, 0-1.65; P = .01). All 3 surgeries resulted in sustained benefits in subjective outcomes. Mesh exposure rates were low (4 of 120 [3%] for sacrocolpopexy and 6 of 115 [5%] for transvaginal mesh) as were the rates of dyspareunia. Among participants undergoing apical repair for vaginal vault prolapse, sacrocolpopexy and transvaginal mesh resulted in similar composite failure rates at study completion; both had lower failure rates than native tissue repair, although only sacrocolpopexy met a statistically significant difference. Low rates of mesh complications and adverse events corroborated the overall safety of each approach. ClinicalTrials.gov Identifier: NCT02676973.

Virtual versus usual in-office care for multiple sclerosis: The VIRTUAL-MS multi-site randomized clinical trial study protocol

BackgroundMultiple sclerosis (MS) affects nearly 1 million people and is estimated to cost $85.4 billion in the United States annually. People with MS have significant barriers to receiving care and telemedicine could substantially improve access to specialized, comprehensive care. In cross-sectional analyses, telemedicine has been shown to be feasible, have high patient and clinician satisfaction, reduce patient costs and burden, and enable a reasonable assessment of disability. However, no studies exist evaluating the longitudinal impact of telemedicine care for MS. Here we describe the study protocol for VIRtual versus UsuAL In-office care for Multiple Sclerosis (VIRTUAL-MS). The main objective of the study is to evaluate the impact of telemedicine for MS care on: patient clinical outcomes, economic costs, patient, and clinician experience. MethodsThis two-site randomized clinical trial will enroll 120 adults with a recent diagnosis of MS and randomize 1:1 to receive in-clinic vs. telemedicine care for 24 months. The primary outcome of the study is worsening in any one of the four Multiple Sclerosis Functional Composite 4 (MSFC4) measures at 24 months. Other study outcomes include patient and clinician satisfaction, major healthcare costs, Expanded Disability Status Scale, treatment adherence, and digital outcomes. ConclusionThe results of this study will directly address the key gaps in knowledge about longitudinal telemedicine-enabled care in an MS population. It will inform clinical care implementation as well as design of trials in MS and other chronic conditions.Trial registration:NCT05660187

Nurse and Social Worker Palliative Telecare Team and Quality of Life in Patients With COPD, Heart Failure, or Interstitial Lung Disease

Many patients with chronic obstructive pulmonary disease (COPD), heart failure (HF), and interstitial lung disease (ILD) endure poor quality of life despite conventional therapy. Palliative care approaches may benefit this population prior to end of life. Determine the effect of a nurse and social worker palliative telecare team on quality of life in outpatients with COPD, HF, or ILD compared with usual care. Single-blind, 2-group, multisite randomized clinical trial with accrual between October 27, 2016, and April 2, 2020, in 2 Veterans Administration health care systems (Colorado and Washington), and including community-based outpatient clinics. Outpatients with COPD, HF, or ILD at high risk of hospitalization or death who reported poor quality of life participated. The intervention involved 6 phone calls with a nurse to help with symptom management and 6 phone calls with a social worker to provide psychosocial care. The nurse and social worker met weekly with a study primary care and palliative care physician and as needed, a pulmonologist, and cardiologist. Usual care included an educational handout developed for the study that outlined self-care for COPD, ILD, or HF. Patients in both groups received care at the discretion of their clinicians, which could include care from nurses and social workers, and specialists in cardiology, pulmonology, palliative care, and mental health. The primary outcome was difference in change in quality of life from baseline to 6 months between the intervention and usual care groups (FACT-G score range, 0-100, with higher scores indicating better quality of life, clinically meaningful change ≥4 points). Secondary quality-of-life outcomes at 6 months included disease-specific health status (Clinical COPD Questionnaire; Kansas City Cardiomyopathy Questionnaire-12), depression (Patient Health Questionnaire-8) and anxiety (Generalized Anxiety Disorder-7) symptoms. Among 306 randomized patients (mean [SD] age, 68.9 [7.7] years; 276 male [90.2%], 30 female [9.8%]; 245 White [80.1%]), 177 (57.8%) had COPD, 67 (21.9%) HF, 49 (16%) both COPD and HF, and 13 (4.2%) ILD. Baseline FACT-G scores were similar (intervention, 52.9; usual care, 52.7). FACT-G completion was 76% (intervention, 117 of 154; usual care, 116 of 152) at 6 months for both groups. Mean (SD) length of intervention was 115.1 (33.4) days and included a mean of 10.4 (3.3) intervention calls per patient. In the intervention group, 112 of 154 (73%) patients received the intervention as randomized. At 6 months, mean FACT-G score improved 6.0 points in the intervention group and 1.4 points in the usual care group (difference, 4.6 points [95% CI, 1.8-7.4]; P = .001; standardized mean difference, 0.41). The intervention also improved COPD health status (standardized mean difference, 0.44; P = .04), HF health status (standardized mean difference, 0.41; P = .01), depression (standardized mean difference, -0.50; P < .001), and anxiety (standardized mean difference, -0.51; P < .001) at 6 months. For adults with COPD, HF, or ILD who were at high risk of death and had poor quality of life, a nurse and social worker palliative telecare team produced clinically meaningful improvements in quality of life at 6 months compared with usual care. ClinicalTrials.gov Identifier: NCT02713347.

Yoga vs Cognitive Processing Therapy for Military Sexual Trauma–Related Posttraumatic Stress Disorder

First-line treatment for posttraumatic stress disorder (PTSD) in the US Department of Veterans Affairs (VA), ie, trauma-focused therapy, while effective, is limited by low treatment initiation, high dropout, and high treatment refraction. To evaluate the effectiveness of Trauma Center Trauma-Sensitive Yoga (TCTSY) vs first-line cognitive processing therapy (CPT) in women veterans with PTSD related to military sexual trauma (MST) and the hypothesis that PTSD outcomes would differ between the interventions. This multisite randomized clinical trial was conducted from December 1, 2015, to April 30, 2022, within 2 VA health care systems located in the southeast and northwest. Women veterans aged 22 to 71 years with MST-related PTSD were enrolled and randomized to TCTSY or CPT. The TCTSY intervention (Hatha-style yoga focusing on interoception and empowerment) consisted of 10 weekly, 60-minute group sessions, and the CPT intervention (cognitive-based therapy targeting modification of negative posttraumatic thoughts) consisted of 12 weekly, 90-minute group sessions. Sociodemographic data were collected via self-report survey. The primary outcome, PTSD symptom severity, was assessed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD Checklist for DSM-5 (PCL-5). Assessments were conducted at baseline, midintervention, 2 weeks post intervention, and 3 months post intervention. Of 200 women veterans who consented to participate, the intent-to-treat sample comprised 131 participants (mean [SD] age, 48.2 [11.2] years), with 72 randomized to TCTSY and 59 randomized to CPT. Treatment was completed by 47 participants (65.3%) in the TCTSY group and 27 (45.8%) in the CPT group, a 42.6% higher treatment completion rate in the TCTSY group (P = .03). Both treatment groups improved over time on the CAPS-5 (mean [SD] scores at baseline: 36.73 [8.79] for TCTSY and 35.52 [7.49] for CPT; mean [SD] scores at 3 months: 24.03 [11.55] for TCTSY and 22.15 [13.56]) and the PCL-5 (mean [SD] scores at baseline: 49.62 [12.19] for TCTSY and 48.69 [13.62] for CPT; mean [SD] scores at 3 months: 36.97 [17.74] for TCTSY and 31.76 [12.47]) (P < .001 for time effects). None of the group effects or group-by-time effects were significant. Equivalence analyses of change scores were not significantly different between the TCTSY and CPT groups, and the two one-sided test intervals fell within the equivalence bounds of plus or minus 10 for CAPS-5 for all follow-up time points. In this comparative effectiveness randomized clinical trial, TCTSY was equivalent to CPT in reducing PTSD symptom severity, with both groups improving significantly. The higher treatment completion rate for TCTSY indicates its higher acceptability as an effective and acceptable PTSD treatment for women veterans with PTSD related to MST that could address current VA PTSD treatment limitations. ClinicalTrials.gov Identifier: NCT02640690.

Multi-Site Randomized Trial of Inpatient Palliative Care for Hospitalized Patients Undergoing Hematopoietic Stem Cell Transplantation

Background: Patients with hematologic malignancies experience a substantial decline in their quality of life (QOL) and psychological health during their hospitalization for hematopoietic stem cell transplantation (HSCT). Early single center studies established the feasibility and promising preliminary efficacy of integrating palliative care during the HSCT hospitalization. However, data to test the efficacy of this care model across diverse care settings are lacking. Methods: We conducted a multi-site randomized trial among 360 adults with hematologic malignancies undergoing autologous or allogeneic HSCT at three academic institutions. Patients were randomly assigned to an inpatient palliative care intervention (n= 180) versus usual care (n=180), stratified by study site and type of HSCT. Intervention participants met with a palliative care clinician at least twice weekly during the HSCT hospitalization to address their physical and psychological symptoms. Patients assigned to usual care received all supportive care measures provided by the HSCT team and could be seen by palliative care upon request. We assessed patient QOL (Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), post-traumatic stress (PTSD) symptoms (PTSD Checklist), symptom burden (Edmonton Symptom Assessment Scale-Revised), and fatigue (FACT-Fatigue, higher scores indicate lower fatigue) at baseline and week-2 during hospitalization. The primary endpoint was QOL at week-2 during the HSCT hospitalization when patients typically experience their QOL nadir during HSCT. We used analysis of covariance, adjusting for baseline scores, to evaluate the effect of the intervention on patient-reported outcomes at week-2. Results: We enrolled 69.5% (360/518) of eligible patients (mean age = 55.4 (SD=12.5), 61.9% male, 76.6% White, 23.4% racial minorities, 8.7% Hispanic ethnicity, and 50.2% underwent allogeneic HSCT) between October 2018 and July 2022. Compared to those receiving usual care, participants receiving the inpatient palliative care intervention reported better QOL (95.5 vs. 89.3, P&amp;lt;0.001), and lower depression (5.9 vs. 6.9, P=0.041) and PTSD symptoms (26.0 vs. 28.2, P = 0.022) at week-2. Intervention participants also reported lower symptom burden (35.3 vs. 40.1, P=0.018) and better fatigue scores (28.6 vs. 25.6, p=0.014) compared to those assigned to usual care at week-2 during HSCT hospitalization. Anxiety symptoms (HADS-A) did not demonstrate a measurable difference between the two groups at week-2 during HSCT. Conclusions: In this multi-site randomized clinical trial, inpatient palliative care led to substantial improvements in patients' QOL, depression and PTSD symptoms, symptom burden, and fatigue during HSCT hospitalization compared to usual care. Integrated palliative care should be considered a new standard of care for patients hospitalized for HSCT.

Commentary on "Fidelity of Delivery in a Multisite Randomized Clinical Trial of Intervention Efficacy for Infants With Unilateral Cerebral Palsy".

Commentary on "Fidelity of Delivery in a Multisite Randomized Clinical Trial of Intervention Efficacy for Infants With Unilateral Cerebral Palsy".

Implications of the Network Theory for the Treatment of Mental Disorders

Conceptualizing mental disorders as latent entities has been challenged by the network theory of mental disorders, which states that psychological problems are constituted by a network of mutually interacting symptoms. While the implications of the network approach for planning and evaluating treatments have been intensively discussed, empirical support for the claims of the network theory regarding treatment effects is lacking. To assess the extent to which specific hypotheses derived from the network theory regarding the (interindividual) changeability of symptom dynamics in response to treatment align with empirical data. This secondary analysis entails data from a multisite randomized clinical trial, in which 254 patients with chronic depression reported on their depressive symptoms at every treatment session. Data collection was conducted between March 5, 2010, and October 14, 2013, and this analysis was conducted between November 1, 2021, and May 31, 2022. Thirty-two sessions of either disorder-specific or nonspecific psychotherapy for chronic depression. Longitudinal associations of depressive symptoms with each other and change of these associations through treatment estimated by a time-varying longitudinal network model. In a sample of 254 participants (166 [65.4%] women; mean [SD] age, 44.9 [11.9] years), symptom interactions changed through treatment, and this change varied across treatments and individuals. The mean absolute (ie, valence-ignorant) strength of symptom interactions (logarithmic odds ratio scale) increased from 0.40 (95% CI, 0.36-0.44) to 0.60 (95% CI, 0.52-0.70) during nonspecific psychotherapy and to 0.56 (95% CI, 0.48-0.64) during disorder-specific psychotherapy. In contrast, the mean raw (ie, valence-sensitive) strength of symptom interactions decreased from 0.32 (95% CI, 0.28-0.36) to 0.26 (95% CI, 0.20-0.32) and to 0.09 (95% CI, 0.02-0.16), respectively. Changing symptom severity could be explained to a large extent by symptom interactions. These findings suggest that specific treatment-related hypotheses of the network theory align well with empirical data. Conceptualizing mental disorders as symptom networks and treatments as measures that aim to change these networks is expected to give further insights into the working mechanisms of mental health treatments, leading to the improvement of current and the development of new treatments. ClinicalTrials.gov Identifier: NCT00970437.

Efficacy of Telephone-Based Cognitive Behavioral Therapy for Weight Loss, Disordered Eating, and Psychological Distress After Bariatric Surgery

Weight regain after bariatric surgery is associated with recurrence of obesity-related medical comorbidities and deterioration in quality of life. Developing efficacious psychosocial interventions that target risk factors, prevent weight regain, and improve mental health is imperative. To determine the efficacy of a telephone-based cognitive behavioral therapy (tele-CBT) intervention at 1 year after bariatric surgery in improving weight loss, disordered eating, and psychological distress. This multisite randomized clinical trial was conducted at 3 hospital-based bariatric surgery programs, with recruitment between February 2018 and December 2021. Eligibility for participation was assessed among 314 adults at 1 year after bariatric surgery who were fluent in English and had access to a telephone and the internet. Patients with active suicidal ideation or poorly controlled severe psychiatric illness were excluded. Primary and secondary outcome measures were assessed at baseline (1 year after surgery), after the intervention (approximately 15 months after surgery), and at 3-month follow-up (approximately 18 months after surgery). Data were analyzed from January to February 2023. The tele-CBT intervention consisted of 6 weekly 1-hour sessions and a seventh booster session 1 month later. The control group received standard postoperative bariatric care. The primary outcome was postoperative percentage total weight loss. Secondary outcomes were disordered eating (Binge Eating Scale [BES] and Emotional Eating Scale [EES]) and psychological distress (Patient Health Questionnaire-9 item scale [PHQ-9] and Generalized Anxiety Disorder-7 item scale [GAD-7]). The hypotheses and data-analytic plan were developed prior to data collection. Among 306 patients 1 year after bariatric surgery (255 females [83.3%]; mean [SD] age, 47.55 [9.98] years), there were 152 patients in the tele-CBT group and 154 patients in the control group. The group by time interaction for percentage total weight loss was not significant (F1,160.61 = 2.09; P = .15). However, there were significant interactions for mean BES (F2,527.32 = 18.73; P < .001), EES total (F2,530.67 = 10.83; P < .001), PHQ-9 (F2,529.93 = 17.74; P < .001), and GAD-7 (F2,535.16 = 15.29; P < .001) scores between the tele-CBT group and control group across all times. This study found that tele-CBT delivered at 1 year after surgery resulted in no change in short-term weight outcomes but improved disordered eating and psychological distress. The impact of these psychosocial improvements on longer-term weight outcomes is currently being examined as part of this longitudinal multisite randomized clinical trial. ClinicalTrials.gov Identifier: NCT03315247.

Testing the Efficacy of a Scalable Telephone-Delivered Guided Imagery Tobacco Cessation Treatment: Protocol for a Randomized Clinical Trial.

Tobacco use continues to be a leading preventable cause of death and disease in the United States, accounting for >480,000 deaths each year. Although treatments for tobacco use are effective for many, there is substantial variability in outcomes, and these approaches are not effective for all individuals seeking to quit smoking cigarettes. New, effective therapeutic approaches are needed to meet the preferences of people who want to stop smoking. Guided imagery (GI) is a mind-body technique that involves the guided visualization of specific mental images, which is enhanced with other sensory modalities and emotions. Preliminary evidence provides initial support for the use of GI as a treatment for cigarette smoking. Meta-analyses have shown that standard treatment for cigarette smoking delivered over the telephone via quitlines is effective. A telephone-based intervention that uses GI might provide another effective treatment option and increase the reach and effectiveness of quitlines. This study aims to test the efficacy of Be Smoke Free, a telephone-delivered GI treatment for smoking cessation. This multisite randomized clinical trial (RCT) will compare a novel telephone-delivered GI tobacco cessation treatment with a standard evidence-based behavioral treatment. The study will be conducted over 5 years. In phase 1, we refined protocols and procedures for the New York State and West Virginia sites for use in the RCT. During phase 2, we will conduct an RCT with 1200 participants: 600 (50%) recruited via quitlines and 600 (50%) recruited via population-based methods. Participants will be randomly assigned to either the GI condition or the behavioral condition; both treatments will be delivered by trained study coaches located at the University of Arizona. Assessments will be conducted at baseline and 3 and 6 months after enrollment by University of Arizona research staff. The primary outcome will be self-reported 30-day point prevalence abstinence 6 months after enrollment. Secondary outcomes include biochemically verified 7-day point prevalence abstinence 6 months after enrollment. Recruitment in West Virginia and New York began in October 2022. As of March 31, 2023, a total of 242 participants had been enrolled. Follow-up assessments began in November 2022. As of March 31, 2023, of the 118 eligible participants, 97 (82.2%) had completed the 3-month assessment, and 93% (26/28) of eligible participants had completed the 6-month assessment. Biochemical verification and qualitative interviews began in April 2023. Recruitment will continue through 2025 and follow-up assessments through 2026. Primary results are expected to be published in 2027. The Be Smoke Free study is a first-of-its-kind RCT that incorporates GI into telephone-based tobacco cessation treatment. If successful, Be Smoke Free will have substantial benefits for the long-term health of people who use tobacco across the United States. ClinicalTrials.gov NCT05277831; https://clinicaltrials.gov/ct2/show/NCT05277831. PRR1-10.2196/48898.

A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression Among University Students

Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT. To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors. This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022. Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435). Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline. The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P = .003) or treatment as usual (40.0% [2.7%]; P = .001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P = .007; self-guided i-CBT: 25.4% [8.8%]; P = .004; treatment as usual: 31.0% [9.4%]; P = .001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P = .14; treatment as usual: 53.0% [6.0%]; P = .25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P = .001; treatment as usual: 41.8% [3.2%]; P < .001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P = .07). Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings. ClinicalTrials.gov Identifier: NCT04780542.

Community Informed Recruitment: A Promising Method to Enhance Clinical Trial Participation.

Low recruitment rates in palliative care clinical trials amongst Black and rural individuals have been attributed to lack of trust and procedural barriers. Community engagement strategies have increased clinical trial participation of under-represented populations. Describe a successful community-engaged recruitment strategy in an ongoing multi-site randomized clinical trial (RCT). Using community-based participatory research principles and input from a prior pilot study's community advisory group (CAG), we designed a novel recruitment strategy for Community Tele-Pal, a three-site, culturally based palliative care tele-consult RCT for Black and White seriously ill inpatients and their family caregivers. Local site CAGs helped design and implement a recruitment strategy in which a CAG member accompanied the study coordinators to introduce the study to eligible patients. Initially, CAG members could not accompany study coordinators in person due to pandemic restrictions. Hence, they created videos of themselves introducing the study, just as they would have done in person. We examined outcomes to date by the three recruitment methods and race. Of the 2879 patients screened, 228 were eligible and approached. Overall, the proportions of patients who consented 102 (44.7%) vs. not consented 126 (55.3%) were similar by race- White (consented= 75 [44.1%]) vs; Black (consented=27 [46.6%]). Proportionally, consent rates favored CAG-involved methods: coordinator only- 47 approached and 13 (12.7%) consented vs. coordinator/CAG video-105 approached and 60 (58.8%) consented. A novel community-enhanced recruitment strategy demonstrated the potential to increase clinical trial participation from historically under-represented populations.

Effect of Perioperative Palliative Care on Health-Related Quality of Life Among Patients Undergoing Surgery for Cancer

Involvement of palliative care specialists in the care of medical oncology patients has been repeatedly observed to improve patient-reported outcomes, but there is no analogous research in surgical oncology populations. To determine whether surgeon-palliative care team comanagement, compared with surgeon team alone management, improves patient-reported perioperative outcomes among patients pursuing curative-intent surgery for high morbidity and mortality upper gastrointestinal (GI) cancers. From October 20, 2018, to March 31, 2022, a patient-randomized clinical trial was conducted with patients and clinicians nonblinded but the analysis team blinded to allocation. The trial was conducted in 5 geographically diverse academic medical centers in the US. Individuals pursuing curative-intent surgery for an upper GI cancer who had received no previous specialist palliative care were eligible. Surgeons were encouraged to offer participation to all eligible patients. Surgeon-palliative care comanagement patients met with palliative care either in person or via telephone before surgery, 1 week after surgery, and 1, 2, and 3 months after surgery. For patients in the surgeon-alone group, surgeons were encouraged to follow National Comprehensive Cancer Network-recommended triggers for palliative care consultation. The primary outcome of the trial was patient-reported health-related quality of life at 3 months following the operation. Secondary outcomes were patient-reported mental and physical distress. Intention-to-treat analysis was performed. In total, 359 patients (175 [48.7%] men; mean [SD] age, 64.6 [10.7] years) were randomized to surgeon-alone (n = 177) or surgeon-palliative care comanagement (n = 182), with most patients (206 [57.4%]) undergoing pancreatic cancer surgery. No adverse events were associated with the intervention, and 11% of patients in the surgeon-alone and 90% in the surgeon-palliative care comanagement groups received palliative care consultation. There was no significant difference between study arms in outcomes at 3 months following the operation in patient-reported health-related quality of life (mean [SD], 138.54 [28.28] vs 136.90 [28.96]; P = .62), mental health (mean [SD], -0.07 [0.87] vs -0.07 [0.84]; P = .98), or overall number of deaths (6 [3.7%] vs 7 [4.1%]; P > .99). To date, this is the first multisite randomized clinical trial to evaluate perioperative palliative care and the earliest integration of palliative care into cancer care. Unlike in medical oncology practice, the data from this trial do not suggest palliative care-associated improvements in patient-reported outcomes among patients pursuing curative-intent surgeries for upper GI cancers. ClinicalTrials.gov Identifier: NCT03611309.

Effect of an Emergency Department Process Improvement Package on Suicide Prevention

Suicide is a leading cause of deaths in the US. Although the emergency department (ED) is an opportune setting, ED-initiated interventions remain underdeveloped and understudied. To determine if an ED process improvement package, with a subfocus on improving the implementation of collaborative safety planning, reduces subsequent suicide-related behaviors. The Emergency Department Safety Assessment and Follow-up Evaluation 2 (ED-SAFE 2) trial, a stepped-wedge cluster randomized clinical trial conducted in 8 EDs across the US, used an interrupted time series design with three 12-month sequential phases: baseline, implementation, and maintenance. A random sample of 25 patients per month per site 18 years and older who screened positive on the Patient Safety Screener, a validated suicide risk screener, were included. The primary analyses focused on those who were discharged from the ED, while secondary analyses focused on all patients who screened positive, regardless of disposition. Data were collected on patients who presented for care from January 2014 to April 2018, and data were analyzed from April to December 2022. Each site received lean training and built a continuous quality improvement (CQI) team to evaluate the current suicide-related workflow in the ED, identify areas of improvement, and implement efforts to improve. Each site was expected to increase their universal suicide risk screening and implement collaborative safety planning for patients at risk of suicide who were discharged home from the ED. Site teams were centrally coached by engineers experienced in lean CQI and suicide prevention specialists. The primary outcome was a composite comprising death by suicide or suicide-related acute health care visits, measured over a 6-month follow-up window. Across 3 phases, 2761 patient encounters were included in the analyses. Of these, 1391 (50.4%) were male, and the mean (SD) age was 37.4 (14.5) years. A total of 546 patients (19.8%) exhibited the suicide composite during the 6-month follow-up (9 [0.3%] died by suicide and 538 [19.5%] of a suicide-related acute health care visit). A significant difference was observed for the suicide composite outcome between the 3 phases (baseline, 216 of 1030 [21%]; implementation, 213 of 967 [22%]; maintenance, 117 of 764 [15.3%]; P = .001). The adjusted odds ratios of risk of the suicide composite during the maintenance phase was 0.57 (95% CI, 0.43-0.74) compared with baseline and 0.61 (0.46-0.79) compared with the implementation phase, which reflect a 43% and 39% reduction, respectively. In this multisite randomized clinical trial, using CQI methods to implement a department-wide change in suicide-related practices, including the implementation of a safety plan intervention, yielded a significant decrease in suicide behaviors in the maintenance period of the study. ClinicalTrials.gov Identifier: NCT02453243.

Passing the SNF Test: A Secondary Analysis of a Sepsis Transition Intervention Trial Among Patients Discharged to Post-Acute Care.

Sepsis survivors discharged to post-acute care facilities experience high rates of mortality and hospital readmission. This study compared the effects of a Sepsis Transition and Recovery (STAR) program vs usual care (UC) on 30-day mortality and hospital readmission among sepsis survivors discharged to post-acute care. Secondary analysis of a multisite pragmatic randomized clinical trial. Sepsis survivors discharged to post-acute care. We conducted a secondary analysis of patients from the IMPACTS (Improving Morbidity During Post-Acute Care Transitions for Sepsis) randomized clinical trial who were discharged to post-acute care. IMPACTS evaluated the effectiveness of STAR, a nurse-navigator-led program to deliver best practice post-sepsis care. Subjects were randomized to receive either STAR or UC. The primary outcome was 30-day readmission and mortality. We also evaluated hospital-free days alive as a secondary outcome. Of 691 patients enrolled in IMPACTS, 175 (25%) were discharged to post-acute care [143 (82%) to skilled nursing facilities, 12 (7%) to long-term acute care hospitals, and 20 (11%) to inpatient rehabilitation]. Of these, 87 received UC and 88 received the STAR intervention. The composite 30-day all-cause mortality and readmission endpoint occurred in 26 (29.9%) patients in the UC group vs 18 (20.5%) in the STAR group [risk difference-9.4% (95% CI-22.2 to 3.4); adjusted odds ratio 0.58 (95% CI 0.28 to 1.17)]. Separately, 30-day all-cause mortality was 8.1% in the UC group compared with 5.7% in the STAR group [risk difference-2.4% (95% CI-9.9 to 5.1)] and 30-day all-cause readmission was 26.4% in the UC group compared with 17.1% in the STAR program [risk difference-9.4% (95% CI-21.5 to 2.8)]. There are few proven interventions to reduce readmission among patients discharged to post-acute care facilities. These results suggest the STAR program may reduce 30-day mortality and readmission rates among sepsis survivors discharged to post-acute care facilities.