Improving Veteran Engagement with Virtual Care Technologies: a Veterans Health Administration State of the Art Conference Research Agenda.

Although the availability of virtual care technologies in the Veterans Health Administration (VHA) continues to expand, ensuring engagement with these technologies among Veterans remains a challenge. VHA Health Services Research & Development convened a Virtual Care State of The Art (SOTA) conference in May 2022 to create a research agenda for improving virtual care access, engagement, and outcomes. This article reports findings from the Virtual Care SOTA engagement workgroup, which comprised fourteen VHA subject matter experts representing VHA clinical care, research, administration, and operations. Workgroup members reviewed current evidence on factors and strategies that may affect Veteran engagement with virtual care technologies and generated key questions to address evidence gaps. The workgroup agreed that although extensive literature exists on factors that affect Veteran engagement, more work is needed to identify effective strategies to increase and sustain engagement. Workgroup members identified key priorities for research on Veteran engagement with virtual care technologies through a series of breakout discussion groups and ranking exercises. The top three priorities were to (1) understand the Veteran journey from active service to VHA enrollment and beyond, and when and how virtual care technologies can best be introduced along that journey to maximize engagement and promote seamless care; (2) utilize the meaningful relationships in a Veteran's life, including family, friends, peers, and other informal or formal caregivers, to support Veteran adoption and sustained use of virtual care technologies; and (3) test promising strategies in meaningful combinations to promote Veteran adoption and/or sustained use of virtual care technologies. Research in these priority areas has the potential to help VHA refine strategies to improve virtual care user engagement, and by extension, outcomes.

Therapist-supported digital mental health intervention for depressive symptoms: A randomized clinical trial.

Depression is a chronic and debilitating mental disorder. Despite the existence of several evidence-based treatments, many individuals suffering from depression face myriad structural barriers to accessing timely care which may be alleviated by digital mental health interventions (DMHI). Accordingly, this randomized clinical trial (ClinicalTrials.gov: NCT04738084) investigated the efficacy of a newer version of the therapist-supported and guided DMHI, the Meru Health Program (MHP), which was recently enhanced with heart rate variability biofeedback and lengthened from 8- to 12-weeks duration, among people with elevated depression symptoms (N = 100, mean age 37). Recruited participants were randomized to the MHP (n = 54) or a waitlist control (n = 46) condition for 12 weeks. The MHP group had greater decreases in depression symptoms compared to the waitlist control (d = -0.8). A larger proportion of participants in the MHP group reported a minimal clinically important difference (MCID) in depression symptoms than participants in the waitlist control group (39.1 % vs. 9.8 %, χ2(1) = 9.90, p = .002). Similar effects were demonstrated for anxiety symptoms, quality of life, insomnia, and resilience. The results confirm the utility of the enhanced MHP in reducing depression symptoms and associated health burdens.

Determinants and outcome correlates of engagement with a mobile mental health intervention for depression and anxiety in middle-aged and older adults.

OBJECTIVES: To examine baseline factors (i.e., age, gender, mobile device proficiency, sensory impairment) associated with app engagement in a 12-week mental health app intervention and to explore whether app engagement predicts changes in depression and anxiety symptoms among middle-aged and older adults. METHOD: Mobile device proficiency, sensory impairment, depression, and anxiety symptoms were measured using questionnaires. App engagement was defined by metrics characterizing the core intervention features (i.e., messages sent to therapist, mindfulness meditation minutes, action tasks completed). Multiple regressions and multilevel models were conducted. RESULTS: Forty-nine participants (M age = 57.40, SD = 11.09 years) enrolled. Women (ß = .35, p < .05) and participants with less sensory impairment completed more action tasks (ß = -.40, p < .05). Depressive and anxiety symptoms measured within the app declined significantly across treatment. Clinical significant improvements were observed for depression in 48.9% and for anxiety in 40% of participants. App engagement metrics were not predictive of depression or anxiety symptoms, either incrementally in time-lagged models or cumulatively in hierarchical linear regression analyses. CONCLUSION: App engagement is multifaceted; participants engaged differently by gender and ability. Participation in this digital mental health intervention reduced depression and anxiety symptoms, but these findings should be interpreted with caution as the study did not include a control condition. Our findings underscore the importance of considering individual factors that may influence use of a digital mental health intervention.

A prognostic index to predict symptom and functional outcomes of a coached, web-based intervention for trauma-exposed veterans.

Researchers at the Department of Veterans Affairs (VA) have studied interventions for posttraumatic stress disorder and co-occurring conditions in both traditional and digital formats. One such empirically supported intervention is web skills training in affective and interpersonal regulation (webSTAIR), a coached, 10-module web program based on STAIR. To understand which patient characteristics were predictive of webSTAIR outcomes in a sample of trauma-exposed veterans (N = 189), we used machine learning (ML) to develop a prognostic index from among 18 baseline characteristics (i.e., demographic, military, trauma history, and clinical) to predict posttreatment posttraumatic stress disorder severity, depression severity, and psychosocial functioning impairment. We compared the ML models to a benchmark of linear regression models in which the only predictor was the baseline severity score of the outcome measure. The ML and "severity-only" models performed similarly, explaining 39%-45% of the variance in outcomes. This suggests that baseline symptom severity and functioning are strong indicators for webSTAIR outcomes in veterans, with higher severity indicating worse prognosis, and that the other variables examined did not contribute significant added predictive signal. Findings also highlight the importance of comparing ML models to an appropriate benchmark. Future research with larger samples could potentially detect smaller patient-level effects as well as effects driven by other types of variables (e.g., therapeutic process variables). As a transdiagnostic, digital intervention, webSTAIR can potentially serve a diverse veteran population with varying trauma histories and may be best conceptualized as a beneficial first step of a stepped care model for those with heightened symptoms or impairment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial.

Toll-like receptor-driven and interleukin-1 (IL-1) receptor-driven inflammation mediated by IL-1 receptor-associated kinase 4 (IRAK4) is involved in the pathophysiology of hidradenitis suppurativa (HS) and atopic dermatitis (AD). KT-474 (SAR444656), an IRAK4 degrader, was studied in a randomized, double-blind, placebo-controlled phase 1 trial where the primary objective was safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics and clinical activity in patients with moderate to severe HS and in patients with moderate to severe AD. KT-474 was administered as a single dose and then daily for 14 d in 105 healthy volunteers (HVs), followed by dosing for 28 d in an open-label cohort of 21 patients. Degradation of IRAK4 was observed in HV blood, with mean reductions after a single dose of ≥93% at 600-1,600 mg and after 14 daily doses of ≥95% at 50-200 mg. In patients, similar IRAK4 degradation was achieved in blood, and IRAK4 was normalized in skin lesions where it was overexpressed relative to HVs. Reduction of disease-relevant inflammatory biomarkers was demonstrated in the blood and skin of patients with HS and patients with AD and was associated with improvement in skin lesions and symptoms. There were no drug-related infections. These results, from what, to our knowledge, is the first published clinical trial using a heterobifunctional degrader, provide initial proof of concept for KT-474 in HS and AD to be further confirmed in larger trials. ClinicalTrials.gov identifier: NCT04772885 .

Stand Down-Think Before You Drink: protocol for an effectiveness-implementation trial of a mobile application for unhealthy alcohol use with and without peer support.

INTRODUCTION: Mobile apps can increase access to alcohol-related care but only if patients actively engage with them. Peers have shown promise for facilitating patients' engagement with mobile apps. However, the effectiveness of peer-based mobile health interventions for unhealthy alcohol use has yet to be evaluated in a randomised controlled trial. The goal of this hybrid I effectiveness-implementation study is to test a mobile app ('Stand Down-Think Before You Drink'), with and without peer support, to improve drinking outcomes among primary care patients. METHODS AND ANALYSIS: In two US Veterans Health Administration (VA) medical centres, 274 primary care patients who screen positive for unhealthy alcohol use and are not currently in alcohol treatment will be randomised to receive usual care (UC), UC plus access to Stand Down (App), or UC plus Peer-Supported Stand Down (PSSD-four peer-led phone sessions over the initial 8 weeks to enhance app engagement). Assessments will occur at baseline and 8-, 20- and 32-weeks postbaseline. The primary outcome is total standard drinks; secondary outcomes include drinks per drinking day, heavy drinking days and negative consequences from drinking. Hypotheses for study outcomes, as well as treatment mediators and moderators, will be tested using mixed effects models. Semi-structured interviews with patients and primary care staff will be analysed using thematic analysis to identify potential barriers and facilitators to implementation of PSSD in primary care. ETHICS AND DISSEMINATION: This protocol is a minimal risk study and has received approval from the VA Central Institutional Review Board. The results have the potential to transform the delivery of alcohol-related services for primary care patients who engage in unhealthy levels of drinking but rarely seek treatment. Study findings will be disseminated through collaborations with healthcare system policymakers as well as publications to scholarly journals and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: NCT05473598.

Testing adaptive interventions to improve PTSD treatment outcomes in Federally Qualified Health Centers: Protocol for a randomized clinical trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) disproportionately affects low-income individuals and is untreated in 70% of those affected. One third of low-income Americans are treated in Federally Qualified Health Centers (FQHCs), which do not have the capacity to provide all patients with first-line treatments such as Prolonged Exposure (PE). To address this problem, FQHCs could use low-intensity interventions (e.g., Clinician-Supported PTSD Coach: CS PTSD Coach) and medium-intensity interventions (e.g., PE for Primary Care: PE-PC) to treat PTSD with fewer resources. However, some patients will still require high-intensity treatments (e.g., full-length PE) for sustained clinical benefit. Thus, there is a critical need to develop stepped-care models for PTSD in FQHCs. METHOD: We are conducting a Sequential, Multiple Assignment, Randomized Trial (SMART) with 430 adults with PTSD in FQHCs. Participants are initially randomized to CS PTSD Coach or PE-PC. After four sessions, early responders step down to lower frequency interaction within their assigned initial treatment strategy. Slow responders are re-randomized to either continue their initial treatment strategy or step up to Full PE for an additional eight weeks. The specific aims are to test the effectiveness of initiating treatment with PE-PC versus CS PTSD Coach in reducing PTSD symptoms and to test the effectiveness of second-stage strategies (continue versus step-up to Full PE) for slow responders. CONCLUSIONS: This project will provide critical evidence to inform the development of an effective stepped-care model for PTSD. Testing scalable, sustainable sequences of PTSD treatments delivered in low-resource community health centers will improve clinical practice for PTSD.

A Randomized Clinical Trial of Clinician-Supported PTSD Coach in VA Primary Care Patients.

BACKGROUND: Posttraumatic stress disorder (PTSD) is common in primary care patients; however, evidence-based treatments are typically only available in specialty mental healthcare settings and often not accessed. OBJECTIVE: To test the effectiveness of a brief primary care-based treatment, Clinician-Supported PTSD Coach (CS PTSD Coach) was compared with Primary Care Mental Health Integration-Treatment as Usual (PCMHI-TAU) in (1) reducing PTSD severity, (2) engaging veterans in specialty mental health care, and (3) patient satisfaction with care. DESIGN: Multi-site randomized pragmatic clinical trial. PARTICIPANTS: A total of 234 veterans with PTSD symptoms who were not currently accessing PTSD treatment. INTERVENTION: CS PTSD Coach was designed to be implemented in Veterans Affairs PCMHI and combines mental health clinician support with the "PTSD Coach" mobile app. Four 30-min sessions encourage daily use of symptom management strategies. MAIN MEASURES: PTSD severity was measured by clinician-rated interviews pre- and post-treatment (8 weeks). Self-report measures assessed PTSD, depression, and quality of life at pretreatment, posttreatment, and 16- and 24-week follow-ups, and patient satisfaction at post-treatment. Mental healthcare utilization was extracted from medical records. KEY RESULTS: Clinician-rated PTSD severity did not differ by condition at post-treatment. CS PTSD Coach participants improved more on patient-reported PTSD severity at post-treatment than TAU participants (D = .28, p = .021). Coach participants who continued to have problematic PTSD symptoms at post-treatment were not more likely to engage in 2 sessions of specialty mental health treatment than TAU participants. Coach participants engaged in 74% more sessions in the intervention and reported higher treatment satisfaction than TAU participants (p < .001). CONCLUSIONS: A structured 4-session intervention designed to align with patient preferences for care resulted in more patient-reported PTSD symptom relief, greater utilization of mental health treatment, and overall treatment satisfaction than TAU, but not more clinician-rated PTSD symptom relief or engagement in specialty mental health.

Design and methods of a randomized controlled trial evaluating the effects of the PE Coach mobile application on prolonged exposure among veterans with PTSD.

BACKGROUND: Little is known about the impact of mobile applications (apps) designed to support patients progressing through an evidence-based psychotherapy. Prolonged exposure (PE) is an efficacious treatment for posttraumatic stress disorder (PTSD) and PE Coach is a treatment companion app that may increase patient engagement with the active components of PE, thereby supporting recovery. METHODS: This paper describes a randomized clinical trial that will evaluate PE delivered with and without PE Coach at post-treatment, and 1-month and 4-months post-treatment. Veterans with PTSD (N = 124) will be randomized (1:1) to conditions and complete up to 15 treatment sessions based on a priori defined termination criteria. We hypothesize that compared to PE without PE Coach, PE with the app will result in greater improvements in PTSD-related social and occupational functioning (primary outcome is the PTSD-Related Functioning Inventory), quality of life, and greater reductions in functional impairment, neurobehavioral symptoms, depression, and suicidal ideation (Aim 1). We also hypothesize that including PE Coach will reduce assessor-masked PTSD symptom severity, relative to PE without the app, as assessed by the revised Clinician-Administered PTSD Scale for DSM-5 (Aim 2). We hypothesize that PE Coach will facilitate increased treatment adherence, as measured by completion of PE homework (Aim 3). We will explore the impact of PE Coach on treatment engagement, as measured by reduced treatment dropout. CONCLUSION: Data on the outcomes of PE Coach can inform dissemination efforts and help evaluate the return on investment to guide future mental health app development. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.govNCT04959695.

A longitudinal assessment of posttraumatic stress symptoms and pain catastrophizing after injury.

PURPOSE/OBJECTIVE: Identifying individuals with high levels of pain catastrophizing (PC) may inform early psychological interventions to prevent the transition from acute to chronic post-injury pain. We examined whether pre-and post-injury posttraumatic stress symptoms (PTSS) predict post-injury PC among emergency department (ED) patients following acute motor vehicle crash (MVC). RESEARCH METHOD/DESIGN: This study represents secondary data analysis of a randomized clinical trial (NCT03247179) examining the efficacy of the PTSD Coach app on post-injury PTSS (PTSSpost). Among 63 injured ED patients (63% female; 57% non-White; average age = 37) with moderate pain (≥4 of 10), we assessed recall of pre-injury PTSS (PTSSrecall: stemming from preexisting exposures) and baseline PC within 24 hr post-MVC; PTSSpost stemming from the MVC was assessed 30-days later, and the outcome of PC was assessed at 90-days post-injury. We controlled for group assignment (intervention vs. control) in all analyses. RESULTS: Results revealed that at baseline and 90-days, PC was higher among non-White versus White participants. After adjusting for relevant covariates, PTSSrecall uniquely predicted post-injury PC and each subscale of PC (helplessness, magnification, and rumination). Similarly, after controlling for PTSSrecall and relevant covariates, PTSSpost uniquely predicted total and subscale post-injury PC. Intervention group participants reported less rumination than control group participants. CONCLUSIONS/IMPLICATIONS: These novel findings highlight that injured Black patients may be vulnerable to post-injury PC, and that both PTSSrecall and PTSSpost significantly predict post-injury PC. Brief PTSS assessment in the ED can identify high-risk patients who may benefit from early intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The PTSD Family Coach App in Veteran Family Members: Pilot Randomized Controlled Trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) among US military veterans can adversely impact their concerned significant others (CSOs; eg, family members and romantic partners). Mobile apps can be tailored to support CSO mental health through psychoeducation, coping skills, and stress monitoring. OBJECTIVE: This study assessed the feasibility, acceptability, and potential efficacy of PTSD Family Coach 1.0, a free, publicly available app that includes psychoeducation, stress management tools, self-assessments, and features for connecting to alternative supports, compared with a psychoeducation-only version of the app for cohabitating CSOs of veterans with PTSD. METHODS: A total of 200 participants with an average age of 39 (SD 8.44) years, primarily female (193/200, 97%), and White (160/200, 80%) were randomized to self-guided use of either PTSD Family Coach 1.0 (n=104) or a psychoeducation-only app (n=96) for 4 weeks. Caregiver burden, stress, depression, anxiety, beliefs about treatment, CSO self-efficacy, and relationship functioning assessed using measures of dyadic adjustment, social constraints, and communication danger signs were administered via a web survey at baseline and after treatment. User satisfaction and app helpfulness were assessed after treatment. Data were analyzed using linear mixed methods. RESULTS: Overall, 50.5% (101/200) of randomized participants used their allocated app. Participants found PTSD Family Coach 1.0 somewhat satisfying (mean 4.88, SD 1.11) and moderately helpful (mean 2.99, SD 0.97) to use. Linear mixed effects models revealed no significant differences in outcomes by condition for caregiver burden (P=.45; Cohen d=0.1, 95% CI -0.2 to 0.4), stress (P=.64; Cohen d=0.1, 95% CI -0.4 to 0.6), depression (P=.93; Cohen d= 0.0, 95% CI -0.3 to 0.3), anxiety (P=.55; Cohen d=-0.1, 95% CI -0.4 to 0.2), beliefs about treatment (P=.71; Cohen d=0.1, 95% CI -0.2 to 0.3), partner self-efficacy (P=.59; Cohen d=-0.1, 95% CI -0.4 to 0.2), dyadic adjustment (P=.08; Cohen d=-0.2, 95% CI -0.5 to 0.0), social constraints (P=.05; Cohen d=0.3, 95% CI 0.0-0.6), or communication danger signs (P=.90; Cohen d=-0.0, 95% CI -0.3 to 0.3). Post hoc analyses collapsing across conditions revealed a significant between-group effect on stress for app users versus nonusers (ß=-3.62; t281=-2.27; P=.02). CONCLUSIONS: Approximately half of the randomized participants never used their allocated app, and participants in the PTSD Family Coach 1.0 condition only opened the app approximately 4 times over 4 weeks, suggesting limitations to this app version's feasibility. PTSD Family Coach 1.0 users reported moderately favorable impressions of the app, suggesting preliminary acceptability. Regarding efficacy, no significant difference was found between PTSD Family Coach 1.0 users and psychoeducation app users across any outcome of interest. Post hoc analyses suggested that app use regardless of treatment condition was associated with reduced stress. Further research that improves app feasibility and establishes efficacy in targeting the domains most relevant to CSOs is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02486705; https://clinicaltrials.gov/ct2/show/NCT02486705.

LINE-1 ORF1p as a candidate biomarker in high grade serous ovarian carcinoma.

Long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients' plasma, implicating ORF1p as a potential biomarker. Interestingly, ORF1p expression is detectable in fallopian tube (FT) epithelial precursors of HGSOC but not in benign FT, suggesting that ORF1p expression in an early event in HGSOC development. Finally, treatment of FT cells with DNA methyltransferase inhibitors led to robust expression and release of ORF1p, validating the regulatory role of DNA methylation in LINE-1 repression in non-tumorigenic tissue.

Internet-based family training with telephone coaching to promote mental health treatment initiation among veterans with posttraumatic stress disorder: A pilot study.

Posttraumatic stress disorder (PTSD) is common among military veterans, yet many affected veterans do not seek treatment. Family members of these veterans often experience compromised well-being and a desire for the veteran to receive mental health care. The Veterans Affairs (VA)-Community Reinforcement and Family Training (VA-CRAFT) for PTSD is an internet-based intervention intended to teach veterans' family members skills to encourage veterans to initiate mental health care. This study assessed the feasibility, acceptability, and potential efficacy of VA-CRAFT with telephone coaching in a sample of 12 spouses and intimate partners of veterans with PTSD. Participants completed the intervention over 12 weeks and were assessed pre- and posttreatment. For feasibility, 75.0% (n = 9) of participants completed the intervention and reported few difficulties and ease of use. Supporting acceptability, all nine completers had mostly favorable impressions of the intervention and perceived it as helpful. Finally, six (50.0%) participants got the PTSD-affected veteran to engage in mental health care; however, aside from potentially increasing treatment talk frequency, outcome expectancy, and self-efficacy, ds = 0.60-1.08, no apparent improvements were observed for any well-being outcomes, ds = 0.01-0.40. Although the findings are promising, given the study limitations, future research is required to evaluate this approach in a full-scale randomized controlled trial.

Peer-supported mobile mental health for veterans in primary care: A pilot study.

One in four veteran primary care patients suffers from a mental health condition; however, most do not receive any treatment for these problems. Mobile health (mHealth) can overcome barriers to care access, but poor patient engagement limits the effectiveness and implementation of these tools. Peers may facilitate patient engagement with mHealth. We designed a protocol for peers to support implementation of mobile mental health tools in primary care and tested the feasibility, acceptability, and clinical utility of this approach. Thirty-nine patients across two Veterans Affairs sites who screened positive for depression during a primary care visit and were not currently in mental health treatment were enrolled. Participants were scheduled for four phone sessions with a peer over 8 weeks and introduced to five mobile apps for a range of transdiagnostic mental health issues (stress, low mood, sleep problems, anger, and trauma). Pre/post phone interviews using quantitative and qualitative approaches assessed participants' self-reported app use, satisfaction with the intervention, symptom change (stress, anxiety, depression, insomnia), and progress with personal health goals. On average, patients reported using 3.04 apps (SD = 1.46). Per the Client Satisfaction Questionnaire, global satisfaction with the intervention was high (M = 25.71 out of 32, SD = 3.95). Pre to post participants reported significant improvements in their level of stress, based on a quantitative measure (p = .008), and 87% reported progress on at least one personal health goal. Findings support the feasibility, acceptability, and clinical utility of peer-supported mobile mental health for veterans in primary care. A randomized controlled trial of an adaptive version of this intervention is recommended. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Primary adrenal insufficiency masking as an adrenal B-cell lymphoma.

We report here a woman in her 70s presenting with adrenal insufficiency secondary to a primary adrenal lymphoma. The patient had a previous history of aphthous ulcers on dexamethasone and was referred to endocrinology with symptoms of fatigue and orthostasis. Subsequent Cosyntropin stimulation showed primary adrenal insufficiency and adrenal CT demonstrated large infiltrative masses. Adrenal biopsy confirmed the diagnosis of primary adrenal lymphoma of the B-cell type. This case demonstrates the importance of including lymphoma in the differential diagnosis of adrenal insufficiency, particularly in the elderly population and in the setting of negative 21-hydroxlyase antibody results.

What will it take to stabilize the Colorado River?

A continuation of the current 23-year-long drought will require difficult decisions to prevent further decline.

A Pilot Randomized Controlled Trial of the Insomnia Coach Mobile App to Assess Its Feasibility, Acceptability, and Potential Efficacy.

Insomnia is highly prevalent among military veterans but access to cognitive-behavioral therapy for insomnia (CBT-I) is limited. Thus, this study examined the feasibility, acceptability, and potential efficacy of Insomnia Coach, a CBT-I-based, free, self-management mobile app. Fifty U.S. veterans, who were mostly male (58%) and mean age 44.5 (range = 28-55) years with moderate insomnia symptoms were randomized to Insomnia Coach (n = 25) or a wait-list control condition (n = 25) for 6 weeks. Participants completed self-report measures and sleep diaries at baseline, posttreatment, and follow-up (12 weeks postrandomization), and app participants (n = 15) completed a qualitative interview at posttreatment. Findings suggest that Insomnia Coach is feasible to use, with three quarters of participants using the app through 6 weeks and engaging with active elements. For acceptability, perceptions of Insomnia Coach were very favorable based on both self-report and qualitative interview responses. Finally, for potential efficacy, at posttreatment, a larger proportion of Insomnia Coach (28%) than wait-list control participants (4%) achieved clinically significant improvement (p = .049) and there was a significant treatment effect on daytime sleep-related impairment (d = -0.6, p = .044). Additional treatment effects emerged at follow-up for insomnia severity (d = -1.1, p = .001), sleep onset latency (d = -0.6, p = .021), global sleep quality (d = -0.9, p = .002), and depression symptoms (d = -0.8, p = .012). These findings provide preliminary evidence that among veterans with moderate insomnia symptoms, a CBT-I-based self-management app is feasible, acceptable, and promising for improving insomnia severity and other sleep-related outcomes. Given the vast unmet need for insomnia treatment in the population, Insomnia Coach may provide an easily accessible, convenient public health intervention for individuals not receiving care.

PTSD Coach Version 3.1: A Closer Look at the Reach, Use, and Potential Impact of This Updated Mobile Health App in the General Public.

BACKGROUND: With widespread smartphone ownership, mobile health apps (mHealth) can expand access to evidence-based interventions for mental health conditions, including posttraumatic stress disorder (PTSD). Research to evaluate new features and capabilities in these apps is critical but lags behind app development. The initial release of PTSD Coach, a free self-management app developed by the US Departments of Veterans Affairs and Defense, was found to have a positive public health impact. However, major stakeholder-driven updates to the app have yet to be evaluated. OBJECTIVE: We aimed to characterize the reach, use, and potential impact of PTSD Coach Version 3.1 in the general public. As part of characterizing use, we investigated the use of specific app features, which extended previous work on PTSD Coach. METHODS: We examined the naturalistic use of PTSD Coach during a 1-year observation period between April 20, 2020, and April 19, 2021, using anonymous in-app event data to generate summary metrics for users. RESULTS: During the observation period, PTSD Coach was broadly disseminated to the public, reaching approximately 150,000 total users and 20,000 users per month. On average, users used the app 3 times across 3 separate days for 18 minutes in total, with steep drop-offs in use over time; a subset of users, however, demonstrated high or sustained engagement. More than half of users (79,099/128,691, 61.46%) accessed one or more main content areas of the app (ie, Manage Symptoms, Track Progress, Learn, or Get Support). Among content areas, features under Manage Symptoms (including coping tools) were accessed most frequently, by over 40% of users (53,314/128,691, 41.43% to 56,971/128,691, 44.27%, depending on the feature). Users who provided initial distress ratings (56,971/128,691, 44.27%) reported relatively high momentary distress (mean 6.03, SD 2.52, on a scale of 0-10), and the use of a coping tool modestly improved momentary distress (mean -1.38, SD 1.70). Among users who completed at least one PTSD Checklist for DSM-5 (PCL-5) assessment (17,589/128,691, 13.67%), PTSD symptoms were largely above the clinical threshold (mean 49.80, SD 16.36). Among users who completed at least two PCL-5 assessments (4989/128,691, 3.88%), PTSD symptoms decreased from the first to last assessment (mean -4.35, SD 15.29), with approximately one-third (1585/4989, 31.77%) of these users experiencing clinically significant improvements. CONCLUSIONS: PTSD Coach continues to fulfill its mission as a public health resource. Version 3.1 compares favorably with version 1 on most metrics related to reach, use, and potential impact. Although benefits appear modest on an individual basis, the app provides these benefits to a large population. For mHealth apps to reach their full potential in supporting trauma recovery, future research should aim to understand the utility of individual app features and identify strategies to maximize overall effectiveness and engagement.

Regional variability and genotypic and pharmacodynamic effects on PrP concentration in the CNS.

Prion protein (PrP) concentration controls the kinetics of prion replication and is a genetically and pharmacologically validated therapeutic target for prion disease. In order to evaluate PrP concentration as a pharmacodynamic biomarker and assess its contribution to known prion disease risk factors, we developed and validated a plate-based immunoassay reactive for PrP across 6 species of interest and applicable to brain and cerebrospinal fluid (CSF). PrP concentration varied dramatically across different brain regions in mice, cynomolgus macaques, and humans. PrP expression did not appear to contribute to the known risk factors of age, sex, or common PRNP genetic variants. CSF PrP was lowered in the presence of rare pathogenic PRNP variants, with heterozygous carriers of P102L displaying 55%, and D178N just 31%, of the CSF PrP concentration of mutation-negative controls. In rodents, pharmacologic reduction of brain Prnp RNA was reflected in brain parenchyma PrP and, in turn in CSF PrP, validating CSF as a sampling compartment for the effect of PrP-lowering therapy. Our findings support the use of CSF PrP as a pharmacodynamic biomarker for PrP-lowering drugs and suggest that relative reduction from individual baseline CSF PrP concentration may be an appropriate marker for target engagement.

Targeted mass spectrometry-based assays enable multiplex quantification of receptor tyrosine kinase, MAP Kinase, and AKT signaling.

SUMMARY: A primary goal of the US National Cancer Institute's Ras initiative at the Frederick National Laboratory for Cancer Research is to develop methods to quantify RAS signaling to facilitate development of novel cancer therapeutics. We use targeted proteomics technologies to develop a community resource consisting of 256 validated multiple reaction monitoring (MRM)-based, multiplexed assays for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. As proof of concept, we quantify the response of melanoma (A375 and SK-MEL-2) and colorectal cancer (HCT-116 and HT-29) cell lines to BRAF inhibition by PLX-4720. These assays replace over 60 Western blots with quantitative mass spectrometry-based assays of high molecular specificity and quantitative precision, showing the value of these methods for pharmacodynamic measurements and mechanism of action studies. Methods, fit-for-purpose validation, and results are publicly available as a resource for the community at assays.cancer.gov. MOTIVATION: A lack of quantitative, multiplexable assays for phosphosignaling limits comprehensive investigation of aberrant signaling in cancer and evaluation of novel treatments. To alleviate this limitation, we sought to develop assays using targeted mass spectrometry for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. The resulting assays provide a resource for replacing over 60 Western blots in examining cancer signaling and tumor biology with high molecular specificity and quantitative rigor.