Preliminary Investigation Into the Effectiveness of Group webSTAIR for Trauma-exposed Veterans in Primary Care.

INTRODUCTION: A substantial number of trauma-exposed veterans seen in primary care report significant symptoms of PTSD and depression. While primary care mental health integration (PCMHI) providers have been successful in delivering brief mental health treatments in primary care, few studies have evaluated interventions that combine mobile health resources with PCMHI groups. This pilot study assessed the potential benefits of webSTAIR, a 10-module transdiagnostic treatment for trauma-exposed individuals, supported by 5 biweekly group sessions delivered via telehealth. The transdiagnostic and mobile health nature of the treatment, as well as the therapist and peer support provided through group sessions, may offer an innovative approach to increasing access to patient-centered and trauma-informed treatment in primary care settings. MATERIALS AND METHODS: Thirty-nine male and female veterans with trauma-related symptoms (i.e., PTSD and/or depression) participated in group webSTAIR. Mixed effects analyses were conducted to assess changes in PTSD and depression at pre-, mid-, and post-treatment. Baseline symptom severity was assessed as a predictor of module completion and group attendance. The project was part of a VHA quality improvement project, and IRB approval was waived by the affiliated university. RESULTS: Analyses revealed significant pre-to-post improvement in both PTSD and depression outcomes with a large effect size for PTSD (Hedges' gav = 0.88) and medium to large for depression (Hedges' gav = 0.73). Of participants who completed the baseline assessment, 90% began webSTAIR; of those, 71% completed the program. Baseline symptoms of PTSD and depression did not predict group attendance or module completion. CONCLUSIONS: Good outcomes and a satisfactory retention rate suggest that group webSTAIR may provide easily accessible, high-quality, and effective treatment for patients presenting with trauma-related problems without increasing therapist or system burdens. The results suggest the value of conducting a randomized controlled trial to test the effectiveness of group webSTAIR relative to PCMHI usual care or other evidence-based, disorder-specific (e.g., PTSD) treatments for trauma-exposed individuals in PCMHI.

Cinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial.

BACKGROUND AND OBJECTIVES: Sensitive, reliable, and scalable biomarkers are needed to accelerate the development of therapies for Parkinson disease (PD). In this study, we evaluate the biomarkers of early PD diagnosis, disease progression, and treatment effect collected in the SPARK. METHODS: Cinpanemab is a human-derived monoclonal antibody binding preferentially to aggregated forms of extracellular α-synuclein. SPARK was a randomized, double-blind, placebo-controlled, phase 2 multicenter trial evaluating 3 cinpanemab doses administered intravenously every 4 weeks for 52 weeks with an active treatment dose-blind extension period for up to 112 weeks. SPARK enrolled 357 participants diagnosed with PD within 3 years, aged 40-80 years, ≤2.5 on the modified Hoehn and Yahr scale, and with evidence of striatal dopaminergic deficit. The primary outcome was change from baseline in the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale total score. Secondary and exploratory biomarker outcomes evaluated change from baseline at week 52 relative to placebo. Dopamine transporter SPECT and MRI were used to quantify changes in the nigrostriatal dopamine pathway and regional atrophy. CSF and plasma samples were used to assess change in total α-synuclein levels, α-synuclein seeding, and neurofilament light chain levels. SPARK was conducted from January 2018 to April 2021 and terminated due to lack of efficacy. RESULTS: Approximately 3.8% (15/398) of SPECT-imaged participants did not have evidence of dopaminergic deficit and were screen-failed. Binary classification of α-synuclein seeding designated 93% (110/118) of the enrolled CSF subgroup as positive for α-synuclein seeds at baseline. Clinical disease progression was observed, with no statistically significant difference in cinpanemab groups compared with that in placebo. Ninety-nine percent of participants with positive α-synuclein seeding remained positive through week 52. No statistically significant changes from baseline were observed between treatment groups and placebo across biomarker measures. Broadly, there was minimal annual change with high interindividual variability across biomarkers-with striatal binding ratios of the ipsilateral putamen showing the greatest mean change/SD over time. DISCUSSION: Biomarker results indicated enrollment of the intended population with early PD, but there was no significant correlation with disease progression or clear evidence of a cinpanemab treatment effect on biomarker measures. Suitable biomarkers for evaluating disease severity and progression in early PD trials are still needed. TRIAL REGISTRATION INFORMATION: NCT03318523 (clinicaltrials.gov/ct2/show/NCT03318523); Submitted October 24, 2017; First patient enrolled January 2018.

An Evaluation of an ACT-Based "Aging Resiliently" Group.

OBJECTIVES: There were two quality improvement aims in this project: (1) to evaluate the outcomes of a six-week closed geriatric focused Acceptance and Commitment Therapy (ACT)-based group called "Aging Resiliently" offered in a primary care setting, and (2) to obtain feedback from group members in order to make relevant modifications to future groups. METHODS: Four cohorts of veterans ages 58 and older participated in the group (N = 17). Paired samples t-tests were computed to determine the significance of changes on pre- and post- self-report measures of depression, experiential avoidance, and life satisfaction. Veterans also provided feedback in the form of an open-ended feedback questionnaire. RESULTS: There were statistically significant improvements in depressive symptoms and satisfaction with life, but not in experiential avoidance. Two major themes emerged from the feedback questionnaire about what group members found to be the most helpful: (1) self-reflection/values, and (2) the social process of the group. CONCLUSIONS: At our institution, the Aging Resiliently group yielded meaningful outcomes for older veterans presenting with different problems related to aging. CLINICAL IMPLICATIONS: This Aging Resiliently group proved to be a potential effective, feasible, and acceptable psychotherapy for older veterans in our established local primary care setting.

Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension.

Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6- and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P<0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P<0.001; 356.4 mL/24 hours, P=0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: -20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681576.

Acute hydrocortisone treatment increases anxiety but not fear in healthy volunteers: a fear-potentiated startle study.

BACKGROUND: The debilitating effects of chronic glucocorticoids excess are well-known, but comparatively little is understood about the role of acute cortisol. Indirect evidence in rodents suggests that acute cortisone could selectively increase some forms of long-duration aversive states, such as "anxiety," but not relatively similar, briefer aversive states, such as "fear." However, no prior experimental studies in humans consider the unique effects of cortisol on anxiety and fear, using well-validated methods for eliciting these two similar but dissociable aversive states. The current study examines these effects, as instantiated with short- and long-duration threats. METHODS: Healthy volunteers (n = 18) received placebo or a low (20 mg) or a high (60 mg) dose of hydrocortisone in a double-blind crossover design. Subjects were exposed repeatedly to three 150-sec duration conditions: no shock; predictable shocks, in which shocks were signaled by a short-duration threat cue; and unpredictable shocks. Aversive states were indexed by acoustic startle. Fear was operationally defined as the increase in startle reactivity during the threat cue in the predictable condition (fear-potentiated startle). Anxiety was operationally defined as the increase in baseline startle from the no shock to the two threat conditions (anxiety-potentiated startle). RESULTS: Hydrocortisone affected neither baseline nor short-duration, fear-potentiated startle but increased long-duration anxiety-potentiated startle. CONCLUSIONS: These results suggest that hydrocortisone administration in humans selectively increases anxiety but not fear. Possible mechanisms implicated are discussed in light of prior data in rodents. Specifically, hydrocortisone might increase anxiety via sensitization of corticotrophin-releasing hormones in the bed nucleus of the stria terminalis.