Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands.

The vascular endothelium from individual organs is functionally specialized, and it displays a unique set of accessible molecular targets. These serve as endothelial cell receptors to affinity ligands. To date, all identified vascular receptors have been proteins. Here, we show that an endothelial lung-homing peptide (CGSPGWVRC) interacts with C16-ceramide, a bioactive sphingolipid that mediates several biological functions. Upon binding to cell surfaces, CGSPGWVRC triggers ceramide-rich platform formation, activates acid sphingomyelinase and ceramide production, without the associated downstream apoptotic signaling. We also show that the lung selectivity of CGSPGWVRC homing peptide is dependent on ceramide production in vivo. Finally, we demonstrate two potential applications for this lipid vascular targeting system: i) as a bioinorganic hydrogel for pulmonary imaging and ii) as a ligand-directed lung immunization tool against COVID-19. Thus, C16-ceramide is a unique example of a lipid-based receptor system in the lung vascular endothelium targeted in vivo by circulating ligands such as CGSPGWVRC.

Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain.

Development of effective vaccines against coronavirus disease 2019 (COVID-19) is a global imperative. Rapid immunization of the entire human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and different vaccine approaches are being pursued. Engineered filamentous bacteriophage (phage) particles have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the development and initial evaluation of two targeted phage-based vaccination approaches against SARS-CoV-2: dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. For peptide-targeted phage, we performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike (S) protein. One of these epitopes displayed on the major capsid protein pVIII of phage induced a specific and sustained humoral response when injected in mice. These phage were further engineered to simultaneously display the peptide CAKSMGDIVC on the minor capsid protein pIII to enable their transport from the lung epithelium into the systemic circulation. Aerosolization of these "dual-display" phage into the lungs of mice generated a systemic and specific antibody response. In the second approach, targeted AAVP particles were engineered to deliver the entire S protein gene under the control of a constitutive CMV promoter. This induced tissue-specific transgene expression, stimulating a systemic S protein-specific antibody response in mice. With these proof-of-concept preclinical experiments, we show that both targeted phage- and AAVP-based particles serve as robust yet versatile platforms that can promptly yield COVID-19 vaccine prototypes for translational development.

Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection.

Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662-C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus.

Next-generation of targeted AAVP vectors for systemic transgene delivery against cancer.

Bacteriophage (phage) have attractive advantages as delivery systems compared with mammalian viruses, but have been considered poor vectors because they lack evolved strategies to confront and overcome mammalian cell barriers to infective agents. We reasoned that improved efficacy of delivery might be achieved through structural modification of the viral capsid to avoid pre- and postinternalization barriers to mammalian cell transduction. We generated multifunctional hybrid adeno-associated virus/phage (AAVP) particles to enable simultaneous display of targeting ligands on the phage's minor pIII proteins and also degradation-resistance motifs on the very numerous pVIII coat proteins. This genetic strategy of directed evolution bestows a next-generation of AAVP particles that feature resistance to fibrinogen adsorption or neutralizing antibodies and ability to escape endolysosomal degradation. This results in superior gene transfer efficacy in vitro and also in preclinical mouse models of rodent and human solid tumors. Thus, the unique functions of our next-generation AAVP particles enable improved targeted gene delivery to tumor cells.

Combination outreach and wellness intervention for distressed rural veterans: results of a multimethod pilot study.

We partnered with veteran-serving nonprofits in order to identify distressed rural veterans and provide them with a mental health workshop in community-based settings. Community organizations helped recruit veterans and provided space for 1-day (5-h) Acceptance and Commitment Therapy (ACT) group workshops conducted in rural locations. Qualitative interviews were conducted at 1- and 3-months post-intervention to assess acceptability. Quantitative measures were conducted at baseline, 1- and 3-months post-intervention to measure effectiveness. We successfully engaged community partners throughout every stage of the research and delivered workshops to thirty-one veterans in rural community-based locations. Veterans appreciated the structure, content, and environment of the workshops; most implemented ACT skills into their daily lives and some initiated new treatment following workshop participation. Quantitative measures showed improvements in functioning (Cohen's d ranging from .27 to .40), reintegration (Cohen's d = .45), meaning and purpose (Cohen's d = .40), and reductions in distress (Cohen's d ranging from .28 to .40) 3-months following workshop participation. Collaborating with rural veteran-serving nonprofit organizations holds promise for engaging hard-to-reach distressed veterans in mental health care.

Comparing integrative cognitive-affective therapy and guided self-help cognitive-behavioral therapy to treat binge-eating disorder using standard and naturalistic momentary outcome measures: A randomized controlled trial.

OBJECTIVE: Innovative treatments and outcome measures are needed for binge-eating disorder (BED). This randomized controlled trial compared Integrative Cognitive-Affective Therapy (ICAT-BED), an individual psychotherapy targeting momentary behavioral and emotional precipitants of binge eating, with an established cognitive-behavioral guided self-help (CBTgsh) treatment using standard and ecological momentary assessment (EMA) outcome measures. METHOD: A total of 112 participants were randomized to 17 weeks of treatment (21 sessions for ICAT-BED and 10 sessions for CBTgsh). Binge-eating frequency was assessed with the Eating Disorder Examination (EDE) as well as EMA using cell phone-based real-time, naturalistic assessment at end of treatment (EOT) and 6-month follow-up. Hypothesized maintenance mechanisms were assessed using self-report questionnaires. RESULTS: Binge-eating frequency as measured by the EDE and real-time assessment showed significant reductions at EOT and follow-up, with no significant differences between treatments. Hypothesized maintenance mechanisms, including emotion regulation, cognitive self-discrepancy, self-directed style, as well as measures of associated eating disorder psychopathology, depression, anxiety, impulsivity, and negative affect, showed similar improvement at EOT and follow-up with no differences between treatments. Abstinence rates at EOT (ICAT-BED: 57.1%; CBTgsh: 42.9%) and 6-month follow-up (ICAT-BED: 46.4%; CBTgsh: 42.9%) were not significantly different. Treatment retention was significantly higher for ICAT-BED (87.5%) than CBTgsh (71.4%). DISCUSSION: These findings suggest that ICAT-BED and CBTgsh were associated with similar improvements in binge eating, psychopathology, and putative maintenance mechanisms as measured by traditional self-report and momentary, naturalistic assessments and that these changes were generally sustained at 6-month follow-up.

Meropenem as an antidote for intentional valproic acid overdose.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug indicated for monotherapy and adjunctive therapy of seizures, and complex manic episodes associated with bipolar disorder [1]. While uncommon due to monitoring, VPA can cause toxicity at supratherapeutic levels [1, 2]. Traditional treatment for VPA toxicity is primarily supportive care, however activated charcoal, l-carnitine, and hemodialysis have been successful in removing free VPA [2]. An interaction between carbapenem antibiotics and VPA is well-established and listed in respective package inserts as a combination to be avoided due to decreased VPA efficacy [1, 3]. Recent literature suggests co-administration of meropenem with VPA reduces mean plasma VPA levels by 50-80% [4, 6]. This case report describes the successful use of carbapenems to intentionally lower toxic VPA levels in a 42 year old female that presented to the emergency department with VPA toxicity from an overdose with divalproex sodium.

Patterns of Treatment Disengagement and Personality Traits Associated With Posttraumatic Stress Disorder in Recent-Era U.S. Veterans Receiving Cognitive Processing Therapy.

Low treatment engagement is a barrier to implementation of empirically supported treatments for posttraumatic stress disorder (PTSD) among veterans. Understanding personality traits that predict dropout may help focus attempts to improve engagement. The current study included 90 veterans who served in recent conflicts in Iraq and/or Afghanistan and participated in a trial of cognitive processing therapy for PTSD. Goals were to characterize (a) personality correlates of PTSD, (b) patterns of engagement (i.e., attendance and homework completion), and (c) personality correlates of reduced engagement. Higher levels of PTSD symptoms were associated with a range of characteristics, including affective lability, r = .44 p < .001; anxiety, r = .38, p < .001; identity problems, r = .57, p < .001; intimacy problems, r = .34, p = .001; low affiliation, r = .33, p = .002; oppositionality, r = .36, p = .001; restricted expression, r = .35, p = .001; and suspiciousness, r = .50, p < .001. Notably, veterans with worse PTSD symptoms endorsed more cognitive dysregulation, r = .40, p < .001; and less insecure attachment, r = .14, p = .190, than expected. Only 52.2% of veterans completed the 12-session course of treatment and 31.0% of participants completed fewer than six sessions. Personality traits did not predict attendance or homework completion. Disengagement continues to be a significant issue in trauma-focused treatment for veterans with PTSD. Understanding veteran-level factors, such as personality traits, may be useful considerations for future research seeking to understand and improve engagement.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Patrones de desconexión del tratamiento y rasgos de personalidad asociados con el trastorno de estrés postraumático en Recientes Veteranos Estadounidenses que reciben terapia de procesamiento cognitivo DESCONEXIÓN DEL TRATAMIENTO Y PERSONALIDAD EN VETERANOS El bajo compromiso con el tratamiento es una barrera para la implementación de tratamientos con apoyo empírico para el trastorno de estrés postraumático (TEPT) entre los veteranos. Comprender los rasgos de personalidad que predicen el abandono puede ayudar a enfocar los intentos de mejorar el compromiso con el tratamiento en esta población. El estudio actual incluyó una muestra de 90 veteranos que habían servido en conflictos recientes en Irak y / o Afganistán y que estaban inscritos en el ensayo de terapia de procesamiento cognitivo para el TEPT. Los objetivos principales del estudio fueron (a) describir los correlatos de la personalidad y el TEPT de los veteranos, (b) caracterizar los patrones de compromiso (es decir, la asistencia y la finalización de la tarea), y (c) identificar los rasgos de personalidad asociados con el poco compromiso . Los niveles más altos de síntomas de TEPT se asociaron con una amplia gama de problemas de personalidad, incluida la labilidad afectiva, ansiedad, desregulación cognitiva, problemas de identidad, problemas de intimidad, baja afiliación, oposicionismo, expresión restringida y desconfianza. En particular, los veteranos con niveles más altos de síntomas de TEPT mostraron más desregulación cognitiva y menos problemas con el apego inseguro de lo esperado. Solo el 52.2% de los veteranos completaron el curso de tratamiento de 12 sesiones. Casi un tercio de los participantes (31.0%) completó menos de seis sesiones. Los rasgos de personalidad no fueron predictivos de la asistencia o la finalización de la tarea en el presente estudio. El abandono del tratamiento con apoyo empírico sigue siendo un problema importante en el tratamiento centrado en el trauma para los veteranos con TEPT. Comprender los factores a nivel de veteranos, como los rasgos de personalidad, puede ser una consideración útil para futuras investigaciones que buscan comprender y mejorar el compromiso con el tratamiento.

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas.

Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived. Here we designed a hybrid adeno-associated virus and phage (AAVP) vector displaying biologically active octreotide on the viral surface for ligand-directed delivery, cell internalization, and transduction of an apoptosis-promoting tumor necrosis factor (TNF) transgene specifically to NETs. These functional attributes of AAVP-TNF particles displaying the octreotide peptide motif (termed Oct-AAVP-TNF) were confirmed in vitro, in SSTR type 2-expressing NET cells, and in vivo using cohorts of pancreatic NET-bearing Men1 tumor-suppressor gene KO mice, a transgenic model of functioning (i.e., insulin-secreting) tumors that genetically and clinically recapitulates the human disease. Finally, preclinical imaging and therapeutic experiments with pancreatic NET-bearing mice demonstrated that Oct-AAVP-TNF lowered tumor metabolism and insulin secretion, reduced tumor size, and improved mouse survival. Taken together, these proof-of-concept results establish Oct-AAVP-TNF as a strong therapeutic candidate for patients with NETs of the pancreas. More broadly, the demonstration that a known, short, biologically active motif can direct tumor targeting and receptor-mediated internalization of AAVP particles may streamline the potential utility of myriad other short peptide motifs and provide a blueprint for therapeutic applications in a variety of cancers and perhaps many nonmalignant diseases as well.

Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial-melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell-cell interactions at the lymphatic-tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer: Analysis of Clinical Samples and BMTP-11 Preclinical Activity.

We previously isolated an IL-11-mimic motif (CGRRAGGSC) that binds to IL-11 receptor (IL-11R) in vitro and accumulates in IL-11R-expressing tumors in vivo. This synthetic peptide ligand was used as a tumor-targeting moiety in the rational design of BMTP-11, which is a drug candidate in clinical trials. Here, we investigated the specificity and accessibility of IL-11R as a target and the efficacy of BMTP-11 as a ligand-targeted drug in lung cancer. We observed high IL-11R expression levels in a large cohort of patients (n = 368). In matching surgical specimens (i.e., paired tumors and nonmalignant tissues), the cytoplasmic levels of IL-11R in tumor areas were significantly higher than in nonmalignant tissues (n = 36; P = 0.003). Notably, marked overexpression of IL-11R was observed in both tumor epithelial and vascular endothelial cell membranes (n = 301; P < 0.0001). BMTP-11 induced in vitro cell death in a representative panel of human lung cancer cell lines. BMTP-11 treatment attenuated the growth of subcutaneous xenografts and reduced the number of pulmonary tumors after tail vein injection of human lung cancer cells in mice. Our findings validate BMTP-11 as a pharmacologic candidate drug in preclinical models of lung cancer and patient-derived tumors. Moreover, the high expression level in patients with non-small cell lung cancer is a promising feature for potential translational applications.

The effects of psychotherapy treatment on outcome in bulimia nervosa: Examining indirect effects through emotion regulation, self-directed behavior, and self-discrepancy within the mediation model.

OBJECTIVE: The purpose of this investigation was to examine the indirect effects of Integrative Cognitive-Affective Therapy (ICAT-BN) and Cognitive-Behavioral Therapy-Enhanced (CBT-E) on bulimia nervosa (BN) treatment outcome through three hypothesized maintenance variables: emotion regulation, self-directed behavior, and self-discrepancy. METHOD: Eighty adults with BN were randomized to 21 sessions of ICAT-BN or CBT-E. A regression-based bootstrapping approach was used to test the indirect effects of treatment on outcome at end of treatment through emotion regulation and self-directed behavior measured at mid-treatment, as well as the indirect effects of treatment at follow-up through emotion regulation, self-directed behavior, and self-discrepancy measured at end of treatment. RESULTS: No significant differences in outcome between treatment conditions were observed, and no significant direct or indirect effects were found. Examination of the individual paths within the indirect effects models revealed comparable treatment effects. Across treatments, improvements in emotion regulation and self-directed behavior between baseline and mid-treatment predicted improvements in global eating disorder scores but not binge eating and purging frequency at end of treatment. Baseline to end of treatment improvements in emotion regulation and self-directed behavior also predicted improvements in global eating disorder scores at follow-up. Baseline to end of treatment improvements in emotion regulation predicted improvements in binge eating and baseline to end of treatment increases in positive self-directed behavior predicted improvements in purging at follow-up. DISCUSSION: These findings suggest that emotion regulation and self-directed behavior are important treatment targets and that ICAT-BN and CBT-E are comparable in modifying these psychological processes among individuals with BN.

Self-weighing behavior in individuals with eating disorders.

OBJECTIVE: To describe the frequency of self-weighing and reactions to prescribed weekly weighing among individuals with eating disorder (ED) diagnoses, and to compare individuals weighing more or less frequently on mass index (BMI) and the Eating Disorder Examination (EDE) subscales. METHOD: Baseline EDE and demographics from five studies (N = 758). RESULTS: Self-weighing was most frequent among individuals with anorexia nervosa (AN), followed by those with bulimia nervosa (BN) and binge eating disorder (BED). On average, participants reacted moderately negative to prescribed weekly weighing. No relationship between weighing frequency and BMI was evident in any sample. There was indication of greater pathology (i.e., restraint, shape concern, weight concern, global) in AN with more frequent weighing. In BN, mixed evidence emerged to support a relationship between more frequent weighing and higher shape concern, weight concern, and global score. In BED, higher restraint was found in those who weighed versus those who did not. DISCUSSION: Weighing frequency in each eating disorder (ED) sample was to some extent associated with greater ED severity, but not BMI. Future research should examine relationships between self-weighing, reactions to changing weighing frequency, and ED symptomatology in both ED and non-ED groups to understand the impact of self-weighing in heterogeneous populations. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:817-821).

Association between objective and subjective binge eating and psychopathology during a psychological treatment trial for bulimic symptoms.

Although loss of control (LOC) while eating is a core construct of bulimia nervosa (BN), questions remain regarding its validity and prognostic significance independent of overeating. We examined trajectories of objective and subjective binge eating (OBE and SBE, respectively; i.e., LOC eating episodes involving an objectively or subjectively large amount of food) among adults participating in psychological treatments for BN-spectrum disorders (n = 80). We also explored whether changes in the frequency of these eating episodes differentially predicted changes in eating-related and general psychopathology and, conversely, whether changes in eating-related and general psychopathology predicted differential changes in the frequency of these eating episodes. Linear mixed models with repeated measures revealed that OBE decreased twice as rapidly as SBE throughout treatment and 4-month follow-up. Generalized linear models revealed that baseline to end-of-treatment reductions in SBE frequency predicted baseline to 4-month follow-up changes in eating-related psychopathology, depression, and anxiety, while changes in OBE frequency were not predictive of psychopathology at 4-month follow-up. Zero-inflation models indicated that baseline to end-of-treatment changes in eating-related psychopathology and depression symptoms predicted baseline to 4-month follow-up changes in OBE frequency, while changes in anxiety and self-esteem did not. Baseline to end-of-treatment changes in eating-related psychopathology, self-esteem, and anxiety predicted baseline to 4-month follow-up changes in SBE frequency, while baseline to end-of-treatment changes in depression did not. Based on these findings, LOC accompanied by objective overeating may reflect distress at having consumed an objectively large amount of food, whereas LOC accompanied by subjective overeating may reflect more generalized distress related to one's eating- and mood-related psychopathology. BN treatments should comprehensively target LOC eating and related psychopathology, particularly in the context of subjectively large episodes, to improve global outcomes.

Self-Discrepancy and Eating Disorder Symptoms Across Eating Disorder Diagnostic Groups.

This study examined self-discrepancy, a construct of theoretical relevance to eating disorder (ED) psychopathology, across different types of EDs. Individuals with anorexia nervosa (AN; n = 112), bulimia nervosa (BN; n = 72), and binge eating disorder (BED; n = 199) completed semi-structured interviews assessing specific types of self-discrepancies. Results revealed that actual:ideal (A:I) discrepancy was positively associated with AN, actual:ought (A:O) discrepancy was positively associated with BN and BED, and self-discrepancies did not differentiate BN from BED. Across diagnoses, A:O discrepancy was positively associated with severity of purging, binge eating, and global ED psychopathology. Further, there were significant interactions between diagnosis and A:O discrepancy for global ED psychopathology and between diagnosis and A:I discrepancy for binge eating and driven exercise. These results support the importance of self-discrepancy as a potential causal and maintenance variable in EDs that differentiates among different types of EDs and symptom severity. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Effects of Cognitive Behavioral Stress Management on Negative Mood and Cardiac Autonomic Activity in ICD Recipients.

BACKGROUND: Behavioral intervention studies in patients with an implantable cardioverter-defibrillator (ICD) show promise in improving psychosocial outcomes but inconclusive effects on cardiovascular outcome. We assessed the effects of cognitive behavioral stress management (CBSM) on mood state and potentially arrhythmogenic cardiovascular responses to mental stress in ICD patients, in support of further larger scale arrhythmia trials. METHODS: A total of 103 ICD recipients were randomly assigned to 10-week programs of CBSM or "Patient Education" (ED). Of these, 83 patients continued to either CBSM (n = 44) or ED (n = 39) intervention. Study end points were mood change, heart rate variability (HRV), double product elevation (DP = heart rate × systolic blood pressure) by math and anger-recall stress, and arrhythmia up to 6 months follow-up. RESULTS: Adjusting for multiple testing, CBSM was associated with moderate effect size reductions in tension/anxiety (P = 0.010), anger/hostility (P = 0.020), perceived stress (P = 0.037), and total mood disturbance (P = 0.025), greatest immediately following intervention (P < 0.05), and partially attributable to increased negative mood following ED (P < 0.01). No significant intervention effects on high frequency or low frequency spectral power of HRV, DP responses, or cardiac arrhythmias were demonstrated. CONCLUSIONS: CBSM intervention in ICD recipients resulted in reduced anxiety, anger, and perceived stress, not sustained at 6 months follow-up, and without conclusive effect on cardiac autonomic or hemodynamic responses to mental stress, or arrhythmia. Findings support conduct of larger behavioral intervention arrhythmia trial, with consideration of reinforcement training and targeting of subgroup responders to therapy.

Fear of Losing Emotional Control Is Associated With Cognitive Processing Therapy Outcomes in U.S. Veterans of Afghanistan and Iraq.

Evidence-based treatments for posttraumatic stress disorder (PTSD) can reduce symptoms and improve veterans' psychological health. Unfortunately, many veterans leave treatment before receiving maximum benefit. Fear of emotions is related to severity of PTSD, and changes in fear of emotions are correlated with changes in PTSD symptoms. This study built upon the literature linking greater fear of emotions to PTSD severity by examining whether pretreatment fear of emotions, measured by the Affect Control Scale, was associated with completion of cognitive processing therapy (CPT) and severity of posttreatment PTSD in a sample of 89 U.S. veterans who had served in Afghanistan and Iraq. About 60% of veterans completed 10 or more therapy sessions. A logistic regression on 51 of the 89 subjects that more fear of anxiety at pretreatment was associated with decreased likelihood of completing treatment, OR = 0.93, 95% CI [0.87, 1.00]. Of those veterans who completed treatment, higher fear of anger at pretreatment was negatively related to severity of PTSD posttreatment (ß = -.29, p = .037), in a model with the other predictors. Assessing veterans for fear of anxiety and anger before CPT and teaching emotion regulation skills to those in need may reduce treatment dropout.

Dimensions of emotion dysregulation in bulimia nervosa.

The goal of this study was to examine associations between dimensions of emotion dysregulation and eating disorder (ED) symptoms in bulimia nervosa (BN). This investigation used baseline data from a BN treatment study that included 80 adults (90% women) with full or subthreshold BN. Participants completed the Difficulties in Emotion Regulation Scale (DERS) and the Eating Disorders Examination interview. The Eating Disorders Examination global score was significantly correlated with the DERS total score, as well as several DERS subscales: nonacceptance, impulse and strategies. Further, the DERS goals subscale was found to be uniquely associated with frequency of purging and driven exercise, although none of the subscales were associated with frequency of objective binge eating. Findings indicate that emotion dysregulation is associated with ED symptoms in BN, suggesting the utility of interventions that address emotion regulation skills deficits in the treatment of the disorder.

Demystifying the virtualization process: A call for standard reporting of virtual modifications to evidence-based psychotherapies, using the FRAME model.

The sudden onset of the coronavirus disease led to a rapid expansion of video telehealth to deliver mental healthcare. Although video telehealth was not a new clinical practice, there was limited guidance on how best to modify evidence-based psychotherapies (EBPs) for virtual delivery (a process also referred to as virtualization). The virtualization process for EBPs remains unclear as newly emerging reports on this topic do not consistently report modification decisions. This commentary calls attention to the need to improve documentation practices to allow a greater understanding of modifications needed to maximize the positive effects of EBPs transported to a virtual format. We used the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) to capture details about the nature, process, and outcomes of intervention modifications across a given clinical setting or population. To illustrate the use of the FRAME, we present a case example describing our experiences with transporting a 1-day in-person Acceptance and Commitment Therapy group workshop to a virtual format. Workshop modifications primarily involved changes to the delivery format, administration procedures, and content. The case example walks through how, why, and by whom specific modifications were made as well as the degree to which fidelity was maintained. In the wake of the telemedicine revolution, further investigation into the virtualization process for EBPs is warranted. Improving reporting practices by using the FRAME or a similar adaptation framework will promote a more rigorous study of virtual modifications to EBPs that inform future guidelines and best practices.

Video telehealth rapidly expanded during COVID-19 as a preferred method for delivering mental health treatment. The sudden, unexpected onset of the pandemic left healthcare systems and individual clinicians little time to shift their services to this virtual format. In addition, there was and remains limited information on the most effective ways to modify evidence-based psychotherapies for virtual delivery (a process known as virtualization). To fill this knowledge gap, this commentary calls for improved documentation and evaluation of the virtualization process. We provide a case example demonstrating how to use the Framework for Reporting Adaptations and Modifications-Expanded­a comprehensive system to detail the nature and process of treatment modifications within a given context. Routine use of this or similar adaptation models within the field of behavioral and social sciences will provide a better understanding of changes needed to ensure the continuity and integrity of evidence-based psychotherapies modified for video telehealth delivery.

Evaluation of the Implementation of the FLOW Program for Increasing Access to Mental Health Care.

The FLOW program was designed to facilitate appropriate and safe transitions of patients from specialty mental health (SMH) to primary care (PC) as a method of improving access and reducing appointment burden on veterans who have improved or remitted. In this study, the team evaluated the implementation of FLOW across nine Veterans Affairs (VA) sites using a mixed-methods evaluation in a cluster-randomized stepped wedge trial design. Outcome assessments used data from VA databases, dashboards, and semi-structured interviews and were guided by the Reach, Adoption, Effectiveness, Implementation, and Maintenance (RE-AIM) framework. Across the sites, mean level reach was 1.36% of all specialty mental health patients transitioned to primary care (standard deviation [SD] = 1.05). Mean provider adoption was 10.2% (SD = 8.3%). Approximately 75% of veterans were fully satisfied with their transition and reported shared decision-making in the decision to transition. Rates of transitions did not decrease over the 6-month maintenance period following implementation. These data suggest that FLOW can be successfully implemented and maintained, although there was wide variation in implementation across sites. Future research should examine how to support sites that struggle with implementation.