Bemarituzumab plus mFOLFOX6 as first-line treatment in East Asian patients with FGFR2b-overexpressing locally advanced or metastatic gastric/gastroesophageal junction cancer: subgroup of FIGHT final analysis.

BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.

Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial.

BACKGROUND: We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2-negative gastric or gastroesophageal junction cancer (GC). METHODS: Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval [CI]) was 9.5 months (7.3-13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7-8.4) with placebo-mFOLFOX6 (hazard ratio [HR], 0.72; 95% CI 0.49-1.08); median OS (95% CI) was 19.2 (13.6-24.2) and 13.5 (9.3-15.9) months, respectively (HR 0.77; 95% CI 0.52-1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26-0.73); OS: HR 0.52 (95% CI 0.31-0.85). No new safety findings were reported. CONCLUSIONS: In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626). CLINICAL TRIAL REGISTRATION: NCT03694522.

Pilot randomized controlled trial of biofeedback on reducing psychological and physiological stress among persons experiencing homelessness.

People experiencing homelessness report increased exposure to traumatic life events and higher rates of depression, anxiety, and post-traumatic stress disorder as compared with the general population. Heart rate variability-biofeedback (HRV-BF) has been shown to decrease symptoms of stress, anxiety, depression, and PTSD. However, HRV-BF has not been tested with the most vulnerable of populations, homeless adults. The purpose of this randomized controlled trial was to compare the effectiveness of an HRV-BF intervention versus a Health Promotion (HP) active control intervention focused on improving mental health symptoms among homeless adults. Guided by a community advisory board, homeless adults residing in Skid Row, Los Angeles (n = 40) were randomized to either the HRV-BF or an active HP control group and received eight weekly, 30-min sessions over two months, delivered by a nurse-led community health worker team. Dependent variables of HRV, mental health, anxiety, depression, and PTSD were measured at baseline, the 8-week session, and/or 2-month follow-up. All intervention sessions were completed by 90% (36/40) of participants. Both the HRV-BF and HP interventions showed significant increases in HRV from baseline to 2-month follow-up, with no significant difference between the intervention groups. The HRV-BF programme revealed a somewhat greater, although non-significant, improvement in anxiety, depression, and PTSD symptoms than the HP programme. The usefulness of both interventions, focused on emotional and physical health, warrants future studies to examine the value of a combined HRV-BF and HP intervention.

Integrated behavioral treatments for comorbid anxiety and substance use disorders: A model for understanding integrated treatment approaches and meta-analysis to evaluate their efficacy.

INTRODUCTION: Substance use disorders (SUD) and anxiety disorders are highly comorbid, and this comorbidity is associated with poor clinical outcomes. Emerging research in the last decade has shifted from addressing these problems separately to the development and evaluation of behavioral treatments that integrate care for anxiety disorders (or elevated symptoms of anxiety) and SUD. METHODS: An extensive literature search revealed a sufficient number of studies (K=11) to conduct a meta-analysis comparing the efficacy of integrated SUD/anxiety disorder behavioral treatment to SUD treatment alone on substance use and anxiety symptom outcomes. Randomized clinical trials including those with SUD and either anxiety disorders or elevations in constructs implicated in the maintenance of anxiety disorder/SUD comorbidity were included. This study meta-analyzes the effects of these studies. RESULTS: Integrated treatments outperformed SUD treatments alone on both substance use and anxiety outcomes, with small to moderate effects favoring integrated treatments. There was no significant heterogeneity across studies in the primary analyses, such that moderator analyses to identify variables that yielded differential patterns of effect sizes were not conducted. DISCUSSION: Integrated treatments for SUD/anxiety disorders demonstrate an incremental but significant and clinically meaningful improvement over SUD treatment alone for SUD/anxiety disorder comorbidity. Implications for future research and clinical practice paradigm shifting are discussed.

Augmenting the efficacy of benzodiazepine taper with telehealth-delivered cognitive behavioral therapy for anxiety disorders in patients using prescription opioids: A pilot randomized controlled trial.

The risks of concomitant benzodiazepine (BZ) and opioid use are significant. Despite the urgent need to reduce BZ use among patients taking opioids, no treatment intervention research to our knowledge has addressed treatment for this concurrent, high-risk use. The current study will evaluate the efficacy of augmenting BZ taper procedures with CBT for anxiety disorders that has been adapted specifically for patients with concomitant BZ and opioid use (either use as prescribed or misuse), a high-risk patient population. Research combining rapidly scalable behavioral interventions ancillary to pharmacological approaches delivered via telehealth in primary care settings is innovative and important given concerning trends in rising prevalence of BZ/opioid co-prescription, BZ-associated overdose deaths, and known barriers to implementation of behavioral health interventions in primary care. CBT delivery using telehealth has the potential to aid adherence and promote access and dissemination of procedures in primary care. Lastly, the current study will utilize an experimental therapeutics approach to preliminarily explore the mechanism of action for the proposed interventions. The overall aim of the present pilot randomized controlled trial is to examine the feasibility and preliminary efficacy of a BZ taper with CBT for anxiety disorders adapted for patients with concomitant BZ (BZT + CBT) and opioid use to a BZ taper with a control health education program (BZT + HE) in a sample of individuals (N = 54) who have been prescribed and are taking benzodiazepines and opioids for at least 3 months prior to baseline and experience anxious distress. Screening and outcome measures, methods, and implications are described. Trial Registration: ClinicalTrials.gov (NCT05573906).

The Role of Positive and Negative Aspects of Life Events in Depressive and Anxiety Symptoms.

Negative or stressful life events are robust risk factors for depression and anxiety. Less attention has been paid to positive aspects of events and whether positivity buffers the impact of negative aspects of events. The present study examined positivity and negativity of interpersonal and non-interpersonal episodic life events in predicting anxiety and depressive symptoms in a sample of 373 young adults. Regressions tested main and interactive effects of positivity and negativity ratings of events in predicting symptom factors (Fears, Anhedonia-Apprehension (AA), General Distress (GD)) relevant to anxiety and depression. A significant interaction demonstrated that positivity protected against high levels of negativity of non-interpersonal events in predicting GD. A main effect of interpersonal negativity predicting higher AA was observed. Results for Fears were non-significant. Findings suggest that positivity of life events may buffer against negativity in predicting symptoms shared between anxiety and depression.

A randomized controlled trial on using predictive algorithm to adapt level of psychological care for community college students: STAND triaging and adapting to level of care study protocol.

BACKGROUND: There is growing interest in using personalized mental health care to treat disorders like depression and anxiety to improve treatment engagement and efficacy. This randomized controlled trial will compare a traditional symptom severity decision-making algorithm to a novel multivariate decision-making algorithm for triage to and adaptation of mental health care. The stratified levels of care include a self-guided online wellness program, coach-guided online cognitive behavioral therapy, and clinician-delivered psychotherapy with or without pharmacotherapy. The novel multivariate algorithm will be comprised of baseline (for triage and adaptation) and time-varying variables (for adaptation) in four areas: social determinants of mental health, early adversity and life stressors, predisposing, enabling, and need influences on health service use, and comprehensive mental health status. The overarching goal is to evaluate whether the multivariate algorithm improves adherence to treatment, symptoms, and functioning above and beyond the symptom-based algorithm. METHODS/DESIGN: This trial will recruit a total of 1000 participants over the course of 5 years in the greater Los Angeles Metropolitan Area. Participants will be recruited from a highly diverse sample of community college students. For the symptom severity approach, initial triaging to level of care will be based on symptom severity, whereas for the multivariate approach, the triaging will be based on a comprehensive set of baseline measures. After the initial triaging, level of care will be adapted throughout the duration of the treatment, utilizing either symptom severity or multivariate statistical approaches. Participants will complete computerized assessments and self-report questionnaires at baseline and up to 40 weeks. The multivariate decision-making algorithm will be updated annually to improve predictive outcomes. DISCUSSION: Results will provide a comparison on the traditional symptom severity decision-making and the novel multivariate decision-making with respect to treatment adherence, symptom improvement, and functional recovery. Moreover, the developed multivariate decision-making algorithms may be used as a template in other community college settings. Ultimately, findings will inform the practice of level of care triage and adaptation in psychological treatments, as well as the use of personalized mental health care broadly. TRIAL REGISTRATION: ClinicalTrials.gov NCT05591937, submitted August 2022, published October 2022.

A Novel and Integrated Digitally Supported System of Care for Depression and Anxiety: Findings From an Open Trial.

BACKGROUND: The global burden of anxiety and depression has created an urgent need for scalable approaches to increase access to evidence-based mental health care. The Screening and Treatment for Anxiety and Depression (STAND) system of care was developed to meet this need through the use of internet-connected devices for assessment and provision of treatment. STAND triages to level of care (monitoring only, digital therapy with coaches, digital therapy assisted by clinicians in training, and clinical care) and then continuously monitors symptoms to adapt level of care. Triaging and adaptation are based on symptom severity and suicide risk scores obtained from computerized adaptive testing administered remotely. OBJECTIVE: This article discusses how the STAND system of care improves upon current clinical paradigms, and presents preliminary data on feasibility, acceptability, and effectiveness of STAND in a sample of US-based university students. METHODS: US-based university students were recruited and enrolled in an open trial of the STAND system of care. Participants were triaged based on initial symptom severity derived from a computerized adaptive test and monitored over 40 weeks on anxiety, depression, and suicide risk to inform treatment adaptation and evaluate preliminary effectiveness. RESULTS: Nearly 5000 students were screened and 516 received care. Depression and anxiety severity scores improved across all tiers (P<.001 in all cases). Suicide risk severity improved in the highest tier (ie, clinical care; P<.001). Acceptability and feasibility were demonstrated. CONCLUSIONS: STAND is a feasible and acceptable model of care that can reach large numbers of individuals. STAND showed preliminary effectiveness on all primary outcome measures. Current directions to improve STAND are described.

Aversive Reactivity: A Transdiagnostic Functional Bridge Between Neuroticism and Avoidant Behavioral Coping.

Aversive reactivity to negative affect has been described as a transdiagnostic mechanism that links distal temperamental vulnerabilities to clinically relevant behaviors. However, the abundance of constructs reflecting aversive reactivity has resulted in a proliferation of models that may ultimately be redundant. We performed a circumscribed review of studies measuring associations between six constructs - anxiety sensitivity, experiential avoidance, distress intolerance, intolerance of uncertainty, thought-action fusion, and negative urgency - and ten relevant coping behaviors. Results suggested that most constructs were measured in relation to a limited number of coping behaviors. Additionally, constructs were most often measured in isolation, rather than with similar constructs. Implications and suggestions for future research and treatment are discussed.

Overall, plant-based, or animal-based low carbohydrate diets and all-cause and cause-specific mortality: A systematic review and dose-response meta-analysis of prospective cohort studies.

INTRODUCTION: In this study, we sought to summarize the associations between overall, plant-, and animal-based low carbohydrate diet (LCD) scores and the risk of all-cause, cardiovascular disease (CVD), and cancer mortality from prospective cohort studies. METHODS: We searched PubMed, Scopus, and Web of Science up to January 2022. We included prospective cohort studies that investigated the relationship between LCD-score and risk of overall, CVD, or cancer mortality. Two investigators assessed the studies for eligibility and extracted the data. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. RESULTS: Ten studies, with 421022 participants, were included in the analysis. In the high-versus-low meta-analysis, overall (HR:1.05,95%CI:0.97, 1.13, I2 =72.0%) and animal-based LCD-scores (HR: 1.08, 95% CI: 0.97-1.21; I2 = 88.0%) were not associated with all-cause mortality, but plant-based LCD-score was associated with a risk reduction (HR:0.87, 95%CI:0.78,0.97; I2 = 88.4%). CVD mortality was not associated with overall, plant-, or animal-based LCD-scores. Overall (HR:1.14, 95%CI:1.05,1.24; I2 = 37.4%) and animal-based LCD scores (HR:1.16,95%CI:1.02,1.31; I2 = 73.7%) were associated with a higher risk of cancer mortality, while plant-based LCD-score was not. A U-shaped relationship was revealed between overall LCD-score and all-cause and CVD mortality. The shape of relationship between LCD and cancer mortality was a linear dose-response. CONCLUSION: In conclusion, diets with a moderate carbohydrate content were associated with the lowest risk of all-cause and CVD mortality. If the sources of macronutrients that replaced carbohydrates were plant-based, the risk of all-cause mortality was reduced linearly with lower carbohydrate content. The risk of cancer mortality increased linearly with the increase in carbohydrate content. Considering the low certainty of evidence, more robust prospective cohort studies are suggested.

Transdiagnostic Processes Linking Posttraumatic Stress Disorder Symptoms to Alcohol Use Severity.

Objective: The high comorbidity between posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is well-established and complex. However, there is a need to explore transdiagnostic constructs that may underlie this association to better understand what accounts for this comorbidity and to inform treatment development. Method: Thus, the present study utilized a large, cross-sectional dataset (N = 513; Mage = 38.25 years, SD = 10.07; 49.9% female), based on national recruitment, to (1) examine whether the associations between PTSD symptom severity (PCL-5) and alcohol use severity (AUDIT) were statistically mediated by (a) anxiety sensitivity (SSASI); and (b) difficulties with emotion regulation (DERS-16); and (2) examine whether coping motives for drinking moderate this indirect effect. Sex assigned at birth was included as a covariate. Results: When examining the hypothesized mediators (SSASI and DERS-16) in separate models, there was a statistically significant indirect effect of PCL-5 on AUDIT through both SSASI and DERS. However, when both SSASI and DERS were entered into a model simultaneously, only SSASI served as a statistically significant mediator. Coping motives for drinking did not moderate the observed indirect effect. Conclusions: The current findings highlight anxiety sensitivity and emotion regulation as transdiagnostic processes that may explain, at least partially, the relationship between PTSD symptom severity and alcohol use; however, stronger evidence was evident for anxiety sensitivity. These findings may help inform the development of refined, streamlined interventions for PTSD and alcohol use that directly target these processes.

Evaluating training needs in clinical psychology doctoral programs.

OBJECTIVE: Advances in clinical psychology must be accompanied by advances in training. This study assessed training content, quality, and needs during clinical psychology doctoral programs among current or past doctoral students. METHODS: Current or past clinical psychology doctoral students (N = 343) completed an anonymous survey assessing training experiences and needs. A descriptive-focused exploratory factor analysis (EFA) also examined whether common subgroups of academic interests emerged. RESULTS: Most participants reported that they sought training beyond required coursework, primarily in clinical training, cultural competency, and professional development, and reported having taken one or more unhelpful course, including discipline-specific knowledge requirements. Descriptive results from the EFA demonstrated common training areas of interest: diversity topics, biological sciences, clinical practice, and research methods. DISCUSSION: This study demonstrates that trainees and early career psychologists are aware of their nuanced and in some cases, unmet training needs. CONCLUSION: This work foregrounds the need to adapt extant training opportunities to support the next generation of clinical psychologists.

Recent advances in the understanding and psychological treatment of social anxiety disorder.

Social anxiety disorder (SAD) is characterized by persistent anxiety or avoidance of social situations because of a fear of negative evaluation. Cognitive behavioral therapy (CBT) (typically with an exposure component) is a first-line treatment for social anxiety, but there remains room for improvement with regard to treatment efficacy. Therefore, the field continues to better understand the mechanisms underlying SAD and its common and complex comorbidities in order to develop targeted interventions to improve symptom outcomes. Additionally, efforts are under way to improve the efficacy and accessibility of CBT. This review outlines major advances in understanding and treating SAD in adults over the past roughly 3 years (2019 to early May 2022). Themes are identified and discussed, as are recommendations for future research.

Examining the Real-Life Journey of Individuals and Families Affected by Single-Ventricle Congenital Heart Disease.

Background The lifetime journey of patients with single-ventricle congenital heart disease is characterized by long-term challenges that are incompletely understood and still unfolding. Health care redesign requires a thorough understanding of this journey to create and implement solutions that improve outcomes. This study maps the lifetime journey of individuals with single-ventricle congenital heart disease and their families, identifies the most meaningful outcomes to them, and defines significant challenges in the journey. Methods and Results This qualitative research study involved experience group sessions and 1:1 interviews of patients, parents, siblings, partners, and stakeholders. Journey maps were created. The most meaningful outcomes to patients and parents and significant gaps in care were identified across the life journey. A total of 142 participants from 79 families and 28 stakeholders were included. Lifelong and life-stage specific journey maps were created. The most meaningful outcomes to patients and parents were identified and categorized using a "capability (doing the things in life you want to), comfort (experience of physical/emotional pain/distress), and calm (experiencing health care with the least impact on daily life)" framework. Gaps in care were identified and classified into areas of ineffective communication, lack of seamless transitions, lack of comprehensive support, structural deficiencies, and insufficient education. Conclusions There are significant gaps in care during the lifelong journey of individuals with single-ventricle congenital heart disease and their families. A thorough understanding of this journey is a critical first step in developing initiatives to redesign care around their needs and priorities. This approach can be used for people with other forms of congenital heart disease and other chronic conditions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04613934.

Experiences and insights from partners of individuals with single-ventricle CHD: a pilot qualitative research study.

INTRODUCTION: With advances in care, an increasing number of individuals with single-ventricle CHD are surviving into adulthood. Partners of individuals with chronic illness have unique experiences and challenges. The goal of this pilot qualitative research study was to explore the lived experiences of partners of individuals with single-ventricle CHD. METHODS: Partners of patients ≥18 years with single-ventricle CHD were recruited and participated in Experience Group sessions and 1:1 interviews. Experience Group sessions are lightly moderated groups that bring together individuals with similar circumstances to discuss their lived experiences, centreing them as the experts. Formal inductive qualitative coding was performed to identify salient themes. RESULTS: Six partners of patients participated. Of these, four were males and four were married; all were partners of someone of the opposite sex. Themes identified included uncertainty about their partners' future health and mortality, becoming a lay CHD specialist, balancing multiple roles, and providing positivity and optimism. Over time, they took on a role as advocates for their partners and as repositories of medical history to help navigate the health system. Despite the uncertainties, participants described championing positivity and optimism for the future. CONCLUSIONS: In this first-of-its-kind pilot study, partners of individuals with single-ventricle CHD expressed unique challenges and experiences in their lives. There is a tacit need to design strategies to help partners cope with those challenges. Further larger-scale research is required to better understand the experiences of this unique population.

A randomized clinical trial of behavioral activation and exposure-based therapy for adults with generalized anxiety disorder.

Objective: Exposure-based therapy (EXP) and behavioral activation (BA) are empirically-supported behavioral intervention techniques that target avoidance and approach behavior to alleviate symptoms. Although EXP is an established treatment for generalized anxiety disorder (GAD), the effectiveness of BA for GAD has not been directly tested or compared with that of EXP. This study examined the efficacy of EXP and BA for adults with GAD. Method: In a randomized clinical trial (clinicaltrials.gov: NCT02807480) with partial blinding in Tulsa, OK, 102 adults with GAD were allocated to manualized, 10-session EXP or BA between April 2016-April 2021. Primary analyses were intention-to-treat and included the 94 (46 EXP, 48 BA) participants who started treatment. The GAD-7 self-report scale was the primary outcome measure. Results: Similar GAD-7 declines were observed at post-treatment for EXP (d=-0.97 [95% CI -1.40 to -0.53]) and BA (d=-1.14 [95% CI -1.57 to -0.70]), and were maintained through 6-month follow-up (EXP: d=-2.13, BA: d=-1.98). Compared to EXP, BA yielded more rapid declines in anxiety and depression scores during therapy (d=0.75-0.77), as well as lower anxiety and depression scores (d=0.13-0.14) and greater participant-rated improvement (d=0.64) at post-treatment. Bayesian analyses indicated 74-99% probability of greater change in BA than EXP at post-treatment. Conclusions: BA and EXP are both effective in treating GAD, and BA may confer greater benefit during treatment. Future research is warranted to inform personalized treatment approaches.

Postoperative diplopia test-repeatability and prediction of surgical outcomes.

BACKGROUND: The postoperative diplopia test (PODT) is used to assess the risk of postoperative diplopia in older children and adults prior to strabismus surgery for nonfunctional reasons. The purpose of this study was to evaluate the test-retest and interobserver reliability of the PODT and its predictive value in assessing diplopia risk. METHODS: In the first phase of this study, the repeatability of the PODT method was prospectively assessed with two groups of patients (group 1, test-retest; group 2, interobserver). In the second phase, notes were reviewed retrospectively to evaluate the predictive value of the PODT. RESULTS: For phase 1, 39 participants were recruited. In group 1, 12 participants showed agreement in the area of suppression for both near and distance fixation; 8 showed variability. In group 2, 10 showed agreement for near, and 9 showed variability; 9 showed agreement for distance, and 10 showed variability. Group 1 differences ranged from 0 to 9 points (median, 0.5; IQR, 0-3); group 2, from 0 to 36 points (median, 1; IQR, 0-4.5). In phase 2, outcomes of 39 strabismus surgeries were reviewed: none of the patients without diplopia on PODT and 2 of 14 patients with diplopia on PODT had persistent diplopia 3 months after surgery. CONCLUSIONS: Many patients develop diplopia postoperatively, but this generally resolves spontaneously. Current testing procedures have excessive test-retest and interobserver variability and insufficient predictive value to be useful in predicting postoperative diplopia.

Fear-potentiated startle predicts longitudinal change in transdiagnostic symptom dimensions of anxiety and depression.

BACKGROUND: Elevated defensive responding, through startle reflex (SR) and skin conductance response (SCR), may contribute to onset and maintenance of depression and anxiety. Most work examining SR and SCR has predicted psychiatric diagnoses. There is a paucity of research examining links between SR or SCR and dimensional measures of psychopathology. METHODS: We used latent growth curve modeling to predict longitudinal change in three symptom factors (i.e., General Distress, Fears, Anhedonia-Apprehension) from SR and SCR measured during a fear-potentiated startle paradigm among adolescents oversampled for neuroticism (N = 129). RESULTS: Elevated SCR in danger phases before and after an unpleasant muscle contraction predicted increasing Fears over time. Elevated SR in safe phases post-contraction also predicted increasing Fears over time. Attenuated SR in safe phases post-contraction predicted elevated General Distress longitudinally. Attenuated SCR pre-contraction in danger phases predicted elevated Anhedonia-Apprehension over time. LIMITATIONS: Our non-clinical sample may limit generalizability of results. Additionally, we did not assess change in SR and SCR over time. CONCLUSIONS: The present study demonstrates that SR and SCR during a fear-potentiated startle paradigm predict longitudinal change in dimensional anxiety and depression symptom factors and relatedly, that SR and SCR may represent risk factors for the exacerbation of symptomatology.

Association Between Benzodiazepine and Opioid Prescription and Mortality Among Patients in a Large Healthcare System.

OBJECTIVE: Coprescription of opioids and benzodiazepines (BDZ) is associated with adverse outcomes, including greater healthcare utilization and overdose risk. This study aims to examine opioid and BDZ coprescription, dosing, and mortality among patients with and without opioid use disorder (OUD) in a large healthcare system. METHODS: Using data from the California state Prescription Drug Monitoring Program during 2010 to 2014 linked with a large healthcare system electronic health record database and mortality records from the Centers for Disease Control National Death Index, this study examined 5202 patients (1978 with OUD, 3224 controls). Multiple logistic regression analyses were conducted to examine relationships between most recent BDZ and opioid prescription, and their interaction with respect to mortality. RESULTS: About 10.5% of the sample died on or before December 31, 2014. About 17.7% were prescribed BDZ during the final month of observation. Individuals with OUD were prescribed higher average BDZ and opioid doses than those without OUD. After adjusting for covariates, increased prescribed doses of BDZ (odds ratio [OR]=1.34, 95%CI: 1.15-1.55 per 10 mg/d increment) and opioids (OR = 1.04, 95%CI: 1.02-1.05 per 10 mg/d increment) were positively associated with mortality. Non-OUD patients who received both BDZ and opioid prescriptions had a higher mortality than those who received only BDZ or opioids (The ratio of odds ratio (ROR) = 3.83, 95%CI: 1.78-8.21). CONCLUSIONS: Study findings highlight significant mortality associated with the coprescription of opioids and BDZ in a general healthcare setting. Further research is needed to elucidate factors associated with mortality among non-OUD patients who are co-prescribed opioids and BDZ.

Targeting maladaptive reactivity to negative affect in emerging adults with cannabis use disorder: A preliminary test and proof of concept.

INTRODUCTION: Cannabis use disorder (CUD) is a growing public health concern, and is highly comorbid with negative affective conditions such as anxiety and depression. Late adolescence and early adulthood represents a time of rapid emotion regulation development, as well as the onset of anxiety, mood, and substance use disorders, especially CUD. Maladaptive cognitive, behavioral, and emotional responding to one's own negative affect (in an effort to eliminate it) is associated with substance use, and represents a novel treatment target to improve outcomes of treatment for substance misuse. METHOD: After development of a manual for a novel intervention, Affect Management Treatment (AMT) for CUD, a pilot randomized clinical trial was conducted in 18-25 year-old participants with CUD to evaluate the impact of this approach on negative affect, constructs (e.g., distress intolerance) representing maladaptive reactivity to negative affect, and cannabis use. Participants (N = 52) received either 12 sessions of standard cognitive behavioral therapy (CBT) for CUD or 12 sessions of AMT and were assessed on measures of negative affect, reactivity to negative affect, cannabis use, and cannabis use problems at baseline, throughout treatment, post-treatment, and 6-mo follow-up. RESULTS: AMT outperformed CBT in reducing negative affect and reactivity to negative affect, and it had a significant impact on cannabis use and cannabis use problems. There were no statistically significant between-group differences on cannabis outcomes. CONCLUSIONS: AMT offers a novel, successful approach to the treatment of CUD.