In vivo screening identifies SPP2, a secreted factor that negatively regulates liver regeneration.

BACKGROUND AND AIMS: The liver is remarkably regenerative and can completely recover even when 80% of its mass is surgically removed. Identification of secreted factors that regulate liver growth would help us understand how organ size and regeneration are controlled but also provide candidate targets to promote regeneration or impair cancer growth. APPROACH AND RESULTS: To enrich for secreted factors that regulate growth control, we induced massive liver overgrowth with either YAP or MYC . Differentially expressed secreted factors were identified in these livers using transcriptomic analysis. To rank candidates by functionality, we performed in vivo CRISPR screening using the Fah knockout model of tyrosinemia. We identified secreted phosphoprotein-2 (SPP2) as a secreted factor that negatively regulates regeneration. Spp2 -deficient mice showed increased survival after acetaminophen poisoning and reduced fibrosis after repeated carbon tetrachloride injections. We examined the impact of SPP2 on bone morphogenetic protein signaling in liver cells and found that SPP2 antagonized bone morphogenetic protein signaling in vitro and in vivo. We also identified cell-surface receptors that interact with SPP2 using a proximity biotinylation assay coupled with mass spectrometry. We showed that SPP2's interactions with integrin family members are in part responsible for some of the regeneration phenotypes. CONCLUSIONS: Using an in vivo CRISPR screening system, we identified SPP2 as a secreted factor that negatively regulates liver regeneration. This study provides ways to identify, validate, and characterize secreted factors in vivo.

HIV Prevalence and HIV Screening History Among a Veterans Association Cohort of People with Opioid and Alcohol Use Disorders.

BACKGROUND: Veterans face high risk for HIV and substance use, and thus could be disproportionately impacted by the HIV and substance use disorder (SUD) "syndemic." HIV prevalence among veterans with SUD is unknown. OBJECTIVE: To project HIV prevalence and lifetime HIV screening history among US veterans with alcohol use disorder (AUD), opioid use disorder (OUD), or both. DESIGN: We conducted a retrospective cohort analysis using national Veterans Health Administration (VHA) data. PARTICIPANTS: We selected three cohorts of veterans with SUD: (1) AUD, (2) OUD, and (3) AUD/OUD. Included veterans had ICD codes for AUD/OUD from 2016 to 2022 recorded in VHA electronic medical records, sourced from the VA Corporate Data Warehouse (CDW). MAIN MEASURES: We estimated HIV prevalence by dividing the number of veterans who met two out of three criteria (codes for HIV diagnosis, antiretroviral therapy, or HIV screening/monitoring) by the total number of veterans in each cohort. We also estimated lifetime HIV screening history (as documented in VHA data) by cohort. We reported HIV prevalence and screening history by cohort and across demographic/clinical subgroups. KEY RESULTS: Our sample included 669,595 veterans with AUD, 63,787 with OUD, and 57,015 with AUD/OUD. HIV prevalence was highest in the AUD/OUD cohort (3.9%), followed by the OUD (2.1%) and AUD (1.1%) cohorts. Veterans of Black race and Hispanic/Latinx ethnicity, with HCV diagnoses, and aged 50-64 had the highest HIV prevalence in all cohorts. Overall, 12.8%, 29.1%, and 33.1% of the AUD/OUD, OUD, and AUD cohorts did not have history of HIV screening, respectively. CONCLUSIONS: HIV prevalence was high in all SUD cohorts, and was highest among veterans with AUD/OUD, with disparities by race/ethnicity and age. A substantial portion of veterans had not received HIV screening in the VHA. Findings highlight room for improvement in HIV prevention and screening services for veterans with SUD.

The Associations Between Gender Minority Stressors and PTSD Symptom Severity Among Trauma-Exposed Transgender and Gender Diverse Adults.

This study investigates associations between minority stressors, traumatic stressors, and post-traumatic stress disorder (PTSD) symptom severity in a sample of transgender and gender diverse (TGD) adults. We utilized surveys and clinical interview assessments to assess gender minority stress exposures and responses, and PTSD. Our sample (N = 43) includes adults who identified as a minoritized gender identity (i.e., 39.5% trans woman or woman, 25.6% trans man or man, 23.3% genderqueer or nonbinary, 11.6% other identity). All participants reported at least one traumatic event (i.e., life threat, serious injury, or sexual harm). The most common trauma events reported by the sample were sexual (39.5%) and physical violence (37.2%), with 40.9% of participants anchoring their symptoms to a discrimination-based event. PTSD symptom severity was positively correlated with both distal (r = 0.36, p = .017) and proximal minority stressors (r = 0.40, p < .01). Distal minority stress was a unique predictor of current PTSD symptom severity (b = 0.94, p = .017), however, this association was no longer significant when adjusting for proximal minority stress (b = 0.18, p = 0.046). This study suggests that minority stress, especially proximal minority stress, is associated with higher PTSD symptom severity among TGD adults.

Relationship between astrocyte reactivity, using novel 11C-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals.

Post mortem neuropathology suggests that astrocyte reactivity may play a significant role in neurodegeneration in Alzheimer's disease. We explored this in vivo using multimodal PET and MRI imaging. Twenty subjects (11 older, cognitively impaired patients and 9 age-matched healthy controls) underwent brain scanning using the novel reactive astrocyte PET tracer 11C-BU99008, 18F-FDG and 18F-florbetaben PET, and T1-weighted MRI. Differences between cognitively impaired patients and healthy controls in regional and voxel-wise levels of astrocyte reactivity, glucose metabolism, grey matter volume and amyloid load were explored, and their relationship to each other was assessed using Biological Parametric Mapping (BPM). Amyloid beta (Aß)-positive patients showed greater 11C-BU99008 uptake compared to controls, except in the temporal lobe, whilst further increased 11C-BU99008 uptake was observed in Mild Cognitive Impairment subjects compared to those with Alzheimer's disease in the frontal, temporal and cingulate cortices. BPM correlations revealed that regions which showed reduced 11C-BU99008 uptake in Aß-positive patients compared to controls, such as the temporal lobe, also showed reduced 18F-FDG uptake and grey matter volume, although the correlations with 18F-FDG uptake were not replicated in the ROI analysis. BPM analysis also revealed a regionally-dynamic relationship between astrocyte reactivity and amyloid uptake: increased amyloid load in cortical association areas of the temporal lobe and cingulate cortices was associated with reduced 11C-BU99008 uptake, whilst increased amyloid uptake in primary motor and sensory areas (in which amyloid deposition occurs later) was associated with increased 11C-BU99008 uptake. These novel observations add to the hypothesis that while astrocyte reactivity may be triggered by early Aß-deposition, sustained pro-inflammatory astrocyte reactivity with greater amyloid deposition may lead to astrocyte dystrophy and amyloid-associated neuropathology such as grey matter atrophy and glucose hypometabolism, although the evidence for glucose hypometabolism here is less strong.

Comparing substance use treatment initiation and retention between telehealth delivered during COVID-19 and in-person treatment pre-COVID-19.

BACKGROUND AND OBJECTIVES: A large portion of veterans referred to substance use disorder (SUD) treatment do not attend their first appointment or leave treatment prematurely. Telehealth options may increase access to care and treatment attendance. This study compared treatment initiation and retention between in-person treatment pre-COVID-19 and telehealth treatment during COVID-19 in a VA hospital outpatient alcohol and drug treatment clinic. METHODS: Electronic health record data were collected on 373 veterans out of 481 referrals. Mixed logistic and negative binomial regression models were used for estimating the effect of treatment modality on treatment initiation and retention, respectively. RESULTS: The odds of initiating treatment were 2.6 times greater when referred to a telehealth appointment during COVID-19 compared to an in-person appointment pre-COVID-19. Months retained in treatment postinitiation was similar between treatment modalities. Each month in treatment corresponded to a subsequently lower rate of treatment session attendance and by the fourth month, the average number of sessions attended was significantly lower for those receiving in-person treatment compared to those receiving telehealth treatment. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The odds of initiating SUD treatment and rate of treatment attendance over time was greater for services delivered via telehealth during COVID-19 compared to in-person pre-COVID-19. Extending telehealth services as an option for individual and group SUD treatment may promote treatment initiation and potentially higher rate of attendance over time. This study provides additional evidence for the feasibility and utility of rapidly expanding telehealth for veterans seeking outpatient substance use treatment.

Do Orthopaedic Virtual Clinic Visits Demonstrate Cost and Time Efficiencies Compared With In-person Visits?

BACKGROUND: There are numerous reasons for the increased use of telemedicine in orthopaedic surgery, one of which is the perception that virtual visits are more cost-effective than in-person visits. However, to our knowledge, no studies have compared the cost and time investment of virtual versus in-person visits using the time-driven activity-based costing (TDABC) method. Unlike methods that estimate cost based on charges for services rendered, TDABC provides a more precise measurement of costs, which is essential for assessing cost-effective innovations and moving to value-based healthcare. QUESTIONS/PURPOSES: (1) Are virtual visits less costly than analogous in-person visits, as measured by TDABC? (2) Does TDABC yield cost estimates that are lower or higher than the ratio of costs to charges (RCC), which is a simple, frequently used costing method? (3) Do the total time commitments of healthcare personnel, and that of the surgeon specifically, vary between the virtual and in-person settings? METHODS: Patients for this prospective, observational study were recruited from the practices of the highest-volume virtual-visit surgeons of three subspecialties (joints, hand, and sports) in a multihospital, tertiary-care academic institution in a metropolitan area in the Midwestern United States. Each surgeon had at least 10 years of clinical practice. Between June 2021 and September 2021, we analyzed both in-person and virtual return visits with patients who had an established relationship with the surgeon, because this represented the most frequent type of virtual visits and enabled a direct comparison between the two settings. New patients were not included in the study because of the limited availability of new-patient virtual visits; such patients often benefit from in-person physical examinations and on-site imaging. Additionally, patients seen for routine postoperative care were excluded because they were primarily seen in person by a physician assistant. Data were acquired during this period until 90 in-person and 90 virtual visits were collected according to selection criteria; no patients were lost to follow-up. Distinct process maps, which represent the steps involved in a clinic visit used to measure healthcare personnel time invested, were constructed for in-person and virtual clinic visits and used to compare total personnel and surgeon time spent. To calculate TDABC-derived costs, time allocated by personnel to complete each step was measured and used to calculate cost based on each personnel member's yearly salary. From the accounting department of our hospital, we acquired RCC cost data according to the level of service for a return visit. RESULTS: The total median cost, as measured by TDABC, was USD 127 (IQR USD 111 to 163) for an in-person visit and USD 140 (IQR USD 113 to 205) for a virtual visit (median difference USD 13; p = 0.16). RCC overestimated TDABC-calculated direct variable cost in five of six service levels (in-person levels 3, 4, and 5 and virtual levels 3 and 5) by a range of USD 25 to 88. Additionally, we found that virtual visits consumed 4 minutes less of total personnel time (in-person: 17 minutes [IQR 13.5 to 23.5 minutes], virtual: 13 minutes [IQR 11 to 19 minutes]; p < 0.001); however, this difference in personnel time did not equate to cost savings because surgeons spent 2 minutes longer on virtual visit activities than they did on in-person activities (in-person: 6 minutes [IQR 4.5 to 9.5 minutes], virtual: 8 minutes [IQR 5.5 to 13 minutes]; p = 0.003). CONCLUSION: Orthopaedic virtual visits did not deliver cost savings compared with in-person visits because surgeons spent more time on virtual visits and participated in virtual visits at the clinical site. Additionally, as anticipated, RCC overestimated costs as calculated by TDABC. These findings suggest that cost is not a primary advantage of transitioning to virtual visits, and that factors such as patient preference and satisfaction should be considered instead. LEVEL OF EVIDENCE: Level II, economic and decision analysis.

Use of Both Alcohol and Cannabis Protective Behavioral Strategies is Associated with Fewer Negative Consequences: A Moderation Analysis.

Background: Concurrent alcohol and cannabis (i.e. marijuana) use (CAM; use of both substances within the same specified time frame) is prevalent among college students and associated with increased risk of negative substance-related consequences. Extant research supports the use of protective behavioral strategies (PBS) for reducing negative consequences associated with both alcohol and cannabis use. However, limited research exists regarding the efficacy of PBS among CAM users, and it is unknown whether using PBS for both alcohol and cannabis augments protective effects. The present study tested four moderation models to evaluate the interactive effects of alcohol and cannabis PBS on alcohol and cannabis negative consequences and use frequency. Methods: A multisite sample of college students (N = 1705) reporting past-month CAM use completed questionnaires regarding substance use behaviors, PBS use, and substance-related negative consequences. Results: Alcohol and cannabis PBS were negatively associated with alcohol and cannabis use, respectively. However, two-way interactions between PBS on substance use were not supported, such that negative associations between PBS and same-substance use were not augmented as other-substance PBS use increased. Interactive effects of alcohol and cannabis PBS on negative alcohol and cannabis consequences were supported, such that negative associations between alcohol PBS and consequences were augmented as cannabis PBS increased and vice versa. Conclusions: Findings suggest that using both types of PBS may increase protective effects against negative consequences among CAM users. Accordingly, promoting both types of PBS may enhance extant harm reduction interventions.

Computerized Relational Agent to Deliver Alcohol Brief Intervention and Referral to Treatment in Primary Care: a Randomized Clinical Trial.

BACKGROUND: Alcohol screening and brief intervention have demonstrated efficacy but limited effectiveness and implementation in real-world primary care settings. OBJECTIVE: To evaluate the effectiveness of a computerized Relational Agent programmed to provide alcohol screening, brief intervention, and referral to treatment. We hypothesized that participants in the experimental condition would report greater reductions in their drinking and higher rates of brief intervention and referrals to specialty care compared to those in treatment as usual (TAU). DESIGN: This was a Hybrid I implementation design and stratified RCT. Participants were randomized to TAU or Relational Agent + TAU and assessed at baseline and 3-month follow-up. PARTICIPANTS: A total of 178 veteran participants were recruited by referral from primary care staff after a positive alcohol screen, or via letter sent do patients screening positive during recent visit. INTERVENTION(S): TAU involved yearly reminders to screen alcohol use and provide brief intervention and treatment referrals, as needed. The Relational Agent added an automated brief intervention, a 1-month follow-up Relational Agent visit, and referral to treatment if needed. MAIN MEASURES: We measured average drinks per day, drinking days per week, number of brief interventions, and number of referrals over 3 months. KEY RESULTS: Participants decreased their drinking in both study conditions, with no significant between-group differences on primary alcohol measures. However, Relational Agent + TAU participants evidenced greater improvements regarding negative alcohol-related consequences over 3 months, and were significantly more likely to receive a brief intervention and referral to specialty care. CONCLUSIONS: The Relational Agent successfully provided brief intervention and referred many more patients to specialty care and was able to intervene with patients with less severe drinking without increasing primary care burden. TRIAL REGISTRATION: clinicaltrials.gov , NCT02030288, https://clinicaltrials.gov/ct2/home.

Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load.

11C-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer's disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), 18F-florbetaben and 11C-BU99008 PET. The 8 amyloid (Aß)-positive CI subjects had higher 11C-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between 11C-BU99008 and 18F-florbetaben. Autoradiography using 3H-BU99008 with post-mortem Alzheimer's brains confirmed through visual assessment that increased 3H-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that 11C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer's disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high Aß load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity.

Interventions to Improve Post-Detoxification Treatment Engagement and Alcohol Recovery: Systematic Review of Intervention Types and Effectiveness.

AIMS: Most inpatient alcohol detoxification patients do not seek treatment post-discharge, which increases the risk of relapse and re-hospitalization. To date, there have been no efforts to synthesize the evidence supporting the broad range of available interventions for this critical transition. The current study is a systematic review and evaluation of interventions designed to promote treatment engagement and recovery following alcohol detoxification. METHODS: The initial literature search yielded 6419 articles, published since 1999, from PubMed, CINAHL, PsycINFO, Psychology & Behavioral Sciences Collection and PsycARTICLES databases, 49 of which were eligible for full review. Data extraction included in-depth evaluation of intervention types, study and research design features, reported outcomes and study quality/bias indicators. All articles were coded by independent raters and final results were obtained through consensus. RESULTS: Interventions included medical/medication, psychological/psychosocial, technological, mutual-help and combined approaches. On average, medical/medication interventions were less, and psychological/psychosocial and technological interventions were more likely to demonstrate efficacy with respect to treatment engagement and recovery. There was significant variability in study quality/bias but no significant differences across intervention types. Studies differed considerably across measured outcomes, internal and external validity, in/exclusion criteria and documentation of co-occurring psychiatric disorders. CONCLUSION: Over half of studies reviewed reported empirical support for the intervention(s) evaluated. Although findings slightly favor non-medical interventions, the variability in study design and quality/bias requires more rigorous follow-up research. Recommendations from this review may guide future implementation and intervention development, which are critically needed to improve post-detoxification care and outcomes for patients with alcohol use disorder.

Validating Data-Driven Methods for Identifying Transgender Individuals in the Veterans Health Administration of the US Department of Veterans Affairs.

We sought to operationalize and validate data-driven approaches for identifying transgender individuals in the Veterans Health Administration (VHA) of the US Department of Veterans Affairs (VA) through a retrospective analysis using VA administrative data from 2006-2018. Besides diagnoses of gender identity disorder (GID), a combination of non-GID data elements was used to identify potentially transgender veterans, including 1) an International Classification of Diseases (Ninth or Tenth Revision) code of endocrine disorder, unspecified or not otherwise specified; 2) receipt of sex hormones not associated with the sex documented in the veteran's records (gender-affirming hormone therapy); and 3) a change in the veteran's administratively recorded sex. Both GID and non-GID data elements were applied to a sample of 13,233,529 veterans utilizing the VHA of the VA between January 2006 and December 2018. We identified 10,769 potentially transgender veterans. Based on a high positive predictive value for GID-coded veterans (83%, 95% confidence interval: 77, 89) versus non-GID-coded veterans (2%, 95% confidence interval: 1, 11) from chart review validation, the final analytical sample comprised only veterans with a GID diagnosis code (n = 9,608). In the absence of self-identified gender identity, findings suggest that relying entirely on GID diagnosis codes is the most reliable approach for identifying transgender individuals in the VHA of the VA.

Feasibility, acceptability and affective consequences of at-home sleep extension in young women with depressive symptoms: A pilot study.

Insufficient sleep is common in young adults and has meaningful consequences for daytime functioning, including increased sleepiness, affective disruption and depressive symptoms. This study provides a preliminary evaluation of the feasibility, acceptability and affective consequences of extended sleep opportunity in young women with insufficient sleep and depressive symptoms. Participants were 32 women, 18-22 years of age, who regularly obtained less than 8-hr sleep/night and had daytime sleepiness and depressive symptoms at or above population averages. Participants were asked to maintain a sleep schedule of their typical duration for 7 days and were then randomly assigned to either extend sleep opportunity (ESO) by 90 min per night or maintain typical sleep opportunity (TSO), for the next 7 days. Sleep characteristics and daytime sleepiness were measured using continuous actigraphy and daily sleep diary, and affect, stress and depressive symptoms were assessed with daily and weekly questionnaires. Extended sleep opportunity increased sleep duration by over 1 hr, improved morning sleepiness and positive affect, and diminished anhedonia and depressive symptoms in study completers (n = 11 ESO, 11 TSO). However, 31.3% of participants (n = 10) were withdrawn from the study due to difficulty maintaining the sleep schedule. These results provide initial evidence that sleep extension is beneficial for young women who usually have inadequate sleep and mood disruption and can maintain a consistent sleep schedule. If extending sleep opportunity improves sleep, daytime sleepiness and affect in young adults who typically have insufficient sleep, it could broaden the range of interventions for sleep and mental wellness.

Treatment experiences among LGBT veterans with discrimination-based trauma exposure: A pilot study.

Past research suggests that rates of trauma exposure and Posttraumatic Stress Disorder (PTSD) are elevated among lesbian, gay, bisexual, and transgender (LGBT) veterans compared to heterosexual and cisgender veterans. Given higher rates of trauma exposure and PTSD, and the culture associated with the Department of Defense's history of policies excluding LGBT people, it is important to understand if LGBT veterans are seeking PTSD treatment following discrimination-based traumatic events, where they seek care, and if they are satisfied with treatment. This study aimed to describe the experiences of discrimination-based trauma-exposed LGBT veterans' (n = 47) experiences with PTSD treatment, including location of treatment (Veterans Health Administration [VHA] versus non-VHA) and satisfaction with care. The majority of veterans had received a PTSD diagnosis from a health-care provider in their lifetimes (78.72%, n = 37), and over half reported currently experiencing PTSD symptoms. Approximately 47% of LGBT veterans with discrimination-based trauma histories preferred to seek PTSD treatment exclusively at VHA (46.81%) or with a combination of VHA and non-VHA services (38.30%). Veterans who received PTSD treatment exclusively from VHA reported higher satisfaction ratings (7.44 on 0-9 scale) than veterans who received PTSD treatment exclusively from outside VHA (5.25 on 0-9 scale). For veterans who sought PTSD treatment at both VHA and non-VHA facilities, there were no significant differences regarding satisfaction ratings for their PTSD treatment in the two settings. Results are discussed in terms of VHA's continued efforts to establish equitable, patient-centered health care for all veterans and the importance of non-VHA facilities to recognize veteran identities.

Examining the Relation Between Social Anxiety and Cannabis Problems Among College Students Through Coping-Related Expectancies and Motives.

Objective: College students high in social anxiety are at increased risk for cannabis-related problems. This may be particularly true when they hold strong coping-related expectancies and motives for cannabis. However, few studies have examined these constructs together in accordance with the motivational model, which posits that substance use is proximally influenced by motives and more distally influenced by expectancies. Thus, the current study examined whether the relation between social anxiety and cannabis-related problems was indirectly explained through coping-related expectancies, motives, and cannabis use. Method: Past-month cannabis users (N = 660; 71.6% female, 47.3% white non-Hispanic) from seven U.S. universities completed an online survey assessing social anxiety, and cannabis use frequency, problems, expectancies, and motives. A saturated path model examined social anxiety as a predictor of cannabis problems via coping-related expectancies and motives, and cannabis frequency. Results: There was a positive indirect effect of social anxiety on cannabis problems through cognitive and behavioral impairment expectancies, depression coping motives, and cannabis use. Social anxiety also indirectly positively related to cannabis problems via social and sexual facilitation expectancies, social anxiety coping motives, and cannabis use. Further, social anxiety indirectly positively related to cannabis problems through relaxation and tension reduction expectancies, both depression and social anxiety coping motives, and cannabis use. These indirect effects were invariant by sex assigned at birth. Conclusions: Results support using a theory-informed model of coping-related cannabis cognitions to understand the relation between social anxiety and cannabis problems. Interventions that modify coping-related cognitions may reduce cannabis-related problems in college students high in social anxiety.

Orthopaedic Hand Patient Support Systems Have Valuable Insight to Patient Function and Pain.

Patient-reported outcome measures (PROs) are increasingly used in clinical assessment. Research on how patient support systems contribute to physician understanding of patient condition is limited. Thus, insights from significant others may provide value, especially when concerns exist regarding patient response validity. Patients recruited from the pre-operative environment undergoing orthopaedic hand procedures responded to PROMIS-Pain Interference (PI), PROMIS-Upper Extremity (UE), PROMIS-Depression (D), and QuickDASH. They then selected a significant other (SO) to do the same. Patients and SOs were also asked to complete the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) as a measure of support-related responses. Patient and SO responses were compared, and support-related responses were added in subsequent analyses to examine their effect on SO PRO assessment.

Expectancy for Adderall influences subjective mood and drug effects regardless of concurrent caffeine ingestion: A randomized controlled trial.

RATIONALE: Nonmedical prescription stimulant use (NPS; use without a prescription or in ways other than prescribed) is common among college students. Despite the potential for negative consequences, students continue engaging in NPS for cognitive enhancement purposes, which may be maintained by expectancy and placebo effects. OBJECTIVES: This study examined if a placebo administered under the guise of Adderall influenced subjective mood/drug effects and cognitive performance. Furthermore, this study examined if concurrent caffeine ingestion incrementally enhanced Adderall-related placebo effects. METHODS: Undergraduate students with features that put them at elevated risk for NPS (N = 121) completed measures of mood and drug effects and cognitive assessments on two separate laboratory visits in this parallel randomized controlled trial. Visit 1 was a baseline control visit, on which no drug was expected or received. On visit 2, subjects were randomized to: (1) expect/receive no drug (control); (2) expect Adderall/receive placebo; or (3) expect Adderall/receive 200 mg caffeine. RESULTS: There were several significant condition × visit interactions for subjective effects, including amphetamine effects, energy and efficiency effects, and feeling high. In most cases, participants who expected Adderall reported greater positive subjective effects on visit 2 compared to controls; however, there were generally not incremental enhancements for those ingesting caffeine compared to placebo. There were no significant effects for any cognitive tests. CONCLUSIONS: Expectation for prescription stimulant effects influenced subjective outcomes in a sample of high-risk college students. These findings may inform expectancy challenge interventions to reduce NPS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03648684.

Alcohol-Related Problems As Moderators of PTSD Symptom Change During Use of a Web-Based Intervention for Hazardous Drinking and PTSD.

OBJECTIVE: Alcohol-related problems (e.g., physical, interpersonal, intrapersonal, impulse control, social responsibility) can have an impact on posttraumatic stress disorder (PTSD) symptoms during treatment. Evidence-based online self-help tools exist to target alcohol use and related problems and co-occurring PTSD symptoms. It is unknown to what degree individuals with varying alcohol-related problems respond differently to web-based interventions for hazardous alcohol use and PTSD. The current study evaluated specific alcohol-related problems as potential moderators of PTSD symptom changes during the VetChange online intervention while controlling for average daily alcohol use, gender, race, and age. METHOD: We conducted a secondary analysis of a randomized controlled trial that included 600 post-9/11 veterans (518 men and 82 women). Mixed-effects regression models of alcohol-related problems on PTSD severity scores over time were performed separately in an initial intervention group (IIG; n = 404) and a delayed intervention group (DIG; n = 196) that was used as a comparison condition. RESULTS: Interpersonal problems emerged as a moderator of PTSD symptom changes in IIG such that veterans endorsing greater interpersonal problems demonstrated larger reductions in PTSD symptoms throughout VetChange. There were no significant moderation effects in DIG. Non-White veterans reported significantly higher PTSD symptoms during VetChange. Post hoc analyses indicated that veterans with higher interpersonal problems were more likely to engage in online intervention content focused on identifying high-risk drinking situations and coping with symptoms. CONCLUSIONS: Findings imply that veterans reporting alcohol-related interpersonal problems may benefit the most from, and be more motivated to use, online interventions for hazardous alcohol use and PTSD symptoms.

Exploring the Minnesota Multiphasic Personality Inventory (MMPI)-3 in a transgender and gender diverse sample.

Comparisons of transgender and gender diverse (TGD) individuals' mental health functioning with that of cisgender individuals rely almost exclusively on screening measures. The limited research with TGD individuals and omnibus assessment measures has primarily used previous iterations of the Minnesota Multiphasic Personality Inventories (MMPIs). This study sought to examine the psychometric functioning of the MMPI-3 with a TGD community sample (n = 97) and compare mean scores across TGD and cisgender subsamples. We expected MMPI-3 substantive scale reliability to be comparable across all samples and subsamples. Individual MMPI-3 scales were expected to demonstrate appropriate convergent and discriminant validity with relevant criterion measures in the TGD sample. Results generally supported MMPI-3 scale score reliability and validity with TGD individuals. Next, three sets of mean score comparisons were conducted across all MMPI-3 substantive scales: (a) TGD individuals not currently in mental health treatment and the MMPI-3 normative sample, (b) TGD individuals not currently in mental health treatment and TGD individuals currently in mental health treatment, and (c) TGD individuals currently in mental health treatment and an outpatient mental health sample. Fewer differences were found between TGD individuals in our sample who were not currently in mental health treatment and the MMPI-3 normative sample compared to previous work. This initial study indicates that MMPI-3 scales largely have appropriate psychometric properties when administered to a TGD sample and that the test may be helpful in identifying mental health needs of TGD individuals. Needs and directions for further research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Patients With and Without Double Crush Syndrome Achieve Similar Rates of Clinical Improvement Following Carpal Tunnel Release.

BACKGROUND: The purpose of this study is to compare outcomes of carpal tunnel release (CTR) in patients with and without double crush syndrome (DCS), defined as concurrent carpal tunnel syndrome (CTS) and cervical radiculopathy at C5-T1 on preoperative nerve conduction studies. METHODS: Patients with preoperative nerve conduction studies who underwent unilateral, isolated CTR were retrospectively identified. All patients completed preoperative and 3-month postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) upper extremity (UE) and pain interference (PI), and Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaires, and responded to the anchor question: "Since your treatment, how would you rate your overall function?" (much worse, worse, slightly worse, no change, slightly improved, improved, much improved). Preoperative, postoperative, and changes in scores for UE, PI, and QuickDASH were compared, as were the anchor question responses and rates of achieving the minimal clinically important difference (MCID). RESULTS: Sixty-three patients with DCS and 115 patients with CTS only were included. At 3- to 4-month follow-up, absolute and change in UE, PI, and QuickDASH scores were not statistically different between patients with DCS and CTS. Rates of anchor question response and MCID achievement were comparable for patients with CTS only and DCS on each questionnaire. The MCID achievement ranged from 48.4% to 68.8% in the unmatched cohort and 48.4% to 60% in the matched group. CONCLUSIONS: At 3 to 4 months, patients with DCS experience similar patient-reported symptomatic and functional improvement, and achieve MCID of outcome measures at comparable rates to patients with CTS only. For patients with nerve compression at the carpal tunnel and cervical spine, CTR is a reasonable first step prior to proceeding with cervical spine decompression.