Mycorrhizal type and tree diversity affect foliar elemental pools and stoichiometry.

Species-specific differences in nutrient acquisition strategies allow for complementary use of resources among plants in mixtures, which may be further shaped by mycorrhizal associations. However, empirical evidence of this potential role of mycorrhizae is scarce, particularly for tree communities. We investigated the impact of tree species richness and mycorrhizal types, arbuscular mycorrhizal fungi (AM) and ectomycorrhizal fungi (EM), on above- and belowground carbon (C), nitrogen (N), and phosphorus (P) dynamics. Soil and soil microbial biomass elemental dynamics showed weak responses to tree species richness and none to mycorrhizal type. However, foliar elemental concentrations, stoichiometry, and pools were significantly affected by both treatments. Tree species richness increased foliar C and P pools but not N pools. Additive partitioning analyses showed that net biodiversity effects of foliar C, N, P pools in EM tree communities were driven by selection effects, but in mixtures of both mycorrhizal types by complementarity effects. Furthermore, increased tree species richness reduced soil nitrate availability, over 2 yr. Our results indicate that positive effects of tree diversity on aboveground nutrient storage are mediated by complementary mycorrhizal strategies and highlight the importance of using mixtures composed of tree species with different types of mycorrhizae to achieve more multifunctional afforestation.

A national study of clinical discussions about cannabis use among Veteran patients prescribed opioids.

BACKGROUND: The Veterans Health Administration tracks urine drug tests (UDTs) among patients on long-term opioid therapy (LTOT) and recommends discussing the health effects of cannabis use. OBJECTIVE: To determine the occurrence of cannabis-related discussions between providers and patients on LTOT during six months following UDT positive for cannabis, and examine factors associated with documenting cannabis use. DESIGN: We identified patients prescribed LTOT with a UDT positive for cannabis in 2019. We developed a text-processing tool to extract discussions around cannabis use from their charts. SUBJECTS: Twelve thousand seventy patients were included. Chart review was conducted on a random sample of 1,946 patients. MAIN MEASURES: The presence of a cannabis term in the chart suggesting documented cannabis use or cannabis-related discussions. Content of those discussions was extracted in a subset of patients. Logistic regression was used to examine the association between patient factors, including state of residence legal status, with documentation of cannabis use. KEY RESULTS: Among the 12,070 patients, 65.8% (N = 7,948) had a cannabis term, whereas 34.1% (N = 4,122) of patients lacked a cannabis term, suggesting that no documentation of cannabis use or discussion between provider and patient took place. Among the subset of patients who had a discussion documented, 47% related to cannabis use for medical reasons, 35% related to a discussion of VA policy or legal issues, and 17% related to a discussion specific to medical risks or harm reduction strategies. In adjusted analyses, residents of states with legalized recreational cannabis were less likely to have any cannabis-related discussion compared to patients in non-legal states [OR 0.73, 95% CI 0.64-0.82]. CONCLUSIONS: One-third of LTOT patients did not have documentation of cannabis use in the chart in the 6 months following a positive UDT for cannabis. Discussions related to the medical risks of cannabis use or harm reduction strategies were uncommon.

Outcomes of Transcarotid Artery Revascularization Stratified by Institutional Designation: Academic Versus Community Hospitals.

BACKGROUND: The extent of practice setting's influence on transcarotid artery revascularization (TCAR) outcomes is not yet established. This study seeks to assess and compare TCAR outcomes in academic and community-based healthcare settings. METHODS: Retrospective review of prospectively maintained, systemwide TCAR databases from 2 institutions was performed between 2015 and 2022. Patients were stratified based on the setting of surgical intervention (i.e., academic or community-based hospitals). Relevant demographics, medical conditions, anatomic characteristics, intraoperative and postoperative courses, and adverse events were captured for multivariate analysis. RESULTS: We identified 973 patients who underwent TCAR, 570 (58.6%) were performed at academic and 403 (41.4%) at community-based hospitals. An academic facility was defined as a designated teaching hospital with 24/7 service-line coverage by a trainee-led surgical team. Baseline comorbidity between cohorts were similar but cases performed at academic institutions were associated with increased complexity, defined by high cervical stenosis (P < 0.001), prior dissection (P < 0.01), and prior neck radiation (P < 0.001). Intraoperatively, academic hospitals were associated with longer operative time (67 min vs. 58 min, P < 0.001), higher blood loss (55 mLs vs. 37 mLs, P < 0.001), and longer flow reversal time (9.5 min vs. 8.4 min, P < 0.05). Technical success rate was not statistically different. In the 30-day perioperative period, we observed no significant difference with respect to reintervention (1.5% vs. 1.5%, P ≥ 0.9) or ipsilateral stroke (2.7% vs. 2.0%, P = 0.51). Additionally, no difference in postoperative myocardial infarction (academic 0.7% vs. community 0.2%, P < 0.32), death (academic 1.9% vs. community 1.4%, P < 0.57), or length of stay (1 day vs. 1 day, P < 0.62) was seen between the cohorts. CONCLUSIONS: Cases performed at academic centers were characterized by more challenging anatomy, more frequent cardiovascular risk factors, and less efficient intraoperative variables, potentially attributable to case complexity and trainee involvement. However, there were no differences in perioperative outcomes and adverse events between the cohorts, suggesting TCAR can be safely performed regardless of practice setting.

Effect of Perioperative Stroke on Survival After Carotid Intervention.

OBJECTIVES: Perioperative stroke is the most dreaded complication of carotid artery interventions and can severely affect patients' quality of life. This study evaluated the impact of this event on mortality for patients undergoing interventional treatment of carotid artery stenosis with three different modalities. METHODS: Patients undergoing carotid revascularization at participating Memorial Hermann Health System facilities were captured from 2003-2022. These patients were treated with either carotid endarterectomy (CEA), transfemoral carotid stenting (TF-CAS), or transcarotid artery revascularization (TCAR). Perioperative outcomes, including stroke and mortality, as well as follow-up survival data at 6-month intervals, were analyzed and stratified per treatment modality. RESULTS: Of the 1681 carotid revascularization patients identified, 992 underwent CEA (59.0%), 524 underwent TCAR (31.2%), and 165 underwent TF-CAS (9.8%). The incidence of stroke was 2.1% (CEA 2.1%, TCAR 1.7%, and TF-CAS 3.6%; P = .326). The perioperative (30-day) death rate was 2.1% (n = 36). The perioperative death rate was higher in patients who suffered from an intraoperative stroke than in those who did not (8.3% vs 1.9%, P = .007). Perioperative death was also different between CEA, TCAR, and TF-CAS for patients who had an intraoperative stroke (.0% vs 33.3% vs .0%, P = .05). TCAR patients were likely to be older (P < .001), have a higher body mass index (P < .001), and have diabetes mellitus (P < .001). Patients who suffered from an intraoperative stroke were more likely to have a symptomatic carotid lesion (58.3% vs 28.8%, P < .001). The TCAR group had a significantly lower survival at 6 months and 12 months when compared to the other two groups (64.9% vs 100% P = .007). CONCLUSION: Perioperative stroke during carotid interventions significantly impacts early patient survival with otherwise no apparent change in mid-term outcomes at 5 years. This difference appears to be even more significant in patients undergoing TCAR, possibly due to their baseline higher-risk profile and lower functional reserve.

R-8 Dispersion Interaction: Derivation and Application to the Effective Fragment Potential Method.

The anisotropic and isotropic R-8 dispersion contributions (disp8) are derived and implemented within the framework of the effective fragment potential (EFP) method formulated with imaginary frequency-dependent Cartesian polarizability tensors distributed at the centroids of the localized molecular orbitals (LMOs). Two forms of damping functions, intermolecular overlap-based and Tang-Toennies, are extended for disp8. To obtain LMO polarizability tensors centered at LMO centroids, an origin-shifting transformation is derived and implemented for the dipole-octopole polarizability tensor and the quadrupole-quadrupole polarizability tensor. The analytic gradient is derived and implemented for the isotropic disp8 contribution. Relative to the previously implemented empirical EFP disp8 energy, the isotropic disp8 component of the interaction energy improves the overall agreement of the EFP dispersion energies with the symmetry-adapted perturbation theory (SAPT) benchmarks, reducing the mean absolute errors (MAEs) and mean absolute percentage errors for most of the databases examined in this work. While the anisotropic disp8 can further enhance the accuracy of the EFP dispersion energy and yield smaller MAEs, significantly overbound dispersion energies are predicted by the anisotropic disp8 when the maximum element in the intermolecular overlap matrix is greater than 0.1, possibly due to the breakdown of the approximations made in the EFP dispersion derivation at a short range. For potential energy scan databases, the newly developed EFP dispersion model with isotropic disp8 yields the overall correct curvature and good agreement with SAPT benchmarks around equilibrium and longer but overestimates the dispersion interactions at a short range. While the overlap-based dispersion-damping functions produce better MAEs than Tang-Toennies damping functions, further improvement is needed to better screen the large attractive dispersion energies at a short range (overlap >0.1).

Mental Health Clinician Practices and Perspectives on Treating Adults with Co-Occurring Posttraumatic Stress and Substance Use Disorders.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) commonly co-occur and represent a complex, challenging clinical comorbidity. Meta-analytic studies and systematic reviews suggest that trauma-focused treatments are more efficacious than non-trauma focused interventions for co-occurring PTSD/SUD. However, relatively little is known about mental health clinicians' practices or preferences for treating co-occurring PTSD/SUD. The present study aimed to describe the current clinical practices of mental health clinicians who treat PTSD and/or SUD-related conditions and to assess interest in novel integrative treatments for PTSD/SUD. METHODS: Licensed mental health clinicians (N = 76; Mage = 39.59, SD = 8.14) who treat PTSD and/or SUD completed an anonymous online survey from April 2021 to July 2021. RESULTS: The majority (61.8%) of clinicians reported using integrative treatments for PTSD/SUD. The most commonly used trauma-focused treatments were 1) Cognitive Processing Therapy (CPT: 71.1%) and 2) Prolonged Exposure Therapy (PE: 68.4%) for PTSD. Approximately half (51.3%) of clinicians endorsed using Relapse Prevention (RP) for SUD. The vast majority (97.4%) of clinicians were somewhat or very interested in a new integrative CPT-RP intervention, and 94.7% of clinicians believed patients would be interested in a CPT-RP intervention. In the absence of an available evidence-based integrative treatment using CPT, 84.0% of clinicians reported modifying extant treatment protocols on their own to address PTSD and SUD concurrently. CONCLUSIONS: The findings demonstrate mental health clinician support of integrative treatments for PTSD/SUD. The most commonly used trauma-focused intervention was CPT and clinicians expressed strong interest in an integrative intervention that combines CPT and RP. Implications for future treatment development are discussed.

PTSD Symptom Severity and Alcohol Use among Firefighters: The Role of Emotion Regulation Difficulties.

OBJECTIVE: Heightened rates of posttraumatic stress disorder (PTSD) symptoms and alcohol use have been documented among firefighters. Emotion regulation difficulties (ERD) are clinically relevant to both PTSD and alcohol use. Few studies have examined the role of ERD in the association of PTSD symptoms with alcohol use severity and alcohol use motives among firefighters. Thus, the present investigation examined the indirect effect of PTSD symptom severity on alcohol use severity and alcohol use motives through ERD. METHODS: The sample was comprised of 685 firefighters (Mage = 38.65, SD = 8.57, 93.6% male) recruited from an urban fire department in the southern U.S. to complete an online survey. Indirect effects were calculated using 10,000 bootstrapped samples. Effects were examined after accounting for years of fire service, occupational stress, trauma load (i.e., number of traumatic event types experienced); in models evaluating alcohol use motives as outcomes, other alcohol use motives (i.e., alternate motives subscales) were included as additional covariates. RESULTS: First, ERD explained the association of PTSD symptom severity with alcohol use coping motives (ß = .01, SE = .003, 95% CI [.004-.01]). Furthermore, ERD did not significantly account for the association of PTSD symptom severity with alcohol use severity (ß = .02, SE = .01, 95% CI [-.004-.04]), alcohol use enhancement motives (ß = -.003, SE = .002, 95%CI [-.007-.000]), alcohol use social motives (ß = .004, SE = .002, 95% CI [-.000-.01]), or alcohol use conformity motives (ß = -.002, SE = .002, 95% CI [-.006-.02]). CONCLUSIONS: Results demonstrated that, among firefighters, PTSD symptom severity is positively related to alcohol use coping motives through heightened ERD. Clinical implications and future directions are discussed.

Gore cTAG sleeve-associated maldeployment for traumatic aortic injury with aberrant right subclavian artery.

A 30-year-old woman presented following a motor vehicle collision with a grade III blunt thoracic aortic injury and an aberrant right subclavian artery. Using intraoperative ultrasound and diagnostic subtraction angiography, we deployed an aortic endograft (cTAG; W.L. Gore & Associates), excluding the injury and aberrant right subclavian artery. The patient immediately lost arterial waveforms in her left arm, confirming incidental coverage of the left subclavian artery, likely due to the polytetrafluoroethylene sheath of the endograft. Her pulses returned after placement of a left subclavian chimney via retrograde brachial artery access.

Insecure Adult Attachment Style and PTSD Symptom Severity among Firefighters: The Role of Distress Tolerance.

Trauma exposure and posttraumatic stress disorder (PTSD) symptoms among firefighters are prevalent and well-documented. Insecure adult attachment style (AAS) and distress tolerance (DT) present two factors with demonstrated relevance to the etiology and maintenance of PTSD. Few studies have examined these constructs in relation to PTSD symptomatology among firefighter populations. The present investigation examined the indirect effect of insecure romantic AAS (i.e., anxious AAS, avoidant AAS) on PTSD symptom severity through DT among firefighters. Exploratory analyses examined this model with each of the PTSD symptom clusters as outcomes. The sample was comprised of 105 firefighters (Mage=40.43, SD=9.15, 95.2% male) recruited from various departments in the southern U.S. An indirect effect was calculated using 10,000 bootstrapped samples. Indirect effects models in the primary analyses were significant when both anxious AAS (ß=.20, SE=.10, CI=.06-.43) and avoidant AAS (ß=.28, SE=.12, CI=.08-.54) were evaluated as predictors. Effects were evident after accounting for gender, relationship status, years of fire service, and trauma load (i.e., number of potentially traumatic event types experienced). Exploratory analyses revealed that anxious and avoidant AAS are both indirectly related to the PTSD intrusion, negative alterations in cognitions and mood, and alterations in arousal and reactivity symptom clusters through DT. Anxious AAS also demonstrated an indirect association with PTSD avoidance symptoms through DT. Attachment styles may influence PTSD symptoms among firefighters through a firefighter's perceived ability to withstand emotional distress. This line of inquiry has potential to inform specialized intervention programs for firefighters. Clinical and empirical implications are discussed.

Comparative mRNA booster effectiveness against death or hospitalization with COVID-19 pneumonia across at-risk US Veteran populations.

Studies of comparative mRNA booster effectiveness among high-risk populations can inform mRNA booster-specific guidelines. The study emulated a target trial of COVID-19 vaccinated U.S. Veterans who received three doses of either mRNA-1273 or BNT162b2 vaccines. Participants were followed for up to 32 weeks between July 1, 2021 to May 30, 2022. Non-overlapping populations were average and high risk; high-risk sub-groups were age ≥65 years, high-risk co-morbid conditions, and immunocompromising conditions. Of 1,703,189 participants, 10.9 per 10,000 persons died or were hospitalized with COVID-19 pneumonia over 32 weeks (95% CI: 10.2, 11.8). Although relative risks of death or hospitalization with COVID-19 pneumonia were similar across at-risk groups, absolute risk varied when comparing three doses of BNT162b2 with mRNA-1273 (BNT162b2 minus mRNA-1273) between average-risk and high-risk populations, confirmed by the presence of additive interaction. The risk difference of death or hospitalization with COVID-19 pneumonia for high-risk populations was 2.2 (0.9, 3.6). Effects were not modified by predominant viral variant. In this work, the risk of death or hospitalization with COVID-19 pneumonia over 32 weeks was lower among high-risk populations who received three doses of mRNA-1273 vaccine instead of BNT162b2 vaccine; no difference was found among the average-risk population and age >65 sub-group.

A national population-based study of cannabis use and correlates among U.S. veterans prescribed opioids in primary care.

BACKGROUND: Cannabis is marketed as a treatment for pain. There is limited data on the prevalence of cannabis use and its correlates among Veterans prescribed opioids. OBJECTIVE: To examine the prevalence and correlates of cannabis use among Veterans prescribed opioids. DESIGN: Cross-sectional study. PARTICIPANTS: Veterans with a urine drug test (UDT) from Primary Care 2014-2018, in 50 states, Washington, D.C., and Puerto Rico. A total of 1,182,779 patients were identified with an opioid prescription within 90 days prior to UDT. MAIN MEASURES: Annual prevalence of cannabis positive UDT by state. We used multivariable logistic regression to assess associations of demographic factors, mental health conditions, substance use disorders, and pain diagnoses with cannabis positive UDT. RESULTS: Annual prevalence of cannabis positive UDT ranged from 8.5% to 9.7% during the study period, and in 2018 was 18.15% in Washington, D.C. and 10 states with legalized medical and recreational cannabis, 6.1% in Puerto Rico and 25 states with legalized medical cannabis, and 4.5% in non-legal states. Younger age, male sex, being unmarried, and marginal housing were associated with use (p < 0.001). Post-traumatic stress disorder (adjusted odds ratio [AOR] 1.17; 95% confidence interval [CI] 1.13-1.22, p < 0.001), opioid use disorder (AOR 1.14; CI 1.07-1.22, p < 0.001), alcohol use disorder or positive AUDIT-C (AOR 1.34; 95% CI 1.28-1.39, p < 0.001), smoking (AOR 2.58; 95% CI 2.49-2.66, p < 0.001), and other drug use disorders (AOR 1.15; 95% CI 1.03-1.29, p = 0.02) were associated with cannabis use. Positive UDT for amphetamines AOR 1.41; 95% CI 1.26-1.58, p < 0.001), benzodiazepines (AOR 1.41; 95% CI 1.31-1.51, p < 0.001) and cocaine (AOR 2.04; 95% CI 1.75-2.36, p < 0.001) were associated with cannabis positive UDT. CONCLUSIONS: Cannabis use among Veterans prescribed opioids varied by state and by legalization status. Veterans with PTSD and substance use disorders were more likely to have cannabis positive UDT. Opioid-prescribed Veterans using cannabis may benefit from screening for these conditions, referral to treatment, and attention to opioid safety.

COVID-19-Related Medical Vulnerability and Mental Health Outcomes Among US First Responders.

OBJECTIVE: The present investigation examined the main and interactive effects of coronavirus disease 2019 (COVID-19)-related medical vulnerability (CMV; the number of medical conditions with potential to elevate COVID-19 risk) and first responder status (emergency medical services roles vs non-emergency medical services roles) on mental health symptoms. METHODS: A national sample of 189 first responders completed an online survey between June and August 2020. Hierarchal linear regression analyses were conducted and included the following covariates: years served as a first responder, COVID-19 exposure, and trauma load. RESULTS: Unique main and interactive effects emerged for both CMV and first responder status. COVID-19-related medical vulnerability was uniquely associated with anxiety and depression, but not alcohol use. Simple slope analyses revealed divergent results. CONCLUSIONS: Findings suggest that first responders with CMV are more likely to experience anxiety and depressive symptoms and that these associations may vary by first responder role.

Alcohol Use Severity, Anger and Drinking Motives among Firefighters.

Background: Firefighters represent an understudied population with high rates of hazardous alcohol use and alcohol use disorder. This population is also at an increased risk of mental health disorders and related symptoms such as anger. Anger is a relatively understudied negative mood state with clinical relevance to alcohol use among firefighters. Anger is associated with greater alcohol use and may spur more approach-motivated reasons for drinking compared to other negative emotions. Objectives: This study sought to examine: 1. whether anger significantly contributes to alcohol use severity in firefighters above and beyond general negative mood; 2. which of four validated drinking motives (e.g., coping, social, enhancement and conformity) act as moderators in the relationship between anger and alcohol use severity in this population. The current study is a secondary analysis of data from a larger study examining health and stress behaviors among firefighters (N = 679) at a large urban fire department in the southern United States. Results: Results revealed that anger was positively associated with alcohol use severity, even after controlling for general negative mood. Further, social and enhancement motives for drinking were significant moderators of the relationship between anger and alcohol use severity. Conclusions: These findings identify anger specifically as an important factor to be considered when assessing alcohol use in firefighters, especially those who are drinking to make social experiences more enjoyable or to enhance their mood. These findings can be used to inform more specialized interventions for alcohol use by targeting anger more specifically in firefighters and other male-dominated first-responder populations.

Posttraumatic Stress, Alcohol Use, and Alcohol Use Motives among Non-Hispanic Black/African American College Students: The Role of Emotion Regulation.

OBJECTIVE: The associations between posttraumatic stress disorder (PTSD) symptom severity, alcohol use, and alcohol use motives are well-established. Emotion regulation difficulties have been implicated in the association between PTSD symptoms and alcohol use. A dearth of empirical work, however, has examined these associations among Black/African American college students, a population with high prevalence of exposure to potentially traumatic events, PTSD symptomatology, and alcohol-related consequences. METHODS: This study examined PTSD symptoms, emotion regulation difficulties, and alcohol use severity and motives among a sample of Black/African American trauma-exposed college students (N = 282; 77.4% identified as female; M age = 22.36, SD = 4.71). RESULTS: PTSD symptom severity was related to alcohol use and coping and conformity motives for alcohol use through heightened emotion regulation difficulties. Findings were significant above and beyond the effects of trauma load (i.e., number of potentially traumatic event types experienced). CONCLUSIONS: This study extends past work to an understudied population and contributes to groundwork for culturally informed interventions.

An Analysis of Sex-Based Outcomes Following Transcarotid Artery Revascularization.

OBJECTIVE: Several studies suggest that females have higher perioperative adverse events and decreased benefit from carotid artery revascularization with transfemoral carotid artery stenting and carotid endarterectomy (CEA) compared to males. However, there are limited data of sex-based outcomes for transcarotid artery revascularization (TCAR). METHODS: A retrospective review of prospectively maintained system-wide TCAR databases was performed between December 2015-January 2022. Patients who underwent TCAR were stratified based on sex. Relevant demographics, medical conditions, anatomical characteristics, intra- and postoperative courses, and adverse events were captured. RESULTS: 729 patients underwent TCAR, 486 (66.6%) male and 243 (33.3%) female. Males were more likely to be diagnosed with coronary artery disease (56.9% vs 47.7%, P<.01) and were active smokers (30.4% vs 21.4%, P < .01). Age, symptomatic status, BMI, hypertension, hyperlipidemia, diabetes mellitus, arrhythmia, chronic obstructive pulmonary disease, history of myocardial infarction, heart failure with reduced ejection fraction <30%, end-stage renal disease and Charlson Comorbidity Index were similar. In the perioperative period, there was no significant difference in reintervention rates (1.6% vs 1.2%, P = .75), cranial nerve palsy (.6% vs .4%, P > .99), ipsilateral stroke (1.9% vs 3.3%, P = .29), stent thrombosis (.4% vs .8%, P > .99), myocardial infarction (0% vs 0%, P > .99) and death (1.2% vs 1.2%, P > .99). In follow-up, no significant difference was found in reintervention, ipsilateral stroke, contralateral stroke, myocardial infarction, in-stent restenosis >50%, stent thrombosis, and death. CONCLUSIONS: Males and females did not have a statistically significant difference in outcomes when comparing ipsilateral stroke, in-stent thrombosis, conversion to CEA, and death after TCAR. However, our cohort comprised predominantly male patients and may conceal statistical significance as the females in our cohort did have a higher tendency toward developing complications. Future studies with a larger female cohort should be conducted to determine whether there is a true disparity of outcomes between the males and females undergoing TCAR.

Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids.

Importance: Cannabis has been proposed as a therapeutic with potential opioid-sparing properties in chronic pain, and its use could theoretically be associated with decreased amounts of opioids used and decreased risk of mortality among individuals prescribed opioids. Objective: To examine the risks associated with cannabis use among adults prescribed opioid analgesic medications. Design, Setting, and Participants: This cohort study was conducted among individuals aged 18 years and older who had urine drug screening in 2014 to 2019 and received any prescription opioid in the prior 90 days or long-term opioid therapy (LTOT), defined as more than 84 days of the prior 90 days, through the Veterans Affairs health system. Data were analyzed from November 2020 through March 2022. Exposures: Biologically verified cannabis use from a urine drug screen. Main Outcomes and Measures: The main outcomes were 90-day and 180-day all-cause mortality. A composite outcome of all-cause emergency department (ED) visits, all-cause hospitalization, or all-cause mortality was a secondary outcome. Weights based on the propensity score were used to reduce confounding, and hazard ratios [HRs] were estimated using Cox proportional hazards regression models. Analyses were conducted among the overall sample of patients who received any prescription opioid in the prior 90 days and were repeated among those who received LTOT. Analyses were repeated among adults aged 65 years and older. Results: Among 297 620 adults treated with opioids, 30 514 individuals used cannabis (mean [SE] age, 57.8 [10.5] years; 28 784 [94.3%] men) and 267 106 adults did not (mean [SE] age, 62.3 [12.3] years; P < .001; 247 684 [92.7%] men; P < .001). Among all patients, cannabis use was not associated with increased all-cause mortality at 90 days (HR, 1.07; 95% CI, 0.92-1.22) or 180 days (HR, 1.00; 95% CI, 0.90-1.10) but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.01-1.07) and 180 days (HR, 1.04; 95% CI, 1.01-1.06). Among 181 096 adults receiving LTOT, cannabis use was not associated with increased risk of all-cause mortality at 90 or 180 days but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.02-1.09) and 180 days (HR, 1.05; 95% CI, 1.02-1.09). Among 77 791 adults aged 65 years and older receiving LTOT, cannabis use was associated with increased 90-day mortality (HR, 1.55; 95% CI, 1.17-2.04). Conclusions and Relevance: This study found that cannabis use among adults receiving opioid analgesic medications was not associated with any change in mortality risk but was associated with a small increased risk of adverse outcomes and that short-term risks were higher among older adults receiving LTOT.

Incidence of Severe COVID-19 Illness Following Vaccination and Booster With BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines.

Importance: Evidence describing the incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines is needed, particularly for high-risk populations. Objective: To describe the incidence of severe COVID-19 illness among a cohort that received vaccination plus a booster vaccine dose. Design, Setting, and Participants: Retrospective cohort study of adults receiving care at Veterans Health Administration facilities across the US who received a vaccination series plus 1 booster against SARS-CoV-2, conducted from July 1, 2021, to May 30, 2022. Patients were eligible if they had received a primary care visit in the prior 2 years and had documented receipt of all US Food and Drug Administration-authorized doses of the initial mRNA vaccine or viral vector vaccination series after December 11, 2020, and a subsequent documented booster dose between July 1, 2021, and April 29, 2022. The analytic cohort consisted of 1 610 719 participants. Exposures: Receipt of any combination of mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), and Ad26.COV2.S (Janssen/Johnson & Johnson) primary vaccination series and a booster dose. Main Outcomes and Measures: Outcomes were breakthrough COVID-19 (symptomatic infection), hospitalization with COVID-19 pneumonia and/or death, and hospitalization with severe COVID-19 pneumonia and/or death. A subgroup analysis of nonoverlapping populations included those aged 65 years or older, those with high-risk comorbid conditions, and those with immunocompromising conditions. Results: Of 1 610 719 participants, 1 100 280 (68.4%) were aged 65 years or older and 132 243 (8.2%) were female; 1 133 785 (70.4%) had high-risk comorbid conditions, 155 995 (9.6%) had immunocompromising conditions, and 1 467 879 (91.1%) received the same type of mRNA vaccine (initial series and booster). Over 24 weeks, 125.0 (95% CI, 123.3-126.8) per 10 000 persons had breakthrough COVID-19, 8.9 (95% CI, 8.5-9.4) per 10 000 persons were hospitalized with COVID-19 pneumonia or died, and 3.4 (95% CI, 3.1-3.7) per 10 000 persons were hospitalized with severe pneumonia or died. For high-risk populations, incidence of hospitalization with COVID-19 pneumonia or death was as follows: aged 65 years or older, 1.9 (95% CI, 1.4-2.6) per 10 000 persons; high-risk comorbid conditions, 6.7 (95% CI, 6.2-7.2) per 10 000 persons; and immunocompromising conditions, 39.6 (95% CI, 36.6-42.9) per 10 000 persons. Subgroup analyses of patients hospitalized with COVID-19 pneumonia or death by time after booster demonstrated similar incidence estimates among those aged 65 years or older and with high-risk comorbid conditions but not among those with immunocompromising conditions. Conclusions and Relevance: In a US cohort of patients receiving care at Veterans Health Administration facilities during a period of Delta and Omicron variant predominance, there was a low incidence of hospitalization with COVID-19 pneumonia or death following vaccination and booster with any of BNT162b2, mRNA-1273, or Ad26.COV2.S vaccines.

Wanting, Liking, and Missing Out: Exploring the Role of Reward Functioning in the Overlap Between PTSD and Depression.

ABSTRACT: Diminished reward functioning (anhedonia) is an aspect of multiple psychiatric diagnoses and is a critical component of depression, yet it has rarely been examined in the context of posttraumatic stress disorder (PTSD). Deficits in reward function may be a transdiagnostic factor contributing to the high rate of comorbidity between PTSD and depression. The present study examined the commonality and distinction between PTSD and depression and their relationship to reward functioning using a bifactor model in a sample of 106 trauma-exposed undergraduates. Results indicated a strong commonality factor between PTSD and depression. Of three indices of reward functioning (i.e., hedonic pleasure, reward motivation, and environmental reward availability), environmental reward availability alone was related to unique latent factors for PTSD and depression, and their commonality. Findings suggest that environmental context may be the key to understanding the role of reward in PTSD, depression, and psychopathology broadly.

Cardiomyocyte BRAF and type 1 RAF inhibitors promote cardiomyocyte and cardiac hypertrophy in mice in vivo.

The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade promotes cardiomyocyte hypertrophy and is cardioprotective, with the three RAF kinases forming a node for signal integration. Our aims were to determine if BRAF is relevant for human heart failure, whether BRAF promotes cardiomyocyte hypertrophy, and if Type 1 RAF inhibitors developed for cancer (that paradoxically activate ERK1/2 at low concentrations: the 'RAF paradox') may have the same effect. BRAF was up-regulated in heart samples from patients with heart failure compared with normal controls. We assessed the effects of activated BRAF in the heart using mice with tamoxifen-activated Cre for cardiomyocyte-specific knock-in of the activating V600E mutation into the endogenous gene. We used echocardiography to measure cardiac dimensions/function. Cardiomyocyte BRAFV600E induced cardiac hypertrophy within 10 d, resulting in increased ejection fraction and fractional shortening over 6 weeks. This was associated with increased cardiomyocyte size without significant fibrosis, consistent with compensated hypertrophy. The experimental Type 1 RAF inhibitor, SB590885, and/or encorafenib (a RAF inhibitor used clinically) increased ERK1/2 phosphorylation in cardiomyocytes, and promoted hypertrophy, consistent with a 'RAF paradox' effect. Both promoted cardiac hypertrophy in mouse hearts in vivo, with increased cardiomyocyte size and no overt fibrosis. In conclusion, BRAF potentially plays an important role in human failing hearts, activation of BRAF is sufficient to induce hypertrophy, and Type 1 RAF inhibitors promote hypertrophy via the 'RAF paradox'. Cardiac hypertrophy resulting from these interventions was not associated with pathological features, suggesting that Type 1 RAF inhibitors may be useful to boost cardiomyocyte function.