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Decades of research have demonstrated the efficacy of cognitive behavioral therapies (CBTs) for a wide variety of psychiatric diagnoses, resulting in the inclusion of CBT as a first-line evidence-based practice (EBP) in treatment guidelines for mood and anxiety disorders. However, some research suggests that many providers do not implement EBPs as intended. Ongoing quality monitoring is needed to support EBP implementation and sustainability, but "gold standard" fidelity monitoring (e.g. observer ratings) is time-consuming, requires extensive training, and may feel intrusive to providers and clients. In the current study, we aimed to develop a scalable method of assessing CBT fidelity that leverages information generated in routine clinical care (e.g. session worksheets and clinician checklists). Ratings of adherence based on worksheets were not correlated with ratings of adherence based on observer ratings. However, ratings of competence based on worksheets were significantly correlated with observer ratings of competence. Ratings of adherence based on clinician checklist ratings were also significantly correlated with observer-rated adherence. Results did not indicate a strong relationship between adherence or competence measured by worksheet ratings or observer and symptom change. However, adherence as measured by clinician checklists were associated with subsequent depression symptom change. Findings have a strong potential to impact fidelity monitoring strategies for a variety of CBTs. Given the limited resources and time to do full audio review in routine care settings, findings suggest that using routine materials generated in session to assess therapist competence may be a feasible alternative to the "gold standard" audio review. The trial is registered at ClinicalTrials.gov, number NCT03479398., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs. In this study, we investigated the role of IL-10 in MM TAM development as well as the therapeutic application of IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated that IL-10 is overexpressed in MM BM and mediates M2-like polarization of TAMs in patient BM, 3D co-cultures in vitro, and mouse models. In turn, TAMs promote MM proliferation and drug resistance, both in vitro and in vivo. Moreover, inhibition of IL-10/IL-10R/STAT3 axis using a blocking IL-10R monoclonal antibody and STAT3 protein degrader/PROTAC prevented M2 polarization of TAMs and the consequent TAM-induced proliferation of MM, and re-sensitized MM to therapy, in vitro and in vivo. Therefore, our findings suggest that inhibition of IL-10/IL-10R/STAT3 axis is a novel therapeutic strategy with monotherapy efficacy and can be further combined with current anti-MM therapy, such as immunomodulatory drugs, to overcome drug resistance. Future investigation is warranted to evaluate the potential of such therapy in MM patients., (© 2024. The Author(s).)

Objective: The Pfirrmann scoring system classifies lumbosacral disc degeneration based on magnetic resonance imaging signal intensity. The relationship between pre-existing disc degeneration and patient-reported outcome measures (PROMs) after one-level lumbar fusion is not well documented. The purpose of this study was to investigate the relationship between the severity of preoperative intervertebral disc degeneration and preoperative and postoperative PROMs in patients undergoing one-level lumbar fusion., Methods: All adult patients who underwent posterior lumbar decompression and fusion or transforaminal lumbar interbody fusion between 2014 and 2022 were included. Patient demographics and comorbidities were extracted from medical records. Lumbar intervertebral discs on sagittal magnetic resonance imaging T2-weighted images were assessed by 2 independent graders utilizing Pfirrmann criteria. Grades I-III were categorized as low-grade disc degeneration, while IV-V were considered high grade. Multivariable linear regression assessed the impact of disc degeneration on PROMs., Results: A total of 150 patients were included, of which 69 (46%) had low-grade disc degeneration, while 81 (54%) had high-grade degeneration. Patients with high-grade degeneration had increased preoperative visual analog scale (VAS)-Leg scores (6.10 vs. 4.54, P = 0.005) and displayed greater 1-year postoperative improvements in VAS-Back scores (-2.11 vs. -0.66, P = 0.002). Multivariable regression demonstrated Pfirrmann scores as independent predictors for both preoperative VAS-Leg scores (P = 0.004) and postoperative VAS-Back improvement (P = 0.005)., Conclusions: In patients undergoing one-level lumbar fusion, higher Pfirmann scores were associated with increased preoperative leg pain and greater 1-year postoperative improvement in back pain. Further studies into the relationship of preoperative disc degeneration and their impact on postoperative outcomes may help guide clinical decision-making and patient expectations., (Copyright © 2024. Published by Elsevier Inc.)

The authors investigated the impact of antiplatelet therapy on the megakaryocyte (MK) and platelet transcriptome. RNA-sequencing was performed on MKs treated with aspirin or P2Y 12 inhibitor, platelets from healthy volunteers receiving aspirin or P2Y 12 inhibition, and platelets from patients with systemic lupus erythematosus (SLE). P2Y 12 inhibition reduced gene expression and inflammatory pathways in MKs and platelets. In SLE, the interferon (IFN) pathway was elevated. In vitro experiments demonstrated the role of P2Y 12 inhibition in reducing IFNα-induced platelet-leukocyte interactions and IFN signaling pathways. These results suggest that P2Y 12 inhibition may have therapeutic potential for proinflammatory and autoimmune conditions like SLE., Competing Interests: This work was supported by National Institutes of Health grants R01HL139909 (to Drs Berger and Buyon), R35HL144993 (to Dr Berger), 1OT2HL156812-01 (to Dr Berger), R01HL167917 (to Dr Barrett), and R01HL118049 (to Dr Voora). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: The comprehensive analysis of MK and platelet transcriptomes suppressed by P2Y12 inhibitors and their role in modulating immune reactions adds insights into understanding immune-mediated disorders and their therapeutic potential. P2Y12 inhibitors might synergize with existing treatments to provide more comprehensive control over immune dysregulation and thrombotic tendencies. TRANSLATIONAL OUTLOOK: Further investigation into the precise molecular mechanisms linking P2Y12 inhibition, platelet function, and immune modulation would provide a deeper understanding of the nonhemostatic effects of platelet directed therapies. This knowledge could uncover novel drug targets within platelet-mediated pathways. In addition to SLE, the role of platelet activation and its modulation by P2Y12 inhibitors could be investigated in other inflammatory conditions, expanding the potential applications of these agents., (© 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background: The first goal of this study was to assess longitudinal changes in burnout among psychotherapists prior to (T1) and during the COVID-19 pandemic (T2). The second objective was to assess the effects of job demands, job resources (including organizational support for evidence-based psychotherapies, or EBPs) and pandemic-related stress (T2 only) on burnout., Method: Psychotherapists providing EBPs for posttraumatic stress disorder in U.S. Department of Veterans Affairs (VA) facilities completed surveys assessing burnout, job resources, and job demands prior to (T1; n = 346) and during (T2; n = 193) the COVID-19 pandemic., Results: Burnout prevalence increased from 40 % at T1 to 56 % at T2 (p < .001). At T1, stronger implementation climate and implementation leadership (p < .001) and provision of only cognitive processing therapy (rather than use of prolonged exposure therapy or both treatments; p < .05) reduced burnout risk. Risk factors for burnout at T2 included T1 burnout, pandemic-related stress, less control over when and how to deliver EBPs, being female, and being a psychologist rather than social worker (p < .02). Implementation leadership did not reduce risk of burnout at T2., Limitations: This study involved staff not directly involved in treating COVID-19, in a healthcare system poised to transition to telehealth delivery., Conclusion: Organizational support for using EBPs reduced burnout risk prior to but not during the pandemic. Pandemic related stress rather than increased work demands contributed to elevated burnout during the pandemic. A comprehensive approach to reducing burnout must address the effects of both work demands and personal stressors., Competing Interests: Conflict of interest Dr. Rosen reported receiving grants from the U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. Kaplan reported no conflicts of interest at the time of publication. Dr. Nelson reported receiving grants from the U.S. Department of Veterans Affairs. Dr. La Bash reported no conflicts of interest at the time of publication. Dr. Chard reported receiving grants from the U.S. Department of Defense, U.S. Department of Veterans Affairs and the Chris Sullivan Foundation. Dr. Eftekhari reported no conflicts of interest at the time of publication. Dr. Kehle-Forbes reported receiving grants from the U.S. Department of Veterans Affairs and the Patient-Centered Outcomes Research Institute. Dr. Wiltsey Stirman reported receiving grants from the U.S. National Institute of Mental Health and the Canadian Institutes of Health Research. Dr. Sayer is the PI of the U.S. Department of Veterans Affairs Health Services Research and Development grant that supported this work., (Published by Elsevier B.V.)

Background: The US Department of Veterans Affairs (VA) has over 15 years of experience in delivery of evidence-based psychotherapies (EBPs). This paper describes strategies for using clinical documentation and administrative data to understand adherence and modifications to EBPs for Posttraumatic Stress Disorder (PTSD)., Methods: This study focused on two EBPs for PTSD, Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE). The sample included VA therapists from across the US who provided CPT and PE and the patients they treated over a 1-year period. The data sources for this study were templated EBP chart notes and VA administrative data. We used a manual review of note content and administrative data rules to code therapy adherence and modifications in 7,297 EBP sessions for 1,257 patients seen by 182 therapists. Two trained coders rated each therapy note and resolved discrepancies through consensus. To contextualize and explain variation in adherence and modifications, we conducted brief 30-45-min semi-structured interviews with a purposive subsample of these therapists ( n = 32)., Findings: Combining manual chart review and administrative data allowed for identification of 11 types of modifications. Raters disagreed on adherence for 30% of notes. The disagreement stemmed from the presence of therapy modifications that were not clearly documented, necessitating the development of decision rules and strategies for modification coding. Both therapists and patients contributed to the variance in the extent to which different modifications occurred. Therapist interviews demonstrated therapist awareness of modifying the protocols in the ways identified through chart review., Conclusion: Healthcare systems can use data collected as part of routine care to understand how and when EBPs are modified but need to develop scalable strategies to document adaptations and modifications to EBPs in routine care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wiltsey Stirman, La Bash, Nelson, Orazem, Klein and Sayer.)

Consultation is an important implementation strategy to improve treatment fidelity and clinical outcomes, yet research has not identified the aspects of consultation that differentially affects clinician skill development and client symptom change. Thus, the present study investigated the effect of the consultant, consultation activities, and consultants' ( n = 6) perceptions of consultees ( n = 60) on post-traumatic stress disorder (PTSD) treatment fidelity and client outcomes. In addition, we assessed the accuracy of consultants' evaluations of clinicians using the Perceived Enthusiasm, Skill, and Participation scale (P-ESP). Results indicated that there was a significant effect of consultant on adherence to, but not competence in, delivering Cognitive Processing Therapy (CPT). The effect of the consultant on PTSD symptom change was not significant. Consultants significantly differed in their discussion of CPT strategies and their application to individual cases, but did not differ on reviewing and providing feedback on fidelity. Consultant perceptions as assessed by the P-ESP were not associated with clinicians' current levels of adherence or competence, suggesting that consultants may not accurately assess clinician skill during consultation. Client PTSD symptom change neither predicted, nor was predicted by, consultants' perceptions of their consultees' skill. This article outlines potential reasons for consultant effects and possible biases at play that may reduce the accuracy of consultant perceptions and presents suggestions on alternative strategies to assess clinician skill during consultation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: Concern about symptom worsening with trauma-focused treatment may be one factor hindering the implementation of evidence-based treatments for PTSD, like cognitive processing therapy (CPT), despite evidence for their efficacy. Previous studies have examined the frequency and effect of symptom exacerbation, or temporary symptom increases, on outcomes, but primarily in randomized clinical trials., Method: We examined this issue in a community sample of participants receiving CPT from front-line clinicians learning to deliver CPT in a randomized controlled implementation trial of training strategies. Patient participants ( n = 183) completed self-report measures of PTSD symptoms at each session., Results: Most participants (67.3%) experienced at least one temporary symptom increase during CPT (only 1.6% continued to have higher symptoms by the end of treatment). Demographic variables, comorbid conditions (i.e., depression, anxiety, substance use), and baseline PTSD symptom levels did not predict symptom increases. Importantly, symptom increases did not predict treatment noncompletion, posttreatment PTSD symptom levels, or loss of probable PTSD diagnosis. Moreover, growth curve modeling revealed that temporary symptom increases did not predict the trajectory of PTSD symptoms over the course of treatment., Conclusions: The rates of symptom increases, which were higher than in previous studies, may be attributed to a routine care sample or to the differences in session timing and measurement. These results add to a nascent literature documenting that symptom increases may be a normal, transient part of treatment that do not impact a patient's ability to have symptom improvement during a course of CPT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow (BM) and represents the second most common hematological malignancy in the world. The MM tumor microenvironment (TME) within the BM niche consists of a wide range of elements which play important roles in supporting MM disease progression, survival, proliferation, angiogenesis, as well as drug resistance. Together, the TME fosters an immunosuppressive environment in which immune recognition and response are repressed. Macrophages are a central player in the immune system with diverse functions, and it has been long established that macrophages play a critical role in both inducing direct and indirect immune responses in cancer. Tumor-associated macrophages (TAMs) are a major population of cells in the tumor site. Rather than contributing to the immune response against tumor cells, TAMs in many cancers are found to exhibit protumor properties including supporting chemoresistance, tumor proliferation and survival, angiogenesis, immunosuppression, and metastasis. Targeting TAM represents a novel strategy for cancer immunotherapy, which has potential to indirectly stimulate cytotoxic T cell activation and recruitment, and synergize with checkpoint inhibitors and chemotherapies. In this review, we will provide an updated and comprehensive overview into the current knowledge on the roles of TAMs in MM, as well as the therapeutic targets that are being explored as macrophage-targeted immunotherapy, which may hold key to future therapeutics against MM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute myeloid leukemia (AML) is the most common type of leukemia and has a 5-year survival rate of 25%. The standard-of-care for AML has not changed in the past few decades. Promising immunotherapy options are being developed for the treatment of AML; yet, these regimens require highly laborious and sophisticated techniques. We create nanoTCEs using liposomes conjugated to monoclonal antibodies to enable specific binding. We also recreate the bone marrow niche using our 3D culture system and use immunocompromised mice to enable use of human AML and T cells with nanoTCEs. We show that CD33 is ubiquitously present on AML cells. The CD33 nanoTCEs bind preferentially to AML cells compared to Isotype. We show that nanoTCEs effectively activate T cells and induce AML killing in vitro and in vivo . Our findings suggest that our nanoTCE technology is a novel and promising immuno-therapy for the treatment of AML and provides a basis for supplemental investigations for the validation of using nanoTCEs in larger animals and patients., Competing Interests: CONFLICTS OF INTEREST AKA and KA have filed a patent with regards to the T cell engagers described in this study. AKA is the founder and owner of Cellatrix LLC and Targeted Therapeutics LLC. Some of the experiments were performed using 3DTEBM products supplied by Cellatrix LLC; however, both companies had no role in the study. Other authors state no conflicts of interest., (Copyright: © 2021 Alhallak et al.)

MM is the second most common hematological malignancy and represents approximately 20% of deaths from hematopoietic cancers. The advent of novel agents has changed the therapeutic landscape of MM treatment; however, MM remains incurable. T cell-based immunotherapy such as BTCEs is a promising modality for the treatment of MM. This review article discusses the advancements and future directions of BTCE treatments for MM.

Objective and Method: Numerous risk factors for posttraumatic stress disorder (PTSD) have been identified; however, many do not inform treatment. Psychological inflexibility is a modifiable factor that can be targeted in psychological treatment. This study examined whether higher levels of psychological inflexibility predicted unique variance in PTSD symptom severity at 1-year follow-up in 236 U.S. veterans of the wars in Iraq in Afghanistan after accounting for the strongest known risk factors for PTSD. PTSD symptom severity was assessed using the Clinician Administered PTSD Scale., Results: In hierarchical regression analyses, higher baseline psychological inflexibility predicted unique variance in 1-year PTSD symptom severity (p < .001, medium effect) after accounting for the strongest predictors, including: serving in the Army, rank, trauma severity, perceived threat, peritraumatic dissociation, recent life stress, and social support. Psychological inflexibility remained a significant predictor of unique variance in 1-year PTSD symptom severity after accounting for all other predictors and personality factors (neuroticism, extroversion, openness to experience, agreeableness, and conscientiousness; p < .001, small effect) and after accounting for all other predictors, personality factors, and baseline PTSD avoidance symptoms (p < .001; small effect)., Conclusions: Findings indicate a key unique association between psychological inflexibility and PTSD symptom severity over time that is not attributable to overlap with personality or PTSD avoidance symptoms. Additional research on psychological inflexibility in the development and maintenance of PTSD is warranted, as well as whether increasing psychological flexibility leads to reductions in PTSD symptoms and improved psychosocial functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: Moral injury may result from perpetration-based and betrayal-based acts that violate deeply held norms; however, researchers and clinicians have little guidance about the moral injury syndrome's specific developmental pathways following morally injurious events. The present study's objective was to examine the direct and indirect pathways proposed in a frequently cited model of moral injury (1) in relation to two types of military-related traumas [experiencing military sexual trauma (MST) and combat exposure]. Methods: Secondary analyses were conducted within a sample of post-9/11 veterans at a Southwestern Veterans Health Care System ( N = 310) across two time-points. Structural equation modeling tested the direct and indirect pathways from MST and combat to a PTSD-depression factor via betrayal, perpetration, guilt, and shame. Results: Betrayal accounted for the association between MST and PTSD-depression (β = 0.10, p < 0.01, 95% CI = 0.01 - 0.11) and perpetration accounted for the association between combat and PTSD-depression (β = 0.07, p < 0.05, 95% CI = 0.02 - 0.14). The indirect path from combat to shame to PTSD-depression was significant (β = 0.16, p < 0.01, 95% CI = 0.07 - 0.28) but the path through guilt was not. The specific indirect paths through perpetration or betrayal to shame or guilt were non-significant. Conclusions: Betrayal and perpetration are associated with PTSD-depression following MST and combat. Results suggest multiple pathways of moral injury development following different military traumas and morally injurious events. Implications for moral injury conceptualization and treatment are discussed.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur and are associated with worse outcomes together than either disorder alone. A lack of consensus regarding recommendations for treating PTSD-AUD exists, and treatment dropout is a persistent problem. Acceptance and Commitment Therapy (ACT), a transdiagnostic, mindfulness- and acceptance-based form of behavior therapy, has potential as a treatment option for PTSD-AUD. In this uncontrolled pilot study, we examined ACT for PTSD-AUD in 43 veterans; 29 (67%) completed the outpatient individual therapy protocol (i.e., ≥ 10 of 12 sessions). Clinician-assessed and self-reported PTSD symptoms were reduced at posttreatment, ds = 0.79 and 0.96, respectively. Self-reported symptoms of PTSD remained lower at 3-month follow-up, d = 0.88. There were reductions on all alcohol-related outcomes (clinician-assessed and self-reported symptoms, total drinks, and heavy drinking days) at posttreatment and 3-month follow-up, d mean = 0.91 (d range: 0.65-1.30). Quality of life increased at posttreatment and follow-up, ds = 0.55-0.56. Functional disability improved marginally at posttreatment, d = 0.35; this effect became significant by follow-up, d = 0.52. Fewer depressive symptoms were reported at posttreatment, d = 0.50, and follow-up, d = 0.44. Individuals experiencing suicidal ideation reported significant reductions by follow-up. Consistent with the ACT theoretical model, these improvements were associated with more between-session mindfulness practice and reductions in experiential avoidance and psychological inflexibility. Recommendations for adapting ACT to address PTSD-AUD include assigning frequent between-session mindfulness practice and initiating values clarification work and values-based behavior assignments early in treatment., (Published 2018. This article is a U.S. Government work and is in the public domain in the U.S.A.)

Background: Identifying scalable strategies for assessing fidelity is a key challenge in implementation science. However, for psychosocial interventions, the existing, reliable ways to test treatment fidelity quality are often labor intensive, and less burdensome strategies may not reflect actual clinical practice. Cognitive behavioral therapies (CBTs) provide clinicians with a set of effective core elements to help treat a multitude of disorders, which, evidence suggests, need to be delivered with fidelity to maximize potential client impact. The current "gold standard" for rating CBTs is rating recordings of therapy sessions, which is extremely time-consuming and requires a substantial amount of initial training. Although CBTs can vary based on the target disorder, one common element employed in most CBTs is the use of worksheets to identify specific behaviors and thoughts that affect a client's ability to recover. The present study will develop and evaluate an innovative new approach to rate CBT fidelity, by developing a universal CBT scoring system based on worksheets completed in therapy sessions., Methods: To develop a scoring system for CBT worksheets, we will compile common CBT elements from a variety of CBT worksheets for a range of psychiatric disorders and create adherence and competence measures. We will collect archival worksheets from past studies to test the scoring system and assess test-retest reliability. To evaluate whether CBT worksheet scoring accurately reflects clinician fidelity, we will recruit clinicians who are engaged in a CBT for depression, anxiety, and/or posttraumatic stress disorder. Clinicians and clients will transmit routine therapy materials produced in session (e.g., worksheets, clinical notes, session recordings) to the study team after each session. We will compare observer-rated fidelity, clinical notes, and fidelity-rated worksheets to identify the most effective and efficient method to assess clinician fidelity. Clients will also be randomly assigned to either complete the CBT worksheets on paper forms or on a mobile application (app) to learn if worksheet format influences clinician and client experience or differs in terms of reflecting fidelity., Discussion: Scoring fidelity using CBT worksheets may allow clinics to test fidelity in a short and effective manner, enhancing continuous quality improvement in the workplace. Clinicians and clinics can use such data to improve clinician fidelity in real time, leading to improved patient outcomes., Trial Registration: ClinicalTrials.gov NCT03479398 . Retrospectively registered March 20, 2018.

The objective of this study was to test the hypothesis that sleep quality mediates the association between traumatic brain injury (TBI) history and current suicidal ideation. Measures of TBI history, sleep quality, and suicidal ideation were administered to 130 Iraq/Afghanistan veterans. As expected, sleep quality mediated the effect of TBI history on current suicidal ideation (indirect effect, 0.0082; 95% confidence interval, 0.0019-0.0196), such that history of TBI was associated with worse sleep quality, which was, in turn, associated with increased suicidal ideation. These findings highlight the importance of assessing TBI history and sleep quality during suicide risk assessments for veterans.